Sherry Boschert

SAN FRANCISCO — Take time to read the updates of guidelines for the management of prediabetes or diabetes carefully, because little pearls can be buried in the text, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association.

He says he has noticed a shift, for example, in nutrition recommendations for the prevention of diabetes in the latest update of the American Diabetes Association's major position statement, “Standards of Medical Care in Diabetes,” which states that for weight loss, “either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year)” (Diabetes Care 2008;31:S1-S108).

“This is a huge change,” said Dr. Bergenstal, executive director of the International Diabetes Center, Minneapolis. “We've always just said it's got to be low-fat calorie-restricted diets.”

The new recommendation is more patient centered and gives providers more leeway to figure out what patients might be willing to do to change their diets and to match the pros and cons of different diets to individual patients.

“For the first year, let people do what they're going to do to lose some weight,” he paraphrased. “I thought that was an interesting and significant change, but it just shows up as a little bullet in the standards of care, so read them carefully.”

The updated guidelines state that for patients with prediabetes, counseling for lifestyle modifications is the standard of care for patients with either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). The goal should be a weight loss of 5%–10% and an increase in physical activity to at least 150 minutes a week of moderate activity such as walking. Follow-up counseling is recommended.

In addition to lifestyle counseling, treatment with metformin may be considered for people at very high risk of developing diabetes: those who are obese, are younger than 60 years old, and have both IFG and IGT plus other risk factors for diabetes (such as a family history of the disease). Patients with prediabetes should be monitored yearly for the development of diabetes.

The guidelines eschewed the use of thiazolidinediones or incretin mimetics in these patients because more data are needed about the risks and benefits of these agents for preventing diabetes, Dr. Bergenstal noted.

In recent studies, other suggested therapies for prediabetes have included walking; combining aerobic exercise and weight lifting; getting adequate sleep; surgery; monitoring caffeine intake and diet; and medications.

Dr. Bergenstal is an advisor to or has received research funding from multiple companies that make medications or devices for diabetes.

SAN FRANCISCO — Take time to read the updates of guidelines for the management of prediabetes or diabetes carefully, because little pearls can be buried in the text, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association.

He says he has noticed a shift, for example, in nutrition recommendations for the prevention of diabetes in the latest update of the American Diabetes Association's major position statement, “Standards of Medical Care in Diabetes,” which states that for weight loss, “either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year)” (Diabetes Care 2008;31:S1-S108).

“This is a huge change,” said Dr. Bergenstal, executive director of the International Diabetes Center, Minneapolis. “We've always just said it's got to be low-fat calorie-restricted diets.”

The new recommendation is more patient centered and gives providers more leeway to figure out what patients might be willing to do to change their diets and to match the pros and cons of different diets to individual patients.

“For the first year, let people do what they're going to do to lose some weight,” he paraphrased. “I thought that was an interesting and significant change, but it just shows up as a little bullet in the standards of care, so read them carefully.”

The updated guidelines state that for patients with prediabetes, counseling for lifestyle modifications is the standard of care for patients with either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). The goal should be a weight loss of 5%–10% and an increase in physical activity to at least 150 minutes a week of moderate activity such as walking. Follow-up counseling is recommended.

In addition to lifestyle counseling, treatment with metformin may be considered for people at very high risk of developing diabetes: those who are obese, are younger than 60 years old, and have both IFG and IGT plus other risk factors for diabetes (such as a family history of the disease). Patients with prediabetes should be monitored yearly for the development of diabetes.

The guidelines eschewed the use of thiazolidinediones or incretin mimetics in these patients because more data are needed about the risks and benefits of these agents for preventing diabetes, Dr. Bergenstal noted.

In recent studies, other suggested therapies for prediabetes have included walking; combining aerobic exercise and weight lifting; getting adequate sleep; surgery; monitoring caffeine intake and diet; and medications.

Dr. Bergenstal is an advisor to or has received research funding from multiple companies that make medications or devices for diabetes.

SAN FRANCISCO — Take time to read the updates of guidelines for the management of prediabetes or diabetes carefully, because little pearls can be buried in the text, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association.

He says he has noticed a shift, for example, in nutrition recommendations for the prevention of diabetes in the latest update of the American Diabetes Association's major position statement, “Standards of Medical Care in Diabetes,” which states that for weight loss, “either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year)” (Diabetes Care 2008;31:S1-S108).

“This is a huge change,” said Dr. Bergenstal, executive director of the International Diabetes Center, Minneapolis. “We've always just said it's got to be low-fat calorie-restricted diets.”

The new recommendation is more patient centered and gives providers more leeway to figure out what patients might be willing to do to change their diets and to match the pros and cons of different diets to individual patients.

“For the first year, let people do what they're going to do to lose some weight,” he paraphrased. “I thought that was an interesting and significant change, but it just shows up as a little bullet in the standards of care, so read them carefully.”

The updated guidelines state that for patients with prediabetes, counseling for lifestyle modifications is the standard of care for patients with either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). The goal should be a weight loss of 5%–10% and an increase in physical activity to at least 150 minutes a week of moderate activity such as walking. Follow-up counseling is recommended.

In addition to lifestyle counseling, treatment with metformin may be considered for people at very high risk of developing diabetes: those who are obese, are younger than 60 years old, and have both IFG and IGT plus other risk factors for diabetes (such as a family history of the disease). Patients with prediabetes should be monitored yearly for the development of diabetes.

The guidelines eschewed the use of thiazolidinediones or incretin mimetics in these patients because more data are needed about the risks and benefits of these agents for preventing diabetes, Dr. Bergenstal noted.

In recent studies, other suggested therapies for prediabetes have included walking; combining aerobic exercise and weight lifting; getting adequate sleep; surgery; monitoring caffeine intake and diet; and medications.

Dr. Bergenstal is an advisor to or has received research funding from multiple companies that make medications or devices for diabetes.

SAN FRANCISCO — The heterogeneous nature of diabetes in the elderly makes it imperative to assess each patient individually before choosing whether to use aggressive or more conservative therapy, Dr. Hermes Florez said.

Some older diabetes patients have newly diagnosed disease and are quite functional, while others have long-standing disease and significant functional decline. Older adults are more likely to have multiple comorbidities and to be taking multiple medications.

Life expectancy also is important to consider. “In a patient who has less than 5 years of life expectancy, can we be aggressive enough with intensive glycemic control to achieve a hemoglobin A1c level of less than 6.5% when that will lead to increased risk of hypoglycemic events, frequent falls, or significant functional or cognitive decline?” he asked at a a meeting sponsored by the American Diabetes Association.

Approximately 40% of adults with type 2 diabetes mellitus are 60 years or older, comprising roughly 40 million people, noted Dr. Florez, an endocrinologist at the University of Miami and the Miami Veterans Affairs Medical Center. Looked at another way, 13% of U.S. residents aged 60 years or older have been diagnosed with diabetes, and another 12% have undiagnosed diabetes.

To help chart an individual's management plan, balance the potential benefits of aggressive glycemic control against the risks from comorbidities, medication side effects, and geriatric syndromes such as dementia, incontinence, and depression, he advised.

Published data suggest that 46% of elderly patients with type 2 diabetes have five or more comorbidities, most commonly cardiovascular problems including hypertension, lipid disorders, or coronary atherosclerosis. Older patients with diabetes and five or more comorbidities are at increased risk for hospitalizations that could have been prevented and that are two to three times longer, compared with hospitalizations of patients who have diabetes alone.

Dr. Florez described the following sample cases, which highlight treatment choices:

Low risk, high benefit. Aggressive treatment was an easy decision for a 70-year-old woman with a 20-year history of diabetes who also had hypertension, lipid abnormalities, and early appearance of retinopathy but who functioned well independently and had no other comorbidities. “She's low risk, with potential for high benefit” from aggressive glycemic control, he said.

High risk, low benefit. The opposite was true for a 68-year-old man with a 4-year history of diabetes who also had severe cardiomyopathy with ventricular tachycardia and was unable to walk. This patient already was taking 14 medications. Intensifying treatment for better blood pressure, lipid levels, or blood-sugar control could pose greater risks than benefits. “Take a conservative approach,” he said.

Low risk, low benefit. Less easy to manage was a 75-year-old woman with new-onset diabetes, none of the associated cardiovascular risk factors (no hypertension or dyslipidemia), no other comorbidities, and no functional impairment. She's at low risk, but would she benefit from intensive therapy to lower her HbA_1c level below 6.5%? “We don't have evidence yet that such a patient will benefit from intensive glycemic control,” Dr. Florez said.

High risk, low benefit. Another tough call was a 72-year-old man with long-standing diabetes of 18 years' duration, a history of multiple hypoglycemic episodes, and complications related to diabetes, including recurrent foot ulcers and retinopathy. Intensive therapy for blood glucose levels, lipids, and blood pressure probably would seem indicated, except that he also had major cognitive deficits. Unless a spouse, or other caregiver can aggressively monitor therapy, intensive treatment poses too much risk for side effects, falls, or further cognitive decline. Treat conservatively, Dr. Florez advised.

Dr. Florez has received research funding from Merck & Co., which makes medications for diabetes.

Balance the potential benefits of aggressive glycemic control against the risks from side effects and comorbidities. DR. FLOREZ

SAN FRANCISCO — The heterogeneous nature of diabetes in the elderly makes it imperative to assess each patient individually before choosing whether to use aggressive or more conservative therapy, Dr. Hermes Florez said.

Some older diabetes patients have newly diagnosed disease and are quite functional, while others have long-standing disease and significant functional decline. Older adults are more likely to have multiple comorbidities and to be taking multiple medications.

Life expectancy also is important to consider. “In a patient who has less than 5 years of life expectancy, can we be aggressive enough with intensive glycemic control to achieve a hemoglobin A1c level of less than 6.5% when that will lead to increased risk of hypoglycemic events, frequent falls, or significant functional or cognitive decline?” he asked at a a meeting sponsored by the American Diabetes Association.

Approximately 40% of adults with type 2 diabetes mellitus are 60 years or older, comprising roughly 40 million people, noted Dr. Florez, an endocrinologist at the University of Miami and the Miami Veterans Affairs Medical Center. Looked at another way, 13% of U.S. residents aged 60 years or older have been diagnosed with diabetes, and another 12% have undiagnosed diabetes.

To help chart an individual's management plan, balance the potential benefits of aggressive glycemic control against the risks from comorbidities, medication side effects, and geriatric syndromes such as dementia, incontinence, and depression, he advised.

Published data suggest that 46% of elderly patients with type 2 diabetes have five or more comorbidities, most commonly cardiovascular problems including hypertension, lipid disorders, or coronary atherosclerosis. Older patients with diabetes and five or more comorbidities are at increased risk for hospitalizations that could have been prevented and that are two to three times longer, compared with hospitalizations of patients who have diabetes alone.

Dr. Florez described the following sample cases, which highlight treatment choices:

Low risk, high benefit. Aggressive treatment was an easy decision for a 70-year-old woman with a 20-year history of diabetes who also had hypertension, lipid abnormalities, and early appearance of retinopathy but who functioned well independently and had no other comorbidities. “She's low risk, with potential for high benefit” from aggressive glycemic control, he said.

High risk, low benefit. The opposite was true for a 68-year-old man with a 4-year history of diabetes who also had severe cardiomyopathy with ventricular tachycardia and was unable to walk. This patient already was taking 14 medications. Intensifying treatment for better blood pressure, lipid levels, or blood-sugar control could pose greater risks than benefits. “Take a conservative approach,” he said.

Low risk, low benefit. Less easy to manage was a 75-year-old woman with new-onset diabetes, none of the associated cardiovascular risk factors (no hypertension or dyslipidemia), no other comorbidities, and no functional impairment. She's at low risk, but would she benefit from intensive therapy to lower her HbA_1c level below 6.5%? “We don't have evidence yet that such a patient will benefit from intensive glycemic control,” Dr. Florez said.

High risk, low benefit. Another tough call was a 72-year-old man with long-standing diabetes of 18 years' duration, a history of multiple hypoglycemic episodes, and complications related to diabetes, including recurrent foot ulcers and retinopathy. Intensive therapy for blood glucose levels, lipids, and blood pressure probably would seem indicated, except that he also had major cognitive deficits. Unless a spouse, or other caregiver can aggressively monitor therapy, intensive treatment poses too much risk for side effects, falls, or further cognitive decline. Treat conservatively, Dr. Florez advised.

Dr. Florez has received research funding from Merck & Co., which makes medications for diabetes.

Balance the potential benefits of aggressive glycemic control against the risks from side effects and comorbidities. DR. FLOREZ

SAN FRANCISCO — The heterogeneous nature of diabetes in the elderly makes it imperative to assess each patient individually before choosing whether to use aggressive or more conservative therapy, Dr. Hermes Florez said.

Some older diabetes patients have newly diagnosed disease and are quite functional, while others have long-standing disease and significant functional decline. Older adults are more likely to have multiple comorbidities and to be taking multiple medications.

Life expectancy also is important to consider. “In a patient who has less than 5 years of life expectancy, can we be aggressive enough with intensive glycemic control to achieve a hemoglobin A1c level of less than 6.5% when that will lead to increased risk of hypoglycemic events, frequent falls, or significant functional or cognitive decline?” he asked at a a meeting sponsored by the American Diabetes Association.

Approximately 40% of adults with type 2 diabetes mellitus are 60 years or older, comprising roughly 40 million people, noted Dr. Florez, an endocrinologist at the University of Miami and the Miami Veterans Affairs Medical Center. Looked at another way, 13% of U.S. residents aged 60 years or older have been diagnosed with diabetes, and another 12% have undiagnosed diabetes.

To help chart an individual's management plan, balance the potential benefits of aggressive glycemic control against the risks from comorbidities, medication side effects, and geriatric syndromes such as dementia, incontinence, and depression, he advised.

Published data suggest that 46% of elderly patients with type 2 diabetes have five or more comorbidities, most commonly cardiovascular problems including hypertension, lipid disorders, or coronary atherosclerosis. Older patients with diabetes and five or more comorbidities are at increased risk for hospitalizations that could have been prevented and that are two to three times longer, compared with hospitalizations of patients who have diabetes alone.

Dr. Florez described the following sample cases, which highlight treatment choices:

Low risk, high benefit. Aggressive treatment was an easy decision for a 70-year-old woman with a 20-year history of diabetes who also had hypertension, lipid abnormalities, and early appearance of retinopathy but who functioned well independently and had no other comorbidities. “She's low risk, with potential for high benefit” from aggressive glycemic control, he said.

High risk, low benefit. The opposite was true for a 68-year-old man with a 4-year history of diabetes who also had severe cardiomyopathy with ventricular tachycardia and was unable to walk. This patient already was taking 14 medications. Intensifying treatment for better blood pressure, lipid levels, or blood-sugar control could pose greater risks than benefits. “Take a conservative approach,” he said.

Low risk, low benefit. Less easy to manage was a 75-year-old woman with new-onset diabetes, none of the associated cardiovascular risk factors (no hypertension or dyslipidemia), no other comorbidities, and no functional impairment. She's at low risk, but would she benefit from intensive therapy to lower her HbA_1c level below 6.5%? “We don't have evidence yet that such a patient will benefit from intensive glycemic control,” Dr. Florez said.

High risk, low benefit. Another tough call was a 72-year-old man with long-standing diabetes of 18 years' duration, a history of multiple hypoglycemic episodes, and complications related to diabetes, including recurrent foot ulcers and retinopathy. Intensive therapy for blood glucose levels, lipids, and blood pressure probably would seem indicated, except that he also had major cognitive deficits. Unless a spouse, or other caregiver can aggressively monitor therapy, intensive treatment poses too much risk for side effects, falls, or further cognitive decline. Treat conservatively, Dr. Florez advised.

Dr. Florez has received research funding from Merck & Co., which makes medications for diabetes.

Balance the potential benefits of aggressive glycemic control against the risks from side effects and comorbidities. DR. FLOREZ

SAN FRANCISCO — Managing blood sugar, lipids, and blood pressure levels in elderly patients with diabetes is important, but don't forget to address their quality of life, Dr. Hermes Florez said at a meeting sponsored by the American Diabetes Association.

Be aware of common geriatric syndromes that affect quality of life as well as morbidity and mortality rates in people with diabetes, urged Dr. Florez, an endocrinologist at the University of Miami and the Miami Veterans Affairs Medical Center.

Screen for and treat the following geriatric syndromes as part of your routine care, he suggested.

Cognitive decline. People with diabetes have an increased risk for vascular dementia or Alzheimer's dementia, compared with people who don't have diabetes. One large study found nearly a doubling in age-adjusted risk for dementia if diabetes is present. Separate data suggest that factors that may contribute to the increased risk include chronic hyperglycemia, repeated episodes of hypoglycemia, polypharmacy, and microvascular or macrovascular complications of diabetes. There seems to be a trend toward greater likelihood of dementia with longer duration of diabetes.

Do at least a quick test for cognitive decline, such as asking the patient to draw a clock face, Dr. Florez said. If you have more time, do a more formal evaluation such as the Mini-Mental State Examination.

Polypharmacy. Although polypharmacy commonly is described as the use of five or more medications, Dr. Florez prefers to think of it as any prescription for a medication that may interact with a medication being used or with a disease it was not intended to treat. Certain antimicrobial medications interact with sulfonylureas, for example. If a patient on an ACE inhibitor for hypertension is prescribed a nonsteroidal anti-inflammatory drug for complaints of pain and stays on the latter for a year or two, a drug-drug interaction can occur that will worsen their hypertension, Dr. Florez said.

One cohort study of 418 elderly patients in Los Angeles found that 13% were taking 5 drugs and 14% were taking 10 or more drugs. Trying to intensify therapy for control of blood sugar, lipids, or blood pressure in these patients is a challenge. “Patients will be struggling to follow your instructions for additional medications,” he said, and some patients will not be able to afford all these medications.

Depression. A common syndrome in older patients with diabetes, depression of even minimal severity increases the risk for microvascular complications, disability, and mortality, compared with nondepressed patients with diabetes. Diabetes patients with depression of any severity are more likely to have poor glycemic control (hemoglobin A1c levels of 8% or higher), compared with nondepressed diabetes patients. “It's important always to ask about mood” and to assess with instruments such as the Geriatric Depression Scale, if indicated, he said.

Falls. It's also important to ask older patients about injurious falls. Frequent falls suggest that a diabetes patient is either having frequent hypoglycemic events or may have significant hyperglycemia and nocturia, increasing night-time wakening and the risk for falls on the way to the bathroom.

Look for reversible treatable causes of falls such as retinopathy, cataracts, and use of medications that can cause orthostatic hypotension, including thiazide diuretics for hypertension or α-2 blockers to treat benign prostatic hypertrophy. Ask about environmental factors in the home that may contribute to falls.

A quick, easy way to assess someone's risk for falling is to ask the patient to stand up from a chair without the use of arms. If you have more time, assessing gait and balance will provide more information.

Urinary incontinence. Poor glycemic control, heart failure, and some medications each can increase the risk of urinary incontinence. Behavioral modification can be helpful in some cases, Dr. Florez said. Poor eating habits and insufficient water intake may cause constipation that leads to urinary incontinence, which can be treated by increased intake of water and fiber.

Dr. Florez has received research funding from Merck & Co., which makes medications for diabetes.

SAN FRANCISCO — Managing blood sugar, lipids, and blood pressure levels in elderly patients with diabetes is important, but don't forget to address their quality of life, Dr. Hermes Florez said at a meeting sponsored by the American Diabetes Association.

Be aware of common geriatric syndromes that affect quality of life as well as morbidity and mortality rates in people with diabetes, urged Dr. Florez, an endocrinologist at the University of Miami and the Miami Veterans Affairs Medical Center.

Screen for and treat the following geriatric syndromes as part of your routine care, he suggested.

Cognitive decline. People with diabetes have an increased risk for vascular dementia or Alzheimer's dementia, compared with people who don't have diabetes. One large study found nearly a doubling in age-adjusted risk for dementia if diabetes is present. Separate data suggest that factors that may contribute to the increased risk include chronic hyperglycemia, repeated episodes of hypoglycemia, polypharmacy, and microvascular or macrovascular complications of diabetes. There seems to be a trend toward greater likelihood of dementia with longer duration of diabetes.

Do at least a quick test for cognitive decline, such as asking the patient to draw a clock face, Dr. Florez said. If you have more time, do a more formal evaluation such as the Mini-Mental State Examination.

Polypharmacy. Although polypharmacy commonly is described as the use of five or more medications, Dr. Florez prefers to think of it as any prescription for a medication that may interact with a medication being used or with a disease it was not intended to treat. Certain antimicrobial medications interact with sulfonylureas, for example. If a patient on an ACE inhibitor for hypertension is prescribed a nonsteroidal anti-inflammatory drug for complaints of pain and stays on the latter for a year or two, a drug-drug interaction can occur that will worsen their hypertension, Dr. Florez said.

One cohort study of 418 elderly patients in Los Angeles found that 13% were taking 5 drugs and 14% were taking 10 or more drugs. Trying to intensify therapy for control of blood sugar, lipids, or blood pressure in these patients is a challenge. “Patients will be struggling to follow your instructions for additional medications,” he said, and some patients will not be able to afford all these medications.

Depression. A common syndrome in older patients with diabetes, depression of even minimal severity increases the risk for microvascular complications, disability, and mortality, compared with nondepressed patients with diabetes. Diabetes patients with depression of any severity are more likely to have poor glycemic control (hemoglobin A1c levels of 8% or higher), compared with nondepressed diabetes patients. “It's important always to ask about mood” and to assess with instruments such as the Geriatric Depression Scale, if indicated, he said.

Falls. It's also important to ask older patients about injurious falls. Frequent falls suggest that a diabetes patient is either having frequent hypoglycemic events or may have significant hyperglycemia and nocturia, increasing night-time wakening and the risk for falls on the way to the bathroom.

Look for reversible treatable causes of falls such as retinopathy, cataracts, and use of medications that can cause orthostatic hypotension, including thiazide diuretics for hypertension or α-2 blockers to treat benign prostatic hypertrophy. Ask about environmental factors in the home that may contribute to falls.

A quick, easy way to assess someone's risk for falling is to ask the patient to stand up from a chair without the use of arms. If you have more time, assessing gait and balance will provide more information.

Urinary incontinence. Poor glycemic control, heart failure, and some medications each can increase the risk of urinary incontinence. Behavioral modification can be helpful in some cases, Dr. Florez said. Poor eating habits and insufficient water intake may cause constipation that leads to urinary incontinence, which can be treated by increased intake of water and fiber.

Dr. Florez has received research funding from Merck & Co., which makes medications for diabetes.

SAN FRANCISCO — Managing blood sugar, lipids, and blood pressure levels in elderly patients with diabetes is important, but don't forget to address their quality of life, Dr. Hermes Florez said at a meeting sponsored by the American Diabetes Association.

Be aware of common geriatric syndromes that affect quality of life as well as morbidity and mortality rates in people with diabetes, urged Dr. Florez, an endocrinologist at the University of Miami and the Miami Veterans Affairs Medical Center.

Screen for and treat the following geriatric syndromes as part of your routine care, he suggested.

Cognitive decline. People with diabetes have an increased risk for vascular dementia or Alzheimer's dementia, compared with people who don't have diabetes. One large study found nearly a doubling in age-adjusted risk for dementia if diabetes is present. Separate data suggest that factors that may contribute to the increased risk include chronic hyperglycemia, repeated episodes of hypoglycemia, polypharmacy, and microvascular or macrovascular complications of diabetes. There seems to be a trend toward greater likelihood of dementia with longer duration of diabetes.

Do at least a quick test for cognitive decline, such as asking the patient to draw a clock face, Dr. Florez said. If you have more time, do a more formal evaluation such as the Mini-Mental State Examination.

Polypharmacy. Although polypharmacy commonly is described as the use of five or more medications, Dr. Florez prefers to think of it as any prescription for a medication that may interact with a medication being used or with a disease it was not intended to treat. Certain antimicrobial medications interact with sulfonylureas, for example. If a patient on an ACE inhibitor for hypertension is prescribed a nonsteroidal anti-inflammatory drug for complaints of pain and stays on the latter for a year or two, a drug-drug interaction can occur that will worsen their hypertension, Dr. Florez said.

One cohort study of 418 elderly patients in Los Angeles found that 13% were taking 5 drugs and 14% were taking 10 or more drugs. Trying to intensify therapy for control of blood sugar, lipids, or blood pressure in these patients is a challenge. “Patients will be struggling to follow your instructions for additional medications,” he said, and some patients will not be able to afford all these medications.

Depression. A common syndrome in older patients with diabetes, depression of even minimal severity increases the risk for microvascular complications, disability, and mortality, compared with nondepressed patients with diabetes. Diabetes patients with depression of any severity are more likely to have poor glycemic control (hemoglobin A1c levels of 8% or higher), compared with nondepressed diabetes patients. “It's important always to ask about mood” and to assess with instruments such as the Geriatric Depression Scale, if indicated, he said.

Falls. It's also important to ask older patients about injurious falls. Frequent falls suggest that a diabetes patient is either having frequent hypoglycemic events or may have significant hyperglycemia and nocturia, increasing night-time wakening and the risk for falls on the way to the bathroom.

Look for reversible treatable causes of falls such as retinopathy, cataracts, and use of medications that can cause orthostatic hypotension, including thiazide diuretics for hypertension or α-2 blockers to treat benign prostatic hypertrophy. Ask about environmental factors in the home that may contribute to falls.

A quick, easy way to assess someone's risk for falling is to ask the patient to stand up from a chair without the use of arms. If you have more time, assessing gait and balance will provide more information.

Urinary incontinence. Poor glycemic control, heart failure, and some medications each can increase the risk of urinary incontinence. Behavioral modification can be helpful in some cases, Dr. Florez said. Poor eating habits and insufficient water intake may cause constipation that leads to urinary incontinence, which can be treated by increased intake of water and fiber.

Dr. Florez has received research funding from Merck & Co., which makes medications for diabetes.

SAN FRANCISCO — The new incretin mimetic exenatide and the incretin enhancer sitagliptin both have unique properties that need to be taken into account when prescribing them, American Diabetes Association president Dr. John B. Buse said at a meeting sponsored by the association.

Injections of exenatide (Byetta) were approved in 2005 as adjunctive therapy for patients with type 2 diabetes. Orally administered sitagliptin (Januvia) was approved in 2006 for use as monotherapy or in combination with metformin or thiazolidinedione for patients with type 2 diabetes.

Dr. Buse has received research funds from Amylin Pharmaceuticals and from Eli Lilly & Co., which market exenatide. He is an adviser and speaker for those companies and for Merck & Co., which markets sitagliptin.

Incretin augments glucose-stimulated insulin secretion by intestinally derived peptides. Exenatide and sitagliptin augment the incretin pathway, which appears to be attenuated in type 2 diabetes. The incretin effect is composed mainly of the peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GLP-1), which normally get inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Exenatide is a GLP-1 receptor analogue that's resistant to DPP-4 degradation and slows gastric emptying. Sitagliptin selectively inhibits DPP-4, giving the incretin enzymes a longer half-life to enhance their effects.

“We don't have long-term safety and efficacy data” for these drugs “like we do with the other four classes of medications for diabetes mellitus,” Dr. Buse cautioned.

During a question-and-answer session, Dr. Buse discussed several aspects of the use of these drugs.

▸ Combining them with insulin. “I think this is a very exciting combination,” he said, though the combination is not adequately studied in clinical trials. “It's something that at our center we use with some regularity.” Sparse data on five patients treated for 5 days with exenatide and insulin at his institution are buried in a larger study published in 2001, said Dr. Buse, professor of medicine at the University of North Carolina, Chapel Hill.

He warned against combining exenatide with rapid-acting insulin. That idea is “fraught with problems, at least from a theoretical basis,” Dr. Buse said, “and is something that I'd be exceptionally cautious about doing.”

▸ Fitting exenatide into the diabetes care algorithm. Experts are wondering whether exenatide might be a reasonable alternative to sulfonylureas or glitazones. Decisions on whether to include exenatide in treatment algorithms will depend “on whether we have data demonstrating its long-term safety and efficacy, and what the effects are on β-cell biology,” he said.

▸ Analyzing the implications of rhinorrhea as a side effect of sitagliptin. Studies of sitagliptin persistently show an elevated but low rate of rhinorrhea—around 11%, compared with 7% in placebo groups—and few other side effects. The drug affects chemokine levels, which has raised concerns that perhaps the rhinorrhea is “a hint that there are immune effects that we haven't been able to measure yet,” he said.

▸ Predicting which type 2 diabetes patients of long duration will respond to these agents. Because exenatide dramatically increases GLP-1 levels, “my guess is that virtually anybody would respond” to it, though it's unclear whether the level of response would justify two injections daily and a cost of around $200 per day, he said. Sitagliptin produces more modest increases in GLP-1 levels. “I just don't know what the effects would be in a patient who has severely impaired β-cell function,” Dr. Buse said.

▸ Considering the drugs' use in bariatric surgery patients, about which data are lacking. “Part of the benefit of bariatric surgery is you actually increase the levels of GLP-1 and perhaps other incretin hormones, so it's an intriguing notion,” Dr. Buse said. “The concern with exenatide would be the nausea from the surgery plus the nausea from the exenatide may be getting somebody in a bad place.”

▸ Predicting potential effects on gastroparesis patients. The clinical trials excluded patients with chronic, serious GI issues, “so we don't really know” the answer, he said. For some patients with intermittent “gastroparesis,” exenatide may limit their eating and help them feel better, “but it's something you want to be very cautious with,” he said.

SAN FRANCISCO — The new incretin mimetic exenatide and the incretin enhancer sitagliptin both have unique properties that need to be taken into account when prescribing them, American Diabetes Association president Dr. John B. Buse said at a meeting sponsored by the association.

Injections of exenatide (Byetta) were approved in 2005 as adjunctive therapy for patients with type 2 diabetes. Orally administered sitagliptin (Januvia) was approved in 2006 for use as monotherapy or in combination with metformin or thiazolidinedione for patients with type 2 diabetes.

Dr. Buse has received research funds from Amylin Pharmaceuticals and from Eli Lilly & Co., which market exenatide. He is an adviser and speaker for those companies and for Merck & Co., which markets sitagliptin.

Incretin augments glucose-stimulated insulin secretion by intestinally derived peptides. Exenatide and sitagliptin augment the incretin pathway, which appears to be attenuated in type 2 diabetes. The incretin effect is composed mainly of the peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GLP-1), which normally get inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Exenatide is a GLP-1 receptor analogue that's resistant to DPP-4 degradation and slows gastric emptying. Sitagliptin selectively inhibits DPP-4, giving the incretin enzymes a longer half-life to enhance their effects.

“We don't have long-term safety and efficacy data” for these drugs “like we do with the other four classes of medications for diabetes mellitus,” Dr. Buse cautioned.

During a question-and-answer session, Dr. Buse discussed several aspects of the use of these drugs.

▸ Combining them with insulin. “I think this is a very exciting combination,” he said, though the combination is not adequately studied in clinical trials. “It's something that at our center we use with some regularity.” Sparse data on five patients treated for 5 days with exenatide and insulin at his institution are buried in a larger study published in 2001, said Dr. Buse, professor of medicine at the University of North Carolina, Chapel Hill.

He warned against combining exenatide with rapid-acting insulin. That idea is “fraught with problems, at least from a theoretical basis,” Dr. Buse said, “and is something that I'd be exceptionally cautious about doing.”

▸ Fitting exenatide into the diabetes care algorithm. Experts are wondering whether exenatide might be a reasonable alternative to sulfonylureas or glitazones. Decisions on whether to include exenatide in treatment algorithms will depend “on whether we have data demonstrating its long-term safety and efficacy, and what the effects are on β-cell biology,” he said.

▸ Analyzing the implications of rhinorrhea as a side effect of sitagliptin. Studies of sitagliptin persistently show an elevated but low rate of rhinorrhea—around 11%, compared with 7% in placebo groups—and few other side effects. The drug affects chemokine levels, which has raised concerns that perhaps the rhinorrhea is “a hint that there are immune effects that we haven't been able to measure yet,” he said.

▸ Predicting which type 2 diabetes patients of long duration will respond to these agents. Because exenatide dramatically increases GLP-1 levels, “my guess is that virtually anybody would respond” to it, though it's unclear whether the level of response would justify two injections daily and a cost of around $200 per day, he said. Sitagliptin produces more modest increases in GLP-1 levels. “I just don't know what the effects would be in a patient who has severely impaired β-cell function,” Dr. Buse said.

▸ Considering the drugs' use in bariatric surgery patients, about which data are lacking. “Part of the benefit of bariatric surgery is you actually increase the levels of GLP-1 and perhaps other incretin hormones, so it's an intriguing notion,” Dr. Buse said. “The concern with exenatide would be the nausea from the surgery plus the nausea from the exenatide may be getting somebody in a bad place.”

▸ Predicting potential effects on gastroparesis patients. The clinical trials excluded patients with chronic, serious GI issues, “so we don't really know” the answer, he said. For some patients with intermittent “gastroparesis,” exenatide may limit their eating and help them feel better, “but it's something you want to be very cautious with,” he said.

SAN FRANCISCO — The new incretin mimetic exenatide and the incretin enhancer sitagliptin both have unique properties that need to be taken into account when prescribing them, American Diabetes Association president Dr. John B. Buse said at a meeting sponsored by the association.

Injections of exenatide (Byetta) were approved in 2005 as adjunctive therapy for patients with type 2 diabetes. Orally administered sitagliptin (Januvia) was approved in 2006 for use as monotherapy or in combination with metformin or thiazolidinedione for patients with type 2 diabetes.

Dr. Buse has received research funds from Amylin Pharmaceuticals and from Eli Lilly & Co., which market exenatide. He is an adviser and speaker for those companies and for Merck & Co., which markets sitagliptin.

Incretin augments glucose-stimulated insulin secretion by intestinally derived peptides. Exenatide and sitagliptin augment the incretin pathway, which appears to be attenuated in type 2 diabetes. The incretin effect is composed mainly of the peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GLP-1), which normally get inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Exenatide is a GLP-1 receptor analogue that's resistant to DPP-4 degradation and slows gastric emptying. Sitagliptin selectively inhibits DPP-4, giving the incretin enzymes a longer half-life to enhance their effects.

“We don't have long-term safety and efficacy data” for these drugs “like we do with the other four classes of medications for diabetes mellitus,” Dr. Buse cautioned.

During a question-and-answer session, Dr. Buse discussed several aspects of the use of these drugs.

▸ Combining them with insulin. “I think this is a very exciting combination,” he said, though the combination is not adequately studied in clinical trials. “It's something that at our center we use with some regularity.” Sparse data on five patients treated for 5 days with exenatide and insulin at his institution are buried in a larger study published in 2001, said Dr. Buse, professor of medicine at the University of North Carolina, Chapel Hill.

He warned against combining exenatide with rapid-acting insulin. That idea is “fraught with problems, at least from a theoretical basis,” Dr. Buse said, “and is something that I'd be exceptionally cautious about doing.”

▸ Fitting exenatide into the diabetes care algorithm. Experts are wondering whether exenatide might be a reasonable alternative to sulfonylureas or glitazones. Decisions on whether to include exenatide in treatment algorithms will depend “on whether we have data demonstrating its long-term safety and efficacy, and what the effects are on β-cell biology,” he said.

▸ Analyzing the implications of rhinorrhea as a side effect of sitagliptin. Studies of sitagliptin persistently show an elevated but low rate of rhinorrhea—around 11%, compared with 7% in placebo groups—and few other side effects. The drug affects chemokine levels, which has raised concerns that perhaps the rhinorrhea is “a hint that there are immune effects that we haven't been able to measure yet,” he said.

▸ Predicting which type 2 diabetes patients of long duration will respond to these agents. Because exenatide dramatically increases GLP-1 levels, “my guess is that virtually anybody would respond” to it, though it's unclear whether the level of response would justify two injections daily and a cost of around $200 per day, he said. Sitagliptin produces more modest increases in GLP-1 levels. “I just don't know what the effects would be in a patient who has severely impaired β-cell function,” Dr. Buse said.

▸ Considering the drugs' use in bariatric surgery patients, about which data are lacking. “Part of the benefit of bariatric surgery is you actually increase the levels of GLP-1 and perhaps other incretin hormones, so it's an intriguing notion,” Dr. Buse said. “The concern with exenatide would be the nausea from the surgery plus the nausea from the exenatide may be getting somebody in a bad place.”

▸ Predicting potential effects on gastroparesis patients. The clinical trials excluded patients with chronic, serious GI issues, “so we don't really know” the answer, he said. For some patients with intermittent “gastroparesis,” exenatide may limit their eating and help them feel better, “but it's something you want to be very cautious with,” he said.

SAN FRANCISCO — Angina pectoris was associated with an approximately 50% increased risk for Alzheimer's disease or dementia within 15 years in a longitudinal study of 20,146 Swedish twins.

Ulrika K. Eriksson and her associates analyzed data from the Swedish Twin Registry and found a 56% increased risk for hospitalization or death resulting from Alzheimer's disease in people with a history of angina pectoris, compared with those without angina pectoris, they reported in a poster presentation at the annual meeting of the Gerontological Society of America. The risk for hospitalization or death from dementia was 53% higher in those with angina pectoris, compared with the controls, said Ms. Eriksson, a doctoral student in medical epidemiology and biostatistics at Karolinska Institutet, Stockholm.

The increased risk was more prominent in women. Women with angina pectoris had a significant 64% increased risk for Alzheimer's disease, compared with women without angina pectoris, but an increased risk for dementia was not significant. Increased risks for Alzheimer's disease and dementia in men with angina pectoris also were not statistically significant.

In previous studies, some risk factors for coronary artery disease have been associated with increased risk for future dementia, she noted.

The Swedish Twin Registry is an ongoing database of twins born in 1903, 1925, and 1936. Questionnaires mailed to the twins in 1963, 1967, and 1973 identified 8% as having a history of angina. The investigators linked two population-based registries to identify hospitalizations or deaths primarily caused by dementia from 1974 to 2001. In all, 5% of the cohort was diagnosed with dementia, 68% of which was Alzheimer's disease.

The increased risk for Alzheimer's disease or dementia in people with angina was significant in the first 15 years (1974–1989) but not for the entire 28-year follow-up period. The increased risk in women with angina also occurred in the first 15 years of follow-up only. These differences over time may be a result of survival bias, the investigators said.

The results were adjusted for age, smoking, education, and BMI. By matching twin pairs in co-twin controls, the investigators adjusted for early life factors and genetic confounding.

SAN FRANCISCO — Angina pectoris was associated with an approximately 50% increased risk for Alzheimer's disease or dementia within 15 years in a longitudinal study of 20,146 Swedish twins.

Ulrika K. Eriksson and her associates analyzed data from the Swedish Twin Registry and found a 56% increased risk for hospitalization or death resulting from Alzheimer's disease in people with a history of angina pectoris, compared with those without angina pectoris, they reported in a poster presentation at the annual meeting of the Gerontological Society of America. The risk for hospitalization or death from dementia was 53% higher in those with angina pectoris, compared with the controls, said Ms. Eriksson, a doctoral student in medical epidemiology and biostatistics at Karolinska Institutet, Stockholm.

The increased risk was more prominent in women. Women with angina pectoris had a significant 64% increased risk for Alzheimer's disease, compared with women without angina pectoris, but an increased risk for dementia was not significant. Increased risks for Alzheimer's disease and dementia in men with angina pectoris also were not statistically significant.

In previous studies, some risk factors for coronary artery disease have been associated with increased risk for future dementia, she noted.

The Swedish Twin Registry is an ongoing database of twins born in 1903, 1925, and 1936. Questionnaires mailed to the twins in 1963, 1967, and 1973 identified 8% as having a history of angina. The investigators linked two population-based registries to identify hospitalizations or deaths primarily caused by dementia from 1974 to 2001. In all, 5% of the cohort was diagnosed with dementia, 68% of which was Alzheimer's disease.

The increased risk for Alzheimer's disease or dementia in people with angina was significant in the first 15 years (1974–1989) but not for the entire 28-year follow-up period. The increased risk in women with angina also occurred in the first 15 years of follow-up only. These differences over time may be a result of survival bias, the investigators said.

The results were adjusted for age, smoking, education, and BMI. By matching twin pairs in co-twin controls, the investigators adjusted for early life factors and genetic confounding.

SAN FRANCISCO — Angina pectoris was associated with an approximately 50% increased risk for Alzheimer's disease or dementia within 15 years in a longitudinal study of 20,146 Swedish twins.

Ulrika K. Eriksson and her associates analyzed data from the Swedish Twin Registry and found a 56% increased risk for hospitalization or death resulting from Alzheimer's disease in people with a history of angina pectoris, compared with those without angina pectoris, they reported in a poster presentation at the annual meeting of the Gerontological Society of America. The risk for hospitalization or death from dementia was 53% higher in those with angina pectoris, compared with the controls, said Ms. Eriksson, a doctoral student in medical epidemiology and biostatistics at Karolinska Institutet, Stockholm.

The increased risk was more prominent in women. Women with angina pectoris had a significant 64% increased risk for Alzheimer's disease, compared with women without angina pectoris, but an increased risk for dementia was not significant. Increased risks for Alzheimer's disease and dementia in men with angina pectoris also were not statistically significant.

In previous studies, some risk factors for coronary artery disease have been associated with increased risk for future dementia, she noted.

The Swedish Twin Registry is an ongoing database of twins born in 1903, 1925, and 1936. Questionnaires mailed to the twins in 1963, 1967, and 1973 identified 8% as having a history of angina. The investigators linked two population-based registries to identify hospitalizations or deaths primarily caused by dementia from 1974 to 2001. In all, 5% of the cohort was diagnosed with dementia, 68% of which was Alzheimer's disease.

The increased risk for Alzheimer's disease or dementia in people with angina was significant in the first 15 years (1974–1989) but not for the entire 28-year follow-up period. The increased risk in women with angina also occurred in the first 15 years of follow-up only. These differences over time may be a result of survival bias, the investigators said.

The results were adjusted for age, smoking, education, and BMI. By matching twin pairs in co-twin controls, the investigators adjusted for early life factors and genetic confounding.

SAN FRANCISCO — Magnetic resonance imaging is often ordered before patients are referred for total knee arthroplasty, yet MRI confers minimal or no benefit, compared with taking weight-bearing and skyline patella-view x-rays of patients with osteoarthritis of the knee, according to Dr. Wayne M. Goldstein.

In a random sample of 50 patients referred for total knee arthroplasty within the past 2 years, Dr. Goldstein and his associates found that 32 had MRI of the knee. Most patients got no x-rays prior to the MRI. Given that knee MRI costs approximately 10 times more than x-rays, this is an example of wasteful spending in the health care industry, according to Dr. Goldstein, who reported the study results in a poster presentation at the annual meeting of the American Academy of Orthopaedic Surgeons.

“Possibly due to lack of musculoskeletal education, or possibly as a result of financial incentive due to ownership, MRI is sometimes ordered instead of x-rays. This study suggests the need for strict guidelines or credentialing of those who order musculoskeletal MRIs,” said Dr. Goldstein of the University of Illinois, Chicago, and the Illinois Bone and Joint Institute, Morton Grove, Ill.

In their review, Dr. Goldstein and his associates determined whether patients had undergone MRIs by reviewing chart data and by calling the referring physicians. Patients in the study all had x-ray evidence of bone-on-bone articulation in one or more compartments.

“The patient is often referred by the primary care physician with the finding of 'torn meniscus,' and many patients expect an arthroscopy and seem upset that the orthopedic surgeon does not use the MRIs to make the diagnosis and direct treatment,” he said.

An MRI can be useful in rare cases, usually in elderly women, to diagnose spontaneous osteonecrosis of the knee or a stress fracture. An example would be an elderly woman with a history of sudden onset of knee pain, especially on weight bearing, with localized tenderness on physical examination and normal findings on a complete series of x-rays.

This narrow usefulness of knee MRI “is, unfortunately, not apparent to a very small segment of orthopedic surgeons,” who were among the referring physicians in the study, Dr. Goldstein said.

Dr. Goldstein routinely obtains radiographs of patients with knee osteoarthritis, including weight bearing and Rosenberg notch views. At his private group practice in Illinois, the charge for an MRI in 2007 was $1,116 (CPT code 73721), compared with $136 for a four-view x-ray series of the knee for arthritis (CPT code 73564). Medicare in 2007 reimbursed $471 for knee MRI and $42 for the x-ray series. In 2008, Medicare decreased reimbursement for the knee MRI to $457 and increased reimbursement for the radiographs to $43. Reimbursement for knee MRI can be significantly higher from commercial insurers.

Medical imaging comprises 10%–15% of Medicare payments to physicians today, compared with 5% a decade ago, and Medicare imaging costs are expected to keep growing at an annual rate of 20% or higher—outpacing the growth in cost for prescription drugs, Dr. Goldstein noted. “Overutilization of MRI contributes to cost, especially in a radiographically proven osteoarthritic knee,” he said.

Osteoarthritis of the knee is a poor indication for MRI when a series of radiographs (example radiograph shown) will suffice. Courtesy Dr. Wayne M. Goldstein

SAN FRANCISCO — Magnetic resonance imaging is often ordered before patients are referred for total knee arthroplasty, yet MRI confers minimal or no benefit, compared with taking weight-bearing and skyline patella-view x-rays of patients with osteoarthritis of the knee, according to Dr. Wayne M. Goldstein.

In a random sample of 50 patients referred for total knee arthroplasty within the past 2 years, Dr. Goldstein and his associates found that 32 had MRI of the knee. Most patients got no x-rays prior to the MRI. Given that knee MRI costs approximately 10 times more than x-rays, this is an example of wasteful spending in the health care industry, according to Dr. Goldstein, who reported the study results in a poster presentation at the annual meeting of the American Academy of Orthopaedic Surgeons.

“Possibly due to lack of musculoskeletal education, or possibly as a result of financial incentive due to ownership, MRI is sometimes ordered instead of x-rays. This study suggests the need for strict guidelines or credentialing of those who order musculoskeletal MRIs,” said Dr. Goldstein of the University of Illinois, Chicago, and the Illinois Bone and Joint Institute, Morton Grove, Ill.

In their review, Dr. Goldstein and his associates determined whether patients had undergone MRIs by reviewing chart data and by calling the referring physicians. Patients in the study all had x-ray evidence of bone-on-bone articulation in one or more compartments.

“The patient is often referred by the primary care physician with the finding of 'torn meniscus,' and many patients expect an arthroscopy and seem upset that the orthopedic surgeon does not use the MRIs to make the diagnosis and direct treatment,” he said.

An MRI can be useful in rare cases, usually in elderly women, to diagnose spontaneous osteonecrosis of the knee or a stress fracture. An example would be an elderly woman with a history of sudden onset of knee pain, especially on weight bearing, with localized tenderness on physical examination and normal findings on a complete series of x-rays.

This narrow usefulness of knee MRI “is, unfortunately, not apparent to a very small segment of orthopedic surgeons,” who were among the referring physicians in the study, Dr. Goldstein said.

Dr. Goldstein routinely obtains radiographs of patients with knee osteoarthritis, including weight bearing and Rosenberg notch views. At his private group practice in Illinois, the charge for an MRI in 2007 was $1,116 (CPT code 73721), compared with $136 for a four-view x-ray series of the knee for arthritis (CPT code 73564). Medicare in 2007 reimbursed $471 for knee MRI and $42 for the x-ray series. In 2008, Medicare decreased reimbursement for the knee MRI to $457 and increased reimbursement for the radiographs to $43. Reimbursement for knee MRI can be significantly higher from commercial insurers.

Medical imaging comprises 10%–15% of Medicare payments to physicians today, compared with 5% a decade ago, and Medicare imaging costs are expected to keep growing at an annual rate of 20% or higher—outpacing the growth in cost for prescription drugs, Dr. Goldstein noted. “Overutilization of MRI contributes to cost, especially in a radiographically proven osteoarthritic knee,” he said.

Osteoarthritis of the knee is a poor indication for MRI when a series of radiographs (example radiograph shown) will suffice. Courtesy Dr. Wayne M. Goldstein

SAN FRANCISCO — Magnetic resonance imaging is often ordered before patients are referred for total knee arthroplasty, yet MRI confers minimal or no benefit, compared with taking weight-bearing and skyline patella-view x-rays of patients with osteoarthritis of the knee, according to Dr. Wayne M. Goldstein.

In a random sample of 50 patients referred for total knee arthroplasty within the past 2 years, Dr. Goldstein and his associates found that 32 had MRI of the knee. Most patients got no x-rays prior to the MRI. Given that knee MRI costs approximately 10 times more than x-rays, this is an example of wasteful spending in the health care industry, according to Dr. Goldstein, who reported the study results in a poster presentation at the annual meeting of the American Academy of Orthopaedic Surgeons.

“Possibly due to lack of musculoskeletal education, or possibly as a result of financial incentive due to ownership, MRI is sometimes ordered instead of x-rays. This study suggests the need for strict guidelines or credentialing of those who order musculoskeletal MRIs,” said Dr. Goldstein of the University of Illinois, Chicago, and the Illinois Bone and Joint Institute, Morton Grove, Ill.

In their review, Dr. Goldstein and his associates determined whether patients had undergone MRIs by reviewing chart data and by calling the referring physicians. Patients in the study all had x-ray evidence of bone-on-bone articulation in one or more compartments.

“The patient is often referred by the primary care physician with the finding of 'torn meniscus,' and many patients expect an arthroscopy and seem upset that the orthopedic surgeon does not use the MRIs to make the diagnosis and direct treatment,” he said.

An MRI can be useful in rare cases, usually in elderly women, to diagnose spontaneous osteonecrosis of the knee or a stress fracture. An example would be an elderly woman with a history of sudden onset of knee pain, especially on weight bearing, with localized tenderness on physical examination and normal findings on a complete series of x-rays.

This narrow usefulness of knee MRI “is, unfortunately, not apparent to a very small segment of orthopedic surgeons,” who were among the referring physicians in the study, Dr. Goldstein said.

Dr. Goldstein routinely obtains radiographs of patients with knee osteoarthritis, including weight bearing and Rosenberg notch views. At his private group practice in Illinois, the charge for an MRI in 2007 was $1,116 (CPT code 73721), compared with $136 for a four-view x-ray series of the knee for arthritis (CPT code 73564). Medicare in 2007 reimbursed $471 for knee MRI and $42 for the x-ray series. In 2008, Medicare decreased reimbursement for the knee MRI to $457 and increased reimbursement for the radiographs to $43. Reimbursement for knee MRI can be significantly higher from commercial insurers.

Medical imaging comprises 10%–15% of Medicare payments to physicians today, compared with 5% a decade ago, and Medicare imaging costs are expected to keep growing at an annual rate of 20% or higher—outpacing the growth in cost for prescription drugs, Dr. Goldstein noted. “Overutilization of MRI contributes to cost, especially in a radiographically proven osteoarthritic knee,” he said.

Osteoarthritis of the knee is a poor indication for MRI when a series of radiographs (example radiograph shown) will suffice. Courtesy Dr. Wayne M. Goldstein

SAN FRANCISCO — Telling a man that he has prostate cancer can give him a heart attack—literally, Dr. Fang Fang said at a symposium on genitourinary cancers.

Men given a diagnosis of prostate cancer were 50% more likely to have a myocardial infarction during the following year compared with men not diagnosed with prostate cancer in an analysis of data from more than 5 million Swedish men, reported Dr. Fang of the Karolinska Institutet, Stockholm, and her associates.

The risk of dying from a cardiovascular event also was 50% higher in the year after a prostate cancer diagnosis compared with no prostate cancer detection in the study, which used data from 1961 through 2004.

In the referent group with no diagnosis of prostate cancer, the investigators calculated 94,044,274 person-years and 883,736 fatal cardiovascular events. Meanwhile, men with a diagnosis of prostate cancer accounted for 149,982 person-years and 7,429 fatal cardiovascular events, for a relative risk of 1.5.

Until 1990, the risk of being hospitalized for cardiovascular problems was 30% higher in the year after diagnosis of prostate cancer.

The first week in particular was a critical time, especially in younger men and in those with no previous history of cardiovascular disease.

“Diagnosis of prostate cancer is a severely stressful event illustrated in the increased risk of death from cardiovascular events immediately following diagnosis,” Dr. Fang said.

“Clinical practice, including careful delivery of the diagnostic message and supportive services offered immediately after the diagnosis, may benefit this vulnerable group of patients,” she said.

Previous studies have linked emotional stress from some life events to cardiovascular morbidity and mortality. Deaths caused by cardiovascular problems increased two- to threefold after a 1994 earthquake in Los Angeles compared with population data from the previous 3 years, she noted.

The death of a child, physiologic challenges, even the excitement of World Cup Soccer matches have been associated with increased cardiovascular risk.

The current study used data from several Swedish national registries to look at the association between prostate cancer diagnosis and cardiovascular risk.

In the first week after learning of their prostate cancer diagnosis, men had an eightfold increased risk of dying of cardiovascular events, compared with men with no prostate cancer; the investigators reached this conclusion after adjusting for effects of age and calendar year of diagnosis.

As time went by during the year following diagnosis, the risk of a fatal cardiovascular event remained elevated but fell—to a quadrupled risk out to the end of the month after diagnosis, a 40% increased risk out to the 6-month mark, and a 10% increased risk for the rest of that first year.

Men aged 54 years or younger were nine times more likely to die from cardiovascular events within a year of prostate cancer diagnosis compared with men who had no prostate cancer. That relative risk also remained elevated but decreased with age—to a twofold risk in men aged 55–74 years and a 30% increased risk in men aged 75 years or older.

Among men diagnosed with prostate cancer, those with no personal history of cardiovascular disease were 50% more likely to have a myocardial infarction in the year after diagnosis compared with men with a history of cardiovascular disease.

The risk for thrombosis increased more than threefold, and risks for stroke or other heart disease also increased in the year following prostate cancer diagnosis when men with no history of cardiovascular disease were compared with those who had a history of cardiovascular problems.

By time period, the risk of cardiovascular death after prostate cancer diagnosis was highest during 1961–1970, tripling in men diagnosed with the cancer compared with those with no diagnosis. That declined to a twofold increased risk of a fatal cardiovascular event after prostate cancer diagnosis during 1971–1980, and a 30% increased risk with diagnosis during 1981–1990, compared with men without prostate cancer.

From 1991 on, “the relative risk for fatal cardiovascular disease went flat” and was no different in men who were or were not diagnosed with prostate cancer. “What happened here?” Dr. Fang asked rhetorically.

But the risk of a nonfatal cardiovascular event still was 14% higher for men in the year following a prostate cancer diagnosis compared with men not diagnosed with prostate cancer.

Despite a leveling of the mortality risk, according to the most recent data, Dr. Fang indicated the risk of cardiovascular events remains a concern, which should be addressed with counseling and other supportive services.

The risks associated with age and the calendar year of diagnosis remained after adjustment of each category for the effects of calendar year or age.

The symposium was sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

SAN FRANCISCO — Telling a man that he has prostate cancer can give him a heart attack—literally, Dr. Fang Fang said at a symposium on genitourinary cancers.

Men given a diagnosis of prostate cancer were 50% more likely to have a myocardial infarction during the following year compared with men not diagnosed with prostate cancer in an analysis of data from more than 5 million Swedish men, reported Dr. Fang of the Karolinska Institutet, Stockholm, and her associates.

The risk of dying from a cardiovascular event also was 50% higher in the year after a prostate cancer diagnosis compared with no prostate cancer detection in the study, which used data from 1961 through 2004.

In the referent group with no diagnosis of prostate cancer, the investigators calculated 94,044,274 person-years and 883,736 fatal cardiovascular events. Meanwhile, men with a diagnosis of prostate cancer accounted for 149,982 person-years and 7,429 fatal cardiovascular events, for a relative risk of 1.5.

Until 1990, the risk of being hospitalized for cardiovascular problems was 30% higher in the year after diagnosis of prostate cancer.

The first week in particular was a critical time, especially in younger men and in those with no previous history of cardiovascular disease.

“Diagnosis of prostate cancer is a severely stressful event illustrated in the increased risk of death from cardiovascular events immediately following diagnosis,” Dr. Fang said.

“Clinical practice, including careful delivery of the diagnostic message and supportive services offered immediately after the diagnosis, may benefit this vulnerable group of patients,” she said.

Previous studies have linked emotional stress from some life events to cardiovascular morbidity and mortality. Deaths caused by cardiovascular problems increased two- to threefold after a 1994 earthquake in Los Angeles compared with population data from the previous 3 years, she noted.

The death of a child, physiologic challenges, even the excitement of World Cup Soccer matches have been associated with increased cardiovascular risk.

The current study used data from several Swedish national registries to look at the association between prostate cancer diagnosis and cardiovascular risk.

In the first week after learning of their prostate cancer diagnosis, men had an eightfold increased risk of dying of cardiovascular events, compared with men with no prostate cancer; the investigators reached this conclusion after adjusting for effects of age and calendar year of diagnosis.

As time went by during the year following diagnosis, the risk of a fatal cardiovascular event remained elevated but fell—to a quadrupled risk out to the end of the month after diagnosis, a 40% increased risk out to the 6-month mark, and a 10% increased risk for the rest of that first year.

Men aged 54 years or younger were nine times more likely to die from cardiovascular events within a year of prostate cancer diagnosis compared with men who had no prostate cancer. That relative risk also remained elevated but decreased with age—to a twofold risk in men aged 55–74 years and a 30% increased risk in men aged 75 years or older.

Among men diagnosed with prostate cancer, those with no personal history of cardiovascular disease were 50% more likely to have a myocardial infarction in the year after diagnosis compared with men with a history of cardiovascular disease.

The risk for thrombosis increased more than threefold, and risks for stroke or other heart disease also increased in the year following prostate cancer diagnosis when men with no history of cardiovascular disease were compared with those who had a history of cardiovascular problems.

By time period, the risk of cardiovascular death after prostate cancer diagnosis was highest during 1961–1970, tripling in men diagnosed with the cancer compared with those with no diagnosis. That declined to a twofold increased risk of a fatal cardiovascular event after prostate cancer diagnosis during 1971–1980, and a 30% increased risk with diagnosis during 1981–1990, compared with men without prostate cancer.

From 1991 on, “the relative risk for fatal cardiovascular disease went flat” and was no different in men who were or were not diagnosed with prostate cancer. “What happened here?” Dr. Fang asked rhetorically.

But the risk of a nonfatal cardiovascular event still was 14% higher for men in the year following a prostate cancer diagnosis compared with men not diagnosed with prostate cancer.

Despite a leveling of the mortality risk, according to the most recent data, Dr. Fang indicated the risk of cardiovascular events remains a concern, which should be addressed with counseling and other supportive services.

The risks associated with age and the calendar year of diagnosis remained after adjustment of each category for the effects of calendar year or age.

The symposium was sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

SAN FRANCISCO — Telling a man that he has prostate cancer can give him a heart attack—literally, Dr. Fang Fang said at a symposium on genitourinary cancers.

Men given a diagnosis of prostate cancer were 50% more likely to have a myocardial infarction during the following year compared with men not diagnosed with prostate cancer in an analysis of data from more than 5 million Swedish men, reported Dr. Fang of the Karolinska Institutet, Stockholm, and her associates.

The risk of dying from a cardiovascular event also was 50% higher in the year after a prostate cancer diagnosis compared with no prostate cancer detection in the study, which used data from 1961 through 2004.

In the referent group with no diagnosis of prostate cancer, the investigators calculated 94,044,274 person-years and 883,736 fatal cardiovascular events. Meanwhile, men with a diagnosis of prostate cancer accounted for 149,982 person-years and 7,429 fatal cardiovascular events, for a relative risk of 1.5.

Until 1990, the risk of being hospitalized for cardiovascular problems was 30% higher in the year after diagnosis of prostate cancer.

The first week in particular was a critical time, especially in younger men and in those with no previous history of cardiovascular disease.

“Diagnosis of prostate cancer is a severely stressful event illustrated in the increased risk of death from cardiovascular events immediately following diagnosis,” Dr. Fang said.

“Clinical practice, including careful delivery of the diagnostic message and supportive services offered immediately after the diagnosis, may benefit this vulnerable group of patients,” she said.

Previous studies have linked emotional stress from some life events to cardiovascular morbidity and mortality. Deaths caused by cardiovascular problems increased two- to threefold after a 1994 earthquake in Los Angeles compared with population data from the previous 3 years, she noted.

The death of a child, physiologic challenges, even the excitement of World Cup Soccer matches have been associated with increased cardiovascular risk.

The current study used data from several Swedish national registries to look at the association between prostate cancer diagnosis and cardiovascular risk.

In the first week after learning of their prostate cancer diagnosis, men had an eightfold increased risk of dying of cardiovascular events, compared with men with no prostate cancer; the investigators reached this conclusion after adjusting for effects of age and calendar year of diagnosis.

As time went by during the year following diagnosis, the risk of a fatal cardiovascular event remained elevated but fell—to a quadrupled risk out to the end of the month after diagnosis, a 40% increased risk out to the 6-month mark, and a 10% increased risk for the rest of that first year.

Men aged 54 years or younger were nine times more likely to die from cardiovascular events within a year of prostate cancer diagnosis compared with men who had no prostate cancer. That relative risk also remained elevated but decreased with age—to a twofold risk in men aged 55–74 years and a 30% increased risk in men aged 75 years or older.

Among men diagnosed with prostate cancer, those with no personal history of cardiovascular disease were 50% more likely to have a myocardial infarction in the year after diagnosis compared with men with a history of cardiovascular disease.

The risk for thrombosis increased more than threefold, and risks for stroke or other heart disease also increased in the year following prostate cancer diagnosis when men with no history of cardiovascular disease were compared with those who had a history of cardiovascular problems.

By time period, the risk of cardiovascular death after prostate cancer diagnosis was highest during 1961–1970, tripling in men diagnosed with the cancer compared with those with no diagnosis. That declined to a twofold increased risk of a fatal cardiovascular event after prostate cancer diagnosis during 1971–1980, and a 30% increased risk with diagnosis during 1981–1990, compared with men without prostate cancer.

From 1991 on, “the relative risk for fatal cardiovascular disease went flat” and was no different in men who were or were not diagnosed with prostate cancer. “What happened here?” Dr. Fang asked rhetorically.

But the risk of a nonfatal cardiovascular event still was 14% higher for men in the year following a prostate cancer diagnosis compared with men not diagnosed with prostate cancer.

Despite a leveling of the mortality risk, according to the most recent data, Dr. Fang indicated the risk of cardiovascular events remains a concern, which should be addressed with counseling and other supportive services.

The risks associated with age and the calendar year of diagnosis remained after adjustment of each category for the effects of calendar year or age.

The symposium was sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

SAN FRANCISCO — Adjuvant androgen deprivation therapy with a gonadotropin-releasing hormone agonist did not increase deaths from cardiovascular causes in a randomized, controlled clinical trial that enrolled 945 men with locally advanced prostate cancer from 1987 to 1992.

“There's been growing concern about potential adverse effects from the use of hormonal therapy in prostate cancer,” said Dr. Jason A. Efstathiou, lead author of a new analysis that made the finding. “This study perhaps provides some evidence to put at ease some of those concerns.”

Dr. Efstathiou of Harvard Medical School, Boston, has no association with companies that make gonadotropin-releasing hormone (GnRH) agonists.

He presented the study at a symposium on genitourinary cancers sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

He and his associates analyzed data from the Radiation Therapy Oncology Group (RTOG) 85–31 study, a large, multicenter, prospective, randomized, controlled trial that compared radiotherapy for locally advanced prostate cancer to radiotherapy plus adjuvant goserelin. The 477 patients randomized to combination therapy took goserelin for a median of 4 years. In the radiotherapy-alone arm, 64% of 468 patients received salvage GnRH agonist therapy for a median of 3 years after the end of radiotherapy.

During a median follow-up of 8 years, 574 men died in the trial, 117 (20%) of them from cardiovascular-related causes. The treatment groups did not differ significantly in the rate of cardiovascular-related deaths, Dr. Efstathiou reported. In the combination therapy group, 65 (14%) men died from cardiovascular causes; meanwhile, there were 52 (11%) cardiovascular-related deaths in the radiotherapy-alone group.

The 9-year cumulative cardiovascular mortality rates were 8% for men who received adjuvant goserelin, and 11% for men treated without adjuvant goserelin. The 5-year cumulative incidence of cardiovascular mortality was 6.5% with adjuvant goserelin and 4.1% without it. These differences between groups were not statistically significant.

The study's finding of no increase in cardiovascular-related mortality remained even when excluding patients from the radiotherapy-only group who received salvage GnRH agonist therapy, or when applying alternative definitions of cardiovascular mortality, or when imputing missing data, or when limiting the analysis to high-risk subjects.

Traditional cardiac risk factors—including the presence of cardiovascular disease or diabetes mellitus—were significantly associated with increased cardiovascular mortality.

GnRH agonist therapy has been shown to decrease the risk of death from prostate cancer in men with locally advanced prostate cancer; in some studies it decreased the all-cause mortality risk. Use of GnRH agonist therapy has increased markedly for men with prostate cancer, including those with lower-stage disease and in older men with significant competing causes of mortality, Dr. Efstathiou noted.

Two separate, large, claims-based analyses have suggested that men with prostate cancer who are treated with GnRH agonists may be at greater risk for new coronary heart disease, myocardial infarction, or diabetes (J. Clin. Oncol. 2006;24:4448–56;Cancer 2007;110:149–500). Little has been known about the potential effect of GnRH therapy on cardiovascular-related mortality, which inspired the current study.

Although it found no increase in cardiovascular-related deaths from GnRH agonist therapy, this does not exclude the possibility that GnRH agonist therapy may be associated with other problems that could lead to deaths, including diabetes, anemia, or fractures, Dr. Efstathiou said.

He received a merit award for his poster and oral presentation at the meeting.

SAN FRANCISCO — Adjuvant androgen deprivation therapy with a gonadotropin-releasing hormone agonist did not increase deaths from cardiovascular causes in a randomized, controlled clinical trial that enrolled 945 men with locally advanced prostate cancer from 1987 to 1992.

“There's been growing concern about potential adverse effects from the use of hormonal therapy in prostate cancer,” said Dr. Jason A. Efstathiou, lead author of a new analysis that made the finding. “This study perhaps provides some evidence to put at ease some of those concerns.”

Dr. Efstathiou of Harvard Medical School, Boston, has no association with companies that make gonadotropin-releasing hormone (GnRH) agonists.

He presented the study at a symposium on genitourinary cancers sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

He and his associates analyzed data from the Radiation Therapy Oncology Group (RTOG) 85–31 study, a large, multicenter, prospective, randomized, controlled trial that compared radiotherapy for locally advanced prostate cancer to radiotherapy plus adjuvant goserelin. The 477 patients randomized to combination therapy took goserelin for a median of 4 years. In the radiotherapy-alone arm, 64% of 468 patients received salvage GnRH agonist therapy for a median of 3 years after the end of radiotherapy.

During a median follow-up of 8 years, 574 men died in the trial, 117 (20%) of them from cardiovascular-related causes. The treatment groups did not differ significantly in the rate of cardiovascular-related deaths, Dr. Efstathiou reported. In the combination therapy group, 65 (14%) men died from cardiovascular causes; meanwhile, there were 52 (11%) cardiovascular-related deaths in the radiotherapy-alone group.

The 9-year cumulative cardiovascular mortality rates were 8% for men who received adjuvant goserelin, and 11% for men treated without adjuvant goserelin. The 5-year cumulative incidence of cardiovascular mortality was 6.5% with adjuvant goserelin and 4.1% without it. These differences between groups were not statistically significant.

The study's finding of no increase in cardiovascular-related mortality remained even when excluding patients from the radiotherapy-only group who received salvage GnRH agonist therapy, or when applying alternative definitions of cardiovascular mortality, or when imputing missing data, or when limiting the analysis to high-risk subjects.

Traditional cardiac risk factors—including the presence of cardiovascular disease or diabetes mellitus—were significantly associated with increased cardiovascular mortality.

GnRH agonist therapy has been shown to decrease the risk of death from prostate cancer in men with locally advanced prostate cancer; in some studies it decreased the all-cause mortality risk. Use of GnRH agonist therapy has increased markedly for men with prostate cancer, including those with lower-stage disease and in older men with significant competing causes of mortality, Dr. Efstathiou noted.

Two separate, large, claims-based analyses have suggested that men with prostate cancer who are treated with GnRH agonists may be at greater risk for new coronary heart disease, myocardial infarction, or diabetes (J. Clin. Oncol. 2006;24:4448–56;Cancer 2007;110:149–500). Little has been known about the potential effect of GnRH therapy on cardiovascular-related mortality, which inspired the current study.

Although it found no increase in cardiovascular-related deaths from GnRH agonist therapy, this does not exclude the possibility that GnRH agonist therapy may be associated with other problems that could lead to deaths, including diabetes, anemia, or fractures, Dr. Efstathiou said.

He received a merit award for his poster and oral presentation at the meeting.

SAN FRANCISCO — Adjuvant androgen deprivation therapy with a gonadotropin-releasing hormone agonist did not increase deaths from cardiovascular causes in a randomized, controlled clinical trial that enrolled 945 men with locally advanced prostate cancer from 1987 to 1992.

“There's been growing concern about potential adverse effects from the use of hormonal therapy in prostate cancer,” said Dr. Jason A. Efstathiou, lead author of a new analysis that made the finding. “This study perhaps provides some evidence to put at ease some of those concerns.”

Dr. Efstathiou of Harvard Medical School, Boston, has no association with companies that make gonadotropin-releasing hormone (GnRH) agonists.

He presented the study at a symposium on genitourinary cancers sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

He and his associates analyzed data from the Radiation Therapy Oncology Group (RTOG) 85–31 study, a large, multicenter, prospective, randomized, controlled trial that compared radiotherapy for locally advanced prostate cancer to radiotherapy plus adjuvant goserelin. The 477 patients randomized to combination therapy took goserelin for a median of 4 years. In the radiotherapy-alone arm, 64% of 468 patients received salvage GnRH agonist therapy for a median of 3 years after the end of radiotherapy.

During a median follow-up of 8 years, 574 men died in the trial, 117 (20%) of them from cardiovascular-related causes. The treatment groups did not differ significantly in the rate of cardiovascular-related deaths, Dr. Efstathiou reported. In the combination therapy group, 65 (14%) men died from cardiovascular causes; meanwhile, there were 52 (11%) cardiovascular-related deaths in the radiotherapy-alone group.

The 9-year cumulative cardiovascular mortality rates were 8% for men who received adjuvant goserelin, and 11% for men treated without adjuvant goserelin. The 5-year cumulative incidence of cardiovascular mortality was 6.5% with adjuvant goserelin and 4.1% without it. These differences between groups were not statistically significant.

The study's finding of no increase in cardiovascular-related mortality remained even when excluding patients from the radiotherapy-only group who received salvage GnRH agonist therapy, or when applying alternative definitions of cardiovascular mortality, or when imputing missing data, or when limiting the analysis to high-risk subjects.

Traditional cardiac risk factors—including the presence of cardiovascular disease or diabetes mellitus—were significantly associated with increased cardiovascular mortality.

GnRH agonist therapy has been shown to decrease the risk of death from prostate cancer in men with locally advanced prostate cancer; in some studies it decreased the all-cause mortality risk. Use of GnRH agonist therapy has increased markedly for men with prostate cancer, including those with lower-stage disease and in older men with significant competing causes of mortality, Dr. Efstathiou noted.

Two separate, large, claims-based analyses have suggested that men with prostate cancer who are treated with GnRH agonists may be at greater risk for new coronary heart disease, myocardial infarction, or diabetes (J. Clin. Oncol. 2006;24:4448–56;Cancer 2007;110:149–500). Little has been known about the potential effect of GnRH therapy on cardiovascular-related mortality, which inspired the current study.

Although it found no increase in cardiovascular-related deaths from GnRH agonist therapy, this does not exclude the possibility that GnRH agonist therapy may be associated with other problems that could lead to deaths, including diabetes, anemia, or fractures, Dr. Efstathiou said.

He received a merit award for his poster and oral presentation at the meeting.

SAN FRANCISCO — Men diagnosed with prostate cancer in the era of prostate-specific antigen screening and treated with radical prostatectomy are unlikely to die of the disease, even if they have adverse risk factors, a review of 6,398 patients found.

The patients were treated between 1987 and 2005, and had a 15-year risk of dying of prostate cancer of 12%. Their 15-year all-cause mortality rate was 38%, Dr. Andrew J. Stephenson reported at a symposium on genitourinary cancers.

The retrospective study was described as the first to assess disease-specific mortality risk in the era of prostate-specific antigen (PSA) screening.

The favorable prognosis may be a result of the effectiveness of prostatectomy or could reflect a lower degree of lethality in most screen-detected prostate cancers, said Dr. Stephenson of the Cleveland Clinic Foundation, and his associates. Before the PSA era, 15%–20% of patients treated with radical prostatectomy died of prostate cancer within the 10–15 years after treatment, population-based studies showed.

“This is important information for patients and physicians to consider when deciding upon treatment options for localized prostate cancer,” he said. “Even patients [with] an extremely low probability of cure based on a PSA criterion [PSA recurrence] still have an excellent chance of being alive 15 years after radical prostatectomy.”

Only 13% of patients had a greater than 5% risk of dying of prostate cancer within 15 years. Among patients treated since 1998, only 3% had a greater than 5% risk of prostate-specific mortality, he reported.

Risk of dying of prostate cancer ranged from 5% to 37% for patients in the lowest and highest quartiles of risk for a PSA-defined recurrence as predicted by a nomogram that was developed by the investigators and was based on five clinical characteristics, with predictions adjusted for the year of surgery.

The 6,398 patients were in a prediction modeling cohort; all had been treated by radical prostatectomy at Memorial Sloan-Kettering Cancer Center, New York, or at Baylor College of Medicine, Houston, during 1987–2005. The investigators also performed external validation of the modeling by applying it to retrospective data on 4,103 patients treated by radical prostatectomy at the Cleveland Clinic during 1989–2005.

In the modeling cohort, 2% of patients died of prostate cancer and 5% died of competing causes. In the validation cohort, 2% died of prostate cancer and 6% died of competing causes. The median follow-up in both cohorts was 48 months.

The predicted risk closely matched observed outcomes. Factors that were significantly associated with prostate-specific mortality included the biopsy Gleason grade, preoperative PSA level, clinical stage, use of neoadjuvant androgen deprivation therapy, and year of surgery.

Surgery in more recent years was associated with improvements in survival until 1998, after which the favorable impact leveled off. PSA velocity and body mass index were not associated with the risk of dying of prostate cancer.

The investigators looked further at survival by risk stratification in 9,481 patients with data using the D'Amico criteria. These criteria for assessing the risk of PSA recurrence after treatment of prostate cancer were described by Dr. Anthony V. D'Amico of Harvard Medical School, Boston (JAMA 1998;280:969–74).

Dr. Stephenson reported the 19% of patients classified as high risk comprised 79% of cancer deaths (and all cancer deaths since 1998). The 15-year risk of dying of prostate cancer in this high-risk subgroup was 19%, compared with a 31% risk of dying from competing causes. The 15-year prostate-specific mortality rate was 10% in patients classified as having intermediate risk of recurrence by D'Amico criteria, and 2% in patients with a good risk profile. The American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology sponsored the symposium.

Even patients with a low probability of cure have an excellent chance of being alive 15 years after radical prostatectomy. DR. STEPHENSON

SAN FRANCISCO — Men diagnosed with prostate cancer in the era of prostate-specific antigen screening and treated with radical prostatectomy are unlikely to die of the disease, even if they have adverse risk factors, a review of 6,398 patients found.

The patients were treated between 1987 and 2005, and had a 15-year risk of dying of prostate cancer of 12%. Their 15-year all-cause mortality rate was 38%, Dr. Andrew J. Stephenson reported at a symposium on genitourinary cancers.

The retrospective study was described as the first to assess disease-specific mortality risk in the era of prostate-specific antigen (PSA) screening.

The favorable prognosis may be a result of the effectiveness of prostatectomy or could reflect a lower degree of lethality in most screen-detected prostate cancers, said Dr. Stephenson of the Cleveland Clinic Foundation, and his associates. Before the PSA era, 15%–20% of patients treated with radical prostatectomy died of prostate cancer within the 10–15 years after treatment, population-based studies showed.

“This is important information for patients and physicians to consider when deciding upon treatment options for localized prostate cancer,” he said. “Even patients [with] an extremely low probability of cure based on a PSA criterion [PSA recurrence] still have an excellent chance of being alive 15 years after radical prostatectomy.”

Only 13% of patients had a greater than 5% risk of dying of prostate cancer within 15 years. Among patients treated since 1998, only 3% had a greater than 5% risk of prostate-specific mortality, he reported.

Risk of dying of prostate cancer ranged from 5% to 37% for patients in the lowest and highest quartiles of risk for a PSA-defined recurrence as predicted by a nomogram that was developed by the investigators and was based on five clinical characteristics, with predictions adjusted for the year of surgery.

The 6,398 patients were in a prediction modeling cohort; all had been treated by radical prostatectomy at Memorial Sloan-Kettering Cancer Center, New York, or at Baylor College of Medicine, Houston, during 1987–2005. The investigators also performed external validation of the modeling by applying it to retrospective data on 4,103 patients treated by radical prostatectomy at the Cleveland Clinic during 1989–2005.

In the modeling cohort, 2% of patients died of prostate cancer and 5% died of competing causes. In the validation cohort, 2% died of prostate cancer and 6% died of competing causes. The median follow-up in both cohorts was 48 months.

The predicted risk closely matched observed outcomes. Factors that were significantly associated with prostate-specific mortality included the biopsy Gleason grade, preoperative PSA level, clinical stage, use of neoadjuvant androgen deprivation therapy, and year of surgery.

Surgery in more recent years was associated with improvements in survival until 1998, after which the favorable impact leveled off. PSA velocity and body mass index were not associated with the risk of dying of prostate cancer.

The investigators looked further at survival by risk stratification in 9,481 patients with data using the D'Amico criteria. These criteria for assessing the risk of PSA recurrence after treatment of prostate cancer were described by Dr. Anthony V. D'Amico of Harvard Medical School, Boston (JAMA 1998;280:969–74).

Dr. Stephenson reported the 19% of patients classified as high risk comprised 79% of cancer deaths (and all cancer deaths since 1998). The 15-year risk of dying of prostate cancer in this high-risk subgroup was 19%, compared with a 31% risk of dying from competing causes. The 15-year prostate-specific mortality rate was 10% in patients classified as having intermediate risk of recurrence by D'Amico criteria, and 2% in patients with a good risk profile. The American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology sponsored the symposium.

Even patients with a low probability of cure have an excellent chance of being alive 15 years after radical prostatectomy. DR. STEPHENSON

SAN FRANCISCO — Men diagnosed with prostate cancer in the era of prostate-specific antigen screening and treated with radical prostatectomy are unlikely to die of the disease, even if they have adverse risk factors, a review of 6,398 patients found.

The patients were treated between 1987 and 2005, and had a 15-year risk of dying of prostate cancer of 12%. Their 15-year all-cause mortality rate was 38%, Dr. Andrew J. Stephenson reported at a symposium on genitourinary cancers.

The retrospective study was described as the first to assess disease-specific mortality risk in the era of prostate-specific antigen (PSA) screening.

The favorable prognosis may be a result of the effectiveness of prostatectomy or could reflect a lower degree of lethality in most screen-detected prostate cancers, said Dr. Stephenson of the Cleveland Clinic Foundation, and his associates. Before the PSA era, 15%–20% of patients treated with radical prostatectomy died of prostate cancer within the 10–15 years after treatment, population-based studies showed.

“This is important information for patients and physicians to consider when deciding upon treatment options for localized prostate cancer,” he said. “Even patients [with] an extremely low probability of cure based on a PSA criterion [PSA recurrence] still have an excellent chance of being alive 15 years after radical prostatectomy.”

Only 13% of patients had a greater than 5% risk of dying of prostate cancer within 15 years. Among patients treated since 1998, only 3% had a greater than 5% risk of prostate-specific mortality, he reported.

Risk of dying of prostate cancer ranged from 5% to 37% for patients in the lowest and highest quartiles of risk for a PSA-defined recurrence as predicted by a nomogram that was developed by the investigators and was based on five clinical characteristics, with predictions adjusted for the year of surgery.

The 6,398 patients were in a prediction modeling cohort; all had been treated by radical prostatectomy at Memorial Sloan-Kettering Cancer Center, New York, or at Baylor College of Medicine, Houston, during 1987–2005. The investigators also performed external validation of the modeling by applying it to retrospective data on 4,103 patients treated by radical prostatectomy at the Cleveland Clinic during 1989–2005.

In the modeling cohort, 2% of patients died of prostate cancer and 5% died of competing causes. In the validation cohort, 2% died of prostate cancer and 6% died of competing causes. The median follow-up in both cohorts was 48 months.

The predicted risk closely matched observed outcomes. Factors that were significantly associated with prostate-specific mortality included the biopsy Gleason grade, preoperative PSA level, clinical stage, use of neoadjuvant androgen deprivation therapy, and year of surgery.

Surgery in more recent years was associated with improvements in survival until 1998, after which the favorable impact leveled off. PSA velocity and body mass index were not associated with the risk of dying of prostate cancer.

The investigators looked further at survival by risk stratification in 9,481 patients with data using the D'Amico criteria. These criteria for assessing the risk of PSA recurrence after treatment of prostate cancer were described by Dr. Anthony V. D'Amico of Harvard Medical School, Boston (JAMA 1998;280:969–74).

Dr. Stephenson reported the 19% of patients classified as high risk comprised 79% of cancer deaths (and all cancer deaths since 1998). The 15-year risk of dying of prostate cancer in this high-risk subgroup was 19%, compared with a 31% risk of dying from competing causes. The 15-year prostate-specific mortality rate was 10% in patients classified as having intermediate risk of recurrence by D'Amico criteria, and 2% in patients with a good risk profile. The American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology sponsored the symposium.

Even patients with a low probability of cure have an excellent chance of being alive 15 years after radical prostatectomy. DR. STEPHENSON

SAN FRANCISCO — The new incretin mimetic exenatide and the incretin enhancer sitagliptin both have unique properties that need to be taken into account when prescribing them, American Diabetes Association president Dr. John B. Buse said at a meeting sponsored by the association.

Injections of exenatide (Byetta) were approved in 2005 as adjunctive therapy for patients with type 2 diabetes. Orally administered sitagliptin (Januvia) was approved in 2006 for use as monotherapy or in combination with metformin or thiazolidinedione for patients who have type 2 diabetes.

Dr. Buse has received research funds from Amylin Pharmaceuticals and from Eli Lilly & Co., which market exenatide. He is an adviser and speaker for those companies and for Merck & Co., which markets sitagliptin.

Incretin augments glucose-stimulated insulin secretion by intestinally derived peptides. Exenatide and sitagliptin augment the incretin pathway, which appears to be attenuated in type 2 diabetes. The incretin effect is composed mainly of the peptides glucose-dependent insulinotropic polypeptide and glucagonlike peptide-1 (GLP-1), which are normally inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Exenatide is a GLP-1 receptor analogue resistant to DPP-4 degradation and slows gastric emptying. Sitaglip- tin selectively inhibits DPP-4, giving the incretin enzymes a longer half-life to enhance their effects.

“We don't have long-term safety and efficacy data” for these medications “as we do with the other four classes of medications for diabetes mellitus,” cautioned Dr. Buse, who discussed several aspects of the use of these drugs.

▸ Combination with insulin. “This is a very exciting combination,” he said, though it has not been adequately studied in clinical trials. Sparse data on five patients treated for 5 days with exenatide and insulin at his institution are buried in a larger study published in 2001, said Dr. Buse, professor of medicine at the University of North Carolina, Chapel Hill. However, he warned against combining exenatide with rapid-acting insulin. “I'd be exceptionally cautious about doing [that].”

▸ Fitting exenatide into the diabetes care algorithm. Experts are wondering whether exenatide might be a reasonable alternative to sulfonylureas or glitazones. Decisions on whether to include exenatide in treatment algorithms will depend “on whether we have data demonstrating its long-term safety and efficacy, and what the effects are on ?-cell biology,” he said.

▸ Rhinorrhea as a side effect of sitagliptin. Studies of sitagliptin persistently show an elevated but low rate of rhinorrhea—around 11%, compared with 7% in placebo groups—and few other side effects. The drug affects chemokine levels, which has raised concerns that the rhinorrhea is “a hint that there are immune effects that we haven't been able to measure yet.” But many drugs are associated with an increased rate of rhinorrhea, so it could be something more benign, he added.

▸ Which patients will respond to these agents. Because exenatide dramatically increases GLP-1 levels, “my guess is that virtually anybody would respond” to it, though it's unclear whether the level of response would justify two injections daily and a cost of around $200 per day, said Dr. Buse. Sitagliptin produces more modest increases in GLP-1 levels, but “I don't know what the effects would be in a patient who has severely impaired β-cell function.”

▸ Their use in bariatric surgery patients. “Part of the benefit of bariatric surgery is you actually increase the levels of GLP-1 and perhaps other incretin hormones, so it's an intriguing notion,” Dr. Buse said. “The concern with exenatide would be the nausea from the surgery plus the nausea from the exenatide maybe getting somebody in a bad place in that regard.”

▸ Effects on gastroparesis patients. The clinical trials excluded patients with chronic, serious GI issues, “so we don't really know” the answer, he said. For some patients whose intermittent “gastroparesis” is a result of overeating that produces bloating and nausea, exenatide may limit their eating and help them feel better, “but you want to be cautious.”

SAN FRANCISCO — The new incretin mimetic exenatide and the incretin enhancer sitagliptin both have unique properties that need to be taken into account when prescribing them, American Diabetes Association president Dr. John B. Buse said at a meeting sponsored by the association.

Injections of exenatide (Byetta) were approved in 2005 as adjunctive therapy for patients with type 2 diabetes. Orally administered sitagliptin (Januvia) was approved in 2006 for use as monotherapy or in combination with metformin or thiazolidinedione for patients who have type 2 diabetes.

Dr. Buse has received research funds from Amylin Pharmaceuticals and from Eli Lilly & Co., which market exenatide. He is an adviser and speaker for those companies and for Merck & Co., which markets sitagliptin.

Incretin augments glucose-stimulated insulin secretion by intestinally derived peptides. Exenatide and sitagliptin augment the incretin pathway, which appears to be attenuated in type 2 diabetes. The incretin effect is composed mainly of the peptides glucose-dependent insulinotropic polypeptide and glucagonlike peptide-1 (GLP-1), which are normally inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Exenatide is a GLP-1 receptor analogue resistant to DPP-4 degradation and slows gastric emptying. Sitaglip- tin selectively inhibits DPP-4, giving the incretin enzymes a longer half-life to enhance their effects.

“We don't have long-term safety and efficacy data” for these medications “as we do with the other four classes of medications for diabetes mellitus,” cautioned Dr. Buse, who discussed several aspects of the use of these drugs.

▸ Combination with insulin. “This is a very exciting combination,” he said, though it has not been adequately studied in clinical trials. Sparse data on five patients treated for 5 days with exenatide and insulin at his institution are buried in a larger study published in 2001, said Dr. Buse, professor of medicine at the University of North Carolina, Chapel Hill. However, he warned against combining exenatide with rapid-acting insulin. “I'd be exceptionally cautious about doing [that].”

▸ Fitting exenatide into the diabetes care algorithm. Experts are wondering whether exenatide might be a reasonable alternative to sulfonylureas or glitazones. Decisions on whether to include exenatide in treatment algorithms will depend “on whether we have data demonstrating its long-term safety and efficacy, and what the effects are on ?-cell biology,” he said.

▸ Rhinorrhea as a side effect of sitagliptin. Studies of sitagliptin persistently show an elevated but low rate of rhinorrhea—around 11%, compared with 7% in placebo groups—and few other side effects. The drug affects chemokine levels, which has raised concerns that the rhinorrhea is “a hint that there are immune effects that we haven't been able to measure yet.” But many drugs are associated with an increased rate of rhinorrhea, so it could be something more benign, he added.

▸ Which patients will respond to these agents. Because exenatide dramatically increases GLP-1 levels, “my guess is that virtually anybody would respond” to it, though it's unclear whether the level of response would justify two injections daily and a cost of around $200 per day, said Dr. Buse. Sitagliptin produces more modest increases in GLP-1 levels, but “I don't know what the effects would be in a patient who has severely impaired β-cell function.”

▸ Their use in bariatric surgery patients. “Part of the benefit of bariatric surgery is you actually increase the levels of GLP-1 and perhaps other incretin hormones, so it's an intriguing notion,” Dr. Buse said. “The concern with exenatide would be the nausea from the surgery plus the nausea from the exenatide maybe getting somebody in a bad place in that regard.”

▸ Effects on gastroparesis patients. The clinical trials excluded patients with chronic, serious GI issues, “so we don't really know” the answer, he said. For some patients whose intermittent “gastroparesis” is a result of overeating that produces bloating and nausea, exenatide may limit their eating and help them feel better, “but you want to be cautious.”

SAN FRANCISCO — The new incretin mimetic exenatide and the incretin enhancer sitagliptin both have unique properties that need to be taken into account when prescribing them, American Diabetes Association president Dr. John B. Buse said at a meeting sponsored by the association.

Injections of exenatide (Byetta) were approved in 2005 as adjunctive therapy for patients with type 2 diabetes. Orally administered sitagliptin (Januvia) was approved in 2006 for use as monotherapy or in combination with metformin or thiazolidinedione for patients who have type 2 diabetes.

Dr. Buse has received research funds from Amylin Pharmaceuticals and from Eli Lilly & Co., which market exenatide. He is an adviser and speaker for those companies and for Merck & Co., which markets sitagliptin.

Incretin augments glucose-stimulated insulin secretion by intestinally derived peptides. Exenatide and sitagliptin augment the incretin pathway, which appears to be attenuated in type 2 diabetes. The incretin effect is composed mainly of the peptides glucose-dependent insulinotropic polypeptide and glucagonlike peptide-1 (GLP-1), which are normally inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Exenatide is a GLP-1 receptor analogue resistant to DPP-4 degradation and slows gastric emptying. Sitaglip- tin selectively inhibits DPP-4, giving the incretin enzymes a longer half-life to enhance their effects.

“We don't have long-term safety and efficacy data” for these medications “as we do with the other four classes of medications for diabetes mellitus,” cautioned Dr. Buse, who discussed several aspects of the use of these drugs.

▸ Combination with insulin. “This is a very exciting combination,” he said, though it has not been adequately studied in clinical trials. Sparse data on five patients treated for 5 days with exenatide and insulin at his institution are buried in a larger study published in 2001, said Dr. Buse, professor of medicine at the University of North Carolina, Chapel Hill. However, he warned against combining exenatide with rapid-acting insulin. “I'd be exceptionally cautious about doing [that].”

▸ Fitting exenatide into the diabetes care algorithm. Experts are wondering whether exenatide might be a reasonable alternative to sulfonylureas or glitazones. Decisions on whether to include exenatide in treatment algorithms will depend “on whether we have data demonstrating its long-term safety and efficacy, and what the effects are on ?-cell biology,” he said.

▸ Rhinorrhea as a side effect of sitagliptin. Studies of sitagliptin persistently show an elevated but low rate of rhinorrhea—around 11%, compared with 7% in placebo groups—and few other side effects. The drug affects chemokine levels, which has raised concerns that the rhinorrhea is “a hint that there are immune effects that we haven't been able to measure yet.” But many drugs are associated with an increased rate of rhinorrhea, so it could be something more benign, he added.

▸ Which patients will respond to these agents. Because exenatide dramatically increases GLP-1 levels, “my guess is that virtually anybody would respond” to it, though it's unclear whether the level of response would justify two injections daily and a cost of around $200 per day, said Dr. Buse. Sitagliptin produces more modest increases in GLP-1 levels, but “I don't know what the effects would be in a patient who has severely impaired β-cell function.”

▸ Their use in bariatric surgery patients. “Part of the benefit of bariatric surgery is you actually increase the levels of GLP-1 and perhaps other incretin hormones, so it's an intriguing notion,” Dr. Buse said. “The concern with exenatide would be the nausea from the surgery plus the nausea from the exenatide maybe getting somebody in a bad place in that regard.”

▸ Effects on gastroparesis patients. The clinical trials excluded patients with chronic, serious GI issues, “so we don't really know” the answer, he said. For some patients whose intermittent “gastroparesis” is a result of overeating that produces bloating and nausea, exenatide may limit their eating and help them feel better, “but you want to be cautious.”