Dibaetes Roundtable 2011

Leading experts weigh in on important issues in managing diabetes.

Diabetes Roundtable 2011 This Physician’s Weekly monograph provides important information to help practitioners improve their care of patients with diabetes.

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Table of Contents 14

hysical Activity Recommendations P for Patients With Diabetes — Sheri R. Colberg, PhD, FACSM

17

Detecting and Diagnosing Gestational Diabetes — Boyd E. Metzger, MD

12

Screening & Treating Diabetic Nephropathy — M. Sue Kirkman, MD

15

Incretin Therapies in Diabetes Care — Jeffrey S. Freeman, DO

17

Weight Issues When Managing Diabetes — Martha M. Funnell, MS, RN, CDE

A Message From the Editor We at Physician’s Weekly are excited to present you with a monograph dedicated to feature stories for clinicians who manage patients with diabetes as well as those who may be at risk for the disease.

In recent months, Physician’s Weekly has published a variety of news items in diabetes, with a focus on information based on clinical evidence-based research. The content in these articles relies on the expertise of our contributing physician authors. Our publication will continue to cover news and information in the field of diabetes in the coming months, and it’s our sincerest hope that you will find this information useful in your practice. Please let us know your thoughts by contacting us at keithd@physweekly.com. Thanks for reading!

Sincerely,

Keith D’Oria Editorial Director, Physician’s Weekly

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May 16, 2011 • Issue No. 19

Physical Activity Recommendations

for Patients With Diabetes Sheri R. Colberg, PhD, FACSM Professor of Exercise Science Human Movement Sciences Department Old Dominion University Adjunct Professor of Internal Medicine Eastern Virginia Medical School

The American College of Sports Medicine and American Diabetes Association have released a joint position statement for exercise in the management of patients with type 2 diabetes. Adhering to the recommendations may help providers prevent or manage diabetes and prediabetes, improve overall health, and boost quality of life.

T

he CDC estimates that 25.8 million Ameri­ cans have diabetes and another 79 million have prediabetes, a condition characterized by A1C, fasting glucose, or oral glucose tolerance levels that are higher than normal but not high enough to be classified as diabetes. Research has shown that regular physical activity (PA) may prevent or delay diabetes

and its complications, but most people with type 2 diabetes are not physically active. “PA is central to the management and prevention of type 2 diabetes and prediabetes,” says Sheri R. Colberg, PhD, FACSM. “It helps treat associated glucose, lipid, and blood pressure control abnormalities, and aids in weight loss and weight maintenance.” She adds that medica-

This Physician’s Weekly feature on physical activity recommendations for patients with diabetes was completed in cooperation with the experts at the American Diabetes Association.

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PA is central to the management and prevention of type 2 diabetes and prediabetes — Sheri R. Colberg, PhD, FACSM

tions used to control type 2 diabetes should augment lifestyle improvements rather than replace them.

Help for Healthcare Providers In the December 2010 issues of Diabetes Care zand Medicine & Science in Sports & Exercise, the American Diabetes Association and the American College of Sports Medicine issued guidelines on exercise for people with type 2 diabetes as a joint position statement. The recommendations, which were developed by Dr. Colberg and a panel of experts, are the first that were created jointly with the two organizations. They incorporated evidence-based data from published clinical studies and trials into the recommendations.

“Research has established the importance of PA to health for all individuals, but these guidelines provide specific advice for those whose diabetes may limit vigorous or other forms of exercise,” Dr. Colberg says. “Both aerobic and resistance training have been shown to improve insulin action, blood glucose control, and fat oxidation and storage in muscle. Resistance exercise can enhance skeletal muscle mass. Exercise can also improve symptoms of depression and improve health-related quality of life. Patients with diabetes who are more fit and perform more PA have lower risks of all-cause and cardiovascular mortality.”

Recommendations to Remember One of the key recommendations for patients with diabetes is to perform moderate-to-vigorous aerobic exercise for at least 150 minutes a week spread out at least 3 days during the week (Table 1). These patients should go no more than 2 consecutive days between sessions of aerobic activity. Aerobic activity alone, however, typically will not provide the full benefits of exercise. The recommendations indicate that resistance exercise (strength training) is an im-

portant component of managing diabetes. The most recent studies have reinforced the additional benefit of combining aerobic and resistance training. The recommendations also address using PA in patients with diabetes-related complications, such as cardiovascular disease, neuropathy, retinopathy, and kidney disease (Table 2).

Recommended Physical Activity for Type 2 Diabetes

Table 1

• P ersons with type 2 diabetes should undertake at least 150 min/week of moderate-to-vigorous aerobic exercise spread out during at least 3 days during the week, with no more than 2 consecutive days between bouts of aerobic activity.

• In addition to aerobic training, persons with type 2 diabetes should undertake moderate-to-vigorous resistance training at least 2–3 days/week.

• Supervised and combined aerobic and resistance training may confer additional health benefits, although milder forms of physical activity (PA), such as yoga, have shown mixed results.

- Persons with type 2 diabetes are encouraged to increase their total daily unstructured PA. - Flexibility training may be included but should not be undertaken in place of other recommended types of PA. Exercise With Non-Optimal Blood Glucose Control • I ndividuals with type 2 diabetes may engage in PA, using caution when exercising with blood glucose levels exceeding 300 mg/dL (16.7 mmol/L) without ketosis, provided they are feeling well and are adequately hydrated.

• P ersons with type 2 diabetes not using insulin or insulin secretagogues are unlikely to experience hypoglycemia related to PA. - Users of insulin and insulin secretagogues are advised to supplement with carbohydrate as needed to prevent hypoglycemia during and after exercise.

Source: Adapted from: Colberg SR, et al. Diabetes Care. 2010;33:e147-e167.

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Dr. Colberg says it is important to consider other health limitations in patients with diabetes. “Most people with type 2 diabetes don’t have sufficient aerobic capacity to undertake sustained vigorous activity for that weekly duration,” she says. “They may have orthopedic or other comorbidities that reduce their ability to meet this recommendation. Accordingly, healthcare providers need to bring patients up to speed slowly. Consider starting patients on brisk walking, gardening, or housework to motivate patients to become less sedentary. After that, ramp up the intensity and duration gradually as patients make progress.”

Physician Prescriptions Matter In the past, many physicians have appeared to be unwilling or cautious about prescribing exercise to people with diabetes for a variety of reasons. Some are concerned because their patients have excessive body weight or fear that health-related complications may have a negative effect on patients. Others may be loath to supervise exercise in their patients due to issues surrounding costs, time, and adherence.

Dr. Colberg says that physicians and healthcare providers need to change their thinking with regards to writing prescriptions for exercise and how to initiate supervised exercising, and that most individuals will not need to undergo exercise stress testing prior to starting a walking program. “The majority of people with diabetes can exercise safely, as long as certain precautions are taken,” she says. “The presence of diabetes complications should not be used as an excuse to avoid participation in PA. It’s paramount that PA be a conscious part of every person’s health plan, and physicians can take the lead by encouraging their patients by writing these prescriptions. Supervision isn’t always necessary, but it has been shown to increase compliance and improve glycemic control.”

The CDC predicts that one in three people in the United States will have diabetes by 2050, and diabe-

Exercise With Long-Term Complications of Diabetes

Table 2

• K nown cardiovascular disease is not an absolute contraindication to exercise.

- Individuals with angina classified as moderate or high risk should likely begin exercise in a supervised cardiac rehabilitation program.

- Physical activity is advised for anyone with peripheral arterial disease.

• I ndividuals with peripheral neuropathy and without acute ulceration may participate in moderate weight-bearing exercise.

- Comprehensive foot care, including daily inspection of feet and use of proper footwear, is recommended for prevention and early detection of sores or ulcers.

- Moderate walking likely does not increase risk of foot ulcers or reulceration with peripheral neuropathy.

• I ndividuals with cardiovascular autonomic neuro­pathy should be screened and receive physician approval and possibly an exercise stress test before exercise initiation.

- Exercise intensity is best prescribed using the heart rate (HR) reserve method with direct measurement of maximal HR. • I ndividuals with uncontrolled proliferative retino­pathy should avoid activities that greatly increase intraocular pressure and hemorrhage risk.

• Exercise training increases physical function and quality of life in individuals with kidney disease and may even be undertaken during dialysis sessions.

- The presence of microalbuminuria per se does not necessitate exercise restrictions.

Source: Adapted from: Colberg SR, et al. Diabetes Care. 2010;33:e147-e167.

tes and prediabetes will cost the nation nearly $500 billion annually by 2020. “The key to changing these trends is to work collaboratively to stop diabetes before it starts,” says Dr. Colberg. “Physicians and other healthcare providers must make every effort to get their patients with diabetes started with PA and increase intensity appropriately. Only with a collaborative effort will the burden of diabetes be slowed.”

Sheri R. Colberg, PhD, FACSM, has indicated to Physician’s Weekly that she has worked as a consultant for Animas Corp., Lifescan Inc., Abbott Diabetes Care, and Can-Am Care. She has also received grants/research aid from the American Diabetes Association and Lifescan Inc. For more information on this article, including references, visit www.physiciansweekly.com.

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June 20, 2011 • Issue No. 24

Detecting and Diagnosing

Gestational Diabetes

Contributing to This Article: Boyd E. Metzger, MD Tom D. Spies Professor of Metabolism and Nutrition Division of Endocrinology, Metabolism, & Molecular Medicine Northwestern University Feinberg School of Medicine

New criteria for diagnosing gestational diabetes are expected to significantly increase the prevalence of the disease, but should also increase awareness about those at risk and the need to optimize outcomes for women and their babies.

This Physician’s Weekly feature on the detection and diagnosis of gestational diabetes was completed in cooperation with the experts at the American Diabetes Association. visit www.physiciansweekly.com

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A

ccording to the CDC, the reported rates of gestational diabetes mellitus (GDM) range from 2% to 10% of all pregnancies. Immediately after pregnancy, 5% to 10% of women with GDM are found to have diabetes. In the United States, women who have had GDM have more than a 60% chance of developing diabetes in the next 10 to 20 years. Poorly controlled diabetes carries more serious risks. These risks include large size, preeclampsia, pre-term delivery, stillbirth and respiratory distress, and other problems for the newborn baby. However, optimizing blood glucose levels before and during pregnancy may reduce these risks.

“GDM used to be defined as any degree of glucose intolerance with onset or first recognition during pregnancy, whether or not the condition persisted after pregnancy, and with the possibility that unrecognized glucose intolerance may have predated or begun concomitantly with pregnancy,” explains Boyd E. Metzger, MD. “This definition led to the development of a uniform strategy for detecting and classifying GDM. The ongoing epidemic of obesity and diabetes, however, has led to more cases of type 2 diabetes in women of childbearing age. As a result, the number of pregnant women with undiagnosed type 2 diabetes has increased. As

Risk Factors for Developing Type 2 Diabetes After Gestational Diabetes

Table 1

The following have been identified as risk factors for developing type 2 diabetes after having gestational diabetes:

such, efforts should be made to screen women for diabetes at their initial prenatal visit using standard diagnostic criteria if they have risk factors for diabetes [Table 1]. When diabetes is found at this visit, women should receive a diagnosis of overt diabetes rather than GDM and treated accordingly.”

New Criteria Published research has documented that GDM carries risks for both mothers and neonates. In the American Diabetes Association’s Standards of Medical Care in Diabetes—2011, the Associa­ tion officially adopted new diagnostic criteria for GDM based largely on findings from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. This was a large-scale multinational epidemiologic study involving about 25,000 pregnant women. It demonstrated that the risk of adverse maternal, fetal, and neonatal outcomes continuously increased as a function of maternal glycemia at 24 to 28 weeks, even within glycemic ranges previously considered normal for pregnancy. For the complications examined in the study, there was no glycemic threshold for risk.

“The objective of the HAPO study was to clarify the associations of levels of maternal glucose lower than those diagnostic of diabetes with perinatal outcome,” says Dr. Metzger. “There were continuous graded relationships between higher maternal glucose and increasing frequency of the primary outcomes. These associations did not differ among centers, so the results are considered applicable to all centers and can be used globally to develop outcome-based criteria for classifying glucose metabolism in pregnancy.”

• History of gestational diabetes.

• Higher pre-pregnancy BMI. • Greater weight gain during pregnancy.

• Higher postpartum waist circumference.

• Diagnosis of gestational diabetes earlier in pregnancy.

• Higher fasting blood glucose levels during pregnancy.

• Higher readings on the 100-g oral glucose tolerance test.

Source: Adapted from: AHRQ. Gestational diabetes: caring for women during and after pregnancy. August 2009. Available at: http://effectivehealthcare.ahrq.gov/ ehc/products/107/163/2009_0804GDM_Clinician_final.pdf.

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Results from the HAPO study have led to careful reconsideration of the diagnostic criteria for GDM. The International Association of Diabetes and Pregnancy Study Groups, an international con­ sensus group with representatives from multiple obstetrical and diabetes organizations, including the American Diabetes Association, developed revised recommendations for diagnosing GDM (Table 2). The group recommended that all women not known to have diabetes undergo a 75-gram oral

Efforts should be made to screen women for diabetes at their initial prenatal visit using standard diagnostic criteria if they have risk factors for diabetes.

— Boyd E. Metzger, MD

glucose tolerance test (OGTT) at 24-to-28 weeks of gestation. Additionally, diagnostic cut points were established for the fasting, 1-hour, and 2-hour plasma glucose measurements.

“The new criteria for diagnosing GDM will sig­ nificantly increase the prevalence of the disease,” says Dr. Metzger. “This is primarily because only one abnormal value—not two—is sufficient to make a diagnosis.” The American Diabetes Association noted in its Standards of Medical Care in Diabetes—2011 that the diagnostic criteria changes were made in the context of worrisome increases in obesity and diabetes rates with the intent of optimizing gestational outcomes for women and their babies. Two randomized controlled treatment trials of “mild” GDM have shown benefit of treatment and the treatment primarily involved lifestyle changes and medical nutritional therapy. However, Dr. Metzger adds that there are few data regarding therapeutic interventions in women who will now be diagnosed with GDM based on the new diagnostic criteria. “We’ll need to design studies to determine the optimal intensity of monitoring and treatment of women with GDM diagnosed by the new criteria,” he says.

Tried and True Screening Practices As with previous recommendations from the American Diabetes Association, clinicians are

Screening For & Diagnosis of Gestational Diabetes

Table 2

• Perform a 75-g oral glucose tolerance test (OGTT), with plasma glucose measurement fasting and at 1 and 2 hours, at 24–28 weeks of gestation in women not previously diagnosed with overt diabetes.

• The OGTT should be performed in the morning after an overnight fast of at least 8 hours.

• The diagnosis of gestational diabetes is made when any of the following plasma glucose values are exceeded: - Fasting ≥92 mg/dl (5.1 mmol/l).

- 1 hour ≥180 mg/dl (10.0 mmol/l).

- 2 hour ≥153 mg/dl (8.5 mmol/l).

Source: Adapted from: American Diabetes Association. Standards of Medical Care in Diabetes—2011. Diabetes Care. 2011;34:S11-S61. Available at: http://care.diabetesjournals.org/content/34/Supplement_1/S11.full.

urged to screen women with a history of GDM for diabetes 6 to 12 weeks postpartum using non-pregnant OGTT criteria because some cases may represent preexisting undiagnosed diabetes.

“Women with a history of GDM have a greatly increased subsequent risk for diabetes and should be followed up with subsequent screening for the development of diabetes or prediabetes,” adds Dr. Metzger. “Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least every 3 years.”

Boyd E. Metzger, MD, has indicated to Physician’s Weekly that he has or has had no financial interests to report.

For more information on this article, including references, visit www.physiciansweekly.com.

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July 25, 2011 • Issue No. 28

Screening & Treating

Diabetic Nephropathy M. Sue Kirkman, MD Senior Vice President of Medical Affairs and Community Information American Diabetes Association

The incidence of diabetic nephropathy is rising throughout the United States, but being proactive about screening patients and treating them when appropriate may reduce the burden of this complication on patients and healthcare systems.

A

ccording to the American Diabetes Association, diabetic nephropathy occurs in 20% to 40% of patients with diabetes and is the single leading cause of end-stage kidney disease. Each year, more than 100,000 people are diagnosed with kidney failure, and diabetes is the most common cause, accounting for nearly 44% of new cases. Even when diabetes is controlled, it can lead to chronic kidney disease (CKD) and kidney failure. “Diabetic nephropathy takes many years to develop,” explains M. Sue Kirkman, MD. “In patients with poor glycemic control, the filtering function of the kidneys

is higher than normal in the first few years of the development of diabetes. Over several years, patients may develop small amounts of albuminuria (microalbuminuria), but the kidney’s filtration function usually remains normal during this period. Greater amounts of albuminuria (macroalbuminuria) may occur in parallel with the kidneys’ filtering function declining. As nephropathy progresses, physical changes in the kidneys can increase blood pressure, which itself further contributes to kidney damage.

As such, early detection and treatment of even mild hypertension are essential for people with diabetes.”

This Physician’s Weekly feature on screening and treating diabetic nephropathy was completed in cooperation with the experts at the American Diabetes Association.

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...Early detection and treatment of even mild hypertension are essential for people with diabetes.

— M. Sue Kirkman, MD

Screening Patients Early The American Diabetes Association recommends that every patient diagnosed with diabetes be screened for diabetic nephropathy (Table 1). “It’s better to diagnose it early and implement preventive measures at that time rather than waiting until more advanced CKD develops,” says Dr. Kirkman. An annual urine albumin assessment and a serum creatinine test with a calculation of the estimated glomerular filtration rate (eGFR) are also recommended. The annual urine albumin assessment is typically a spot urine albuminto-creatinine ratio. The serum creatinine and eGFR are tested to measure kidney function. “This second test is important because there is a fair amount of CKD that is not accompanied by albuminuria in patients with type 2 diabetes,” Dr. Kirkman says. “Simply looking for albumin excretion alone is probably not sufficient to catch kidney disease.”

A key part of screening patients with diabetes is to become aware of the risk factors for nephropathy. Patients with longer duration of diabetes, poorly con-

Table 1

trolled diabetes for long periods of time, and uncontrolled hypertension are at greater risk for diabetic nephropathy than others. Smoking and obesity have also been identified as risk factors for nephropathy.

In addition, African-Americans, Native-Americans, and Hispanics/Latinos tend to have a higher risk for CKD than other racial and ethnic groups. “When physicians see patients with these risk factors, it’s important to screen them as early as possible for diabetic nephropathy,” says Dr. Kirkman. “If kidney disease is detected, it should be addressed as part of a comprehensive approach to the treatment of diabetes.”

Preventing & Slowing Kidney Disease Great strides have been made in slowing the onset and progression of kidney disease in people with diabetes, and antihypertensive drugs have been particularly useful. “Two types of medications—ACE inhibitors and angiotensin receptor blockers (ARBs)—have proven effective in slowing the progression of CKD,” Dr. Kirkman says (Table 2). In addition to an ACE

Management of Chronic Kidney Disease in Diabetes

GFR

Recommended

All patients

• Yearly measurement of creatinine and estimated glomerular filtration rate (GFR), urinary albumin excretion, potassium.

• Referral to nephrology if possibility for non-diabetic kidney disease exists (duration of type 1 diabetes <10 years, heavy proteinuria, abnormal findings on renal ultrasound, resistant hypertension, rapid fall in GFR, or active urinary sediment).

45–60 ml/min/1.73 m2

• Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus, parathyroid hormone at least yearly • Consider need for dose adjustment of medications.

• Monitor estimated GFR every 6 months.

• Assure vitamin D sufficiency.

• C onsider bone density testing.

• Referral for dietary counseling.

30–44 ml/min/1.73 m

• Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroid hormone, hemoglobin, albumin, weight every 3–6 months.

<30 ml/min/1.73 m2

• Referral to nephrologist.

2

• Monitor estimated GFR every 3 months.

• C onsider need for dose adjustment of medications.

Source: Adapted from: American Diabetes Association. Diabetes Care. 2011;34:S11-S61.

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inhibitor or an ARB, a diuretic can be helpful in patients with salt-sensitive hypertension or fluid retention. β-blockers, calcium channel blockers, and other antihypertensives may also be needed to control blood pressure. ACE inhibitors and ARBs not only lower blood pressure, but help protect the kidneys’ glomeruli. They lower proteinuria and slow kidney deterioration even in people with diabetes who do not have hypertension. Both may also lower the risk of cardiovascular events. However, they do not seem to prevent the onset of albuminuria in patients with either type 1 or type 2 diabetes.

Excessive consumption of protein may be harmful to the kidneys, so people with CKD resulting from diabetes should consume no more than the recommended dietary allowance for protein. For people with greatly reduced kidney function, a diet containing reduced amounts of protein may help delay the onset of kidney failure. “Physicians should monitor both diet and medications closely when treating people with diabetic nephropathy,” adds Dr. Kirkman.

“Continued surveillance can assess both responses to therapy and the progression of the disease.”

Managing Complications Complications of kidney disease correlate with the level of kidney function. When eGFR levels are lower than 60 ml/min/1.73 m2, screening for complications of diabetic nephropathy should be initiated.

Early vaccination against hepatitis B is indicated in patients who are likely to progress to end-stage kidney disease. “Physicians should consider referring patients to other experts in the care of kidney disease when there is uncertainty or difficultly with management issues or if advanced kidney disease is present,” Dr. Kirkman says. “Consultation with nephrologists when late-stage kidney disease develops may reduce costs, improve quality of care, and keep people off dialysis longer. All physicians, however, can help the cause by not delaying the education of patients about the progressive nature of diabetic nephropathy as well as the importance of aggressively treating glucose, blood pressure, and other modifiable risk factors.”

Diabetic Nephropathy: Treatment Recommendations

Table 2

• I n the treatment of the non-pregnant patient with microalbuminuria or macroalbuminuria, either ACE inhibitors or ARBs should be used.

•W hile there are no adequate head-to-head comparisons of ACE inhibitors and ARBs, there is clinical trial support for each of the following statements: - In patients with type 1 diabetes, with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy.

- In patients with type 2 diabetes, hypertension, and microalbuminuria, both ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria.

- In patients with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency (serum creatinine >1.5 mg/dl), ARBs have been shown to delay the progression of nephropathy.

- If one class is not tolerated, the other should be substituted.

• R eduction of protein intake to 0.8–1.0 g · kg body wt−1 · day−1 in individuals with diabetes and the earlier stages of CKD and to 0.8 g · kg body wt−1 · day−1 in the later stages of CKD may improve measures of renal function (urine albumin excretion rate, GFR) and is recommended.

•W hen ACE inhibitors, ARBs, or diuretics are used, monitor serum creatinine and potassium levels for the development of acute kidney disease and hyperkalemia.

• C ontinued monitoring of urine albumin excretion to assess both response to therapy and progression of disease is recommended.

•W hen eGFR <60 ml/min/1.73 m2, evaluate and manage potential complications of CKD. • C onsider referral to a physician experienced in the care of kidney disease when there is uncertainty about the etiology of kidney disease (heavy proteinuria, active urine sediment, absence of retinopathy, rapid decline in GFR), difficult management issues, or advanced kidney disease.

Abbreviations: ARBs, angiotensin receptor blockers; CKD, chronic kidney disease; GFR, glomerular filtration rate; eGFR, estimated glomerular filtration rate.

Source: Adapted from: American Diabetes Association. Diabetes Care. 2011;34:S11-S61.

M. Sue Kirkman, MD, has indicated to Physician’s Weekly that she has or has had no financial interests to report.

For more information on this article, including references, visit www.physiciansweekly.com.

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May 16, 2011 â&#x20AC;˘ Issue No. 19

Incretin Therapies in Diabetes Care

Jeffrey S. Freeman, DO Professor of Internal Medicine Chairman, Division of Endocrinology and Metabolism Philadelphia College of Osteopathic Medicine

D

iabetes is an epidemic in the United States.

According to the most recent CDC estimates, the disease affects approximately 25.8 million Americans, representing 8.3% of the total population. Over the course of several years, safer and more effective therapies and treatment options have emerged to improve patient management. A greater

understanding of the pathogenesis of diabetes has led to the development of additional therapies to individualize treatment approaches.

Examining the Incretin System Type 2 diabetes is a progressive disease that results from a complex process that includes declining bcell function and insulin resistance. Other factors that play a role include unsuppressed glucagon and impaired incretin function. The role of the incretin system in diabetes has been studied for several decades, and therapeutic agents that target these hormones have become available. These incretin hormones are synthesized predominantly in the small bowel. The major incretins in humans are GLP-1 (glucagon-like polypeptide) and GIP (glucosevisit www.physiciansweekly.com

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The glucose-lowering effects of incretin based therapies can provide the most beneficial improvements if they’re used early in the course of treatment. dependent insulinotropic polypeptide). These hormones can increase insulin secretion, reduce glucagon secretion, slow gastric emptying, and enhance early satiety, all of which may ultimately improve glucose homeostasis.

Native GLP-1 has a short half-life of approximately 3 minutes and is degraded by the dipeptidyl peptidase-4 (DPP-4) enzyme. Synthetic GLP-1 agonists are not degraded by this enzyme and provide pharmacologic levels of GLP. By achieving these levels of GLP-1, delayed gastric emptying and early satiety occurs. DPP-4 inhibitors delay the breakdown of endogenous GLP-1, and therefore provide levels of GLP-1 slightly higher than normal. Both of these agents lower fasting and postprandial glucose and lower A1C. Hypoglycemia, a complication that is frequently encountered with other glucose-lowering agents, is less common with the GLP-1 receptor agonists and DPP-4 inhibitors. GLP-1 receptor agonists and DPP-4 inhibitors are the incretins that are clinically available. The GLP-1 therapies are administered via injection, while the DPP-4 inhibitors are oral agents, which are taken once daily.

Important Considerations Both the GLP-1 receptor agonists and DPP-4 inhibitors are effective therapies in drug-naïve patients as monotherapy and in combination with metformin, thiazolidinediones, sulfonylureas, and other agents. They lower fasting and postprandial glucose as well as A1C. The use of GLP-1 receptor agonists may result in weight loss. Data on the durability of these drugs are accumulating.

Research continues to accumulate on the longterm efficacy, safety, and durability of these agents.

These studies include cardiovascular disease outcomes data, effects of GLP-1 agonists in cardiac contractility, and promoting islet cell survival in islet cell transplants. DPP-4 inhibitors are available in a single pill and in combination with metformin. They are currently being studied to formulate other combinations.

Initiate Early, Educate Thoroughly The glucose-lowering effects of incretin based therapies can provide the most beneficial improvements if they’re used early in the course of treatment. There are more viable b-cells available earlier in the course of disease rather than later when the disease is well established with declining b-cell function. In particular, they can be used confidently after targets have not been achieved with metformin. The newer guidelines from the American Association of Clinical Endocrinologists recommend the use of GLP-1 and DPP-4 inhibitors throughout the course of disease. However, when A1C is above 9%, triple-drug combina­tion can be implemented.

It’s important to discuss the safety of incretinbased therapies prior to their use. This includes addressing the issues of renal safety, pancreatitis, medullary thyroid cancer, and other conditions listed and discussed in the product insert. Patients should collaborate with their healthcare team and engage in healthy lifestyle behaviors to optimize results.

Jeffrey S. Freeman, DO, has indicated to Physician’s Weekly that he has served as a paid speaker for Boehringer Ingelheim, GlaxoSmithKline, Merck, and Novo Nordisk. For more information on this article, including references, visit www.physiciansweekly.com.

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June 20, 2011 â&#x20AC;˘ Issue No. 24

Weight Issues When Managing Diabetes

Martha M. Funnell, MS, RN, CDE Research Investigator Department of Medical Education University of Michigan Medical School

P

atients with diabetes often struggle with being overweight or obese, and achieving or maintaining a healthy weight can be a serious and lifelong challenge for these individuals. Lifestyle

modifications can improve glycemic control as well as body weight, blood pressure, and lipid profiles.

However, behavioral changes are typically challenging and may require the help of others on the diabetes care team. Compounding the problem is that most patients will require multiple medications to manage their diabetes, and an unwanted side effect of some of these therapies is weight gain. This is often a special concern for many people with diabetes who are already overweight or obese. However, while there is the potential for weight gain, these medications are valuable treatments. When used properly, their benefits outweigh their risks. visit www.physiciansweekly.com

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There are several therapies for patients with diabetes that have been associated with weight loss or are weight neutral.

— Martha M. Funnell, MS, RN, CDE

The Effect of Diabetes Therapies on Weight

Educate Patients & Manage Expectations

Research has shown that insulin, sulfonylureas, and thiazolidinediones may cause weight gain in some patients with diabetes. Weight gain with diabetes medications occurs for a number of reasons. When blood glucose levels are elevated, the excess glucose is excreted through the urine. With treatment, more glucose is available to be used by the body. Any glucose not used by the cells is stored as fat. As a result, patients who continue to consume the same number of calories may gain weight. The use of insulin and sulfonylureas may cause hypoglycemia, which needs to be treated with a fast-acting source of glucose, which can add calories. Thiazolidinediones can cause fat cells to store more fatty acids from the blood, causing those fat cells to enlarge. They can also lead to fluid retention, which may increase body weight.

The side effects of weight gain or weight loss should be taken into consideration and incorporated into the conversation with the patient when considering and prescribing diabetes medications. Although healthcare providers are often limited by time constraints, it’s critical that patients understand the potential for changes in weight and strategies to prevent weight gain in order to help patients have realistic expectations about prescribed therapies. Patients should also be informed that the management of their diabetes is likely to require adjustments to their medication regimens throughout their course of treatment. Be up front about potential side effects, and educate patients on why they’re taking a particular drug and its potential benefits.

Conversely, there are several therapies for patients with diabetes that have been associated with weight loss or are weight neutral. Metformin and incretin therapies, particularly glucagon-like peptide-1 (GLP-1) receptor agonists, have been associated with weight loss in clinical studies. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to be weight neutral. While metformin, GLP-1 receptor agonists, and DPP-4 inhibitors have been associated with these benefits, it’s important to remind patients that they’re not specifically indicated for weight loss.

They’re designed, like other diabetes medications, to lower blood glucose levels.

Managing expectations is critical to ensuring patients’ trust and helping them to stick with their diabetes care plan, including taking medications.

Remind patients that the ultimate goals of the diabetes drugs they take are to help prevent or delay the complications of diabetes so that they have the best possible quality of life. Developing handouts with resources for nutritional and exercise support and other information for patients can help educate them on side effects, including the impact on weight. It’s also important to have a positive attitude with patients about their ability to manage their diabetes and their weight effectively, and offer them encouragement and support.

Martha M. Funnell, MS, RN, CDE, has indicated to Physician’s Weekly that she has worked as a consultant for Novo Nordisk, Eli Lilly and Company, sanofi-aventis, Intuity Medical, and Merck. For more information on this article, including references, visit www.physiciansweekly.com.

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