American College of Physicians: Internal Medicine — Doctors for Adults ®

Advertisement

ACP DiabetesMonthly



In the News for the month of November 2012




Highlights

CABG associated with better outcomes than stents in diabetic patients

Among diabetics, coronary artery bypass grafting (CABG) was associated with lower rates of death from any cause, myocardial infarction (MI), or stroke than percutaneous coronary intervention (PCI) with a drug-eluting stent, a study found. More...

Low glycemic index bean diet improved HbA1c, BP

Eating at least a cup of beans per day for three months lowered diabetic patients' hemoglobin A1c (HbA1c) scores and blood pressure, a new study found. More...

ADA, AGS issue consensus report on diabetes in older adults

The American Diabetes Association (ADA) and the American Geriatrics Society (AGS) released a joint consensus report last month on diabetes in older adults. More...


Test yourself

MKSAP Quiz: hypoglycemic episodes and high HbA1c

This month's quiz asks readers to evaluate a 68-year-old woman with diabetes and new-onset hypoglycemic episodes. More...


From ACP InternistWeekly

Sulfonylureas associated with higher CV risk than metformin

As initial monotherapy for type 2 diabetes, sulfonylureas were associated with more cardiovascular events and deaths than metformin, a new study found. More...


From ACP Internist

Preventing and treating diabetic nephropathy

Managing kidney disease in diabetes requires meeting individualized parameters and balancing risks in nephrology and cardiology, according to experts featured in a recent article in ACP Internist. More...


From ACP Journal Club

Intensive BP control and/or glucose control did not reduce microvascular events in hypertensive type 2 diabetes

More than 4,000 patients with type 2 diabetes, hypertension and cardiovascular disease (CVD) or CVD risk factors were randomized to a systolic blood pressure (BP) target of less than 120 mm Hg or less than 140 mm Hg. More...

Review: Quality improvement strategies reduce HbA1c, LDL cholesterol, and BP in diabetes

Researchers reviewed more than 140 randomized trials of quality improvement (QI) strategies for managing adult patients with diabetes. More...


FDA update

New drugs approved for diabetes

The first generic version of pioglitazone hydrochloride (Actos) and a new indication for ranibizumab injection (Lucentis) were recently announced by the FDA. More...


Tool of the month

Give patients advice on self-monitoring their blood glucose

Recommendations for self-monitoring vary depending on the type of diabetes and treatment regimen of individual patients. More...


Keeping tabs

Spotlight on lifestyle interventions for National Diabetes Month

World Diabetes Day is to be held on Nov. 14 and President Obama recently proclaimed November to be National Diabetes Month. More...


Physician editor: David V. O'Dell, MD, FACP



Highlights


.
CABG associated with better outcomes than stents in diabetic patients

Among diabetics, coronary artery bypass grafting (CABG) was associated with lower rates of death from any cause, myocardial infarction (MI), or stroke than percutaneous coronary intervention (PCI) with a drug-eluting stent, a study found.

From 2005 to 2010, researchers randomly assigned 1,900 patients with diabetes and multivessel coronary artery disease (83% had three-vessel disease) to undergo either PCI with drug-eluting stents or CABG. The patients were followed for at least two years (median among survivors, 3.8 years). All patients received accompanying treatment for elevated cholesterol, blood pressure or glycated hemoglobin.

Results appeared online Nov. 4 at the New England Journal of Medicine.

Overall, any of the negative outcomes occurred more frequently in the PCI group, with five-year rates of 26.6% in the PCI group and 18.7% in the CABG group (P=0.005). Death from any cause and MI were lower in the CABG group, but strokes were higher, with five-year rates of 2.4% in the PCI group versus 5.2% in the CABG group (P=0.03).

Researchers wrote, "The increased use of internal mammary grafting in these trials has been postulated to play a key role in the improved survival with CABG. When considered together, the data provide a convincing signal that PCI results in increased long-term mortality, as compared with CABG, in patients with diabetes and multivessel coronary artery disease."

An editorial commented that the trial provides compelling evidence of the comparative effectiveness of CABG versus PCI in this population. "Mortality has been consistently reduced by CABG, as compared with PCI, in more than 4,000 patients with diabetes who have been evaluated in 13 clinical trials," the editorial stated. "The controversy should finally be settled."


.
Low glycemic index bean diet improved HbA1c, BP

Eating at least a cup of beans per day for three months lowered diabetic patients' hemoglobin A1c (HbA1c) scores and blood pressure, a new study found.

The trial randomized 121 patients with type 2 diabetes to either a low glycemic index diet (increasing daily bean consumption by at least one cup per day) or a diet higher in insoluble fiber (consumption of more whole wheat products). Participants reported their consumption for three months, and the primary outcome of the study was change in HbA1c. Results were published by Archives of Internal Medicine on Oct. 22.

The bean-eating group reduced their HbA1cs by 0.5% (95% CI, 0.6% to 0.4%) compared to a 0.3% reduction (95% CI, 0.4% to 0.2%) in the whole wheat group. They also showed significant improvement in blood pressure (−4.5 mm Hg systolic [95% CI, −7.0 to −2.0 mm Hg]) and heart rate, compared to no change in the wheat-eating group. Thanks to these changes in risk factors, the bean group also had a greater reduction in their coronary heart disease risk score.

Study authors concluded that incorporating legumes into a low glycemic index diet improved blood sugar control and coronary heart disease risk scores and could perhaps be analogous to the effect of acarbose (which has been associated with reductions in hypertension). The use of whole wheat as a positive control might have minimized the treatment difference, they added. This finding could be important, especially for patients from cultures in which traditional high bean intake has been replaced with Western diets, they concluded.

However, an accompanying commentary cautioned that the observed benefits from the bean diet could also be attributed to reduced calorie intake. Evidence on the association between glycemic index or dietary fiber consumption and health of patients with type 2 diabetes has been mixed and the issue is controversial, the commentary said. Legumes can certainly be components of a healthy diet, for people with and without diabetes, but no single nutritional therapy can be proven best for all patients with diabetes, the commentary concluded.


.
ADA, AGS issue consensus report on diabetes in older adults

The American Diabetes Association (ADA) and the American Geriatrics Society (AGS) released a joint consensus report last month on diabetes in older adults.

The consensus report was developed after an ADA-convened consensus development conference in February 2012 that focused on diabetes and older adults (i.e., those at least 65 years of age). The following questions were examined:

  • What are the epidemiology and pathogenesis of diabetes in older adults?
  • What is the evidence for preventing and treating diabetes and its common comorbidities in older adults?
  • What current guidelines exist for treating diabetes in older adults?
  • What issues need to be considered in individualizing treatment recommendations for older adults?
  • What are consensus recommendations for treating older adults with or at risk for diabetes?
  • How can gaps in the evidence best be filled?

The writing group examined the evidence on screening methods for diabetes, prediabetes, and chronic diabetes complications; prevention or delay of type 2 diabetes; and interventions to treat diabetes (including glycemic control, lipid lowering and blood pressure control). It looked at existing guidelines and determined which specifically address diabetes in older adults and which do not include detailed recommendations by age group. Individualized treatment, the writing group said, should examine comorbid conditions and geriatric syndromes (including functional impairment, polypharmacy, depression, and vision and hearing impairment), nutrition issues, physical activity and fitness, and age-specific aspects of pharmacotherapy, among other factors.

The report includes a framework for determining treatment goals in regards to glycemia, blood pressure and dyslipidemia in this population, along with additional consensus recommendations for screening and prevention, management, pharmacotherapy, and care in settings outside the home. Future research, the report said, should include more frail older patients with multiple comorbidities and should focus more on "real world" settings.

The full report was co-published Oct. 25 by Diabetes Care and the Journal of the American Geriatrics Society.



Test yourself


.
MKSAP Quiz: hypoglycemic episodes and high HbA1c

A 68-year-old woman comes to the office for a follow-up evaluation. She has had type 2 diabetes mellitus for the past 13 years and has experienced two early-morning hypoglycemic episodes in the past 3 months.

mksap.jpg

Although her self-monitoring of fasting blood glucose levels over the past 6 months has consistently shown results in the 110 to 140 mg/dL (6.1 to 7.8 mmol/L) range, her hemoglobin A1c value during this same period has exceeded 8.5%. Her current diabetes regimen consists of metformin, 850 mg three times daily, and insulin detemir, 38 units at night. She has no other medical problems.

Which of the following is the most appropriate next step in management?

A. Add exenatide to her regimen.
B. Check her serum fructosamine level.
C. Increase the insulin detemir dosage.
D. Measure 2-hour postprandial glucose levels.

Click here or scroll to the bottom of the page for the answer and critique.


.

From ACP InternistWeekly


.
Sulfonylureas associated with higher CV risk than metformin

As initial monotherapy for type 2 diabetes, sulfonylureas were associated with more cardiovascular events and deaths than metformin, a new study found.

The retrospective cohort study included about 250,000 patients of the Veterans Health Administration who initiated oral therapy for diabetes and who did not have chronic kidney disease (serum creatinine of 1.5 mg/dl or greater) or other serious medical illness. About 150,000 of them took metformin and 99,000 took a sulfonylurea. The groups were compared on a composite outcome of death or hospitalization for acute myocardial infarction or stroke.

annals.jpg

Results appeared in Annals of Internal Medicine on Nov. 6.

Sulfonylurea users had 18.2 composite events per 1,000 person-years compared to 10.4 per 1,000 person-years among metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0]; adjusted hazard ratio, 1.21 [95% CI, 1.13 to 1.30]). The results were consistent when the researchers assessed subgroups by sulfonylurea type (glyburide or glipizide), cardiovascular disease history, age, body mass index, albuminuria and propensity score.

The study suggests that sulfonylureas are associated with an increased risk of cardiovascular disease events and death compared to metformin, and it supports the use of metformin as first-line therapy, the study authors concluded. They cautioned that the study is limited by its mostly white male population and that confounding by indication is a risk. It's also still unknown whether the difference in outcomes results from more harm from sulfonylureas or greater benefit from metformin. Sulfonylureas are associated with increases in weight, lipid levels and hypoglycemia compared to metformin, the authors noted.

Cardiovascular risks have been a concern with sulfonylureas for a long time, noted both the study and an accompanying editorial. A study in 1970 showed increased risk of all-cause and cardiovascular mortality with tolbutamide, but randomized trials comparing cardiovascular outcomes of diabetes drugs have been avoided since then, the editorialist said. This nonrandomized study should be considered hypothesis-generating rather than definitive, but the findings are creditable, important and have implications for millions of patients, according to the editorial.



From ACP Internist


.
Preventing and treating diabetic nephropathy

Managing kidney disease in diabetes requires meeting individualized parameters and balancing risks in nephrology and cardiology.

Learn whether more aggressive treatment is warranted in this population by reading "'Goldilocks' goal for diabetics and CKD" in the November/December ACP Internist.



From ACP Journal Club


.
Intensive BP control and/or glucose control did not reduce microvascular events in hypertensive type 2 diabetes

As part of the ACCORD trial, more than 4,000 patients with type 2 diabetes, hypertension and cardiovascular disease (CVD) or CVD risk factors were randomized to a systolic blood pressure (BP) target of less than 120 mm Hg or less than 140 mm Hg (as well as intensive and standard glycemic targets). After about four years of follow-up, no significant difference was seen between blood pressure groups on the primary composite outcome of renal failure, retinal photocoagulation or vitrectomy for retinopathy. Authors concluded that intensive blood pressure control did not reduce microvascular events more than standard control, regardless of intensity of glycemic control.

The study was published by Kidney International on March 2. The following commentary by Juan P. Brito, MD, and ACP Member Victor M. Montori, MD, MSc, was published in the ACP Journal Club section of the Oct. 16 Annals of Internal Medicine.

How far should BP be lowered to prevent microvascular complications in patients with type 2 diabetes? Favorable results from the UK Prospective Diabetes Study, which sought a BP target < 150/85 mm Hg, and from the Appropriate Blood Pressure Control in Diabetes trial, which sought a BP target < 130/80 mm Hg, supported the notion that "lower is better." However, the ACCORD-BP trial failed to find favorable results with a target systolic BP < 120 mm Hg. New microalbuminuria events were reduced by 16% (hazard ratio 0.84), but intensive BP control did not reduce the incidence of advanced kidney or eye disease, regardless of intensity of glycemic control.

These results strongly suggest that compared with more modest targets, lowering BP to < 120/80 mm Hg with current therapies may offer no benefits that patients would value but could cause serious adverse effects.

Only 124 patients developed renal failure in this study (which makes the results imprecise), and about half of those who developed renal failure and had follow-up albumin measures did not have micro- or macroalbuminuria at baseline or develop these markers during follow-up. Therefore, microalbuminuria may not be as reliable a surrogate for advanced renal outcomes as previously believed.

Although BP and glycemic control continue to play an important role in the management of patients with type 2 diabetes and hypertension, current evidence supports moderate targets and avoiding overtreatment.


.
Review: Quality improvement strategies reduce HbA1c, LDL cholesterol, and BP in diabetes

Researchers reviewed more than 140 randomized trials of quality improvement (QI) strategies for managing adult patients with diabetes. Some of the most commonly studied strategies were clinician education, case management, team changes, patient education and promotion of self-management. After conducting a meta-analysis with a random effects model, the reviewers concluded that overall the QI strategies reduced glycated hemoglobin levels, low-density lipoprotein cholesterol levels, and blood pressure compared to results in control patients.

The study was published by The Lancet on June 9. The following commentary by Sean F. Dinneen, MD, and Máire O'Donnell, PhD, was published in the ACP Journal Club section of the Oct. 16 Annals of Internal Medicine.

The health systems, institutions, and traditions within which we function often make it difficult for us to deliver care to the highest standard. QI initiatives represent an attempt to achieve these high standards within the constraints of the day-to-day working environment. The comprehensive systematic review and meta-analysis by Tricco and colleagues include studies that evaluate a wide range of QI interventions and make heartening reading. The authors report the effects of QI interventions across a wide range of outcomes, including frequency of use of certain drugs (including statins and aspirin), compliance with screening (for microvascular complications), and smoking cessation rates. QI strategies were, in general, effective over a median follow-up of 12 to 18 months. However, the effects were modest at best, as shown by only marginal—and not statistically significant—improvements in the proportion of patients achieving smoking cessation, using statins, or with control of hypertension.

An interesting aspect of the analysis is the dominance of hemoglobin A1c (HbA1c) as the preferred outcome measure in QI trials. Of 142 trials included in the review, 120 included HbA1c as an outcome; the next most common outcome measure was blood pressure (65 trials). With strategies as diverse as education of patients and health care professionals, team changes, and "facilitated relay" of clinical information included in the analysis, it seems unlikely that a biochemical measure of glycemic control will adequately reflect overall effects on care. Others have also noted an overreliance on measures of glycemic control when evaluating education programs for patients with diabetes. Nevertheless, until we devise easier-to-measure, standardized approaches for other patient-important outcomes, HbA1c will continue to be used as the primary quality measure for diabetes care.



FDA update


.
New drugs approved for diabetes

The first generic version of pioglitazone hydrochloride (Actos) was recently approved to improve blood glucose control in adults with type 2 diabetes, along with diet and exercise.

In addition, ranibizumab injection (Lucentis) received FDA approval for a new indication to treat diabetic macular edema. Clinical trials showed 34% to 45% of patients who received monthly injections of 0.3 mg gained at least three lines of vision compared with 12% to 18% of those who did not receive an injection. The most common side effects include bleeding of the conjunctiva, eye pain, floaters and increased intraocular pressure.

Representatives of the FDA also recently explained the reasoning behind their approval of two new drugs (lorcaserin and fixed dose combination of phentermine-topiramate) for chronic weight management in a perspective article in the Oct. 25 New England Journal of Medicine. The representatives explained that both drugs, when combined with both reduced-calorie diets and increased physical activity, met FDA criteria for clinically meaningful weight loss. The FDA is requiring the manufacturers to conduct postapproval clinical trials.



Tool of the month


.
Give patients advice on self-monitoring their blood glucose

The American Diabetes Association (ADA) recommends that persons with type 1 diabetes self-monitor their glucose at least 3 times daily. Patients with type 1 diabetes who use basal-bolus insulin regimens should self-monitor their blood glucose at least four times daily (e.g., before meals and at bedtime) and use the data they gather to adjust insulin dosages on a meal-by-meal, day-to-day basis. Regardless of treatment regimen, patients with type 2 diabetes need to have a blood glucose meter and know how to use it. Self-monitoring of blood glucose should be done frequently enough to provide feedback about progress toward goals and to help patients recognize when glycemic control is deteriorating, such as during times of illness or stress.

  • There is no consensus regarding the frequency of self-monitoring in patients who are not taking insulin.
  • Patients with type 2 diabetes who use insulin or insulin secretagogues (sulfonylureas, meglitinides) are at risk for hypoglycemia and may need to monitor more frequently compared with those using lifestyle modifications, either alone or in combination with nonsecretagogue oral agents.
  • Patients with type 1 or type 2 diabetes may need to monitor their blood glucose more frequently when there are changes in insulin or medication dosages, activity, or meals, or during illness or stressful events.
  • In selected adults with type 1 diabetes, continuous glucose monitoring (CGM) in conjunction with intensive insulin regimens has been shown to reduce hemoglobin A1c.

From the ACP Diabetes Care Guide.



Keeping tabs


.
Spotlight on lifestyle interventions for National Diabetes Month

World Diabetes Day is to be held on Nov. 14 and President Obama recently proclaimed November to be National Diabetes Month.

The National Institutes of Health (NIH) is marking the occasion by focusing on the importance of lifestyle changes to treat and prevent diabetes. A press release from the agency described the resources available to the public as part of the National Diabetes Education Program, including the Just One Step and the Make A Plan tools. The American Diabetes Association is offering online and offline activities focused on healthy living and the issues facing diabetes patients.

Lifestyle interventions for patients with type 2 diabetes also recently made the news because the NIH announced it was halting the Look AHEAD (Action in Health for Diabetes) study. The trial had randomized more than 5,000 patients to an intensive lifestyle intervention or a general program of support and education. After up to 11 years of follow-up, researchers concluded that the intervention was having no impact on rates of heart disease, stroke or cardiovascular-related death.

However, the diet and exercise intervention did offer other benefits. Participants maintained an average weight loss of nearly 5% after four years in the program, compared to about 1% in the control group. They also had less sleep apnea and need for diabetes medications and better mobility and better quality of life. Researchers plan to continue following the patients and report their findings (including sub-group analyses) in a peer-reviewed publication, according to an NIH press release.


.


MKSAP Answer and Critique



The correct answer is D. Measure 2-hour postprandial glucose levels. This item is available to MKSAP 15 subscribers as item 33 in the Endocrinology section. Part A of MKSAP 16 was released on July 31. More information is available online.

This patient requires measurement of her 2-hour postprandial blood glucose levels. A common clinical scenario in diabetes management is the patient whose hemoglobin A1c values are suboptimal despite fasting blood glucose monitoring results suggesting good glycemic control. Several possible explanations for this phenomenon exist, including a falsely altered hemoglobin A1c value in the setting of hemoglobinopathy or hemolytic anemia; however, there is no reason to suspect a blood disorder in this patient. The most common cause is elevated postprandial blood glucose levels. The possibility of postprandial hyperglycemia should be assessed by measuring blood glucose levels 2 hours after meals several times each week. If elevated blood glucose levels are noted postprandially, the addition of a mealtime rapid-acting insulin analogue, such as insulin aspart, insulin lispro, or insulin glulisine, is appropriate. These insulin preparations, which have peak action within 30 to 90 minutes and a duration of action of 2 to 4 hours, successfully modulate the postprandial rise in glucose.

Although adding exenatide to insulin may reduce postprandial hyperglycemia, it would not reveal the reason for the discrepancy between the fasting blood glucose levels and the hemoglobin A1c values. Exenatide is approved by the U.S. Food and Drug Administration for use in combination with metformin, with a sulfonylurea, or with a combination of metformin and a sulfonylurea but not with insulin.

When a hemoglobinopathy or a hemolytic anemia is responsible for incorrect hemoglobin A1c readings, another biochemical measure of long-term glucose levels, such as fructosamine or glycated albumin, can be used instead of hemoglobin A1c. Because these conditions are unlikely in this patient, measurement of her serum fructosamine level is inappropriate.

Basal insulin analogues, such as insulin glargine and insulin detemir, are effective agents to control fasting glucose levels and, in most circumstances, hemoglobin A1c values. However, they cannot reduce postprandial glucose excursions. Additionally, increasing the dosage of insulin detemir may increase the incidence of overnight hypoglycemia without addressing postprandial glucose spikes.

Key Point

  • When the hemoglobin A1c value is higher than that suggested by the fasting glucose readings, the postprandial glucose level should be checked.

Click here to return to the rest of ACP DiabetesMonthly.

Top




About ACP DiabetesMonthly

ACP DiabetesMonthly is a monthly newsletter produced by the staff of ACP Internist. It is automatically sent to all College members who have an e-mail address on file with ACP.

To add your e-mail address to your member record and to begin receiving ACP DiabetesMonthly, please click here.

Copyright © by American College of Physicians.

Test yourself

A 69-year-old woman is evaluated for a lump under her arm found on self-examination. She is otherwise healthy and has no other symptoms. Medical and family histories are unremarkable, and she takes no medications. A needle aspirate of the right axillary mass reveals adenocarcinoma. Bilateral mammography and breast MRI are normal. CT scan of the chest, abdomen, and pelvis demonstrates the enlarged axillary lymph node and no other abnormalities. What is the most appropriate initial treatment?

Find the answer

What will you learn from your Annals Virtual Patient?

Reviews of the World's Top Medical Journals—FREE to ACP Members! Annals Virtual Patients is a unique patient care simulator that mirrors real patient care decisions and consequences. CME Credit and MOC Points are available. Start off with a FREE sample case. Start your journey now.

Products and Resources for Patients

Products and Resources for PatientsACP has developed easy- to-use materials designed to help educate your patients on self-management of a wide variety of common health conditions. Order yours today!