Top POEMs of 2011: Diabetes Mellitus

Intensive Glucose Control Increases Mortality in T2DM (ACCORD)

Clinical Question: Does intensive glucose control in patients with type 2 diabetes improve outcomes more than usual control?

Bottom Line: This study confirms the initial findings of the ACCORD study: In middle-aged or older patients with cardiovascular risk factors, the best target for glycated hemoglobin is between 7.0% and 7.9%. (Level of Evidence: 1b)

Reference: The ACCORD study group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011;364(9):818-828.

Study Design: Randomized controlled trial (double-blinded)

Funding Source: Government

Allocation: Concealed

Setting: Outpatient (any)

Synopsis: The ACCORD study randomized persons aged 40 to 79 years with type 2 diabetes mellitus and known cardiovascular disease or cardiovascular risk factors to either intensive glucose control (glycated hemoglobin target < 6.0%) or usual control (7.0% to 7.9%). The study was stopped after 3.7 years when a significant increase in all-cause mortality was detected in the intensive therapy group. At that time, the median glycated hemoglobin levels were 6.4% and 7.5% in the intensive and usual treatment groups, respectively. At that time, the target for patients in the intensive therapy group was relaxed to a target glycated hemoglobin between 7.0% and 7.9%; follow-up continued for an additional 17 months. This report describes the results at the end of the entire 5 year follow-up period. At that time, the median glycated hemoglobin levels were 7.2% and 7.6%. Essentially, there was little difference between the outcomes of the original study and those at 5 years. Although nonfatal myocardial infarctions were still less common after 5 years (hazard ratio [HR] = 0.82; 95% CI, 0.7 - 0.96), cardiovascular and all-cause deaths (HR = 1.19; 1.03 - 1.38) were more common.

MARK H. EBELL, MD, MS
Associate Professor
University of Georgia
Athens, GA

Intensive Glucose Lowering Does Not Benefit Patients with Type 2 Diabetes

Clinical Question: Does intensive glucose lowering in patients with type 2 diabetes decrease their risk of death or sequelae of diabetes?

Bottom Line: Combining the results of 13 trials enrolling more than 34,500 patients, this meta-analysis found no benefit to attempting intensive glucose lowering in adults with type 2 diabetes, with the exception of a decrease in the likelihood of nonfatal myocardial infarction (but not cardiovascular mortality). The more studies that accumulate, the less benefit is shown with intensive glucose lowering. (Level of Evidence: 1a-)

Reference: Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 2011;343:d4169.

Study Design: Meta-analysis (randomized controlled trials)

Funding Source: Government

Setting: Various (meta-analysis)

Synopsis: These French investigators searched 3 databases, including the Cochrane Database, as well as reference lists of other meta-analyses, to identify randomized controlled trials assessing intensive glucose lowering treatment versus standard care or less intensive treatment. Two investigators independently evaluated the studies for inclusion, extracted the data, and assessed the quality of the research. They included 13 trials of 34,533 patients. Attempting intensive glucose lowering did not affect mortality (risk ratio = 1.04; 99% CI, 0.91-1.19) or cardiovascular death (risk ratio = 1.11; 0.86 - 1.43), though nonfatal myocardial infarction risk was lower with treatment (risk ratio = 0.85; 0.74-0.96). On the other hand, severe hypoglycemia (low enough to require medical intervention) was doubled in the intensive treatment group (risk ratio = 2.33; 1.62 - 3.36). Over 5 years, the risk of severe hypoglycemia requiring medical treatment ranged from 1.9% to 6.6% of patients. Restricting the analysis to only high-quality studies removed heterogeneity but also removed the benefit seen for nonfatal myocardial infarction risk. It did not change other results but revealed a 47% increase in the risk of heart failure. Microvascular effects of diabetes -- retinopathy, renal failure, and amputation -- were not affected by intensive glucose lowering, but there was heterogeneity among the results related to the quality of the trial. Removing the results of the oft-maligned University Group Diabetes Project did not affect the results.

ALLEN F. SHAUGHNESSY, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA

Mediterranean Diet Delays Onset of Diabetes

Clinical Question: For patients at high cardiovascular risk, can dietary counseling on a Mediterranean-type diet decrease the incidence of type 2 diabetes?

Bottom Line: Extensive and ongoing dietary counseling about a Mediterranean-type diet (including a high consumption of vegetables, legumes, nuts, and olive oil and a low consumption of meat and dairy products) decreased the incidence of diabetes, as compared with counseling about a low-fat diet, over 4 years in patients with 3 or more cardiovascular risk factors. The patients in this study were also supported with large quantities of free olive oil or mixed nuts. (Level of Evidence: 1b)

Reference: Salas-Salvado J, Bullo M, Babio N, et al, for the PREDIMED Study Investigators. Reduction in the incidence of type 2 diabetes with the Mediterranean diet. Results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care 2011;34(1):14-19.

Study Design: Randomized controlled trial (nonblinded)

Funding Source: Industry + government

Setting: Outpatient (any)

Synopsis: The Spanish researchers conducting this study enrolled 418 patients at higher risk for cardiovascular disease (defined as having at least 3 risk factors, but not diabetes). The patients were then randomized to counseling about either a low-fat diet or about 1 of 2 Mediterranean diets. All patients had quarterly individual interviews and group sessions with a dietitian, aimed at creating dietary patterns, recipes, and shopping lists; they were not counseled about calorie reduction or physical activity. Patients in the low-fat group were also counseled about fat reduction in their diet. Patients in the Mediterranean diet groups were given free allotments of olive oil (1L/week!) or mixed nuts (30 g/day). After a median follow-up of 4.0 years, diagnoses of diabetes were significantly lower in the olive oil group (10.1%) and the mixed nuts group (11.0%) than in the low-fat group (17.9%), an average 52% reduction in diabetes incidence with the Mediterranean diet counseling (95% CI, 27%-86%). Body weight and caloric expenditure were not decreased, on average, despite the decrease in diabetes incidence.

ALLEN F. SHAUGHNESSY, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA

POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com)

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