Intensive Diabetes Intervention May Lead to Remission

Joe Barber Jr, PhD

December 18, 2012

An intensive lifestyle intervention appears to be associated with a greater likelihood of achieving a partial remission of diabetes than standard support and education, according to the findings of an observational analysis.

Edward W. Gregg, PhD, from the Wake Forest School of Medicine in Winston-Salem, North Carolina, and colleagues published their findings in the December 19 issue of JAMA.

The authors mention that although diabetes is considered a progressive, incurable disease, there is some evidence that it is reversible. "[The] notion that type 2 diabetes is irreversible is supported by the strong association with genetics and family history, the high prevalence of microvascular complications, and the loss of beta cell mass and function frequently already present at diagnosis," the authors write. "Despite these observations, 16% of US adults who report a previous diabetes diagnosis take no hypoglycemic medications, and studies of bariatric surgery suggest that many diabetes cases among obese patients can indeed resolve."

In the study, the authors analyzed data collected in the Action for Health for Diabetes (Look AHEAD) study, a randomized controlled trial comparing an intensive lifestyle intervention with diabetes support and education. Among the 4503 adults included in the study, participants in the intensive lifestyle intervention group compared with those in the support and education group were more likely to experience at least a partial remission of diabetes at both year 1 (11.5% [95% confidence interval [CI], 10.1% - 12.8%] vs 2.0% [95% CI, 1.4% - 2.6%]; P < .001) and year 4 (7.3% [95% CI, 6.2% - 8.4%] vs 2.0% [95% CI, 1.5% - 2.7%]; P < .001).

The authors excluded participants who met the definition of nondiabetes at baseline (fasting glucose levels < 126 mg/dL and HbA1c levels < 6.5% while taking no medication). The authors then performed multivariate analysis with adjustment for intervention group and variables such as age, race, and body mass index tertile.

The intensive intervention group was more likely to have a continuous, sustained remission for 2 years (9.2% vs 1.7; P < .001), 3 years (6.4% vs 1.3% ), or 4 years (3.5% vs 0.5%; P = .02). Intensive intervention participants additionally lost significantly more weight after 1 year (8.6% vs 0.7%; P < .001) and 4 years (4.7% vs 0.8%; P < .001).

In multivariate analysis, a diabetes duration of between 2 and 7 years (odds ratio [OR], 0.43; 95% CI, 0.32 - 0.58; P < .001), an HbA1c level higher than 7.6% (OR, 0.40; 95% CI, 0.27 - 0.60; P < .001), insulin use (OR, 0.23; 95% CI, 0.11 - 0.51; P < .001), and weight loss of between 1% and 6.5% (OR, 0.37; 95% CI, 0.26 - 0.53; P < .001) were associated with a lower likelihood of remission, whereas a 1-year fitness improvement of 17.9% or more was associated with a higher likelihood of remission (OR, 1.80; 95% CI, 1.14 - 2.86; P = .01).

The authors included the exploratory nature of the analyses, the lack of adjustment of P values for multiple comparisons, the less-than-ideal study population, and the more intensive intervention than commonly used in clinical and community settings as study limitations.

"In spite of these limitations, this is the largest study to our knowledge to examine the association of a lifestyle intervention with type 2 diabetes remission," the authors write. "Our findings suggest that an intensive lifestyle intervention may be associated with a partial diabetes remission in a subset of patients with type 2 diabetes, particularly those whose diabetes is of short duration, who have lower HbA1c levels, and who do not yet require insulin therapy."

In a linked commentary, David E. Arterburn, MD, MPH, from the Group Health Research Institute in Seattle, Washington, and Patrick J. O'Connor, MD, MPH, from HealthPartners Institute for Education and Research in Minneapolis, Minnesota, noted that although diabetes prevention strategies should be more broadly applied, additional measures will be needed. "Research, education, and policy efforts need to be focused further upstream, toward primary prevention: reducing incident obesity in children, adolescents, and adults, especially among those with a family history of obesity or diabetes," they write. "Prevention of diabetes and obesity should be a rallying cry for all clinicians who care about the health of the nation."

These conclusions were echoed by K.M. Venkat Narayan, MD, from Emory University in Atlanta, Georgia. "These data, together with data from the diabetes prevention trials, clearly point to the importance of early initiation of intensive lifestyle interventions for people with prediabetes or diabetes," Dr. Narayan told Medscape Medical News by email. "Everyone diagnosed with prediabetes or diabetes should be given intensive lifestyle intervention, similar to what was done in the Diabetes Prevention Program or the Look AHEAD trial."

One coauthor reported having board memberships with Eli Lilly, Boehringer Ingelheim, and Johnson & Johnson and receiving consultancy support from Pfizer and one coauthor received consultancy support from diaDexus. Dr. Arterburn received institutional grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, the Department of Veterans Affairs, and the Informed Medical Decisions Foundation and payment for travel expenses from the Informed Medical Decisions Foundation. Dr O'Connor received institutional grants from the National Institutes of Health and the Agency for Healthcare Research and Quality and payment for lectures from the Montana Diabetes Program and the Centers for Disease Control and Prevention. He also reported institutional patents related to software to calculate medication effects. The remaining authors and Dr. Narayan have disclosed no relevant financial relationships.

JAMA. 2012;308:2489-2496. Abstract