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Reductions in fasting glucose, body weight delay progression of early type 2 diabetes
In adults with early type 2 diabetes, reductions in glucose level, driven by reductions in weight, can delay progression of the disease independent of any improvements in beta-cell function, according to a secondary analysis of the Early Diabetes Intervention Program.
“We have demonstrated that in the Early Diabetes Intervention Program, the on-study reduction in fasting glucose was strongly associated with protection from progression,” Kieren Mather, MD, FRCPC, professor of medicine at Indiana University School of Medicine, and colleagues wrote. “This effect was seen after adjustment for the baseline fasting glucose and is therefore not simply an effect of reducing glucose values in those closest to the threshold; rather, it represents the integrated beneficial effect of study interventions.”
Mather and colleagues analyzed data from 219 adults with overweight participating in the Early Diabetes Intervention Program (EDIP), a randomized controlled trial evaluating the effects of acarbose (maximum dose, 100 mg twice daily) vs. placebo in a population with early, screening-detected type 2 diabetes (2-hour oral glucose tolerance test measurements of 11.1, but a fasting glucose of less than 7.8 mmol/L). Participants met with a study dietitian and received recommendations for an appropriate diet, but no specific weight-loss target. Participants were weighed and asked to provide diet recalls at quarterly visits. Diabetes progression was defined as reaching fasting glucose of at least 7.8 mmol/L on two consecutive quarterly visits. Researchers used Cox proportional hazards models and analysis of variance to evaluate determinants of progression.
During follow-up, 62 participants experienced disease progression (mean age, 53 years; 41.9% men; 25.5% assigned acarbose; 31.2% assigned placebo); 134 were non-progressors (mean age, 55 years; 30.6% men; 74.5% assigned acarbose; 68.8% assigned placebo). Researchers found that progression-free status was associated with reductions in weight, fasting glucose and 2-hour OGTT, and increases in the HDL cholesterol/triglyceride ratio. In multivariable Cox regression analysis, only the association between progression-free status and reduction in fasting glucose persisted.
The reduction in fasting glucose, in turn, was primarily associated with reductions in body weight and in 2-hour OGTT.
“Notably, we observed a threshold effect for weight loss, where 5% to 6% weight loss was most reliably associated with improvements in fasting glucose,” the researchers wrote. “These changes took place despite the baseline states of fasting hyperglycemia, poor beta-cell function and lack of improvement in beta-cell function.”
The researchers noted that acarbose therapy was associated with greater reductions in fasting glucose, but the effect was of borderline significance and weaker than the overall roles of weight reduction and lowering of 2-hour glucose values, which were not unique to acarbose therapy. – by Regina Schaffer
Disclosure: Two researchers report participating in a separate clinical trial receiving support from Abbott, Merck, Novo Nordisk and Sanofi.