Abstract P423: Individual and Combined Effects of Diet, Exercise, and Metformin on Risk of Microvascular Complications in Older Type 2 Diabetes Patients: Post-Hoc Analysis of Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial Data

Abstract

Introduction: Microvascular complications are a major burden on the health of type 2 diabetes (T2D) patients. The literature has yielded mixed results regarding synergistic effects of common diabetes treatments (i.e., metformin, exercise, and diet) on microvascular complication risk. Some trials demonstrated that the combination of metformin and exercise diminished beneficial effects. We aimed to explore this ambiguity in findings by examining the effects of metformin, exercise, and diet on microvascular complication risk over time among T2D patients in the U.S. and Canada. Hypothesis: We hypothesize that the combined effects of metformin, exercise, and diet would be better than their individual effects on microvascular complication risk. Methods: We analyzed data from 923 participants [mean age: 62.6; 39.2% female; mean years with diabetes: 10.7] of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) (2003-2009) trial. Adequate exercise was defined as > 150 mins of moderate-intensity physical activity per week. Metformin use was defined as yes vs. no. An adequate diet score was ≤ 2.4 of the summary fat intake score (range: 0 - 5). We defined composite outcomes for microvascular complications (i.e., nephropathy, retinopathy, and neuropathy) based on several measurements including serum creatinine doubling, decrease in estimated glomerular filtration ratio (≥ 20 ml/min/1.73 m2 decrease), vision loss, Michigan Neuropathy Screening Instrument. We performed longitudinal analysis with synergy factor (SF) approach using multinomial logistic regression models adjusted for sex, diabetes years, education, alcohol, treatment arm, and baseline outcome. Results: Among individuals with poor diet score, those taking metformin but not adequate exercise had an odds ratio of 1.12 (95% CI: 0.65 - 1.94, p = 0.68) for microvascular complication. Those not taking metformin but had adequate exercise had an odds ratio of 2.71 (95% CI: 1.12 - 6.59, p < 0.05). However, taking metformin and having adequate exercise produced an odds ratio of 0.90 (95% CI: 0.49 - 1.67, p = 0.75), which was 0.30 times less than the predicted odds of the joint effect (SF = 0·30, 95% CI: 0 - 0.59, p = 0·05). Individuals with an adequate diet, adequate exercise, and taking metformin had an odds ratio of 0.85 (95% CI: 0.48 - 1.49, p = 0.57). However, we did not find these associations to be statistically significant. A similar pattern holds for individual microvascular complication outcomes. Conclusion: Additional randomized controlled trials are needed to confirm the potential additive beneficial effect of metformin, adequate exercise, and adequate diet combination over their individual effects on odds of microvascular complications.