Statin use and risk of developing diabetes: results from the Diabetes Prevention Program

Objective Several clinical trials of cardiovascular disease prevention with statins have reported increased risk of type 2 diabetes (T2DM) with statin therapy. However, participants in these studies were at relatively low risk for diabetes. Further, diabetes was often based on self-report and was not the primary outcome. It is unknown whether statins similarly modify diabetes risk in higher risk populations. Research design and methods During the Diabetes Prevention Program Outcomes Study (n=3234), the long-term follow-up to a randomized clinical trial of interventions to prevent T2DM, incident diabetes was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting glucose. Lipid profile was measured annually, with statin treatment determined by a participant’s own physician outside of the protocol. Statin use was assessed at baseline and semiannual visits. Results At 10 years, the cumulative incidence of statin initiation prior to diabetes diagnosis was 33%–37% among the randomized treatment groups (p=0.36). Statin use was associated with greater diabetes risk irrespective of treatment group, with pooled HR (95% CI) for incident diabetes of 1.36 (1.17 to 1.58). This risk was not materially altered by adjustment for baseline diabetes risk factors and potential confounders related to indications for statin therapy. Conclusions In this population at high risk for diabetes, we observed significantly higher rates of diabetes with statin therapy in all three treatment groups. Confounding by indication for statin use does not appear to explain this relationship. The effect of statins to increase diabetes risk appears to extend to populations at high risk for diabetes. Trial registration number NCT00038727; Results

Antidepressant Medicine Use and Risk of Developing Diabetes During the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study

OBJECTIVE — To assess the association between antidepressant medicine use and risk of developing diabetes during the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS — DPP/DPPOS participants were assessed for diabetes every 6 months and for antidepressant use every 3 months in DPP and every 6 months in DPPOS for a median 10.0-year follow-up. RESULTS — Controlled for factors associated with diabetes risk, continuous antidepressant use compared with no use was associated with diabetes risk in the placebo (adjusted hazard ratio 2.34 [95 % CI 1.32–4.15]) and lifestyle (2.48 [1.45–4.22]) arms, but not in the metformin arm (0.55 [0.25–1.19]). CONCLUSIONS — Continuous antidepressant use was significantly associated with diabe-tes risk in the placebo and lifestyle arms. Measured confounders and mediators did not account for this association, which could represent a drug effect or reflect differences not assessed in this study between antidepressant users and nonusers. Diabetes Care 33:2549–2551, 2010 Our earlier report from the DiabetesPrevention Program (DPP) (1) wasthe first to examine antidepressant medicine (ADM)-related diabetes risk in an overweight population with elevated fasting glucose and impaired glucose tol-erance. We found in the placebo and life-style arms that when other factors associated with diabetes risk (age, sex, ed-ucation, fasting plasma glucose at base-line, weight at baseline, weight change during the study, and depression symp-toms at baseline and during the study) were controlled, baseline ADM use and continuous ADM use during the study (compared with no use) were associated with significantly increased diabetes risk; in the lifestyle arm, intermittent ADM use during the study was also associated with increased diabetes risk. Among met-formin arm participants, ADM use was not associated with developing diabetes. The present study extends the dura-tion of follow-up in our previous report by including 7 years of the Diabete

Changes in Health State Utilities With Changes in Body Mass in the Diabetes Prevention Program

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93702/1/oby.2009.114.pd

Lifestyle and metformin interventions have a durable effect to lower CRP and tPA levels in the diabetes prevention program except in those who develop diabetes.

OBJECTIVE: We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes. RESEARCH DESIGN AND METHODS: The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were randomized to lifestyle, metformin, or placebo interventions for 3.4 years. Diabetes was diagnosed semiannually by fasting glucose and annually by oral glucose tolerance testing. In addition to baseline testing, anthropometry was performed every 6 months; fasting insulin yearly; and hs-CRP, tissue plasminogen activator (tPA), and fibrinogen at 1 year and end of study (EOS). RESULTS: CRP and tPA levels were unchanged in the placebo group but fell in the lifestyle and metformin groups at 1 year and remained lower at EOS. These reductions were not seen in those who developed diabetes over the course of the study despite intervention. Fibrinogen was lower at 1 year in the lifestyle group. Differences in weight and weight change explained most of the influence of diabetes on the CRP response in the lifestyle group, but only partly in the placebo and metformin groups. Weight, insulin sensitivity, and hyperglycemia differences each accounted for the influence of diabetes on the tPA response. CONCLUSIONS: Lifestyle and metformin interventions have durable effects to lower hs-CRP and tPA. Incident diabetes prevented these improvements, and this was accounted for by differences in weight, insulin resistance, and glucose levels

Depression Symptoms and Antidepressant Medicine Use in Diabetes Prevention Program Participants

OBJECTIVE: To assess depression markers (symptoms and antidepressant medicine use) in Diabetes Prevention Program (DPP) participants and to determine whether changes in depression markers during the course of the study were associated with treatment arm, weight change, physical activity level, or participant demographic characteristics. RESEARCH DESIGN AND METHODS: DPP participants (n = 3,187) in three treatment arms (intensive lifestyle, metformin, and placebo) completed the Beck Depression Inventory (BDI) and reported on use of antidepressant medicines at randomization and subsequently at each annual visit (average duration in study 3.2 years). RESULTS: On study entry, 10.3% of participants had BDI scores > or =11, which was used as a threshold for mild depression, 5.7% took antidepressant medicines, and 0.9% had both depression markers. During the DPP, the proportion of participants with elevated BDI scores declined (from 10.3% at baseline to 8.4% at year 3), while the proportion taking antidepressant medicines increased (from 5.7% at baseline to 8.7% at year 3), leaving the proportion with either marker unchanged. These time trends were not significantly associated with the DPP treatment arm. Depression markers throughout the study were associated with some participant demographic factors, adjusted for other factors. Men were less likely to have elevated depression scores and less likely to use antidepressant medicine at baseline (9.0% of men and 17.9% of women had at least one marker of depression) and throughout the study (P or =11 (P = 0.03), but white participants were more likely to be taking antidepressant medicine than any other racial/ethnic group (P <0.0001). CONCLUSIONS: DPP participation was not associated with changes in levels of depression. Countervailing trends in the proportion of DPP participants with elevated depression symptoms and the proportion taking antidepressant medicine resulted in no significant change in the proportion with either marker. The finding that those taking antidepressant medicine often do not have elevated depression symptoms indicates the value of assessing both markers when estimating overall depression rates

The prevention of type 2 diabetes

Type 2 diabetes mellitus (T2DM) affects more than 7% of adults in the US and leads to substantial personal and economic burden. In prediabetic states insulin secretion and action—potential targets of preventive interventions—are impaired. In trials lifestyle modification (i.e. weight loss and exercise) has proven effective in preventing incident T2DM in high-risk groups, although weight loss has the greatest effect. Various medications (e.g. metformin, thiazolidinediones and acarbose) can also prevent or delay T2DM. Whether diabetes-prevention strategies also ultimately prevent the development of diabetic vascular complications is unknown, but cardiovascular risk factors are favorably affected. Preventive strategies that can be implemented in routine clinical settings have been developed and evaluated. Widespread application has, however, been limited by local financial considerations, even though cost-effectiveness might be achieved at the population level