Effect of progression from impaired glucose tolerance to diabetes on cardiovascular risk factors and its amelioration by lifestyle and metformin intervention: the Diabetes Prevention Program randomized trial by the Diabetes Prevention Program Research Group

Abstract

Objective: Although subjects with diabetes have increased risk for cardiovascular disease (CVD), the evolution of this increased risk as pre-diabetic individuals progress to diabetes is not understood. This study examines the longitudinal relationship between selected CVD risk factors (blood pressure, triglycerides, HDL and LDL cholesterol, and LDL peak particle density [PPD]) and glycemia in the three treatment groups of the Diabetes Prevention Program.

Research design and methods: A total of 3,234 participants with impaired glucose tolerance (IGT) were followed for a mean of 3.2 years after randomization to intensive lifestyle intervention (ILS), metformin, or placebo. Using repeated-measures models, adjusted mean levels of risk factors were estimated for an annual change in glycemic status. Tests were also conducted to assess the risk factor trends with improvement or worsening of glycemic status.

Results: CVD risk factor values and changes from baseline became more unfavorable as glucose tolerance status deteriorated but improved with reversion to normal glucose tolerance (NGT), especially in the ILS intervention group (trend test P < 0.001 for all risk factors except for LDL PPD [P = 0.02] in ILS and HDL cholesterol [P = 0.02] in placebo). Although there were few significant differences in the transition from IGT to diabetes, there were strong relationships between risk factors and continuous measures of glycemia.

Conclusions: Progression from IGT to diabetes is associated with mild deterioration, whereas reversion to NGT is associated with improvement in risk factors. Early intervention with ILS, but less so with metformin, in participants at high risk for diabetes improves the cardiovascular risk and glucose tolerance profile simultaneously.

Trial registration: ClinicalTrials.gov NCT00004992.

Figure 1

Mean interval change in cardiovascular risk factors by category of glucose tolerance interval change and by treatment group. The mean interval changes with their five 95% confidence limits for SBP, DBP, triglycerides, HDL cholesterol, LDL cholesterol, and LDL-PPD are arranged from left to right in each panel by treatment group, according to whether there was improvement in glucose tolerance status (IGT to NGT), maintenance of improvement (NGT to NGT), no change (IGT to IGT), deterioration back to baseline status (NGT to IGT), or conversion to diabetes (DM) (IGT/NGT to diabetes). ○, ILS group; ■, MET group; ▵, placebo group.

Figure 2

Mean cardiovascular risk factor interval changes adjusted for age, sex, and baseline risk factor values by quartiles of change in measures of glycemia and by treatment groups at 1-year intervals. The symbols and horizontal black line denote the mean change and 95% CI in selected cardiovascular risk factors for the three treatment groups: ○, ILS group; ■, MET group; ▵, placebo group. The numbers on the symbols correspond to the quartile of change in each of the measures of glycemia at 1-year intervals. The trend test across quartiles of glycemia showed a significant association (all P < 0.01) with SBP, triglycerides, HDL cholesterol, and LDL-PPD (except fasting glucose).