Microvascular Residual Risk Studies

There were two primary outcomes:

• Development of diabetes (fasting plasma glucose ³7·0 mmol/L or 2 hour concentration ³ 11·1 mmol/L, confirmed by a repeat test within 6 weeks)
• Prevalence of microvascular disease, based on an aggregate outcome including three components of diabetes-related microvascular disease: nephropathy, retinopathy, and neuropathy (see below).

Microvascular complications were defined as specified below.

• Nephropathy: albuminuria ³30 mg/g creatinine in a spot urine collection on two consecutive tests, an estimated glomerular filtration rate (eGFR) <45 mL/min/1·73 m² on two consecutive tests, or renal failure (end-stage renal disease, dialysis, or transplantation). Subjects receiving antihypertensive pharmacotherapy at the final visit who did not meet albuminuria or eGFR criteria at that time were regarded as having reached the nephropathy outcome if the nephropathy criteria were met previously at two consecutive visits.
• Retinopathy: evaluated with seven-field stereoscopic fundus photography if the Early Treatment Diabetic Retinopathy Study grade was ³20 in either eye, or with treatment of retinopathy with laser or intravitreal injections.
• Neuropathy: loss of light touch sensation (<8 of 10 applications detected on the dorsum of the great toe in either foot), measured with a 10 g Semmes-Weinstein monofilament.

The primary outcomes were analysed on an intention-to-treat basis on the basis of subjects’ original DPP treatment assignment. The aggregate microvascular outcome was analysed with the global test using general estimating equation models to estimate average prevalence and account for correlations among the individual outcomes.

• The mean follow-up period was 15 years. Over this time, there were significant reductions in diabetes incidence compared with placebo in both the lifestyle intervention group and the metformin group (see Table 1). However, in both groups, the benefit of intervention decreased over time.
• For the total cohort, there was no significant difference in the aggregate microvascular outcome at the end of the study. However, women in the lifestyle group had a lower prevalence of the microvascular aggregate outcome than those in either the placebo or metformin groups (Table 1)

Table 1. Impact of lifestyle intervention or metformin on development of diabetes or microvascular outcomes at 15 years

CI confidence interval

• Across all groups, there was a lower prevalence of the microvascular outcome in subjects who did not develop diabetes than in those who did (relative risk 0·72, 95% CI 0·63–0·83; p<0·0001 for all treatment groups combined).

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