BMI and BMI change following incident type 2 diabetes and risk of microvascular and macrovascular complications: the EPIC-Potsdam study

Abstract

Aims/hypothesis: Studies suggest decreased mortality risk among people who are overweight or obese compared with individuals with normal weight in type 2 diabetes (obesity paradox). However, the relationship between body weight or weight change and microvascular vs macrovascular complications of type 2 diabetes remains unresolved. We investigated the association between BMI and BMI change with long-term risk of microvascular and macrovascular complications in type 2 diabetes in a prospective cohort study.

Methods: We studied participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, who were free of cancer, cardiovascular disease and microvascular disease at diagnosis (n = 1083). Pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI were evaluated in multivariable-adjusted Cox models.

Results: There were 85 macrovascular (myocardial infarction and stroke) and 347 microvascular events (kidney disease, neuropathy and retinopathy) over a median follow-up of 10.8 years. Median pre-diagnosis BMI was 29.9 kg/m² (IQR 27.4-33.2), and the median relative annual BMI change was -0.4% (IQR -2.1 to 0.9). Higher pre-diagnosis BMI was positively associated with total microvascular complications (multivariable-adjusted HR per 5 kg/m² [95% CI]: 1.21 [1.07, 1.36], kidney disease 1.39 [1.21, 1.60] and neuropathy 1.12 [0.96, 1.31]) but not with macrovascular complications (HR 1.05 [95% CI 0.81, 1.36]). Analyses according to BMI categories corroborated these findings. Effect modification was not evident by sex, smoking status or age groups. In analyses according to BMI change categories, BMI loss of more than 1% indicated a decreased risk of total microvascular complications (HR 0.62 [95% CI 0.47, 0.80]), kidney disease (HR 0.57 [95% CI 0.40, 0.81]) and neuropathy (HR 0.73 [95% CI 0.52, 1.03]), compared with participants with a stable BMI; no clear association was observed for macrovascular complications (HR 1.04 [95% CI 0.62, 1.74]). The associations between BMI gain compared with stable BMI and diabetes-related vascular complications were less apparent. Associations were consistent across strata of sex, age, pre-diagnosis BMI or medication but appeared to be stronger among never-smokers compared with current or former smokers.

Conclusions/interpretation: Among people with incident type 2 diabetes, pre-diagnosis BMI was positively associated with microvascular complications, while a reduced risk was observed with weight loss when compared with stable weight. The relationships with macrovascular disease were less clear.

Keywords: BMI; CVD; Diabetes-related vascular complications; Nephropathy; Neuropathy; T2D; Weight change.

Fig. 1

Association between pre-diagnosis BMI and risk of microvascular and macrovascular complications of type 2 diabetes. (a) Total vascular complications. (b) Macrovascular complications. (c) Microvascular complications. (d) Kidney disease. (e) Neuropathy. Pre-diagnosis BMI was assessed as a continuous variable using restricted cubic spline regression, adjusted for age, sex, education, smoking status, smoking duration, physical activity, alcohol consumption, MedPyr score, family history of diabetes, myocardial infarction and stroke. Splines (black lines) and 95% CIs (blue shading) from ten imputation datasets are shown. Knot placement was 5th, 50th and 95th percentile. Median BMI of 29.9 kg/m² served as reference. Test for non-linearity: total complications, p = 0.55; macrovascular complications, p = 0.64; microvascular complications, p = 0.36; kidney disease, p = 0.46; neuropathy, p = 0.86