The EPIC-Potsdam Study: Association of BMI and BMI Changes with Micro-and Macro-vascular Complications in T2DM

4 Mar, 21

Introduction

Studies including meta-analysis have suggested that type-2 diabetes mellitus (T2DM) patients, those who are overweight or obese have a decreased risk of mortality when compared with normal-weight individuals (obesity paradox). However, the current data on the link between body weight or weight change and microvascular vs. macrovascular complications associated with T2DM is either limited or conflicting.

Aim

To determine the association of body mass index (BMI) and BMI change with long-term risk of microvascular and macrovascular complications in T2DM

Patient Profile

Patients with incident T2DM who had participated in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study
All study participants were free of cancer, cardiovascular disease (CVD) and microvascular disease at diagnosis (n =1083; 54.2% males)

Methods

Study Design

EPIC-Potsdam was a prospective cohort study

Assessments

Pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI were evaluated using multivariable adjusted Cox models. Based on BMI, the study participants were categorized as follows:
- Normal weight: 18.5–24.9 kg/m²
- Overweight: 25.0–29.9 kg/m²
- Obese I: 30.0–34.9 kg/m²
- Obese II: ≥35.0 kg/m²
Changes in lifestyle factors were assessed as the difference between post-diagnosis and pre-diagnosis measurements.
Relative change in BMI was categorized as:
- BMI gain (>1%)
- Stable BMI (≤1% gain or loss)
- BMI loss (>1%)

Outcomes

Microvascular complications (diabetic kidney disease, retinopathy and neuropathy)
Macrovascular complications (myocardial infarction or stroke)

Median Follow-up

For total complications: 10.8 years
For macrovascular complications: 11.6 years
For microvascular complications: 11.1 years
For kidney disease and neuropathy: 11.4 years

Results

A total of 85 macrovascular (myocardial infarction and stroke) and 347 microvascular events (kidney disease [207], neuropathy [211] and retinopathy) were recorded during a median follow-up period of 10.8 years.
Median pre-diagnosis BMI was 29.9 kg/m², and the median relative annual BMI change was −0.4%.
Higher pre-diagnosis BMI had a positive association with total microvascular complications (multivariable-adjusted HR per 5 kg/m²) but not with (macrovascular complications (Table 1).

Table 1: Hazard ratios for various outcomes during the study

Outcome	(aHR) (95% CI)
Microvascular complications	1.21 (1.07, 1.36)
Kidney disease	1.39 (1.21, 1.60)
Neuropathy	1.12 (0.96, 1.31)
Macrovascular complications	1.05 (0.81, 1.36)

Adjusted hazard ratio: aHR, 95% confidence interval: 95% CI

These findings were validated further through analyses as per BMI categories. Factors such as gender, smoking status or age groups did not influence this association.
As per analyses based on the BMI change categories, BMI loss of more than 1% vs. stable BMI was associated with a substantially decreased risk of total microvascular complications, and kidney disease (Table 2). No clear association was evident for BMI loss of more than 1% and risk of macrovascular complications (HR 1.04 [95% CI 0.62, 1.74]).

Table 2: Risk reduction for microvascular complications with BMI loss >1%

Outcomes	HR (95% CI)	Risk Reduction (RR)
Total microvascular complications	0.62 (0.47, 0.80)	38%
Kidney disease	0.57 (0.40, 0.81)	43%

The associations between BMI gain (vs. stable BMI) and diabetes-related vascular complications were less apparent.
Associations were consistent across strata of gender, age and smoking status for pre-diagnosis BMI; whereas for BMI change, the associations were strengthened among never-smokers.

Conclusions

Among people with incident T2DM, pre-diagnosis BMI had a positive linear association with microvascular complications (both kidney disease and neuropathy).
Weight loss after diagnosis as compared to stable weight was associated with a reduced risk of microvascular complications. The associations between BMI change and macrovascular disease were not apparent.
The study underscores the critical role of weight management in preventing major diabetes-associated complications.

Diabetologia. 2021 Jan 15 (Published Ahead of Print); doi: 10.1007/s00125-020-05362-7.