Body Mass Index and Cerebral Microbleeds in Type 2 Diabetes: Sex-Specific Thresholds from an Exploratory Study

To prospectively investigate the association between baseline body mass index (BMI) and the risk of incident cerebral microbleeds (CMBs) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM), and to explore potential gender-specific risk thresholds in an exploratory analysis.

This single-center prospective observational cohort study consecutively enrolled T2DM patients without baseline CMBs from April 2022 to March 2023. Baseline demographic, clinical, and biochemical data were collected. BMI was categorized according to Chinese criteria (normal weight BMI < 24 kg/m², overweight 24-28 kg/m², and obesity BMI ≥ 28 kg/m²). All participants underwent follow-up 3.0T magnetic resonance imaging (including susceptibility-weighted imaging sequence) every 12-18 months or earlier if clinically indicated to detect incident CMBs. The primary outcome was the occurrence of ≥1 incident CMBs during follow-up. Cox proportional hazards models were used to calculate hazard ratios (HRs). Restricted cubic spline (RCS) models and two-piecewise linear regression were employed to analyze the nonlinear relationship and threshold effects between BMI and CMBs risk.

The study ultimately included 936 T2DM patients without baseline CMBs, with a median follow-up of 30.00 months (range: 6-42 months; IQR: 12.0, 36.0 months). During follow-up, 100 patients (10.68%) developed incident CMBs. Multivariable Cox regression analysis revealed that compared with the normal weight group, the obesity group (BMI ≥ 28 kg/m²) had a significantly higher risk of incident CMBs (HR = 2.58, 95% CI: 1.46-4.54, p < 0.001). Each 1 kg/m² increase in baseline BMI was associated with a 15% increased risk of incident CMBs (HR = 1.15, 95% CI: 1.09-1.22, p < 0.001). Threshold effect analysis showed a nonlinear association between BMI and CMBs risk (p for nonlinearity < 0.001). The exploratory inflection point was 21.10 kg/m² for males; beyond this threshold, each unit increase in BMI increased CMBs risk by 18% (HR = 1.18, 95% CI: 1.10-1.26, p < 0.001). For females, the exploratory inflection point was 26.80 kg/m², beyond which risk increased by 25% per unit increase (HR = 1.25, 95% CI: 1.02-1.54, p = 0.029).

In this single-center Chinese cohort, higher baseline BMI was associated with incident CMBs in middle-aged and elderly T2DM patients. Exploratory analysis suggested potential sex-specific inflection points (male: 21.10 kg/m²; female: 26.80 kg/m²). This study may inform future research on gender-differentiated weight management strategies, but these findings are not yet ready for clinical implementation.