Effect Modification of Body Mass Index and Kidney Function on Insulin Sensitivity Among Patients With Moderate CKD and Healthy Controls

Introduction: Insulin resistance and obesity are prevalent in chronic kidney disease (CKD) patients. The interaction of body mass index (BMI) and kidney function across the continuum of estimated glomerular filtration rate (eGFR) is unknown.

Methods: In a cross-sectional study of 139 patients, 52 with CKD stages 3 and 4 and 87 patients with normal eGFR, we measured the insulin sensitivity index (ISI) using the hyperinsulinemic euglycemic clamp and homeostasis model assessment of insulin resistance (HOMA-IR). We investigated the interaction between eGFR and BMI in their association with ISI and HOMA-IR using linear models with robust standard errors.

Results: Median age was 56 (42, 66) years, 50.4% were female, and 36% were African American. Patients with low eGFR (∼30 ml/min per 1.73 m²) had low ISI (2.3 mg/min per μU/ml) regardless of BMI. Among patients with preserved eGFR (>90 ml/min per 1.73m²), BMI had a greater effect on ISI (6.3 mg/min per μU/ml at a BMI of 20 kg/m² vs. 4.6 mg/min per μU/ml at a BMI of 30 kg/m²) (P for interaction = 0.046). In models adjusted for demographics, and log transformed interleukin-6, high-sensitivity C-reactive protein, leptin, and adiponectin, a 1-SD (28 ml/min per 1.73 m²) lower eGFR was associated with a statistically significant 1.14-unit decrease in ISI (95% confidence interval = -1.80, -0.48) among nonobese patients. Among obese patients, the effect estimate was -0.25 (95% confidence interval = -0.88, 0.39). The association between BMI and HOMA-IR was stronger in patients with lower eGFR (P for interaction = 0.005).

Conclusion: Both eGFR and BMI are independently associated with insulin sensitivity, but the strength of the association between BMI and insulin sensitivity varies significantly across eGFR.