Increased Body Mass Index Variability as an Independent Predictor of Diabetic Kidney Disease Progression

Background: There is emerging data on the potential role of body mass index (BMI) variability as a predictor of cardiovascular disease.The effect of BMI variability on kidney disease progression in people with type 1 diabetes mellitus (T1DM) is unknown. Our aim was to explore if BMI variability was associated with kidney disease progression in an urban ethincally diverse cohort of people with T1DM . Methods: We evaluated 3,437 people with type 1 diabetes (50% female, mean age of 36.4 years 13% non white) attending routine out-patient care at two large university hospitals in London with baseline eGFR ≥45 ml/min/1.73m2 between 2004 and 2018. Clinical and biochemical data was collected from hospital outpatient electronic health records. eGFR was estimated using CKD Epi race free equation. eGFR results during and soon after acute hospitalisations were excluded. BMI variability was assessed using three distinct methods: visit-adjusted standard deviation (VadjSD), variability independent of the mean (VIM), and average real variability (ARV). The primary kidney endpoint was defined as an eGFR decline of ≥50% from baseline to a final eGFR <30 ml/min/1.73m2. Multivariate Fine and Gray models, accounting for death as a competing event, were utilised. Results: Baseline mean (standard deviation) BMI was 25.0 (4.8) kg/m2 . Of the 3437 people 200 people (5.8%) developed the kidney endpoint. All three BMI variability indices were independently associated with CKD progression: VadjSD hazard ratio (HR) and 95% confidence intervals (95% CI) of 2.48 (95% CI [1.97-3.12]), VIM HR 1.96 (95% CI [1.64-2.35]), and ARV HR 4.06 (95% CI [2.03-9.09]) after adjusting for traditional CKD risk factors and baseline BMI.BMI variability remained a significant predictor of kidney disease progression in death as competing risk analyses. The significant impact of BMI variability on eGFR decline was observed in all ethnic groups. Conclusion: BMI variability is an independent risk factor for kidney disease progression in people with type 1 diabetes. Our results suggest that BMI variability which is an index/marker of ‘cardio-metabolic cycling’ influences kidney disease progression. Further research is needed to understand the underlying mechanisms of this association in people with diabetes.