BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children

A Lauria, A Barker, N Schloot, N Hosszufalusi, J Ludvigsson, C Mathieu, D Mauricio, M Nordwall, B Van der Schueren, T Mandrup-Poulsen, W A Scherbaum, I Weets, F K Gorus, N Wareham, R D Leslie, P Pozzilli

Objective: Body weight related insulin resistance probably plays a role in progression to type 1 diabetes but has an uncertain impact following diagnosis. In this study we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. Design: Multicentre longitudinal study carried out at diagnosis and up to 1 year follow-up. Methods: Data on C-peptide was collected from 7 diabetes centres in Europe. Patients were grouped according to age at diagnosis (<5 yrs, n=126; >5 yrs< 10 yrs, n=295; >10 yrs<18yrs, n=421; >18 yrs, n=410). Linear regression was used to investigate if BMI was an independent predictor of change in fasting C-peptide over 1-year. Models were additionally adjusted for baseline insulin dose and HbA1c . Results: In individuals diagnosed between 0-5 years, 5-10 years and those diagnosed > 18 years we found no association between BMI and C-peptide decline. In patients aged 10-18 years higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1-year with a decrease (β 95% CI; p-value) of 0.025 (0.010, 0.041) nM per 1 kg/m2 higher baseline BMI (p=0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose ( β= 0.026, 95% CI= 0.0097, 0.042; p= 0.002). Conclusions: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in age group 10-18 years. This should be considered in studies of beta-cell function in type 1 diabetes.