Frequency and characteristics of diabetes in lipodystrophies and insulin receptoropathies compared with type 1 and type 2: results from the multicenter DPV registry

Abstract

Objective: To investigate the frequency, treatment and outcome of patients with diabetes due to severe insulin resistance syndromes (SIRS). Research Design and Methods: Based on data from the multicenter prospective Diabetes Registry DPV, we analyzed diagnosis, treatment and outcome of 636,777 patients with diabetes from 1995 to 2022. Results: Diabetes due to SIRS was documented in 67 cases (62.7% females), 25 (37%) had lipodystrophies (LD) and 42 (63%) had congenital defects of insulin signaling. The relative frequency compared to type 1 diabetes (T1D) was about 1:2300. Median age at diabetes diagnosis in patients with SIRS was 14.8 years (interquartile range [IQR] 12.8–33.8). 38 patients with SIRS (57%) received insulin and 34 (51%) other antidiabetics, mostly metformin. 16% of patients with LD were treated with fibrates. Three out of eight patients with generalized LD (37.5%) were treated with metreleptin and one patient with Rabson-Mendenhall syndrome was treated with recombinant IGF-1. The median HbA1c at follow-up was 7.1% [54 mmol/mol]. Patients with LD had higher triglycerides than patients with T1D and T2D (P<0.001 and P=0.022, respectively), and also significantly higher liver enzymes and lower HDL cholesterol than patients with T1D (P<0.001). Patients with insulin receptor disorders were significantly less likely to be treated with antihypertensive medication than patients with T2D (P=0.042), despite having similar levels of hypertension. Conclusions: Diabetes due to SIRS is rare diagnosed and should be suspected in lean children or young adults without classical type 1 diabetes. Awareness of cardiovascular risk factors in these patients should be raised.