Features of Slowly Progressive Type 1 Diabetes Mellitus in Overweight Adolescents

Background: he obesity epidemic has led to an increase in the incidence of type 1 diabetes mellitus (T1DM) on the background of overweight. The combination of T1DM and obesity can lead to an erroneous diagnosis of type 2 diabetes (T2DM). Methods: The study included 35 adolescents with T1DM. Inclusion criteria were obesity at onset, high titer of diabetes-associated autoantibodies, and insulin requirement less than 0.5 U/kg with a diabetes duration of more than 6 months. We assessed the level of HbA1c, fasting level of insulin and c-peptide, and level during the Mixed-Meal Tolerance Test, the immunological status of GADA, IA-2, ZnT8, ICA. Results: The age of onset was 12.7 years [10.6; 14.5], the tanner stage of puberty was 4 [3; 5]. Sex distribution: boys (n = 25) - 71.5%, girls (n = 10) - 28.5%. HbA1c at the time of onset equaled 8,9% [7.4; 10.45]. Ketosis/diabetic ketoacidosis was registered in 47.8%. The duration of the diabetes was 1.7 years at the moment of examination [0.7; 2.9]. The fasting level of C-peptide - 1.37 mμg/ml [1.0.9; 2.19], insulin level (n = 26) - 13.93 uU/ml [9.57; 19.77]. The maximum level of stimulated secretion of C-peptide (n = 21) - 5.13 mμg/ml [3.05; 6.07], of insulin secretion (n = 21) - 58.59 uU/ml [31.02; 79.74]. Higher HOMA of insulin resistance (n = 25) was detected in 72% of the examined patients. In the study of pancreatic autoantibodies, an increase in ICA was detected in 57% (median of titer 1.68 [0.28;11.7]), IA-2 - 67% (192.8 ME/ml [65; 310.1]), GAD - 59% (90.25 ME/ml [32.27; 214.6]), ZnT8 - 82% (350.5 [90.4; 506.05]). The presence of 2 or more autoantibodies is found in 94% of cases. Dyslipidemia was observed in 34.8%, arterial hypertension was identified in 23% of patients. Received therapy: insulin 82%; metformin 0.02%; metformin + insulin 5.7%. Median daily dose per patient was 0.3 U/kg [0.2; 0.5]. Conclusion: T1DM in adolescents with obesity and overweight has a similar clinical picture both with T1DM (insulin dependence, high titer of autoantibodies, ketosis) and T2DM (slow progression of the disease, low insulin requirement, preserved secretion of c-peptide, and insulin for more than 1.5 years). We hypothesize that obesity and insulin resistance may contribute to DM onset at an earlier date, even if a satisfactory function of pancreatic beta-cells is still preserved. Given that the onset of the disease in our group falls on adolescence it seems that pubertal insulin resistance also contributes to the features of the course of the disease. Understanding the role of obesity in the progression of disorders of carbohydrate metabolism will allow postponing the acute manifestation of the disease and initiation of insulin therapy through lifestyle modifications in patients at risk. A long period of preserved insulin secretion opens up the possibility of new personalized therapies.