[Role of cumulative hemoglobin A1c levels and insulin doses in insulin resistance-related metabolic disorders in patients with type 1 diabetes].

Abstract

Objective: To examine the effect of cumulative hemoglobin A_1c (HbA_1c) levels and insulin dosage on insulin resistance (IR)-related metabolic disturbances in newly diagnosed patients with type 1 diabetes (T1D). Methods: This retrospective cohort study included T1D patients admitted to the Second Xiangya Hospital of Central South University from November 2015 to March 2023. Clinical data collected comprised age, sex, disease duration, insulin dosage, body mass index, waist circumference, blood pressure, HbA_1c levels, islet autoantibodies, and fasting blood lipid profiles. IR-related metabolic disturbances assessed were overweight, obesity, central obesity, hypertension, and dyslipidemia. Cox regression and cluster analyses were applied to assess the influence of cumulative HbA_1c and insulin dosage on these metabolic disturbances. Results: A total of 235 patients were included, with 97 males (41.3%) and 138 females (58.7%). The median age was 19.8 (13.3, 31.1) years, and the median follow-up duration was 30.8 (20.8, 45.6) months. During follow-up, 41.6% (72/173) of patients developed IR-related metabolic disturbances. Multivariate Cox regression analysis revealed that a cumulative HbA_1c ≥60 mmol/mol was an independent risk factor for any IR-related metabolic disturbance [HR (95%CI): 1.739 (1.067-2.835) ] and for triglyceride abnormalities [HR (95%CI): 3.277 (1.176-9.127)]. Additionally, a cumulative insulin dosage ≥0.5 U·kg^-1·d^-1 was identified as an independent risk factor for overweight, obesity, or central obesity [HR (95%CI): 2.374 (1.059-5.323)]. Cluster analysis further identified that patients with higher levels of cumulative HbA_1c and insulin dosage, particularly those with adolescent-onset diabetes, had the highest likelihood of developing hypertension (HR=2.460, 95%CI 1.008-6.005), overweight/obesity/central obesity (HR=2.707, 95%CI 1.062-6.900), triglyceride abnormalities (HR=5.495, 95%CI 1.842-16.391), high-density lipoprotein cholesterol abnormalities (HR=11.054, 95%CI 4.107-29.751), and any IR-related metabolic disturbance (HR=5.833, 95%CI 2.602-13.077). Conclusions: Elevated cumulative HbA_1c and insulin dosage levels in T1D patients are associated with an increased risk of developing IR-related metabolic disturbances. These findings underscore the urgent need for novel therapeutic strategies tailored to this population.