Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis

Objective: The aim of this study was to perform a systematic review and meta-analysis on insulin resistance in adult patients with type 1 diabetes mellitus compared to healthy controls, assessed by hyperinsulinemic euglycemic clamp studies. Design and methods: We conducted a systematic search of publications using PubMed, EMBASE, Web of Science and COCHRANE Library. Hyperinsulinemic euglycemic clamp studies comparing adult patients with type 1 diabetes mellitus to healthy controls were eligible. Primary outcome measures were pooled mean differences of insulin sensitivity of endogenous glucose production (EGP), of glucose uptake and of lipolysis. We estimated mean (standardized) differences and 95% CIs using random effects meta-analysis. Results: We included 38 publications in this meta-analysis. The weighed mean differences in EGP during hyperinsulinemia between patients and controls was 0.88 (95% CI: 0.47, 1.29) in the basal state and 0.52 (95% CI: 0.09, 0.95) in insulin stimulated conditions, indicating decreased hepatic insulin sensitivity in patients. Insulin sensitivity of glucose uptake was either reported as M value (M), glucose infusion rate (GIR), glucose disposal rate (GDR) or metabolic clearance rate (MCR). Weighed mean differences were similar for M -3.98 (95% CI: -4.68, -3.29) and GIR -4.61 (95% CI: -5.86, -3.53). Weighed mean difference for GDR was -2.43 (95% CI: -3.03, -1.83) and -3.29 (95% CI: -5.37, -1.22) for MCR, indicating decreased peripheral insulin sensitivity in patients. Insulin mediated inhibition of lipolysis was decreased in patients, reflected by increased non-esterified fatty acid levels. Conclusions: Insulin resistance is a prominent feature of patients with type 1 diabetes mellitus and involves hepatic, peripheral and adipose tissues.