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

Abstract

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 K3.98 (95% CI: K4.68, K3.29) and GIR K4.61 (95% CI: K5.86, K3.53). Weighed mean difference for GDR was K2.43 (95% CI: K3.03, K1.83) and K3.29 (95% CI: K5.37, K1.22) 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.

Double diabetes: A distinct high‐risk group?

“…A meta‐analysis of 65 studies, which included 516 325 adults without diabetes, has shown that insulin resistance, measured by homeostatic model assessment, is a good predictor of cardiovascular disease . In line with these findings, insulin resistance in T1D has been associated with increased risk of cardiovascular disease . Furthermore, the CACTI study demonstrated that insulin resistance, measured by clamp techniques, predicted the presence of coronary artery calcification in people with T1D …”

“…For example, repeated hypoglycaemia or even the fear of hypoglycaemia results in maladaptive eating habits that favour the development of obesity . Peripheral insulin resistance precipitated by subcutaneous insulin administration rather than the physiological portal vein delivery, is another additional factor in the development of DD . DD in people with T1D, therefore, develops secondary to a combination of lifestyle behaviour akin to individuals without diabetes, and diabetes‐specific mechanisms related to hypoglycaemia, and the non‐physiological administration of insulin subcutaneously.…”

“…33 In line with these findings, insulin resistance in T1D has been associated with increased risk of cardiovascular disease. 34 Furthermore, the CACTI study demonstrated that insulin resistance, measured by clamp techniques, predicted the presence of coronary artery calcification in people with T1D. 35 The "gold standard" method by which to measure insulin resistance is the euglycaemic-hyperinsulinemic clamp, 36 but, because of the invasive and time-consuming nature of the procedure, it is not suitable for daily clinical practice.…”

Pancreatic islet inflammation: an emerging role for chemokines

“…However, there are a number of commonalities between T1D and T2D that are worth considering. First, insulin resistance is a risk factor for both T1D (Donga, et al 2015; Fourlanos, et al 2004) and T2D (Kahn 1998; Samuel and Shulman 2016). Second, pro-inflammatory cytokines (e.g., IL-1β, IFN-γ, TNF-α, etc.)…”

Myostatin inhibition therapy for insulin-deficient type 1 diabetes

“…Although T1DM is primarily a disease of insulin deficiency, T1DM patients are insulin-resistant compared with non-diabetic subjects; with insulin resistance observed both during puberty and in those with long-standing T1DM345678. While insulin resistance in T1DM was previously thought to be directly related to adiposity and elevated HbA1c389, recent evidence has demonstrated insulin resistance in multiple tissues of those with T1DM despite good glycemic control and a BMI similar to that of non-diabetics1011.…”