Endocrine Abstracts

Background and aims: Insulin resistance is increasingly prevalent in patients with type 1 diabetes (T1D). Insulin resistance is associated with both cardiovascular complications and non-alcoholic fatty liver disease (NAFLD), but its assessment is challenging in T1D due to the technical difficulties of the euglycaemic clamp technique. The estimated glucose disposal rate (eGDR) is a validated alternative to quantify insulin resistance in T1D, but its role in clinical practice is largely unexplored. This study aims to explore the association between eGDR and micro- and macrovascular complications and NAFLD, compared to body mass index (BMI) or HbA1c alone.

Materials and methods : individuals with T1D were included in this cross-sectional study. eGDR was categorised in four groups (≥ 8, 6-7.9, 4-5.9 and < 4 mg/kg/min). NAFLD was determined by ultrasound combined with elastometry (Saverymuttu grade ≥ 1 and controlled attenuation parameter ≥ 248 dB/m). Microvascular complications were assessed with fundoscopy, microfilament test of the feet and 24-hour microalbuminuria. Macrovascular events were defined by clinical coronary, cerebrovascular or peripheral arterial events or significant stenosis requiring intervention. Multiple logistic regression was performed to identify independent associations with vascular complications and NAFLD, after adjusting for the most relevant confounders.

Results: A total of 510 individuals were consecutively included. NAFLD was present in 21.8% of cases. Median age was 48 [32-59] years with diabetes duration of 27 [15-36] years. An eGDR < 4 was present in 7.8 % of cases, obesity prevalence was 19.1 %. Odds ratios (OR) for nephropathy and NAFLD in obese compared with normal weight individuals were 2.19 (95 % CI: 1.13-4.10; P = 0.020) and 10.32 (95 % CI: 5.73-18.60; p < 0.001). While the association with retinopathy was absent (OR 1.21 [95 % CI: 0.67-2.19; P = 0.538]), the association with macrovascular disease just barely failed to reach statistical significance (OR 2.47 [95 % CI: 0.92-6.65; P = 0.074]). Comparing individuals with eGDR ≥ 8 mg/kg/min, indicating high insulin sensitivity, to those with an eGDR < 4 mg/kg/min indicating insulin resistance, showed significantly higher OR for nephropathy, NAFLD and macrovascular disease of 9.96 (95 % CI: 3.85-25.77; p < 0.001), 8.88 (95 % CI: 3.87-20.38; p < 0.001) and 6.06 (95 % CI: 1.60-22.73; P = 0.007), respectively in multivariable regression models including common risk factors. The association with retinopathy barely failed to reach a clinical and statistical significance (OR 2.11 [95 % CI: 0.91-4.93; P = 0.083].

Conclusion: Obesity, insulin resistance and NAFLD are prevalent in T1D and diabetes complications are not only related to BMI or metabolic control. Insulin resistance is associated with the presence of NAFLD and micro- and macrovascular complications. This work was presented orally at the 14th Advanced Technologies & Treatments for Diabetes (2021) conference and the 57th European Association for the Study of Diabetes (2021) conference.