Endocrine Abstracts

Background and aims: People with type 1 diabetes (T1D) are increasingly suffering from overweight and at risk of developing insulin resistance (IR). IR may hamper glucose control and augment the risk of cardiovascular disease (CVD). Simultaneously, non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent in T1DM. The pathophysiology of NAFLD is linked to IR. The gold standard to assess IR is the euglycaemic clamp, an invasive and time-consuming test that cannot be performed in routine screening. The estimated glucose disposal rate (eGDR) can be used as an accurate, alternative estimation of IR. This study aims to determine the prevalence of NAFLD in T1D, to estimate IR using the eGDR and elucidate associations between NAFLD, IR and CVD.

Materials and methods: 296 T1D subjects were consecutively screened for NAFLD using ultrasound criteria and underwent anthropometry, clinical examination and laboratory testing. The eGDR was calculated as follows: eGDR (mg/kg per min)=21.158+(–0.09*waist circumference (cm))+ (–3.407*hypertension)+(–0.551*HbA1c (%)). A history of past CVD was determined by assessing the individual patient files. The eGDR was divided into 3 categories (<5.39; 5.39–7.75; >7.75 mg/kg per min), with the lowest category representing the highest degree of IR (Epstein et al., 2013).

Results: Median age was 48 years (range 18–88), median diabetes duration was 27 years (range 1–61), mean HbA1c: 7.6±1.0%, mean BMI: 26.2±4.5 kg/m². 36.1% of cases were overweight, 19.6% were obese. NAFLD was present in 20.6% of cases. Subjects with vs. without NAFLD were older (51±16 vs 46±16 y, P=0.013), had higher BMI (29.8±5.0 vs 25.2±3.9 kg/m2, P<0.001), ALT (32±21 vs 24±11 U/l, P<0.001), γ-GT (38±33 vs 28±27 U/l, P=0.039), triglycerides (111±86 vs 79±39 mg/dl, P<0.001) and lower HDL-cholesterol levels (57±15 vs 64±17 mg/dl, P=0.001). Concerning IR, only 5.7% of subjects fell in the highest category, but 26.4% expressed mild IR. NAFLD prevalence was 41%, 40% and 12% in the high, medium and low IR groups respectively (P<0.001). eGDR was lower in NAFLD subjects (7.1±2.0 vs 8.8±1.6 mg/kg per min, P<0.001). Composite CVD was present in 8.8% (coronary artery disease (CAD) 5.8%, peripheral arterial disease (PAD) 4.7%, cerebrovascular accident (CVA) 1.4%). The prevalence of composite CVD (21.3 vs 5.5%, P<0.001), CAD (13.1 vs 3.9%, P=0.011), PAD (11.7 vs 2.7%, P=0.009) and CVA (4.9 vs 0.4%, P=0.029) were higher in the NAFLD group. The prevalence of composite CVD was 23.5%, 16.0% and 4.9% in the high, medium and low IR groups respectively (P=0.001). Independent risk factors for composite CVD were the presence of NAFLD (OR:3.96 [95%CI: 3.40–11.23], P=0.010), eGDR (OR:1.3, [95%CI: 1.00–1.80], P=0.047) and age (OR:1.1, [95%CI: 1.02–1.12], P=0.005) when including these parameters and BMI, gender and diabetes duration in the regression model.

Conclusion: NAFLD and IR are common in T1D and both are independently correlated with the presence of cardiovascular events, with the highest odds ratio for NAFLD. Although cross-sectional data do not prove causality, these results suggest a possible pivotal role for NAFLD and/or IR in the cardiometabolic risk profile of T1D. Longitudinal studies are needed to further investigate the role of NAFLD and/or IR as independent risk factors in T1DM.