Endocrine Abstracts

Background and Aims

People with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD) despite insulin therapy to treat hyperglycaemia. Insulin resistance may be a contributing factor to CVD. Insulin resistance is strongly associated with NAFLD, which is increasingly linked to CVD. The estimated glucose disposal rate (eGDR) correlates well with the euglycemic clamp, which is the gold standard to assess insulin resistance in T1D, but is unsuited for clinical practice or large studies. This study aimed to assess the association between eGDR, NAFLD and CVD.

Methods

Adult T1D subjects were consecutively screened for liver steatosis using ultrasound (US), the Fatty Liver Index (FLI) and controlled attenuation parameter (CAP). Secondary causes of liver steatosis were excluded, implying that liver steatosis was due to NAFLD in all cases. The eGDR was calculated based on hypertension, HbA1c and waist circumference. CVD was assessed based on documented major adverse cardiovascular events (non-fatal myocardial infarction, non-fatal ischemic stroke or peripheral vascular disease in need of therapeutic intervention).

Results

CVD was present in 34 out of 355 subjects. Divided into tertiles (<5.39, 5.39–7.79, >7.79), 36.6% expressed low eGDR; 32.7% intermediate eGDR and 30.7% high eGDR. The eGDR is inversely associated with insulin resistance. There was moderate correlation between eGDR and FLI (r = 0.68, P < 0.001) and weak correlation with US (r = 0.33, P < 0.001) and CAP (r = 0.50, P < 0.001). In the low eGDR group (= insulin resistant group) was not only steatosis (38.5% vs. 11.2% (intermediate eGDR) and 12.8% (high eGDR)), but also composite CVD (18.5% vs. 6.0% and 2.8%) significantly more present (P < 0.001 for both). Low eGDR (OR: 4.2 [2.2–8.2], P < 0.001), but not BMI or dyslipidaemia was independently associated with US-defined NAFLD. Low eGDR was also independently associated with FLI-determined NAFLD (OR: 5.5 [1.7–17.6], P = 0.004) together with BMI (OR: 1.6 [1.4–1.9], P < 0.001). Low eGDR (OR: 8.0 [2.3–27.4], P = 0.001) and NAFLD (OR: 2.7 [1.2–6.1], P = 0.022 (US-defined), OR: 2.9 [1.4–6.0], P = 0.005 (FLI-defined)) were independently associated with CVD, but presence of metabolic syndrome, dyslipidaemia and BMI were not.

Conclusions

Insulin resistance, as assessed by eGDR, is prevalent in T1D. eGDR correlates with the presence of NAFLD. Both eGDR and NAFLD correlate with major cardiovascular adverse events.