Insulin resistance predicts atherosclerosis in Type 1 diabetes
MedWire News: Insulin resistance in Type 1 diabetes extends beyond glucose control to regulation of fat metabolism and appears to be associated with increased coronary artery calcification (CAC), results of the CACTI study show.
The findings suggest that insulin resistance, possibly through lipotoxicity, may play a role in the residual risk for cardiovascular disease (CVD), thus representing an "important therapeutic target that is not currently considered in Type 1 diabetes," say Irene Schauer (University of Colorado, Denver, USA) and colleagues in the journal Diabetes.
Standard prediction rules for CVD risk are not accurate in Type 1 diabetic populations and tight glycemic control improves, but does not normalize CVD risk.
Currently, the mechanism of accelerated atherosclerosis in Type 1 diabetes is unclear and identification of those patients at highest risk and most in need of aggressive risk factor modification is inaccurate.
Attempting to address these shortcomings, the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study followed-up 40 patients with Type 1 diabetes and 47 non-diabetic patients for 6 years for CVD outcomes.
Insulin action was measured by a three-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m2/min), while electron beam computed tomography was used for measuring CAC.
Schauer et al report that peripheral glucose utilization was lower in patients with Type 1 diabetes compared with non-diabetic controls after adjustment for age, gender, body mass index, fasting glucose, and final clamp glucose and insulin, with mean glucose infusion rates of 6.19 versus 12.71 mg/kgFFM/min.
Insulin-induced non-esterified fatty acid (NEFA) suppression was also lower in Type 1 diabetic patients compared with non-diabetic patients after adjustment, with NEFA levels during 8 mU/m2/min insulin infusion of 370 vs 185 µM.
Notably, glucose utilization and NEFA levels were correlated with CAC volume and predicted the presence of CAC, with odds ratios of 0.45 and 2.40 for presence of CAC associated with a one standard deviation increase in glucose utilization and NEFA levels, respectively.
Insulin resistance did not correlate with glycosylated hemoglobin or continuous glucose monitoring parameters.
Thus, insulin resistance may contribute to the increased risk for CVD in patients with Type 1 diabetes, say Schauer and colleagues.
"We are developing an insulin sensitivity prediction model based on this study, and will apply this model to baseline and follow-up data to allow a prospective analysis of the correlation of estimated insulin resistance with CAC and to increase the power of the analysis in the diabetic cohort," the researchers add.
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By Andrew Czyzewski