Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes

Abstract

OBJECTIVETo assess insulin action on peripheral glucose utilization and nonesterified fatty acid (NEFA) suppression as a predictor of coronary artery calcification (CAC) in patients with type 1 diabetes and nondiabetic controls.RESEARCH DESIGN AND METHODSInsulin action was measured by a three-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m2/min) in 87 subjects from the Coronary Artery Calcification in Type 1 Diabetes cohort (40 diabetic, 47 nondiabetic; mean age 45 ± 8 years; 55% female).RESULTSPeripheral glucose utilization was lower in subjects with type 1 diabetes compared with nondiabetic controls: glucose infusion rate (mg/kg FFM/min) = 6.19 ± 0.72 vs. 12.71 ± 0.66, mean ± SE, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and final clamp glucose and insulin. Insulin-induced NEFA suppression was also lower in type 1 diabetic compared with nondiabetic subjects: NEFA levels (μM) during 8 mU/m2/min insulin infusion = 370 ± 27 vs. 185 ± 25, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and time point insulin. Lower glucose utilization and higher NEFA levels, correlated with CAC volume (r = −0.42, P < 0.0001 and r = 0.41, P < 0.0001, respectively) and predicted the presence of CAC (odds ratio [OR] = 0.45, 95% CI = 0.22–0.93, P = 0.03; OR = 2.4, 95% CI = 1.08–5.32, P = 0.032, respectively). Insulin resistance did not correlate with GHb or continuous glucose monitoring parameters.CONCLUSIONSType 1 diabetic patients are insulin resistant compared with nondiabetic subjects, and the degree of resistance is not related to current glycemic control. Insulin resistance predicts the extent of coronary artery calcification and may contribute to the increased risk of cardiovascular disease in patients with type 1 diabetes as well as subjects without diabetes.

Type 1 Diabetes Mellitus and Cardiovascular Disease

“…Measurement of insulin resistance is challenging in patients receiving insulin. Research studies have used regression equations derived from clamp studies; the derived estimated glucose disposal rate 157 predicts both CVD and diabetic nephropathy. 158,159 Subsequent observations from the EURODIAB Study also suggested that insulin resistance-related risk factors predicted CHD events in patients with T1DM, 138 and insulin resistance explains some portion of lipid abnormalities in young patients with T1DM.…”

The Effect of Admission Renal Function on the Treatment and Outcome of Patients with Acute Coronary Syndrome

“…Different factors associated with impaired renal function are believed to contribute to adverse outcomes of patients with ACS. These factors include insulin resistance [4,5], oxidative stress [6], inflammation [7], endothelial dysfunction [8], vascular calcifications [9], and hypercoagulability [10]. Furthermore, the presence of chronic kidney disease is associated with a higher prevalence of baseline cardiovascular comorbidities including diabetes, heart failure, previous myocardial infarction, and stroke [1,2,11].…”

Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study

“…The mechanisms of IR in T1DM is likely due to a combination of supraphysiologic levels of exogenous insulin and obesity. In the past, it was thought that IR in T1D was primarily related to hyperglycemia (16), however, it was recently proposed that adults with T1DM have both impaired glucose utilization and impaired insulin-induced non-esterified fatty acid suppression, independent of glycemic control (17). Skeletal muscle IR is a known feature of T1DM and is due to decreased glucose transport into myocytes from impaired insulin-stimulated upregulation of GLUT4 mRNA (18).…”