Insulin resistance, defective insulin-mediated fatty acid suppression, and coronary artery calcification in subjects with and without type 1 diabetes: The CACTI study.
OBJECTIVE
To 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.


METHODS
Insulin 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).


RESULTS
Peripheral 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.


CONCLUSIONS
Type 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.
Schauer
Irene E
IE
Department of Medicine, University of Colorado Denver, Aurora, USA. irene.schauer@ucdenver.edu
Snell-Bergeon
Janet K
JK
Bergman
Bryan C
BC
Maahs
David M
DM
Kretowski
Adam
A
Eckel
Robert H
RH
Rewers
Marian
M
D000005:Abdomen / Q000033:anatomy & histology; D015502:Absorptiometry, Photon / Q000379:methods; D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D002118:Calcium / Q000097:blood; D015331:Cohort Studies; D003331:Coronary Vessels / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000401:mortality; D004784:Environmental Monitoring; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D005990:Glycerol / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013154:Spleen / Q000033:anatomy & histology; D014057:Tomography, X-Ray Computed; D055815:Young Adult
D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005990:Glycerol; D002118:Calcium