Sex-specific differences in insulin resistance in type 1 diabetes: The CACTI cohort

Abstract

Objective: To test the hypothesis that multitissue deficits in insulin sensitivity are greater among women than men with type 1 diabetes compared to respective controls.

Research design and methods: Three-stage hyperinsulinemic-euglycemic clamps (4, 8, 40 mU/m2/min) were performed on 41 people with type 1 diabetes and 47 adults without diabetes (mean ± SD age 46 ± 8). Infusions of [1-13C]palmitate, [1,1,2,3,3-2H2]glycerol, and [6,6-2H2]glucose isotope tracers were used to determine free fatty acid (FFA), glycerol, and glucose kinetics in 52 of these participants (25 M and 27 W).

Results: There was no difference in age or BMI by type 1 diabetes status in either sex. Free fatty acid rate of appearance (FFA Ra) was higher in both sexes with type 1 diabetes compared to those without diabetes during stages 1 and 2. The same was seen with glycerol for stages 1 and 2. During stage 3 glucose rate of disappearance (Rd) was lower in those with type 1 diabetes among both sexes. All had sex by type 1 diabetes interactions with greater deficits in insulin sensitivity in women. While there was no sex by diabetes interaction in regards to glucose rate of appearance (Ra), those with type 1 diabetes had a higher glucose Ra than those without diabetes.

Conclusions: We found that type 1 diabetes affected adipose and skeletal muscle insulin sensitivity to a greater extent in women than in men, perhaps contributing to the greater relative increase in cardiovascular risk in women with type 1 diabetes.

Keywords: Cardiovascular disease; Diabetes; Gender differences; Insulin resistance; Type 1.

Conflict of interest statement

Conflicts of Interest: There are no conflicts of interest.

Copyright © 2018. Published by Elsevier Inc.

Figures

Figure A.1. Skeletal Muscle Insulin Sensitivity

(A.1) M-value by sex and diabetes status, (A.2)) Glucose rate of disappearance. Results are shown by sexes based on diabetes status and expressed by least significant means (LSM). *: P

Figure B. Adipose Tissue Insulin Sensitivity

(B.1) Non Esterified Fatty Acid levels by time and diabetes status, (B.2) Free Fatty Acid rate of appearance, (B.3) Glycerol by time and diabetes status, (B.4) Glycerol rate of appearance. Results are shown by sexes based on diabetes status. Results are expressed by least significant means (LSM). *: P

Figure C.1. Hepatic Insulin Sensitivity

(C) Glucose rate of appearance between sexes based on diabetes status. Results are expressed as least significant means (LSM). *: P