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

J Diabetes Complications. 2018 Apr;32(4):418-423. doi: 10.1016/j.jdiacomp.2018.01.002. Epub 2018 Jan 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / metabolism
  • Adult
  • Cardiovascular Diseases / etiology
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Humans
  • Insulin / metabolism*
  • Insulin / therapeutic use
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Random Allocation
  • Sex Factors


  • Insulin