Lipoprotein subfraction cholesterol distribution is more atherogenic in insulin resistant adolescents with type 1 diabetes

Abstract

Aims/hypothesis: Adolescents with type 1 diabetes (T1D) often have a less atherogenic-appearing fasting lipid profile than controls, despite increased rates of cardiovascular disease (CVD) as adults. We previously reported an atherogenic lipoprotein subfraction cholesterol distribution associated with insulin resistance (IR) in T1D adults. We sought to determine if T1D youth have more atherogenic profile than controls via a cross-sectional study.

Methods: Following 3 days of controlled diet and restricted exercise, fasting plasma samples were drawn from 28 T1D youth [50% female, age 15.3 ± 2 yr, body mass index (BMI) 48%ile; diabetes duration 73 ± 52 months, hemoglobin A1c (HbA1c) 8.3 ± 1.4%] and 17 non-diabetic controls (47% female, age: 15.0 ± 2 yr, BMI 49%ile) prior to a hyperinsulinemic euglycemic clamp. Lipoproteins were fractionated by fast protein liquid chromatography (FPLC) and lipoprotein cholesterol distribution determined. Outcome measures were IR assessed by glucose infusion rate (GIR) and FPLC lipoprotein subfraction cholesterol distribution.

Results: T1D youth were more IR (GIR 9.1 ± 3.6 vs. 14.7 ± 3.9 mg/kg/min, p < 0.0001) and had more cholesterol distributed as small dense low density lipoprotein-cholesterol (LDL-C) and less as large buoyant high density lipoprotein-cholesterol (HDL-C) than controls (p < 0.05), despite no differences in the fasting lipid panel. T1D girls lacked the typical female less-atherogenic profile, whereas control girls tended to have a shift toward less dense LDL-C and HDL-C vs. control boys. Among T1D, IR but not HbA1c was associated with a more atherogenic lipoprotein profile.

Conclusions/interpretations: Normal weight T1D youth, especially females, had more atherogenic LDL-C and HDL-C distributions which correlated with lower insulin sensitivity. IR may contribute to the increased CVD burden in T1D.

Keywords: cardiovascular disease; insulin resistance; lipids; pediatrics; type 1 diabetes.

Figure 1. Lipoprotein Subfraction Data from Youth with and without T1D

A Overall plot of percent distribution of cholesterol in each of the study groups. B Absolute differences in FPLC lipoprotein distribution by T1D status (mean proportion in T1D in each lipoprotein subfraction minus mean proportion in control in each lipoprotein subfraction, so that a mean above zero indicates more cholesterol in T1D participants and a mean below zero indicates less.”Arrows indicate fractions in which statistically significant differences exist.

Figure 2. Differences by Gender and Diabetes Status

A. Differences in FPLC lipoprotein distribution by sex in T1D participants (Male T1D – Female T1D). B. Differences in FPLC lipoprotein distribution by sex in control participants (Male control – Female control). C. Differences in FPLC lipoprotein distribution by T1D status in female participants (Female T1D – Female control). D. Differences in FPLC lipoprotein distribution by T1D status in male participants (Male T1D – Male control).

Figure 3. Effect of Glucose Control and Insulin Resistance in Altering Lipoprotein Subfraction Patterns in Youth with T1D

A Differences in FPLC lipoprotein distribution youth with T1D by HbA1C. Differences are shown between those subjects at goal (HbA1c<8%) compared to those above goal (HbA1c >8%). B Differences in FPLC lipoprotein distribution in youth with T1D by Glucose infusion rate (GIR). Differences are shown between subjects above and below the mean GIR.