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 years, BMI 48%ile; diabetes duration 73 ± 52 months, HbA1c 8.3±1.4%) and 17 non-diabetic controls (47% female, age 15.0±2 years, 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 LDL-C and less as large boyant 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 towards 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.

Vascular and metabolic effects of metformin added to insulin therapy in patients with type 1 diabetes: A systematic review andmeta‐analysis

“…Of note, in the present study, Sarnblad et al 36 and Cree-Green et al 24 have conducted studies in adolescents, and emphasized the effect of metformin on peripheral IR, showing considerable significance to obtain metabolic effects in T1DM. Obesity, mitochondrial dysfunction, 43 and unique pubertal changes in hormones 44 have been proven to be closely related to peripheral insulin sensitivity. However, considering the small number of trials on insulin resistance included in our study, the different methods used to study insulin resistance, the possible flaws caused by the more accurate protocol hot GINF not mentioned to be used in the trials using the Although several previous meta-analyses [45][46][47] have provided little evidence that metformin improves glycaemic control, our metaanalysis provided up-to-date evidence that metformin reduced the HbA1c levels slightly, and plasma glycaemia in patients with T1DM.…”

Obese adolescents with polycystic ovarian syndrome have elevated cardiovascular disease risk markers

“…We have previously shown alteration in these profiles for both adults and youth with type 1 diabetes, who have an increased risk of CVD mortality. 46,53 The adult women with type 1 diabetes had a shift of LDL fractions to the denser more atherogenic type. 46 In youth with type 1 diabetes, LDL was shifted towards denser fractions, with the adolescent females having a more ‘male’ atherogenic profile.…”

Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review

“…This IR in T1DM occurs irrespective of obesity and metabolic syndrome features (58, 61–63). Moreover, IR confers higher risk for a more atherogenic lipoprotein profile (64, 65) and micro- and macrovascular complications in T1DM youth (66) and adults (67, 68). …”