Apolipoprotein C-III protein concentrations and gene polymorphisms in Type 1 diabetes: Associations with microvascular disease complications in the DCCT/EDIC cohort

DCCT/EDIC Research Group,; Klein, Richard L.; McHenry, M.Brent; Lok, Kerry H.; Hunter, Steven J.; Le, Ngoc-Anh; Jenkins, Alicia J.; Zheng, Deyi; Semler, Andrea; Page, Grier; Brown, W.Virgil; Lyons, Timothy J.; Garvey, W.Timothy

doi:10.1016/j.jdiacomp.2004.04.005

« Previous Next »Journal of Diabetes and Its Complications
Volume 19, Issue 1 , Pages 18-25, January 2005

Apolipoprotein C-III protein concentrations and gene polymorphisms in Type 1 diabetes:

Associations with microvascular disease complications in the DCCT/EDIC cohort

DCCT/EDIC Research Group
Richard L. Klein
- Corresponding author. Department of Medicine, Division of Endocrinology, Metabolism and Medical Genetics, Medical University of South Carolina, 114 Doughty Street, P.O. Box 250770, Charleston, SC 29425, USA. Tel.: +1-843-789-6801; fax: +1-843-876-5133.
- Department of Medicine, Division of Endocrinology, Metabolism, and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA
- Research Service, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA
M.Brent McHenry
- Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC, USA
Kerry H. Lok
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
Steven J. Hunter
- Department of Medicine, Division of Endocrinology, Metabolism, and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA
Ngoc-Anh Le
- Division of Atherosclerosis and Lipid Metabolism, Emory University, Atlanta, GA, USA
Alicia J. Jenkins
- Department of Medicine, Division of Endocrinology, Metabolism, and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA
- Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, Australia
- Section of Endocrinology Diabetes and Hypertension, Oklahoma University Health Sciences Foundation, Oklahoma City, OK, USA
Deyi Zheng
- Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC, USA
Andrea Semler
- Department of Medicine, Division of Endocrinology, Metabolism, and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA
Grier Page
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
W.Virgil Brown
- Division of Atherosclerosis and Lipid Metabolism, Emory University, Atlanta, GA, USA
Timothy J. Lyons
- Section of Endocrinology Diabetes and Hypertension, Oklahoma University Health Sciences Foundation, Oklahoma City, OK, USA
W.Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA

Received 3 September 2003; received in revised form 21 April 2004; accepted 30 April 2004.

Abstract

Aim

We investigated the associations of apolipoprotein C-III (apoCIII) protein and apoCIII gene variation with microvascular disease complications in Type 1 diabetes.

Methods

The serum apoCIII concentration, and both a T⁻⁴⁵⁵→C and a SacI gene polymorphisms were determined in 409 patients in the DCCT/EDIC cohort of patients with Type 1 diabetes. Correlations with albumin excretion rate (AER) and the severity of retinopathy were investigated.

Results

Higher apoCIII concentrations were associated (P<.0001) with increased triglycerides (r=.78), total (r=.61) and LDL (r=.40) cholesterol, apoAI (r=.26), and apoB (r=.50), AER (r=.08), and the severity of retinopathy (ETDRS score, r=.11), and these relationships persisted after controlling for age, gender, body mass index (BMI), and HbA1c level. The apoCIII concentration was significantly higher in the group of patients with macroalbuminuria (AERs 300 mg/24 h) compared to the groups with microalbuminuria (AER 40–299 mg/24 h; P<.0001) or normoalbuminuria (AER <40 mg/24 h) (P<.0001). The apoCIII concentration also was significantly higher in the group of patients with severe retinopathy (ETDRS 10–23) compared to those with moderate (ETDRS 4–9; P<.02) or mild retinopathy (ETDRS 1–3; P<.0001). Neither the T⁻⁴⁵⁵→C polymorphism nor a SacI polymorphism in the 3′ UTR were associated with circulating apoCIII concentrations, nor the severity of nephropathy or retinopathy.

Conclusions

Elevated apoCIII levels have been associated with increased macrovascular disease risk. In the DCCT/EDIC cohort of patients, there was an independent positive association of apoCIII level with microvascular complications of Type 1 diabetes.

Abbreviations: ApoCIII, apolipoprotein C-III, UTR, untranslated region, DCCT/EDIC, Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications, ETDRS, Early Treatment Diabetic Retinopathy Study, AER, albumin excretion rate