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Clinical and Genetic Determinants of Progression of Type 2 Diabetes: A DIRECT Study

  • Kaixin Zhou
  • Louise A. Donnelly
  • Andrew D. Morris
  • Paul Franks
  • Chris Jennison
  • Colin N. A. Palmer
  • Ewan R. Pearson
Publishing year: 2014
Language: English
Pages: 718-724
Publication/Series: Diabetes Care
Volume: 37
Issue: 3
Document type: Journal article
Publisher: American Diabetes Association

Abstract english

OBJECTIVETo identify the clinical and genetic factors that explain why the rate of diabetes progression is highly variable between idividuals following diagnosis of type 2 diabetes.RESEARCH DESIGN AND METHODSWe studied 5,250 patients with type 2 diabetes using comprehensive electronic medical records in Tayside, Scotland, from 1992 onward. We investigated the association of clinical, biochemical, and genetic factors with the risk of progression of type 2 diabetes from diagnosis to the requirement of insulin treatment (defined as insulin treatment or HbA(1c) 8.5% [69 mmol/mol] treated with two or more noninsulin therapies).RESULTSRisk of progression was associated with both low and high BMI. In an analysis stratified by BMI and HbA(1c) at diagnosis, faster progression was independently associated with younger age at diagnosis, higher log triacylglyceride (TG) concentrations (hazard ratio [HR] 1.28 per mmol/L [95% CI 1.15-1.42]) and lower HDL concentrations (HR 0.70 per mmol/L [95% CI 0.55-0.87]). A high Genetic Risk Score derived from 61 diabetes risk variants was associated with a younger age at diagnosis and a younger age when starting insulin but was not associated with the progression rate from diabetes to the requirement of insulin treatment.CONCLUSIONSIncreased TG and low HDL levels are independently associated with increased rate of progression of diabetes. The genetic factors that predispose to diabetes are different from those that cause rapid progression of diabetes, suggesting a difference in biological process that needs further investigation.


  • Endocrinology and Diabetes


  • Genetic and Molecular Epidemiology
  • ISSN: 1935-5548
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49



Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00