Clinical and genetic determinants of progression of type 2 diabetes: a DIRECT study.

Abstract:

OBJECTIVE:To identify the clinical and genetic factors that explain why the rate of diabetes progression is highly variable between individuals following diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS:We 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 HbA1c ≥8.5% [69 mmol/mol] treated with two or more noninsulin therapies). RESULTS:Risk of progression was associated with both low and high BMI. In an analysis stratified by BMI and HbA1c 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. CONCLUSIONS:Increased 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.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Zhou K,Donnelly LA,Morris AD,Franks PW,Jennison C,Palmer CN,Pearson ER

doi

10.2337/dc13-1995

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

718-724

issue

3

eissn

0149-5992

issn

1935-5548

journal_volume

37

pub_type

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