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

Zhou, Kaixin; Donnelly, Louise A.; Morris, Andrew D.; Franks, Paul LU ; Jennison, Chris; Palmer, Colin N. A. and Pearson, Ewan R. (2014) In Diabetes Care 37(3). p.718-724
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
37
issue
3
pages
718 - 724
publisher
American Diabetes Association
external identifiers
  • wos:000331708600027
  • scopus:84896728658
ISSN
1935-5548
DOI
10.2337/dc13-1995
language
English
LU publication?
yes
id
674ed9b1-e968-4720-81d6-3ac15e0ee7da (old id 4495909)
date added to LUP
2014-07-01 07:35:22
date last changed
2017-01-01 06:17:09
@article{674ed9b1-e968-4720-81d6-3ac15e0ee7da,
  abstract     = {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.},
  author       = {Zhou, Kaixin and Donnelly, Louise A. and Morris, Andrew D. and Franks, Paul and Jennison, Chris and Palmer, Colin N. A. and Pearson, Ewan R.},
  issn         = {1935-5548},
  language     = {eng},
  number       = {3},
  pages        = {718--724},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Clinical and Genetic Determinants of Progression of Type 2 Diabetes: A DIRECT Study},
  url          = {http://dx.doi.org/10.2337/dc13-1995},
  volume       = {37},
  year         = {2014},
}