Clinical and genetic determinants of progression of type 2 diabetes

A DIRECT Study

Kaixin Zhou, Louise A. Donnelly, Andrew D. Morris, Paul W. Franks, Chris Jennison, Colin N. A. Palmer, Ewan R. Pearson (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Objective The rate at which diabetes progresses following diagnosis of type 2 diabetes is highly variable between individuals.Research Design and Methods We studied 5250 patients with type 2 diabetes using comprehensive electronic medical records on all patients in Tayside, Scotland from 1992 onwards. We investigated the association of clinical, biochemical and genetic factors with the risk of progression of type 2 diabetes from diagnosis to requirement for insulin treatment (defined as insulin treatment or HbA1c ?8.5%/69 mmol/mol treated with two or more non-insulin diabetes 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 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 of diagnosis, a younger age at starting insulin, but was not associated with the progression rate from diabetes to requirement for insulin treatment.Conclusions Increased triacylglyceride and low HDL 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.
    Original languageEnglish
    Pages (from-to)718-724
    JournalDiabetes Care
    Volume37
    Issue number3
    Early online date1 Nov 2013
    DOIs
    Publication statusPublished - 1 Mar 2014

    Fingerprint

    Type 2 Diabetes Mellitus
    Insulin
    Biological Phenomena
    Electronic Health Records
    Scotland
    Therapeutics
    Molecular Biology
    Research Design

    Cite this

    Zhou, Kaixin ; Donnelly, Louise A. ; Morris, Andrew D. ; Franks, Paul W. ; Jennison, Chris ; Palmer, Colin N. A. ; Pearson, Ewan R. / Clinical and genetic determinants of progression of type 2 diabetes : A DIRECT Study. In: Diabetes Care. 2014 ; Vol. 37, No. 3. pp. 718-724.
    @article{892d419faeef418fb7866480188b025b,
    title = "Clinical and genetic determinants of progression of type 2 diabetes: A DIRECT Study",
    abstract = "Objective The rate at which diabetes progresses following diagnosis of type 2 diabetes is highly variable between individuals.Research Design and Methods We studied 5250 patients with type 2 diabetes using comprehensive electronic medical records on all patients in Tayside, Scotland from 1992 onwards. We investigated the association of clinical, biochemical and genetic factors with the risk of progression of type 2 diabetes from diagnosis to requirement for insulin treatment (defined as insulin treatment or HbA1c ?8.5{\%}/69 mmol/mol treated with two or more non-insulin diabetes 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 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 of diagnosis, a younger age at starting insulin, but was not associated with the progression rate from diabetes to requirement for insulin treatment.Conclusions Increased triacylglyceride and low HDL 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 = "Kaixin Zhou and Donnelly, {Louise A.} and Morris, {Andrew D.} and Franks, {Paul W.} and Chris Jennison and Palmer, {Colin N. A.} and Pearson, {Ewan R.}",
    year = "2014",
    month = "3",
    day = "1",
    doi = "10.2337/dc13-1995",
    language = "English",
    volume = "37",
    pages = "718--724",
    journal = "Diabetes Care",
    issn = "0149-5992",
    publisher = "American Diabetes Association",
    number = "3",

    }

    Clinical and genetic determinants of progression of type 2 diabetes : A DIRECT Study. / Zhou, Kaixin; Donnelly, Louise A.; Morris, Andrew D.; Franks, Paul W.; Jennison, Chris; Palmer, Colin N. A.; Pearson, Ewan R. (Lead / Corresponding author).

    In: Diabetes Care, Vol. 37, No. 3, 01.03.2014, p. 718-724.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Clinical and genetic determinants of progression of type 2 diabetes

    T2 - A DIRECT Study

    AU - Zhou, Kaixin

    AU - Donnelly, Louise A.

    AU - Morris, Andrew D.

    AU - Franks, Paul W.

    AU - Jennison, Chris

    AU - Palmer, Colin N. A.

    AU - Pearson, Ewan R.

    PY - 2014/3/1

    Y1 - 2014/3/1

    N2 - Objective The rate at which diabetes progresses following diagnosis of type 2 diabetes is highly variable between individuals.Research Design and Methods We studied 5250 patients with type 2 diabetes using comprehensive electronic medical records on all patients in Tayside, Scotland from 1992 onwards. We investigated the association of clinical, biochemical and genetic factors with the risk of progression of type 2 diabetes from diagnosis to requirement for insulin treatment (defined as insulin treatment or HbA1c ?8.5%/69 mmol/mol treated with two or more non-insulin diabetes 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 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 of diagnosis, a younger age at starting insulin, but was not associated with the progression rate from diabetes to requirement for insulin treatment.Conclusions Increased triacylglyceride and low HDL 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.

    AB - Objective The rate at which diabetes progresses following diagnosis of type 2 diabetes is highly variable between individuals.Research Design and Methods We studied 5250 patients with type 2 diabetes using comprehensive electronic medical records on all patients in Tayside, Scotland from 1992 onwards. We investigated the association of clinical, biochemical and genetic factors with the risk of progression of type 2 diabetes from diagnosis to requirement for insulin treatment (defined as insulin treatment or HbA1c ?8.5%/69 mmol/mol treated with two or more non-insulin diabetes 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 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 of diagnosis, a younger age at starting insulin, but was not associated with the progression rate from diabetes to requirement for insulin treatment.Conclusions Increased triacylglyceride and low HDL 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.

    U2 - 10.2337/dc13-1995

    DO - 10.2337/dc13-1995

    M3 - Article

    VL - 37

    SP - 718

    EP - 724

    JO - Diabetes Care

    JF - Diabetes Care

    SN - 0149-5992

    IS - 3

    ER -