Impaired pancreatic beta cell compensatory function is the main cause of type 2 diabetes in individuals with high genetic risk: a 9 year prospective cohort study in the Chinese population

Diabetologia. 2016 Jul;59(7):1458-1462. doi: 10.1007/s00125-016-3939-y. Epub 2016 Mar 23.


Aims/hypothesis: We aimed to evaluate the combined effects of type 2 diabetes risk variants on predicting deterioration of blood glucose and progression of beta cell function and insulin sensitivity in a 9 year prospective cohort from the Chinese population.

Methods: We constructed a weighted genetic risk score (GRS) model based on 40 variants associated with type 2 diabetes validated in an established cross-sectional Chinese population (n = 6,822). The weighted scores were categorised into tertiles to assess the predictive capacity for incidence of type 2 diabetes and impaired glucose regulation (IGR), as well as for changes in Stumvoll first- and second-phase insulin secretion indices and Gutt's insulin sensitivity index (ISI) in a community-based 9 year prospective cohort (n = 2,495), including 2,192 individuals with normal glucose tolerance and 303 with IGR at baseline, through logistic, Cox and multiple linear regression tests.

Results: Weighted GRS predicted the incidence of type 2 diabetes and IGR in logistic regression (OR 1.236, 95% CI 1.100, 1.389, p = 0.0004) as well as in the Cox model (HR 1.129, 95% CI 1.026, 1.242, p = 0.0128) after adjusting for age, sex, BMI, smoking and alcohol status at baseline. Moreover, we observed that weighted GRS was able to predict deterioration in beta cell function (β = -0.0480, p = 9.66 × 10(-5) and β = -0.0303, p = 3.32 × 10(-5) for first- and second-phase insulin secretion, respectively), but not insulin sensitivity (p = 0.3815), during the 9 year follow-up period.

Conclusions/interpretation: The weighted GRS predicted blood glucose deterioration arising from change in beta cell function in the Chinese population. Individuals in the intermediate- or high-weighted GRS group exhibited progressive deterioration of beta cell function.

Keywords: Beta cell function; Prospective study; Weighted genetic risk score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group
  • Blood Glucose / metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Genotype
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / physiology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Prospective Studies
  • Risk Factors


  • Blood Glucose
  • Insulin