Deteriorating beta-cell function in type 2 diabetes: a long-term model

QJM. 2003 Apr;96(4):281-8. doi: 10.1093/qjmed/hcg040.


Background: Type 2 diabetes is characterized by insulin resistance and the progressive loss of islet beta-cell function. Although the former is already established at diagnosis and changes little thereafter, beta-cell function continues to decline, leading to secondary failure of anti-hyperglycaemic therapies.

Aim: To develop a quantitative model of the process of beta-cell function decay over time, using trial data.

Design: Re-analysis of published data.

Methods: The results of the Belfast Diet Study were re-analysed. Assuming patients are diagnosed at different stages in the disease process, time displacement of data was used to obtain a bi-partite spline model describing loss of insulin secretion over a 6-year period.

Results: The model was developed combining two phases, in which a long slow gradual loss of beta-cell function leads to a crisis in metabolic regulation, precipitating a much more rapid decay phase. This paradigm was consistent with a previous non-linear model of beta-cell mass regulation.

Discussion: This model may have important implications for targeting appropriate therapy to patients in each phase: delaying or avoiding full clinical type 2 diabetes in the first phase; and preventing the development of diabetic complications in the second phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Humans
  • Insulin / blood
  • Islets of Langerhans / physiopathology*
  • Middle Aged
  • Time Factors


  • Blood Glucose
  • Insulin