Cause or effect? A review of clinical data demonstrating beta cell dysfunction prior to the clinical onset of type 1 diabetes

Mol Metab. 2019 Sep;27S(Suppl):S129-S138. doi: 10.1016/j.molmet.2019.06.010.


Background: Limited successes of conventional approaches to type 1 diabetes (T1D) prevention and treatment have highlighted the need for improved understanding of risk factors contributing to or hastening progression to clinical diagnosis.

Scope of review: This review summarizes beta cell function metabolic phenotyping data from clinical studies conducted in at-risk individuals before T1D onset and healthy controls. Data are drawn from studies comparing at-risk individuals who progress to T1D to at-risk individuals who do not progress to T1D, as well as from studies comparing at-risk individuals to controls without a T1D family history.

Major conclusions: Rapid loss of beta cell insulin secretion occurs in the months immediately preceding clinical onset. However, evidence of beta cell dysfunction is present even years earlier. Comparisons to controls without a family history suggest that many individuals in families impacted by T1D have evidence of beta cell dysfunction, even individuals who are unlikely to develop clinical disease. These findings may mean that underlying metabolic beta cell dysfunction contributes to T1D development and may explain some of the heterogeneity observed in the disease.

Keywords: Beta cell; Insulin secretion; Risk prediction; Type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology*
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology*