Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes

Nat Rev Endocrinol. 2016 Jul;12(7):394-406. doi: 10.1038/nrendo.2016.50. Epub 2016 Apr 15.

Abstract

Insights into the genetic basis of type 2 diabetes mellitus (T2DM) have been difficult to discern, despite substantial research. More is known about rare forms of diabetes mellitus, several of which share clinical and genetic features with the common form of T2DM. In this Review, we discuss the extent to which the study of rare and low-frequency mutations in large populations has begun to bridge the gap between rare and common forms of diabetes mellitus. We hypothesize that the perceived division between these diseases might be due, in part, to the historical ascertainment bias of genetic studies, rather than a clear distinction between disease pathophysiologies. We also discuss possible implications of a new model for the genetic basis of diabetes mellitus subtypes, where the boundary between subtypes becomes blurred.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus / genetics
  • Diabetes Mellitus, Type 2 / classification
  • Diabetes Mellitus, Type 2 / genetics*
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation
  • Rare Diseases
  • Sequence Analysis, DNA

Supplementary concepts

  • Diabetes Mellitus, Permanent Neonatal
  • MODY, Type 6
  • Maturity-Onset Diabetes of the Young, Type 1
  • Maturity-Onset Diabetes of the Young, Type 2
  • Maturity-Onset Diabetes of the Young, Type 3
  • Maturity-Onset Diabetes of the Young, Type 4