Genetics of type 2 diabetes mellitus and other specific types of diabetes; its role in treatment modalities

Diabetes Metab Syndr. Jan-Mar 2012;6(1):54-8. doi: 10.1016/j.dsx.2012.05.014. Epub 2012 Jul 4.

Abstract

Type 2 diabetes mellitus (T2DM) is among the most challenging health issues of the 21st century and is associated with an alarming rise in the incidence. The pathophysiological processes that lead to development of T2DM are still unclear, however impairment in insulin secretion and/or action is clearly indicated. Type 2 diabetes is a polygenic disorder with multiple genes located on different chromosomes contributing to its susceptibility. Analysis of the genetic factors is further complicated by the fact that numerous environmental factors interact with genes to produce the disorder. Only a minority of cases of type 2 diabetes are caused by single gene defects and one example is maturity onset diabetes of the young (MODY). Previous studies indicated that variants in genes encoding the pancreatic β-cell K+ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are associated with neonatal diabetes. Six different types of maturity onset diabetes of young (MODY) have been identified based on characteristic gene defect. The common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ (PPAR-γ) gene was confirmed in several studies to be associated with type 2 diabetes as well. More recently, studies reported variants within a novel gene, TCF7L2, as a putative susceptibility gene for type 2 diabetes across many ethnic backgrounds around the world. MODY patients respond better to sulphonylureas and metformin, while neonatal diabetes patients with genetic mutations can be changed from insulin to oral drugs. We hereby provide a comprehensive review on the role of genetics in type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin
  • Insulin Resistance / genetics
  • Metformin / therapeutic use*
  • Multifactorial Inheritance / genetics*
  • Mutation*
  • PPAR gamma / genetics
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Potassium Channels, Inwardly Rectifying / genetics
  • Receptors, Drug / genetics
  • Sulfonylurea Compounds / therapeutic use
  • Sulfonylurea Receptors
  • Transcription Factor 7-Like 2 Protein / genetics
  • Treatment Outcome

Substances

  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Hypoglycemic Agents
  • Insulin
  • Kir6.2 channel
  • PPAR gamma
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Compounds
  • Sulfonylurea Receptors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Metformin