see also:

• diabetes mellitus

• type 2 diabetes (T2D) is a complex metabolic disease associated with:
  • obesity (BMI > 120% of ideal) - 90% are obese
  • age > 45yrs
  • energy dense diets may be an independent risk factor
  • insulin resistance
    • eg. polycystic ovary syndrome (PCOS) / polyendocrine metabolic ovarian syndrome (PMOS)
  • reduced glucose-stimulated insulin secretion (GSIS) due to pancreatic β-cell mitochondrial dysfunction
  • other factors such as schizophrenia, hypertension, hyperlipidaemia, depression
• it is thought that T2DM develops when a diabetogenic lifestyle (ie. excessive caloric intake, inadequate caloric expenditure, obesity) is superimposed on a susceptible genotype
• “secondary diabetes” may occur due to:
  • corticosteroids
  • Cushing's syndrome
  • acromegaly
  • phaeochromocytoma
  • use of antipsychotic medications

• family history of T2DM in a 1st degree relative is a significant risk factor
• Hispanic, Native American, African American, Asian American, or Pacific Islander descent
• risk is higher for a given BMI in those with Asian ancestries when compared to Europeans
• over-expression of regulator of calcineurin 1 (RCAN1) gene causes mitochondrial dysfunction in pancreatic beta cells that mimic changes in type 2 diabetes and reduce insulin secretion ¹⁾
• transcription factor 7–like 2 (TCF7L2) gene
• maturity onset diabetes of youth (MODY) is an autosomal dominant disorder consisting of at least 11 genetic subtypes

• in utero environment resulting in low birth weight may predispose some individuals to develop type 2 diabetes mellitus

• risk for onset of T2DM correlates with BMI although this is different for different ethnic genetic backgrounds
• PH gestational diabetes

• also approx. double risk if PH gestational hypertension or pre-eclampsia

• it is considered to be an autoimmune destruction of pancreatic β-cells in those who have genetic susceptibility and an environmental trigger (perhaps viral or toxin related)
• monozygotic twins will share the diagnosis more than 50% of the time by the age of 40 years
• child of mother with T1DM has 2-3% risk while child of father with T1DM has 5-6% risk, and 30% if both parents have T1DM
• most prevalent in northern Europeans, least prevalent in east Asians