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
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
prenatal factors
in utero environment resulting in low birth weight may predispose some individuals to develop type 2 diabetes mellitus
obesity
risk for onset of T2DM correlates with BMI although this is different for different ethnic genetic backgrounds
PH gestational diabetes
hypertension
also approx. double risk if PH gestational hypertension or pre-eclampsia
hyperlipidaemia
type 1 diabetes mellitus
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