Type 2 diabetes is determined primarily by lifestyle factors and genes.
Lifestyle
A number of lifestyle factors are known to be important to the development of type 2 diabtetes. In one study, those who had high levels of physical activity, a healthy diet, did not smoke, and consumed alcohol in moderation had an 82% lower rate of diabetes. When a normal weight was included the rate was 89% lower. In this study a health diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, and a lower mean glycemic index. Obesity has been found to contribute to approximately 55% type 2 diabetes, and decreasing consumption of saturated fats and trans fatty acids well replacing them with unsaturated fats may decrease the risk. The increased rate of childhood obesity in between the 1960s and 2000s is beleived to have lead to the increase in type 2 diabetes in children and adolescents.
Environmental toxins may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of some plastics, and the incidence of type 2 diabetes.
Medical conditions
Subclinical Cushing's syndrome (cortisol excess) may be associated with DM type 2. The percentage of subclinical Cushing's syndrome in the diabetic population is about 9%. Diabetic patients with a pituitary microadenoma can improve insulin sensitivity by removal of these microadenomas.
Hypogonadism is often associated with cortisol excess, and testosterone deficiency is also associated with diabetes mellitus type 2,even if the exact mechanism by which testosterone improve insulin resistance is still not known.
Genetics
Both type 1 and type 2 diabetes are partly inherited. Type 1 diabetes may be triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular HLA genotypes (i.e., the genetic "self" identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger.
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 have a much higher risk of developing type 2, increasing with the number of those relatives. Concordance among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX.[21] KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates proglucagon gene expression and thus the production of glucagon-like peptide-1. Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.
Monogenic forms, e.g., MODY, constitute 1–5 % of all cases.
Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich's ataxia. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.
Gene expression promoted by a diet of fat and glucose as well as high levels of inflammation related cytokines found in the obese results in cells that "produce fewer and smaller mitochondria than is normal," and are thus prone to insulin resistance.