Non-insulin-dependent diabetes mellitus (NIDDM) is a metabolic disease characterized by insulin resistance and hyperglycemia often associated with hypertension, lipid disturbances, and obesity. The underlying pathology of NIDDM is impaired beta-cell function, but insulin resistance may be the primary cause of the beta-cell failure. Insulin resistance may also be responsible for the obesity associated with NIDDM, although obesity itself has a reciprocal effect on insulin resistance; excess weight worsens insulin resistance, while weight loss lowers blood glucose and lipid levels and blood pressure. More than 75% of patients with newly diagnosed NIDDM are obese (usually with upper-body or "androgenic" obesity).

Insulin resistance has also been implicated in the pathologic conditions that constitute "the metabolic syndrome", including hypertension, lipid disturbances, and coronary, cerebral, and peripheral vascular disease. Insulin resistance in NIDDM was recognized decades ago when it was noted that patients often have hyperglycemia despite high plasma concentrations of insulin. When insulin resistance first develops, glucose intolerance develops. In patients with impaired glucose tolerance, the annual risk of progression to full blown diabetes is 2-5%.

Other factors for NIDDM include increasing age, physical inactivity, and genetics. It has been suggested that there is a "thrifty genotype," a genetic tendency to store up for lean times that is not advantageous in times of plenty. It has also been suggested that a thrifty metabolism might be acquired. Recent studies indicate that fetal malnutrition or poor nutrition in early childhood may contribute to a thrifty metabolism, resulting in metabolic dysfunction in adulthood, including insulin resistance. It is also possible that low birth weight signals poor fetal development of the pancreas, especially beta-cells, which later cannot compensate for insulin resistance. Low birth weight is known to be a risk factor for NIDDM in later life.

The best prevention for NIDDM is avoiding obesity and increasing one's physical activity. Exercise improves insulin sensitivity; even when weight remains the same. For both types of diabetes, IDDM and NIDDM, control of blood glucose levels, lipid levels, blood pressure, and weight will reduce the risk of vascular damage with associated coronary artery disease, kidney disease, and retinal damage.