In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver. As the disease progresses, the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary.
There are numerous theories as to the exact cause and mechanism in type 2 diabetes. Central obesity (fat concentrated around the waist in relation to abdominal organs, but not subcutaneous fat) is known to predispose individuals to insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines that may possibly impair glucose tolerance. Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes. Other factors include aging (about 20% of elderly patients in North America have diabetes) and family history (type 2 is much more common in those with close relatives who have had it). In the last decade, type 2 diabetes has increasingly begun to affect children and adolescents, probably in connection with the increased prevalence of childhood obesity seen in recent decades in some places. Environmental exposures 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 polycarbonate plastic from some producers, and the incidence of type 2 diabetes.
Type 2 diabetes may go unnoticed for years because visible symptoms are typically mild, non-existent or sporadic, and usually there are no ketoacidotic episodes. However, severe long-term complications can result from unnoticed type 2 diabetes, including renal failure due to diabetic nephropathy, vascular disease (including coronary artery disease), vision damage due to diabetic retinopathy, loss of sensation or pain due to diabetic neuropathy, liver damage from non-alcoholic steatohepatitis and heart failure from diabetic cardiomyopathy.
Studies have suggested show that hormones like cortisol and possibly testosterone play a crucial role in the sugar absorption and in the insulin resistance. It has been suggested that subclinical Cushing's syndrome (cortisol excess) is associated with diabetes mellitus type 2. The percentage of subclinical Cushing's syndrome on diabetic population seems to be about 9%, but it also seems that the real percentage is higher than previously believed. Diabetic patients with a pituitary microadenoma can significantly improve insulin sensitivity and glucose tolerance by transsphenoidal surgery, because the remotion of microadenomas can decrease ACTH and cortisol levels.
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.
