Type 2 Diabetes

Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is characterized differently and is due to:

• insulin resistance or
• reduced insulin sensitivity,
• combined with relatively reduced insulin secretion

The defective responsiveness of body tissues to insulin almost certainly involves the insulin receptor in cell membranes. However, the specific defects are not known. Diabetes mellitus due to a known specific defect are classified separately.
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, 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, likely 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, 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
• heart failure from diabetic cardiomyopathy.
Type 2 diabetes is usually first treated by
• increasing physical activity
• decreasing carbohydrate intake
• losing weight

These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits.

It is sometimes possible to achieve long-term, satisfactory glucose control with these measures alone.

However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue.

The usual next step, if necessary, is treatment with oralantidiabetic drugs. Insulin production is initially only moderately impaired in type 2 diabetes, so oral medication (often used in various combinations) can be used to improve insulin production (e.g., sulfonylureas), to regulate inappropriate release of glucose by the liver and attenuate insulin resistance to some extent (e.g., metformin), and to substantially attenuate insulin resistance (e.g., thiazolidinediones).

According to one study, overweight patients treated with metformin compared with diet alone, had relative risk reductions of 32% for any diabetes endpoint, 42% for diabetes related death and 36% for all cause mortality and stroke.

Oral medication may eventually fail due to further impairment of beta cell insulin secretion. At this point, insulin therapy is necessary to maintain normal or near normal glucose levels.