Sunday 27 February 2011

Diabetes Mellitus type 2

Signs and symptoms

The classical symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), fatigue and weight loss.

Cause

Type 2 diabetes is due to a combination of lifestyle and genetic factors.

Lifestyle

A number of lifestyle factors are known to be important to the development of type 2 diabetes. 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 healthy 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% of cases of type 2 diabetes, and decreasing consumption of saturated fats and trans fatty acids while replacing them with unsaturated fats may decrease the risk. The increased rate of childhood obesity in between the 1960s and 2000s is believed to have led 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

There are many factors which can potentially give rise to or exacerbate type 2 diabetes. These include obesity, hypertension, elevated cholesterol (combined hyperlipidemia), and with the condition often termed metabolic syndrome (it is also known as Syndrome X, Reavan's syndrome, or CHAOS). Other causes include acromegaly, Cushing's syndrome, thyrotoxicosis, pheochromocytoma, chronic pancreatitis, cancer, and drugs. Additional factors found to increase the risk of type 2 diabetes include aging, high-fat diets and a less active lifestyle.
Subclinical Cushing's syndrome (cortisol excess) may be associated with type 1 diabetes. 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 type 2 diabetes, even if the exact mechanism by which testosterone improve insulin sensitivity is still not known.

Genetics

There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 increases risks of developing type 2 diabetes very substantially. In addition, there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes.
About 55 percent of type 2 diabetes patients are obese at diagnosis —chronic obesity leads to increased insulin resistance that can develop into type 2 diabetes, most likely because adipose tissue (especially that in the abdomen around internal organs) is a (recently identified) source of several chemical signals to other tissues (hormones and cytokines).
Other research shows that type 2 diabetes causes obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance.
However, environmental factors (almost certainly diet and weight) play a large part in the development of type 2 diabetes in addition to any genetic component. This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment as compared to the same genetic pool who have not. Immigrants to Western developed countries, for instance, as compared to lower incidence countries of origins.
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 diabetes have a much higher risk of developing type 2 diabetes, 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. 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.

Pathophysiology

Insulin resistance means that body cells do not respond appropriately when insulin is present. Unlike type 1 diabetes mellitus, insulin resistance is generally "post-receptor", meaning it is a problem with the cells that respond to insulin rather than a problem with the production of insulin.
This is a more complex problem than type 1, but is sometimes easier to treat, especially in the early years when insulin is often still being produced internally. Severe complications can result from improperly managed type 2 diabetes, including renal failure, erectile dysfunction, blindness, slow healing wounds (including surgical incisions), and arterial disease, including coronary artery disease. The onset of type 2 diabetes has been most common in middle age and later life, although it is being more frequently seen in adolescents and young adults due to an increase in child obesity and inactivity. A type of diabetes called MODY is increasingly seen in adolescents, but this is classified as a diabetes due to a specific cause and not as type 2 diabetes.
Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus or diabetes due to a specific cause. Examples include diabetes mellitus such as MODY or those caused by hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g., long-term steroid use).

source:wikipedia, free encyclopedia