Diabetes mellitus is a clinically and genetically heterogeneous group of disorders of impaired carbohydrate, protein and fat metabolism.The major types: type 1, type 2, and gestational diabetes have one common feature, abnormally high levels of glucose in the blood (hyperglycemia).Chronic hyperglycemia is associated with long-term damage to, and even failure of, various organs including the eyes, kidneys, nerves, heart, and blood vessels. 

Diabetes is a major health issue throughout the world.In the United States, it affects about 6% of the population (16 million people) and is the seventh leading cause of death, accounting for about 65,000 deaths annually.This may be an underestimate however, as death certificates of people with diabetes often list diabetic complications, rather than diabetes, as the primary cause of death.Heart disease is the leading cause of diabetes-related deaths.

About 90-95% of diabetes cases are type 2.This form of the disease typically occurs in adults and is characterized by two defects: impaired pancreatic beta cell insulin secretion and peripheral tissue insulin resistance.In the case of impaired insulin secretion, the beta cells do not secrete adequate insulin (in response to an increased blood glucose concentration) to properly stimulate glucose uptake by muscle and adipose tissue.In the case of insulin resistance, muscle and adipose tissue do not respond appropriately to increased blood insulin and uptake of glucose is impaired.Insulin resistance is generally believed to be the initiating defect which then leads to insulin secretion insufficiency.Although many diabetics have both defects, either can result in a diagnosis of diabetes.

Type 2 diabetes is often recognized by classic symptoms of polyuria (frequent urination), polydipsia (excessive thirst), and unexplained weight loss but it can be, and frequently is, asymptomatic.For this reason, prevalence rates may underestimate disease frequency.Population studies have revealed that, for every diagnosed case, there is typically another undiagnosed; the risk of developing diabetes increases with age, obesity, and physical inactivity; and disease prevalence varies in populations of different ethnic origin.These and other studies have led to the identification of several environmental and genetic risk factors for diabetes and to metabolic abnormalities associated with it.How these factors interact to cause disease is still unclear, however.Only in some very rare forms of type 2 diabetes have specific causative gene mutations been identified.In most cases, the biochemical pathways, genes and proteins involved in disease development and the mechanisms by which environmental factors contribute to susceptibility are still poorly understood or unknown.

More on type 2 diabetes: Go to www.diabetes.org

Risk factors for type 2 diabetes

Several risk factors for type 2 diabetes have been identified:

·Age

·Sex

·Ethnic origin

·Family history of diabetes

·Diet

·Physical inactivity

·Obesity

·Prior gestational diabetes

·Low birthweight

·Insulin resistance and hyperinsulinemia

·Hyperglycemia

·Dyslipidemia

·Hyperdynamic circulation

·Albuminuria

The 1989 National Health Interview Survey (NHIS) revealed a number of sociodemographic characteristics of people with type 2 diabetes.They tend to be older (median age 64 years), are slightly more likely to be female (58.4%), and although they are predominantly white (69.6%), there is a disproportionate rate of the disease in blacks and Mexican Americans.The highest proportion of type 2 diabetics live in the southeastern United States (39.2%), particularly blacks (60.1%).They frequently live in urban areas, are often unemployed, and even after accounting for age, have less education and lower income levels than non-diabetics.

Age:Type 2 diabetes is most prevalent in the 65-74 year old age group.Mean age at diagnosis is 51 years and does not differ markedly by sex.Susceptible individuals In high-risk Hispanic and black populations develop the disease at earlier ages.

Sex:Although there are slightly more female than male diabetics, there is little evidence that disease risk differs between men and women when other factors are accounted for.Higher rates of obesity among females, particularly in black and Mexican American populations, may account for a significant portion of the increased risk.. 

Ethnic origin:Worldwide, there are dramatic differences in type 2 diabetes prevalence among different populations.Some traditional societies (e.g. Mapuche Indians in Chile and Bantu in Tanzania) have virtually no cases while in others (e.g. the Micronesians of Nauru and Pima Indians of Arizona) almost 50% of the adult population is affected.In the U.S., the disease is about twice as common in blacks and Hispanics as in whites.Although geographic and ethnic differences can be partly explained by underlying differences in the prevalence of obesity and other behavioral risk factors, there appear to be genetic (or unknown nongenetic) risk factors that differ by ethnicity.Population admixture studies in Hispanics and blacks suggest that genes present in high risk populations are associated with disease risk.

Family history of diabetes:Many studies have shown that family members of diabetics have an increased risk of disease.Twin studies in particular, indicate that genetic factors play a major role in the etiology of type 2 diabetes.These studies also support a role for nongenetic factors, since concordance rates are much less than 100%.Linkage and association studies in various populations have identified genetic loci associated with the disease.

Diet:Studies exploring associations between diabetes and various dietary components (such as total and complex carbohydrate intake and fiber intake) have had mixed results.There is evidence that dietary fat intake may play a role in disease development.High fat diets have been associated with obesity, altered fat distribution, and increased risk of diabetes.Omega-3 fatty acids appear to reduce serum lipids, platelet aggregation, blood pressure, and insulin resistance and hence, could have a protective effect against diabetes, hypertension and heart disease.Alcohol intake may also contribute to diabetes risk, at least in men, although this area requires further research.

Physical inactivity:Low levels of physical activity have been associated with an increased risk of diabetes.It has been suggested that the protective effect of increased physical activity may be due to the prevention of insulin resistance.Insulin sensitivity declines with age and may be partly due to declining physical activity.

Obesity:Total body adiposity has long been recognized as a risk factor for type 2 diabetes but all obese people do not develop diabetes and some thin people do.The nature of the relationship between obesity and diabetes is not entirely clear.It could be that obesity is the etiologic pathway of a distinct subtype of diabetes, or that a similar genetic predisposition leads independently to both conditions, perhaps with the aid of different additional genetic or environmental factors. Duration of obesity and body fat distribution are alsorisk factors with higher durations and central, abdominal obesity associated with greater risk.

Prior gestational diabetes:Glucose intolerance first detected during pregnancy and which resolves after birth is called gestational diabetes.Some researchers have questioned whether this is really a separate type of diabetes or simply preexisting type 2 diabetes.Women who develop gestational diabetes are at increased risk for type 2 diabetes in the future.There is also evidence that a diabetic maternal intrauterine environment may affect the incidence of obesity and diabetes in the offspring.

Low birthweight:Low birthweight, particularly thinness at birth, is associated with increased risk for diabetes.It was initially suggested that poor fetal nutrition leads to poor development of pancreatic beta cells and their dysfunction later in life but this explanation is incompatible with the hyperinsulinemia observed in high risk populations and the fact that higher baseline insulin levels are predictive of diabetes in these and low risk populations.Although the mechanism remains unclear, low birthweight is a risk factor for diabetes. 

Insulin resistance and hyperinsulinemia:Insulin resistance plays a key role in the pathogenesis of type 2 diabetes.Given that insulin is active in glucose, lipid and protein metabolism, many defects could lead to insulin resistance and hyperinsulinemia.Fasting insulin levels correlate well with more sophisticated measures of insulin resistance and are predictive of diabetes in some populations.

Hyperglycemia:Elevated glucose levels are predictive of type 2 diabetes and are the basis for diagnosis.Animal studies suggest that chronic hyperglycemia is detrimental to insulin secretion and may also induce insulin resistance.It has been suggested that gluco-toxicity may perpetuate the diabetic state and eventually lead to a loss of beta cell function.

Dyslipidemia:Increased triglycerides and decreased high density lipoprotein cholesterol (HDL) levels have been consistently associated with type 2 diabetes.Evidence suggests that this type of dyslipidemia may be the result of insulin resistance. 

Hyperdynamic circulation:Elevated blood pressure levels and heart rate often precede the development of diabetes.As with the association between triglycerides and diabetes, the chronology of changes is not clear.

Albuminuria:Elevated urinary albumin excretion occurs early in the course of diabetes but again, the chronology of changes is not clear.