The prevalence of diabetes mellitus is increasing rapidly throughout the world. In 2003 it was estimated that there were 194 million people with diabetes worldwide, with 90–95% having type 2 diabetes. By 2025 the total number of people with diabetes is predicted to reach 333 million, a 72% increase in prevalence.
While all areas of the world are affected, the highest rates of increase are occurring in areas undergoing rapid economic growth and development, which are associated with changes in lifestyle, especially changes in diet and physical activity, as well as growth and aging of the population. In the United States, the increased prevalence of type 2 diabetes is closely associated with a sedentary lifestyle and the development of overweight or obesity. Current data indicate that 66% of adult Americans are overweight, as defined by a body mass index (BMI) >25, and 32% are obese with a BMI ≥30. Additionally, 24% meet the National Cholesterol Education Program Adult Treatment Panel III (ATP-III) definition of the metabolic syndrome and are considered to be at increased risk for developing cardiovascular disease.
There are currently an estimated 24 million people with diabetes in the United States and 57 million with impaired glucose tolerance (IGT), a high-risk condition for progression to overt type 2 diabetes. In this population, cardiovascular disease is the major cause of mortality, accounting for 70–80% of deaths, and microvascular complications, including diabetic retinopathy leading to visual loss, nephropathy leading to end-stage renal disease requiring dialysis or kidney transplantation, and the disabilities associated with diabetic neuropathy are creating a major health burden for people with diabetes and an increased cost to society. In 2002 the total excess costs of diabetes in the United States were $132 billion. Of this, $39 billion (30%) were indirect costs associated with absence from work and lost productivity, whereas $93 billion (70%) were the direct cost of medical care. The increasing prevalence of type 2 diabetes, which is now also occurring in younger age groups, has become recognized as a major health problem throughout the world and effective strategies for prevention, early detection, and treatment are a high priority.
Pathophysiology of Type 2 Diabetes
To develop effective approaches to the prevention of type 2 diabetes, a better understanding of the underlying pathophysiology of the disease is needed. The regulation of blood glucose concentration is complex and involves factors affecting the digestion and absorption of dietary carbohydrates, the regulation of hepatic glucose uptake and production, and the effectiveness of insulin to stimulate glucose uptake in insulin-sensitive tissues, particularly skeletal muscle and adipose tissue. Following meal ingestion, there is a rapid release of insulin from pancreatic beta cells and suppression of glucagon secretion from pancreatic alpha cells. This results in suppression of hepatic glucose production and stimulation of glucose uptake in peripheral tissues, thus modulating the postprandial rise in blood glucose concentration. In the fasting state, blood glucose concentration is maintained by hepatic glucose production.
In type 2 diabetes, excessive hepatic glucose production, combined with decreased peripheral glucose utilization, results in fasting hyperglycemia. Following meal ingestion, the rapid “first phase” of insulin secretion is significantly decreased or absent and the suppression of glucagon secretion is impaired. Both of these processes contribute to postprandial hyperglycemia. Type 2 diabetes is most commonly associated with obesity and insulin resistance. While the cause of insulin resistance is not fully understood, both genetic and environmental factors play a contributing role. Metabolic factors include intra-abdominal obesity, increased hepatic triglyceride content, and increased plasma free fatty acid concentrations. A variety of adipose tissue-derived cytokines, including leptin, adiponectin, retinol-binding protein 4, IL-6, TNF-α, and other inflammatory proteins affect insulin sensitivity and low levels of physical activity and aging also contribute to insulin resistance.
Thus, as individuals become older, less physically active, and more obese, insulin resistance increases. However, insulin resistance alone does not result in the development of type 2 diabetes. If pancreatic beta cell function is normal, plasma glucose concentrations are maintained within a normal range, but at the expense of hyperinsulinemia in both the fasting and the postprandial states. If beta cell function is decreased, impaired glucose metabolism results and may progress to overt type 2 diabetes over time. Data from the United Kingdom Prospective Diabetes Study (UKPDS) indicate that people with newly diagnosed type 2 diabetes have already lost approximately 50% of their beta cell function and beta cell function characteristically continues to decrease with increased duration of disease, making type 2 diabetes a “progressive disease” requiring intensification of treatment over time. The mechanism of the loss of beta cell function in the prediabetic state is not well understood. Predisposing genetic factors undoubtedly play a role but are not currently well defined. Other factors such as toxic effects of glucose and free fatty acids may also play a role in regulating beta cell function and mass.
Identification of High-Risk Populations
The prevalence of type 2 diabetes varies across different racial and ethnic groups, as well as in groups of similar genetic and cultural background who are living in different environments. In the United States, type 2 diabetes is more common in the African-American, Hispanic, and Asian populations than in non-Hispanic whites. Native Americans have the highest rates of type 2 diabetes with its prevalence as high as 50% of the adult population in some groups. While these higher rates of diabetes can be explained in part by genetic predisposition, environmental factors are also clearly important. In screening for high-risk individuals, one of the most important factors is a positive family history for type 2 diabetes, particularly if one or both parents have the disease or if there is a history of type 2 diabetes in a first-degree relative.
Women who have polycystic ovary syndrome, a history of large babies (≥9 lbs at birth) or a history of gestational diabetes, are also at high risk. The presence of overweight or obesity also increases risk progressively with increasing BMI and waist circumference. Screening for impaired glucose metabolism or type 2 diabetes is most commonly done by measuring plasma glucose concentration after an overnight fast or 2 h after a 75 g oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), defined as a 2 h value on the OGTT of 140–199 mg/dl, is a strong predictor of risk for progression to 2DM with rates of 3–12% per year reported in various studies.
The presence of impaired fasting glucose (IFG), defined as a fasting plasma glucose concentration of 100–125 mg/dl, is also an independent predictor of progression to diabetes, although not as strong as IGT. Together, IFG and/or IGT have been termed “prediabetes,” indicating the increased risk of progression to overt type 2 diabetes. The presence of the metabolic syndrome, using modified ATP-III criteria, has also been shown to be associated with increased risk for developing type 2 diabetes. Thus, people with increased risk factors for type 2 diabetes as outlined above should be screened for type 2 diabetes on a regular basis and appropriate strategies to prevent or delay the progression to overt diabetes should be undertaken if IFG, IGT, or the metabolic syndrome is present.
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