Type 2 diabetes mellitus

Diabetes Mellitus (DM) type 2 is a common metabolic disorder characterized by chronic hyperglycemia (high blood glucose). In 2012, it was estimated that approximately $9.3\%$9, point, 3, percent of the United States population had diabetes, with roughly $90\%$90, percent of these cases being type 2. In contrast to type 1, in which pancreatic β-cells are actively destroyed by an autoimmune process, type 2 diabetes has no clear destruction of β-cells—cells responsible for the synthesis and secretion of the regulatory hormone insulin. Instead, it appears that a number of factors produce a relative insufficiency of insulin to adequately control and process glucose in peripheral tissues. As such, type 2 DM is often referred to as “insulin resistant” diabetes. Table 1 shows some normal functions of insulin.

Table 1: Normal functions of insulin. The effects of insulin on various metabolic functions are shown with respect to anatomical distribution.

Insulin resistance is defined as the failure of tissues to respond normally to insulin, leading to decreased uptake of glucose in muscle, reduced glycolysis, fatty acid oxidation in the liver, and unregulated gluconeogenesis. As the β-cells themselves are still capable of producing and secreting insulin, the hyperglycemic conditions wrought by insulin resistance continue to up-regulate these functions. This produces significant strain on the cells, and may ultimately lead to β-cell failure due to this increased stress.

Certain environmental factors may play an important role in the development of clinically evident type 2 DM such as a sedentary lifestyle, diet, aging, and obesity. The physiologic changes seen in obesity, including increased adipose tissue and free fatty acids, inflammation and associated inflammatory mediators, insulin resistance and an overall increased metabolic load, increase stress on pancreatic B-cells, ultimately leading to decreased B-cell function and mass.

However, environmental factors alone may not be sufficient to explain the entire disease process in type 2 DM. The descendants of an indigenous group of American Indians in Arizona and Mexico, known as the Pima Indians, have the highest prevalence of type 2 diabetes in the world, and have served as an important model for exploring the multifactorial nature of type 2 DM. Data was collected comparing the prevalence of insulin resistance/ diabetes, obesity, and physical activity level in Pima Indians living in the United States, versus a group living in Mexico. This data was compared against population data for the same variables for Mexico as a whole. The results of this experiment are shown in Table 2.

Table 2: Risk factors and the prevalence of type 2 diabetes in Pima Indians. Type 2 DM and obesity prevalence are reported for each of three separate populations in addition to the average physical activity for a given individual in each population (hours/week). The represented groups are Pima Indians living in the United States, Pima Indians living in Mexico, and population data for Mexico as a whole. Note that ‘Other(Mexico)’ describes population data for all Mexicans.

Table 2 adapted from: Schulz, L. O. Effects Of Traditional And Western Environments On Prevalence Of Type 2 Diabetes In Pima Indians In Mexico And The U.S.. Diabetes Care, 29, 1866-1871.