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Type 2 diabetes mellitus (T2DM) is a complex, chronic metabolic disorder. It is a major public health issue and an important contributor to morbidity and mortality all over the world.1,2 Diabetes reduces the life expectancy of its victims by approximately 10 years. Mortality and morbidity increase because of increased risk of cardiovascular disease, stroke, visual impairment, renal disease, and amputations.

According to the Centers for Disease Control and Prevention report on ED visits of ≥18-year-old adults in 2014, 14.2 million were reported with diabetes as any listed diagnosis. These included 245,000 visits for hypoglycemia and 207,000 for hyperglycemic crisis.3


T2DM is a complex heterogeneous metabolic disorder, characterized by chronic elevation of plasma glucose levels. The pathogenesis is complex and involves interaction of genetic and environmental factors. The most important pathophysiologic features of T2DM are decreased insulin sensitivity (insulin resistance) and impaired insulin secretion

It is generally believed that, in T2DM, fasting hyperglycemia is caused by increased production of glucose by liver, which is not suppressed because of hepatic resistance to insulin action. Normally, after meals, glucose uptake in peripheral tissues increases and glucose production by gluconeogenesis and glycogenolysis decreases. Insulin acts both directly and indirectly to inhibit gluconeogenesis and glycogenolysis. In T2DM, owing to hepatic resistance to insulin, the liver is programmed to both overproduce and underuse glucose.

However, postprandial hyperglycemia results from several mechanisms: abnormal insulin secretion by pancreatic β cells in response to a meal, impaired regulation of hepatic glucose production, and reduced glucose uptake by peripheral tissues, particularly the skeletal muscle, that are insulin sensitive.4

Insulin resistance is the diminished tissue response to insulin at one or more sites in the complex pathways of hormone action and requires higher than normal plasma insulin levels to maintain normoglycemia. The major sites of insulin resistance in T2DM are the liver, skeletal muscle, and adipose tissue.

Insulin secretion is usually impaired and generally insufficient to compensate for insulin resistance.5 The mechanism behind impaired insulin release in T2DM is complicated and includes glucotoxic and lipotoxic effects, as well as deposition of amyloid within islet cells. Glucotoxicity is the negative effect of prolonged and excessive glucose on β-cell function. Lipotoxicity is the exposure to increased levels of free fatty acid, which also impairs β-cell function.6

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, secreted by intestinal L cells following glucose intake, stimulate pancreatic β cells and are responsible for 50% to 70% of total insulin secretion. In people with T2DM, the incretin system is functionally impaired,7,8 leading to hyperglycemia.

Chronic hyperglycemia is the cornerstone of microvascular complications. Dyslipidemia and hypertension that often accompany T2DM play an important part in macrovascular complications....

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