What is the pathophysiology of type 2 diabetes mellitus (DM)?

Updated: Jul 08, 2020
  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
  • Print
Answer

In a state of health, normoglycemia is maintained by fine hormonal regulation of peripheral glucose uptake and hepatic production. Type 2 diabetes mellitus results from a defect in insulin secretion and an impairment of insulin action in hepatic and peripheral tissues, especially muscle tissue and adipocytes. [9]  A postreceptor defect is also present, causing resistance to the stimulatory effect of insulin on glucose use. As a result, a relative insulin deficiency develops, unlike the absolute deficiency found in patients with type 1 diabetes. The specific etiologic factors are not known, but genetic input is much stronger in type 2 diabetes than in the type 1 form. [10]

Impaired glucose tolerance (IGT) is a transitional state from normoglycemia to frank diabetes, but patients with impaired glucose tolerance exhibit considerable heterogeneity. Type 2 diabetes, or glucose intolerance, is part of a dysmetabolic syndrome (syndrome X) that includes insulin resistance, hyperinsulinemia, obesity, hypertension, and dyslipidemia. Current knowledge suggests that the development of glucose intolerance or diabetes is initiated by insulin resistance and worsened by the compensatory hyperinsulinemia. Insulin resistance is not only predictive for type 2 diabetes and associated with myriad metabolic derangements in fasting conditions, but nondiabetic insulin-resistant individuals are subjected to a similar adverse postprandial metabolic setting and cardiometabolic risk as those with type 2 diabetes. [11]  In addition, the prevalence of hypertension rises with exacerbation of stages of impaired glucose metabolism; however, only in the early stages of impaired insulin metabolism do hyperglycemia and hyperinsulinemia appear to be significant contributors to the presence of hypertension. [12]

The paths to beta-cell dysfunction or demise are less well defined in type 1 diabetes. The progression to type 2 diabetes is influenced by genetics and environmental or acquired factors, such as a sedentary lifestyle and dietary habits that promote obesity. Most patients with type 2 diabetes are obese, and obesity is associated with insulin resistance. Insulin resistance is not only predictive for type 2 diabetes and associated with myriad metabolic derangements in fasting conditions, but nondiabetic insulin-resistant individuals are subjected to a similar adverse postprandial metabolic setting and cardiometabolic risk as those with type 2 diabetes. [11]  Central adiposity is more important than increased generalized fat distribution. In patients with frank diabetes, glucose toxicity and lipotoxicity may further impair insulin secretion by the beta cells.  [13]   [14]   [15]   [16] Moreover, "in obesity, inflammation, with increased accumulation and inflammatory polarization of immune cells, takes place in various tissues, including adipose tissue, skeletal muscle, liver, gut, pancreatic islet, and brain, and may contribute to obesity-linked metabolic dysfunctions, leading to insulin resistance and type 2 diabetes." [17]


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!