Diabetes Mellitus - Type II
| Overview |
|---|
- Type II Diabetes Mellitus (Type II DM) is a major source morbidity and mortality throughout the world. The etiology of Type II DM is currently poorly understood but appears to be associated with extensive derangements of whole-body metabolism resulting in resistance of peripheral tissues to insulin action. Genetic factors clearly play a large role, apparently more so than in Type I DM, although inheritance of the disease is clearly dependent on contributions from multiple genes. These genetic factors are strongly influenced by environmental variables and development of Type II DM is associated with obesity and metabolic syndrome. Whatever the ultimate etiology, autoimmunity does not appear to play any role in development of Type II DM.
| Pathogenesis |
|---|
- Overview
- The following discussion of Type II DM is highly simplified but provides an adequate framework for understanding its pathogenesis. Type II DM appears to progress through two phases, the first characterized by compensatory insulin secretion by the endocrine pancreas and the second characterized by declining endocrine pancreatic function.
- Compensated Insulin Resistance
- Type II DM appears to begin with multi-tissue resistance to physiological insulin actions. Resistance does not appear to be due to defects in the Insulin Receptor itself, but post-receptor signal transduction. For example, adipose tissue and muscle display reduced uptake of blood glucose in response to normal levels of insulin. In addition, the liver does not sufficiently inhibit gluconeogenesis in response to normal levels of insulin. To compensate for insulin resistance, beta cells of the endocrine pancreas synthesize and release additional insulin and thus the initial stages of Type II DM are characterized by abnormally high insulin levels. The compensatorily higher concentrations of plasma insulin are able to maintain fairly normal blood glucose levels for several years.
- Decompensated Insulin Resistance
- Possibly based on their genetics, the beta cells of some individuals cannot maintain the extra levels of insulin release required to overcome peripheral insulin resistance. In fact, insulin levels progressively decline over the course of this stage as Islets of Langerhans become destroyed as described in the morphology section below. Correspondingly, blood glucose levels progressively increase leading to hyperglycemia and associated clinical consequences.
| Clinical Consequences |
|---|
- The clinical consequences of Type I DM overlap with those of Type II DM and are discussed together in Diabetes Mellitus Acute Complications and Diabetes Mellitus Chronic Complications.
| Morphology |
|---|
- The morphology of the endocrine pancreas remains fairly normal until the later stages of the disease associated with progressive decline in insulin levels. Here, amyloid is seen to be deposited throughout the Islets of Langerhans, leading to progressive obliteration of the islets. Importantly, consistent with the non-immune etiopathogenesis of Type II DM, no inflammation of the islets is observed.