TYPE 2 DIABETES • Was previously referred to as non-insulin dependent diabetes mellitus or adult onset diabetes. • Is a more complex condition than type 1 diabetes as there is a combination of resistance to the actions of insulin in liver and muscle together with impaired pancreatic β-cell function leading to 'relative' insulin deficiency. • Insulin resistance appears to come first, and leads to elevated insulin secretion in order to maintain normal blood glucose levels. • However, in susceptible individuals the pancreatic β cells are unable to sustain the increased demand for insulin and a slowly progressive insulin deficiency develops. PATHOPHYSIOLOGY • Type 2 diabetes is characterized by impaired insulin secretion and resistance to insulin action. In the presence of insulin resistance, glucose utilization by tissues is impaired, hepatic glucose and free fatty acid production is increased, and excess glucose accumulates in the circulation. • This hyperglycemia stimulates the pancreas to produce more insulin in an attempt to overcome insulin resistance. The simultaneous elevation of both glucose and insulin levels is strongly suggestive of insulin resistance • Genetic predisposition may play a role in the development of type 2 diabetes. People with type 2 diabetes have a stronger family history of diabetes than those with type 1. • Obesity (particularly visceral or central) is very common in type 2 DM. In the early stages of the disorder, glucose tolerance remains near-normal, despite insulin resistance, because the pancreatic beta cells compensate by increasing insulin output. • As insulin resistance and compensatory hyperinsulinemia progress, the pancreatic islets in certain individuals are unable to sustain the hyperinsulinemic stateA further decline in insulin secretion and an increase in hepatic glucose production lead to overt diabetes with fasting hyperglycemia. Ultimately, beta cell failure may ensue. BETA CELL DESFUNCTION • beta cells are triggered by rising blood glucose levels. Starting with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation of glucose by the help of an enzyme Glucose Kinase, causes a rise in the ATP:ADP ratio. This rise inactivates the potassium channel that depolarizes the membrane, causing the calcium channel to open up allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to the exocytotic release of insulin from their storage granule. • Those people who have mutant Glucose Kinase,They can not secrete insulin effecetively. INSULIN RESISTANCE • Most individuals with type 2 exhibit decreased tissue responsiveness to insulin.Excess weight or hyperglycemia may contribute to hyperinsulinemia, which in time may lead to a decrease in or downregulation of the number of insulin receptors on the surface of target tissues and organs. • Evidence suggests that decreased peripheral glucose uptake and utilization in muscle is the primary site of insulin resistance and results in prolonged postprandial hyperglycemia. • Resistance may be secondary to decreased numbers of insulin receptors on the cell surface, decreased affifinity of receptors for insulin, or defects in insulin signaling and action that follows receptor binding. Defects in insulin signaling and action are referred to as postreceptor or postbinding defects and are likely to be the primary sites of insulin resistance. CLINICAL PRESENTATION • Type 2 diabetes is typically diagnosed incidentally during a routine physical examination or when the patient seeks attention for another complaint. Because symptoms are mild in their onset,patients will rarely complain of fatigue, polyuria, and polydipsia but may admit to them during clinical examination. • Because these patients have suffificient insulin concentrations to prevent lipolysis, there is usually no history of ketosis except in situations of unusual stress (e.g., infections, trauma). • Weight loss is therefore uncommon because relatively high endogenous insulin levels promote lipogenesis. • Macrovascular disease is also often evident at diagnosis. Microvascular complications at diagnosis suggest the presence of undiagnosed or subclinical diabetes for 7 to 10 years. TREATMENT • There are three major components to the treatment of diabetes: • diet, drugs (insulin and antidiabetic agents [oral and injectable]) exercise. • Type 2 diabetes management should begin with Medical nutrition therapy (MNT). • An exercise regimen to increase insulin sensitivity and promote weight loss should also be instituted. • Pharmacologic approaches to the management of type 2 DM include oral glucose-lowering agents, insulin, and other agents that improve glucose control. BARIATRIC SURGERY FOR TYPE 2 DIABETES • Gastric reduction surgery, with either gastric banding or bypassprocedures, has become an option for adult patients with type 2diabetes who are obese (BMI >35 kg/m2), unable to lose weightby other methods, and whose diabetes or other comorbidities are difficult to control through lifestyle and drug therapy. • Bariatricsurgery can lead to complete resolution of diabetes (normalization of BG) in up to 78% of patients. • Glycemia can normalize after intestinal bypass procedures (Roux-en-Y gastric bypass)quickly after surgery, independent of weight, possibly owing to increases in incretin hormone levels. Although this evidenceis exciting, bariatric surgery is not riskfree, and patients may endure long-term problems such as malabsorption. HYPEROSMOLAR HYPERGLYCEMIA NONKETOTIC COMA (HHNC) • Occurs in Type 2 Diabetes • Characterised by hyperglycemia and dehydration. • Dehydration in untreated & poorly controlled treatment. • Because patient has some endogenous insulin, no ketosis develops. • Blood sugars can be >800-1000. • Can result in hypovolemic shock, renal problems, stroke, coma and even death. • Persons with HHNC are not acidotic unless DKA is also present. • Can also be caused by the use of medication that elevates the blood sugar or causes dehydration, such as phenytoin, steroids, diuretics, and β blockers, and with peritoneal dialysis and hemodialysis. SIGN & SYMPTOM • Declining mental status and even seizures. • Plasma glucose of over 600 mg/dL. • Serum osmolality higher than 320 mmol/L. TREATMENT • Aggressive rehydration and restoration of glucose and electrolyte homeostasis; the rate of correction of these variables must be monitored closely. • Low-dose insulin therapy may be required.
