In type 2 diabetes, dysfunction of beta cells manifested as insulin secretion and a decrease in insulin sensitivity manifested as an increase in insulin resistance contribute to hyperglycemia.
Dysfunction of alpha cells also occurs in the progression of type 2 diabetes as the ability of glucose to modulate glucagon secretion impaired which leads to increase in hepatic glucose production and consequently hyperglycemia.
Beta cells dysfunction
Evidence from clinical studies suggests that dysfunction of beta cells occurs early in the course of development of type 2 diabetes. Deterioration of glycemic control seems to be due to progressive beta cell dysfunction and failure.
Type 2 diabetes occurs as a result of absolute or relative insulin deficiency, usually in the presence of insulin resistance. When insulin resistance is present, the pancreas is called upon to increase insulin output to maintain normal glucose tolerance.
It has been hypothesized that the continued high demand on the beta cell for insulin contributes to beta cell failure, but this has not seen firmly established. Other factors such as genetics, glucotoxicity, and lipotoxicity may also contribute to impaired beta cell function.
Beat cell dysfunction appears to progress over time with the treatment of diabetes with the usual agents employed for glucose control. Some research methods for measuring beta cell function are;
- HOMA (Homeostasis Model Assessment) test. It is a method used to estimate beta cell function, insulin resistance, and insulin sensitivity from fasting blood samples like fasting plasma glucose and fasting plasma insulin values.
- Proinsulin/insulin ratio. It is indicative of beta cell dysfunction it the ratio is increased.
- C-peptide measurement. it is a measure of a marker of beta cell secretory function as it is secreted in equimolar concentrations with insulin.
In the gradual transition to type 2 diabetes, many patients initially have impaired glucose tolerance, which deteriorates progressively over several years. Often, insulin resistance is present but is generally not sufficient by itself to cause type 2 diabetes.
Many people with insulin resistance never develop diabetes. Researchers believe the progression to type 2 diabetes requires beta cell failure; beta cells become so impaired that they cannot secrete enough insulin to compensate for the degree of insulin resistance.
It has been seen that beta cell function continues to decline after diagnosis of type 2 diabetes, while insulin sensitivity remains relatively stable. Beta cell in patients with type 2 diabetes exhibit both functional secretory defects and altered cell survival. Functional beta cell changes may include;
- Defective patterns of insulin release.
- Decreased insulin production.
- Defects in beta cell responsiveness to hyperglycemia.
- Altered rates of conversion of the inactive form of insulin to the active form. The proinsulin is an inactive form of insulin.
Altered Beta cell survival
- Adequate beta cell mass is essential for normal glucose homeostasis. Beta cell mass is generally reduced in patients with long-standing type 2 diabetes, as opposed to an increased beta cell mass suggested in some research in obese patients without diabetes.
- Beta cell loss exceeds new beta cell production or cell proliferation in the progression of type 2 diabetes.
- Furthermore, there is secretion and extracellular deposition of the protein amyloid in the islets of the pancreas. Amylin is the peptide that makes up these deposits is normally co-secreted with insulin by beta cells. With progression, the prevalence of amyloid in the pancreas increases over time. It is considered as a marker for progressive beta cell dysfunction.
As a result of the loss of beta cell mass, there is a relative apparent increase in alpha cell mass which leads to hepatic glucose production in type 2 diabetes.