The types of diabetes with known causes are included and grouped in “other specific types of diabetes”. The “other specific types of diabetes” was previously known as MODY or maturity onset of diabetes of the young. The causes of “other specific types of diabetes” are several and varied and ranges from genetic defect to defect in insulin function to infection to drug or chemical-induced. The known causes of the “other specific types of diabetes” are discussed below.

Genetic defects of beta-cell function:

Diabetes due to genetic defect in beta-cell of pancreas function generally appears before the age of 25 years and with mild hyperglycemia. The genetic defect in beta-cell of pancreas function may be due to mutation in different (several) locations and mutation at different location causes different types of diabetes.

• Mutation in hepatocyte nuclear transcription factor-4alpha (HNF4A) causes MODY-1. The hepatocyte nuclear transcription factor 4 alpha gene is located in chromosome 20q which is a transcription factor that is involved in the regulation of the expression of HNF1alpha.
• Mutation in enzyme glucokinase gene causes MODY-2. Glucokinase enzyme converts glucose to glucose-6-phosphate, which in turn stimulates insulin secretion by the beta cells of pancreas. Glucokinase enzyme thus acts as the "glucose sensor" for the beta cells. Glucokinase gene is located in chromosome-7p.
• Mutation in hepatocyte nuclear transcription factor-1 alpha (HNF1A) causes MODY-3. This is the commonest form of mutation in chromosome-12.
• Mutation in Insulin Promoter Factor-1 (IPF-1) causes MODY-4 which causes total pancreatic agenesis.
• Mutation in hepatocyte nuclear transcription factor-1beta (HNF1B) causes MODY-5.
• Mutation in NeuroD1 causes MODY-6.
• Point mutations in mitochondrial DNA are also associated with diabetes mellitus (and also deafness). The most common mutation occurs at position 3243 in the tRNA leucine gene.
• Mutation at subunits of ATP-sensitive potassium channel can also cause diabetes.
• Mutation in the gene responsible for proinsulin or insulin conversion causes diabetes. This can occur in some families and the inherited traits results in mild carbohydrate intolerance.

Genetic defect in the action of Insulin:

The genetic defect in the action of insulin can cause diabetes. Mutation in the insulin receptor gene causes change in the functioning of insulin receptor and lead to insulin resistance. The metabolic abnormalities that may occur due to mutation in insulin receptor may vary from hyperinsulinaemia and modest hyperglycemia to overt symptomatic diabetes. The genetic defect in the action of insulin can cause following types of diabetes.

• Type-A insulin resistance, which may lead to enlarged ovarian cysts and virilization.
• Lipodystrophy syndromes can also caused by genetic defect in the action of insulin.
• Leprechaunism occurs in children due to genetic defect in the action of insulin and has characteristic facial features.
• Rabson-Mendenhall syndrome is also a childhood syndrome with diabetes due to genetic defect in the action of insulin. The feature of Rabson-Mendenhall syndrome includes abnormalities of teeth and nails and pineal gland hyperplasia.

Diabetes due to diseases of the Exocrine Pancreas:

Any injury to pancreas can cause diabetes, even without any reduction in numbers of beta cells of pancreas e.g. pancreatitis, pancreatectomy, cancers of pancreas, cystic fibrosis, hemochromatosis, fibrocalculous pancreatopathy, mutations in carboxyl ester lipase. The injury should damage the pancreas extensively for diabetes to occur. But in case of pancreatic cancers, especially adenocarcinomas, involvement of only a small portion of the pancreas can cause diabetes. Cystic fibrosis and haemochromatosis can cause extensive damage to the pancreatic beta cells and impair insulin secretion.

Endocrinopathies:

There are many hormones such as growth hormone, cortisol, glucagon, epinephrine etc. which antagonizes (oppose) the action of insulin and excessive secretion of any of these hormones can lead to diabetes. The diseases due to excess of these hormones include acromegaly (excess growth hormone in adults), Cushing's syndrome, glucagonoma and pheochromocytoma (excess epinephrine). If the cause of the excess hormone is removed the hyperglycemia (diabetes) generally disappears.

Somatostatinoma (tumor secreting excess somatostatin), and aldosteronoma induced hypokalaemia, can cause diabetes, by inhibiting insulin secretion, as hypokalaemia (low potassium) inhibit secretion of insulin from beta cells. The diabetes generally resolves after removal of tumors.

Drug- or Chemical-induced Diabetes:

There are many drugs and chemicals which impair insulin secretion and/or insulin action, such as Vacor (a rat poison), pentamidine, nicotinic acid, glucocorticoids, thyroid hormone, diazoxide, beta-adrenergic agonists (such as salbutamol), thiazides, phenytoin, ? -interferon, protease inhibitors, clozapine etc. Many of these drugs/chemicals do not directly cause diabetes, but may precipitate diabetes in persons with pre-existing insulin resistance. Vacor (a rat poison) and pentamidine permanently destroy pancreatic beta cells which secrete insulin.

Infection:

Infection can result in diabetes, especially if it damage and /or involve pancreas. Certain viruses can cause diabetes by destroying beta-cells of pancreas, such as rubella (congenital rubella), Coxsackie B, cytomegalovirus and other viruses (adenovirus and mumps).

Uncommon forms of Immune-mediated diabetes:

Certain uncommon immunological diseases are associated with diabetes which may be different from type-2 diabetes in pathogenesis or etiology and these individuals present with symptoms of hypoglycemia, instead of hyperglycemia. Example includes diabetes caused by anti-insulin receptor antibodies which binds to the insulin receptor which reduce the binding of insulin to target tissues. These anti-insulin receptor antibodies act as insulin agonist after binding with insulin receptors and cause hypoglycemia.

Other examples of uncommon immunological disease associated with diabetes include “stiff-person” syndrome (which is an autoimmune disorder of the central nervous system and characterized by stiffness of the axial muscles with painful spasms, hence the name and approximately half will develop diabetes), systemic lupus erythematosus, insulin autoimmune syndrome etc.

Other genetic syndromes sometimes associated with diabetes:

Several genetic diseases/syndromes can sometimes, although rarely be associated with diabetes such as Down's syndrome, Klinefelter's syndrome, Turner's syndrome, Wolfram's syndrome (an autosomal recessive disorder characterized by insulin-deficient diabetes and the absence of beta cells at autopsy), Friedreich's ataxia, Huntington's chorea, Laurence-Moon-Biedl syndrome, Prader-Willi syndrome, myotonic dystrophy, porphyria etc.