Several genes have been linked to some of the less common forms of diabetes and associated conditions. Researchers have identified certain genes that may be a factor in syndromes of extreme insulin resistance, diabetes-deafness syndromes and maturity-onset diabetes of the young (MODY).

MODY is a rare form of diabetes that is caused by inherited genetic defects. It accounts for less than 5 percent of diabetes cases, according to the American Diabetes Association. In most cases, MODY occurs in three or more generations of a family and often develops in the teen years or early 20s. Children of patients with MODY have a 50 percent risk of developing the condition. The disorder is sometimes considered a variation of type 2 diabetes but can be misdiagnosed as type 1.

There are several types of MODY. Each appears to be caused by a single-gene mutation. The genetic defects primarily affect the function of beta cells (pancreas cells that produce insulin), causing the development of this disease. The six forms of MODY and the associated genetic mutation are:

• MODY1 (hepatic nuclear factor-4alpha or HNF-4alpha)
• MODY2 (pancreatic glucokinase or GCK)
• MODY3 (HNF-1alpha)
• MODY4 (insulin promoter factor-1 or IPF-1)
• MODY5 (HNF-1beta)
• MODY6 (neurogenic differentiation factor-1 or neuroD1)

Other rare forms of diabetes can also be caused by single genes. The action of insulin and cellular sensitivity to insulin may be affected by the insulin receptor gene. A genetic mutation can also affect a molecule called PPAR-gamma, which affects insulin action and is a target for some antidiabetic agents, medications for type 2 diabetes.

Certain genetic defects of the beta cell can lead to Wolfram syndrome. This disorder is also known by the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness), which refers to many of the conditions that occur in conjunction with it. The gene responsible, WSF1, is active in the pancreas and nerve cells.

Several diabetic disorders involve defects in the insulin receptor gene. Indicators are hyperinsulinemia and the skin condition acanthosis nigricans. These disorders include:

• Type A insulin resistance. A condition in which the body’s cells lose their ability to use insulin. Insulin resistance can cause an increased production of male hormones in girls, leading to polycystic ovarian syndrome.
  
  
• Leprechaunism (also called Donohue syndrome). A rare fatal form of mental and physical retardation that often causes death within the first year of life.
  
  
• Rabson-Mendenhall syndrome. Another rare congenital disorder involving severe insulin resistance and poor prognosis.

There are also numerous genetic syndromes that can lead to secondary diabetes or prediabetes. Although many subcategories exist, the main classifications include:

• Pancreatic deficiencies
• Mutant insulin syndromes
• Glucokinase gene mutations
• Mitochondrial DNA gene mutation
• Chromosomal defects
• Hereditary neuromuscular disorders