Diabetes Health Article

Signs and symptoms

The onset of IDDM is marked by the sudden, dramatic appearance of one or more of the following symptoms:

• Frequent urination
• Extreme thirst and/or hunger
• Rapid weight loss
• Irritability
• Weakness and exhaustion
• Nausea and vomiting

NIDDM usually develops much more gradually. Symptoms can be subtle and include any of the above symptoms, in addition to the following:

• Itching
• Blurry vision
• Obesity
• Tingling or numbness in feet
• Slow healing of the skin or gums
• Recurrent bladder infections

Diabetes can affect many of the body's organs and systems. Individuals with IDDM are prone to a potentially life-threatening complication called ketosis, in which elevated tissue and fluid levels of ketones may lead to toxic results. People with diabetes are also prone to infections. Infections of the kidney can lead to kidney disease and failure. A specific type of infection by an organism called Mucormycosis tends to occur following ketosis events in individuals with IDDM. This infection usually begins in the nasal passages and can become quite serious if it spreads to the soft tissues and bones of the face, the eye, the skull, or the brain. Gangrene can occur in individuals with poorly controlled disease and has the potential to result in limb amputation. There is an increased risk for cataracts, as well as glaucoma. Left untreated, such complications can lead to blindness. Vascular disease is common in both IDDM and NIDDM. Atherosclerosis—hardening of the arteries—can occur early and advance quickly, increasing the risk for stroke, kidney disease, and heart disease. Heart attack is the most common cause of death in diabetes. Disease of the peripheral blood vessels occurs commonly, particularly when kidney disease is also present. This can lead to increased bruising and development of ulcers, particularly in the leg.

Diagnosis

Diagnosis of diabetes can be based on the presence of suggestive symptoms, together with lab results that support the specific diagnosis.

IDDM is a distinct disease that, in most all cases, is easy to diagnose based on clinical symptoms and lab values. The identification of certain autoantibodies (immune system proteins directed against 'self' tissues) is particularly helpful in diagnosing IDDM. The onset of IDDM is almost always rapid and dramatic. Rarely, onset can be gradual and result in a diagnostic dilemma in which it is difficult to distinguish from NIDDM, particularly in an individual who is age 35-50 and not obese. Testing for autoantibodies in such individuals can help distinguish the two diseases. Although not typically done, testing for the presence of HLA-DR3 and/or HLA-DR4 may also be informative. Individuals who have a relative with IDDM are also at increased risk of a variety of other autoimmune diseases—notably thyroid disease, autoimmune gastritis, and adrenal disease.

For individuals at increased risk of diabetes, a screening glucose tolerance test is recommended periodically and may identify diabetes before symptoms become obvious. Since gestational diabetes is such a common pregnancy complication, and the impact of unmanaged disease on the fetus is serious, all pregnant women are screened between the 24th and 28th weeks of pregnancy. For those at increased risk for NIDDM due to an affected relative, increased screening for risk factors for cardiovascular disease is also recommended.

Genetic testing

IDDM The fact that only about one-half of one percent of individuals with DR3 or DR4 develop IDDM is one indicator that HLA-typing on all individuals in the population is not a useful approach for determining IDDM risk. When there is a family history of IDDM, however, HLA-typing may have a role. When considering the risk for someone with a family history to develop IDDM, using the risk figures generated from large population studies based on family history alone (not HLA typing) is most appropriate. However, these risks could potentially be modified by HLA typing results. For example, there is a 1/14 risk for IDDM in the sibling of an affected individual. If HLA typing reveals that the sibling has inherited a completely different set of HLA types, the risk can be more accurately given as 1/100. On the other hand, if there are shared DR3/DR4 HLA types, this increases the risk to 1/5-1/4. Given HLA typing results or not, an individual with a sibling with IDDM is at sufficiently increased risk to warrant increased screening and education about early signs of the disease.

NIDDM NIDDM genetic susceptibility is highly heterogeneous. There are no single genes that alone increase susceptibility to a significantly high degree that testing should be considered. Like in IDDM, it is even more appropriate in NIDDM to discuss genetic susceptibility relative to population studies that determine risk based on family history alone (not based on genetic testing). These studies indicate that individuals with a parent, sibling, or child with NIDDM is at a 10-15% risk to develop NIDDM and a 20-30% risk for IGT, which may be an early sign of developing NIDDM. Symptoms that suggest a diagnosis of NIDDM can occur in younger individuals or those that do not fit the typical profile of someone with NIDDM in other ways (i.e. not obese). In these cases, genetic testing may play a role to help determine the true diagnosis of that individual and/or allow for a more accurate risk assessment.

MODY As discussed previously, there is a unique form of NIDDM called MODY. MODY is caused primarily by mutations in the glucokinase gene. Genetic testing for this form of diabetes is available and can be very helpful in diagnosis and risk assessment for other family members, if a glucokinase mutation is detected.

NIDDM DUE TO INSULIN GENE MUTATIONS In families with late onset of NIDDM, characteristic lab values, and a dominant pattern of inheritance, insulin gene testing is available. Other lab techniques are able to distinguish variant forms of insulin that result from known mutations. A positive genetic diagnosis of this type of NIDDM can be very helpful in risk assessment for other family members.

SYNDROMES WITH DIABETES AS A FEATURE There are also several underlying syndromes and diseases of which NIDDM, IDDM, and/or IGT are potential complications. These are generally accompanied by several other signs and symptoms. If one of these syndromes is suspected, the availability, benefits, and limitations of genetic testing can be considered. Mitochondrial DNA testing may be indicated in families that show NIDDM and/or IDDM transmitted only from mothers to children together with other features characteristic of mitochondrial syndromes. In some cases, genetic testing may be appropriate and can assist in diagnosis, medical management for other potential complications, and risk assessment for other family members.