Diabetes Mellitus?

[alicesmith_07]

Is Diabetes Mellitus Hereditary?

[Cindy]

Diabetes mellitus (DM) is a chronic metabolic disorder caused by an absolute or relative deficiency of insulin, an anabolic hormone. Insulin is produced by the beta cells of the islets of Langerhans located in the pancreas, and the absence, destruction, or other loss of these cells results in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]). Most children with diabetes have IDDM and a lifetime dependence on exogenous insulin.

Type 2 diabetes (non–insulin-dependent diabetes mellitus [NIDDM]) is a heterogeneous disorder. Most patients with NIDDM have insulin resistance, and their beta cells lack the ability to overcome this resistance. Although this form of diabetes was previously uncommon in children, in some, countries 20% or more of new patients with diabetes in childhood and adolescence have NIDDM, a change associated with increased rates of obesity. Other patients may have inherited disorders of insulin release leading to maturity onset diabetes of the young (MODY).

This chapter addresses only IDDM.

Pathophysiology
Insulin is essential to process carbohydrates, fat, and protein. Insulin reduces blood glucose levels by allowing glucose to enter muscle cells and by stimulating the conversion of glucose to glycogen (glycogenesis) as a carbohydrate store. Insulin also inhibits the release of stored glucose from liver glycogen (glycogenolysis) and slows the breakdown of fat to triglycerides, free fatty acids, and ketones. It also stimulates fat storage. Additionally, insulin inhibits the breakdown of protein and fat for glucose production (gluconeogenesis) in both liver and kidneys.

Hyperglycemia (ie, random blood glucose concentration more than 200 mg/dL or 11 mmol/L) results when insulin deficiency leads to uninhibited gluconeogenesis and prevents the use and storage of circulating glucose. The kidneys cannot reabsorb the excess glucose load, causing glycosuria, osmotic diuresis, thirst, and dehydration. Increased fat and protein breakdown leads to ketone production and weight loss. Without insulin, a child with IDDM wastes away and eventually dies from diabetic ketoacidosis (DKA).

An excess of insulin prevents the release of glucose into the circulation and results in hypoglycemia (blood glucose concentrations of < 60 mg/dL or 3.5 mmol/L). Glucose is the sole energy source for erythrocytes, kidney medulla, and the brain.

Frequency
United States
Overall incidence is approximately 15 cases per 100,000 individuals annually and probably increasing. An estimated 3 children out of 1000 develop IDDM by age 20 years.

International
DM exhibits wide geographic variation in incidence and prevalence. Annual incidence varies from 0.61 cases per 100,000 persons in China, to 41.4 cases per 100,000 in Finland. Substantial variations exist between nearby countries with differing lifestyles, such as Estonia and Finland, and between genetically similar populations such as those in Iceland and Norway. Even more striking are the differences in incidence between mainland Italy (8.4/100,000) and the Island of Sardinia (36.9/100,000). These variations strongly support the importance of environmental factors in the development of IDDM. Most countries report that incidence rates have at least doubled or more in the last 20 years. Incidence appears to increase with distance from the equator.

Mortality/Morbidity
Information on mortality rates is difficult to ascertain without complete national registers of childhood diabetes, although age-specific mortality is probably double that of the general population. Particularly at risk are children aged 1-4 years who may die with DKA at the time of diagnosis. Adolescents are also a high-risk group. Most deaths result from delayed diagnosis or neglected treatment and subsequent cerebral edema during treatment for DKA, although untreated hypoglycemia also causes some deaths. Unexplained death during sleep may also occur.

IDDM complications are comprised of 3 major categories: acute complications, long-term complications, and complications caused by associated autoimmune diseases.


Acute complications reflect the difficulties of maintaining a balance between insulin therapy, dietary intake, and exercise. Acute complications include hypoglycemia, hyperglycemia, and DKA.
Long-term complications arise from the damaging effects of prolonged hyperglycemia and other metabolic consequences of insulin deficiency on various tissues. While long-term complications are rare in childhood, maintaining good control of diabetes is important to prevent complications from developing in later life. The likelihood of developing complications appears to depend on the interaction of factors such as metabolic control, genetic susceptibility, lifestyle (eg, smoking, diet, exercise), pubertal status, and gender.Long-term complications include the following:
Retinopathy
Cataracts
Hypertension
Progressive renal failure
Early coronary artery disease
Peripheral vascular disease
Neuropathy, both peripheral and autonomic
Increased risk of infection
Associated autoimmune diseases are common with IDDM, particularly in children who have the human leukocyte antigen DR3 (HLA-DR3). Some conditions may precede development of diabetes; others may develop later. As many as 20% of children with diabetes have thyroid autoantibodies.

Race

Different environmental effects on IDDM development complicate the influence of race, but racial differences clearly exist.
Whites have the highest reported incidence of IDDM; Chinese have the lowest.
IDDM is 1.5 times more likely to develop in American whites than in American blacks or Hispanics.
Current evidence suggests that when immigrants from an area with low incidence move to an area with higher incidence, their IDDM rates tend to increase toward the higher level.

Sex

The influence of sex varies with the overall incidence rates.
Males are at greater risk in regions of high incidence, particularly older males, whose incidence rates often show seasonal variation.
Females appear to be at a greater risk in low-incidence regions.

Age

Generally, incidence rates increase with age until mid-puberty then decline after puberty, but IDDM can occur at any age. Onset in the first year of life, though unusual, can occur and must be considered in any infant or toddler, because these children have the greatest risk for mortality if diagnosis is delayed. Their symptoms may include the following:
Severe monilial diaper/napkin rash
Unexplained malaise
Poor weight gain or weight loss
Increased thirst
Vomiting and dehydration, with a constantly wet napkin/diaper
Where prevalence rates are high, a bimodal variation of incidence has been reported that shows a definite peak in early childhood (ie, 4-6 y) and a second, much greater peak of incidence during early puberty (ie, 10-14 y).



CLINICALSection 3 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References


History

The most easily recognized symptoms are secondary to hyperglycemia, glycosuria, and ketoacidosis (KA).
Hyperglycemia: Hyperglycemia alone may not cause obvious symptoms, although some children report general malaise, headache, and weakness. They may also appear irritable and become ill-tempered. The main symptoms of hyperglycemia are secondary to osmotic diuresis and glycosuria.
Glycosuria: This condition leads to increased urinary frequency and volume (eg, polyuria), which is particularly troublesome at night (eg, nocturia) and often leads to enuresis in a previously continent child. These symptoms are easy to overlook in infants because of their naturally high fluid intake and diaper/napkin use.
Polydipsia: Increased thirst, which may be insatiable, is secondary to the osmotic diuresis causing dehydration.
Weight loss: Insulin deficiency leads to uninhibited gluconeogenesis, causing breakdown of protein and fat. Weight loss may be dramatic, even though the child's appetite usually remains good. Failure to thrive and wasting may be the first symptoms noted in an infant or toddler and may precede frank hyperglycemia.
Nonspecific malaise: While this condition may be present before symptoms of hyperglycemia, or as a separate symptom of hyperglycemia, it is often recognized only retrospectively.
Symptoms of ketoacidosis

Severe dehydration
Smell of ketones
Acidotic breathing (ie, Kussmaul respiration), masquerading as respiratory distress
Abdominal pain
Vomiting
Drowsiness and coma
Other nonspecific findings

Hyperglycemia impairs immunity and renders a child more susceptible to recurrent infection, particularly of the urinary tract, skin, and respiratory tract.
Candidiasis may develop, especially in groin and flexural areas.

Physical

Apart from wasting and mild dehydration, children with early diabetes have no specific clinical findings.
Physical examination may reveal findings associated with other autoimmune endocrinopathies, which have a higher incidence in children with IDDM (eg, thyroid disease with symptoms of overactivity or underactivity and possibly a palpable goiter).
Cataract is a rare presenting problem, typically occurring in girls with a long prodrome of mild hyperglycemia.
Necrobiosis lipoidica usually, but not exclusively, occurs in people with diabetes. Necrobiosis most often develops on the front of the lower leg as a well-demarcated, red, atrophic area. The condition is associated with injury to dermal collagen, granulomatous inflammation, and ulceration. The cause of necrobiosis is unknown, and the condition is difficult to manage.

Causes
Most cases (95%) of IDDM are the result of environmental factors interacting with a genetically susceptible person. This interaction leads to the development of autoimmune disease directed at the insulin-producing cells of the pancreatic islets of Langerhans. These cel

[wantsshy]

It certainly can be yes, especially type 1 or "juvenile diabetes" type 2 is usually more lifestyle/weight related but genetics can still be a big factor