DIABETES

DAIBETES

Diabetes mellitus (pronounced /ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɨs/; /mɨˈlaɪtəs/ or /ˈmɛlɨtəs/)—often referred to simply as diabetes—is a disease in which the body does not produce or properly use insulin, a hormone produced in the pancreas. Insulin is needed to turn sugar and other food into energy. In diabetes, the body either doesn’t make enough insulin or can’t use its own insulin as well as it should, or both. This causes sugar to accumulate in the blood, leading to various potential complications. The American Diabetes Association reported in 2009 that there are 23.6 million children and adults in the United States—7.8% of the population, who have diabetes. While an estimated 17.9 million in the US alone have been diagnosed with diabetes, nearly one in four (5.7 million) diabetics are unaware that they have the disease.

Four types of diabetes are recognized:

* Type 1:

Results from the body’s failure to produce insulin. It is estimated that 5-10% of Americans who are diagnosed with diabetes have type 1 diabetes. Presently almost all persons with type 1 diabetes must take insulin injections. Type 1

* Type 2:

Results from a condition in which the body fails to use insulin properly, combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes.

• * Gestational diabetes: Pregnant women who have never had diabetes before but who have high blood sugar (glucose) levels during pregnancy are said to have gestational diabetes. Gestational diabetes affects about 4% of all pregnant women and is usually of type 2.
• * Pre-diabetes: Termed “America’s largest healthcare epidemic,”[4]:10-11pre-diabetes is a condition that occurs when a person’s blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 diabetes. As of 2009 there are 57 million Americans who have pre-diabetes.

All forms of diabetes have been treatable since insulin became medically available in 1921, but there is no cure, although gestational diabetes usually resolves after delivery. Diabetes and its treatments can cause many complications. Acute complications including hypoglycemia, diabetic ketoacidosis, or nonketotic hyperosmolar coma may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease, chronic renal failure, retinal damage, which can lead to blindness, several types of nerve damage, and microvascular damage, which may cause erectile dysfunction and poor wound healing. Poor healing of wounds, particularly of the feet, can lead to gangrene, and possibly to amputation. Adequate treatment of diabetes, as well as increased emphasis on blood pressure control and lifestyle factors such as not smoking and maintaining a healthy body weight, may improve the risk profile of most of the chronic complications. In the developed world, diabetes is the most significant cause of adult blindness in the non-elderly and the leading cause of non-traumatic amputation in adults, and diabetic nephropathy is the main illness requiring renal dialysis in the United States.

Signs and symptoms

The classical symptoms are polyuria and polydipsia which are, respectively, frequent urination and increased thirst and consequent increased fluid intake. Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children. However, in type 2 diabetes symptoms usually develop much more slowly and may be subtle or completely absent. Type 1 diabetes may also cause a rapid yet significant weight loss (despite normal or even increased eating) and irreducible mental fatigue. All of these symptoms except weight loss can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled, although unexplained weight loss may be experienced at the onset of the disease. Final diagnosis is made by measuring the blood glucose concentration.
When the glucose concentration in the blood is raised beyond its renal threshold, reabsorption of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing dehydration and increased thirst.
Prolonged high blood glucose causes glucose absorption, which leads to changes in the shape of the lenses of the eyes, resulting in vision changes; sustained sensible glucose control usually returns the lens to its original shape. Blurred vision is a common complaint leading to a diabetes diagnosis; type 1 should always be suspected in cases of rapid vision change, whereas with type 2 changes is generally more gradual, but should still be suspected.
Patients (usually with type 1 diabetes) may also initially present with diabetic ketoacidosis (DKA), an extreme state of metabolic dysregulation characterized by the smell of acetone on the patient’s breath; a rapid, deep breathing known as Kussmaul breathing; polyuria; nausea; vomiting and abdominal pain; and any of many altered states of consciousness or arousal (such as hostility and mania or, equally, confusion and lethargy). In severe DKA, coma may follow, progressing to death. Diabetic ketoacidosis is a medical emergency and requires immediate hospitalization.
A rarer but equally severe possibility is hyperosmolar nonketotic state, which is more common in type 2 diabetes and is mainly the result of dehydration due to loss of body water. Often, the patient has been drinking extreme amounts of sugar-containing drinks, leading to a vicious circle in regard to the water loss.

Genetics

Both type 1 and type 2 diabetes are at least partly inherited. Type 1 diabetes appears to be triggered by some (mainly viral) infections, or less commonly, by stress or environmental exposure (such as exposure to certain chemicals or drugs). There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular HLA genotypes (i.e., the genetic “self” identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger. There is also maturity onset diabetes of the young (MODY) which is a group of several single gene (monogenic) disorders with strong heritability patterns which present as type 2 diabetes early in life, usually before 30 years, and sometimes in childhood.
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 have a much higher risk of developing type 2, increasing with the number of those relatives. Concordance among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX.[18] KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates proglucagon gene expression and thus the production of glucagon-like peptide-1.[2] Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.[19]
Monogenic forms, e.g., MODY, constitute 1-5 % of all cases.
Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich’s ataxia. Wolfram’s syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.

Diagnosis

The diagnosis of type 1 diabetes, and many cases of type 2, is usually prompted by recent-onset symptoms of excessive urination (polyuria) and excessive thirst (polydipsia), often accompanied by weight loss. These symptoms typically worsen over days to weeks; about a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening; detection of hyperglycemia during other medical investigations; and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that is frequently caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.
A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/l) is considered diagnostic for diabetes mellitus.
Patients with fasting glucose levels from 100 to 125 mg/dL (6.1 and 7.0 mmol/l) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL or 7.8 mmol/l, but not over 200, two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus as well as cardiovascular disease.

While not used for diagnosis, an elevated level of glucose irreversibly bound to hemoglobin (termed glycosylated hemoglobin or HbA1c) of 6.0% or higher (the 2003 revised U.S. standard) is considered abnormal by most labs; HbA1c is primarily used as a treatment-tracking test reflecting average blood glucose levels over the preceding 90 days (approximately) which is the average lifetime of red blood cells which contain hemoglobin in most patients. However, some physicians may order this test at the time of diagnosis to track changes over time. The current recommended goal for HbA1c in patients with diabetes is 6.5%.