Diabetes mellitus is a medical disorder characterized by varying or persistent hyperglycemia (elevated blood sugar levels), especially after eating. All types of diabetes mellitus share similar symptoms and complications at advanced stages. Hyperglycemia itself can lead to dehydration and ketoacidosis. Longer-term complications include cardiovascular disease (doubled risk), chronic renal failure (it is the main cause for dialysis), retinal damage which can lead to blindness, nerve damage which can lead to erectile dysfunction (impotence), gangrene with risk of amputation of toes, feet, and even legs. The more serious complications are more common in people who have a difficult time controlling their blood sugars with medications (glycemic control).

The most important forms of diabetes are due to decreased or the complete absence of the production of insulin (type 1 diabetes), or decreased sensitivity of body tissues to insulin (type 2 diabetes, the more common form). The former requires insulin injections for survival; the latter is generally managed with diet, weight reduction and exercise in about 20% of cases, though the majority require these strategies plus oral medication (insulin is used if the tablets are ineffective).

Causes and types

Since insulin is the principal hormone that regulates uptake of glucose into cells (primarily muscle and fat cells) from the blood, deficiency of insulin or its action plays a central role in all forms of diabetes.

Type 1 diabetes

Type 1 diabetes (formerly known as insulin-dependent diabetes, childhood diabetes, or juvenile onset diabetes) is most commonly diagnosed in children and adolescents, but can occur in adults as well. It is characterized by β-cell destruction, which usually leads to an absolute deficiency of insulin. Most cases of type 1 diabetes are immune-mediated characterized by autoimmune destruction of the body's β-cells in the Islets of Langerhans of the pancreas, destroying them or damaging them sufficiently to reduce insulin production. Currently, type 1 diabetes is treated with insulin injections, lifestyle adjustments, and careful monitoring of blood glucose levels using blood test kits.

Type 2 diabetes

Type 2 diabetes is characterized by "insulin resistance" as body cells do not respond appropriately when insulin is present. This is a more complex problem than type 1, but is often easier to treat, since insulin is still produced, especially in the initial years. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. Type 2 is initially treated by changes in diet and through weight loss. The next step, if necessary, is treatment with oral antidiabetic drugs: the sulfonylureas, metformin, or (if these are insufficient) thiazolidinediones. If these fail, insulin therapy may be necessary to maintain normal glucose levels.

Gestational diabetes

Gestational diabetes mellitus appears in about 2-5% of all pregnancies. It is temporary and fully treatable, but if untreated it may cause problems with the pregnancy, including macrosomia (high birth weight) of the child. It requires careful medical supervision during the pregnancy. In addition, about 20-50% of these women go on to develop type 2 diabetes.

Genetics

Both type 1 and type 2 diabetes are at least partly inherited. Type 1 diabetes appears to be triggered by infection, stress, or environmental factors (e.g. exposure to a causative agent). There is a genetic element in the susceptibility of individuals to some of these triggers which has been traced to particular HLA genotypes.

There is an even stronger inheritance pattern for Type 2 diabetes; those with type 2 ancestors or relatives have very much higher chances of developing Type 2. Concordance among monozygotic twins is close to 100%, and 25% of those with the disease have a family history of diabetes. It is also often connected to obesity, which is found in approximately 85% of (North American) patients diagnosed with that form of the disease, so some experts believe that inheriting a tendency toward obesity seems also to contribute.

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 25% of people with new type 1 diabetes have developed a degree of diabetic ketoacidosis by the time the diabetes is recognized.

1. Diabetes screening is recommended for many types of people at various stages of life or with several different risk factors, like random glucose, a fasting glucose and insulin, a glucose 2 hours after 75 g of glucose, or a formal glucose tolerance test.

2. Many medical conditions are associated with a higher risk of various types of diabetes and warrant screening. A partial list includes: high blood pressure, elevated cholesterol levels, coronary artery disease, past gestational diabetes, polycystic ovary syndrome, chronic pancreatitis, hepatic steatosis (fatty liver), cystic fibrosis, several mitochondrial neuropathies and myopathies, myotonic dystrophy, Friedreich's ataxia, some of the inherited forms of neonatal hyperinsulinism and many others. Risk of diabetes is higher with chronic use of several medications, including high dose glucocorticoids, some chemotherapy agents (especially L-asparaginase), and some of the antipsychotics and mood stabilizers (especially phenothiazine and some atypical antipsychotics).

3. Diabetes is often detected when a person suffers a problem 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.

Criteria for diagnosis

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of

· Fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dl);

· Plasma glucose at or above 11.1 mmol/L (200 mg/dl) two hours after a 75 g glucose load; or

· Symptoms of diabetes and a random plasma glucose at or above 11.1 mmol/L (200 mg/dL).

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is an acute, dangerous complication and is always a medical emergency. Prompt proper treatment usually results in full recovery, though death can result from inadequate treatment or a variety of complications.

Hypoglycemia

Hypoglycemia in patients with diabetes almost always arises as a result of poor management of the disease either from too much or poorly timed insulin or oral hypoglycemics or too much exercise, not enough food, or poor timing of either. If blood glucose levels are low enough, the patient may become agitated, sweaty, and have many symptoms of sympathetic activation of the autonomic nervous system - they may experience feelings similar to dread and immobilized panic. Consciousness can be altered, or even lost, in extreme cases, leading to coma and/or seizures or even death and brain damage.

Long-term complications

Among the major risks of the disorder are chronic problems affecting multiple organ systems, which will eventually arise in patients with poor glycemic control. Many of these arise are

Small vessel disease complications:

· Proliferative retinopathy and macular edema which can lead to severe vision loss or blindness;

· Peripheral neuropathy which, particularly when combined with damaged blood vessels, can lead to foot ulcers, and possibly progressing to necrosis, infection and gangrene, sometimes requiring limb amputation, see below

· Diabetic nephropathy (due to microangiopathy) which can lead to renal failure

Large vessel disease complications:

· Ischemic heart disease caused by both large and small vessel disease

· Stroke

· Peripheral vascular disease which contributes to foot ulcers and the risk of amputation

Management of the disease

Diabetes management includes proper planning of

· Insulin

· Meal plan

· Blood glucose monitoring

· Exercise

Type 1 Diabetes

Persons with type 1 diabetes require insulin every day. Insulin can either be injected, which involves the use of a needle and syringe, or it can be given by an external or internal insulin pump, insulin pen, jet injector, or insulin patch. Extra amounts of insulin may be taken before meals, depending on the blood glucose level and food to be eaten.

Insulin cannot be taken as a pill. Because it is a protein, it would be broken down during digestion just like the protein in food. It must be injected into the fat under the skin for insulin to get into the blood. The amount of insulin needed depends on height, weight, age, food intake, and activity level. Insulin doses must be balanced with meal times and activities, and dosage levels can be affected by illness, stress, or unexpected events.

Type 2 Diabetes

Persons with type 2 diabetes may continue to produce adequate insulin for sometime but their bodies can become incapable of using it, called as insulin resistance and may indicate the need for oral medications that can help stimulate the pancreas to release insulin or optimize the body's ability to use the insulin secreted.

Diet and exercise can often bring blood glucose levels down to normal. When these measures are no longer enough, the next step is the addition of medications that lower blood glucose levels.

Oral anti-diabetic medications

Diabetic pills that lower the blood sugar levels include the following types:

Biguanides-Biguanides decrease the amount of sugar produced in the liver and also lower the amount of insulin in the body.

Sulfonylureas-Sulfonylureas stimulate the production of insulin in the pancreas and help the body to use the insulin that is currently being produced.

Meglitinides-Meglitinides stimulate the production of insulin in the pancreas, but are shorter-acting than sulfonylureas.

Thiazolidinediones-Thiazolidinediones help make the cells in the body more sensitive to insulin.

Alpha-glucosidase inhibitors-Alpha-glucosidase inhibitors block the enzymes that digest starches, resulting in a slower rise in the blood sugar.

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