Diabetes Evaluation and Treatment

Diabetes mellitus often referred to simply as diabetes (Ancient Greek: "to pass through"), is a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia).

Blood glucose levels are controlled by a complex interaction of multiple chemicals and hormones in the body, including the hormone insulin made in the beta cells of the pancreas.

Diabetes mellitus refers to the group of diseases that lead to high blood glucose levels due to defects in either insulin secretion or insulin action.

Diabetes develops due to:

• A diminished production of insulin (in type 1)
• Resistance to its effects (in type 2)
• Both lead to hyperglycemia, which largely causes the
• Acute signs of diabetes:
• excessive urine production
• resulting compensatory thirst and increased fluid intake
• blurred vision
• unexplained weight loss
• lethargy and changes in energy metabolism.

All forms of diabetes have been treatable since insulin became medically available in 1921, but there is no cure.

The injections by a syringe, insulin pump, or insulin pen deliver insulin, which is a basic treatment of type 1 diabetes.

Type 2 is managed with a combination of

• dietary treatment
• exercise
• medications
• insulin supplementation

Diabetes and its treatments can cause many complications.
Acute complications (hypoglycemia, ketoacidosis, or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled.

Serious long-term complications include:
cardiovascular disease (doubled risk), chronic renal failure, retinal damage (which can lead to blindness), nerve damage (of several kinds), 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.

To avoid the serious long-term complications:
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.
Classification

The term diabetes, without qualification, usually refers to diabetes mellitus, which is associated with excessive sweet urine (known as "glycosuria") but there are several rarer conditions also named diabetes.

The most common of these is diabetes insipidus in which the urine is not sweet (insipidus meaning "without taste" in Latin); it can be caused by either kidney or pituitary gland damage
The term "type 1 diabetes" has universally replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes (IDDM).

The term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and non-insulin-dependent diabetes (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature. Various sources have defined "type 3 diabetes" as, among others, gestational diabetes, insulin-resistant type 1 diabetes (or "double diabetes"), type 2 diabetes which has progressed to require injected insulin, and latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes.) There is also maturity onset diabetes of the young (MODY) which is a group of several single gene (monogenic) disorders with strong family histories that present as type 2 diabetes before 30 years of age.

Type 1 Diabetes mellitus

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to a deficiency of insulin. This type of diabetes can be further classified as immune-mediated or idiopathic.
The majority of type 1 diabetes is of the immune-mediated variety, where beta cell loss is a T-cell mediated autoimmune attack.

There is no known preventive measure which can be taken against type 1 diabetes; it is about 10% of diabetes mellitus cases. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages.

Type 1 diabetes can affect children or adults but was traditionally termed "juvenile diabetes" because it represents a majority of the diabetes cases in children.

The principal treatment of type 1 diabetes, even in its earliest stages, is the delivery of artificial insulin via injection combined with careful monitoring of blood glucose levels using blood testing monitors.

Without insulin, diabetic ketoacidosis often develops which may result in coma or death. Treatment emphasis is now also placed on lifestyle adjustments (diet and exercise) though these cannot reverse the progress of the disease.

Apart from the common subcutaneous injections, it is also possible to deliver insulin by a pump, which allows continuous infusion of insulin 24 hours a day at preset levels, and the ability to program doses (a bolus) of insulin as needed at meal times. An inhaled form of insulin was approved by the FDA in January 2006, although it was discontinued for business reasons in October 2007.

Non-insulin treatments, such as monoclonal antibodies and stem-cell based therapies, are effective in animal models but have not yet completed clinical trials in humans.

Type 1 treatment must be continued indefinitely in essentially all cases. Treatment need not significantly impair normal activities, if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment is burdensome for patients; insulin is replaced in a non-physiological manner, and this approach is therefore far from ideal. The average glucose level for the type 1 patient should be as close to normal (80–120 mg/dl, 4–6 mmol/l) as is safely possible.

Some physicians suggest up to 140–150 mg/dl (7-7.5 mmol/l) for those having trouble with lower values, such as frequent hypoglycemic events. Values above 400 mg/dl (20 mmol/l) are sometimes accompanied by discomfort and frequent urination leading to dehydration. Values above 600 mg/dl (30 mmol/l) usually require medical treatment and may lead to ketoacidosis, although they are not immediately life-threatening.

However, low levels of blood glucose, called hypoglycemia, may lead to seizures or episodes of unconsciousness and absolutely must be treated immediately, via emergency high-glucose gel placed in the patient's mouth or an injection of glucagon.

Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is characterized differently and is due to:

• insulin resistance or
• reduced insulin sensitivity,
• combined with relatively reduced insulin secretion

The defective responsiveness of body tissues to insulin almost certainly involves the insulin receptor in cell membranes. However, the specific defects are not known. Diabetes mellitus due to a known specific defect are classified separately.
In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood.

At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver.

As the disease progresses, the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary.

There are numerous theories as to the exact cause and mechanism in type 2 diabetes. Central obesity (fat concentrated around the waist in relation to abdominal organs, but not subcutaneous fat) is known to predispose individuals to insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines that may possibly impair glucose tolerance.

Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes.

Other factors include aging, family history (type 2 is much more common in those with close relatives who have had it).

In the last decade, type 2 diabetes has increasingly begun to affect children and adolescents, likely in connection with the increased prevalence of childhood obesity seen in recent decades in some places.

Environmental exposures may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of polycarbonate plastic, and the incidence of type 2 diabetes.

Type 2 diabetes may go unnoticed for years because visible symptoms are typically mild, non-existent or sporadic, and usually there are no ketoacidotic episodes.

However … severe long-term complications can result from unnoticed type 2 diabetes, including:

• renal failure due to diabetic nephropathy,
• vascular disease (including coronary artery disease),
• vision damage due to diabetic retinopathy,
• loss of sensation or pain due to diabetic neuropathy,
• liver damage from non-alcoholic steatohepatitis
• heart failure from diabetic cardiomyopathy.
Type 2 diabetes is usually first treated by
• increasing physical activity
• decreasing carbohydrate intake
• losing weight

These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits.

It is sometimes possible to achieve long-term, satisfactory glucose control with these measures alone.

However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue.

The usual next step, if necessary, is treatment with oral antidiabetic drugs. Insulin production is initially only moderately impaired in type 2 diabetes, so oral medication (often used in various combinations) can be used to improve insulin production (e.g., sulfonylureas), to regulate inappropriate release of glucose by the liver and attenuate insulin resistance to some extent (e.g., metformin), and to substantially attenuate insulin resistance (e.g., thiazolidinediones).

According to one study, overweight patients treated with metformin compared with diet alone, had relative risk reductions of 32% for any diabetes endpoint, 42% for diabetes related death and 36% for all cause mortality and stroke.

Oral medication may eventually fail due to further impairment of beta cell insulin secretion. At this point, insulin therapy is necessary to maintain normal or near normal glucose levels.

Gestational Diabetes

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%–5% of all pregnancies and may improve or disappear after delivery.

Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type 2 diabetes later in life. Even though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother.

Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment.

Induction may be indicated with decreased placental function. A cesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia. A 2008 study completed in the U.S. found that more American women are entering pregnancy with preexisting diabetes. In fact the rate of diabetes in expectant mothers has more than doubled in the past 6 years.

This is particularly problematic as diabetes raises the risk of complications during pregnancy, as well as increasing the potential that the children of diabetic mothers will also become diabetic in the future

Signs and symptoms

The classical triad of diabetes symptoms is polyuria, polydipsia and polyphagia, which are, respectively:

• frequent urination
• increased thirst and consequent increased fluid intake
• increased appetite

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 fatigue.

All of these symptoms except weight loss can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled.

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 change is generally more gradual, but should still be suspected.