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Thread: In-Depth: Diabetes mellitus (DM) - Overview

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    Diabetes mellitus (DM)


    MCI Screening Test Topic




    Diabetes mellitus


    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).
    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.



    Complications

    Hypoglycemia
    ◦Hypoglycemia is probably the most disliked and feared complication of diabetes, from the point of view of the child and the family. Children hate the symptoms of a hypoglycemic episode and the loss of personal control it may cause.

    ◦Insulin inhibits glucogenesis and glycogenolysis, while stimulating glucose uptake. In nondiabetic individuals, insulin production by the pancreatic islet cells is suppressed when blood glucose levels fall below 83 mg/dL (4.6 mmol/L). If insulin is injected in a treated diabetic child who has not eaten adequate amounts of carbohydrates, blood glucose levels progressively fall.

    ◦The brain depends upon glucose as a fuel. As glucose levels drop below 65 mg/dL (3.2 mmol/L) counterregulatory hormones (eg, glucagon, cortisol, epinephrine) are released, and symptoms of hypoglycemia develop. These symptoms include sweatiness, shaking, confusion, behavioral changes, and, eventually, coma when blood glucose levels fall below 30-40 mg/dL. The glucose level at which symptoms develop varies greatly from individual to individual (and from time to time in the same individual), depending in part on the duration of diabetes, frequency of hypoglycemic episodes, rate of fall of glycemia, and overall control.

    ◦Manage mild hypoglycemia by giving rapidly absorbed PO carbohydrate or glucose; for a comatose patient, administer an intramuscular injection of the hormone glucagon, which stimulates the release of liver glycogen and releases glucose into the circulation. Where appropriate, an alternative therapy is intravenous glucose (preferably no more than a 10% glucose solution). All treatments for hypoglycemia provide recovery in approximately 10 minutes.

    ◦Occasionally, a child with hypoglycemic coma may not recover within 10 minutes, despite appropriate therapy. Under no circumstances should further treatment be given, especially intravenous glucose, until the blood glucose level is checked and still found subnormal. Overtreatment of hypoglycemia can lead to cerebral edema and death. If coma persists, seek other causes.

    ◦Hypoglycemia is a particular concern in children younger than 4 years because the condition may lead to possible intellectual impairment later in life.
    Hyperglycemia◦In an otherwise healthy individual, blood glucose levels usually do not rise above 180 mg/dL (9 mmol/L). In a child with diabetes, blood sugar levels rise if insulin is insufficient for a given glucose load. The renal threshold for glucose reabsorption is exceeded when blood glucose levels exceed 180 mg/dL (10 mmol/L), causing glycosuria with the typical symptoms of polyuria and polydipsia.
    ◦All children with diabetes experience episodes of hyperglycemia.
    Diabetic ketoacidosis

    ◦DKA is much less common than hypoglycemia, but it is potentially far more serious, creating a life-threatening medical emergency.

    ◦Ketosis usually does not occur when insulin is present. In its absence, however, severe hyperglycemia, dehydration, and ketone production contribute to the development of DKA.
    •DKA usually follows increasing hyperglycemia and symptoms of osmotic diuresis. Users of insulin pumps, by virtue of absent reservoirs of subcutaneous insulin, may present with ketosis and more normal blood glucose levels. They are more likely to present with nausea, vomiting, and abdominal pain, symptoms similar to food poisoning.
    Injection-site hypertrophy
    ◦If children persistently inject their insulin into the same area, subcutaneous tissue swelling may develop, causing unsightly lumps and adversely affecting insulin absorption. Rotating the injection sites resolves the condition.

    ◦Fat atrophy can also occur, possibly in association with insulin antibodies. This condition is much less common but more disfiguring.

    •Diabetic retinopathy

    ◦The most common cause of acquired blindness in many developed nations, diabetic retinopathy is rare in the prepubertal child or within 5 years of onset of diabetes.

    ◦Prevalence and severity of retinopathy increases with age and is greatest in patients whose diabetic control is poor. Prevalence rates seem to be declining, yet an estimated 80% of people with IDDM develop retinopathy.

    ◦Diabetic retinopathy's first symptoms are dilated retinal venules and the appearance of capillary microaneurysms, a condition known as background retinopathy. These changes may be reversible or their progression may be halted with improved diabetic control, although some patient's conditions may worsen initially.

    ◦Subsequent changes in background retinopathy are characterized by increased vessel permeability and leaking plasma that form hard exudates, followed by capillary occlusion and flame-shaped hemorrhages. The patient may not notice these changes unless the macula is involved. Laser therapy may be required at this stage to prevent further visual loss. Proliferative retinopathy follows with further vascular occlusion, retinal ischemia, proliferation of new retinal blood vessels and fibrous tissue, then progressing to hemorrhage, scarring, retinal detachment, and blindness. Prompt retinal laser therapy may prevent blindness in the later stages, so regular screening is vital.
    •Diabetic nephropathy and hypertension
    ◦Diabetic nephropathy's exact mechanism is unknown. Peak incidence is in postadolescents, 10-15 years after diagnosis, and may involve up to 30% of people with IDDM.

    ◦Microalbuminuria is the first evidence of nephropathy. The exact definition varies slightly between nations but an increased AER is commonly defined as a ratio of first morning–void urinary albumin levels to creatinine levels that exceeds 10 mg/mmol, or as a timed overnight AER of more than 20 mcg/min but less than 200 mcg/min. Early microalbuminuria may resolve. Glomerular hyperfiltration occurs, as do abnormalities of the glomerular basement membrane and glomeruli.

    ◦In a patient with nephropathy, AER increases until frank proteinuria develops, and this may progress to renal failure. Blood pressure rises with increased AER, and hypertension accelerates the progression to renal failure.

    ◦Progression may be delayed or halted by improved diabetes control, by administration of angiotensin-converting enzyme inhibitors (ACE inhibitors), and by aggressive blood pressure control.

    ◦Regular urine screening for microalbuminuria provides opportunities for early identification and treatment to prevent renal failure.
    •A child younger than 15 years with persistent proteinuria may have a nondiabetic cause and should be referred to a pediatric nephrologist for further assessment.
    •Diabetic neuropathy affects both the peripheral and autonomic nerves. Hyperglycemic effects on axons and microvascular changes in endoneural capillaries are amongst the proposed mechanisms.
    •Autonomic changes involving cardiovascular control (eg, heart rate, postural responses) have been described in as many as 40% of children with diabetes. Cardiovascular control changes become more likely with increasing duration and worsening control.
    •In adults, peripheral neuropathy usually occurs as a distal sensory loss.

    •Macrovascular disease

    •While this complication is not seen in pediatric patients, it is a significant cause of morbidity and premature mortality in adults with diabetes.

    •People with IDDM have twice the risk of fatal myocardial infarction (MI) and stroke than people unaffected with diabetes; for women, the MI risk is 4 times greater. People with IDDM also have 4 times greater risk for atherosclerosis.

    •The combination of peripheral vascular disease and peripheral neuropathy can cause serious foot pathology.

    •Smoking, hypertension, hyperlipidemia, and poor diabetic control greatly increase the risk of vascular disease.

    •Associated autoimmune diseases are relatively common in children and include the following:

    •Hypothyroidism affects 2-5% of children with diabetes.

    •Hyperthyroidism affects 1% of children with diabetes; the condition is usually discovered at the time of diabetes diagnosis.

    •Although Addison disease is uncommon, affecting fewer than 1% of children with diabetes, it is a life-threatening condition that may reduce the insulin requirement and increase the frequency of hypoglycemia. (These effects may also be the result of unrecognized hypothyroidism.)


    •Celiac disease, associated with an abnormal sensitivity to gluten in wheat products, is probably a form of autoimmune disease and may occur in as many as 5% of children with IDDM.

    •Necrobiosis lipoidica is probably another form of autoimmune disease. This condition is usually, but not exclusively, found in patients with IDDM. Necrobiosis lipoidica affects 1-2% of children and may be more common in children with poor diabetic control.

    •Limited joint mobility, primarily affecting hands and feet, is believed to be associated with poor diabetic control.

    •Originally described in approximately 30% of patients with IDDM, limited joint mobility occurs in 50% of patients older than 10 years who have had diabetes longer than 5 years. The condition restricts joint extension, making it difficult to press the hands flat against each other. The skin of patients with severe joint involvement has a thickened and waxy appearance.

    •Limited joint mobility is associated with increased risks for diabetic retinopathy and nephropathy. Improved diabetes control over the past several years appears to have reduced the frequency of these additional complications by an approximate 4-fold factor. More recent patients also have markedly fewer severe joint mobility limitations.
    -----------------------



    Possible mechanism for development of type 1 diabetes.

    The effects of insulin deficiency.


    Representation of activity profile of available insulins.[/



    Some of the available insulin injection devices



    A selection of available insulin pumps



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    Last edited by trimurtulu; 02-08-2009 at 11:11 PM.

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