Causes of Diabetes Melletes

• Impaired fasting glucose

• Medications
  –Corticosteroids are a common cause
  –Common medications include growth hormone, estrogen (including oral contraceptives), nicotinic acid, salicylates and NSAIDs, thiazide and loop diuretics, phenytoin, and epinephrine
• Diabetes mellitus type I
  –Diabetic ketoacidosis
• Diabetes mellitus type II
• Pancreatic disease
  –Acute or chronic pancreatitis
  –Pancreatectomy
  –Pancreatic carcinoma
  –Hemochromatosis
  –Cystic fibrosis
• Increased counter-regulatory hormones associated with acute disease
  –Myocardial infarction
  –Stroke or other neurologic disease
  –Renal insufficiency
  –Hepatic insufficiency
• Acromegaly
• Cushing's syndrome
• Pheochromocytoma
• Hyperthyroidism (thyroid storm)
• Glucagonoma
• Gestational diabetes
• Amyloidosis

• Type I diabetes mellitus
  –Most common form of diabetes in children
  –Prevalence: 1.9/1,000
  –Autoimmune-mediated destruction of pancreatic islets (β-cells)
  –Absolute insulin deficiency
  –Often presents with ketosis and DKA

• Type II diabetes mellitus
  –Increasing prevalence in children, especially among obese
  –In children, onset usually in mid-puberty
  –More frequent in blacks, Hispanics, Pacific Islanders, Asians, and Native Americans (Pima Indians)
  –Strong association with family history of type II diabetes
  –Insulin resistance and inadequate insulin secretion results in relative insulin deficiency

• Maturity-onset diabetes of the young (MODY)
  –Infrequent
  –Autosomal dominant disease
  –Onset usually between 9 and 25 years old
  –Genetic defects in enzymes or nuclear transcription factors involved in islet cell development or the regulation of insulin secretion
• Drug- or chemical-induced diabetes
  –Glucocorticoids, β-adrenergic agonists, phenytoin, asparaginase, cyclosporine, tacrolimus, vacor, pentamidine, diazoxide, nicotinic acid, thyroid hormone, thiazides
• Other endocrinopathies: Cushing disease, acromegaly, pheochromocytoma
• Exocrine pancreatic diseases
  –Cystic fibrosis
  –Hemochromatosis
• Pancreatectomy
• Physiological stress (trauma, infection)
• Infections
  –CMV
  –Congenital rubella
• Genetic syndromes: Prader-Willi syndrome, Down syndrome, Turner syndrome, Klinefelter syndrome, Wolfram syndrome

Polydipsia:

• Diabetes mellitus (type I and type II)
  –Hyperglycemia drives an osmotic diuresis that causes polyuria, which then leads to dehydration, increased thirst, and polydipsia
• Diabetes insipidus
  –Abnormal water balance due to vasopressin (ADH) deficiency or resistance, causing excretion of large amounts of dilute urine
• Central or neurogenic diabetes insipidus (vasopressin deficiency)
  –Congenital
  –Familial (autosomal dominant)
  –Acquired: Neurosurgery, tumor (e.g., craniopharyngioma), head trauma, infiltrative/inflammatory, infectious
  • Nephrogenic diabetes insipidus (decreased responsiveness of the kidneys to vasopressin)
    –Familial (X-linked dominant and recessive forms)
    –Acquired: Renal disease, obstructive uropathy, hypercalcemia/hypercalciuria
    –Hypokalemia, drug-induced (e.g., lithium, diuretics, ethanol, cisplatin)
    –Gestational DI: Increased clearance of ADH by placental vasopressinase, lower osmolar threshold for thirst and ADH release
  • Primary polydipsia
    –Compulsive water drinking
    –Dipsogenic DI
  • Primary hyperaldosteronism
  • Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) syndrome
  • Bartter syndrome
  • Hypertension (e.g., pheochomocytoma)
  • Neuroblastoma
  • Cystinosis
  • Congestive heart failure

Diabetes insipidus

Diabetes insipidus characteristically produces polydipsia and may also cause excessive voiding of dilute urine and mild to moderate nocturia. Fatigue and signs of dehydration occur in severe cases.

Diabetes mellitus

Polydipsia is a classic finding with diabetes mellitus — a consequence of the hyperosmolar state. Other characteristic findings include polyuria, polyphagia, nocturia, weakness, fatigue, and weight loss. Signs of dehydration may occur.

Hypercalcemia

As hypercalcemia progresses, the patient develops polydipsia, polyuria, nocturia, constipation, paresthesia and, occasionally, hematuria and pyuria. Severe hypercalcemia can progress quickly to vomiting, a decreased level of consciousness, and renal failure. Depression, mental lassitude, and increased sleep requirements are common.

Hypokalemia

Hypokalemia is an electrolyte imbalance that can cause nephropathy, resulting in polydipsia, polyuria, and nocturia. Related hypokalemic signs and symptoms include muscle weakness or paralysis, fatigue, decreased bowel sounds, hypoactive deep tendon reflexes, and arrhythmias.

Psychogenic polydipsia

Psychogenic polydipsia is an uncommon disorder that causes polydipsia and polyuria. It may occur with any psychiatric disorder, but is more common with schizophrenia. Signs of psychiatric disturbances, such as anxiety or depression, are typical. Other findings include a headache, blurred vision, weight gain, edema, elevated blood pressure and, occasionally, stupor and coma. Signs of heart failure may develop with overhydration.

Renal disorders (chronic)

Chronic renal disorders, such as glomerulonephritis and pyelonephritis, damage the kidneys, causing polydipsia and polyuria. Associated signs and symptoms include nocturia, weakness, elevated blood pressure, pallor and, in later stages, oliguria.

Sheehan’s syndrome

Polydipsia, polyuria, and nocturia occur with Sheehan’s syndrome, a disorder of postpartum pituitary necrosis. Other features include fatigue, failure to lactate, amenorrhea, decreased pubic and axillary hair growth, and a reduced libido.

Sickle cell anemia

As nephropathy develops, polydipsia and polyuria occur. They may be accompanied by abdominal pain and cramps, arthralgia and, occasionally, lower extremity skin ulcers and bone deformities, such as kyphosis and scoliosis.

Other causes:-

Drugs

Diuretics and demeclocycline may produce polydipsia. Phenothiazines and anticholinergics can cause dry mouth, making the patient so thirsty that he drinks compulsively.

In diabetes mellitus, glucose is inadequately utilized either because insulin isn’t synthesized or because tissues are resistant to the hormonal action of endogenous insulin. During pregnancy, the fetus relies on maternal glucose as a primary fuel source. Pregnancy triggers protective mechanisms that have anti-insulin effects: increased hormone production (placental lactogen, estrogen, and progesterone), which antagonizes insulin’s effects; degradation of insulin by the placenta; and prolonged elevation of stress hormones (cortisol, epinephrine, and glucagon), which raise blood glucose levels.

In a normal pregnancy, an increase in anti-insulin factors is counterbalanced by an increase in insulin production to maintain normal blood glucose levels. However, females who are prediabetic or diabetic are unable to produce sufficient insulin to overcome the insulin antagonist mechanisms of pregnancy, or their tissues are insulin-resistant. As insulin requirements rise toward term, the patient who’s prediabetic may develop gestational diabetes, necessitating dietary management and, possibly, exogenous insulin to achieve glycemic control, whereas the patient who’s insulin-dependent may need increased insulin dosage.