Hyperglycemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of glucose circulates in the blood plasma.

The origin of the term is Greek: hyper-, meaning excessive; -glyc-, meaning sweet; and -emia, meaning "of the blood".

Causes

Diabetes mellitus

Chronic hyperglycemia that persists even in fasting states is most commonly caused by diabetes mellitus, and in fact chronic hyperglycemia is the defining characteristic of the disease. Acute episodes of hyperglycemia without an obvious cause may indicate developing diabetes or a predisposition to the disorder. This form of hyperglycemia is caused by low insulin levels. These low insulin levels inhibit the transport of glucose across cell membranes therefore causing high blood glucose levels.

Eating disorders

Certain eating disorders can produce acute non-diabetic hyperglycemia, as in the binge phase of bulimia nervosa, when the subject consumes a large amount of calories at once, frequently from foods that are high in simple and complex carbohydrates. Certain medications increase the risk of hyperglycemia, including beta blockers, thiazide diuretics, corticosteroids, niacin, pentamidine, protease inhibitors, L-asparaginase,[1] and some antipsychotic agents.[2]

A high proportion of patients suffering an acute stress such as stroke or myocardial infarction may develop hyperglycemia, even in the absence of a diagnosis of diabetes. Human and animal studies suggest that this is not benign, and that stress-induced hyperglycemia is associated with a high risk of mortality after both stroke and myocardial infarction.[3]

Causes by Organ System

Cardiovascular

Myocardial Infarction

Chemical / poisoning Arizona bark scorpion poisoning, 1,3-Dichloropropene
Dermatologic Leschke syndrome, Ichthyosis and male hypogonadism, Acanthosis Nigricans
Drug Side Effect Acetaminophen and Oxycodone, Amprenavir, Arsenic trioxide, Asparaginase, Basiliximab, Bendrofluazide, Bumetanide, Ceritinib, Chlorpromazine, Chlortalidone, Cidofovir, Clozapine, Cyclopenthiazide, Daclizumab, Diazoxide, Dolutegravir, Diflorasone, Elvitegravir, Everolimus, Febuxostat, Formoterol, Frusemide, Gemtuzumab ozogamicin, Goserelin, Glucocorticoids, Growth hormone, Hydrochlorothiazide, Iloperidone, Indinavir, Indomethacin, Interferon gamma, Isoniazid , lamivudine, Lanreotide, Leflunomide, Leuprolide, Loperamide, Mometasone furoate, Naphazoline, Niacin, Nicotinicacid, Nilutamide, Olanzapine, Omacetaxine, Oral contraceptives, Oxaprozin, Oxcarbazepine, Pasireotide, Pegaspargase, Pegylated interferon alfa-2b, Pentamidine Isethionate, Pramipexole, Prednisolone, Repaglinide, Rifaximin, Ritodrine, Ritonavir, Saquinavir, Somatostatin, Somatostatinoma, Sucralfate Lanreotide, Thalidomide, Trametinib, Thiabendazole, Tiagabine, Tipranavir, Ziprasidone

, Skipping insulin / hypoglycemic drugs

Ear Nose Throat No underlying causes
Endocrine Diabetic Ketoacidosis, Acromegaly, Impaired Glucose Tolerance (IGT), Type 1 Diabetes - juvenile diabetes or insulin dependent diabetes, Type 2 Diabetes - adult or non-insulin dependent diabetes, Bard-Pic syndrome , Cushing's syndrome , Rabson-Mendenhall syndrome, Glucagonoma syndrome , Phaeochromocytoma, VIPoma, Retinohepatoendocrinologic syndrome, Transient neonatal diabetes mellitus, Insulin-resistance syndrome, type A, Maturity onset diabetes of the young, DIDMOAD syndrome, Permanent neonatal diabetes mellitus, Leprechaunism, Hyperaldosternonism, Hyperthyroidism, Pituitary tumour, Hyperglycemic Hyperosmolar Nonketotic Syndrome
Environmental No underlying causes
Gastroenterologic Acute pancreatitis, Cystic fibrosis, Cirrhosis, Chronic pancreatitis , Hemochromatosis, Hepatic disorder, Hepatic insufficiency, Fibrocalculous pancreatopathy, Bard-Pic syndrome
Genetic Familial partial lipodystrophy type 3 (FPLD3), MODY syndrome, Fanconi-Bickel syndrome, Haemochromatosis, MELAS, Congenital partial lipodystrophy, Diabetes-deafness syndrome, Leprechaunism, Friedreich ataxia, Down's Syndrome, Huntington's Chorea, Klinefelter's Syndrome, Laurence-Moon-Biedel Syndrome, Prader-Willi Syndrome, Turner's Syndrome
Hematologic

Thiamine-responsive megaloblastic anemia syndrome, Porphyria

Iatrogenic Surgery, Subtotal pancreatectomy, Pancreatectomy
Infectious Disease Cytomegalovirus, Congenital German Measles, Septicaemia
Musculoskeletal / Ortho Myotonic dystrophy, Anophthalmia - short stature - obesity - hyperglycemia, Radio digito -- facial dysplasia, Christian-Demyer-Franken syndrome , Brunzell syndrome , Wolcott-Rallison syndrome, Acromegaly, Increased stress, Decreased activity or exercising less than usual, Strenuous physical activity, Muscle diseases, Lack of exercise
Neurologic MELAS , Friedreich ataxia, DEND syndrome, Stroke, Subarachnoid hemorrhage, Status Epilepticus
Nutritional / Metabolic Lipotrophic Diabetes, Familial partial lipodystrophy type 3 (FPLD3), Fanconi-Bickel syndrome, Haemochromatosis, Cephalothoracic progressive lipodystrophy, Abdominal obesity metabolic syndrome, Acquired total lipodystrophy, Chromium deficiency, Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency, Metabolic Syndrome, Hyperprolinemia type 2, Wernicke Encephalopathy, Obesity, Rabson-Mendenhall syndrome
Obstetric/Gynecologic Gestational Diabetes , Pregnancy
Oncologic Glucagonoma , Phaeochromocytoma, VIPoma, Pancreatic cancer, Functioning pancreatic endocrine tumor, Conn's Syndrome
Ophthalmologic Anophthalmia - short stature - obesity - hyperglycemia, Retinohepatoendocrinologic syndrome
Overdose / Toxicity Niacin overdose , Felodipine toxicity, Phenytoin toxicity, Nimodipine toxicity, Isoniazid toxicity, Amlodipine toxicity, Isradipine toxicity
Psychiatric No underlying causes
Pulmonary

Cystic fibrosis

Renal / Electrolyte

Renal insufficiency, Hypokalemia

Rheum / Immune / Allergy

Amyloidosis, Insulin receptor antibodies

Sexual

Ichthyosis and male hypogonadism

Trauma No underlying causes
Urologic No underlying causes
Dental No underlying causes
Miscellaneous Wolfram's disease, Illness, Trauma, Stress

Causes in Alphabetical Order

Complete List of Differential Diagnoses[4][5]

Sydromes Associated with Diabetes

Measurement and definition

Glucose levels are measured in either:

  1. Milligrams per deciliter (mg/dL), in the United States and other countries (e.g., Japan, France, Egypt, Colombia); or
  2. Millimoles per liter (mmol/L), which can be acquired by dividing (mg/dL) by factor of 18.

Scientific journals are moving towards using mmol/L; some journals now use mmol/L as the primary unit but quote mg/dl in parentheses.[6]

Comparatively:[7]

  • 72 mg/dL = 4 mmol/L
  • 90 mg/dL = 5 mmol/L
  • 108 mg/dL = 6 mmol/L
  • 126 mg/dL = 7 mmol/L
  • 144 mg/dL = 8 mmol/L
  • 180 mg/dL = 10 mmol/L
  • 270 mg/dL = 15 mmol/L
  • 288 mg/dL = 16 mmol/L
  • 360 mg/dL = 20 mmol/L
  • 396 mg/dL = 22 mmol/L
  • 594 mg/dL = 33 mmol/L

Glucose levels vary before and after meals, and at various times of day; the definition of "normal" varies among medical professionals. In general, the normal range for most people (fasting adults) is about 80 to 120 mg/dL or 4 to 7 mmol/L. A subject with a consistent range above 126 mg/dL or 7 mmol/L is generally held to have hyperglycemia, whereas a consistent range below 70 mg/dL or 4 mmol/L is considered hypoglycemic. In fasting adults, blood plasma glucose should not exceed 126 mg/dL or 7 mmol/L. Sustained higher levels of blood sugar cause damage to the blood vessels and to the organs they supply, leading to the complications of diabetes.

Chronic hyperglycemia can be measured via the HbA1c test. The definition of acute hyperglycemia varies by study, with mmol/L levels from 8 to 15.[8][9]

Symptoms

The following symptoms may be associated with acute or chronic hyperglycemia, with the first three comprising the classic hyperglycaemic triad:

  • Polyphagia - frequent hunger, especially pronounced hunger
  • Polydipsia - frequent thirst, especially excessive thirst
  • Polyuria - frequent urination, especially excessive urination
  • Blurred vision
  • Fatigue
  • Weight loss
  • Poor wound healing (cuts, scrapes, etc.)
  • Dry mouth
  • Dry or itchy skin
  • Impotence (male)
  • Recurrent infections such as vaginal yeast infections, groin rash, or external ear infections (swimmer's ear)

Frequent hunger without other symptoms can also indicate that blood sugar levels are too low. This may occur when people who have diabetes take too much oral hypoglycemic medication or insulin for the amount of food they eat. The resulting drop in blood sugar level to below the normal range prompts a hunger response. This hunger is not usually as pronounced as in Type I diabetes, especially the juvenile onset form, but it makes the prescription of oral hypoglycemic medication difficult to manage.

Polydipsia and polyuria occur when blood glucose levels rise high enough to result in excretion of excess glucose via the kidneys (glycosuria), producing osmotic diuresis.

Symptoms of acute hyperglycemia may include:

  • Ketoacidosis
  • A decreased level of consciousness or confusion
  • Dehydration due to glycosuria and osmotic diuresis
  • Acute hunger and/or thirst
  • Impairment of cognitive function, along with increased sadness and anxiety[10][11]

Laboratory Findings

  • Complete lab workup
  • Glucose
  • C-peptide

Electrolyte and Biomarker Studies

  • Electrolytes

Treatment

Treatment of hyperglycemia requires elimination of the underlying cause, e.g., treatment of diabetes when diabetes is the cause. Acute and severe hyperglycemia can be treated by direct administration of insulin in most cases, under medical supervision.

  • IV fluids
  • Discontinue use of harmful/offending medications
  • Closely monitor glucose and electrolytes
  • Correct electrolyte disturbances
  • Regular glucose testing, blood pressure, lipid profile, renal function
  • Regular ophthalmology and podiatric examinations
  • Treat underlying etiologies

Pharmacotherapy

Acute Pharmacotherapies

  • Insulin administration (IV or subcutaneous)
  • Oral hypoglycemic medications

See also

References

  1. Cetin M, Yetgin S, Kara A; et al. (1994). "Hyperglycemia, ketoacidosis and other complications of L-asparaginase in children with acute lymphoblastic leukemia". J Med. 25 (3–4): 219–29. PMID 7996065.
  2. Luna B, Feinglos MN (2001). "Drug-induced hyperglycemia". JAMA. 286 (16): 1945–8. PMID 11667913.
  3. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001). "Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview". Stroke. 32 (10): 2426–32. doi:10.1161/hs1001.096194. PMID 11588337.
  4. isbn=140510368X Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:79
  5. isbn=1591032016 Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:189-191
  6. What are mg/dl and mmol/l? How to convert?
  7. Mg/dL to mmol/L Conversions
  8. Acute Stress Hyperglycemia
  9. Giugliano D, Marfella R, Coppola L; et al. (1997). "Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia". Circulation. 95 (7): 1783–90. PMID 9107164.
  10. Pais I, Hallschmid M, Jauch-Chara K; et al. (2007). "Mood and cognitive functions during acute euglycaemia and mild hyperglycaemia in type 2 diabetic patients". Exp. Clin. Endocrinol. Diabetes. 115 (1): 42–6. doi:10.1055/s-2007-957348. PMID 17286234.
  11. Sommerfield AJ, Deary IJ, Frier BM (2004). "Acute hyperglycemia alters mood state and impairs cognitive performance in people with type 2 diabetes". Diabetes Care. 27 (10): 2335–40. PMID 15451897.

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