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, and some antipsychotic agents.

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.

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

• Dolutegravir
• Elvitegravir
• Indinavir
• Interferon gamma
• Niacin
• Nilutamide
• Oxaprozin
• Pegaspargase
• Tiagabine

Complete List of Differential Diagnoses

• 1,3-Dichloropropene

• Abdominal obesity metabolic syndrome

• Acanthosis Nigricans

• Acquired total lipodystrophy

• Acromegaly

• Acute pancreatitis

• Amlodipine toxicity

• Amprenavir

• Amyloidosis

• Anophthalmia - short stature - obesity - hyperglycemia

• Arizona Bark Scorpion poisoning

• Arsenic trioxide

• Asparaginase

• Bard-Pic syndrome

• Bendrofluazide

• Brunzell syndrome

• Bumetanide

• Cephalothoracic progressive lipodystrophy

• Chlortalidone

• Christian-Demyer-Franken syndrome

• Chromium deficiency

• Chronic pancreatitis

• Cirrhosis

• Congenital German Measles

• Congenital partial lipodystrophy

• Conn's Syndrome

• Cushing's syndrome

• Cyclopenthiazide

• Cystic fibrosis

• Cytomegalovirus

• Daclizumab

• Decreased activity or exercising less than usual

• Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency

• DEND syndrome

• Diabetes-deafness syndrome

• Diabetic Ketoacidosis

• Diazoxide

• DIDMOAD syndrome

• Down's Syndrome

• Dystrophia Myotonica

• Familial partial lipodystrophy type 3 (FPLD3)

• Fanconi-Bickel syndrome

• Felodipine toxicity

• Fibrocalculous pancreatopathy

• Freidriech's Ataxia

• Frusemide

• Functioning pancreatic endocrine tumor

• Gemtuzumab ozogamicin

• Gestational Diabetes, Pregnancy

• Glucagonoma

• Glucocorticoids

• Growth hormone

• Haemochromatosis

• Hemochromatosis

• Hepatic disorder

• Hepatic insufficiency

• Huntington's Chorea

• Hydrochlorothiazide

• Hyperaldosternonism

• Hyperglycemic Hyperosmolar Nonketotic Syndrome

• Hyperprolinemia type 2

• Hyperthyroidism

• Hypokalemia

• Ichthyosis and male hypogonadism

• Illness

• Impaired Glucose Tolerance (IGT)

• Increased stress

• Indomethacin

• Insulin receptor antibodies

• Insulin-resistance syndrome, type A

• Isoniazid

• Isoniazid toxicity

• Isradipine toxicity

• Klinefelter's Syndrome

• Lack of exercise

• Lanreotide

• Laurence-Moon-Biedel Syndrome

• Leprechaunism

• Leschke syndrome

• Lipotrophic Diabetes

• Maturity onset diabetes of the young

• MELAS

• MELAS

• Metabolic Syndrome

• MODY syndrome

• Muscle diseases

• Myocardial Infarction

• Myotonic dystrophy

• Niacin

• Niacin overdose

• Nicotinic acid

• Nimodipine toxicity

• Obesity

• Olanzapine

• Oral contraceptives

• Pancreatectomy

• Pancreatic cancer

• Pentamidine

• Permanent neonatal diabetes mellitus

• Phaeochromocytoma

• Phenytoin toxicity

• Pituitary tumour

• Porphyria

• Prader-Willi Syndrome

• Prednisolone

• Rabson-Mendenhall syndrome

• Radio digito -- facial dysplasia

• Renal insufficiency

• Retinohepatoendocrinologic syndrome

• Ritodrine

• Ritonavir

• Saquinavir

• Septicaemia

• Skipping insulin / hypoglycemic drugs

• Somatostatin

• Somatostatinoma

• Status Epilepticus

• Strenuous physical activity

• Stress

• Stroke

• Subarachnoid hemorrhage

• Subtotal pancreatectomy

• Surgery

• Thiabendazole

• Thiamine-responsive megaloblastic anemia syndrome

• Transient neonatal diabetes mellitus

• Trauma

• Turner's Syndrome

• Type 1 Diabetes - juvenile diabetes or insulin dependent diabetes

• Type 2 Diabetes - adult or non-insulin dependent diabetes

• VIPoma

• Wernicke Encephalopathy

• Wolcott-Rallison syndrome

• Wolfram Syndrome

• Ziprasidone

Sydromes Associated with Diabetes

• Down's Syndrome
• Dystrophia Myotonica
• Freidriech's Ataxia
• Huntington's Chorea
• Klinefelter's Syndrome
• Laurence-Moon-Biedel Syndrome
• Porphyria
• Prader-Willi Syndrome
• Turner's Syndrome
• Wolfram Syndrome

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.

Comparatively:

• 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.

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

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

• Hypoglycemia
• Glucose
• Diabetes

External links

• High blood sugar “Hyperglycemia” article from the Diabetes Care Group
• Symptoms of hyperglycemia