What causes glucose intolerance?

Updated: Jul 08, 2020
  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Genetic defects of beta-cell function include the following:

  • Mutation on chromosome 12, the hepatocyte nuclear factor (HNF-1) alpha -MODY3

  • Mutation on chromosome 7p, the glucokinase gene -MODY2

  • Mutation on chromosome 20, HNF-4 alpha -MODY1

  • Point mutations in mitochondrial DNA

Defects in insulin action include the following:

  • Structure and function of insulin receptor: postreceptor signal transduction pathways

  • Type A insulin resistance

  • Leprechaunism

  • Rabson-Mendenhall syndrome

  • Lipoatrophic diabetes

Diseases of the exocrine pancreas include the following:

(Note that the malnutrition-related diabetes has been eliminated from the above list, as evidence is lacking on protein deficiency as a direct cause of diabetes, and fibrocalculous pancreatopathy has been reclassified as a disease of the exocrine pancreas.)

Endocrine diseases associated with excess production of insulin antagonists include the following:

Drugs or chemical agents with adverse effects on glucose tolerance include the following:

  • Thiazides

  • Diazoxide

  • Glucocorticoids

  • Calcineurin inhibitors, such as cyclosporine and tacrolimus

  • Oral contraceptives

  • Beta-adrenergic agonists

  • Nicotinic acid

  • Thyroid hormone

  • Pentamidine

  • Alpha interferon

  • Atypical antipsychotics, especially clozapine and olanzapine

  • Antiretroviral drugs

  • Vacor

Infections associated with beta-cell destruction include the following:

  • Rubella

  • Coxsackievirus B

  • Mumps

  • Cytomegalovirus

  • Adenovirus

Genetic syndromes that predispose an individual to impaired glucose tolerance include the following:

  • Klinefelter syndrome

  • Turner syndrome

  • Wolfram syndrome

  • Friedreich ataxia

Pregnancy can be associated with gestational diabetes mellitus, and the risk of diabetes increases with parity.

Obesity is a powerful determinant of glucose intolerance in the general population and develops through the interaction of genetics and acquired factors such as physical inactivity and dietary habits.

Immune-mediated causes of impaired glucose tolerance include stiff person syndrome and anti-insulin receptor abnormalities. Other causes of glucose intolerance are liver disease (as in cirrhosis) and renal failure.

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