According to the American Diabetes Association, a normal fasting plasma glucose (FPG) level is less than 100 mg/dl; impaired fasting glucose (IFG) is defined as an FPG from 100 to 125 mg/dl; and any patient with an FPG greater than or equal to 126 mg/dL carries a provisional diagnosis of diabetes.1 When the oral glucose tolerance test is used for evaluation, similar definitions exist. Patients with IFG or impaired glucose tolerance (IGT) have “pre-diabetes,” and are at a high risk for developing diabetes. Elevated blood glucose levels can have major consequences, particularly in high-risk populations.2
Macrovascular and microvascular complications, impaired wound healing, and a compromised immune system can occur in the setting of sustained, elevated blood glucose concentrations. Aside from patients with diabetes who have elevated blood glucose levels, schizophrenic patients might be predisposed to glucose intolerance and diabetes independent of treatment.3
It is not known whether IGT seen in schizophrenics is due to lifestyle risk factors (e.g., smoking, poor diet, being overweight, lack of exercise) or some genetic or biological component of the disease. However, this is complicated by the fact that many of these patients are treated with second-generation antipsychotics (SGAs), which might increase the risk of developing diabetes.4 Because of this, a warning regarding the risk of developing hyperglycemia and diabetes was mandated by the Food and Drug Administration (FDA) for SGA manufacturers.5
Hyperglycemia symptoms include polyuria, polydipsia, weight loss (sometimes with polyphagia), and blurred vision. Impairment of growth and susceptibility to certain infections might occur with chronic hyperglycemia. Hyperglycemia with ketoacidosis or the nonketotic hyperosmolar syndrome are acute, life-threatening consequences of uncontrolled diabetes. It is important for hospitalists and other healthcare professionals to be aware of drugs that can cause hyperglycemia or impair glucose tolerance. In some cases, the drug can be continued; in other cases, an alternate agent should be provided if necessary for patient management.
Certain drugs and drug classes known to cause hyperglycemia include: thiazide diuretics, glucocorticoids, oral contraceptives and sex hormones (e.g., testosterone), protease inhibitors, SGAs, thyroid hormone, phenytoin, niacin/nicotinic acid, diazoxide, and alfa-interferon.1-3,6
Limited evidence exists for some other agents/classes, including: asparaginase, beta-agonists, beta-blockers, calcium channel blockers, clonidine, cyclosporine, levodopa, lithium, minoxidil, phenothiazines, and others.7 The Seventh Report of the Joint National Committee (JNC 7) recommends thiazide diuretics as a first-line treatment for most patients with Stage 1 hypertension, alone or in combination for patients with diabetes.8 These thiazide doses tend to be smaller and, therefore, tend to have minimal effects on blood glucose levels.
In 2004, a consensus guideline was developed on antipsychotic drugs, obesity, and diabetes.9 It describes baseline and followup monitoring of patients treated with SGAs. The baseline includes personal/family history, weight/body mass index, waist circumference, blood pressure, FPG, and a fasting lipid profile. Monitoring of these parameters is then designated at specified times throughout treatment (e.g., weeks four, eight, 12, etc.). Haupt et al recently compared monitoring of lipids and glucose in a population of insured patients receiving SGAs in a retrospective cohort of patients pre- and post-guideline.10 Baseline lipid and glucose testing rates increased minimally post-guideline versus pre-guideline.
The results of this study demonstrate that even though monitoring guidelines to prevent potentially adverse outcomes in a patient population at high risk for developing adverse outcomes are available, clinicians do not always follow them. In order to improve patient outcomes, identified at-risk populations (e.g., patients receiving SGAs) need to be more closely evaluated and monitored throughout therapy to prevent IGT and/or diabetes. TH
Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City.
- American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2009;32:S62-S67.
- Luna B, Feinglos MN. Drug-induced hyperglycemia. JAMA. 2001;286:1945-1948.
- Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68(Suppl 1):20-27.
- Tahir R. Metabolic effects of atypical antipsychotics. US Pharm. 2007;32:HS3-HS14.
- Warning about hyperglycemia and atypical antipsychotic drugs. U.S. Food & Drug Administration Web site. Available at: www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/printer.cfm?id=229. Accessed March 31, 2009.
- Kaufman MB, Simionatto C. A review of protease inhibitor-induced hyperglycemia. Pharmacotherapy. 1999;19:114-117.
- Pandit MK, Burke J, Gustafson AB, Minocha A, Peiris AN. Drug-induced disorders of glucose tolerance. Ann Intern Med. 1993;118:529-539.
- Chobanian AV, Bakris GL, Clack HR, et al. The seventh report of the joint national committee on prevention, detection, evaluations, and treatment of high blood pressure. JAMA. 2003;289:2560-2572.
- American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27:596-601.
- Haupt DW, Rosenblatt LC, Kim E, Baker RA, Whitehead R, Newcomer JW. Prevalence and predictors of lipid and glucose monitoring in commercially insured patients treated with second-generation antipsychotic agents. Am J Psychiatry. 2009;166:345-353.
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