Diabetes Associated With Other Factors

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Type 2 diabetes can also be associated with the following other clinical states, drugs, and chemicals:

1. Genetic syndromes—Huntington's chorea, muscular dystrophy, and lipodystrophic diseases.

2. Pancreatic diseases—chronic pancreatitis, pancreatectomy states, hemochromotosis, and cystic fibrosis.

3. Endocrinopathies—primary aldosteronism, Cushing syndrome, acromegaly, pheochro-mocytoma, glucogonoma, polycystic ovaries.

4. Drugs—thiazide diuretics, P-blockers, glucocorticoids, phenytoin, nicotinic acid, cat-echolamines, estrogen and progesterone preparations, and antidepressant medications (especially clozapine, olanzapine and risperidone) (8).

5. Chemicals—tetrachlorodibenzo(para)dioxin (TCDD).

Usually, in these conditions, treatment of the underlying condition or elimination of the offending drug enhances glycemic control, although some chemicals may cause permanent alterations and establishment of the diabetic state.

US regulators have determined that six antipsychotic medications can increase the risk of impaired glucose tolerance and diabetes. These medications are:

1. Zyprexa (olanzapine).

2. Risperdal (risperidone).

3. Clozaril (clozapine).

4. Seroquel (quetiapine).

5. Geodon (ziprasidone).

6. Abilify (aripiprazol).

Recent studies involving almost 20,000 schizophrenic patients across the United States showed that patients taking Risperdal had an increase in diabetes of 49%; a 27% increase for Zyprexa, and patients taking Seroquel had 3.34 times as many cases of diabetes as those on older antipsychotic medications. It is important to consider that schizophrenic patients have a greater tendency to be overweight, and weight gain can increase the risk for type 2 diabetes (9).

In a recent study in the Journal of Clinical Pharmacology, diabetic patients with psychoses had a 3% higher risk of developing diabetes within 1 month of first taking olanzapine and a 42.6% increase risk within 12 months of treatment, compared with controls. Thus, management of patients with psychoses should routinely include body weight and blood glucose monitoring with advice to promote exercise and minimize weight gain (10).

For those individuals at risk for developing diabetes, fasting blood glucose should be measured within 4 months of starting an antipsychotic medication and at regular intervals (at least yearly) if weight gain develops. The physician should be alert for the symptoms of diabetes, such as fatigue, polyuria, and polydipsia.

Table 2

Criteria for the Diagnosis of Diabetes

• Symptoms of diabetes and a random plasma glucose >200 mg/dL (11.1 mmol)

• 2-h postprandial glucose >200 mg/dL tolerance test with 75 g anhydrous glucose

• Impaired fasting glucose: >100 mg/dL (5.5 mmol) and <126 mg/dL (7 mmol)

• Impaired glucose tolerance: postprandial glucose >140 mg/dL (7.8 mmol) and <200 mg/dL (11.1 mmol)

One of the more curious recent associations has been exposure to the herbicide, Agent Orange, and its contaminant, TCDD, and its association with the subsequent development of type 2 diabetes, as now recognized by the Veterans Administration (VA).

Agent Orange was a mixture of two herbicides—trichlorophenoxyacetic acid (2,4,5-T) and dichlorophenoxyacetic acid (2,4-D). Both of these herbicides, especially 2,4,5-T, contained a contaminant, as a byproduct of their manufacturing, TCDD. The substance is a very potent chemical inducer, affecting the reproduction of various enzyme and co-enzymes systems within the body (11).

TCDD, or "dioxin," has been implicated as a cause of birth defects, impaired immune function, gastrointestinal disturbances (including hemorrhaging, porphyrin disturbances, especially porphyria cutanea tarda), acute and subacute central and peripheral neuropathies, skin disturbances (such as chloracne), various malignancies (including: soft-tissue sarcoma, Hodgkin's and non-Hodgkin's lymphoma, multiple myeloma, prostate cancer, chronic lymphocytic leukemia, and nasopharyngeal, liver, lung, trachea and bronchus, and gastrointestinal carcinomas), lipid disturbances, and type 2 diabetes (12).

The decision of the VA regarding the service connection was prompted by a report in November 2000 cited in Disabled American Veteran magazine issued by the National Academy of Sciences Institute of Medicine that found "limited, suggestive evidence of a link between type 2 diabetes and Agent Orange and other herbicides used in Vietnam."

According to current statistics from the VA, 9% of the 2.3 million Vietnam veterans still alive have type 2 diabetes; 16% of those currently hospitalized have type 2 diabetes.

Documentation of the type 2 phenotype must be demonstrated with C-peptide levels and absence of anti-islet cell and insulin antibodies.

Steroid therapy can often unmask diabetic tendencies or aggravate glycemic control. Steroids vary according to their mineralocorticoid and glucocorticoid potency. Dexam-ethasone is the most potent glucocorticoid, followed by methylprednisolone, prednisone and hydrocortisone. The order is reversed for their mineralocorticoid potencies. Steroids exert their glycemic effects by aggravating insulin resistance.

Thiazide diuretics, by inhibiting insulin output from the pancreas, can worsen hyper-glycemia, especially with higher doses than can induce hypokalemia.

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