Diabetes mellitus case study

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Green, J., Casabonne D., and Newton, R. Coxsackie B virus serology and Type 1 diabetes mellitus A systematic review of published case-control studies, Diabet Med., 21,507,2004. 

Myeloperoxidase is an extremely potent, antimicrobial protein that is present in neutrophils at up to 5% of the total cell protein. Its role in the killing of a wide range of bacteria, fungi, viruses, protozoa and mammalian cells (e.g. tumour cells) is well established from in vitro studies. It also plays an important role in the inactivation of toxins and the activation of latent proteases, as well as in other functions described in section 5.4.1. In view of this apparent central role in neutrophil function during host defence, one would think that any deficiencies in this enzyme would have disastrous consequences on the ability of the host to combat infections. Until the early 1980s, this key role for myeloperoxidase in host protection seemed substantiated by the extremely low incidence of reports of patients with deficiencies of this enzyme. Indeed, up to this time, only 15 cases from 12 families had been reported worldwide. Sometimes these patients were asymptomatic but often suffered Candida infections, particularly if their myeloperoxidase deficiency was also associated with diabetes mellitus. 

In a cohort study (164) in 1785 women, 69 incident cases of diabetes mellitus were diagnosed, with an average incidence of 1.5 cases per 100 patient-years. In patients taking protease inhibitors, incidence rates were about twice as high (2.8 cases per 100 patient-years) as among users of NNRTIs or untreated patients (1.2%) and uninfected controls (1.4%). In a multivariate model use of protease inhibitors (HR = 2.9 1.5, 5.6), age, and BMI were independent risk factors for diabetes. 

In patients with chronic hepatic B or C the respective prevalences of pancreatic autoantibodies increased from 2% and 3% at baseline to 5% and 7% after interferon (544). In all, 31 published cases of type 1 diabetes mellitus attributed to interferon alfa treatment were detailed, mostly in patients with hepatitis C. Irreversible diabetes required permanent insulin treatment in all but eight cases. At least one marker of pancreatic autoimmunity was positive in nine of 18 patients before treatment, and in 23 of 30 patients at the onset of diabetes. In accordance with these results and the likelihood of a genetic predisposition, the authors recommended screening for islet cell and glutamic acid decarboxylase autoantibodies before and during interferon alfa treatment. However, owing to the low number of reported cases and the paucity of studies that have examined the relation between pancreatic autoimmunity and the occurrence of diabetes, further research on the predictive potential of such a systematic investigation is warranted. 

The data cut-off point for this study was 31 August 2000. Only incident cases of diabetes mellitus that resulted in intervention with antidiabetic drugs were selected and only patients taking antipsychotic drug... 

In a retrospective, case-control study of the use of phencyclidine in 23 of 13 653 pregnant women, the phencyclidine users had smaller infants (2698 versus 3011 g), which may have been partly accounted for by a reduction in gestational age (37.3 versus 38.3 weeks) (24). The users were more likely to have used tobacco, alcohol, or marijuana and had a higher incidence of syphilis and diabetes mellitus. 

In another Finnish study, about 116 000 children bom in Finland between 1 October 1985 and 31 August 1987 were randomized to receive four doses of Hib vaccine (PPR-D, Connaught) starting at 3 months of life or one dose starting after 24 months of life (16). A control cohort included all 128 500 children born in Finland in the 24 months before the study. The difference in cumulative incidence between those who received four doses of the vaccine and those who received none was 54 cases of diabetes per 100 000 at 7 years (relative risk = 1.26). Most of the extra cases of diabetes occurred in statistically significant clusters starting about 38 months after immunization and lasting about 6-8 months. The authors concluded that exposure to Hib immunization is associated with an increased risk of type 1 diabetes mellitus. 

In one study, in which prospective ophthalmic examinations were made before and at regular 2-week intervals after the beginning and end of treatment, 28 of 81 patients who received a uniform total dose of natural interferon aha (478 MU) for chronic hepatitis C developed the typical findings of interferon-induced asymptomatic retinopathy (cottonwool spots and/or retinal hemorrhages) (84). In contrast, there were no lesions in the 25 patients with chronic hepatitis C who did not receive interferon alfa or in the 20 with diabetes mellitus and/or hjrpertension but without chronic hepatitis C. Most of the cases were observed within 4 months of treatment, and the lesions always abated after withdrawal or even despite continuation, suggesting that treatment can be continued unless patients develop sjmp-toms. Indeed, most patients with retinopathy associated with interferon alfa remained asymptomatic. 

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