Study in an inner-city HIV (Viramune drug treating HIV infection) clinic in south central Los Angeles demonstrated that among those who attend the clinic, the prevalence of diabetes (Generic Glucophage is used to treat a type of diabetes mellitus) among patients on protease inhibitors is 12%. None of the patients who were not taking Pis developed diabetes. During the follow-up, the incidence of diabetes was 7.2% over a three-year period (2.4% per year) only among those who were taking Pis. Hypertriglyceridemia was observed among HIV-infected patients on Pis with and without diabetes (avandia 4 mg treat high blood sugar levels (sugar diabetes) called type 2 diabetes). BMI was not statistically different between these two groups.

In his study, Carr et al. observed impaired glucose tolerance in 16% of protease-inhibitor recipients and diabetes mellitus (actos medication treat type II of diabetes) in 7%. In a large multicenter study, the incidence of diabetes based on self-reports was 2.5% in HIV-infected women on protease inhibitors. Compared to our study, both studies have similar incidence and prevalence of diabetes (Actoplus Met canadian is for people with type 2 diabetes) among those who are taking protease inhibitors.

However, our data demonstrated higher prevalence of diabetes compared to other published data on HIV infected (Generic Zerit еreating HIV infection when used in combination with other medicines) subjects (12% vs. 5%), possibly because of higher number of African Americans in our population. African Americans are known to have higher prevalence of diabetes compared to Caucasians. In a recent study, it has been observed that among non-HIV-infected African Americans with low or high consumption of fibers, the incidence of diabetes (Starlix medication is an oral antidiabetic agent used in the management of Type 2 diabetes mellitus) is 18.1% and 19.1% over nine years, respectively,9 with an average incidence of diabetes of 1.9% per year compared to incidence of 2.4% per year in our HIV subjects on Pis.

To the best of our knowledge, no study examined the prevalence of diabetes in early epidemic of HIV infection when Pis were not available. In our own personal observation of a cohort of homosexual Caucasian males infected with HIV (Generic Retrovir еreating HIV infection when used along with other medicines) from 1984 to 1990 (when Pis were not yet available), only one over 240 patients had developed diabetes mellitus. Acknowledging the limited value of historical data and the possibility of detection bias, and regardless of the previous observation, our current study documented an increase in prevalence of diabetes (Generic Capoten treating high blood pressure, heart failure, or certain diabetic kidney problems) among PI users from 12% at baseline to 17% at the end of the study.

Pis significantly decrease mortality and morbidity, and improve malnutrition among HIV-infected patients, but with the advent of Pis and other antiretroviral treatment, a complex metabolic syndrome has emerged. This complex is mostly associated with the use of Pis; however, a contribution of non-nucleo-side reverse transcriptase and nucleoside reverse transcriptase inhibitors in the increased risk of development of lipodystrophy has been described.

It appears that Pis facilitate and/or accelerate the process of diabetogenesis. The pathogenesis, however, is not fully understood. Accumulation of intra-abdominal fat and decrease of subcutaneous fat are both known to be associated with dyslipidemia, insulin resistance and diabetes (Generic Avandamet is used for improving blood sugar levels, with diet and exercise, in patients with type 2 diabetes). HAART-associated dysmetabolic syndrome has some similarity with Cushing’s syndrome. Even though several studies did not demonstrate an excess of glucocorticoids in the serum of patients with AIDS, an alteration of hypothalamic-pituitary-adrenal axis has been described.

The development of diabetes (Canadian Diabecon is a complex herbal formula supplement offering gentle and safe glycemic control) and hypertriglyceridemia could also be related to the development of subcutaneous fat atrophy. Adiponectin is a hormone secreted from subcutaneous fat. Reduced levels of adiponectin correlates with severe insulin resistance, which may have a role in the development of insulin resistance and diabetes in patients taking Pis.

The pathophysiology of diabetes in HAART-associated dysmetabolic syndrome has also been attributed to the inhibitory effect of one of Pis (indiniavir) on the glucose transporter 4 (Glut-4) on adipocytes and rat muscle. Incubation of muscles with indinavir reduced the insulin-stimulated increase in 3Methyl glucose transport dose dependency up to 58%. Also, the insulin-stimulated increase in cell-surface GLUT4 was reduced by approximately 70%.

Indinavir also downregulates Proteasome Prolif-erator Activator Receptor у (PPAR y) expression in adipocytes in culture. A decrease in the number of newly formed adipocytes and the lower level of the adipogenic protein markers, such as sterol regulatory element-binding protein-1 (SREBP-1), PPAR y, and the insulin receptor (IR) of the indinavir-treated cells have been shown previously.

In our study, not all subjects were taking indinavir, and these in-vitro studies cannot solely explain the other aspect of the HAART dysmetabolic syndrome.
The third hypothesis suggests a possibility of an increased activity in adipose 11 beta hydroxysteroid dehydrogenase type-1 activity under the effect of protease inhibitors. The increased activity of 11 beta hydroxysteroid dehydrogenase type-1, which is present in visceral fat, would accelerate retrograde conversion of inactive cortisone to the active Cortisol, which in turn increases lipolysis and increases free fatty acid in the portal system, causing insulin resistance and hyperlipidemia. This hypothesis may also explain some of the Cushing’s aspect of this complex syndrome.

In summary, we observed a high prevalence of diabetes among patients treated with protease inhibitors especially those who were older and African-American. Therefore, we suggest that fasting plasma glucose in HIV-infected patients on Pis be monitored early in the course of therapy, especially among those who are older or who have other risk factors for developing diabetes.