didanosine and Diabetes-Mellitus

Abacavir use has been associated with an increased risk of cardiovascular disease (CVD) and metabolic events in HIV-infected patients, although this finding was not consistently found. It is unclear whether abacavir only increases this risk in subpopulations of HIV-infected patients. It may be hypothesized that inosine 5'-triphosphate pyrophosphohydrolase (ITPase), an enzyme involved in the metabolism of purine analogues used in HIV treatment, plays a role in the risk of CVD and metabolic events in HIV-infected patients.. ITPase activity and ITPA genotype were determined in 393 HIV-infected patients. ITPase activity <4 mmol IMP/mmol Hb/h was considered decreased. ITPA polymorphisms tested were: c.94C>A (rs1127354) and c.124 + 21A>C (rs7270101). ORs were determined using generalized estimating equation models for developing CVD in patients who had ever been exposed to abacavir, tenofovir or didanosine and for developing metabolic events in patients currently using these drugs.. In patients using abacavir, metabolic events were associated with ITPase activity. No association was demonstrated for tenofovir or didanosine. The OR for metabolic events was 3.11 in patients using abacavir with normal ITPase activity (95% CI 1.34-7.21; P = 0.008) compared with patients with decreased ITPase activity [adjusted for age, BMI, cumulative duration of combination ART (cART) use and the use of PI and NNRTI]. CVD was not associated with ITPase activity or ITPA genotype.. This study shows, for the first time, that ITPase activity is associated with the occurrence of metabolic events in patients using abacavir. Further studies are needed to confirm this association and to elucidate the possible mechanism.

Topics: Adult; Aged; Diabetes Mellitus; Didanosine; Dideoxynucleosides; Erythrocytes; Female; Genotype; HIV Infections; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Pyrophosphatases; Reverse Transcriptase Inhibitors; Tenofovir

To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009.. Prospective study of 1046 patients at 47 French clinical sites.. Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure.. Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes.. In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.

Topics: Adiposity; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Mass Index; Cohort Studies; Diabetes Mellitus; Didanosine; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Indinavir; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Factors; Stavudine; Waist-Hip Ratio

In a nationwide, population-based cohort study we assessed the risk of diabetes mellitus (DM) in HIV-infected individuals compared with the general population, and evaluated the impact of risk factors for DM in HIV-infected individuals.. We identified 4,984 Danish-born HIV-infected individuals from the Danish HIV Cohort Study and a Danish born population-based age- and gender-matched comparison cohort of 19,936 individuals (study period: 1996-2009). Data on DM was obtained from the Danish National Hospital Registry and the Danish National Prescription Registry. Incidence rate ratios (IRR) and impact of risk factors including exposure to Highly Active Antiretroviral Therapy (HAART) and antiretroviral drugs were estimated by Poisson regression analyses.. In the period 1996-1999 risk of DM was higher in HIV-infected individuals compared to the comparison cohort (adjusted IRR: 2.83; 95%CI: 1.57-5.09), both before (adjusted IRR: 2.40; 95%CI: 1.03-5.62) and after HAART initiation (adjusted IRR: 3.24; 95% CI: 1.42-7.39). In the period 1999-2010 the risk of DM in HIV-infected individuals did not differ from that of the comparison cohort (adjusted IRR: 0.90; 95% CI: 0.72-1.13), although the risk was decreased before HAART-initiation (adjusted IRR: 0.45; 95%CI: 0.21-0.96). Increasing age, BMI and the presence of lipoatrophy increased the risk of DM, as did exposure to indinavir, saquinavir, stavudine and didanosine.. Native HIV-infected individuals do not have an increased risk of developing DM compared to a native background population after year 1998. Some antiretroviral drugs, not used in modern antiretroviral treatment, seem to increase the risk of DM.

Topics: Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Body Mass Index; Cohort Studies; Denmark; Diabetes Complications; Diabetes Mellitus; Didanosine; Female; HIV Infections; Humans; Incidence; Indinavir; Male; Middle Aged; Regression Analysis; Risk Factors; Saquinavir; Stavudine; Treatment Outcome

Topics: Acanthosis Nigricans; Adult; Diabetes Mellitus; Didanosine; HIV Infections; HIV Protease Inhibitors; Humans; Insulin Resistance; Male; Ritonavir; Zidovudine

We determined the frequency and clinical nature of severe hyperglycemia in a university clinic for HIV-1-infected patients. The medical records of 1392 adult HIV-infected patients were reviewed for cases of severe hyperglycemia, defined as two or more serum glucose values >250 mg/dl or diabetes treatment during clinic care. Demographic information, family histories of diabetes mellitus, body weights, CD4+ lymphocyte counts, and use of corticosteroids, megestrol acetate, pentamidine, or didanosine were recorded for subjects meeting the case definition. Comparisons were made between preexisting diabetic (group 1) and incident hyperglycemic cases (group 2). Less than 2% of the total clinic population experienced severe hyperglycemia: 12 in group 1 and 13 in group 2. Group 2 had lower body weights (mean, 70.6 kg versus 90.0 kg; p < 0.05) and more advanced HIV disease (mean CD4 count, 79/mm3 versus 550/mm3; p < 0.05) than group 1. Group 2 cases had evidence of drug-associated hyperglycemia; four cases demonstrated hyperglycemia coinciding with large fluctuations in weight during megestrol therapy. Among megestrol recipients, cases did not differ from noncases in demographics, weight, or CD4 count. Severe hyperglycemia is uncommon in adult HIV-infected patients. Approximately one half of these patients have preexisting diabetic conditions; many of the remainder may have drug-induced hyperglycemia, especially as a result of corticosteroids or megestrol acetate.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-HIV Agents; Diabetes Complications; Diabetes Mellitus; Didanosine; Female; HIV Infections; Humans; Hyperglycemia; Male; Megestrol Acetate; Middle Aged; Pentamidine; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Adult; Diabetes Mellitus; Didanosine; Female; Humans