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Eleven-year incident glucose disorders [45%] in treated HIV-infection. The St Vincent's HIV and Diabetes Study
 
 
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"Baseline characteristics are shown in Table 1: mean (±SD) age 42⋅9±8⋅2years, BMI 24⋅3±2⋅6kg/m2, known HIV-infection duration 8⋅4±4⋅1years; 30% had a prior AIDS-defining illness (n=32). The mean glucose was 4⋅9±0⋅6mmol/L; 96 had normal fasting glucose, 8 had IFG. Follow-up was 11⋅8±3⋅4years (median 12⋅8years)......During the follow-up period, 50 participants developed a new glucose disorder (45⋅8%): pre-diabetes in n=37 (32⋅3%) and type 2 diabetes in n=13 (12⋅5%)."
 
AIDS Dec 12 2017 - McMahon Chelsea N.; Petoumenos, Kathy; Hesse, Karl; Carr, Andrew; Cooper, David A.; Samaras, Katherine
 
Conclusion
 
In this population, treated HIV-infection was associated with high rates of incident glucose disorders in the long-term, with strikingly high rates detected by OGTT [oral glucose tolerance test ] screening. Modest abdominal fat gain, even in the healthy weight range, was associated with a 2-3 fold increased risk of incident glucose disorders. Accurate determination of glucose status in treated HIV-infection will identify individuals for early intervention with preventive weight management strategies for cardiometabolic health maintenance and diabetes prevention. ....... The introduction of combined antiretroviral therapy (cART) has dramatically transformed the natural history of HIV-infection and the lives of people living with it, impacting the development of AIDS, life expectancy and quality of life. In 2015, approximately 17 million people globally were receiving cART1. These benefits are, however, at the cost of cART-associated cardiometabolic consequences that include diabetes mellitus (diabetes)2-5. These appear to be increased by cumulative exposure, especially with the early nucleoside reverse transcriptase inhibitors (NRTIs)6-8. Notably, early NRTIs are most strongly implicated in the pathogenesis of HIV-related lipodystrophy8. Although these medications are infrequently prescribed in resource-rich countries today, they may still be first-line in some resource-limited settings where the highest prevalence of HIV-infection exists.
 
"In this longitudinal cohort study, high rates of incident glucose disorders were found in men with longstanding treated HIV-infection. To our knowledge, this is the longest duration of follow-up for incident glucose disorders in treated HIV-infection .....Strikingly high rates of glucose disorders were detected: 60% of the subgroup had IGT or diabetes.In those with normal fasting glucose, the OGTT found IGT in 45% and diabetes in 10%, detecting approximately twice the rate of glucose disorders as fasting glucose alone......As the glycosylated haemoglobin measure has been shown to under-diagnose glucose disorders20 and under-estimate glucose control in treated HIV-infection21, our findings suggest that the OGTT should be considered best practice for accurate ascertainment of glucose status in treated HIV-infection."
 
"In this study, we determined the long-term incidence of diabetes and pre-diabetes in a cohort of men with treated-HIV infection who, in 1997, underwent detailed phenotyping for a study examining the natural history of lipodystrophy13. Baseline factors were examined for their association with long-term incident glucose disorders.....This prospective cohort study (St Vincent's HIV and Diabetes Study) examined baseline data from 144 HIV-infected men recruited between August-September 1997 for metabolic complication evaluation13......Of the original 144 participants, 4 had diabetes at baseline and were excluded; 36 had dropped out of HIV ambulatory clinic care and 104 had long-term glucose levels available. Baseline characteristics are shown in Table 1: mean (±SD) age 42⋅9±8⋅2years, BMI 24⋅3±2⋅6kg/m2, known HIV-infection duration 8⋅4±4⋅1years; 30% had a prior AIDS-defining illness (n=32). The mean glucose was 4⋅9±0⋅6mmol/L; 96 had normal fasting glucose, 8 had IFG-pre-diabetes (impaired fasting glucose . Follow-up was 11⋅8±3⋅4years (median 12⋅8years)......During the follow-up period, 50 participants developed a new glucose disorder (45⋅8%): pre-diabetes in n=37 (32⋅3%) and type 2 diabetes in n=13 (12⋅5%). The incidence of glucose disorders was 34⋅5/1,000 PYFU: pre-diabetes 24⋅3/1,000 PYFU and diabetes 10⋅2/1,000 PYFU. Figure 2 shows the cumulative incidences of glucose disorders and diabetes......Detection of incident glucose disorders was further examined in a subgroup who accepted the invitation for an OGTT at 10-12 years follow-up (n=33, 32%)......The OGTT identified incident glucose disorders in 61% (n=20): IGT in 45% (n=15) and diabetes in 15% (n=5). Of 29 OGTT participants with normal fasting glucose at the time of the OGTT, IGT-impaired glucose tolerance was identified in n=13 (45%) and diabetes in n=3 (10⋅3%)......In Cox regression models, age was significantly and independently associated with risk for incident glucose disorders and diabetes, with a trend was observed for the presence of an AIDS-defining illness at baseline......The incidence rate in our cohort was similar to cohorts in France and Taiwan (14⋅19 and 13⋅119 per 1,000 PYFU, respectively), but exceeds that found in D:A:D (5⋅72/1,000 PYFU)8, the Swiss cohort (4⋅4/1,000 PYFU over 4⋅3 years)10 and a recent Thai study (5⋅0/1,000 PYFU, mostly females over 7 years)11. Higher incidence rates have been reported in the US Women's Interagency HIV Study (17⋅0-25⋅0/1,000 PYFU)7,17, an Italian cohort (20⋅6/1,000 PYFU)18, and the US Multicenter AIDS Cohort Study (47⋅0/1,000 PYFU)16. Notable differences between study cohorts may explain these differences, including sex, age, obesity, HIV-duration and diabetes ascertainment methodology. "
 
"As for the general population, the current study found that traditional risk factors held the strongest associations with incident glucose disorders, namely increasing abdominal adiposity, age and elevated C-peptide, rather than HIV-infection specific risk factors. Older age at baseline was a significant determinant of increased of incident glucose disorders and diabetes, consistent with prior studies in people with treated HIV-infection9,10. Abdominal fat gain was also a strong independent predictor of incident glucose disorders in this cohort. Few studies have examined longitudinal weight gain and risk of incident diabetes in treated HIV-infection. To our knowledge, this is the first study to report that early- and medium-term gains in abdominal fat (measured directly by DEXA) are associated with increased risk of incident glucose disorders. In those who gained abdominal fat over 12-months and 2-4 years observation, we found a 2 to 3-fold increased risk of incident glucose disorders at long-term follow-up, independent of covariates. Importantly, the majority of participants were in the healthy BMI range and none were obese. Further, the mean difference in abdominal fat gain in participants who developed glucose disorders was modest (230-320g), suggesting that predominantly healthy-weight men with treated HIV-infection may be at greater susceptibility to diabetes with modest abdominal fat gain.
 
Of the HIV-specific factors examined, only longer known HIV-infection duration at follow-up was associated with increased incident diabetes. Cohort participants with and without incident glucose disorders had similar cART exposure durations. Nelfinavir appeared to be associated with reduced incident diabetes risk in multivariate models; this results might be explained by prescription bias: many PIs available at that time were identified to increase insulin resistance and nelfinavir may have been preferentially prescribed. Overall, no increased risk of diabetes was observed with specific exposure to stavudine, zidovudine, or didanosine, in contrast to other studies7,8,17, which may be due to cohort differences in age, sex, size and cART era. Prior studies have shown relationships between medication exposure and incident diabetes. D:A:D reported that cumulative cART exposure independently increased incident diabetes relative risk by 11%8. Stavudine exposure was associated with a 19% incident diabetes relative risk increase, with lesser risk observed with zidovudine and didanosine; in contrast, ritonavir and nevirapine appeared protective8. Cohort data examination over the longer-term with appropriate diabetes ascertainment will assist in clarifying any relationships between cART exposure and glucose disorders."
 
"Introduction
 
HIV-infection currently affects 36⋅7 million people worldwide1. The introduction of combined antiretroviral therapy (cART) has dramatically transformed the natural history of HIV-infection and the lives of people living with it, impacting the development of AIDS, life expectancy and quality of life. In 2015, approximately 17 million people globally were receiving cART1. These benefits are, however, at the cost of cART-associated cardiometabolic consequences that include diabetes mellitus (diabetes)2-5. These appear to be increased by cumulative exposure, especially with the early nucleoside reverse transcriptase inhibitors (NRTIs)6-8. Notably, early NRTIs are most strongly implicated in the pathogenesis of HIV-related lipodystrophy8. Although these medications are infrequently prescribed in resource-rich countries today, they may still be first-line in some resource-limited settings where the highest prevalence of HIV-infection exists.
 
There are few long-term studies reporting the incidence of diabetes in people living with treated HIV-infection. The longest study to date, with up to 10 years follow-up, reported an incidence of 14⋅1 cases/1,000 patient years follow-up (PYFU)9. Three shorter-term studies reported lower incidence rates8,10,11. The Data Collection on Adverse Event of Anti-HIV Drugs (D:A:D) reported incident diabetes at 5⋅72/1,000 PYFU in 33,389 HIV-infected people over 3⋅8 years8. Other studies of 4-7 years follow-up reported incidence rates of 4⋅4-5⋅0/1,000 PYFU10,11. Further, changes in diabetes incidence are evident over time, at least in HIV-infected youth12, where a near ten-fold increase in incidence has been observed: from 0⋅15/1,000 PYFU in 2000-2007, to 1⋅67/1.000 PYFU subsequently12. Risk factors for diabetes in treated HIV-infection include older age9,11, higher body mass index (BMI)8,9,11, lipodystrophy5,9, dyslipidaemia8,9,11, and exposure to stavudine8,9, zidovudine8, didanosine8,9, and indinavir9. Whilst differences in age, cART exposures and observation duration may explain some of the incidence rate differences in prior studies, much remains unclear about factors which may promote diabetes risk in HIV-infection, particularly the impact of the obesity epidemic.
 
In this study, we determined the long-term incidence of diabetes and pre-diabetes in a cohort of men with treated-HIV infection who, in 1997, underwent detailed phenotyping for a study examining the natural history of lipodystrophy13. Baseline factors were examined for their association with long-term incident glucose disorders."

 
 
 
 
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