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Type 2 diabetes prevalence [doubled] and its risk factors in HIV: A cross-sectional study
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In this ethnically diverse cohort of HIV patients we have shown that there is an alarmingly high prevalence of dysglycaemia: approximately 1 in 3 patients have prediabetes or T2D. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847234/
Among 249 HIV-infected patients, the mean age was 46.3 years, and 54% were male. Prevalence of prediabetes was approximately 30%, and BMI ≥30 kg/m2 was found to be a significant risk factor for developing prediabetes.....http://spectrum.diabetesjournals.org/content/early/2018/03/12/ds17-0009
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PLoS One. 2018
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847234/
Results
T2D prevalence was 15.1% in 2015 with a relative risk of 2.4 compared to the general population. The prevalence compared to 6.8% ten years earlier. The 2015 versus the 2005 cohort was significantly older (median age 49 (42-57) years versus 41 (IQR 35-47), p<0.001), had a higher BMI (27.4 (23.3-29.9) versus 24.9 (22.4-28.0) kg/m2 respectively, p = 0.019) and hypertensive (37.9% versus 19.6 respectively, p<0.001). The strongest predictors of dysglycaemia in the 2015 cohort were hepatic steatosis and hypertension, odds ratios (OR) and 95% confidence intervals (CI) 6.74 (3.48-13.03) and 2.92 (1.66-5.16) respectively, and also HIV-related factors of weight gain following antiretroviral initiation and longer known duration of HIV infection (OR 1.07 (1.04-1.11) and 1.06 (1.02-1.10) respectively).
Conclusions
The alarmingly high prevalence of T2D in HIV requires improved screening, targeted to older patients and those with a longer duration of exposure to antiretrovirals. Effective diabetes prevention and management strategies are needed urgently to reduce this risk; such interventions should target both conventional risk factors, such as abdominal obesity, and HIV-specific risk factors such as weight gain following initiation of antiretrovirals.
In this ethnically diverse cohort of HIV patients we have shown that there is an alarmingly high prevalence of dysglycaemia: approximately 1 in 3 patients have prediabetes or T2D. We have determined the role of a range of both HIV-specific and conventional risk factors in predicting the prevalence of T2D, and demonstrated the importance of modifiable risk factors. Compared to 2005 the 2015 cohort were older, had longer duration of HIV status and greater exposure to ART therapy, all significant determinants of dysglycaemia. However, our analysis also recognised the importance of a number of other determinants such as central adiposity which were more prevalent in the 2015 cohort. Given the burden of T2D in PLWH there is an urgent need to mitigate these modifiable risk factors through intervention in terms of both prevention and treatment.
The key risk factors for T2D in the general population, body mass and waist circumference, disproportionately affect people from minority ethnic groups [19], and these risk factors are pronounced in this ethnically diverse cohort.
Historically HIV was a disease associated with wasting and premature death and therefore these conventional risk factors were of little relevance. However, PLWH are now living longer and we have demonstrated that the rates of overweight and abdominal obesity are increasing and are now comparable with the general population [20]. Our regression models help explain the rise in T2D prevalence in our cohort, with changes in the incidence of conventional risk factors combined with HIV-specific factors contributing to T2D risk. The duration of HIV infection, ARV treatment and particularly the use of metabolically toxic ARVs, weight gain following initiation of ARVs, and the presence of lipodystrophy are all significantly associated with an increased risk of dysglycaemia. These were more likely to affect the 2015 cohort than in 2005, apart from lipodystrophy for which we observed a lower prevalence. Modifiable factors contributed significantly more to risk of dysglycaemia in our cohort than fixed factors, including age. In our cohort, hepatic steatosis and hypertension were the strongest predictors of dysglycaemia. HIV-specific factors also contributed significantly, particularly weight gain following initiation of ARVs, mirroring other recent observations [21]. It is not known if lifestyle treatment of hepatic steatosis directly reduces risk of development of diabetes, however pharmacological treatment of hypertension has been associated with a reduced risk for diabetes in the general population.
Given our findings suggesting a link between both hepatic steatosis and hypertension with diabetes risk, we believe that further research is required in people living with HIV.
The prevalence of T2D in the 2005 cohort was 6.8% whilst in our 2015 cohort it was 15.1%, driven in part by increasing age and BMI. Few studies elsewhere have examined change in prevalence of T2D in PLWH, however a change in prevalence of T2D was observed in an ethnically diverse HIV cohort in France [22]. A rise in incidence was associated with age and obesity, and historic exposure to ARVs linked with metabolic toxicities, as observed in the study presented here. Conversely, a study of a Danish population showed no increased risk for T2D in HIV, however this study was confined to White participants, the cohort was relatively young, and had lower levels of obesity [17]. Excess mortality when BMI is above normal has been well-demonstrated in the general population [23], and is of concern in PLWH: in one US cohort, multimorbidity associated with obesity affected 65% of HIV patients [24]. The prevalence of T2D in our 2015 cohort exceeded the upper end of a range in PLWH that has been described as 2.6-14% [1]. This may in part reflect collection of our data as recently as 2015, and might be a portent of a more general trend, especially given the ageing nature of the cohort. Our high prevalence might also reflect socioeconomic challenges faced by a high proportion of our largely inner city cohort. It is unlikely that the difference in sampling strategies between the cohorts contributed to the high prevalence in 2015 as although Black Caribbean and Black African participants were fairly represented in 2015, the difference to 2005 was not statistically significant.
It is well established that dietary change, increased physical activity and weight loss all reduce diabetes risk in the general population [25]. This approach may be especially relevant to PLWH given the low levels of physical activity and fruit and vegetable consumption and high prevalence of overweight and obesity that we observed [20]. Dietetic intervention in PLWH has been shown to prevent weight gain and subsequent development of hyperlipidaemia after initiation of ARVs [26]. The association between dysglycaemia and weight gain following initiation of ARVs that we observed is another rationale for recommending dietetic intervention at this stage.
The strengths and limitations of our research warrant consideration. A principle strength for investigation of factors associated with diabetes risk in the 2015 cohort is the lack of missing data other than Vitamin D measurements. Our participants were recruited from the same clinical cohort at two time points, and this allowed us to compare factors associated with diabetes risk. Clinical definitions and diagnostic criteria were applied consistently in both 2005 and 2015. At both time points glycaemic status was characterised by glucose measured in a truly fasting state, and did not rely on HbA1c, which can be underestimated in people treated with ARVs [27].
A limitation is that our sampling methods differed between the two cohorts, although both included partial randomisation and excluded recruitment from specialist metabolic HIV clinics. It is possible that the 2015 sample does not fairly represent the total clinical cohort considering factors other than age, gender and ethnicity, for example socioeconomic status or educational attainment. Fewer predictor variables were collected in 2005 compared to 2015. Data collection from 2005 was not designed to allow subgroup analysis of factors contributing to diabetes risk, and so changes over time cannot be assessed. Regarding potential non-ARV pharmacological contribution to dysglycaemia, data collection was limited to exposure to corticosteroids and metformin. Furthermore, medical records predating 1996 were rarely available, and we relied on participant recollection which may not have been wholly accurate. Smoking status, physical activity levels and consumption of fruits and vegetables were self-reported and open to misreporting. Hepatic steatosis rates derived from the medical notes may have been overestimated in those with dysglycaemia due to selective screening in those perceived to be at risk of hepatic fibrosis. A limitation is the lack of an HIV negative control group for comparison.
In conclusion, the alarmingly high prevalence of T2D in our cohort of PLWH has implications for the tens of millions of PLWH worldwide. This is compounded by an increase in associated comorbidities in PLWH, including cardiovascular disease [6]. Additionally there are distinct challenges associated with the management of T2D in HIV. Some ARVs can impair glycosylated haemoglobin (HbA1c) assays resulting in underestimation [27,28] and some ARVs significantly interact with hypoglycaemic agents [29]. Overall it is known that HIV patients with T2D have a poorer response to diabetes treatments compared to matched HIV negative individuals [30]. We suggest a response is urgently needed. Enhanced screening for diabetes risk in PLWH should be considered and should account for the broad range of risk factors that affect PLWH, both conventional and HIV-specific. Interventions that tackle these risk factors are needed. Selection of ARVs with less effect on insulin resistance in those with dysglycaemia or significant risk factors, and proactive lifestyle management of the increased risk of diabetes that occurs due to weight gain following initiation of HAART, should be considered. Furthermore, there is an urgent need to understand whether diet and lifestyle interventions that are effective at tackling diabetes risk factors in the general population, for example those that reduce blood pressure and hepatic steatosis, are effective in PLWH. Diabetes risk should not be considered in isolation in PLWH, and disease specific screening and management of other comorbidities in PLWH with diabetes should be undertaken [1,31].
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