New-onset diabetes in HIV-treated adults

Putcharoen, Opass; Wattanachanya, Lalita; Sophonphan, Jiratchaya; Siwamogsatham, Sarawut; Sapsirisavat, Vorapot; Gatechompol, Sivaporn; Phonphithak, Supalak; Kerr, Stephen J.; Chattranukulchai, Pairoj; Avihingsanon, Yingyos; Ruxrungtham, Kiat; Avihingsanon, Anchalee

doi:10.1097/qad.0000000000001496

Cited by 40 publications

(26 citation statements)

References 31 publications

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“…Our study showed that the risk of death in patients diagnosed DM tended to be higher after 4 years of follow-up, a finding similar to that reported by a previous study in Thailand [34]. Although causes of death were not available, we hypothesized that the increasing risk of death with DM may have been related to cardiovascular and renal complications as well as HIV infection itself.…”

Section: Discussionsupporting

confidence: 89%

Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: a retrospective cohort study

et al. 2018

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BackgroundSince 2005, Thailand has scaled up one of the largest antiretroviral treatment (ART) programs in South East Asia. Although diabetes mellitus (DM) incidence is increasing in low and middle-income countries, its burden and contributing factors in the HIV infected population are not well known.MethodsUsing the Thai National AIDS Program data over a period of 8-years, we identified patients diagnosed with DM based on the following records: 1) fasting plasma glucose equal to or greater than 126 mg/dl following the 2013 American Diabetes Association criteria or 2) diagnosis codes E11-E14 of the 2010 WHO International Classification of Diseases, or 3) anti-diabetic drugs. Incidence was the number of new cases divided by that of person-years of follow-up (PYFU). Competing risks survival regression, treating death without DM as a competing event, was used to identify factors associated with DM. The risk of death in patients diagnosed with DM was estimated using Cox regression models.ResultsData of 763,666 PYFU from 199,707 patients (54.2% male; median age 36.2 years at registration with the program) were available and 8383 cases were diagnosed with DM, resulting in an incidence rate of 11.0 per 1000 PYFU. New DM diagnosis was more likely in men (adjusted sub-distribution hazard ratio 1.2), older patients (compared to patients 18 to 34 years old: 1.8 for 35 to 44; 3.0 for 45 to 59; 3.8 for ≥60), and if ART was initiated (1.3). In 2014, 1313 (16.6%) of 7905 diabetic patients had DM complications (11.5% microvascular complications and 6.9% macrovascular complications). Patients diagnosed with DM were at higher risk of death compared to the others.ConclusionsDM incidence was higher in this Thailand cohort of HIV infected adults than in the general population. Risk factors were similar to those in the general population, in addition to starting ART.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-5967-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: a retrospective cohort study

et al. 2018

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“…This is a prospective study in an ongoing HIV Thai adult cohort (HIV-NAT 006 cohort, clinical trial number: NCT00411983). The details of this cohort have previously been described [ 16 – 18 ]. Participants were eligible for inclusion in this analysis if they achieved and maintained suppressed viremia at HIV-RNA < 50 copies/mL after starting cART.…”

Section: Methodsmentioning

confidence: 99%

CD4/CD8 ratio normalization rates and low ratio as prognostic marker for non-AIDS defining events among long-term virologically suppressed people living with HIV

et al. 2018

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BackgroundImmune restoration is often incomplete after ART in HIV patients, both quantitatively and qualitatively. We studied the incidence and probability of CD4/CD8 normalization in an adult Thai HIV cohort and explored the predictive value of the ratio for developing of non-AIDS defining events (NAEs).MethodsWe analyzed data from HIV-infected Thai adults between 1996 and 2017 in the HIV-NAT 006 prospective long-term cohort in Bangkok, Thailand. Normalization was defined as CD4/CD8 ratio ≥ 1 on two consecutive visits, and normalization probability was calculated using the Kaplan–Meier method. NAEs were a composite endpoint including cardiovascular or cerebrovascular diseases, chronic kidney diseases, non-AIDS defining malignancies and death. Multivariate Cox regression was used to evaluate demographic, disease and treatment characteristics associated with CD4/CD8 ratio normalization and NAEs.ResultsA total of 800 ART-naïve patients with baseline CD4/CD8 ratio of < 0.8 who started combination ART, and had sustained virological suppression were enrolled. Participants were on ART for a median of 8.9 years and virologically suppressed for 6.1 years. The probabilities of CD4/CD8 normalization at 2, 5 and 10 years after virological suppression were 5.1%, 18.6% and 39.1%, respectively. Factors associated with normalization in multivariate analysis were female sex (hazard ratio [HR]: 2.47, 95% CI 1.71–3.56, p < 0.001) and baseline CD4 counts ≥ 350 cells/mm3 (HR: 3.62, 95% CI 2.36–5.55), p < 0.001) vs. < 200 cells/mm3 as reference. The second analysis explored the predictive value of CD4/CD8 ratio for NAEs. Older age (HR: 1.09, 95% CI 1.05–1.13, p < 0.01) and current CD4/CD8 ratio < 0.3 (HR: 3.02, 95% CI 1.27–7.21, p = 0.01) or between 0.3 and 0.45 (HR: 2.03, 95% CI 1.03–3.98, p = 0.04) vs. > 0.45 were independently associated with higher risk of progression to NAEs in the multivariate analysis.ConclusionsOur findings showed that complete immune recovery is uncommon in an Asian setting and earlier ART initiation at higher CD4 counts may have increased the ratio sooner. The findings demonstrate the use of CD4/CD8 ratio as a prognostic marker for clinical progression of NAEs.Trial registration HIV-NAT 006 cohort, clinical trial number: NCT00411983

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“…A study in Taiwan suggested PLHIV to be as much as sixfold more likely to develop diabetes than the rest of the population, 69 and a recent Thai study of PLHIV showed diabetes developed at a younger age compared with the general population. 70 Increased rates of diabetes have also been reported in PLHIV in South Africa, 71 Tanzania 72 and Ethiopia. 71 Older ART drugs such as stavudine and zidovudine are known to increase the risk of metabolic syndrome and diabetes, and are used less now, so future studies may not confirm this relationship.…”

Section: Diabetes and Specific Infectionsmentioning

confidence: 98%

The double burden of diabetes and global infection in low and middle-income countries

Dunachie

Chamnan

2018

Transactions of the Royal Society of Tropical Medicine and Hygiene

141

106

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Four out of five people in the world with diabetes now live in low- and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. Diabetes increases susceptibility to infection and worsens outcomes for some of the world’s major infectious diseases such as tuberculosis, melioidosis and dengue, but the relationship between diabetes and many neglected tropical diseases is yet to be accurately characterised. There is some evidence that chronic viral infections such as hepatitis B and HIV may predispose to the development of type 2 diabetes by chronic inflammatory and immunometabolic mechanisms. Helminth infections such as schistosomiasis may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes. A greater understanding of the impact of diabetes on risks and outcomes for infections causing significant diseases in LMIC is essential in order to develop vaccines and therapies for the growing number of people with diabetes at risk of infection, and to prioritise research agendas, public health interventions and policy. This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.

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New-onset diabetes in HIV-treated adults

Cited by 40 publications

References 31 publications

Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: a retrospective cohort study

Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: a retrospective cohort study

CD4/CD8 ratio normalization rates and low ratio as prognostic marker for non-AIDS defining events among long-term virologically suppressed people living with HIV

The double burden of diabetes and global infection in low and middle-income countries

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