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Project Topic
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Emerging data suggest that HIV-infected people have disproportionately higher risk of diabetes than HIV-uninfected people. Multiple factors may contribute to elevated diabetes risk including increased prevalence of conventional non-communicable diseases (NCDs) risk factors, use of some antiretroviral drugs regimens, and inflammation and immune activation secondary to environmental- and HIV-enteropathy. To date, enteropathy has been little studied in relation to HIV and diabetes in Sub-Saharan Africa. Enteropathy leads to systemic inflammation which may in turn result in insulin resistance and it may reduce secretion of incretins, the gut hormones which stimulate synthesis and secretion of insulin. Both mechanisms could potentially result in higher diabetes risk in HIV patients. Further research is required, for example, evaluation of romising products like immunosuppressants,glucagon-like peptide (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, in order to improve the treatment of diabetes in HIV patients. This study will investigate if enteropathy is associated with higher risk of diabetes in HIV patients using a cross-sectional study design. To implement it cost-efficiently, we will nest it to CICADA study; a Danida-funded cohort study investigating risk factors for diabetes (excluding enteropathy) among HIV-infected patients in Mwanza. CICADA has recruited 1945 patients during 2016/2017, and will follow up these patients during 2017/2018 and 2018/2019 by which point we expect about 1550 participants retained in the cohort. Data collection for the current study will coincide with the final CICADA follow-up. Data on demography, socioeconomic status, conventional NCDs risk factors, HIV and TB status, antiretroviral use history, anthropometry, body composition, lipid profile, CD4 count, C-reactive protein, alpha1-acid glycoprotein, insulin, and diabetes status will be retrieved from the CICADA database for the current study. Data on gut enteropathy biomarkers i.e plasma citrulline, GLP-1,glucagon like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), fecalmyeloperoxidase (MPO), neopterin, and alpha-1-antitrypsin, intestinal permeability (by 4-sugar test), lipopolysaccharide binding protein, tumour necrosis factor-a receptor, interleukin 6, and fecal elastase (as an indicator of pancreatic function) will be collected for the proposed study. Data will be entered in Cspro and managed and analysed in STATA. Both linear and logistic regression will be used to assess the associations between exposure variables (markers of enteropathy) and diabetes. In addition, causal inference techniques will be used to investigate associations between enteropathy biomarkers and diabetes. The project will support capacity building in health research for the applicant and 1 MSc and 1 PhD students.
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