Glucose Metabolism, Insulin and Cardiovascular Function in HIV Positive Adults in Ethiopia

Research output: Book/ReportPh.D. thesisResearch

  • Hiwot Amare Hailemariam
Background: Malnutrition could increase the risk of gaining fat mass instead of fat-free mass during anti-retroviral therapy (ART) initiation among human immunodeficiency virus (HIV) patients. Nutritional supplementation has been incorporated in HIV treatment guidelines. We have previously shown that taking lipid-based nutrient supplements (LNS) for three months led to a weight gain, almost exclusively as fat-free mass. Malnutrition, the HIV virus and inflammation
are associated with hyperglycemia. However, the consequences of the intake of LNS with ART on glucose metabolism and blood pressure are not well studied. Traditional risk factors of atherosclerosis, opportunistic infections (OIs), and drugs including ART are also associated with cardiovascular diseases (CVDs) among HIV patients. In previously malnourished HIV+ individuals taking long-term ART, the prevalence of CVDs is not well studied.
Methods: In the first study, we assessed glucose metabolism and insulin function of ART naïve HIV+ as compared to HIV negative (HIV-) individuals. The outcomes were prediabetes and diabetes assessed by fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), and glycated hemoglobin (HbA1c). Homeostasis model assessment index of insulin resistance (HOMA-IR), MATSUDA index, Stumvoll early and late phase insulin secretion indices and 30-minute
insulinogenic index were also outcomes of the study. In the second study, a secondary analysis of a randomized controlled trial was done to evaluate the effect of supplementation on glucose metabolism and insulin function at three months of ART. And also, the effect of LNS/whey and LNS/soy on glucose and insulin were also studied. Changes in FPG, 30-minute plasma glucose (30mPG), 2hPG, HbA1c, fasting plasma insulin (p-insulin), homeostasis model assessment index
for β-cell function (HOMA-B), and HOMA-IR were the outcomes of this study. A one-year follow-up study of HIV patients was also done to assess changes in FPG, 30mPG, 2hPG, HbA1c, p-insulin, HOMA-IR, and blood pressure. In the final paper, the cardiovascular status of HIV patients on long term ART was done. HIV negative (HIV-) comparison group with sex and agematched in 1:1 ratio was recruited. The outcomes were the presence of carotid plaques, left ventricular ejection fraction (LVEF), mitral valve E/A ratio (MVEA), and nitro-terminal Probrain natriuretic peptide (NT-Pro-BNP). 
Results: At the time of ART initiation, the prevalence of diabetes based on oral glucose tolerance test was 7.6% whereas diabetes diagnosed with HbA1c was 8.5%. FPG (B 0.3, 95%CI 0.1; 0.5) and 2hPG (B 1.0, 95%CI 0.6; 1.3) were associated positively with α1-acid glycoprotein (AGP). The first phase insulin secretion decreased by 27% (eB 0.73, 95%CI 0.63; 0.85) whereas late phase insulin secretion decreased by 18% (eB 0.82, 95%CI 0.75; 0.91) with 1g/l increase in AGP. After three-month of ART, LNS supplemented group had higher HbA1c (2mmol/mol) as compared to the non-supplemented group. LNS/whey led to a higher HbA1c as compared to LNS/soy. Higher 30mPG and 2hPG were found in the supplemented group. More than 50% increases in p-insulin, HOMA-B, and HOMA-IR was seen in the supplemented group as compared to non-supplemented group. After 12 months of follow up, FPG, 30mPG, 2hPG decreased as compared to baseline value at the time of ART initiation. Whereas, p-insulin (10B 3.1; 95%CI 2.4, 4.0) and HOMA-IR (10B 3.1; 95%CI 2.3, 4.0) and blood pressure (B 4.0; 95%CI 2.5, 5.5) increased during the first 12-month of ART. A higher increase in p-insulin, HOMA-IR, and blood pressure was predicted by fat-free mass index at the time of ART initiation predicted. Moreover, HbA1c increment was predicted by fat mass index at baseline. After nine to ten years of ART, the mean CD4 count was 535 (±221) cells/μl. Most HIV+ (96.9%) were World Health Organization-stage I patients. MVEA (P< 0.001) and LVEF (P<0.001) were lower among HIV+ as compared to HIV-. There was no significant difference in NT-Pro-BNP between HIV+ and HIV-. HIV increased the odds of having carotid plaques by 5.3 (95%CI3.2; 8.7) times as compared to HIV-. HIV increased the odds of left ventricular systolic dysfunction by 2.9 (95%CI1.6; 5.1) times as compared to HIV-. The odds of diastolic dysfunction were 2.6 (95%CI 1.6; 4.3) times higher among HIV+ as compared to HIV-. 
Conclusions: Prediabetes and diabetes were frequent among ART naïve HIV patients. Diabetes was associated with insulin deficiency and inflammation but not waist circumference and age. Among HIV patients, short-term intake of LNS since the time of ART initiation led to insulin resistance, increased p-insulin and p-glucose levels, and tended to increase HbA1c. During the first year of ART, all glucose parameters declined but p-insulin and blood pressure rose. With long-term ART intake, HIV patients show early signs of CVDs signified by higher odds of carotid atherosclerosis, LV systolic, and diastolic dysfunction as compared to HIV-. Whether longer exposure to LNS leads to increased risk of dysglycemia need further study. Moreover, increased insulin during the first year of ART could be due to the recovery of β-cells or a sign of insulin resistance and needs further elucidation. Early ART initiation despite consideration of CD4 count or viral load (test and treat strategy) and cardiovascular screening could lead to reduced CVDs.
Original languageEnglish
Place of PublicationCopenhagen
PublisherDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
Number of pages142
ISBN (Print)9788772093994
Publication statusPublished - 2021

ID: 256509917