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Published on: January 7, 2018
Insulin resistance and intestinal integrity in children with and without HIV infection in Uganda
S Dirajlal-Fargo1,2,3, L Shan3, A Sattar3
1University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Insights
Children with perinatally acquired HIV infection (PHIVs) on antiretroviral therapy show higher insulin resistance. This metabolic disturbance is linked to higher body mass index (BMI), not immune activation or gut integrity issues.
Area of Science:
- Pediatric Infectious Diseases
- Metabolic Health
- HIV Research
Background:
- Cardiometabolic complications are a concern in children with perinatally acquired HIV infection (PHIVs) and perinatally HIV-exposed but uninfected (HEU) children.
- The relationship between these complications, systemic inflammation, and gut integrity markers in these populations is not well understood.
Purpose of the Study:
- To assess insulin resistance in PHIVs compared to HEUs and HIV-unexposed, uninfected children (HUUs).
- To explore the association between insulin resistance and biomarkers of intestinal damage and translocation in these groups.
Main Methods:
- A cross-sectional study involving 172 children (aged 2-10 years) in Uganda: PHIVs (on stable ART with viral load <400 copies/mL), HEUs, and HUUs.
- Insulin resistance was measured using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).
- Systemic inflammation, monocyte activation, and gut integrity markers were quantified. Statistical analyses included Kruskal-Wallis tests, Pearson correlation, and multiple linear regressions.
Main Results:
- PHIVs exhibited higher waist:hip ratio, HDL cholesterol, triglycerides, and HOMA-IR index compared to HEUs and HUUs (P ≤ 0.02).
- Insulin resistance correlated with higher BMI and HDL cholesterol, and lower soluble tumor necrosis factor receptor I (sTNFR1) (P ≤ 0.02).
- No correlation was found between HOMA-IR index and other inflammatory or gut biomarkers (P ≥ 0.05). BMI remained independently associated with HOMA-IR after adjusting for age and sTNFR1 (β = 0.16; P < 0.01).
Conclusions:
- Despite viral suppression, Ugandan children with PHIVs demonstrate glucose metabolism disturbances.
- Higher BMI, rather than immune activation or altered gut integrity, was associated with insulin resistance in this pediatric HIV-infected population.
Objectives:
The risk of cardiometabolic complications in children with perinatally acquired HIV infection (PHIVs) and in perinatally HIV-exposed but uninfected children (HEUs) and its relationship to systemic inflammation and markers of gut integrity are not well established. In this current study, we assed insulin resitance in PHIV compared to HEUs and HIV unexposed uninfected children and explored potential association with intestinal damage biomarkers.
Methods:
This was a cross-sectional study in PHIVs, HEUs and HIV-unexposed, uninfected children (HUUs) aged 2-10 years enrolled in Uganda. PHIVs were on stable antiretroviral therapy (ART) with HIV viral load < 400 HIV-1 RNA copies/mL. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). We measured markers of systemic inflammation, monocyte activation and gut integrity. Kruskal-Wallis tests were used to compare markers by HIV status; Pearson correlation and multiple linear regressions were used to assess associations of the HOMA-IR index with biomarkers of intestinal damage and translocation.
Results:
Overall, 172 participants were enrolled in the study (57 PHIVs, 59 HEUs and 56 HUUs). The median age was 7.8 [interquartile range (IQR) 6.39, 8.84] years, 55% were female and the median body mass index (BMI) was 15 (IQR 14.3, 15.8) kg/m2 . Among PHIVs, the median CD4% was 37%, and 93% had viral load ≤ 20 copies/mL. PHIVs had higher waist:hip ratio, high-density lipoprotein (HDL) cholesterol, triglycerides and HOMA-IR index than the other groups (P ≤ 0.02). Factors correlated with insulin resistance included higher BMI and HDL cholesterol and lower soluble tumour necrosis factor receptor I (sTNFRI) (P ≤ 0.02). There was no correlation between any of the other inflammatory or gut biomarkers and HOMA-IR index (P ≥ 0.05). After adjusting for age and sTNFRI, BMI remained independently associated with the HOMA-IR index (β = 0.16; P < 0.01).
Conclusions:
Despite viral suppression, Ugandan PHIVs have disturbances in glucose metabolism. Higher BMI, and not immune activation or alteration of gut integrity, was associated with insulin resistance in this population.
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