Incretins (Glucagon like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) regulate glucose homeostasis in HIV-uninfected individuals. Inflammation has been implicated as a cause for insulin resistance (IR) among PLWH. Little is known about IR among Asian Indian PLWH, even though India has the highest burden of diabetes and third highest number of PLWH globally. We aimed to assess the relationship between different hormonal and inflammatory markers with IR in Indian PLWH.
Cross-sectional, conveniently sampled non-diabetic HIV-infected adults (≥18 years) who received HAART≥1 year at a large public sector ART clinic in Pune, India were included. Participants whose Quantitative Insulin Sensitivity Check Index (QUICKI) <0.339 were classified as insulin resistant. Logistic regression was used to identify associations between fasting GIP, GLP-1, leptin, ghrelin, C-peptide, PAI-1 (plasminogen activator inhibitor-1), resistin, visfatin, IL-6, IL-10, TNF-α, MCP-1 and IR.
Of 350 adults included, 115 (33%) were insulin resistant. Median age was 40 years (IQR:35-45), 157 (45%) were male, median time updated CD4 was 471 cells/µL (IQR:298 – 655), 221 (63%) had undetectable viral loads, 73 (21%) were receiving PI based regimens, median fasting insulin was 42 pmol/L (IQR:26-65). When compared to insulin sensitive individuals, those with IR had higher BMI (p<0.001), longer duration of ART use (p=0.008), a higher proportion were hypertensive (p=0.02) and dyslipidemic (p<0.001), had higher GIP (p<0.001), GLP-1 (p<0.001), C-peptide (p<0.001). In multivariable models adjusted for age, sex, BMI, CD4 count, viral load, HAART duration, dyslipidemia, PI use; C-peptide (Odds Ratio (OR), 95% Confidence Interval (95% CI):11.4, 4.9 – 26.3, p<0.001) and GLP-1 (OR, 95% CI: 1.004 , 1.002 – 1.006, p<0.001) were associated with IR. We found no association between GIP, IL-6, IL-10, TNF-α, MCP-1 and IR.
GLP-1 but not GIP was associated with IR. Furthermore, we found a strong association between C-peptide and IR. We found no association between inflammatory markers and IR in our population of non-diabetic PLWH. Elucidation of the pathways regulating IR in PLWH require further investigation.