Is there a discrepancy between plasma and interstitial fluid glucose and HbA1c in people living with HIV?

Abstract

Background: Diabetes is reported to be more common in people living with HIV(PLWH). HIV clinical guidelines recommend screening for diabetes in adults on antiretroviral therapy (ART), but there is no agreed screening method for diabetes. Studies report that HbA1c is falsely low in PLWH, but the study participants were taking older preparations of ART that are rarely used today. Continuous glucose monitors (CGM) report interstitial glucose and can explore HbA1c-glucose discrepancy but have not been used in PLWH. Data from Southern Africa on diabetes and HIV, where the prevalence of HIV is highest, are scarce.

Aims: To investigate the presence of, and reasons for, a discrepancy between HbA1c and glycaemia, including interstitial glucose, measured using CGM, glucose and Fructosamine, in people living with and without HIV.

Methods: PLWH and age-and sex-matched HIV-negative participants were purposely recruited from clinics in Lusaka, Zambia and Brighton, UK. Each participant wore a Dexcom G6 CGM for up to 10 days and had paired HbA1c measured. Bland-Altman plot was used to assess the agreement between HbA1c and a CGM-derived measure: Glucose Management Indicator(GMI). Regression analysis was performed on data from the Brighton study to assess the influence of HIV on HbA1c including additional predictor variables used in previous studies exploring hbA1c discrepancy.

Results In Brighton: 60 PLWH (90% male, 50% with T2DM, mean age[±SD] 57[±10.7] years, 100% undetectable viral load (VL)) and 48 people without HIV (92% male, 30% with T2DM, mean age 57.7[±8.9] years) were recruited. In Lusaka: 21 PLWH (33% male, mean age 39 [±9] years, 81% undetectable VL) and 30 people without HIV (30% male, mean age 40 [±10] years). The Bland-Altman plots: Brighton - difference HbA1c-GMI in PLWH -3mmol/mol (95% Limits of Agreement (LoA) -19.1-+13.9), in participants without HIV -2.1mmol/mol (95%LoA -15.1-+10.9); Lusaka – difference HbA1c-GMI in PLWH -5.9mmol/mol (95%LoA -16.4-+4.6), in participants without HIV -5.5mmol/mol (95%LoA -13.4-+2.3). Regression analysis using the Brighton data found that HIV serostatus did not have a significant influence on the relationship between markers of glycaemia and HbA1c.

Conclusion: In two cohorts from Brighton and Lusaka, the mean difference between HbA1c and GMI were similar in PLWH and HIV-negative controls. The 95% LoA were wide and the ranges contain 0. Regression analysis using Brighton data found HIV serostatus did not influence HbA1c. These studies support that HbA1c should be included for screening for diabetes within HIV clinical guidelines.

Date of Award	Feb 2023
Original language	English
Awarding Institution	University of Brighton
Supervisor	Juliet Wright (Supervisor), Tom J. Levett (Supervisor), Ali Chakera (Supervisor) & Professor Nick Oliver (Supervisor)