Introduction Hemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders. Methods Blood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT). Results The mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26, P < 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+ AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM. Conclusions HbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency.

Background Although the burden of impaired renal function is rising in sub-Saharan Africa (SSA), little is known about correlates of impaired renal function in the region. We determined factors associated with estimated glomerular filtration rate (eGFR) and impaired renal function in HIV-infected and HIV-uninfected adults. Methods We undertook cross-sectional analysis of data from 1947 adults at enrolment for a cohort study on diabetes and associated complications in HIV patients in Mwanza, north-western Tanzania. A structured questionnaire was used to collect data on sociodemography, smoking, alcohol, physical activity, antiretroviral therapy (ART) and anthropometry. We measured blood pressure, tested blood samples for creatinine, glucose and HIV, and performed Kato Katz for Schistosoma mansoni. Correlates of eGFR (mL/min/1.73 m2) and impaired renal function (eGFR< 60 mL/min/1.73 m2) were determined using linear regression and logistic regression, respectively. Results 655 (34%) participants were HIV-uninfected, 956 (49%) were ART-naive HIV-infected and 336 (17%) were HIV-infected adults on ART. The mean age was 41 years (SD12) and majority (59%) were females. Overall, the mean eGFR was 113.6 mL/min/1.73 m2 but 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naive HIV-infected and 129.5 mL/min/1.73 m2 in HIV-infected ART-experienced adults, and respective prevalence of impaired renal function was 7.0, 5.7, 8.1 and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol drinking, higher body mass index and diabetes mellitus. Anaemia was associated with 1.9 (95% Confidence Interval (CI):1.2, 2.7, p = 0.001) higher odds of impaired renal function compared to no anaemia and this effect was modified by HIV status (p value 0.02 for interaction). Conclusion Impaired renal function is prevalent in this middle-aged study population. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults and those with high socioeconomic status. Interventions targeting modifiable risk factors such as alcohol and weight reduction are warranted.

This study aimed to investigate sickle cell trait (SCT) associations with physical activity, markers of insulin secretion and resistance, and glucose among people living with HIV infection (PLWH), both antiretroviral therapy (ART) naive and experienced, and HIV‐uninfected adults. This was a cross‐sectional study conducted in Mwanza, Northwestern Tanzania. We used data of 668 participants attained from two sub‐studies of CICADA study. Mean age was 40 (SD 11.5) years, 402 (61.7%) were females and 157 (24.1%) had SCT. PLWH were 422 (64.7%), of these, 80 (18.9%) were on ART. People with SCT had higher risk of having an isolated β‐cell dysfunction compared to those without SCT (RRR = 1.82, CI: 1.10, 3.01, p = 0.02). People with SCT but without HIV infection had lower average acceleration on the trunk longitudinal axis (ACCx) and higher level of self‐reported physical activity. 30 min oral glucose tolerance test among PLWH on ART was higher in those with SCT compared to those without SCT. People with SCT are at higher risk of having β‐cell dysfunction and those with SCT on ART are at more risk of developing diabetes. Future studies to investigate the interaction between SCT and HIV/ART on risk of diabetes should be considered.

BACKGROUND: Hemoglobin A1c (HbA1c) measures the average of the past three month's glucose concentration and is recommended for diagnosing and monitoring diabetes. However in people with shorter red blood cells life spans like those with sickle cell trait (SCT), the test may underestimate the prevalence of diabetes. There are no data on the extent of this problem in East African region where the prevalence of SCT approaches 22%. OBJECTIVE: To compare diabetes diagnosis outcomes among adults with and without SCT by HbA1c and 2hrs oral glucose tolerance test (OGTT). METHODOLOGY: This was a cross sectional study conducted among patients who were previously recruited in the Chronic Infection, Cormobidities and Diabetes in Africa (CICADA) study, a cohort study investigating risk factors for diabetes in North western Tanzania during 2016 to 2021. Participants were included in this study if aged ≥18 years and were residents of Mwanza. After identification of eligible participants, stored blood samples were analyzed for SCT and other hemoglobinopathies i.e. thalassemia and G6PD deficiency through gene extraction, PCR and gel electrophoresis. Demographic, and anthropometric data as well as HbA1c and OGTT, hemoglobin, and lipids test results were available as part of CICADA study. Data were managed and analysed in stata. Student ttest was used for comparison of continuous variables while for categorical variables chi squire test was used. To investigate the validity of HbA1c, regression models were used to evaluate the association between SCT and diabetes diagnosis by HbA1c and OGTT separately. P< 0.05 indicated significant differences. RESULTS: 480 participants were included. Their mean age was 40.8 (±11.8) years, 292 (60.8%) were females, 128 (26.7%) had SCT and no sickle cell disease(SCD) which is homozygous trait observed. Those with SCT had lower body mass index (BMI) ((21.6(±4.3) vs. 22.5 (±5.0), P= 0.01) and lower HbA1c (5.2% vs. 5.9%, P<0.0001) compared to those without SCT. In multivariable logistic regression analysis adjusted for sex, age, BMI, another hemoglobinopathy which is thalassemia , G6PD deficiency , hemoglobin and lipids , participants with SCT were 88% less likely to be diagnosed with diabetes by HbA1c compared to those without SCT (OR=0.12, 95% CI (0.1,0.2), P <0.001). In contrast to logistic regression model adjusted for the same variables as above, SCT was not associated with diabetes diagnosis by OGTT (1.44, 95% CI (0.9, 2.3), P= 0.12). CONCLUSION: When compared with OGTT the findings shows that HbA1c systematically underestimate the prevalence of diabetes among people with SCT. The use of HbA1c for diabetes diagnosis should be done with caution especially in areas with high prevalence of SCT like in North Western Tanzania. Further research is needed to optimize the use of HbA1c in diagnosing and monitoring diabetes among people with SCT. Disclosures No relevant conflicts of interest to declare.

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function. Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes. Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.