Influence of hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency on diagnosis of diabetes by HbA1c among Tanzanian adults with and without HIV: A cross-sectional study

Abstract

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.

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022

“…Another genetic variant, X-linked glucose-6-phosphate dehydrogenase G202A, carried by 11% of African Americans, was associated with a decrease in A1C of about 0.8% in homozygous men and 0.7% in homozygous women compared with those without the variant (34). For example, in Tanzania, where there is a high likelihood of hemoglobinopathies in people with HIV, A1C may be lower than expected based on glucose, limiting its usefulness for screening (35).…”

Association of sickle cell trait with β‐cell dysfunction and physical activity in adults living with and without HIV in Tanzania

“…CICADA study recruited 1947 participants from 2016 to 2017. We previously investigated the influence of SCT and other hemoglobinopathies on the levels of hemoglobin A1c (HbA1c) and plasma glucose during an oral glucose tolerance test (OGTT) among 431 participants who were randomly selected from CICADA study [1] and the role of objectively measured physical activity on diabetes among 391 participants, conveniently sampled from CICADA study, in another sub‐study [35]. The current study used data from all 431 participants from the SCT and other hemoglobinopathies sub‐study for SCT/SCD data and, in addition, 237 archived frozen blood samples of participants from the physical activity and diabetes sub‐study were assessed for SCT/SCD (Fig.…”

“…Sickle cell trait (SCT) is the heterozygous form of sickle cell disease (SCD) most prevalent in Sub‐Saharan Africa (SSA) where it affects about a quarter of the population [1–3]. SCD is one of the most common and severe inherited red blood cell disorder caused by a structural change of normal hemoglobin (HbA) to abnormal hemoglobin called sickle hemoglobin (HbS) accompanied with a number of complications, including severe anemia, renal impairment, stroke, and pain [4, 5].…”

Misleading HbA1c Measurement in Diabetic Patients with Hemoglobin Variants

“…Many factors, e.g., blood transfusion, hemoglobin variants, hemorrhage, iron deficiency, anemia, and red blood cell half-life, are considered to affect HbA1c measurements [ 4 , 5 , 6 ]. Recent studies revealed that hemoglobinopathies can affect HbA1c measurements; for example, the Hb1Ac level was underestimated in patients with Hb variant phonotypes [ 7 , 8 ].…”

“…HbE is frequently found in Bangladesh, Myanmar, East and Southeast Asia [ 9 ]. During the study of patients with diabetes, Hb variants were found in as high as one-third of all patients [ 8 ]. Thalassemia is the most common hemoglobinopathy in Thailand with varied frequencies among different areas, from 3–9% for β-thalassemia, 20–30% for α-thalassemia, and 10–60% for HbE phenotypes [ 10 , 11 , 12 , 13 ].…”