Serum Fructosamine is a Valid Measure of Glycemic Status in the Presence of the Sickle Cell Mutation

Background: The glycosylated hemoglobin (HbA1c) test can be unreliable in the presence of hemoglobinopathies and remains cost-prohibited and impractical in many developing countries. The increasing burden of type 2 diabetes (T2D) in sub-Saharan Africa (SSA) where sickle cell anemia, the most common inherited hemoglobinopathy, is prevalent calls for alternative tests for the management of T2D. In the present study, we evaluated the utility of serum fructosamine (FRA) as a biomarker of glycemic control that is not affected by abnormal hemoglobin or red blood cell (RBC) turnover. Methods: The accuracy of FRA in monitoring and diagnosing T2D was evaluated using the Area under the Receiver Operating Characteristics (AUROC) and other measures in a training dataset of 618 Nigerians [155 (25·1%) carrying sickle cell trait (HbAS) and 463 (74·9%) without sickle cell trait (HbAA)]. The FRA’s diagnostic cut-off was validated in an independent cohort of 634 West Africans. Findings: FRA was similar between HbAS and HbAA participants (Median = 287 vs 275 umol/L, p=0·11) despite statistically different HbA1c median among the two groups. FRA was highly correlated with both HbA1c (r HbAA = 0·80, r HbAS =0·82, p<0·001) and fasting glucose (FG) (r HbAA =0·72, r HbAS = 0·83, p<0·001) independent of sickle cell trait (SCT). With optimal thresholds of 352·5 umol/L and 309·5 umol/L, FRA had 81·5% [CI 95%:0·76-0·87] and 82·4%, [CI 95% 0·77-0·88] sensitivities and 97·4% [CI 95%:0·95-1·00] and 92·4% [95% CI 0·90-0·95] specificities for identifying individuals with controlled glycemic index and individuals with T2D respectively and independently of SCT. The diagnosis cut-off was validated in a multi-ethnic population with a good positive predictive value (94·6%). Interpretation: We showed that FRA is an effective alternative to HbA1c for monitoring and diagnosing T2D in populations where SCT is prevalent. Funding: National Institutes of Health. Conflict of Interest: The authors have no conflict of interest to disclose. Ethical Approval: The study protocol was approved by the institutional ethicsreview board (IRB) of the National Institutes of Health/National Human Genome Research Institute (protocol HG-09-N070) and the IRBs of each participating institution, including University of Lagos, Lagos, Nigeria; College of Medicine, University of Ibadan, Ibadan, Nigeria; University of Nigeria Teaching Hospital, Enugu, Nigeria; University of Science and Technology, Kumasi, Ghana; University of Ghana Medical School, Accra, Ghana. Written informed consent was obtained from each participant prior to enrollment.