Type 2 diabetes mellitus burdens among adults with sickle cell disease: A 12‐year single health system‐based cohort analysis

1 School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China 2 Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois, USA 3 Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA 4 Flatiron Health, New York, New York, USA 5 Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA 6 Division of Hematology &Oncology, Department ofMedicine, Comprehensive Sickle Cell Center, University of Illinois at Chicago, Chicago, Illinois, USA 7 Section of Academic InternalMedicine &Geriatrics, Department ofMedicine, University of Illinois at Chicago, Chicago, Illinois, USA


To the Editor:
Recent observational studies have demonstrated similar type 2 diabetes mellitus (T2DM) prevalence in commercially insured sickle cell disease (SCD) patients compared with the general population. [1,2] However, several important questions about T2DM in SCD remain unanswered. Past studies are limited due to lack of definitive genotype information [3][4][5]; it is possible that different SCD genotypes (sickle cell anemia (HbSS), sickle hemoglobin C disease (HbSC), sickle β +thalassemia (HbSβ + ), and sickle β 0 -thalassemia (HbSβ 0 )) demonstrate varying risks of T2DM and its associated complications. Additionally, important information on anthropometrics were lacking in most epidemiology studies. It is unclear whether low lean body weight and fat mass in anthropomorphic studies associated with SCD conferred protection against T2DM [6,7].
In this single health-system based, retrospective cohort study, we extracted 12 years (2008-2019) of electronic health records (EHR) data from a large, urban, tertiary health care system. Patients who self-identified as African American (AA) were included in the analysis.

SCD genotypes were ascertained through a combination of chart
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  (Table 1 and Table S1). It is worth noting that we identified higher rates of T2DM-related complications compared to our previous study using nationally representative sample of commercially insured SCD patients. Given that SCD alone can cause end organ damage, additional diabetic complications could accelerate functional decline of the kidney, lung, and central nervous system [9]. Mechanistic studies demonstrated that endothelial injury could have contributed to the development of acute myocardial infarction and unstable angina [10]. Our findings were based on records from a tertiary health system; therefore, it may represent a sicker group of patients who required medical attention in the first place. AA males have lower likelihood visiting healthcare facilities due to complex reasons, and in our identified patient population [11], underrepresentation could undermine the accuracy in estimating the overall T2DM burden. During the COVID-19 pandemic, individuals with SCD are experiencing even more diagnostic, treatment, and logistical challenges in meeting the healthcare needs.
A fundamental strength of this study is the identification of the cohort through a combination of inpatient, outpatient, laboratory, and pharmacy records from a 12-year span. Furthermore, we conducted medical chart review and cross-validation for key patient features such as SCD genotypes and BMI. While such an approach allowed an effective comparison of SCD with thousands of general patients sharing similar characteristics and followed at the same institution, these records are often incomplete and may be subject to suboptimal coding quality.
Overall, these results are consistent with our previous findings using a national claims database, the elevated risks for both T2DM-related microvascular and macrovascular complications warrant further investigation.

CONFLICT OF INTEREST
Dr. Calip reports current employment with Flatiron Health, Inc., which is an independent subsidiary of the Roche group. No other authors have disclosures to report.

AUTHOR CONTRIBUTIONS
J.Z., G.S.C., J.H., and W.L.G. designed and performed the research study.
J.Z. analyzed the data. All authors contributed to the drafting, revision, and final approval of the manuscript.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.