Ryan Sun’s research while affiliated with University of Illinois Chicago and other places

We observed diabetes mellitus (DM) in 9.3% of adults with sickle cell disease (SCD) and DM predicted a 7-fold greater risk for chronic kidney disease progression adjusting for high-risk APOL1. Our results emphasize the clinical significance of DM in SCD.

Background: Approximately 10% of adults with sickle cell disease (SCD) have diabetes mellitus (DM) (PMID 30714090). Glycemic control is challenging to evaluate in the setting of hemoglobinopathies, such as SCD, due to potentially inaccurate hemoglobin A1c (HbA1c) measurements (PMID 30897962). Fructosamine has been proposed as a marker of glycemic control in patients with hemoglobinopathies, although its use remains unvalidated in clinical studies (PMID 27457632). The ideal glycemic monitoring strategy in patients with SCD is unclear. Therefore, the objective of this study was to evaluate the performance of fructosamine and HbA1c in predicting glycemic burden in adults with SCD. Methods: We analyzed 439 patients followed between Jan 2010 and Feb 2023 at the University of Illinois Sickle Cell Center. DM was defined by a diagnostic code in the electronic health record plus either prescription of an outpatient antidiabetic agent or an outpatient random serum glucose >200 mg/dL. Comparisons of clinical and laboratory variables by DM status were performed using the Wilcoxon rank sum, Pearson's chi-squared, and Fisher's exact test. Correlation analyses were conducted to evaluate the association of fructosamine and HbA1c with time-paired mean serum glucose concentrations, and of HbA1c with indirect bilirubin (I Bili), absolute reticulocyte counts (retic), and lactate dehydrogenase (LDH) concentration. Multivariate regression models for HbA1c used mean serum glucose concentration and either I Bili, retic, or LDH as covariates with an interaction term. Results: The median age of the cohort at the time of enrollment was 32 years (interquartile range [IQR] 25-43 years), 57% were female, 76% were hemoglobin SS, and 46% were on hydroxyurea. 41 (9.3%) patients had DM (Table). SCD patients with DM were older, more frequently on angiotensin converting enzyme inhibitors or angiotensin receptor blockers, had higher serum triglyceride concentrations, lower baseline eGFR, and higher baseline urine albumin-to-creatinine ratios compared to those without DM (p ≤ 0.004). In 39 patients with 157 observations, fructosamine concentration correlated poorly with 14-day time-paired mean glucose concentrations ( r s +0.02, p = 0.8; R2 0.01). In 19 patients with 176 observations, HbA1c significantly correlated with 30-day time-paired mean glucose concentrations ( r s +0.36, p < 0.001; R2 0.25). HbA1c progressively increased with higher glucose category (p < 0.001), while there was no association between fructosamine concentrations and glucose category (p = 0.5) (Figure). Increased hemolysis was associated with decreased HbA1c (I Bili r s -0.44, p < 0.001; retic r s -0.33, p = 0.002; LDH r s -0.18, p = 0.2). After adjustment for hemolytic markers with interaction effects, HbA1c continued to predict 30-day time-paired mean glucose concentration (I Bili β HbA1c +20.8, p < 0.001; retic β HbA1c +24.1, p < 0.001; LDH β HbA1c +26.0, p = 0.002). The addition of these hemolytic and interaction terms generally improved the fit of the model (Unadjusted R2 0.24 versus adjusted for I Bili R2 0.42, retic R2 0.22, or LDH R2 0.55). Conclusions: Our findings suggest that fructosamine concentration is a poor glycemic marker in adults with SCD. We observe that increased hemolytic markers are associated with decreased HbA1c, and the addition of a corrective hemolysis interaction term may improve the predictive ability of HbA1c for mean glucose concentration. Further studies are urgently needed to develop and validate glycemic monitoring strategies, such as continuous glucose monitoring, in this group of patients.

Sickle cell anemia (SCA) negatively impacts the ability to achieve educational and occupational goals increasing vulnerability to socioeconomic challenges. In a cross‐sectional analysis of 332 SCA adults, we investigated whether the distressed community index (DCI) was associated with SCA‐related complications and nutritional status. More patients with higher DCI had Medicaid insurance. A higher DCI was independently associated with tobacco use and lower body mass index, serum albumin, and vitamin D 25‐OH levels after adjusting for insurance status but was not associated with SCA‐related complications. Future studies investigating access to healthy foods may help improve health equity in patients with SCA.

Background Eligibility assessment of patients with sickle cell disease (SCD) for allogeneic hematopoietic stem cell transplant (HSCT) is a complex yet vital component of pre-transplant evaluation. Psychosocial assessment tools have been modeled after those completed in solid organ transplantation but no studies have validated these tools in this population and therefore a standardized assessment is lacking. Because adult SCD patients face the burdens of chronic disease and racial disparities, we hypothesized that psychosocial frailties would be prevalent in those undergoing HSCT. Methods Adult patients diagnosed with sickle cell disease who received HSCT between 2014 and 2021 and had a documented pre-HSCT social worker semi-structured qualitative interview addressing patient's living arrangement, family structure, education, employment, financial situation, social habits and understanding of the transplant were included. Our goal was to use these interviews to identify domains of psychosocial frailties and to eventually develop a tool in this SCD patient population that could be used pre-HSCT. Interviews. A codebook was developed by the research team consisting of clinical experts and a qualitative expert. This process was repeated to theme saturation, resulting in a RedCap scoring tool with 12 psychosocial frailty domains related to housing, transportation, interpersonal issues with family, marital status, dependency, unemployed work status, mental health diagnosis, dependence on government subsidies, and the presence of a reliable 24-hour caregiver. Two reviewers independently coded the data from notes into Redcap and discrepancies were addressed with the team. Results Of the 65 SCD patients who received HSCT, 40 patients met inclusion criteria. The median age at the time of transplant was 29 (18-55) years and 19 patients (47.5%) were male. 21 (52.5%) patients received a haploidentical HSCT, while 19 (47.5%) received a matched relator donor HSCT. Insurance was either private (n=20, 50%), Medicaid for (n=11, 27.5%), or Medicare/Medicaid (n=5, 12.5%). For marital status, 15 (37.5%) were married and 23 (57.5%) were not married. Most patients had either a high school (n=17, 42.5%) or college (n=13, 32.5%) degree. 40% of patients were unemployed at the time of transplant. We then examined the frequency of individual and total psychosocial frailties experienced within each patient and among the entire cohort. In 40 patients, a total of 150 psychosocial frailties existed. The most frequent psychosocial frailties were related to marital status (n=25), government subsidy dependency (n=18), housing dependency (n=18), financial dependency (n=17), unemployed work status (n=16), and any transportation vulnerability (n=17). The median number of psychosocial vulnerabilities experienced by each patient was 4 (range: 0-9), with 10 (25%) patients having more than 5 vulnerabilities. Specific vulnerabilities are listed in Table 2. After a median follow up of 36.7 (3-101.3) months, there were 3 deaths, with 0, 4, and 9 pre-HSCT psychosocial frailties experienced by each patient. 8 (53%) patients with a psychosocial frailty ≥ 5 were re-hospitalized within 100 days of HSCT. Conclusions Here we report for the first time an analysis of a qualitative dataset to understand and determine the prevalence of psychosocial frailties that adult sickle cell patients experience during allo-HSCT. We observed a very high number of frailties within the entire cohort including financial and housing dependency, not having a 24-hour caregiver after HSCT, and reliance on government subsidies for support. However, despite these psychosocial frailties, HSCT was successfully performed in these patients and based on this, should not be a barrier to receiving this life-saving procedure. Confirming these findings in a larger cohort in order to assess the impact on survival and specific transplant outcomes is warranted.