Background: With the prevalence of abnormal glucose tolerance (Abnl-GT) soaring in sub-Saharan Africa, there is a growing appreciation that the major etiology of Abnl-GT in Africans may be beta-cell failure rather than insulin resistance (IR). As optimal therapy depends on etiology, distinguishing between beta-cell failure and IR is critical. However, identifying IR with formulas such as the Matsuda Sensitivity Index which requires insulin to be assayed in plasma, is expensive and rarely available in medical clinics in most African countries. Therefore, our goal was to use data from the Matsuda Index as the diagnostic standard, and determine how well the widely available, low-cost Triglyceride-Glucose Index (TyG) performs in distinguishing between beta-cell failure and IR in Africans with Abnl-GT. Methods: OGTTs and fasting triglyceride (TG) levels were obtained in 589 African immigrants living in the Washington DC area (Male: 64%, Age: 39±11, (mean±SD) range 20 -69y; BMI 27.9±4.5 kg/m 2 range 19.5-41.9). Glucose tolerance status was determined by ADA criteria for the OGTT. IR was defined as the lowest quartile of the population distribution of the Matsuda Index (≤2.89). As a primary etiology, beta-cell failure was defined as Abnl-GT in the absence of IR. Insulin secretion was calculated using the insulinogenic index. The formula for TyG was: ln(fasting glucose & fasting TG)/2. IR by TyG was defined by the highest quartile of its distribution across the cohort(≥3.38). Results: Abnl-GT occurred in 39% (228/589) of the enrollees. Among participants with Abnl-GT, the prevalence of beta-cell failure and IR were: 59% (134/228) vs. 41% (94/228), P <0.001, respectively. Compared to Africans with Abnl-GT and IR, Africans with Abnl-GT and beta-cell failure had less IR & lower insulin secretion (both P<0.001). Overall, with data from the Matsuda Index as the diagnostic standard, TyG correctly identified the etiology of Abnl-GT in 90% (205/228) of the participants with Abnl-GT, specifically 93% (125/134) with beta-cell failure and 85% (80/94) of participants with IR. Conclusions: As the TyG correctly identified the etiology of Abnl-GT in 90% of Africans, it may be a feasible, economically viable alternative to the Matsuda Index in determining whether Africans with Abnl-GT have beta-cell failure or IR. With correct information about Abnl-GT etiology, therapy for can be optimized.

Since the mid-20th century, the Healthy Immigrant Effect (HIE) has been used to describe better cardiometabolic health in African immigrants than African Americans (AA). However, with heart disease and diabetes (DM) rapidly increasing in Africa, it is unknown whether African immigrants who entered the United States (US) in the 21st century have better cardiometabolic health than AA. Therefore, we undertook a pilot study of 17 African immigrants and 17 AA who were matched by sex, age, and BMI (Male: 35% (12/34), Age: 42±16, (mean±SD), range 20-67y, BMI: 30.2±5.8, range 20.2-41.9 kg/m2). Africans entered the US from 2000 to 2022 and were 18y or older at immigration. Biological Age was determined by the Phenotypic Age equation. The Framingham Risk Score (FRS) was used to estimate the 10y risk of a cardiac event. To detect DM, OGTT were performed. Biological Age tended to be lower in African immigrants than AA (38±16 vs 41±16y, P=0.06). Yet, there was no difference by group in FRS (4.4±5.5 vs 4.5±5.2, P=0.95) or DM prevalence (12% (2/17) vs 12% (2/17), P=0.99). African immigrants had a lower rate of health insurance coverage (59% (10/17) vs 88% (15/17), P=0.05) and a higher rate of low income (<45k)(47% (8/17) vs 29% (5/17), P=0.29) than AA. Yet, African immigrants had better diet, activity, sleep, smoking and alcohol habits than AA (Table). Overall, based on lower Biological Age, the HIE may be valid in the 21st century and explained by health behaviors. E.A. Huefner: None. C. Worthy: None. M. Sayed: None. J. Hurston: None. C. DuBose: None. L. Mabundo: None. M.F. Horlyck-Romanovsky: None. A.E. Sumner: None.

According to the International Diabetes Federation, the prevalence of type 2 diabetes (DM) in sub-Saharan Africa will increase by 134% in the next 25 years. Furthermore, recent data suggests that the most widely used diagnostic tests, fasting blood glucose (FPG) (≥126 mg/dL) and A1C (≥6.5%) underperform in Africans. Thus, rigorous testing by the OGTT for the detection of DM in Africans is critical. The OGTT allows for assessment of 2h glucose, a postprandial equivalent. Therefore, OGTT were performed in 601 African-born Blacks enrolled in the Africans in America cohort (male: 63% (377/601), age: 39±11, (mean±SD) range 20-69, BMI: 27.7±4.5, range (18.2-42.0)). DM diagnosis was based on ADA glucose criteria for the OGTT. To determine if confounding factors were present, tests were done to assess hemoglobin, hemoglobin type, nutritional status and renal and hepatic function. Assays for G6PD deficiency were performed in 228 consecutively enrolled participants. DM occurred in 7% (42/601) of participants. Sickle cell trait (SCT) or HbC Trait occurred in 17% (100/601) of participants overall and 33% (14/42) of individuals with DM. No participants (0/601) had anemia (Hgb<11 g/dL), nutritional deficiencies or renal or hepatic dysfunction. G6PD deficiency was identified in 10% (22/228) of participants overall, and no one with DM (0/18). Diagnostic sensitivity of FPG for the detection of DM was 16% (7/42). Sensitivity of A1C was 28% (12/42). Sensitivity of both tests combined was 33% (14/42). When the Africans with SCT or HbC trait were excluded, sensitivity of FPG was 21% (6/28) and A1C was 29% (8/28). For both tests combined, the sensitivity increased to only 36% (10/28). In short, FPG and A1C underperform in the detection of DM in Africans even in the absence of SCT, HbC trait and metabolic disorders and nutritional deficiencies. This data raises concern that the DM epidemic in Africa may be worse than predicted. Disclosure C. Worthy: None. M. Sayed: None. E.A. Huefner: None. J. Hurston: None. C. DuBose: None. A.E. Sumner: None.

With acculturation superimposed on nutritional transitions, urbanization and globalization, 21st century attitudes of African immigrants towards optimal body size are unknown. To gain perspective on body image, we assessed in 412 Africans living in America: 1) ideal body size 2) body size dissatisfaction and 3) cardiometabolic health by body size category. Participants chose 2 silhouettes from the Stunkard Figure Rating Scale, one for their wish body size and one for their perceived body size. The scale has 9 silhouettes corresponding to body size categories: Underweight: 1-2; Normal-Weight: 3-4; Overweight: 5-7; Obesity: 8-9. Body size dissatisfaction was calculated as the difference between perceived and wish body size. Cardiometabolic health was determined by BP, glucose and lipids. Enrollees lived in the Washington, DC area (BMI 27.9±4.6 (mean±SD), range 19.5-47.3 kg/m2, female: 42% (174/412); age 39±11y, range 20-69y). As their wish body size, no one (0/412) chose silhouettes in the obese category. In fact, the body size silhouettes most preferred were in the normal-weight category. Dissatisfaction because perceived body size was too large occurred in 63% (260/412). Whereas dissatisfaction because body size was too small occurred in 12% (49/412). However, body size dissatisfaction was higher in women than men (84% (146/174) vs. 69% (164/238), P<0.001). BMI of women who thought they were too large was 30.3±4.6 kg/m2. Their wish body size silhouettes were: 1 to 6. BMI of women who thought they were too small was 23.4±3.3 kg/m2. Their wish body size silhouettes were: 3 to 6. BMI of men who thought they were too large was 29.2±3.9 kg/m2 and they chose for their wish body size: 1 to 5. BMI of men who thought they were too small was 23.0±2.7 kg/m2. Their wish silhouettes were: 4 to 6. Cardiometabolic health was most optimal for women and men with normal-weight BMI. Overall, Africans living in America did not value obesity and preferred a healthier normal-weight body size. Disclosure J. Hurston: None. C. Worthy: None. E.A. Huefner: None. M. Sayed: None. C. DuBose: None. L. Mabundo: None. M.F. Horlyck-Romanovsky: None. A.E. Sumner: None.

Background: Both health and health behavior are highly influenced by cultural attitudes towards body size. However, the body size of preference and the degree to which body size dissatisfaction occurs in African-born Blacks living in the United States is unknown. Methods: To address this data gap, height and weight were measured, and BMI calculated in 412 African-born Blacks living in the Washington, DC area (female: 42% (174/412), age 39±11y (mean±SD), range 20-69y, range, BMI 27.9±4.6kg/m 2 , range 19.5-47.3kg/m 2 ). The Stunkard Figure Rating Scale was used to assess both body size preference and body size dissatisfaction. The Stunkard scale has 9 silhouettes which correspond to four BMI categories: Underweight: 1-2; Normal-Weight: 3-4; Overweight: 5-7; Obesity: 8-9. Participants chose the silhouettes which corresponded to their perceived BMI and to their ideal BMI. Body size dissatisfaction was calculated as the difference between perceived and ideal BMI. Results: Women had a higher BMI than men (29.1±5.0 vs. 27.0±4.2, P <0.001). As their ideal body size, 75% (131/174) of women and 60% (143/238) of men chose the two silhouettes in the normal weight BMI category, specifically 3 or 4. However, silhouette 4 was chosen more often than silhouette 3 (61% vs. 39%, P <0.001). In addition, and very importantly, as their body size of preference, no participant chose silhouettes in the obese BMI category. Overall, body size dissatisfaction occurred in 75% (309/412) of participants with women being more dissatisfied than men (84% (146/174) vs. 69% (164/238), P <0.001). Dissatisfaction due to feeling too large occurred in 63% (260/412); whereas dissatisfaction due to feeling too small occurred in 12% (49/412). Mean BMI in participants who were dissatisfied because they were too large was: 29.8±4.3 kg/m 2 . Whereas mean BMI in participants who were dissatisfied because they felt too small was: 23.1±2.8 kg/m 2 . Silhouettes of preference in 74% (36/49) of the participants who thought they were too small were 4 and 5. Conclusion: Neither high nor low BMI categories were valued by the participants. Overall, the majority of African-born Blacks living in the United States preferred a body size in the normal-weight BMI range.

Emerging data suggests that type 2 diabetes (DM) incidence is rapidly rising in Africa. Beta-cell failure rather than insulin resistance (IR) may be the precipitator. As causative data allows for optimization of therapy, screening strategies to determine when beta-cell failure is the primary cause of DM are essential. OGTT were performed in 589 African-born Blacks (Male: 64% (374/589), Age: 39±11y (mean±SD), BMI: 27.1±4.5 kg/m2). Insulin resistance (IR) was defined by the threshold at the lowest quartile of the population distribution for Matsuda Insulin Sensitivity Index (MISI) (≤2.89) and upper quartile for HOMA-IR, Lipid Accumulation Product (LAP) and TG-Glucose Index (TyG) (Table). With the MISI as the standard, the ability to predict IR by each index was assessed by AUC-ROC. Beta-cell failure was defined by the presence of DM in the absence of IR. K-statistic was used for beta-cell failure detection by each index relative to the MISI. DM was identified in 7% (40/589). In Africans with DM, beta-cell failure occurred in 45% (18/40); IR in 55% (22/40). AUC-ROC for IR prediction was highest for HOMA-IR (Table). By k-statistic criteria, the ability of HOMA-IR to detect beta-cell failure was excellent, but only fair for LAP and TyG. Overall, nearly half of Africans with DM have beta-cell failure as the primary cause, denoting the critical need for determining DM pathophysiology, and HOMA-IR may be the most clinically relevant test to detect etiology. Disclosure M. Sayed: None. P. Thyparambil Aravindakshan: None. C. Worthy: None. E.A. Huefner: None. J. Hurston: None. C. DuBose: None. R. Jagannathan: None. A.E. Sumner: None.

Since the mid-20th century, the Healthy Immigrant Effect (HIE) has been used to describe better cardiometabolic health in African immigrants than African Americans (AA). However, with heart disease and diabetes (DM) rapidly increasing in Africa, it is unknown whether African immigrants who entered the United States (US) in the 21st century have better cardiometabolic health than AA. Therefore, we undertook a pilot study of 17 African immigrants and 17 AA who were matched by sex, age, and BMI (Male: 35% (12/34), Age: 42±16, (mean±SD), range 20-67y, BMI: 30.2±5.8, range 20.2-41.9 kg/m2). Africans entered the US from 2000 to 2022 and were 18y or older at immigration. Biological Age was determined by the Phenotypic Age equation. The Framingham Risk Score (FRS) was used to estimate the 10y risk of a cardiac event. To detect DM, OGTT were performed. Biological Age tended to be lower in African immigrants than AA (38±16 vs 41±16y, P=0.06). Yet, there was no difference by group in FRS (4.4±5.5 vs 4.5±5.2, P=0.95) or DM prevalence (12% (2/17) vs 12% (2/17), P=0.99). African immigrants had a lower rate of health insurance coverage (59% (10/17) vs 88% (15/17), P=0.05) and a higher rate of low income (<45k)(47% (8/17) vs 29% (5/17), P=0.29) than AA. Yet, African immigrants had better diet, activity, sleep, smoking and alcohol habits than AA (Table). Overall, based on lower Biological Age, the HIE may be valid in the 21st century and explained by health behaviors. Disclosure E.A. Huefner: None. C. Worthy: None. M. Sayed: None. J. Hurston: None. C. DuBose: None. L. Mabundo: None. M.F. Horlyck-Romanovsky: None. A.E. Sumner: None.

Background: Thousands of people have already died as a result of the 2019 coronavirus disease pandemic (COVID-19), which was brought on by the SARS-CoV-2 coronavirus.There were many unimaginable cases of illness in Washington in 2020 as a first case, and then it was transmitted to Wuhan, Germany, France, Italy, Spain, the United Kingdom and China.The newly discovered SARS-CoV, MERS-CoV, and SARS-CoV-2 are believed to be natural and not laboratory synthetic.The COVID-19 pandemic may be due to the contamination of infected people and objects with infected materials that spread across the world.Main body: Human COVID-19 infection symptoms can range from being asymptomatic to being fatal, including respiratory failure, multiple organ dysfunction, and death.Large-scale genetic association studies have demonstrated that immune system components such as interferons, interleukins, toll-like receptors, and human leukocyte antigen as well as COVID-19 receptor variations (angiotensinconverting enzymes, transmembrane serine protease-2) are important host determinants of COVID-19 severity.Conclusion: The current review aims to demonstrate the human genetic factors that affect COVID-19 severity.