Estimating insulin sensitivity and ß-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model.

Efficient and accurate methods to estimate insulin sensitivity (SI) and ß-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.NEW & NOTEWORTHY The pathogenesis of type 2 diabetes (T2D) is determined by a balance between insulin sensitivity (SI) and ß-cell function (BCF), which can be determined by gold standard direct measurements or estimated by fitting differential equation models to oral glucose tolerance tests (OGTTs). We propose and validate a new differential equation model that is simpler to use than current models and requires less data while maintaining good correlation and agreement with gold standards. Matlab and Python code is freely available.

Fructosamine is Not a Reliable Test for the Detection of Hyperglycemia: Insight from the Africans in America Study.

Objective: To improve detection of abnormal glucose tolerance (Abnl-GT), attention has moved beyond the oral glucose tolerance test (OGTT), to non-fasting markers of glycemia, specifically, HbA1c, fructosamine (FA) and glycated albumin (GA). Emerging data suggest that in African descent populations, the combination of HbA1c and GA is superior to the combination of HbA1c and FA. However, the diagnosis of Abnl-GT is usually based on tests which are performed only once. As reproducibility of Abnl-GT diagnosis by HbA1c, fructosamine (FA) and glycated albumin (GA) is unknown, reproducibility of Abnl-GT diagnosis by HbA1c, FA and GA were assessed in 209 African-born Blacks living in America. Methods: At Visits 1 and 2 (9 ± 4 days apart), samples were obtained for HbA1c, FA and GA levels. Glucose tolerance status was determined at Visit 1 by OGTT. Reproducibility was based on the К-statistic and paired t-tests. Thresholds for the diagnosis of Abnl-GT by FA and GA which corresponded to an HbA1c of 5.7% were 235umol/L and 14.6%, respectively. Results: Abnl-GT occurred in 38% (80/209). Diagnostic reproducibility was excellent for HbA1c (К≥0.86) and GA (К≥0.89), but only moderate for FA (К=0.59). Neither HbA1c nor GA levels varied between visits (both P≥0.3). In contrast, FA was significantly lower at Visit 2 than Visit 1(P<0.01). Conclusion: As HbA1c and GA provided similar diagnostic results on different days and FA did not, HbA1C and GA are superior to FA in both clinical care settings and epidemiologic studies.

Estimating Insulin Sensitivity and Beta-Cell Function from the Oral Glucose Tolerance Test: Validation of a new Insulin Sensitivity and Secretion (ISS) Model.

Efficient and accurate methods to estimate insulin sensitivity (SI) and beta-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes. Many methods exist, ranging in input data and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic models (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new ISS (Insulin Secretion and Sensitivity) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. The model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. The model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including post-challenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts including individuals at high risk of prediabetes (adult women with a wide range of BMI and adolescents with obesity). The new model had strong correlation with gold-standard estimates from intravenous glucose tolerance tests and hyperinsulinemic-euglycemic clamp. The ISS model has broad clinical applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.

A Scoping Review of Trials Designed to Achieve Remission of Type 2 Diabetes with Lifestyle Intervention Alone: Implications for Sub-Saharan Africa.

According to the International Diabetes Federation, sub-Saharan Africa is experiencing the highest anticipate increase in the prevalence of type 2 diabetes (T2D) in the world and has the highest percent of people living with T2D who are undiagnosed. Therefore, diagnosis and treatment need prioritization. However, pharmacological hypoglycemics are often unavailable and bariatric surgery is not an option. Therefore, the ability to induce T2D remission through lifestyle intervention alone (LSI-alone) needs assessment. This scoping review evaluated trials designed to induce T2D remission by LSI-alone. PubMed, Embase, Cochrane, and CINAHL databases were searched for trials designed to induce T2D remission through LSI-alone. Of the 928 identified, 63 duplicates were removed. With abstract review, 727 irrelevant articles were excluded. After full-text review, 112 inappropriate articles were removed. The remaining 26 articles described 16 trials. These trials were published between 1984 and 2021 and were conducted in 10 countries, none of which were in Africa. Remission rates varied across trials. Predictors of remission were 10% weight loss and higher BMI, lower A1C and shorter T2D duration at enrollment. However, LSI-alone regimens for newly diagnosed and established T2D were very different. In newly diagnosed T2D, LSI-alone were relatively low-cost and focused on exercise and dietary counseling with or without calorie restriction (~1500 kcal/d). Presumably due to differences in cost, LSI-alone trials in newly diagnosed T2D had higher enrollments and longer duration. For established T2D trials, the focus was on arduous phased dietary interventions; phase 1: low-calorie meal replacement (<1000 kcal/day); phase 2: food re-introduction; phase 3: weight maintenance. In short, LSI-alone can induce remission in both newly diagnosed and established T2D. To demonstrate efficacy in Africa, initial trials could focus on newly diagnosed T2D. Insight gained could provide proof of concept and a foundation in Africa on which successful studies of LSI-alone in established T2D could be built.

Prevalence and influences of diabetes and prediabetes among adults living with HIV in Africa: a systematic review and meta-analysis.

INTRODUCTION: In people living with human immunodeficiency virus (PLHIV), traditional cardiovascular risk factors, exposure to HIV per se and antiretroviral therapy (ART) are assumed to contribute to cardiometabolic diseases. Nevertheless, controversy exists on the relationship of HIV and ART with diabetes. To clarify the relationship between HIV and type 2 diabetes, this review determined, in PLHIV in Africa, diabetes and prediabetes prevalence, and the extent to which their relationship was modified by socio-demographic characteristics, body mass index (BMI), diagnostic definitions used for diabetes and prediabetes, and HIV-related characteristics, including CD4 count, and use and duration of ART. METHODS: For this systematic review and meta-analysis (PROSPERO registration CRD42021231547), a comprehensive search of major databases (PubMed-MEDLINE, Scopus, Web of Science, Google Scholar and WHO Global Health Library) was conducted. Original research articles published between 2000 and 2021 in English and French were included, irrespective of study design, data collection techniques and diagnostic definitions used. Observational studies comprising at least 30 PLHIV and reporting on diabetes and/or prediabetes prevalence in Africa were included. Study-specific estimates were pooled using random effects models to generate the overall prevalence for each diagnostic definition. Data analyses used R statistical software and "meta" package. RESULTS: Of the 2614 records initially screened, 366 full-text articles were assessed for eligibility and 61 were selected. In the systematic review, all studies were cross-sectional by design and clinic-based, except for five population-based studies. Across studies included in the meta-analysis, the proportion of men was 16-84%. Mean/median age was 30-62 years. Among 86,412 and 7976 participants, diabetes and prediabetes prevalence rates were 5.1% (95% CI: 4.3-5.9) and 15.1% (9.7-21.5). Self-reported diabetes (3.5%) was lower than when combined with biochemical assessments (6.2%; 7.2%). DISCUSSION: While not statistically significant, diabetes and prediabetes were higher with greater BMI, in older participants, urban residents and more recent publications. Diabetes and prediabetes were not significantly different by HIV-related factors, including CD4 count and ART. CONCLUSIONS: Although HIV-related factors did not modify prevalence, the diabetes burden in African PLHIV was considerable with suboptimal detection, and likely influenced by traditional risk factors. Furthermore, high prediabetes prevalence foreshadows substantial increases in future diabetes in African PLHIV.

Non-invasive type 2 diabetes risk scores do not identify diabetes when the cause is ß-cell failure: The Africans in America study.

Background: Emerging data suggests that in sub-Saharan Africa ß-cell-failure in the absence of obesity is a frequent cause of type 2 diabetes (diabetes). Traditional diabetes risk scores assume that obesity-linked insulin resistance is the primary cause of diabetes. Hence, it is unknown whether diabetes risk scores detect undiagnosed diabetes when the cause is ß-cell-failure. Aims: In 528 African-born Blacks living in the United States [age 38 ± 10 (Mean ± SE); 64% male; BMI 28 ± 5 kg/m2] we determined the: (1) prevalence of previously undiagnosed diabetes, (2) prevalence of diabetes due to ß-cell-failure vs. insulin resistance; and (3) the ability of six diabetes risk scores [Cambridge, Finnish Diabetes Risk Score (FINDRISC), Kuwaiti, Omani, Rotterdam, and SUNSET] to detect previously undiagnosed diabetes due to either ß-cell-failure or insulin resistance. Methods: Diabetes was diagnosed by glucose criteria of the OGTT and/or HbA1c ≥ 6.5%. Insulin resistance was defined by the lowest quartile of the Matsuda index (≤ 2.04). Diabetes due to ß-cell-failure required diagnosis of diabetes in the absence of insulin resistance. Demographics, body mass index (BMI), waist circumference, visceral adipose tissue (VAT), family medical history, smoking status, blood pressure, antihypertensive medication, and blood lipid profiles were obtained. Area under the Receiver Operator Characteristics Curve (AROC) estimated sensitivity and specificity of each continuous score. AROC criteria were: Outstanding: >0.90; Excellent: 0.80-0.89; Acceptable: 0.70-0.79; Poor: 0.50-0.69; and No Discrimination: 0.50. Results: Prevalence of diabetes was 9% (46/528). Of the diabetes cases, ß-cell-failure occurred in 43% (20/46) and insulin resistance in 57% (26/46). The ß-cell-failure group had lower BMI (27 ± 4 vs. 31 ± 5 kg/m2 P < 0.001), lower waist circumference (91 ± 10 vs. 101 ± 10cm P < 0.001) and lower VAT (119 ± 65 vs. 183 ± 63 cm3, P < 0.001). Scores had indiscriminate or poor detection of diabetes due to ß-cell-failure (FINDRISC AROC = 0.49 to Cambridge AROC = 0.62). Scores showed poor to excellent detection of diabetes due to insulin resistance, (Cambridge AROC = 0.69, to Kuwaiti AROC = 0.81). Conclusions: At a prevalence of 43%, ß-cell-failure accounted for nearly half of the cases of diabetes. All six diabetes risk scores failed to detect previously undiagnosed diabetes due to ß-cell-failure while effectively identifying diabetes when the etiology was insulin resistance. Diabetes risk scores which correctly classify diabetes due to ß-cell-failure are urgently needed.

The Africans in America study demonstrates that subclinical cardiovascular risk differs by etiology of abnormal glucose tolerance.

Abnormal-glucose tolerance (Abnl-GT) is due to an imbalance between ß-cell function and insulin resistance (IR) and is a major risk factor in cardiovascular disease (CVD). In sub-Saharan Africa, ß-cell failure is emerging as an important cause of Abnl-GT (Abnl-GT-ß-cell-failure). Visceral adipose tissue (VAT) volume and hyperlipidemia are major contributors to CVD risk when Abnl-GT is due to IR (Abnl-GT-IR). Yet, the CVD profile associated with Abnl-GT-ß-cell failure is unknown. Therefore, our goals in 450 African-born Blacks (Male: 65%; Age: 39 ± 10 years; BMI 28 ± 5 kg/m2), living in America were to: (1) determine Abnl-GT prevalence and etiology; (2) assess by Abnl-GT etiology, associations between four understudied subclinical CVD risk factors in Africans: (a) subclinical myocardial damage (high-sensitivity troponin T (hs-cTnT)); (b) neurohormonal regulation (N-terminal pro-Brain-natriuretic peptide (NT-proBNP)); (c) coagulability (fibrinogen); (d) inflammation (high-sensitivity C-reactive protein (hsCRP)), as well as HbA1c, Cholesterol/HDL ratio and VAT. Glucose tolerance status was determined by the OGTT. IR was defined by the threshold at the lowest quartile for the Matsuda Index (≤ 2.97). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-ß-cell-failure was defined as Abnl-GT without IR. VAT was assessed by CT-scan. For both the Abnl-GT-ß-cell-failure and Abnl-GT-IR groups, four multiple regression models were performed for hs-cTnT; NT-proBNP; fibrinogen and hsCRP, as dependent variables, with the remaining three biomarkers and HbA1c, Cholesterol/HDL and VAT as independent variables. Abnl-GT occurred in 38% (170/450). In the Abnl-GT group, ß-cell failure occurred in 58% (98/170) and IR in 42% (72/170). VAT and Cholesterol/HDL were significantly lower in Abnl-GT-ß-cell-failure group vs the Abnl-GT-IR group (both P < 0.001). In the Abnl-GT-ß-cell-failure group: significant associations existed between hscTnT, fibrinogen, hs-CRP, and HbA1c (all P < 0.05), and none with Cholesterol/HDL or VAT. In Abnl-GT-IR: hs-cTnT, fibrinogen and hsCRP significantly associated with Cholesterol/HDL (all P < 0.05) and NT-proBNP inversely related to fibrinogen, hsCRP, HbA1c, Cholesterol/HDL, and VAT (all P < 0.05). The subclinical CVD risk profile differed between Abnl-GT-ß-cell failure and Abnl-GT-IR. In Abnl-GT-ß-cell failure subclinical CVD risk involved subclinical-myocardial damage, hypercoagulability and increased inflammation, but not hyperlipidemia or visceral adiposity. For Abnl-GT-IR, subclinical CVD risk related to subclinical myocardial damage, neurohormonal dysregulation, inflammation associated with hyperlipidemia and visceral adiposity. ClinicalTrials.gov Identifier: NCT00001853.

Combining HbA1c and glycated albumin improves detection of dysglycaemia in mixed-ancestry South Africans.

Background: Combining HbA1c with glycated albumin (GA) may improve detection of dysglycaemia. As BMI correlates positively with HbA1c and negatively with GA, HbA1c may be more effective in obese and GA in nonobese individuals. Methods: To relate these findings to Africans, we assessed in 1274 South Africans living in CapeTown (male 26%; age 48±16y; BMI 28.7 kg/m2 (range 15.6-73.8); obesity 39.9% and no prior diabetes history) the: (1) correlation of BMI with HbA1c and GA, (2) ability of HbA1c and GA separately and jointly, to detect OGTT-diagnosed dysglycaemia (diabetes plus prediabetes). Data collection took place between 2014 and 2016 in the City of Cape Town. Dysglycaemia was diagnosed by glucose criteria for the OGTT. Youden index was used to optimize diagnostic thresholds for HbA1c and GA. Findings: Normal glucose tolerance, prediabetes and diabetes occurred in 76%, 17% and 7%, respectively. BMI positively correlated with HbA1c [r = 0·34 [95%CI: 0·29,0·39)] and negatively with GA [-0·08 (0·13,0·03)]. For HbA1c the optimal threshold by Youden-index for dysglycaemia diagnosis was: 6·0% (95%CI: 5·8,6·2) and for GA: 13·44% (12·72,14·71). In the nonobese, obese and total cohort, HbA1c-alone detected: 51% (42-60), 72% (65,78), 63% (57,68), respectively; GA-alone detected 55% (52% (46,63), 52% (44, 59) and 53% (47,53), respectively; whereas: HbA1c+GA detected: 69% (60,76), 82% (75,87) and 76% (71, 81). Therefore, for the total cohort detection of dysglycaemia HbA1c-alone vs HbA1c+GA detected 63% (57,68) vs 76% (71,81). Interpretation: The opposite correlations of HbA1c and GA with BMI have now been demonstrated in an African-based population. Improving detection of dysglycaemia by combining HbA1c and GA has important implications for diabetes risk screening. Funding: AES is supported by the intramural programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Minority Health and Health Disparities of the National Institutes of Health (NIH, Bethesda, Maryland, USA). DBS is supported by the intramural program of the Clinical Center of NIH. The South African Medical Research Council (SAMRC) funded the VMH study with funds from the National Treasury under its Economic Competitiveness and Support Package (MRC-RFA-UFSP-01-2013/VMH Study).

Sleep and Economic Status Are Linked to Daily Life Stress in African-Born Blacks Living in America.

To identify determinants of daily life stress in Africans in America, 156 African-born Blacks (Age: 40 ± 10 years (mean ± SD), range 22-65 years) who came to the United States as adults (age ≥ 18 years) were asked about stress, sleep, behavior and socioeconomic status. Daily life stress and sleep quality were assessed with the Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. High-stress was defined by the threshold of the upper quartile of population distribution of PSS (≥16) and low-stress as PSS < 16. Poor sleep quality required PSQI > 5. Low income was defined as <40 k yearly. In the high and low-stress groups, PSS were: 21 ± 4 versus 9 ± 4, p < 0.001 and PSQI were: 6 ± 3 versus 4 ± 3, p < 0.001, respectively. PSS and PSQI were correlated (r = 0.38, p < 0.001). The odds of high-stress were higher among those with poor sleep quality (OR 5.11, 95% CI: 2.07, 12.62), low income (OR 5.03, 95% CI: 1.75, 14.47), and no health insurance (OR 3.01, 95% CI: 1.19, 8.56). Overall, in African-born Blacks living in America, daily life stress appears to be linked to poor quality sleep and exacerbated by low income and lack of health insurance.

Intergenerational differences in dietary acculturation among Ghanaian immigrants living in New York City: a qualitative study.

Dietary acculturation may explain the increasing risk of diet-related diseases among African immigrants in the United States (US). We interviewed twenty-five Ghanaian immigrants (Youth n 13, Age (Mean ± sd) 20 y ± 5⋅4, Parents (n 6) and Grandparents (n 6) age 58⋅7 ± 9⋅7) living in New York City (NYC) to (a) understand how cultural practices and the acculturation experience influence dietary patterns of Ghanaian immigrants and (b) identify intergenerational differences in dietary acculturation among Ghanaian youth, parents and grandparents. Dietary acculturation began in Ghana, continued in NYC and was perceived as a positive process. At the interpersonal level, parents encouraged youth to embrace school lunch and foods outside the home. In contrast, parents preferred home-cooked Ghanaian meals, yet busy schedules limited time for cooking and shared meals. At the community level, greater purchasing power in NYC led to increased calories, and youth welcomed individual choice as schools and fast food exposed them to new foods. Global forces facilitated nutrition transition in Ghana as fast and packaged foods became omnipresent in urban settings. Adults sought to maintain cultural foodways while facilitating dietary acculturation for youth. Both traditional and global diets evolved as youth and adults adopted new food and healthy social norms in the US.

Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study.

INTRODUCTION: Uncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is ß-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to ß-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America. RESEARCH DESIGN AND METHODS: Oral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-ß-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan. RESULTS: The prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and ß-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-ß-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m2), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm2), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group. CONCLUSIONS: Beta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to ß-cell failure rather than IR, the clinical course and optimal interventions may differ. TRIAL REGISTRATION NUMBER: NCT00001853.

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment.

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort. Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity. Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (ß = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity. Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study.

Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer's disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer's and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 ± 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitiveexe-func); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitiveexe-func control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitiveexe-func control and neuronal glia injury (Adjusted R2 0.30; p ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitiveexe-func, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; p ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke.

Africans Who Arrive in the United States before 20 Years of Age Maintain Both Cardiometabolic Health and Cultural Identity: Insight from the Africans in America Study.

The overall consensus is that foreign-born adults who come to America age < 20 y achieve economic success but develop adverse behaviors (smoking and drinking) that lead to worse cardiometabolic health than immigrants who arrive age ≥ 20 y. Whether age of immigration affects the health of African-born Blacks living in America is unknown. Our goals were to examine cultural identity, behavior, and socioeconomic factors and determine if differences exist in the cardiometabolic health of Africans who immigrated to America before and after age 20 y. Of the 482 enrollees (age: 38 ± 1 (mean ± SE), range: 20-65 y) in the Africans in America cohort, 23% (111/482) arrived age < 20 y, and 77% (371/482) arrived age ≥ 20 y. Independent of francophone status or African region of origin, Africans who immigrated age < 20 y had similar or better cardiometabolic health than Africans who immigrated age ≥ 20 y. The majority of Africans who immigrated age < 20 y identified as African, had African-born spouses, exercised, did not adopt adverse health behaviors, and actualized early life migration advantages, such as an American university education. Due to maintenance of cultural identity and actualization of opportunities in America, cardiometabolic health may be protected in Africans who immigrate before age 20. In short, immigrant health research must be cognizant of the diversity within the foreign-born community and age of immigration.

The OGTT is highly reproducible in Africans for the diagnosis of diabetes: Implications for treatment and protocol design.

Whether an OGTT reproducibly detects either type 2 diabetes (T2D) or prediabetes in Africans in unknown. Therefore, 131 Africans had two OGTT. Diagnostic reproducibility for T2D was excellent (κ = 0.84), but only moderate for prediabetes (κ = 0.51). A single OGTT positive for T2D may be sufficient to guide clinical care and inform epidemiologic study design. ClinicalTrials.gov Identifier: NCT00001853.

Improved Detection of Abnormal Glucose Tolerance in Africans: The Value of Combining Hemoglobin A1c With Glycated Albumin.

OBJECTIVE: In African-born Blacks living in America, we determined by BMI category 1) prevalence of abnormal glucose tolerance (Abnl-GT) and 2) diagnostic value and reproducibility of hemoglobin A1c (HbA1c), fructosamine, and glycated albumin (GA). RESEARCH DESIGN AND METHODS: Participants (n = 416; male, 66%; BMI 27.7 ± 4.5 kg/m2 [mean ± SD]) had an oral glucose tolerance test with HbA1c, GA, and fructosamine assayed. These glycemic markers were repeated 11 ± 7 days later. Abnl-GT diagnosis required 0 h ≥5.6 mmol/L (≥100 mg/dL) and/or 2 h ≥7.8 mmol/L (≥140 mg/dL). Thresholds for HbA1c, GA, and fructosamine were the values at the 75th percentile for the population (39 mmol/mol [5.7%], 14.2%, and 234 µmol/L, respectively). RESULTS: Abnl-GT prevalence in the nonobese was 34% versus 42% in the obese (P = 0.124). Reproducibility was excellent for HbA1c and GA (both κ ≥ 0.8), but moderate for fructosamine (κ = 0.6). Focusing on HbA1c and GA in the nonobese, we found as single tests the sensitivities of HbA1c and GA were 36% versus 37% (P = 0.529). Combining HbA1c and GA, sensitivity increased to 58% because GA identified 37% of Africans with Abnl-GT not detected by HbA1c (P value for both tests vs. HbA1c alone was <0.001). For the obese, sensitivities for HbA1c, GA, and the combined tests were 60%, 27%, and 67%, respectively. Combined test sensitivity did not differ from HbA1c alone (P = 0.25) because GA detected only 10% of obese Africans with Abnl-GT not detected by HbA1c. CONCLUSIONS: Adding GA to HbA1c improves detection of Abnl-GT in nonobese Africans.

Stress Measured by Allostatic Load Varies by Reason for Immigration, Age at Immigration, and Number of Children: The Africans in America Study.

Stress leads to physiologic dysfunction and cardiometabolic disease. Allostatic load score (ALS) measures stress-induced cardiovascular, metabolic, and inflammatory biomarkers. We estimated the odds of high ALS by reason for and age at immigration, duration of American residence, number of children, and socioeconomic status in 193 African immigrants (male: 65%, age 41 ± 10 y (mean ± Standard Deviation (SD)), range 22-65 y). ALS was calculated with High-ALS defined as ALS ≥ 3.0 and Low-ALS defined as ALS < 3.0. Oral glucose tolerance tests (OGTT) were performed, the cardiovascular disease (CVD) risk estimated, and TNF-α, an inflammatory cytokine, measured. Logistic regression was used to estimate odds of High-ALS. In the High- and Low-ALS groups, ALS were 4.0 ± 1.2 vs. 1.3 ± 0.7, diabetes prevalence: 14% vs. 4%, CVD risk: 23% vs. 8%, TNF-α levels: 15 ± 9 vs. 11 ± 6 pg/mL, respectively (all p ≤ 0.01). Immigrants were more likely to be in the High-ALS group if their reason for immigration was work or asylum/refugee (OR 2.18, p = 0.013), their age at immigration was ≥30 y (OR 3.28, p < 0.001), their duration of residence in United States was ≥10 y (OR 3.16, p = 0.001), or their number of children was ≥3 (OR 2.67, p = 0.019). Education, income, health insurance, marital status, and gender did not affect High-ALS odds. Factors adversely influencing allostatic load and cardiometabolic health in African immigrants were age at and reason for immigration, duration of residence in America, and number of children.

Body adiposity measured by bioelectrical impedance is an alternative to dual-energy x-ray absorptiometry in black Africans: The Africans in America Study.

OBJECTIVES: The prevalence of cardiometabolic disease has risen in Africa and parallels the obesity epidemic. To assess cardiometabolic risk, body composition measurements by dual-energy X-ray absorptiometry (DXA) are ideal. In communities with limited resources, alternative measures may be useful but have not been compared extensively in black Africans. Therefore, the aim of this study was to identify alternative methods of body composition assessment, such as body adiposity index (BAI) and bioelectrical impedance analysis (BIA), for use in African-born blacks. METHODS: This was a cross-sectional study with African-born blacks. BAI and five BIA predictive equations (using variations of height, weight, age, sex, and impedance) were compared with DXA to estimate percent fat. Participants were 266 African-born blacks (39 ± 10 y, body mass index 28 ± 4 kg/m2, and 68% men) living in metropolitan Washington DC. Equivalence (90% confidence interval, -3 to 3), concordance, and Bland-Altman analyses (bias <2%, R2 closest to zero) compared BAI or BIA predictive equations to DXA as the criterion method. RESULTS: DXA percent fat was 27.2% ± 5.5% and 40.3% ± 6.9% in men and women, respectively. BAI underestimated percent fat in men (bias: 1.88 ± 4.71, R2 = 0.25, P < 0.001) and women (bias: 6.47 ± 4.94, R2 = 0.08, P = 0.01). Of the five BIA predictive equations, the equation reported by Sun et al. had the best agreement with DXA percent fat for men (bias: -0.91 ± 3.67, R2 = 0.02, P = 0.05) and women (bias: -0.92 ± 4.02, R2 = 0.003, P = 0.58). Percent fat from the Sun et al. equation best agreed with DXA percent fat. CONCLUSION: BIA with the Sun et al. predictive equation was the best alternative to DXA for body fat assessment in African-born blacks.

Identifying Africans with undiagnosed diabetes: Fasting plasma glucose is similar to the hemoglobin A1C updated Atherosclerosis Risk in Communities diabetes prediction equation.

AIMS: Seventy percent of Africans living with diabetes are undiagnosed. Identifying who should be referred for testing is critical. Therefore we evaluated the ability of the Atherosclerosis Risk in Communities (ARIC) diabetes prediction equation with A1C added (ARIC + A1C) to identify diabetes in 451 African-born blacks living in America (66% male; age 38 ± 10y (mean ± SD); BMI 27.5 ± 4.4 kg/m2). METHODS: All participants denied a history of diabetes. OGTTs were performed. Diabetes diagnosis required 2-h glucose ≥200 mg/dL. The five non-invasive (Age, parent history of diabetes, waist circumference, height, systolic blood pressure) and four invasive variables (Fasting glucose (FPG), A1C, triglycerides (TG), HDL) were obtained. Four models were tested: Model-1: Full ARIC + A1C equation; Model-2: All five non-invasive variables with one invasive variable excluded at a time; Model-3: All five non-invasive variables with one invasive variable included at a time; Model-4: Each invasive variable singly. Area under the receiver operator characteristic curve (AROC) predicted diabetes. Youden Index identified optimal cut-points. RESULTS: Diabetes occurred in 7% (30/451). Model-1, the full ARIC + A1C equation, AROC = 0.83. Model-2: With FPG excluded, AROC = 0.77 (P = 0.038), but when A1C, HDL or TG were excluded AROC remained unchanged. Model-3 with all non-invasive variables and FPG alone, AROC=0.87; but with A1C, TG or HDL included AROC declined to ≤0.76. Model-4: FPG as a single predictor, AROC = 0.87. A1C, TG, or HDL as single predictors all had AROC ≤ 0.74. Optimal cut-point for FPG was 100 mg/dL. CONCLUSIONS: To detect diabetes, FPG performed as well as the nine-variable updated ARIC + A1C equation.