RESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Teste de Tolerância a Glucose , Resistência à Insulina/fisiologia , Secreção de Insulina , Diabetes Mellitus Tipo 2/diagnóstico , Glicemia , Insulina/metabolismo , Glucose , Técnica Clamp de GlucoseRESUMO
RATIONALE: In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index. OBJECTIVE: In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels. METHODS AND RESULTS: In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m2, we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P=0.001). Black women had smaller postprandial changes in large (P=0.005) and medium TRLPs (P=0.007). CONCLUSIONS: Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01809288.
Assuntos
Adiposidade/etnologia , População Negra , Diabetes Mellitus Tipo 2/etnologia , Resistência à Insulina/etnologia , Lipoproteínas/sangue , Obesidade/etnologia , Estado Pré-Diabético/etnologia , Estearoil-CoA Dessaturase/fisiologia , Triglicerídeos/sangue , População Branca , Adulto , África/etnologia , Negro ou Afro-Americano , Glicemia/metabolismo , Estudos Transversais , Suscetibilidade a Doenças , Emigrantes e Imigrantes , Ingestão de Energia , Jejum/sangue , Feminino , Humanos , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/anatomia & histologia , Fígado/anatomia & histologia , Menopausa , Pessoa de Meia-Idade , Período Pós-Prandial , Estearoil-CoA Dessaturase/sangueRESUMO
Cardiovascular disparities remain pervasive in the United States. Unequal disease burden is evident among population groups based on sex, race, ethnicity, socioeconomic status, educational attainment, nativity, or geography. Despite the significant declines in cardiovascular disease mortality rates in all demographic groups during the last 50 years, large disparities remain by sex, race, ethnicity, and geography. Recent data from modeling studies, linked micromap plots, and small-area analyses also demonstrate prominent variation in cardiovascular disease mortality rates across states and counties, with an especially high disease burden in the southeastern United States and Appalachia. Despite these continued disparities, few large-scale intervention studies have been conducted in these high-burden populations to examine the feasibility of reducing or eliminating cardiovascular disparities. To address this challenge, on June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened experts from a broad range of biomedical, behavioral, environmental, implementation, and social science backgrounds to summarize the current state of knowledge of cardiovascular disease disparities and propose intervention strategies aligned with the National Heart, Lung, and Blood Institute mission. This report presents the themes, challenges, opportunities, available resources, and recommended actions discussed at the workshop.
Assuntos
Pesquisa Biomédica/tendências , Doenças Cardiovasculares/terapia , Educação/tendências , Disparidades em Assistência à Saúde/tendências , National Heart, Lung, and Blood Institute (U.S.)/tendências , Relatório de Pesquisa/tendências , Pesquisa Biomédica/economia , Pesquisa Biomédica/métodos , Doenças Cardiovasculares/economia , Doenças Cardiovasculares/epidemiologia , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/métodos , Serviços de Saúde Comunitária/tendências , Educação/economia , Educação/métodos , Disparidades em Assistência à Saúde/economia , Humanos , National Heart, Lung, and Blood Institute (U.S.)/economia , Estados Unidos/epidemiologiaRESUMO
Allostatic load is a physiological measure of the cumulative burden of stress on the body assessed by markers of physiological dysregulation. It is a multisystem construct that quantifies biological risk which leads to poor health and maladaptive trajectories. In this overview, which is based on a presentation made at the Flip the Script: Understanding African American Women's Resilience in the Face of Allostatic Load meeting at Ohio State University in August 2018, we build upon previous reviews by discussing four key aspects of allostatic load, specifically its: (1) importance, (2) operationalization, (3) use in minority health and health disparities research, and (4) value in such research. Operationalized in various ways, allostatic load is composed of 10 original markers and additional markers deriving from research among minority and disparity populations. The markers represent four biological systems: (1) cardiovascular, (2) metabolic, (3) inflammatory, and (4) neuroendocrine. System-specific racial/ethnic and sex-based differences have been observed. An overall score can be determined using sample-generated or empirically derived clinically relevant cut points. In summary, allostatic load provides an overall and a body system-specific mechanistic link between exposures to stressors and health outcomes that may help explain health disparities among minority populations.
Assuntos
Alostase/fisiologia , Biomarcadores/análise , Negro ou Afro-Americano/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Grupos Minoritários/estatística & dados numéricos , Estresse Psicológico/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Ohio , Estados UnidosRESUMO
CONTEXT: Morphological characteristics of the glucose curve during an oral glucose tolerance test (OGTT) (time to peak and shape) may reflect different phenotypes of insulin secretion and action, but their ability to predict diabetes risk is uncertain. OBJECTIVE: To compare the ability of time to glucose peak and curve shape to detect prediabetes and ß-cell function. DESIGN AND PARTICIPANTS: In a cross-sectional evaluation using an OGTT, 145 adults without diabetes (age 42±9 years (mean±SD), range 24-62 years, BMI 29.2±5.3 kg/m2 , range 19.9-45.2 kg/m2 ) were characterized by peak (30 minutes vs >30 minutes) and shape (biphasic vs monophasic). MAIN OUTCOME MEASURES: Prediabetes and disposition index (DI)-a marker of ß-cell function. RESULTS: Prediabetes was diagnosed in 36% (52/145) of participants. Peak>30 minutes, not monophasic curve, was associated with increased odds of prediabetes (OR: 4.0 vs 1.1; P<.001). Both monophasic curve and peak>30 minutes were associated with lower DI (P≤.01). Time to glucose peak and glucose area under the curves (AUC) were independent predictors of DI (adjR2 =0.45, P<.001). CONCLUSION: Glucose peak >30 minutes was a stronger independent indicator of prediabetes and ß-cell function than the monophasic curve. Time to glucose peak may be an important tool that could enhance prediabetes risk stratification.
Assuntos
Teste de Tolerância a Glucose/normas , Estado Pré-Diabético/diagnóstico , Adulto , Área Sob a Curva , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Tempo , Adulto JovemRESUMO
Importance: Hemoglobin A1c (HbA1c) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it. Objective: To evaluate the association between SCT and HbA1c for given levels of fasting or 2-hour glucose levels among African Americans. Design, Setting, and Participants: Retrospective cohort study using data collected from 7938 participants in 2 community-based cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). From the CARDIA study, 2637 patients contributed a maximum of 2 visits (2005-2011); from the JHS, 5301 participants contributed a maximum of 3 visits (2000-2013). All visits were scheduled at approximately 5-year intervals. Participants without SCT data, those without any concurrent HbA1c and glucose measurements, and those with hemoglobin variants HbSS, HbCC, or HbAC were excluded. Analysis of the primary outcome was conducted using generalized estimating equations (GEE) to examine the association of SCT with HbA1c levels, controlling for fasting or 2-hour glucose measures. Exposures: Presence of SCT. Main Outcomes and Measures: Hemoglobin A1c stratified by the presence or absence of SCT was the primary outcome measure. Results: The analytic sample included 4620 participants (mean age, 52.3 [SD, 11.8] years; 2835 women [61.3%]; 367 [7.9%] with SCT) with 9062 concurrent measures of fasting glucose and HbA1c levels. In unadjusted GEE analyses, for a given fasting glucose, HbA1c values were statistically significantly lower in those with (5.72%) vs those without (6.01%) SCT (mean HbA1c difference, -0.29%; 95% CI, -0.35% to -0.23%). Findings were similar in models adjusted for key risk factors and in analyses using 2001 concurrent measures of 2-hour glucose and HbA1c concentration for those with SCT (mean, 5.35%) vs those without SCT (mean, 5.65%) for a mean HbA1c difference of -0.30% (95% CI, -0.39% to -0.21%). The HbA1c difference by SCT was greater at higher fasting (P = .02 for interaction) and 2-hour (P = .03) glucose concentrations. The prevalence of prediabetes and diabetes was statistically significantly lower among participants with SCT when defined using HbA1c values (29.2% vs 48.6% for prediabetes and 3.8% vs 7.3% for diabetes in 572 observations from participants with SCT and 6877 observations from participants without SCT; P<.001 for both comparisons). Conclusions and Relevance: Among African Americans from 2 large, well-established cohorts, participants with SCT had lower levels of HbA1c at any given concentration of fasting or 2-hour glucose compared with participants without SCT. These findings suggest that HbA1c may systematically underestimate past glycemia in black patients with SCT and may require further evaluation.
Assuntos
Negro ou Afro-Americano , Glicemia/análise , Jejum/sangue , Hemoglobinas Glicadas , Traço Falciforme/sangue , Glicemia/metabolismo , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Following immigration to the US, many Africans transition from a low-normal to a high-normal or overweight body mass index (BMI). This weight change is associated with a high rate of prediabetes in the nonobese. Studies in East Asians reveal that glycated albumin is effective in identifying prediabetes in nonobese Asians. Whether this is true in African immigrants is unknown. Therefore, we evaluated the ability of hemoglobin A1c (Hb A1c) and glycated albumin to detect prediabetes in nonobese (BMI <30 kg/m2) and obese (BMI ≥30 kg/m2) African immigrants. METHODS: Oral glucose tolerance tests (OGTTs) were performed in 236 self-identified healthy African immigrants [mean (SD) BMI 27.6 (4.4) kg/m2]. Prediabetes diagnosis was based on glucose criteria for the OGTT. Diagnostic sensitivity of Hb A1c and glycated albumin was determined by thresholds at the upper quartile for each [Hb A1c ≥5.7% (39 mmol/mol), glycated albumin ≥13.77%]. RESULTS: Based on glucose criteria for the OGTT, prediabetes was detected in 36% (85/236). BMI and Hb A1c were positively correlated (r = 0.22, P < 0.001), whereas BMI and glycated albumin were negatively correlated (r = -0.24, P < 0.001). Although the sensitivities of Hb A1c and glycated albumin were similar in nonobese immigrants (37% vs 42%, P = 0.75), prediabetes was detected in 21 nonobese Africans by glycated albumin alone, in 18 by Hb A1c alone, and in 4 by both tests. Therefore, sensitivity of the combined tests was better than for Hb A1c alone(72% vs 37%, P < 0.01). In the obese, Hb A1c was a much better diagnostic test than glycated albumin (64% vs 16%, P < 0.01) and combining the tests did not improve sensitivity (72% vs 64%, P = 0.50). CONCLUSIONS: Glycated albumin contributes by identifying prediabetes not detected by Hb A1c in nonobese African immigrants. ClinicalTrials.gov Identifier: NCT00001853.
Assuntos
Negro ou Afro-Americano , Hemoglobinas Glicadas/análise , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Albumina Sérica/análise , Adulto , População Negra , Índice de Massa Corporal , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose , Produtos Finais de Glicação Avançada , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Albumina Sérica GlicadaRESUMO
BACKGROUND: Quantitative evaluation of insulin regulation on plasma glucose and free fatty acid (FFA) in response to external glucose challenge is clinically important to assess the development of insulin resistance (World J Diabetes 1:36-47, 2010). Mathematical minimal models (MMs) based on insulin modified frequently-sampled intravenous glucose tolerance tests (IM-FSIGT) are widely applied to ascertain an insulin sensitivity index (IEEE Rev Biomed Eng 2:54-96, 2009). Furthermore, it is important to investigate insulin regulation on glucose and FFA in postprandial state as a normal physiological condition. A simple way to calculate the appearance rate (Ra) of glucose and FFA would be especially helpful to evaluate glucose and FFA kinetics for clinical applications. METHODS: A new MM is developed to simulate the insulin modulation of plasma glucose and FFA, combining IM-FSIGT with a mixed meal tolerance test (MT). A novel simple functional form for the appearance rate (Ra) of glucose or FFA in the MT is developed. Model results are compared with two other models for data obtained from 28 non-diabetic women (13 African American, 15 white). RESULTS: The new functional form for Ra of glucose is an acceptable empirical approximation to the experimental Ra for a subset of individuals. When both glucose and FFA are included in FSIGT and MT, the new model is preferred using the Bayes Information Criterion (BIC). CONCLUSIONS: Model simulations show that the new MM allows consistent application to both IM-FSIGT and MT data, balancing model complexity and data fitting. While the appearance of glucose in the circulation has an important effect on FFA kinetics in MT, the rate of appearance of FFA can be neglected for the time-period modeled.
Assuntos
Glicemia/análise , Ácidos Graxos não Esterificados/metabolismo , Alimentos , Teste de Tolerância a Glucose/métodos , Glucose/metabolismo , Adulto , Negro ou Afro-Americano , Algoritmos , Teorema de Bayes , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Estados UnidosRESUMO
UNLABELLED: African ancestry is associated with low vitamin D levels but high bone density. Fifty percent of African immigrants had low vitamin D levels, but <10 % had evidence of deficiency. The value of providing vitamin D supplementation to African immigrants without evidence of deficiency needs to be determined. INTRODUCTION: The Endocrine Society and Institute of Medicine (IOM) have concluded from studies in largely white populations that 25(OH)D is necessary for bone health. However, their definition of vitamin D insufficiency differs. The Endocrine Society recommends a 25(OH)D threshold of <30 ng/mL. The IOM uses a lower threshold of 25(OH)D of <20 ng/mL. As African ancestry is associated with decreased 25(OH)D but increased bone mineral density (BMD), the applicability of these thresholds to Africans is unknown. Therefore, we examined in African immigrants the relationship of 25(OH)D to parathyroid hormone (PTH) and BMD. METHODS: One hundred eighty-six African immigrants(69 % male, age 38 ± 10 (mean ± SD), range 20-64 years) living in metropolitan Washington, DC, were enrolled. BMD was determined from whole-body dual-energy X-ray absorptiometry (DXA) scans. Decreased BMD required T-scores ≤-1.0. The threshold for low 25(OH)D was the concentration of 25(OH)D at which PTH became suppressed. This is known as the inflection point. Biochemical deficiency required low 25(OH)D and PTH of >65 pg/mL. Clinical deficiency required low 25(OH)D and T-scores ≤-1.0. RESULTS: 25(OH)D <30 and <20 ng/mL occurred in 83 and 46 % of African immigrants, respectively. PTH inversely correlated with 25(OH)D (r = -0.31, P = 0.002). The inflection point occurred at a 25(OH)D concentration of 20 ng/mL. Biochemical and clinical deficiency occurred in only 8 and 3 % of immigrants, respectively. CONCLUSION: As PTH became suppressed at 25(OH)D of 20 ng/mL, the 25(OH)D <20 ng/mL threshold for insufficiency may apply to African immigrants. However, ~50 % of African immigrants have 25(OH)D <20 ng/mL, but only <10 % had evidence of deficiency. The value of providing vitamin D supplementation to the large number of African immigrants with 25(OH)D <20 ng/mL and no detectable evidence of deficiency needs to be determined.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Deficiência de Vitamina D/etnologia , Absorciometria de Fóton/métodos , Adulto , Densidade Óssea/fisiologia , District of Columbia/epidemiologia , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Prevalência , Estações do Ano , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Adiponectin is a biomarker that is associated with type 2 diabetes and hypertension. Lower circulating level is a risk factor. Higher levels are protective. African Americans have a higher prevalence of type 2 diabetes and hypertension and lower levels of adiponectin when compared to other racial/ethnic groups. Little is known about the association of adiponectin on these health outcomes among African Americans. The purpose of the study was to assess the association of adiponectin on type 2 diabetes and hypertension likelihood among African American men and women in the Jackson Heart Study. METHODS: Separate multivariate logistic regressions were conducted stratified by sex based on cross-sectional data with type 2 diabetes and hypertension as the outcomes. Adiponectin was divided into four quartiles with the highest quartile as the reference. Data was collected from 2000-2004 on 3,663 participants. Data analysis was conducted in calendar year 2014. Two- tailed P < .05 was established as level of significance. RESULTS: In the adjusted multivariate models, adiponectin level was inversely associated with type 2 diabetes among women (odds ratio [OR], 95% confidence interval [CI] = 1.47, [1.02, 2.11], P = .04). There was no association among men. Women with the lowest level of adiponectin were less likely to be hypertensive (OR, 95% CI = 0.66, [0.46, 0.95], p = .02). There was no association among men. CONCLUSION: Findings reveal differential associations between levels of adiponectin with type 2 diabetes and hypertension likelihood among African American women. More research is needed to elucidate this differential association.
Assuntos
Adiponectina/sangue , Negro ou Afro-Americano/estatística & dados numéricos , Diabetes Mellitus Tipo 2/etnologia , Hipertensão/etnologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Análise Multivariada , Prevalência , Fatores de Risco , Fatores SexuaisRESUMO
In the 20th century, Africans in Sub-Saharan Africa had lower rates of cardiometabolic disease than Africans who migrated. However, in the 21st century, beyond infectious diseases, the triple epidemics of obesity, diabetes and hypertension have taken hold in Africa. Therefore, Africans are acquiring these chronic diseases at different rates and different intensity prior to migration. To ensure optimal care and health outcomes, the United States practice of grouping all African-descent populations into the "Black/African American" category without regard to country of origin masks socioeconomic and cultural differences and needs re-evaluation. Overall, research on African-descent populations would benefit from a shift from a racial to an ethnic perspective. To demonstrate the value of disaggregating data on African-descent populations, the epidemiologic transition, social, economic, and health characteristics of African immigrants are presented.
Assuntos
Negro ou Afro-Americano , Diabetes Mellitus/etnologia , Emigrantes e Imigrantes , Obesidade/etnologia , Grupos Raciais , África Subsaariana/etnologia , Humanos , Hipertensão/etnologia , Estados Unidos/epidemiologiaRESUMO
Diagnosing diabetes by shortening the OGTT to 1-h and substituting 1-h post-load glucose (PG) ≥ 209 mg/dL for 2-h PG≥200 mg/dL has been proposed. One-hour PG≥209 mg/dL is from a meta-analysis without any African-descent populations. Our data suggest 1-h PG≥183 mg/dL maybe more optimal for Africans. As with waist circumference guidelines, population-specific thresholds may be appropriate.
Assuntos
Glicemia , Teste de Tolerância a Glucose , Humanos , Glicemia/análise , Feminino , Masculino , População Negra , Pessoa de Meia-Idade , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Estados Unidos/epidemiologia , População AfricanaRESUMO
AIMS: The gold standard clamp measurements for insulin sensitivity (cSI), ß-cell function (cBCF) and disposition index (cDI = cSI*cBCF), are not practical in large-scale studies. We sought to: 1) validate a mathematical model-derived DI from oral glucose tolerance tests (OGTT) with insulin (mDI) and without (mDI-woI) against cDI and oral disposition index (oDI) evaluate the ability of the novel indices to detect prediabetes and type 2 diabetes. METHODS: We carried out a secondary analysis of previously reported cross-sectional observational studies. The Insulin Sensitivity and Secretion mathematical model for glucose-insulin dynamics was applied to five-point and three-point OGTTs synchronized with hyperinsulinemic-euglycemic and hyperglycemic clamps from 130 youth with obesity (68 NGT, 33 IGT, 29 T2D). RESULTS: Model-derived DI correlated well with clamp DI (R = 0.76 (logged)). Between NGT and IGT, mDI and mDI-woI decreased more than oDI and cDI, (60 and 59% vs 29 and 27%), and by receiver operating characteristic (ROC) analysis were superior at detecting IGT than oDI and cDI (AUC 0.88, 0.87 vs 0.68, 0.65), as was mean glucose (AUC 0.87). CONCLUSIONS: mDI-woI is better than oDI or the labor-intensive cDI for detecting dysglycemia in obese youth. Bypassing insulin measurements with mDI-woI from the OGTT provides a cost-effective approach for large-scale epidemiological studies of dysglycemia in youth.
RESUMO
BACKGROUND: Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT. METHODS: Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT. RESULTS: Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 µg/mL vs. 6.0 ± 4.4 µg/mL; p < 0.01) and mean volume of SAT (1,721 ± 803 cm(3) vs. 2,668 ± 968 cm(3); p < 0.01) but significantly higher mean volume of VAT (884 ± 416 cm(3) vs. 801 ± 363 cm(3); p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (ß = - 0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (ß = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of SAT. Insulin resistance mediated the association of SAT with adiponectin in women. CONCLUSION: In African Americans, abdominal visceral adipose tissue had an inverse association with serum adiponectin concentrations only among women. Abdominal subcutaneous adipose tissue appeared as a protective fat depot in men.
Assuntos
Adiponectina/sangue , Adiposidade/etnologia , Negro ou Afro-Americano , Gordura Intra-Abdominal/metabolismo , Obesidade/etnologia , Gordura Subcutânea/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/etnologia , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Tomografia Computadorizada de Feixe Cônico , Escolaridade , Feminino , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/diagnóstico por imagem , Modelos Lineares , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Tomografia Computadorizada Multidetectores , Análise Multivariada , Obesidade/sangue , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/etnologia , Gordura Subcutânea/diagnóstico por imagem , Circunferência da Cintura , Adulto JovemRESUMO
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.
RESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2 , Infecções por HIV , Estado Pré-Diabético , Masculino , Adulto , Humanos , Idoso , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Prevalência , África/epidemiologiaRESUMO
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 Ð-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 (Ð≥0.86) and GA (Ð≥0.89), but only moderate for FA (Ð=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.
RESUMO
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.
RESUMO
Insulin resistance is associated with endothelial dysfunction. Because African-American women are more insulin-resistant than white women, it is assumed that African-American women have impaired endothelial function. However, racial differences in postprandial endothelial function have not been examined. In this study, we test the hypothesis that African-American women have impaired postprandial endothelial function compared with white women. Postprandial endothelial function following a breakfast (20% protein, 40% fat, and 40% carbohydrate) was evaluated in 36 (18 African-American women, 18 white women) age- and body mass index (BMI)-matched (age: 37 ± 11 yr; BMI: 30 ± 6 kg/m(2)) women. Endothelial function, defined by percent change in brachial artery flow-mediated dilation (FMD), was measured at 0, 2, 4, and 6 h following a meal. There were no significant differences between the groups in baseline FMD, total body fat, abdominal visceral fat, and fasting levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, or serum estradiol. Although African-American women were less insulin-sensitive [insulin sensitivity index (mean ± SD): 3.6 ± 1.5 vs. 5.2 ± 2.6, P = 0.02], both fasting triglyceride (TG: 56 ± 37 vs. 97 ± 49 mg/dl, P = 0.007) and incremental TG area under the curve (AUC(0-6hr): 279 ± 190 vs. 492 ± 255 mg·dl(-1)·min(-1)·10(-2), P = 0.008) were lower in African-American than white women. Breakfast was associated with a significant increase in FMD in whites and African-Americans, and there was no significant difference in postprandial FMD between the groups (P > 0.1 for group × time interactions). Despite being insulin-resistant, postprandial endothelial function in African-American women was comparable to white women. These results imply that insulin sensitivity may not be an important determinant of racial differences in endothelial function.
Assuntos
Endotélio Vascular/fisiologia , Resistência à Insulina/etnologia , Período Pós-Prandial/fisiologia , Adulto , Negro ou Afro-Americano , Glicemia , Índice de Massa Corporal , Artéria Braquial/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Triglicerídeos/sangue , População BrancaRESUMO
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).