Transcriptomic Analysis of Alzheimer's Disease Pathways in a Pakistani Population.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan. Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population. Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; n = 33 subjects) coupled with Affymetrix Arrays (n = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways. Results: We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in CAPNS2 and CAPN1. The global gene expression study observed that 61% and 39% of genes were significantly (p-value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., Amyloid Processing, Neuroinflammation Signaling, and ErbB4 Signaling. The top-scoring networks in Diseases and Disorders Development were Neurological Disease, Organismal Injury and Abnormalities, and Psychological Disorders. Conclusions: Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to Amyloid Processing, which could play potential role in future studies to identify sensitive, early biomarkers of AD in general.

Transcriptomics of MASLD Pathobiology in African American Patients in the Washington DC Area †.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is becoming the most common chronic liver disease worldwide and is of concern among African Americans (AA) in the United States. This pilot study evaluated the differential gene expressions and identified the signature genes in the disease pathways of AA individuals with MASLD. Blood samples were obtained from MASLD patients (n = 23) and non-MASLD controls (n = 24) along with their sociodemographic and medical details. Whole-blood transcriptomic analysis was carried out using Affymetrix Clarion-S Assay. A validation study was performed utilizing TaqMan Arrays coupled with Ingenuity Pathway Analysis (IPA) to identify the major disease pathways. Out of 21,448 genes in total, 535 genes (2.5%) were significantly (p < 0.05) and differentially expressed when we compared the cases and controls. A significant overlap in the predominant differentially expressed genes and pathways identified in previous studies using hepatic tissue was observed. Of note, TGFB1 and E2F1 genes were upregulated, and HMBS was downregulated significantly. Hepatic fibrosis signaling is the top canonical pathway, and its corresponding biofunction contributes to the development of hepatocellular carcinoma. The findings address the knowledge gaps regarding how signature genes and functional pathways can be detected in blood samples ('liquid biopsy') in AA MASLD patients, demonstrating the potential of the blood samples as an alternative non-invasive source of material for future studies.

Insights on the pathogenesis of type 2 diabetes as revealed by signature genomic classifiers in an African American population in the Washington, DC area.

AIMS: African Americans (AA) in the United States have a high risk of type 2 diabetes mellitus (T2DM) and suffer from disparities in the prevalence, mortality, and comorbidities of the disease compared to other Americans. The present study aimed to shed light on the molecular mechanisms of disease pathogenesis of T2DM among AA in the Washington, DC region. METHODS: We performed TaqMan Low Density Arrays (TLDA) on 24 genes of interest that belong to three categories: metabolic disease and disorders, cancer-related genes, and neurobehavioural disorders genes. The 18 genes, viz. ARNT, CYP2D6, IL6, INSR, RRAD, SLC2A2 (metabolic disease and disorders), APC, BCL2, CSNK1D, MYC, SOD2, TP53 (Cancer-related), APBA1, APBB2, APOC1, APOE, GSK3B, and NAE1 (neurobehavioural disorders), were differentially expressed in T2DM participants compared to controls. RESULTS: Our results suggest that factors including gender, smoking habits, and the severity or lack of control of T2DM (as indicated by HbA1c levels) were significantly associated with differential gene expression. APBA1 was significantly (p-value <0.05) downregulated in all diabetes participants. Upregulation of APOE and CYP2D6 genes and downregulation of the INSR gene were observed in the majority of diabetes patients. CONCLUSIONS: Tobacco smoking and gender were significantly associated with case-control differences in expression of the APBA1 and APOE genes (connected with Alzheimer's disease) and the INSR and CYP2D6 (associated with metabolic disorders). The results highlight the need for more effective management of T2DM and for tobacco smoking cessation interventions in this community, and further research on the associations of T2DM with other disease processes, including cancer and neurobehavioral pathways.

To the Future: The Role of Exosome-Derived microRNAs as Markers, Mediators, and Therapies for Endothelial Dysfunction in Type 2 Diabetes Mellitus.

The prevalence of diabetes mellitus (DM) is increasing at a staggering rate around the world. In the United States, more than 30.3 million Americans have DM. Type 2 diabetes mellitus (T2DM) accounts for 91.2% of diabetic cases and disproportionately affects African Americans and Hispanics. T2DM is a major risk factor for cardiovascular disease (CVD) and is the leading cause of morbidity and mortality among diabetic patients. While significant advances in T2DM treatment have been made, intensive glucose control has failed to reduce the development of macro and microvascular related deaths in this group. This highlights the need to further elucidate the underlying molecular mechanisms contributing to CVD in the setting of T2DM. Endothelial dysfunction (ED) plays an important role in the development of diabetes-induced vascular complications, including CVD and diabetic nephropathy (DN). Thus, the endothelium provides a lucrative means to investigate the molecular events involved in the development of vascular complications associated with T2DM. microRNAs (miRNA) participate in numerous cellular responses, including mediating messages in vascular homeostasis. Exosomes are small extracellular vesicles (40-160 nanometers) that are abundant in circulation and can deliver various molecules, including miRNAs, from donor to recipient cells to facilitate cell-to-cell communication. Endothelial cells are in constant contact with exosomes (and exosomal content) that can induce a functional response. This review discusses the modulatory role of exosomal miRNAs and proteins in diabetes-induced endothelial dysfunction, highlighting the significance of miRNAs as markers, mediators, and potential therapeutic interventions to ameliorate ED in this patient group.

Biomarkers of metabolic disorders and neurobehavioral diseases in a PCB- exposed population: What we learned and the implications for future research.

Polychlorinated biphenyls (PCBs) are one of the original twelve classes of toxic chemicals covered by the Stockholm Convention on Persistent Organic Pollutants (POP), an international environmental treaty signed in 2001. PCBs are present in the environment as mixtures of multiple isomers at different degree of chlorination. These compounds are manmade and possess useful industrial properties including extreme longevity under harsh conditions, heat absorbance, and the ability to form an oily liquid at room temperature that is useful for electrical utilities and in other industrial applications. They have been widely used for a wide range of industrial purposes over the decades. Despite a ban in production in 1979 in the US and many other countries, they remain persistent and ubiquitous in environment as contaminants due to their improper disposal. Humans, independent of where they live, are therefore exposed to PCBs, which are routinely found in random surveys of human and animal tissues. The prolonged exposures to PCBs have been associated with the development of different diseases and disorders, and they are classified as endocrine disruptors. Due to its ability to interact with thyroid hormone, metabolism and function, they are thought to be implicated in the global rise of obesity diabetes, and their potential toxicity for neurodevelopment and disorders, an example of gene by environmental interaction (GxE). The current review is primarily intended to summarize the evidence for the association of PCB exposures with increased risks for metabolic dysfunctions and neurobehavioral disorders. In particular, we present evidence of gene expression alterations in PCB-exposed populations to construct the underlying pathways that may lead to those diseases and disorders in course of life. We conclude the review with future perspectives on biomarker-based research to identify susceptible individuals and populations.

Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes Mellitus in a Pakistani Population.

The epidemic of type 2 diabetes mellitus (T2DM) is an important global health concern. Our earlier epidemiological investigation in Pakistan prompted us to conduct a molecular investigation to decipher the differential genetic pathways of this health condition in relation to non-diabetic controls. Our microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their canonical pathways. High-throughput qRT-PCR TaqMan Low Density Array (TLDA) was performed to validate the selected differentially expressed genes of our interest, viz., ARNT, LEPR, MYC, RRAD, CYP2D6, TP53, APOC1, APOC2, CYP1B1, SLC2A13, and SLC33A1 using a small population validation sample (n = 15 cases and their corresponding matched controls). Overall, our small pilot study revealed a discrete gene expression profile in cases compared to controls. The disease pathways included: Insulin Receptor Signaling, Type II Diabetes Mellitus Signaling, Apoptosis Signaling, Aryl Hydrocarbon Receptor Signaling, p53 Signaling, Mitochondrial Dysfunction, Chronic Myeloid Leukemia Signaling, Parkinson's Signaling, Molecular Mechanism of Cancer, and Cell Cycle G1/S Checkpoint Regulation, GABA Receptor Signaling, Neuroinflammation Signaling Pathway, Dopamine Receptor Signaling, Sirtuin Signaling Pathway, Oxidative Phosphorylation, LXR/RXR Activation, and Mitochondrial Dysfunction, strongly consistent with the evidence from epidemiological studies. These gene fingerprints could lead to the development of biomarkers for the identification of subgroups at high risk for future disease well ahead of time, before the actual disease becomes visible.

Epidemiological Investigation of Type 2 Diabetes and Alzheimer's Disease in a Pakistani Population.

The epidemic of type 2 diabetes mellitus (T2DM) and the possibility of it contributing to the risk of Alzheimer's disease (AD) have become important health concerns worldwide and in Pakistan, where the co-occurrence of T2DM and AD is becoming more frequent. To gain insights on this phenomenon, a cross-sectional study was initiated. We recruited and interviewed 820 research participants from four cities in Pakistan: 250 controls, 450 T2DM, 100 AD, and 20 with both diseases. Significant differences between groups were observed for age (p < 0.0001), urban vs. rural locality (p = 0.0472) and residing near industrial areas. The average HbA1c (%) level was 10.68 ± 2.34 in the T2DM group, and females had a lower level than males (p = 0.003). In the AD group, significant relationships existed between education and family history. Overall, the results suggest that T2DM and AD were associated with both socio-demographic and environmental factors in Pakistani participants. Detailed molecular investigations are underway in our laboratory to decipher the differential genetic pathways of the two diseases to address their increasing prevalence in this developing nation.

Adiponectin, Leptin, IGF-1, and Tumor Necrosis Factor Alpha As Potential Serum Biomarkers for Non-Invasive Diagnosis of Colorectal Adenoma in African Americans.

The potential role of adiponectin, leptin, IGF-1, and tumor necrosis factor alpha (TNF-α) as biomarkers in colorectal adenoma is not clear. Therefore, we aimed to investigate the blood serum levels of these biomarkers in colorectal adenoma. The case-control study consisted of serum from 180 African American patients with colon adenoma (cases) and 198 healthy African Americans (controls) at Howard University Hospital. We used ELISA for adiponectin, leptin, IGF-1, and TNF-α detection and quantification. Statistical analysis was performed by t-test and multivariate logistic regression. The respective differences in median leptin, adiponectin, IGF-1, and TNF-α levels between control and case groups (13.9 vs. 16.4), (11.3 vs. 46.0), (4.5 vs. 12.9), and (71.4 vs. 130.8) were statistically significant (P < 0.05). In a multivariate model, the odds ratio for adiponectin, TNF-α, and IGF-1 were 2.0 (95% CI = 1.6-2.5; P < 0.001), 1.5 (95% CI = 1.5(1.1-2.0); P = 0.004), and 1.6 (95% CI = 1.3-2.0; P < 0.001), respectively. There was a positive correlation between serum adiponectin and IGF-1 concentrations with age (r = 0.17, P < 0.001 and r = 0.13, P = 0.009), TNF-α, IGF-1, and leptin concentration with body mass index (BMI) (r = 0.44, P < 0.001; r = 0.11, P = 0.03; and r = 0.48, P < 0.001), respectively. Also, there was a negative correlation between adiponectin and leptin concentrations with BMI (r = -0.40, P < 0.001), respectively. These data support the hypothesis that adiponectin, IGF-1, and TNF-α high levels correlate with higher risk of colon adenoma and can thus be used for colorectal adenomas risk assessment.

Patient perceptions of a pharmacy star rating model.

OBJECTIVES: To identify patients' understanding of what constitutes a "quality pharmacy" and to obtain their feedback regarding the development and use of the pharmacy star rating model, a pharmacy-specific aggregate performance score based on the Centers for Medicare and Medicaid Services' Medicare Star Rating. DESIGN: Prospective cross-sectional study. SETTING AND PARTICIPANTS: Focus groups were conducted in Arizona, California, Mississippi, Maryland, and the District of Columbia, and one-on-one interviews were conducted in Indiana. Eligible patients were required to routinely use a community pharmacy. MAIN OUTCOME MEASURES: Consumer insights on their experiences with their pharmacies and their input on the pharmacy star rating model were attained. Key themes from the focus groups and interviews were obtained through the use of qualitative data analyses. RESULTS: Forty-nine subjects from 5 states and DC participated in 6 focus groups and 4 one-on-one interviews. Eighty-eight percent of participants reported currently taking at least 1 medication, and 87% reported having at least 1 health condition. The 7 themes identified during qualitative analysis included patient care, relational factors for choosing a pharmacy, physical factors for choosing a pharmacy, factors related to use of the pharmacy star rating model, reliability of the pharmacy star rating model, trust in pharmacists, and measures of pharmacy quality. Most participants agreed that the ratings would be useful and could aid in selecting a pharmacy, especially if they were moving to a new place or if they were dissatisfied with their current pharmacy. CONCLUSION: Pharmacy quality measures are new to patients. Therefore, training and education will need to be provided to patients, as pharmacies begin to offer additional clinical services, such as medication therapy management and diabetes education. The use of the pharmacy star rating model was dependent on the participants' situation when choosing a pharmacy.

Impact of CMS Competitive Bidding Program on Medicare Beneficiary Safety and Access to Diabetes Testing Supplies: A Retrospective, Longitudinal Analysis.

OBJECTIVE: In 2011, the Centers for Medicare & Medicaid Services (CMS) launched the Competitive Bidding Program (CBP) in nine markets for diabetes supplies. The intent was to lower costs to consumers. Medicare claims data (2009-2012) were used to confirm the CMS report (2012) that there were no disruptions in acquisition caused by CBP and no changes in health outcomes. RESEARCH DESIGN AND METHODS: The study population consisted of insulin users: 43,939 beneficiaries in the nine test markets (TEST) and 485,688 beneficiaries in the nontest markets (NONTEST). TEST and NONTEST were subdivided: those with full self-monitoring of blood glucose (SMBG) supply acquisition (full SMBG) according to prescription and those with partial/no acquisition (partial/no SMBG). Propensity score-matched analysis was performed to reduce selection bias. Outcomes were impact of partial/no SMBG acquisition on mortality, inpatient admissions, and inpatient costs. RESULTS: Survival was negatively associated with partial/no SMBG acquisition in both cohorts (P < 0.0001). Coterminous with CBP (2010-2011), there was a 23.0% (P < 0.0001) increase in partial/no SMBG acquisition in TEST vs. 1.7% (P = 0.0002) in NONTEST. Propensity score-matched analysis showed beneficiary migration from full to partial/no SMBG acquisition in 2011 (1,163 TEST vs. 605 NONTEST) was associated with more deaths within the TEST cohort (102 vs. 60), with higher inpatient hospital admissions and associated costs. CONCLUSIONS: SMBG supply acquisition was disrupted in the TEST population, leading to increased migration to partial/no SMBG acquisition with associated increases in mortality, inpatient admissions, and costs. Based on our findings, more effective monitoring protocols are needed to protect beneficiary safety.

miRNA-15a, miRNA-15b, and miRNA-499 are Reduced in Erythrocytes of Pre-Diabetic African-American Adults.

AIMS: The use of circulatory miRNAs as biomarkers and therapeutic targets for T2DM is an explosive area of study. However, no study has investigated circulatory miRNA expression exclusively in African-American adults. The aim of this study was to identify the expression of nine selected miRNAs in erythrocytes of pre-diabetic and type 2 diabetic African-American adults. MAIN METHODS: Patients were recruited from the Howard University Hospital Diabetes Treatment Center following an 8 to 10 hour overnight fast. Expression of the nine selected miRNAs (miRNA-499, miRNA-146, miRNA-126, miRNA-223, miRNA-15a, miRNA-15b, miRNA-224, miRNA-326, and miRNA-375) was evaluated using quantitative real time PCR. KEY FINDINGS: miRNA-15a, miRNA-15b, and miRNA-499 were significantly reduced in erythrocytes of pre-diabetic African-American adults. In the T2DM group, we found significant correlations between miRNA-15a and BMI (r=0.59, p=0.04), miRNA-15a and weight (r=0.52, p=0.01), and miRNA-15b and diastolic blood pressure (r=-0.52, p=0.02). In the pre-diabetic group, we found significant correlations between miRNA-15b and weight (r=0.90, p=0.02) and miRNA-499 and HbA1c (r=-0.89, p=0.01). SIGNIFICANCE: To our knowledge, this is the first study investigating miRNA expression in erythrocytes of non-diabetic high-risk obese--pre-diabetic and type 2 diabetic African-American adults. The findings of this study are consistent with previous reports of reduced expression of miRNA-15a, miRNA-15b, and miRNA-499 in human plasma or serum and in animal models. The current findings support the use of circulating miRNA-15a, miRNA-15b, and miRNA-499 as potential biomarkers for T2DM in African-American adults.

Characteristics and health perceptions of complementary and alternative medicine users in the United States.

BACKGROUND: Complementary and alternative medicine (CAM) use has been increasing and these unconventional therapies do have important adverse effects. We evaluated predictors of CAM use among U.S. adults. METHODS: We analyzed the 2007 Health Information National Trends Survey (n=7503) and used logistic regression models to evaluate the association of demographic, lifestyle characteristics and healthcare perceptions of respondents who used CAM within the previous 12 months (n=1980) versus those who did not (n=5523). We used survey weights in all analyses and performed variance estimations using Taylor series linearization to account for the complex survey design. RESULTS: Females (odds ratio [OR]=1.46; 95% confidence interval [CI]: 1.15-1.86), college graduates (OR=1.61; 95% CI: 1.24-2.08) and those who considered the quality of their healthcare to be poor (OR=2.16; 95% CI: 1.28-3.65) were more likely to use CAM, whereas blacks (OR=0.58; 95% CI: 0.39-0.85) were less likely to use CAM. Among CAM users, 47.6% did not inform their doctors. However, no factor predicted those who did not inform their doctors of their CAM use. CONCLUSIONS: Many adults in the United States use CAM without informing their doctors. Care providers should inquire about CAM usage from their patients, document them and counsel their patients regarding their use of these less regulated therapies.

Maintenance of long-term adequate levels of vitamin d lowers HbA1c in African American patients with type 2 diabetes.

OBJECTIVES: We examined the long-term effects of enhanced Vitamin D (VitD) supplementation on parameters of type 2 diabetes mellitus (T2DM): serum hemoglobin A1c, low density lipoprotein, high density lipoprotein, and triglyceride for the purpose of determining beneficial VitD levels in T2DM African Americans (AA). DESIGN AND METHODS: Following inclusion criteria, retrospective charts of patients aged > or = 30 years were reviewed. VitD supplementation was given to patients as part of drug regimen over a three year continuum. Pearson correlations were used to assess the relationship between VitD levels and levels of each parameter. Repeated measure analysis of variance was conducted to identify difference in mean levels of each parameter between years with VitD included as part of therapy. RESULTS: Vitamin D supplementation was inversely associated with HbA1c (r = -.286, P = .031). No correlation was found between levels of VitD and levels of LDL, HDL or TG. Hemoglobin A1c levels were found to be significantly different under VitD treatment between year 1 (mean VitD 24.75 microg/mL, mean HbA1c 9.15%, P = .000) and year 2 (mean VitD 33.84 microg/mL, mean HbA1c 7.91%, P = .000) and between year 1 and year 3 (mean VitD 34.46 microg/mL, mean 7.98% HbA1c P = .000). CONCLUSION: In T2DM AA, significant improvements in HbA1c are obtained with enhanced VitD supplementation as part of drug regimen over time. Our investigation provides the first known evidence of a relationship between enhanced VitD supplementation as part of a pre-existing medical regimen taken over long term and determinants of T2DM in a group of overweight and obese AA with T2DM.

BMI and the risk of colorectal adenoma in African-Americans.

OBJECTIVES: Obesity is associated with the activation of the molecular pathways that increase the risk of colorectal cancer. Increasing body mass index may accelerate the development of adenomatous polyps, the antecedent lesion of colorectal cancer. The aim of this study was to assess the BMI effect on the risk of colonic polyp and adenoma in African-American. METHODS: The records of 923 patients who underwent colonoscopy were examined. Demographic and clinical data were collected before colonoscopy. Polyp and adenoma diagnosis were confirmed by pathology examinations. RESULTS: Overall, 43% of the patients were male, median age was 57 years and 77% had BMI ≥ 25.0 kg/m(2) . The frequency of colorectal polyps and adenomas were 61 and 35%, respectively. BMI ≥ 25.0 (OR = 1.61, 95% CI = 1.14-2.26), smoking (OR = 1.61, 95% CI = 1.15-2.26) and history of colon polyps (OR = 1.64, 95% CI = 1.09-2.47) were associated with higher risk of colon polyp. BMI ≥ 25.0 (OR = 1.81, 95% CI = 1.24-2.62), age (OR = 1.04, 95% CI = 1.02-2.05 for each year), male gender (OR = 1.38, 95% CI = 1.02-1.86), and smoking (OR = 1.73, 95% CI = 1.23-2.42) were associated with higher risk of colon adenoma. CONCLUSION: Male and overweight African-Americans are at higher risk of colorectal adenoma. The findings of this study could be applied for risk stratification and modifying the colorectal cancer prevention including screening guideline in African Americans.

Previously unrecognized trends in diabetes consumption clusters in medicare.

OBJECTIVE: To examine the annual cost profiles of Medicare beneficiaries with diabetes to identify patterns in their consumption of benefits. METHODS: Retrospective expenditure data were collected from Medicare records. Beneficiaries with diabetes were grouped into 5 consumption clusters ranging from "crisis consumers" at the high end to "low consumers" at the low end. RESULTS: The percentages of beneficiaries and expenditures for the consumption clusters remained generally constant from year to year. As expected, most of Medicare's budget each year was spent on crisis, heavy, and moderate consumers. However, a notable proportion of low and light consumers from one year go on to become crisis and heavy consumers in subsequent years. A review of total 2001 through 2006 inpatient costs for the year 2000 clusters revealed that 47% of these costs were for year 2000 low and light consumers and only 27% were for year 2000 crisis and heavy consumers. CONCLUSIONS: This analysis revealed previously unrecognized trends, whereby a notable proportion of low and light consumers during one year went on to become crisis and heavy consumers in subsequent years, representing a large proportion of inpatient costs. These findings have important implications for disease management programs, which typically focus intervention efforts exclusively on crisis and heavy consumers.

A reversible cause of skin hyperpigmentation and postural hypotension.

Vitamin B12 deficiency results in neuropsychiatric, hematologic, gynecologic, cardiovascular, and cutaneous manifestations. It is seen most commonly in the elderly, malabsorption diseases (>60% of all cases), vegans, and vegetarians. Manifestations of pernicious anemia may be similar to Addison disease and may lead to a misdiagnosis. Herein, we report two cases of vitamin B12 deficiency in which clinical features shared many similarities with Addison disease. Both patients presented with progressive darkening of hands and postural hypotension that reversed with replenishment of vitamin B12. Vitamin B12 deficiency should be considered in patients presenting with skin lesions especially with other coexisting autoimmune diseases.

Diabetic cheiroarthropathy: a case report and review of the literature.

Diabetes mellitus is associated with a wide variety of rheumatologic manifestations which can significantly affect a patient's quality of life. One of these manifestations includes diabetic cheiroarthropathy (DCA) which affects the hands. We review a case of a 28-year-old female patient with type 1 diabetes mellitus who was diagnosed with DCA after complaining of limited movements of all joints in her hands and tightening of the skin. We examine how the diagnosis was made, the treatment administered, and the successful clinical outcome. Clinicians should be able to identify and treat this affliction. The diagnosis is mainly clinical. It is imperative to remember that the presence of DCA carries with it a significant relationship with microvascular disease.

Fasting plasma ghrelin levels are reduced, but not suppressed during OGTT in obese African American adolescents.

OBJECTIVE: Our study aimed to evaluate total plasma ghrelin (TGh) concentration and its correlation with leptin and insulin in obese African American (AA) adolescents with a family history of type 2 diabetes. PARTICIPANTS AND METHODS: Insulin, leptin, and TGh were measured for 15 non-obese controls in fasted state and 19 obese AA adolescents on samples collected during oral glucose tolerance test (OGTT) using radioimmunoassay kits. The hormonal concentrations were compared at fasting levels between obese and non-obese AA adolescents. Insulin, leptin, and TGh concentrations were also compared during OGTT in the obese group. RESULTS: Fasting TGh was significantly lower in obese AA adolescents compared to non-obese controls, while fasting leptin and insulin were significantly higher in obese AA adolescents compared to non-obese controls. During OGTT, for the obese group, TGh increased significantly and plasma leptin decreased significantly. A significant negative correlation was found between TGh and leptin at 30 and 120 min, but at no other time points (0, 60, and 90 min). A significant positive correlation was found between TGh and insulin at 30 min during OGTT, but no other time points. CONCLUSIONS: TGh was lower in obese AA adolescents with a family history of type 2 diabetes and a significant correlation occurred between TGh and leptin and TGh and insulin during OGGT at specific time points in our obese group. These findings indicate that insulin resistant obese AA adolescents have impaired ghrelin suppression.

The metabolically healthy but obese phenotype in African Americans.

Obesity has become one of the leading public health concerns in the United States and worldwide. While obesity is associated with the metabolic syndrome, some obese individuals do not possess the constellation of the metabolic abnormalities and are referred to as metabolically healthy but obese (MHO) persons. Limited data exist on the prevalence and characteristics of the MHO in African Americans. The authors studied 126 obese African Americans and defined the MHO phenotype as an individual with a body mass index ≥30 kg/m(2) , high-density lipoprotein cholesterol ≥40 mg/dL, absence of type 2 diabetes mellitus, and absence of arterial hypertension. The correlates of the MHO phenotype with anthropometrical and metabolic indices were examined, as well as the effect of age on these correlates. Results showed that 36 (28.5%) of the individuals were identified with the MHO phenotype. Waist circumference (WC) and waist-to-hip ratio (WHR) were significantly lower (P<.05) in MHO than in non-MHO patients. While there were significant lower levels of low-density lipoprotein and triglycerides in MHO among patients younger than 40 years, the significance was lost among patients 40 years or older. This study indicates that increased WC and WHR may be early premetabolic syndrome markers in obese individuals and should warrant aggressive risk factor reduction therapy to prevent future development of related cardiovascular conditions.