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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.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.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-value0.05) 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.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.

Biological markers for Metabolic Syndrome, such as serum lipids and Hemoglobin A1c may have genetic variability among African Americans versus their Caucasian American counterparts. Although cases of Type 2 diabetes and its sequela significantly outweigh Caucasian Americans in the US, paradoxically research has found a lower prevalence of Metabolic Syndrome among blacks versus whites despite there being higher rates of Type 2 diabetes among the former population. Research has shown Metabolic Syndrome lipid parameters among African Americans are more favorable despite outstanding Type 2 diabetes incidence. With the emergence of the Human Genome Project and Genome Wide Association Studies, genetic differences in these parameters have been uncovered and genetic variability may play a role in such paradoxical mismatch. It may be reasonable to consider modifying Metabolic Syndrome parameters as given this new biological evidence. Hemoglobin A1c, also a biological marker used to monitor glucose levels over time, shows variability in its measurements with respect to African Americans. Genetic factors may play a role in the discrepancies among African Americans populations when using this parameter to monitor blood glucose. Precision medicine is now at the forefront of a biomedical new age, to find therapies that cater to specific populations based on genetic research. African Americans may not benefit from such a revolutionary paradigm shift in medicine due to evidence of lack of inclusivity in such studies like the Human Genome Project. Consideration should be made to the future of molecular medicine to include more minority populations such as African Americans in order to cater to specific differences rather than generalized standards of care.

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.

Introduction Thyroid storm is a life-threatening endocrinological emergency. It creates a hypermetabolic state caused by excessive release of thyroid hormones, causing adrenergic hyperactivity following a precipitant(s). An uncommon precipitant of thyroid storm is a thyroid abscess. Clinical Case A 48-year-old man with a PMHx of COPD on home oxygen, OSA, HTN, left thyroid lobe nodule and recent treatment for community-acquired pneumonia the prior week presented to the ED with complaints of right neck pain and swelling of 5 days duration. Patient had associated diarrhea, fever, nausea, vomiting and palpitations. VS: Temp 101.9 F, BP 164/120, RR 20 and HR 160. Physical examination revealed a right non-mobile tender neck mass, rales on the lower lobe of the left lung, and drenching sweats. CT of the neck showed a prominent soft tissue mass on the right side of the neck with irregular margins abutting the right thyroid lobe, suggesting possible abscess. A subsequent thyroid US revealed a large heterogeneous nonvascular right thyroid mass measuring approximately 12×7×7 cm. Initial labs: TSH < 0. 005 mU/L (normal range 0.45-5. 0 mU/L), FT4 2.54 mU/L (normal range 0.9 to 2.3 mU/L); TSHrAB, TSI and TPO were negative. Thyroid storm was diagnosed using the Burch Wartofsky score (45 points). He was treated with propythiouracil, hydrocortisone, propranolol and antibiotics. FT4 normalized after 2 days on admission at which time he was taken for surgical drainage of his right thyroid abscess. 80 cc of pus was aspirated and cultured with isolation of Klebsiella Pneumoniae. Blood cultures also revealed K. Pneumoniae. Repeat Thyroid US showed resolution of abscess. Patient remained in hospital for ongoing treatment of his pneumonia. Clinical Lesson: Acute suppurative thyroiditis (AST) is a rare, life-threatening infection of the thyroid gland. Thyroid gland is rich in iodine, blood supply and lymphatics with a thick capsule which is relatively resistant to infection from neighboring sites. AST is more common in women and affects the left lobe of thyroid. Our patient is a man and his thyroid abscess was on the right lobe. The most common route of infection in AST is a congenital pyriform sinus fistula which was ruled out in our patient with direct laryngoscopy. Common presenting symptoms include fever, neck pain, and dysphagia. Pathogens commonly found to cause AST include Streptococcus and Staphylococcus. Our patient presents as an interesting case of AST from K. Pneumoniae with hematogenous spread that precipitated a thyroid storm. Thyroid storm incidence is noted to be Presentation: No date and time listed

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&rsquo, 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.

Objective: Evaluate the impact of demographic and socio-economic factors on diabetic control (Hba1c) among patients in an outpatient setting. Methods: A prospective study from January 2015 to May 2017 involving 211 patients with diabetes mellitus managed at an outpatient endocrinology clinic. Serial measurements of HbA1c were collected at baseline, 3 and 6 months. HbA1c was treated as a continuous variable and presented as mean ± standard deviation. Baseline HbA1c level was compared among dichotomized socio-economic variables (married vs. not married; employed vs. unemployed; health literacy (using the REALM survey) and educational level using t-test. A multivariable linear regression model was used to examine the association between Hb1Ac control and patient demographic and socio-economic characteristics. Results: Among study participants, 96% were African American, 63.5% female, with mean age of 53 ± 14.7) and baseline mean Hb1Ac of 8.80 ± 2.30. In univariate analysis, higher baseline Hb1Ac was observed in patients with REALM score below 7 vs. above 7, (9.30%±2.36 vs. 8.49% ± 2.27, p-value = 0.01), unemployed vs. unemployed (9.17%± 2.46 vs. 8.56%± 2.23, p-value = 0.08), and high school or lower vs. college and above (9.08% ± 2.36 vs. 8.7%± 2.28, p-value = 0.10). Single and divorced patients had higher baseline HbA1C (8.94 ± 2.4 and 8.90 ± 2.4 respectively) compared to their married counterpart (8.65%±2.4)Adjusting for baseline Hb1Ac level, gender, race marital status, employment status and educational level, multivariable regression analysis showed that higher educational level was significantly associated with change in HbA1c values. Patients with college education and above showed significant reduction in HbA1C (regression coefficient -0.75, 95% CI -1.27 to -0.230, p=0.005) compared to those with high school attainment and lower. Conclusion: In this prospective study involving predominantly African Americans, higher educational attainment was independently associated with better glycemic control. Disclosure K.M. Folawewo: None. M.U. Hodge: None. G. Nunlee-Bland: None. N. Osman: None. A. Zenebe: None. W. Odonkor: None. V. Ganta: None. R. Ogunti: None.

Hyperprolactinemia and multiple sclerosis (MS) have a direct relationship and hyperprolactinemia may precede clinical signs of MS as a heralding manifestation of disease. Prolactin has significant pro-inflammatory effects in addition to its lactotrophic properties and can also lower the body’s immune tolerance, inducing autoimmunity. High levels of prolactin have been thought to contribute to the inflammation of multiple sclerosis. However, elevated levels of prolactin, especially in pregnant women, can be protective for MS patients and induce remission. Prolactin is neuroregenerative and stimulates the precursors for oligodendrocytes, the cells responsible for myelination. Our hypothesis is that an elevated prolactin level detected during an MS flare should not be treated with dopamine agonist, but rather allowed to decrease as the MS improves with treatment. Case Presentation A 24 year old woman with a history of marijuana use is referred to our clinic for elevated prolactin levels associated with galactorrhea for 3 months duration. In addition to marijuana use, patient was also sexually active and having regular menses, with menarche at age 11 years old. On physical exam, the patient was found to have bilateral nipple discharge with stimulation, and visual fields were intact to confrontation. At the time of referral, the patient’s prolactin was 92.3 ng/dL (4.8−23.3 ng/mL) TSH was normal, and pregnancy test negative.An MRI showed multiple areas of enhancement compatible with active demyelination, concerning for multiple sclerosis. The pituitary gland was enlarged, without evidence of adenoma. A follow up prolactin level was 101 ng/dL and upon further discussion, patient also admitted to some “funny feeling” and weakness in her right hand and a feeling of being “off balance” diagnosed as a left ear infection. Patient was advised to seek urgent treatment for multiple sclerosis. She was admitted, where she was seen by neurology and diagnosed with relapsing remitting multiple sclerosis. She was initially treated with a course of IV methylprednisolone. She was discharged after this course and followed with neurology as an outpatient. For a few months our patient went into remission and her prolactin improved to 24 ng/dL. A few months later, she had a significant increase in her prolactin to 71.5 ng/dL accompanied by evidence of disease progression on MRI and symptoms of weakness and falls. Neurologists changed her medication from Copaxone to Tecfidera and patient improved clinically and has not had any further flares. Notably, she never received any dopaminergic agent to treat her prolactin level, which improved significantly.Our case illustrates that prolactin may be a disease marker in the acute phase of MS and can be restorative. Further more it will improve when the MS is treated and we should not use any dopamine agonist.

BACKGROUND: Steroid cell tumor is a rare sex cord stromal tumor. There are 3 types including steroid cell tumor not otherwise specified (NOS), stromal luteoma and leydig cell tumors. Steroid cell tumor (NOS) is the most common of all the subtypes. About 75% of the steroid cell tumor (NOS) are secretory. They can secrete androgens and estrogens. In a few cases, cortisol and renin secretion have been reported. The patient’s clinical features depend on the hormone secreted. CASE PRESENTATION Here, we report a case of a 22-year-old woman who was seen at an outpatient clinic for hirsutism, irregular menstrual bleeding, and progressive weight gain. Examination revealed androgenic facial hair growth, clitoromegaly and obesity. Initial differentials on presentation were PCOS, ovarian or adrenal pathology. Initial LH, FSH values were normal. Lab investigation showed elevated testosterone, DHEAS and 17-OH progesterone levels. Baseline labs showed Androstenedione of 3345 ng/dl (41-262 ng/dl), DHEAS of 595.5 ug/dl (110- 431.7 ug/dl), 17-OH progesterone was 2394 ng/dl (follicular: 15-70 ng/dl, Luteal: 35-290 ng/dl), total and free testosterone was 558 ng/dl (premenopausal; 10-55ng/dl) and 33.0 pg/ml, (0.8-1.4pg/ml), respectively. Patient subsequently had an ACTH stimulation test which showed an increase in 17-OH progesterone from 384 ng/dl to 657 ng/dl and a repeat showed an elevation from 204 to 322 ng/dl, ruling out a late onset CAH. She was then sent for pelvic sonogram which showed the presence of a left ovarian mass 4.9x 4.8x 4.8 cm and a pelvic CT scan confirmed a left ovarian mass measuring 6.8x5.5x 5.5 cm and an unremarkable right ovary. She underwent a laparoscopic unilateral salpino-oophorectomy and histology confirmed the diagnosis of an ovarian steroid cell tumor (NOS). Post-surgery, the androgen levels returned to normal. The patient is now being followed for recurrence. CONCLUSION Women who present with virilism should be evaluated adequately with comprehensive history taking and physical examination along with appropriate biochemical tests and imaging studies to confirm tumor location and plan for surgery.

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.

Introduction: A 200% increase in population growth among those over 85 is projected in the United States by 2050. Approximately half of women over 50 will experience an osteoporotic fracture in their lifetime. Osteoporosis disproportionately affects old-old adults (those between 85 and 95) as more than half of those admitted to the hospital for hip fracture are over 80 years of age. Older adults are also likely to need dental care. The American Dental Association guidelines offer preventive recommendations for those over 60 years of age but do not address the nuances of treatment options for nonagenarian persons. This case illustrates the treatment dilemma of nonagenarians wishing to optimize both bone and dental health. Case: We have a 95-year-old performance artist, who seeks to optimize bone health in the face of recommended dental work. She has been physically active her whole life and consumes adequate quantities of calcium and Vitamin D. She doesn’t smoke but has needed periodic glucocorticoids for exacerbations of chronic lung disease. At age 84 she began ibandronate but stopped due to worsening of esophageal reflux. She was then treated with teriparatide for 2 years. DEXA scans have shown declining hip T scores from -2.8 at age 88 to -3.5 at age 94 (osteoporotic bone density: T-score lower than -2.5). Her dentist recommended the extraction of several teeth before beginning zoledronate. She refused tooth extraction and sought treatment options to enhance her bone density. Discussion: Persons of advanced age are likely to have oral health problems requiring dental treatment. Bone health treatments such as bisphosphonates and denosumab are generally safe but can potentially cause osteonecrosis of the jaw even with simple tooth extraction in old-old population. Specific guidelines are lacking for treatment to maintain bone and dental health. The American Association of Oral and Maxillofacial Surgeons suggests that extractions and implants can be conducted as usual in patients who have been treated with oral bisphosphonates for less than four years and lack other clinical risk factors. A delay of two months is suggested for those who have been treated for more than four years or has taken glucocorticoids concomitantly. The approach is uncertain for old-old adults who are taking treatment but develop a need for dental surgery. More research is needed about options for optimizing dental health while enhancing bone density in aging population.

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.

The epidemic of type 2 diabetes mellitus (T2DM) and the possibility of it contributing to the risk of Alzheimer&rsquo, 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 &lt, 0.0001), urban vs. rural locality (p = 0.0472) and residing near industrial areas. The average HbA1c (%) level was 10.68 &plusmn, 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.

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.

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

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/m2. 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.

We have previously demonstrated that Adiponectin, leptin, TNF-alpha, and IGF-1 were highly prevalent in patients with colon adenomas when compared to healthy individuals. In the present study, we aimed to establish specific miRNA signatures in obese and diabetic African American patients developing colorectal adenomas. Patients & Methods: Serum samples from 72 individuals (18 normal, 18 adenoma-obese, 18 adenoma-diabetic, and 18 adenoma-obese-diabetic) seen at Howard University Hospital were collected. All selected patients were age and gender-matched across the 4 groups. Serum RNA extracts were used for library preparation and sequencing on an Illumina NextSeq 500 using SR75 High Output kit. Sequencing data were processed through the miasma-Seq pipeline. CutAdapt was used to trim Illumina adapters and remove reads that were less than 15 bp long. Reads were aligned to the UCSC hg38 human genome reference sequence using Bowtie2. Annotation data in the form of a GFF file from mirBase was used to count the number of reads falling in each hairpin locus. To estimate differential expression between different groups of samples, the count data were used in the DESeq2 R package and the 4 patient groups comparisons were performed. MiRNAs with statistically significant (p < 0.05) expression difference from normal and log 2 FC > 2 and/or < -2 were selected for functional analysis using Ingenuity Pathway Analysis (IPA). Results: Comparisons to normals revealed that 11 miRNAs [hsa-mir-34a, hsa-mir-133a-1, hsa-mir-127, hsa-mir-99b, hsa-mir-485, hsa-mir-378d-2, hsa-mir-3168, hsa-mir-3679, hsa-mir-378e, hsa-mir-4635, hsa-mir-6509] were down-regulated in Adenoma-Obese; 3 miRNAs were down-regulated [hsa-mir-1228, hsa-mir-3912, hsa-mir-4665] and 3 up-regulated [hsa-mir-455, hsa-mir-219b, hsa-mir-8072 ] in Adenoma-Diabetic patients; and 2 down-regulated [hsa-mir-487b, hsa-mir-6777] and 1 up-regulated miRNA [hsa-mir-4525] in Adenoma-Obese-Diabetic patients. The IPA analysis revealed that many of the altered miRNA have known roles in carcinogenic and metabolic syndrome pathways. Conclusion: From the pairwise comparison, diabetes seems to be associated with more alterations of the miRNA profile in the analyzed samples when compared to patients developing colon adenomas on an obesity background. MiRNA-4525 can be used as a potential serum marker in obese patients while miRNA-455, miRNA-219b, and miRNA-8072 can serve as such in diabetic patients. Except for miRNA-455 that was previously described as a promotor of migration and invasion in breast cancer, the other mi-RNAs are novel and their mechanisms of action need further study. Citation Format: Hassan Brim, Mohammad Daremipouran, Gail Nunlee-Bland, Adeyinka Laiyemo, Hassan Ashktorab. Serum analysis of obese and diabetic African American colon adenoma patients reveals novel potential miRNA markers of carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2578.

Background C-peptide blood levels can indicate whether or not a person is producing insulin and roughly how much. C-peptide is secreted as a byproduct of the biosynthesis of insulin from proinsulin. C-peptide has proposed biological activity and a well-established diagnostic value. The significance of C-peptide concentration in the plasma and urine in the pediatric population needs further delineation. Aim: To determine the significance of plasma C-peptide in obese African American adolescents with mild insulin resistance but no evidence of diabetes. Methods This study included 19 African American adolescents with body mass index (BMI) in at least the 85th percentile evaluated with anthropometric measurements, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) score, and oral glucose tolerance test (OGTT), and 24-hour urine collections. The study also included an age-matched control group of 15 healthy African American adolescent controls and were not subjected for OGTT. The correlation among BMI, fasting plasma C-peptide concentrations, and 24-hour-urine C-peptide concentrations was calculated, t Tests were conducted to compare plasma C-peptide and 24-hour-urine C-peptide concentrations for the test group and controls. Results Mean HOMA score (3.96 ± 1.84) signified mild insulin resistance among the adolescent test group. The test subjects exhibited adequate glucose tolerance (glucose range, 89.4-122.5 mg/dL) during the OGTT. A significant positive relationship was observed between BMI and fasting plasma C-peptide concentration in the control group ( r = 0.537) but not the test group ( r = 0.335). An insignificant positive relationship was exhibited between BMI and 24-hour-urine C-peptide concentration in the test group ( r = 0.150) and controls ( r = 0.254). Conclusions The positive relationship among BMI, plasma C-peptide, and urine C-peptide is worth further evaluation in studies conducting multiple rounds of OGTT with a larger sample of pediatric subjects. The potential diagnostic value of C-peptide may facilitate early detection of insulin resistance in the pediatric population.

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.

Current treatment of type 2 diabetes begins with diet and lifestyle modifications accompanied by use of oral antihyperglycemic medications. Despite multiple therapeutic options for people with type 2 diabetes, the disorder continues to progress, resulting in the gradual deterioration of glycemic control over time (1). This is the result of insulin resistance and progressive decline in β-cell function, combined with increased hepatic glucose output as a result of glucagon dysregulation (2). These factors lead to elevations in both fasting and prandial glucose levels. It is well known that poor glycemic control is associated with increased risk of microvascular and macrovascular complications. Ultimately, basal insulin, premixed insulin, and/or prandial insulin are added to the treatment regimen (3). The U.K. Prospective Diabetes Study and its follow-up found that patients with uncontrolled type 2 diabetes receiving intensive insulin therapy had significantly lower risks of microvascular and macrovascular complications, as well as lowered mortality rates compared to diabetes patients on standard therapy (1,4). However, intensive insulin therapy is associated with weight gain and hypoglycemia (1). A plethora of other treatment options are available for diabetes patients, many of which are either weight neutral or promote weight loss. The downside of having these additional treatment options is that the wide range of choices may present a challenge to prescribers when determining the optimal therapeutic regimen. In making these decisions, health care providers should consider patients’ disease progression state, comorbidities, and concomitant treatments (5). GLP-1 receptor agonists are one of the newer drug classes to appear on the market. These agents have been proven to be effective without increased risk of hypoglycemia or weight gain (6,7). They are ideal for patients who have had episodes of hypoglycemia on large insulin doses and for obese patients who could benefit from the …

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).Following inclusion criteria, retrospective charts of patients agedor = 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.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).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.

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.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.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.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.

J Clin Hypertens (Greenwich). 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/m2, 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

This article describes the design and implementation of an online diabetes self-management intervention for a sample of inner-city African Americans with diabetes. Study participants were randomly assigned to the treatment (26) and control (21) conditions. The results indicate that treatment group participants were more likely to achieve positive outcomes in terms of lowered hemoglobin A1c and body mass index measurements than were control group members. These findings support the development of telehealth interventions to promote effective chronic disease management in medically underserved communities.

Objective The study aim determined if low 25-hydroxy vitamin D levels correlated with low levels of adiponectin and insulin resistance in African American adolescents with body mass index > or = 85th %. Patients and methods Fasting blood levels of adiponectin, 25-hydroxy vitamin D, insulin, glucose, lipid, leptin and glycosylated hemoglobin were measured in a total of 34 (19 study and 15 control) African American adolescents between the ages of 10 and 20 years. Nutritional vitamin D intake and body composition measurements were assessed. Insulin resistance was calculated using the homeostasis model assessment. Results Adiponectin, fasting insulin, glucose, leptin, triglycerides, HDL, and 25-hydroxy vitamin D levels all reached statistical significance in the group with body mass index > or = 85th percentile when compared to the control population. There was no difference in vitamin D intake between the two groups. Conclusions Low vitamin D levels correlated with low adiponectin levels and obesity and insulin resistance.