Prediabetes is an incremental risk factor for adverse cardiac events: A nationwide analysis.

Background and aims: Prediabetes is defined as a state of impaired glucose metabolism with hemoglobin A1c (HbA1c) levels that precede those of a diabetic state. There is increasing evidence that suggests that hyperglycemic derangement in prediabetes leads to microvascular and macrovascular complications even before progression to overt diabetes mellitus. We aim to identify the association of prediabetes with acute cardiovascular events. Methods: We utilized the National inpatient sample 2018-2020 to identify adult hospitalizations with prediabetes after excluding all hospitalizations with diabetes. Demographics and prevalence of other cardiovascular risk factors were compared in hospitalizations with and without prediabetes using the chi-square test for categorical variables and the t-test for continuous variables. Multivariate regression analysis was further performed to study the impact of prediabetes on acute coronary syndrome, acute ischemic stroke, intracranial hemorrhage, and acute heart failure. Results: Hospitalizations with prediabetes had a higher prevalence of cardiovascular risk factors like hypertension, hyperlipidemia, obesity, and tobacco abuse. In addition, the adjusted analysis revealed that hospitalizations with prediabetes were associated with higher odds of developing acute coronary syndrome (OR-2.01; C.I:1.94-2.08; P<0.001), acute ischemic stroke (OR-2.21; 2.11-2.31; p<0.001), and acute heart failure (OR-1.41; C.I.: 1.29-1.55; p<0.001) as compared to hospitalizations without prediabetes. Conclusions: Our study suggests that prediabetes is associated with a higher odds of major cardiovascular events. Further prospective studies should be conducted to identify prediabetes as an independent causative factor for these events. In addition, screening and lifestyle modifications for prediabetics should be encouraged to improve patient outcomes.

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.

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.

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.

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.

Vitamin D deficiency and insulin resistance in obese African-American adolescents.

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.

Significance of plasma C-peptide in obese African American adolescents.

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.

Decreased total carbonic anhydrase esterase activity and decreased levels of carbonic anhydrase 1 isozyme in erythrocytes of type II diabetic patients.

In this exploratory study, we investigated total erythrocyte carbonic anhydrase (CA) estrase activity as well as CA I isozyme concentration in patients with diabetes mellitus type II (DM) and healthy individuals of Howard University Hospital community. Total estrase activity of CA was measured spectrophotometrically using p-nitrophenol acetate before and after inhibition with acetazolamide. CA I isozyme was measured by radial immunodiffusion using monoclonal antibody (CA I) in agarose plates. The study involved 20 consented participants; 10 normal (N) and 10 (DM), 21 to 84 years of age. The study was approved by the Howard University Institution Review Board. The CA activity was measured following lysis of cells as U/min/mL and CA I concentration as mg/l. We observed CA activity as 46.3+/-4(N) and 25+/-2.1 (DM) whereas CA I concentration as 1896+/-125 (N) and 1104 +/-63 (DM). We speculate that the change in the CA activity may of fundamental importance in the regulation of intracellular; pH(i) for the basic control of metabolism in diabetes mellitus. Further, we propose that CA activity is a good candidate for a biomarker of diabetes mellitus for the early detection of insulin resistance because the CA activity variation was proportional to the severity of the diabetes.