Predictors of HbA1c among Adipocytokine Biomarkers in African-American Men with Varied Glucose Tolerance.

This study explored adipocytokine associations with acute and chronic hyperglycemia in African-American men (AAM). Fourteen adipocytokines were measured from men with normal glucose tolerance (NGT) or type 2 diabetes (T2D, drug-naïve MF(-) or using metformin MF(+)). Acute and chronic hyperglycemia were evaluated by 120 min oral glucose tolerance test (OGTT) and glycohemoglobin A1c (HbA1c). AAM with T2D (n = 21) compared to NGT (n = 20) were older, had higher BMI and slightly higher glucose and insulin. In the fasted state, TNF-α, IL-6, PAI-1, IL-13, adiponectin, adipsin, and lipocalin were lower in T2D vs. NGT. At 120 min post-glucose load, TNF-α, IL-6, IL-13, IL-8, PAI-1, adiponectin, adipsin, lipocalin, and resistin were lower in T2D vs. NGT. There were no statistical differences for GM-CSF, IL-7, IL-10, IP-10, and MCP-1. Regression analysis showed that fasting IL-8, TNF-α, adiponectin, lipocalin, resistin, adipsin, and PAI-1 were associated with HbA1c. After adjusting for age, BMI, glucose tolerance, and metformin use, only adipsin remained significantly associated with HbA1c (p = 0.021). The model including adipsin, TNF-α, age, BMI, and group designation (i.e., NGT, MF(-), MF(+)) explained 86% of HbA1c variability. The data suggested that adipsin could be associated with HbA1c in AAM with varied glucose tolerance.

Gut microbiota varies by opioid use, circulating leptin and oxytocin in African American men with diabetes and high burden of chronic disease.

OBJECTIVE: The gut microbiota is known to be related to type 2 diabetes (T2D), psychiatric conditions, and opioid use. In this study, we tested the hypothesis that variability in gut microbiota in T2D is associated with psycho-metabolic health. METHODS: A cross-sectional study was conducted among African American men (AAM) (n = 99) that were outpatients at a Chicago VA Medical Center. The main outcome measures included fecal microbiota ecology (by 16S rRNA gene sequencing), psychiatric disorders including opioid use, and circulating leptin and oxytocin as representative hormone biomarkers for obesity and psychological pro-social behavior. RESULTS: The study subjects had prevalent overweight/obesity (78%), T2D (50%) and co-morbid psychiatric (65%) and opioid use (45%) disorders. In the analysis of microbiota, the data showed interactions of opioids, T2D and metformin with Bifidobacterium and Prevotella genera. The differential analysis of Bifidobacterium stratified by opioids, T2D and metformin, showed significant interactions among these factors indicating that the effect of one factor was changed by the other (FDR-adjusted p [q] < 0.01). In addition, the pair-wise comparison showed that participants with T2D not taking metformin had a significant 6.74 log2 fold increase in Bifidobacterium in opioid users as compared to non-users (q = 2.2 x 10-8). Since metformin was not included in this pair-wise comparison, the significant 'q' suggested association of opioid use with Bifidobacterium abundance. The differences in Bifidobacterium abundance could possibly be explained by opioids acting as organic cation transporter 1 (OCT1) inhibitors. Analysis stratified by lower and higher leptin and oxytocin (divided by the 50th percentile) in the subgroup without T2D showed lower Dialister in High-Leptin vs. Low-Leptin (p = 0.03). Contrary, the opposite was shown for oxytocin, higher Dialister in High-Oxytocin vs. Low-Oxytocin (p = 0.04). CONCLUSIONS: The study demonstrated for the first time that Bifidobacterium and Prevotella abundance was affected by interactions of T2D, metformin and opioid use. Also, in subjects without T2D Dialister abundance varied according to circulating leptin and oxytocin.

Oxytocin is lower in African American men with diabetes and associates with psycho-social and metabolic health factors.

OBJECTIVE: Recently, it has been suggested that oxytocin (OT) has a role in metabolism and neuropsychiatry health and disease, and therefore, it may represent a potential therapeutic target. The current study aimed to investigate relationships between OT and glycemic status along with psycho-social and behavioral factors. DESIGN AND METHODS: A total of 92 obese or overweight, African American, male subjects were enrolled in the study. Biometric and biochemical data were collected including oral glucose tolerance testing and urinary OT (measured by ELISA). Subjects also completed questionnaires on social and lifestyle factors. RESULTS: OT levels were found to be significantly lower in subjects with type 2 diabetes mellitus (T2DM) compared to normal glucose tolerance (p<0.05). When stratified by OT tertiles, subjects with higher OT had lower weight, body mass index (BMI) and hemoglobin A1c, but higher eGFR which remained significant after BMI adjustment. The highest OT tertile also had more smokers and more users of psychiatric medications. A stepwise ordered logistic regression supported these findings and could account for 21% of the variation in OT categories (pseudoR2 = 0.21). CONCLUSIONS: In this unique population, OT was found lower in subjects with diabetes but higher with better renal function, cigarette smoking and use of psychiatric medications. Future studies are needed to confirm these findings and examine the potential therapeutic role of OT.

EFFECT OF HIGH-DOSE VITAMIN D REPLETION ON GLYCEMIC CONTROL IN AFRICAN-AMERICAN MALES WITH PREDIABETES AND HYPOVITAMINOSIS D.

OBJECTIVE: This double-blind, randomized, controlled trial evaluated whether 12 months of high-dose vitamin D2 supplementation improved insulin sensitivity and secretion and glycemic status. METHODS: African-American males (AAM) with prediabetes (glycosylated hemoglobin [A1C] 5.7-6.4%), hypovitaminosis D (25-hydroxyvitamin D [25OHD] 5-29 ng/mL), and prevalent medical problems were supplemented with vitamin D3 (400 IU/day) and then randomized to weekly placebo or vitamin D2 (50,000 IU). The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from an oral glucose tolerance test [OGTT]) after 12 months of treatment. Secondary outcomes included other glycemic indices, A1C, and incident diabetes. RESULTS: Baseline characteristics were similar in vitamin D-supplemented (n = 87) and placebo (n = 86) subjects completing the trial with average concentrations 14.4 ng/mL, 362 mL × min(-1) × m(-2), and 6.1% for 25OHD, OGIS and A1C, respectively. After 12 months, the vitamin D-supplemented group had a change in serum 25OHD +35 versus +6 ng/mL for placebo, P<.001; OGIS +7.8 versus -16.0 mL × min(-1) × m(-2) for placebo, P = .026; and A1C -0.01 versus +0.01% for placebo, P = .66. Ten percent of subjects in both groups progressed to diabetes. A posthoc analysis of participants with baseline impaired fasting glucose (IFG) showed that more subjects in the vitamin D subgroup (31.6%) than placebo (8.3%) returned to normal glucose tolerance, but the difference did not reach significance (P = .13). CONCLUSION: The trial does not provide evidence that 12 months of high-dose D2 repletion improves clinically relevant glycemic outcomes in subjects with prediabetes and hypovitaminosis D (NCT01375660).