Prediabetic Research Articles

A-035 Profiling of circulating-microRNAs' signatures in Pre-diabetic versus Diabetic patients

Abstract Background MicroRNAs (miRs) are small non-coding RNAs involved in the process of gene regulation, and hence affect various diseases including metabolic pathways in diabetes. Given their key roles, they are promising candidates as potential biomarkers or better understanding of disease etiology. In this study, our aim is to identify miRs signatures of plasma circulating-miRs related to glycemic control, vitamin D deficiency and platelet activation in diabetic, pre-diabetic versus non-diabetic patients. Methods Plasma samples were collected from 24 patients (both sexes) in total (eight non-diabetic (ND) control, twelve diabetic (DM), and four pre-diabetic (PD)), classified based on their glycemic control (HbA1c levels). miRs were extracted using the miRNeasy Serum/Plasma Advanced kit of Qiagen, run and analyzed on Next Generation Sequencing (NGS). Results Differential expression analysis revealed miRs expression variations between diabetic to pre-diabetic and non-diabetic groups. Expression levels of 131 miRs varied significantly between DM to ND group (92 down- and 39 up- regulated), and 141 miRs in PD compared to ND (97 down- and 39 up- regulated). Although DM and PD had similar differential expression, three miRs (has-miR4776-5p, -6778-3p, and 5002-3p) were over-expressed in PD with very low p-value. Differential expression comparisons accounting sex were performed showing significant differences between males to females that will be presented here. Conclusions Our findings supports the important involvement of circulating miRs in the regulation of glucose homeostasis and pathogenesis of diabetes.Further investigation of candidate miRs could identify promising new biomarkers for the early diagnosis and prevention of Diabetes and related health complications.

Effects of Gossypetin on Glucose Homeostasis in Diet-Induced Pre-Diabetic Rats.

Natural flavonoids exert many potential health benefits, including anti-hyperglycaemic effects. However, the effects of gossypetin (GTIN) on glucose homeostasis in pre-diabetes have not yet been investigated. This study examined the effects of GTIN on key markers of glucose homeostasis in a diet-induced pre-diabetic rat model. Pre-diabetes was induced by allowing the animals to feed on a high-fat high-carbohydrate (HFHC) diet supplemented with 15% fructose water for 20 weeks. Following pre-diabetes induction, the pre-diabetic animals were sub-divided into five groups (n = 6), where they were either orally treated with GTIN (15 mg/kg) or metformin (MET) (500 mg/kg), both with and without dietary intervention, over a 12-week period. The results demonstrated that animals in the untreated pre-diabetic (PD) control group exhibited significantly higher fasting and postprandial blood glucose levels, as well as elevated plasma insulin concentrations and increased homeostatic model assessment for insulin resistance (HOMA2-IR) index, relative to the non-pre-diabetic (NPD) group. Similarly, increased caloric intake, body weight and plasma ghrelin levels were observed in the PD control group. Notably, these parameters were significantly reduced in the PD animals receiving GTIN treatment. Additionally, glycogen levels in the liver and skeletal muscle, which were disturbed in the PD control group, showed significant improvement in both GTIN-treated groups. These findings may suggest that GTIN administration, with or without dietary modifications, may offer therapeutic benefits in ameliorating glucose homeostasis disturbances associated with the PD state.

Pregestational Prediabetes Induces Maternal Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation and Results in Adverse Foetal Outcomes.

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats.

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6-6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM.

Evaluation of Anemia Effect on HbA1c Level Measurement in Type 2 Diabetic People


 
 
 Objective: For many years HbA1c used as diagnostic criteria for diabetes, however, measurement of HbA1 has some limitations that cannot be accurately assess blood glucose levels in conditions such as changes in red blood cell life. in this study, we evaluated and compared the levels of HbA1C in diabetic, pre-diabetic and non- diabetic individuals to understand the role and relationship of different values of RBC`s indices in these conditions.
 Materials and Methods: This study performed between august to December of year 2021, and the demographic information and hematologic indices of 706 individuals which referred to laboratories in Gorgan city were investigated. According to results of FBS and HbA1c, individuals categorized in three distinct healthy (H), pre-diabetic (PD), and diabetic (D) groups base on latest ADA criteria.
 Results: Evaluation of HbA1c level based on the presence or absence of anemia showed that in diabetic group with anemia significantly had a lower level 8.4 (± 1.5) than people without anemia 8.6 (± 1.5) (P= 0.045). Conclusion: In this study, it was shown that changes in RBC indices in anemia can lead to inaccurate measurement of HbA1c level.
 
 

Investigation into changes in inflammatory and immune cell markers in pre-diabetic patients from Durban, South Africa

The prevalence of pre-diabetes is increasing in rapidly urbanizing cities, especially in individuals aged 25 − 45 years old. Studies also indicate that this condition is associated with aberrant immune responses that are also influenced by environmental factors. This study sought to investigate changes in the concentration of immune cells and select inflammatory markers in patients with pre-diabetes in Durban, South Africa. Blood samples collected from King Edward Hospital, after obtaining ethics approval, were divided into non-diabetic (ND), pre-diabetic (PD) and type 2 diabetic (T2D) using ADA criteria. In each sample, the concentration of immune cells and select inflammatory markers were determined. The results showed a significant increase in eosinophil and basophil levels in the PD group as compared to the ND group. Compared to ND, the PD and T2D groups had significant increases in serum TNFα, CD40L and fibrinogen concentrations. Additionally, there were decreases in serum CRP, IL-6, and P-selectin in the PD group while these markers increased in the T2D group. These findings were indicative of immune activation and highlight the impact of pre-diabetes in this population. More studies are recommended with a higher number of samples that are stratified by gender and represent the gender ratio in the city.

High-fat, high-carbohydrate diet-induced prediabetes preconception in Sprague-Dawley rats as a risk factor for the development of preeclampsia: assessing changes in placental metabolic insults.

Hyperglycemia preconception deranges the establishment of a functional placenta; however, the risk of developing preeclampsia (PE) in prediabetic patients remains obscure. The aim was to assess abnormal placental changes as a risk factor for the development of PE in high-fat, high-carbohydrate (HFHC) diet-induced prediabetic (PD) rats. HFHC diet-induced female prediabetic Sprague-Dawley rats were mated, and blood glucose concentrations, mean arterial pressure (MAP), and body weights were monitored on gestational days (GNDs) 0, 9, and 18. On GND 18, animals were euthanized. Blood and placentas were collected for biochemical analysis. Prediabetic rats showed significantly increased blood glucose concentration, proinflammatory cytokines, MAP, placental weight, and fetoplacental ratio compared with non-prediabetic (NPD) rats. Prediabetic rats showed significantly decreased placental vascular endothelial growth factor receptor 1 (VEGFR1) and placental growth factor (PLGF) and plasma nitric oxide (NO) compared with NPD. Prediabetes may have promoted endothelial dysfunction in the placenta and hypoxia, thus reducing PLGF and VEGFR1, which may have promoted proinflammation, endothelial dysfunction associated with NO decline, and hypertension, which is also observed in preeclamptic patients. Prediabetes may have promoted lipogenesis in placentas and fetuses that may have induced macrosomia and IUGR, also observed in preeclamptic patients. The findings from this study highlight the need for screening and monitoring of prediabetes during pregnancy to reduce the risk of developing preeclampsia.

Association between Altered Thyroid Function and Prediabetes in Diet-Induced Prediabetic Male Sprague Dawley Rats

There is a correlation between the existence of type 2 diabetes mellitus (T2DM) and the development of thyroid disorders. Prediabetes is a progressive state of moderate insulin resistance that often precedes the onset of T2DM. However, the association between prediabetes and thyroid function is unknown. This study assessed changes in markers of thyroid function in diet-induced prediabetes. Twelve male Sprague Dawley rats (n = 12) were randomly assigned into two groups. Rats in the non-prediabetic (NPD) group were fed a standard rat diet, while rats in the prediabetic (PD) were fed a high-fat high-carbohydrate diet for 20 weeks to induce prediabetes. Thereafter, fasting blood glucose levels were measured. Plasma samples were assessed for triiodothyronine (T3), thyroxine (T4), thyroxine peroxidase (TPO) antibody, insulin, and glycated hemoglobin (HbA1c) concentrations. The elevated blood glucose, HbA1c, and plasma insulin levels coincided with increased T3 and reduced T4 levels in the PD group when compared to the NPD group. There was also an increase in the concentration of TPO antibodies in the PD group. Additionally, there was a significant correlation between the thyroid hormone concentrations and HbA1c levels. In conclusion, these results indicated that there is a positive association between thyroid dysfunction and diet-induced prediabetes in rats.

17β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation of Mesenteric Arteries in Ovariectomized UC Davis Type 2 Diabetes Mellitus Rats in Prediabetic State.

We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhibited a greater vascular dysfunction than males. Thus, the aim of this study was to investigate whether the female sex hormone, estrogen preserves mesenteric arterial vasorelaxation in UCD-T2DM female rats at an early prediabetic state. Age-matched female Sprague Dawley and prediabetic (PD) UCD-T2DM rats were ovariectomized (OVX) and subcutaneously implanted with either placebo or 17β-estradiol (E2, 1.5 mg) pellets for 45 days. We assessed the contribution of endothelium-derived relaxing factors (EDRF) to acetylcholine (ACh)-induced vasorelaxation, using pharmacological inhibitors. Responses to sodium nitroprusside (SNP) and phenylephrine (PE) were also measured. Additionally, metabolic parameters and expression of some targets associated with vascular and insulin signaling were determined. We demonstrated that the responses to ACh and SNP were severely impaired in the prediabetic state (PD OVX) rats, while E2 treatment restored vasorelaxation in the PD OVX + E2. Moreover, the responses to PE was significantly enhanced in MA of PD OVX groups, regardless of placebo or E2 treatment. Overall, our data suggest that 1) the impairment of ACh responses in PD OVX rats may, in part, result from the elevated contractile responses to PE, loss of contribution of endothelium-dependent hyperpolarization (EDH) to vasorelaxation, and a decreased sensitivity of MA to nitric oxide (NO), and 2) the basis for the protective effects of E2 may be partly attributed to the elevation of the NO contribution to vasorelaxation and its interaction with MA as well as potential improvement of insulin signaling. Here, we provide the first evidence of the role of E2 in protecting MA from early vascular dysfunction in prediabetic female rats.

PRE DIABETES IN YOUNG MEDICAL STUDENTS

Abstract Introduction: A study was conducted among students of a public medical college in Lahore, Pakistan to determine proportion of pre diabetic students (Blood sugar levels between 100 mg/dl - 125 mg/dl, accord- Waseem M.1 Fourth Year MBBS Student Sheikh Khalifa Bin Zayed Al-Nahyan Medical College, Lahore Bokhari F.A.2 Assistant Professor, Department of Physiology, Sheikh Khalifa Bin Zayed Al-Nahyan Medical College, Lahore Jalal M.A.3 Fourth Year MBBS Student Sheikh Khalifa Bin Zayed Al-Nahyan Medical College, Lahore Zahra Z.4 Fourth Year MBBS Student Sheikh Khalifa Bin Zayed Al-Nahyan Medical College, Lahore Khalid M.5 Fourth Year MBBS Student Sheikh Khalifa Bin Zayed Al-Nahyan Medical College, Lahore Aman M.6 Fourth Year MBBS Student Sheikh Khalifa Bin Zayed Al-Nahyan Medical College, Lahore ing to American Diabetes Association) and its relation with body mass index, family history of Diabetes, die-tary habits, socioeconomic status and physical activity. Methods: A cross sectional survey was conducted at Sheikh Zayed Medical Complex in February 2013 on medical students of either gender. Data was collected on a validated questionnaire. Fasting blood sugar lev-els of 65 students (enrolled after taking informed con-sent) were taken by trained co investigators through standardized glucose meter. Results: A total of 65 medical students (43 males and 22 females) enrolled in this study. Their ages ranged from 18 to 23 years (mean age 20.56 ± 0.97 years). No student was found to be pre diabetic. Fasting blood sugar level in male participant with a family historyof diabetes was significantly higher (85 ± 6.228 vs. 79.857 ± 6.602, P = 0.016). Conclusion: In this study, no student was found to be pre diabetic, though male participants with a family history of diabetes had higher fasting blood sugar levels. However, a larger study sample is required so that any significant finding may be shown, if it exists. Data on prevalence of pre-dia-betes in youth in South Asia is scarce. The high incidence of diabetes in developing countries un-derlines the need to explore prevalence of pre dia-betes in the younger population. Key Words: Pre diabetes, Impaired Fasting Glucose (IFG).

Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients.

Diabetes has become a major public health concern worldwide, most of which are type 2 diabetes (T2D). The diagnosis of T2D is commonly based on plasma glucose levels, and there are no reliable clinical biomarkers available for early detection. Recent advances in proteome technologies offer new opportunity for the understanding of T2D; however, the underlying proteomic characteristics of T2D have not been thoroughly investigated yet. Here, using proteomic and glycoproteomic profiling, we provided a comprehensive landscape of molecular alterations in the fasting plasma of the 24 Chinese participants, including eight T2D patients, eight prediabetic (PDB) subjects, and eight healthy control (HC) individuals. Our analyses identified a diverse set of potential biomarkers that might enhance the efficiency and accuracy based on current existing biological indicators of (pre)diabetes. Through integrative omics analysis, we showed the capability of glycoproteomics as a complement to proteomics or metabolomics, to provide additional insights into the pathogenesis of (pre)diabetes. We have newly identified systemic site-specific N-glycosylation alterations underlying T2D patients in the complement activation pathways, including decreased levels of N-glycopeptides from C1s, MASP1, and CFP proteins, and increased levels of N-glycopeptides from C2, C4, C4BPA, C4BPB, and CFH. These alterations were not observed at proteomic levels, suggesting new opportunities for the diagnosis and treatment of this disease. Our results demonstrate a great potential role of glycoproteomics in understanding (pre)diabetes and present a new direction for diabetes research which deserves more attention.

Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity.

Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose of this study was to investigate the impact of T2D on the pancreatic fat depot. Pancreatic fat pads from 17 partial pancreatectomized patients (PPP) were collected, pancreatic preadipocytes isolated, and in vitro differentiated. Patients were grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD), and T2D. Transcriptome profiles of preadipocytes and adipocytes were assessed by RNAseq. Insulin sensitivity was estimated by quantifying AKT phosphorylation on Western blots. Lipogenic capacity was assessed with oil red O staining, lipolytic activity via fatty acid release. Secreted factors were measured using ELISA. Comparative transcriptome analysis of preadipocytes and adipocytes indicates defective upregulation of genes governing adipogenesis (NR1H3), lipogenesis (FASN, SCD, ELOVL6, and FADS1), and lipolysis (LIPE) during differentiation of cells from T2D-PPP. In addition, the ratio of leptin/adiponectin mRNA was higher in T2D than in NGT-PPP. Preadipocytes and adipocytes of NGT-PPP were more insulin sensitive than T2D-PPP cells in regard to AKT phosphorylation. Triglyceride accumulation was similar in NGT and T2D adipocytes. Despite a high expression of the receptors NPR1 and NPR2 in NGT and T2D adipocytes, lipolysis was stimulated by ANP 1.74-fold in NGT cells only. This stimulation was further increased by the PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole and forskolin increased lipolysis receptor independently 1.88-fold and 1.48-fold, respectively, solely in NGT cells. In conclusion, the metabolic status persistently affects differentiation and lipolysis of pancreatic adipocytes. These alterations could aggravate the development of T2D.

Oxygen-18 and carbon-13 isotopes in eCO2 and erythrocytes carbonic anhydrase activity of Finnish prediabetic population

Complex human physiological processes create the stable isotopic composition of exhaled carbon dioxide (eCO2), measurable with noninvasive breath tests. Recently, isotope-selective breath tests utilizing natural fluctuation in 18O/16O isotope ratio in eCO2 have been proposed for screening prediabetic (PD) individuals. It has been suggested that 18O/16O fractionation patterns reflect shifts in the activity of carbonic anhydrase (CA), an enzyme involved in the metabolic changes in the PD state. To evaluate the applicability of the breath sampling method in Finnish PD individuals, breath delta values (BDVs, ‰) of 18O/16O (δ 18O) were monitored for 120 min in real-time with a high-precision optical isotope ratio spectrometer, both in the fasting state and during a 2 h oral glucose tolerance test (2 h OGTT) with non-labeled glucose. In addition, the BDV of 13C/12C (δ 13C) was measured, and total erythrocyte CA activity was determined. δ 18O and CA did not demonstrate any statistically significant differences between PD and non-diabetic control (NDC) participants. Instead, δ 13C was significantly lower in PD patients in comparison to NDCs in the fasting state and at time points 90 and 120 min of the 2 h OGTT, thus indicating slightly better potential in identifying Finnish PD individuals. However, overlapping values were measured in PD participants and NDCs, and therefore, δ 13C cannot be applied as a sole measure in screening prediabetes at an individual level. Thus, because the combination of environmental and lifestyle factors and anthropometric parameters has a greater effect on glucose metabolism and CA activity in comparison to the PD state, 18O/16O and 13C/12C fractionations or CA activity did not prove to be reliable biomarkers for impaired glucose tolerance in Finnish subjects.This study was conducted under the clinicaltrials.gov ID NCT03156478.

Biochemical evaluation of vitamin D levels in pre diabetes, type 2 diabetes mellitus and its correlation with glycated hemoglobin

Introduction: Globally, 1 billion people are suffering with deficiency or insufficiency of vitamin D. Vitamin D deficiency is also associated with metabolic disorders. This study evaluates Vitamin D levels in prediabetes, T2DM patients and its correlation with HbA1c. Materials and Methods: This study was done in Department of Physiology in association with Department of Endocrinology, JNU Institute of Medical Sciences & Research Center, Jaipur. A total of 155 subjected were enrolled into the study. They were divided into three groups, 65 age and gender matched healthy subjects were taken as group I (controls) (HbA1c: 5.5 to 6.5 %), 45 prediabetic subjects were taken as group II (HbA1c: 6.5 to 7.5 %) and 45 T2DM subjects were taken as group III (HbA1c: >7.5%). Age of the study subjects was 45 to 65 years. Serum sample was used for the estimation of random sugar (GOD-POD method) by using ERBA chemistry analyzer, vitamin D by ELISA method, using mini VIDAS and EDTA sample for HbA1c by using BIORAD D10. Results: In this study, random blood sugar and HbA1c levels were significantly elevated in pre diabetic (group II), T2DM (group III) subjects compared with controls (group I). Significant reduction was observed in prediabetic, T2DM subjects compared to controls in respect to vitamin D levels. Negative correlation was observed between HbA1c and vitamin D. Conclusion: In conclusion, the results of this study showed, significant reduction and negative correlation between serum vitamin D levels and HbA1c in prediabetic and T2DM patients. This study results indicates that there may be need to screen pre diabetic and T2DM patients with poor glycemic control for Vitamin D status. Keywords: Glycated hemoglobin, Glycemic control, T2DM, Vitamin D deficiency.

Abstract PO-183: Pre-diabetes, diabetes and the risk for adenoma detection

Abstract Background U.S Multi-Society Task Force of Colorectal Cancer (MSTF) has suggested that screening begin at a younger age in Blacks to detect precancerous adenomas. Our group conducted a multi-institution retrospective study of clinical data collected in 2012 to identify biological factors associated with adenoma detection. However, the results of the investigation revealed that the included Urban Safety Net Hospital (USNH) had a relatively lower adenoma detection rate (ADR) that may have confounded other analysis in the study. After successful initiatives to improve ADR, this interim study compares the incidence of adenomas in non-diabetic (ND), pre- diabetic (PD) and Type II diabetic (T2DM) categories. Methods This study is a retrospective analysis of prospectively collected data from January 2017 to June 2018. Chart review was used to build a registry of subjects within ages 45 - 75 years old that completed an initial screening colonoscopy. Subjects at high risk for adenoma or colorectal cancer (hereditary syndromes, inflammatory bowel disease), symptomatic presentation, poor bowel prep, or incomplete colonoscopy were excluded from the study. ND, PD and T2DM groups were established by clinical diagnosis or HgbA1c levels according to American Diabetes Association guidelines. 12 Subjects with an unknown diabetes status were also excluded from this analysis. Chi- square analysis was performed to determine significance at a threshold of p ≤ 0.05 for unadjusted p-values. Preliminary Results As shown in Table 1, 248 patients met the inclusion criteria. 94% of patients identified as Black or African American, <1 % as Caucasian and 5% declined to identify with a race or was left unknown. 94 and 89 out of 248 subjects had pre-diabetes or diabetes, respectively. The overall adenoma detection rate is at 29%. The percentage of detected adenomas in the ND, PD and T2DM group were 22%, 33%, and 29% respectively. Discussion As evidence by an ADR of 29%, preliminary data from 2017 shows quality improvement in colonoscopies performed at this USNH. In this cohort that is 94% Black, the incidence of T2DM and PD is higher than the CDC’s national averages for individuals ≥ 45 years old. 62% of this population sample are diabetic or pre-diabetic. At a sample size of 284 subjects, this ongoing study is underpowered and cannot yet conclude an association between a diagnosis of PD, T2DM, and the incidence of adenomas. However, there is a trend that shows that a higher proportion of adenomas are in the PD and the T2DM groups in comparison to the ND group. The relatively high proportion of adenomas in the PD group suggests that the associated risk for colorectal cancer may occur prior to diagnosis with T2DM. Citation Format: Dimitri F. Joseph, Ellen Li, Laura Martello-Rooney, Michelle Follen, Evan Grossman. Pre-diabetes, diabetes and the risk for adenoma detection [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-183.

Identification of circulatory miRNAs as candidate biomarkers in prediabetes - A systematic review and bioinformatics analysis

Circulatory miRNAs (micro ribo nucleic acid) have been identified as potential biomarker in diabetes mellitus and a few studies have shown its role in pre diabetic conditions. A systematic review would give a lead to identify and shortlist miRNAs as biomarkers in pre diabetes. Following stringent inclusive and exclusive criteria based on Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, we have included 24 potential studies for this systematic review and bioinformatics analysis of miRNAs in pre diabetes. Basic study characteristics, expression levels of miRNAs and methods of study were extracted manually. miRNAs showing constitutively dysregulated expression in at least two studies in same direction were included for further pathway analysis using miRpath analysis. There were 56 miRNAs showing dysregulated expression across pre diabetic patients. Among these, 11 miRNAs were shortlisted as potential biomarkers in pre diabetes condition. These miRNA were associated mainly with pathways including lipid metabolisms. Clinical utility of these shortlisted miRNAs should be validated with larger cohorts.

The effects of exercise treatment on learning and memory ability, and cognitive performance in diet-induced prediabetes animals

Changes associated with cognitive function in the high-fat high-carbohydrate diet-induced prediabetes animal model and effect of exercise remain unclear. Rats were randomly assigned to the following groups (n = 6): non-diabetic (ND), prediabetic (PD), intermittent exercising PD (PD + IE) and regular exercising PD (PD + RE). After exercise cessation, oral glucose tolerance (OGT), Novel Object Recognition Test (NORT) and Morris-Water Maze (MWM) tests were performed to assess cognitive function. After sacrifice, malonaldehyde, glutathione peroxidase, interleukin-1β and dopamine concentration in the prefrontal cortex (PFC) and hippocampus were measured. Impaired OGT response in PD animals was accompanied by poor performance on behavioural tasks. This was associated with increased oxidative stress markers and impaired dopamine neurotransmission as evidence by elevated dopamine concentration in the PFC and hippocampal tissue. Improved OGT response by exercise was coupled with improved performance on behavioural tasks, oxidative stress markers and increased interleukin-1β concentration. In regular exercise, this was further coupled with improved dopamine neurotransmission. Cognitive function was affected during prediabetes in animals. This was partly due to oxidative stress and impaired dopamine neurotransmission. Both intermittent and regular exercise improved cognitive function. This was partly mediated by improved glucose tolerance and oxidative stress as well as a subclinical increase in interleukin-1β concentration. In regular exercise, this was further mediated by improved dopamine neurotransmission.

Assessing Risk for Mortality in Trauma: The Value of Admission Hemoglobin A1c

Recent efforts have been made to identify admission characteristics of trauma patients that are associated with increased risk of mortality. Contemporary literature has established an increased risk of mortality with admission hyperglycemia. However, the effects of longstanding hyperglycemia, as surrogated by hemoglobin A1c (HbA1c), has not been studied. A prospective trauma database was retrospectively reviewed identifying patients with collected HbA1c at admission. Three cohorts were defined by HbA1c: normal (N), <5.7; prediabetic (PD) 5.7-6.5; and diabetic (D) >6.5. Regression models were used to evaluate the risk of increased hospital and intensive care unit (ICU) length of stay (LOS), ventilator days, and mortality. Relative risk (RR) and 95% CI are provided as measures of significance. A total of 2978 patients were included in the analysis (N: n = 1895, PD: n = 744, and D: n = 339). The D cohort was more likely to be older, female, obese, suffered blunt trauma, and triaged at the highest activation acuity level (P < .0001). Mean injury severity score (ISS) was similar between groups. The D group was more likely to have longer ICU-LOS (RR 1.5; 95% CI 1.10-2.07) and ventilator days (RR 1.52; 95% CI 1.03-2.26) than the N group. Relative to the N group, the risk of mortality was 50% higher in the PD (RR 1.49; 95% CI 1.17-1.90) and in the D cohorts (RR 1.50; 95% CI 1.03-2.18). Trauma patients with an elevated admission HbA1c have a significantly higher risk of mortality regardless of their history of diabetes. These data add to the body of literature that documents the untoward effect of hyperglycemia on the trauma patient.

Prediabetes uncovers differential gene expression at fasting and in response to oral glucose load in immune cells

Metabolic disorders including diabetes are associated with immune cell dysfunction. However, the effect of normal glucose metabolism or impairment thereof on immune cell gene expression is not well known. Hence, in this cross-sectional pilot study, we sought to determine the differences in gene expression in the peripheral blood mono-nuclear cells (PBMCs) of normal glucose tolerant (NGT) and prediabetic (PD) Asian Indian men, at fasting and in response to 75g oral glucose load. Illumina HT12 bead chip-based microarray was performed on PBMCs at fasting and 2-h post load conditions for NGT (N=6) and PD (N=9) subjects. Following normalization and due quality control of the raw data, differentially expressed genes (DEGs) under different conditions within and across the two groups were identified using GeneSpring GX V12.0 software. Paired and unpaired Student's t-tests were applied along with fold change cut-offs for appropriate comparisons. Validation of the microarray data was carried out through real-time qPCR analysis. Significantly regulated biological pathways were analyzed by employing DEGs and DAVID resource. Deconvolution of the DEGs between NGT and PD subjects at fasting was performed using CIBERSORT and genes involved in regulatory T-cell (Treg) function were further analyzed for biological significance. Glucose load specifically altered the expression of 112 genes in NGT and 356 genes in PD subjects. Biological significance analysis revealed transient up-regulation of innate and adaptive immune response related genes following oral glucose load in NGT individuals, which was not observed in PD subjects. Instead, in the PD group, glucose load led to an increase in the expression of pro-atherogenic and anti-angiogenic genes. Comparison of gene expression at fasting state in PD versus NGT revealed 21,707 differentially expressed genes. Biological significance analysis of the immune function related genes between these two groups (at fasting) revealed higher gene expression of members of the TLR signaling, MHC class II molecules, and T-cell receptor, chemotaxis and adhesion pathways in PD subjects. Expression of interferon-γ (IFN-γ) and TNFα was higher and that of type-1 interferons and TGF-β was lower at fasting state in PD subjects compared to NGT. Additionally, expression of multiple proteasome subunits and protein arginine methyl transferase genes (PRMTs) were higher and that of Treg specific genes was significantly distinct at fasting in PD subjects compared to NGT. Prediabetes uncovers constitutive TLR activation, enhanced IFN-γ signaling, and Treg dysfunction at fasting along with altered gene expression response to oral glucose load.

Potential Ameliorative Effects of Chromium Supplementation on Glucose Metabolism, Obesity, and Genomic Stability in Prediabetic Rat Model.

Chromium (III) (Cr(III)) effect on improving glucose, body mass loss, and genomic stability has been extensively studied in models of type 2 diabetes. However, there is a lack of studies evaluating its effect on prediabetes. Thus, this study evaluates the effects of Cr(III) as dietetic supplementation on glucose metabolism, obesity, and genomic stability on prediabetic rat model using high-invert sugar. Male Wistar rats were divided randomly into four treatment groups: (1) control, receiving standard diet (control); (2) prediabetic (PD), receiving a 32% of invert sugar; (3) Cr(III), receiving chromium (III) chloride (CrCl3•6H2O) (58.4mg/L); and (4) Cr(III) + PD, receiving CrCl3•6H2O in combination with high-invert sugar. Cr(III) supplementation significantly reduced blood glucose (123.00 ± 8.29mg/dL vs. 115.30 ± 9.31mg/dL, p = 0.015) and partially reduced area under the 120-min blood glucose response curve (AUC) in PD rats (p = 0.227). Moreover, Cr(III) attenuated weight gain (187.29 ± 38.56g vs. 167.22 ± 29.30g, p = 0.004), significantly reducing body mass index (0.68 ± 0.04g/cm2 vs. 0.63 ± 0.04g/cm2, p < 0.001), Lee index (0.30 ± 0.01 vs. 0.28 ± 0.01, p < 0.001), and peritoneal fat (p < 0.001). Regarding genomic stability, high-invert sugar, Cr(III), or the combination of both did not produce changes in oxidative stress, DNA damage in pancreas, or cytotoxicity markers. These data suggest that Cr(III) supplementation improved partially glucose metabolism and reduced obesity in rat model PD due to high-invert sugar without influence in genomic stability.