Glucose Tolerance Subjects Research Articles

257-OR: Short-Term Hyperglucagonemia Induces Adipose Tissue Insulin Resistance and Inflammation In Vivo

Although the effect of glucagon on glucose metabolism has been well characterized, its effect on adipose tissue and lipid metabolism in humans in vivo has been poorly studied with controversial results. We examined the effect of short-term hyperglucagonemia on adipocyte metabolism in 8 healthy normal glucose tolerant subjects (5M/3F, age=35±5, BMI = 24±1) who received a 12-hour (6PM to 6AM) glucagon infusion (6ng/kg/min) with 14C-glycerol infusion; subcutaneous abdominal adipose tissue biopsy was obtained at 6AM. 8 weeks later subjects returned for a repeat study with 12-hour infusion of normal saline. Plasma glucagon increased from 57±3 to 219±21 pg/ml within one hour and remained elevated throughout the study. Glycerol turnover rate (5.1±0.6 vs. 3.8±0.6 µmol/kg•min, p<0.05) increased by 34%, and the adipose tissue insulin resistance index (fasting plasma FFA x Insulin) more than doubled (5.8±0.8 vs. 2.8±0.7 mM•mU/L, p<0.05) after 12-hour glucagon infusion compared to saline. mRNA expression of genes involved in lipolysis in adipose tissue were upregulated after glucagon infusion (ATGL, 1.14±0.07 vs. 0.77±0.03; HSL, 1.17±0.03 vs. 0.9±0.13; MGL, 1.2±0.04 vs. 0.82±0.2, all p<0.05). Plasma concentration of proinflammatory markers (IL-1β, 0.65±0.05 vs. 0.49±0.05 pg/mL; TNF-α, 2.03±0.23 vs. 1.75±0.17 pg/mL, both p<0.05) and lipidomes involved in inflammatory pathways (lysophosphatidylcholine, 126±11 vs. 51±7 nmol/ml, p<0.005; phosphatidylcholine, 385±24 vs. 306±25 nmol/ml, p<0.01; ceramide, 1.7±0.2 vs. 1.2±0.2 nmol/ml, p<0.01) also increased after 12-hour glucagon infusion. H&E and CD68 immunofluorescence staining in adipose tissue displayed the crown-like structures (CLS) and increased infiltration of macrophages following glucagon infusion. Conclusion: Short-term (12-hour) physiologic hyperglucagonemia stimulates adipose tissue lipolysis, induces adipocyte insulin resistance, and promotes adipose tissue and systemic inflammation. Disclosure X. Chen: None. M. Fourcaudot: None. L. Norton: None. R. A. Defronzo: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. D. Tripathy: None. Funding Foundation for Advancing Veterans’ Health Research

Fetal Abdominal Obesity Detected At 24 to 28 Weeks of Gestation Persists Until Delivery Despite Management of Gestational Diabetes Mellitus.

BackgroundFetal abdominal obesity (FAO) has been reported to be affected at gestational diabetes mellitus (GDM) diagnosis at 24 to 28 weeks of gestation in older and/or obese women. This study investigated whether the management of GDM improves FAO in GDM subjects near term.MethodsMedical records of 7,099 singleton pregnant women delivering at CHA Gangnam Medical Center were reviewed retrospectively. GDM was diagnosed by 100-g oral glucose tolerance test after 50-g glucose challenge test based on Carpenter–Coustan criteria. GDM subjects were divided into four study groups according to maternal age and obesity. FAO was defined as ≥90th percentile of fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference per actual GA by the last menstruation period, biparietal diameter, or femur length, respectively.ResultsAs compared with normal glucose tolerance (NGT) subjects near term, FAORs and odds ratio for FAO were significantly higher in old and/or obese women with GDM but not in young and nonobese women with GDM. For fetuses of GDM subjects with FAO at the time of GDM diagnosis, the odds ratio for exhibiting FAO near term and being large for GA at birth were 7.87 (95% confidence interval [CI], 4.38 to 14.15) and 10.96 (95% CI, 5.58 to 20.53) compared with fetuses of NGT subjects without FAO at GDM diagnosis.ConclusionDespite treatment, FAO detected at the time of GDM diagnosis persisted until delivery. Early diagnosis and treatment might be necessary to prevent near term FAO in high-risk older and/or obese women.

Fasting Glucagon Level in Type 2 Diabetes and Impaired Glucose Tolerance and Its Association With Diabetes-Associated Clinical Parameters: A Study From Karachi, Pakistan.

Aim and objectiveThe study aims to analyze fasting glucagon in patients with type 2 diabetes and impaired glucose tolerance and correlate it with anthropometric and biochemical parameters in a large proportion of Pakistani people with diabetes. MethodologyThe participants of the study were categorized into three groups based on oral glucose tolerance test, as per American Diabetes Association guidelines. Group A consisted of normal glucose tolerance subjects (n=30), Group B consisted of subjects with impaired glucose tolerance (n=30), and Group C had full-blown subjects with type 2 diabetes (n=30). Biochemical parameters, such as fasting glucagon, fasting plasma and 2-hour glucose, glycated hemoglobin, and lipid profile, and anthropometric parameters, such as body mass index (BMI), waist and hip circumference, waist-to-hip ratio, and systolic and diastolic blood pressure, were measured.ResultsThe mean values of fasting glucagon level in Group A, Group B, and Group C were 39.24±4.5, 44.5±8.25, and 49.02±9.15 pg/ml, respectively. Statistically significant difference was not found in fasting glucagon level among these groups (p-value 0.614). Fasting glucagon was positively and independently correlated with 2-hour plasma glucose, systolic blood pressure, diastolic blood pressure, BMI, hip and waist circumference, and hip-to-waist ratio in Group C. In Group B, fasting glucagon was positively correlated with 2-hour plasma glucose, BMI, and hip circumference, while it was not correlated with fasting plasma glucose in both groups. In Group A, fasting glucagon found positively correlated with systolic blood pressure and hip circumference.ConclusionOur observation suggests that fasting plasma glucose is not concomitant with glucagon levels; however, glucagon suppression, after glucose intake, was dysregulated in type 2 diabetes and impaired glucose tolerance. Moreover, glucagon is associated with central obesity in type 2 diabetic patients..

Ayurvedic Herbal Preparation Supplementation Does Not Improve Metabolic Health in Impaired Glucose Tolerance Subjects; Observations from a Randomised Placebo Controlled Trial.

The increased usage of alternative Ayurvedic treatments as potential health-beneficial therapies emphasizes the importance of studying its efficacy in sound placebo-controlled intervention trials. An example of such a traditional Ayurvedic herbal preparation is Mohana Choorna, a mixture composed of 20 different herbs and used to prevent and treat type 2-diabetes (T2D). We studied the efficacy of “Mohana Choorna” on T2D-related parameters in subjects with impaired glucose tolerance. In a double blind, placebo-controlled cross-over trial, 19 overweight (BMI > 27 kg/m2) subjects aged 50–70 years with an impaired glucose tolerance received two four-week interventions, i.e., herbal or placebo with a four-week wash-out between interventions. HbA1c, glucose, insulin, triglycerides, cholesterol, blood pressure and augmentation index were measured before and after both interventions at fasting and during a glucose tolerance test. After both interventions, urine was collected to measure treatment exposure using LCMS-based metabolomics and whole genome gene-expression in adipose tissue of 13 subjects. The herbal intervention did not affect plasma glucose triglycerides, cholesterol, blood pressure or the augmentation index but showed a trend towards an increased insulin, HOMA-IR and postprandial insulin levels (p = 0.054, p = 0.056 and p = 0.095 respectively). An increase in expression of inflammation-related gene sets in adipose tissue was observed after the herbal intervention compared to placebo. Urine metabolomic analysis did not reveal a correlation of the presence of specific plant metabolites with “health markers”. Our findings suggest that there is no substantiating evidence to claim that four weeks’ use of the Ayurvedic herbal supplement Mohana Choorna beneficially affects glucose homeostasis.

Evaluation of therapeutic potential of Arhar honey (Cajanus cajan) in subjects with impaired glucose tolerance

Background: In Indian Medicine System, Arhar honey is believed as one of the valuable medicinal foods. Honey is being used since ancient times owing to its functional properties and nutritive value. Aims: We aimed to evaluate the effect of honey supplementation on fasting blood glucose (FBG) level and lipid profile of the subjects with impaired glucose tolerance (IGT) and healthy subjects. Methods: The selection of subjects was done through oral glucose tolerance test (World Health Organization/Food and Agriculture Organization, 1998). On the basis of blood glucose level, 28 subjects were selected by purposive random sampling and were divided into two groups. Group I included normal healthy subjects having FBG in the range of 70–100 mg/dl (n = 14), and Group II was comprised of subjects having FBG level between 100 and 125 mg/dl falling in the category of IGT (n = 14). 70 g honey was administered to subjects in both the groups on an empty stomach for 60 days and its effect on body weight, body mass index (BMI), blood pressure, FBG, glycated hemoglobin (HbA1c), and lipid profile was observed. Results: Honey administration lowered blood glucose levels and lipid levels in subjects with IGT and normal healthy subjects. Other benefits of honey administration include an increase in high-density lipoprotein cholesterol levels and a reduction in BMI. Conclusion: Consumption of honey has shown a reduction in body weight, BMI, FBG, HbA1c, and improvement in lipid profile in IGT subjects.

Analysis of the Exonic Single Nucleotide Polymorphism rs182428269 of the NRF2 Gene in Patients with Diabetic Foot Ulcer

The pivotal role of Nuclear factor erythroid-2-related factor 2 (NRF2) in redox homeostasis and wound healing has been well documented. However, the genetic mechanisms that regulate NRF2 in type 2 diabetes and diabetic foot ulcers remain unexplored. The present study investigated the association of single nucleotide polymorphism rs182428269 (-127C/T) in subjects with type 2 diabetes and diabetic foot ulcers. This cross-sectional study comprised 400 participants that included group I: normal glucose tolerant subjects (NGT, n=150), group II: type 2 diabetes mellitus subjects (T2DM, n=150) and group III: infected diabetic foot ulcer subjects (DFU, n=100). The non-synonymous SNP rs182428269 was selected based on in silico analysis and genotyped by PCR-restriction fragment length polymorphism (RFLP) followed by bidirectional Sanger sequencing. In addition, the gene expression of NRF2 in patients with polymorphism was analyzed by qPCR to evaluate the functional impact of the SNP. NRF2 expression was significantly decreased among the T2DM and DFU subjects when compared to the NGT subjects. Of particular interest, the homozygous mutant (TT) genotype of rs182428269 polymorphism was significantly associated with an increased risk for the development of T2DM (OR=1.95 (1.02-3.72), p=0.04) and DFU (OR=5.66 (2.98-10.76), p=0.0001). Furthermore, a progressive decline in NRF2 expression was observed among the T2DM and DFU subjects with "TT" genotype compared to the "CC" and "CT" genotypes. NRF2 polymorphism rs182428269 is associated with the pathogenesis of T2DM and DFU.

Effect of Mild Physiologic Hyperglycemia on Insulin Secretion, Insulin Clearance, and Insulin Sensitivity in Healthy Glucose-Tolerant Subjects.

The aim of the current study was to evaluate the effect of sustained physiologic increase of ∼50 mg/dL in plasma glucose concentration on insulin secretion in normal glucose-tolerant (NGT) subjects. Twelve NGT subjects without family history of type 2 diabetes mellitus (T2DM; FH-) and 8 NGT with family history of T2DM (FH+) received an oral glucose tolerance test and two-step hyperglycemic clamp (100 and 300 mg/dL) followed by intravenous arginine bolus before and after 72-h glucose infusion. Fasting plasma glucose increased from 94 ± 2 to 142 ± 4 mg/dL for 72 h. First-phase insulin secretion (0-10 min) increased by 70%, while second-phase insulin secretion during the first (10-80 min) and second (90-160 min) hyperglycemic clamp steps increased by 3.8-fold and 1.9-fold, respectively, following 72 h of physiologic hyperglycemia. Insulin sensitivity during hyperglycemic clamp declined by ∼30% and ∼55% (both P < 0.05), respectively, during the first and second hyperglycemic clamp steps. Insulin secretion/insulin resistance (disposition) index declined by 60% (second clamp step) and by 62% following arginine (both P < 0.005) following 72-h glucose infusion. The effect of 72-h glucose infusion on insulin secretion and insulin sensitivity was similar in subjects with and without FH of T2DM. Following 72 h of physiologic hyperglycemia, metabolic clearance rate of insulin was markedly reduced (P < 0.01). These results demonstrate that sustained physiologic hyperglycemia for 72 h 1) increases absolute insulin secretion but impairs β-cell function, 2) causes insulin resistance, and 3) reduces metabolic clearance rate of insulin.

Placenta expression of vitamin D and related genes in pregnant women with gestational diabetes mellitus

Objectives and MethodsA total of 41 GDM and 40 normal glucose tolerance subjects were recruited. Through detecting the level of Serum vitamin D with electrochemical luminescence and vitamin D receptor (VDR) with Enzyme-linked immunosorbent assay (ELISA) in maternal and cord blood, the expression leves of CYP24A1, CYP27B1, VDR protein and mRNA in placenta and umbilical cord with western blotting and RT-PCR, and the DNA methylation levels of CYP24A1 and CYP27B1 gene in placenta with methylation-specific PCR (MSP) and direct bisulfite sequencing (BSP) analysis to explore the potential role of the vitamin D and its related genes in gestational diabetes mellitus (GDM). ResultsSerum vitamin D concentrations were significantly higher in normal pregnant than women with GDM in maternal blood (P < 0.01) and cord blood (P = 0.014). Compared to the control group, the expression levels of CYP24A1 protein (P < 0.01) and mRNA (P = 0.021) and VDR protein (P = 0.026) and mRNA (P = 0.023) in the GDM group were significantly higher in placenta and umbilical cord tissues (P = 0.015, P < 0.01, P = 0.028, P < 0.01, respectively), while that of CYP27B1 protein (P < 0.01) and mRNA (P = 0.042) was significantly lower (P = 0.022, P = 0.032, respectively). Moreover, partial DNA methylation of CYP24A1 and CYP27B1 genes was observed in both GDM and control groups. ConclusionsVitamin D deficiency participates in the pathogenesis of GDM, and changes in the expression of genes related to the vitamin D metabolic pathway are closely related to vitamin D levels in the pregnancy and fetus. However, DNA methylation of CYP24A1 and CYP27B1 might not be involved in the pathogenesis of GDM.

Impact of type 2 diabetes variants identified through genome-wide association studies in early-onset type 2 diabetes from South Indian population.

The prevalence of early-onset type 2 diabetes (EOT2D) is increasing in Asian countries. Genome-wide association studies performed in European and various other populations have identified associations of numerous variants with type 2 diabetes in adults. However, the genetic component of EOT2D which is still unexplored could have similarities with late-onset type 2 diabetes. Here in the present study we aim to identify the association of variants with EOT2D in South Indian population. Twenty-five variants from 18 gene loci were genotyped in 1,188 EOT2D and 1,183 normal glucose tolerant subjects using the MassARRAY technology. We confirm the association of the HHEX variant rs1111875 with EOT2D in this South Indian population and also the association of CDKN2A/2B (rs7020996) and TCF7L2 (rs4506565) with EOT2D. Logistic regression analyses of the TCF7L2 variant rs4506565(A/T), showed that the heterozygous and homozygous carriers for allele ‘T’ have odds ratios of 1.47 (95% confidence interval [CI], 1.17 to 1.83; p = 0.001) and 1.65 (95% CI, 1.18 to 2.28; p = 0.006) respectively, relative to AA homozygote. For the HHEX variant rs1111875 (T/C), heterozygous and homozygous carriers for allele ‘C’ have odds ratios of 1.13 (95% CI, 0.91 to 1.42; p = 0.27) and 1.58 (95% CI, 1.17 to 2.12; p = 0.003) respectively, relative to the TT homozygote. For CDKN2A/2B variant rs7020996, the heterozygous and homozygous carriers of allele ‘C’ were protective with odds ratios of 0.65 (95% CI, 0.51 to 0.83; p = 0.0004) and 0.62 (95% CI, 0.27 to 1.39; p = 0.24) respectively, relative to TT homozygote. This is the first study to report on the association of HHEX variant rs1111875 with EOT2D in this population.

Integrated biomarker for type 2 diabetes mellitus and impaired fasting glucose based on metabolomics analysis using ultra-high performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing but its early diagnosis in high risk populations remains challenging using only fasting blood glucose (FBG) or hemoglobin A1c measurements. It is, therefore, important to search for an integrated biomarker for early diagnosis by determining metabolites associated with the progression of the disease. We recruited 149 participants (51 T2DM patients, 50 individuals with impaired fasting glucose (IFG) and 48 normal glucose tolerance subjects). Their serum samples were analyzed based on a metabolomics approach using ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS). The changes in metabolites were profiled and evaluated using univariate and multivariate analyses. Furthermore, a biomarker model was established and the potential biomarkers were evaluated using binary logistic regression analysis and receiver operating characteristic analysis with AUC (area under the curve). Pathway analysis of differential metabolites was performed to reveal the important biological information. Thirty-eight differential metabolites were identified as significantly associated with T2DM patients and 23 differential metabolites with IFG individuals, mainly amino acids, carnitines, and phospholipids. By evaluating 17 potential biomarkers, we defined a novel integrated biomarker consisting of 2-acetolactate, 2-hydroxy-2,4-pentadienoate, L-arabinose and L-glutamine. The AUCs of the integrated biomarker with IFG and T2DM patients were 0.874 and 0.994, respectively, which showed a superior diagnostic performance. The levels of 2-acetolactate and 2-hydroxy-2,4-pentadienoate were strongly positively correlated with FBG, while L-glutamine and L-arabinose were strongly negatively associated with FBG. After pathway analysis, it was suggested that the majority of the influenced metabolic pathways associated with diabetes referred to amino acid metabolism. The integrated biomarker could diagnose IFG and T2DM with a superior diagnostic performance. This finding provides support for novel biomarkers in the diagnosis and treatment of diabetes.

Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis

Type 2 diabetes is characterized by peripheral insulin resistance and insufficient insulin release from pancreatic islet β cells. However, the role and sequence of β cell dysfunction and mass loss for reduced insulin levels in type 2 diabetes pathogenesis are unclear. Here, we exploit freshly explanted pancreas specimens from metabolically phenotyped surgical patients using an in situ tissue slice technology. This approach allows assessment of β cell volume and function within pancreas samples of metabolically stratified individuals. We show that, in tissue of pre-diabetic, impaired glucose-tolerant subjects, β cell volume is unchanged, but function significantly deteriorates, exhibiting increased basal release and loss of first-phase insulin secretion. In individuals with type 2 diabetes, function within the sustained β cell volume further declines. These results indicate that dysfunction of persisting β cells is a key factor in the early development and progression of type 2 diabetes, representing a major target for diabetes prevention and therapy.

Erythrocyte glucose-6-phosphate dehydrogenase activity and risk of gestational diabetes.

Glucose-6-phosphate dehydrogenase (G6PD) is the regulating enzyme in the pentose phosphate pathway. A link between the activity of G6PD and diabetes mellitus has previously been reported. The association of G6PD activity with the pathogenesis of gestational diabetes mellitus (GDM) has not yet been investigated. The aim of the present study was to investigate the association of erythrocyte G6PD activity with major characteristics of GDM. This case-control study was conducted at Hafez Hospital, Shiraz University of Medical Sciences, Shiraz, Iran from March to November 2017. Eighty-four age-matched pregnant women including GDM (n = 33), impaired glucose tolerance (IGT; n = 7), and normal glucose tolerance (NGT; n = 44) subjects were enrolled in this study. The levels of erythrocyte G6PD activity, fasting plasma glucose (FPG), insulin, malondialdehyde (MDA), and ferric reducing power (FRAP) of serum were measured. The level of homeostasis model for the assessment of insulin resistance (HOMA-IR) was calculated. The data were analyzed using SPSS software. P < 0.05 was considered statistically significant. The values of FPG, insulin, HOMA-IR, G6PD activity, and FRAP were significantly higher in GDM patients compared to NGT subjects. G6PD activity was correlated with FPG ((r = 0.224; P = 0.041). Binary logistic regression analysis revealed independent association of body mass index >25.88 [OR = 3.23, 95% CI 1.071-9.75, P = 0.037], HOMA- IR >2.33 [OR = 7.15, 95% CI 2.26-22.56, P < 0.001], and G6PD activity>21.17U/g Hb [OR = 4.63, 95% CI 1.49-14.38, P = 0.008] with an increased risk of GDM. No significant change was observed among serum MDA levels in the three groups. The findings demonstrate that increased G6PD activity is positively associated with the risk of GDM.

Prolonged plasma glucose elevation on oral glucose tolerance test in young healthy Japanese individuals.

AimsThis study aims to assess insulin secretion and resistance through oral glucose tolerance test (OGTT) among young Japanese individuals.Subjects and methodsWe enrolled 595 young healthy Japanese individuals aged 22‐29 years. They underwent an OGTT, and their results were divided into 4 groups (I‐IV), according to the time at which their plasma glucose concentration declined below the fasting glucose concentration (30, 60 or 120 minutes or never as groups I, II, III and IV, respectively).ResultsWe classified 575 normal glucose‐tolerant subjects into 4 groups (I‐IV) with I: 28 (4.9%), II: 120 (20.9%), III: 143 (24.9%) and IV: 284 (49.4%) individuals. The Matsuda, insulinogenic and disposition indices were decreased from groups I to IV. ROC curves of disposition index reflecting the composition of insulin secretion and sensitivity classified the prolonged glucose elevation group (group III + IV) from the rapid glucose lowering group (group II; AUC = 0.847).ConclusionsEven in a young and healthy Japanese individual within the physiological range of glycaemic control, there is a sequential decrease in insulin sensitivity and secretion.

Dyslipidemia in diabetes: a population-based study in Bali.

PurposeTo establish the lipid pattern in subjects with diabetes mellitus (DM) and factors that are correlated with insulin resistance and lipid disorders in a population of Bali.MethodsA cross-sectional population-based study which enrolled 1840 subjects (age 13–100 years) from 7 villages was carried out. Several clinical parameters were measured including age, gender, body mass index, waist circumference (WC), fasting blood glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) A (apoA), apoB, non-HDL-C, T/HDL-C ratio, LDL-C/apoB ratio, apoB/A ratio, plasma insulin, and homeostasis of model assessment-insulin resistance (HOMA-IR).ResultsTC, TG, and non-HDL-C levels were higher in DM subjects than in normal glucose tolerance (NGT) subjects in both genders; total/HDL-C ratio was higher in subjects with DM than in NGT subjects only in men; LDL-C levels, apoB levels, and apoB/A ratios were higher and LDL/apoB was lower in subjects with DM than in NGT in women. In subjects with DM, the target for LDL-C (79%), non-HDL-C (85.2%), apoB (80%), HDL-C (34.9%), TG (46.7%), and small-dense low density lipoprotein (42.2%) was not achieved.ConclusionFBG was correlated with TC, TG, LDL-C, apoB, non-HDL-C levels, LDL/apoB, and apoB/apoA ratios. Subjects with DM had higher levels of TC, TG, and non-HDL-C levels in both genders; T/HDL-C ratio only in men; LDL-C, apoB/apoA ratio and lower LDL/apoB ratio only in women. Obesity was correlated with lipid levels. WC was correlated with LDL/apoB ratio, insulin level, HOMA-IR, and TG; highest absolute strength of correlation was with LDL/apoB ratio. Insulin resistance was correlated with lipid levels or ratios, especially in women. In women, HOMA-IR had a positive correlation with total/HDL-C ratio, non-HDL-C, apoB, and a negative correlation with HDL-C levels.

Increased Fasting Plasma Retinol-binding Protein-4 (Rbp4) Associates with Impaired Glucose Tolerant Subjects Visited in a Tertiary Hospital of Bangladesh

Animal studies have been suggested that Retinol-binding Protein-4 (RBP4) associates in the development of type 2 diabetes (T2D) but human studies are still controversial. Therefore, the present study aims to investigate plasma RBP4 in subjects with Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) whether its changes commences before the onset of T2D. This study has investigated 13 IFG, 43 IGT and 16 IFG-IGT along with 50 healthy subjects. Fasting insulin and RBP4 were measured using Enzyme-Linked Immunosorbent Assay (ELISA) technique. Insulin sensitivity (HOMA %S) and insulin secretory capacity (HOMA %B) were estimated using fasting plasma glucose and fasting insulin values through HOMA-CIGMA software. Fasting plasmaRBP4 (ng/ml) level was significantly higher in IGT and IFG-IGT subjects compared to controls. In binary logistic regression analysis RBP4 was found to be significantly associated with IGT (B=0.123, p=0.001) and IFG-IGT subject (B=0.146, p=0.012). RBP4 was found to be significantly correlated with thewaist-hip ratio (r=0.323, p=0.035), fasting insulin (r=0.338, p=0.027) and HOMA-IR (r=0.336, p=0.037) in IGT subjects; after adjusted the effects of age and BMI, RBP4 has still associated with IR in IGT (B=0.400, p=0.009). The above results could be concluded as a) RBP4 has been increased in IGT and IFG-IGT subjects; b) RBP4 is positively associated with insulin resistance (IR) in IGT subjects.

STUDY OF SERUM ADIPONECTIN LEVEL IN IMPAIRED GLUCOSE TOLERANCE SUBJECTS.

13Jun 2019 STUDY OF SERUM ADIPONECTIN LEVEL IN IMPAIRED GLUCOSE TOLERANCE SUBJECTS. Poonam Yadav and G.G. Kaushik. M.Sc. (Med.) Student, Department of Biochemistry, J.L.N. Medical College, Ajmer (Rajasthan). Rajasthan University of Health Sciences, Jaipur. Senior Professor, Department of Biochemistry, J.L.N. Medical College, Ajmer (Rajasthan). Rajasthan University of Health Sciences, Jaipur.

Elevated one hour with normal fasting and 2 h plasma glucose helps to identify those at risk for development of Type2 Diabetes-11 years observational study from south India

AimsTo compare conversion rates of diabetes in subjects with elevated 1 h plasma glucose (1hrPG) during an OGTT with normal glucose tolerance(NGT) subjects over a period of 11 years. Methods4023 subjects were selected from electronic data base of medical records.233 subjects who were followed up for a period of 11 years were included.160 with isolated prediabetes and their combinations were excluded.The remaining 73 were categorized into group1 NGT (n = 37) and group-2 (n = 36) with elevated 1hrPG.Kaplan Meier curves for incident diabetes and Cox proportional hazard model were compared between groups. ResultsDuring follow up, 10.8% and 44.4% converted to DM in group1 and group2 (p = 0.003). Elevated 1hrPG was associated with incident diabetes(HR 7.9[95%CI 2.2–28.1](p = 0.001)provided better risk assessment.The adjusted risk of event in subjects with elevated 1hrPG is likely to be 7 times more when compared to NGT.Subjects with elevated1hrPG remained free of diabetes for a median period of 7.6 years (95% CI 5.8–7.8) whereas NGT subjects remained free for 10 years (95% CI 8.5–10.0) (p < 0.001). ConclusionIn conclusion, conversion to DM was higher and risk was 7 times more in subjects with elevated 1hrPG. Elevated 1hrPG during OGTT has to be considered as a distinct entity.

726-P: Impaired Glucose Tolerance Blunts Exercise-Training Induced Improvements in Aerobic Exercise Capacity

Background: Low aerobic exercise capacity independently and strongly predicts metabolic disease and mortality. While aerobic exercise training can increase exercise capacity and reduce health risks, people with impaired glucose tolerance (IGT; i.e., prediabetes, T1D and T2D) have lower exercise capacity than glucose-tolerant subjects, even when exercise training “dose” is matched. We tested the hypothesis that low exercise capacity in IGT is caused by blunted exercise training-induced improvements in exercise capacity. Methods: IGT was induced in CD-1 mice by a) diet-induced insulin resistance (Western Diet, WD; 40% kcal from fat), or b) streptozotocin injection (STZ; 2x 40 mg/kg) to reduce circulating insulin. Control and STZ mice consumed standard chow (10% fat). Eight weeks following treatment, mice were partitioned into sedentary or exercise-trained (voluntary wheel running) groups. Exercise capacity (meters, m) was measured before and after a 3-week training intervention, and the change (Δ) in exercise capacity was calculated. Body composition was measured (DEXA) and tissues were harvested to measure metabolic health outcomes. Results: Baseline exercise capacity and total running distance were similar among Control, WD and STZ groups. Mice from all treatment groups displayed metabolic benefits from training, including increased muscle GLUT4 and mitochondrial content, and reduced adiposity. In contrast, exercise capacity only improved with training in Control mice (Δ124.82±40.25 m), whereas WD-trained (Δ29.69±24.11 m) and STZ-trained (Δ37.10±25.76 m) animals had no significant increase in exercise capacity. These data demonstrate that IGT can prevent improvements in exercise capacity with exercise training, despite the induction of other beneficial metabolic health outcomes. Conclusions: Our data identify IGT as a negative regulator of improved exercise capacity with training and a novel mechanism underlying low exercise capacity in diabetes. Disclosure T. MacDonald: None. P. Pathak: None. S. Lessard: None. Funding American Heart Association (1-19-PDF-168)

435-P: Elevated One-Hour Post-Challenge Glucose Levels Associated with Increased Arterial Stiffness

We reported a positive correlation between brachial-ankle pulse wave velocity (baPWV) and one-hour post-challenge glucose (1-h PG). Furthermore, the subpopulation defined by 1-hour PG beyond 183 mg/dL (corresponded to Impaired glucose tolerance range of 2-h PG) in normal glucose tolerant (NGT) subjects. These findings suggested that if NGT subjects convert to higher 1-h PG levels from a normal 1-h PG range they will develop arterial stiffness. To address this issue, we initiated a clinical study that included 40 NGT subjects (23 men and 17 women, mean age 60.9 ±9.7 years), with a comprehensive medical check-up was performed on each subject at Kan-etsu Chuo Hospital every year. In addition, over the 9-year period these individuals were annually assessed by a 75-g oral glucose tolerance test (OGTT) and for atrial stiffness by baPWV. Based on the 75-g OGTT, NGT subjects alone were selected according to the 2006 WHO criteria. NGT subjects in this study were identified as individuals having a normal range of all measured parameters. In this population, there was no significant correlation between baPVW and all measured parameters. One-h post challenge glucose (1-h PG) in 28 subjects was below 154 mg/dL and their baPWV was not changed (1266.4 ±125.42 cm/sec from 1243.62 ±108.1) after nine years. On the other hand, 1-h PG in the rest of 12 subjects was significantly increased to 160.33 ±4.73 from 124.67 ±20.13 and their baPVW was also significantly elevated to 1489.33 ±41.05 from 1255.01 ±64.08 after nine years. We found that rapid blood glucose change in NGT could be a risk factor for arterial stiffness and we would like to point out the possibility for physicians to select high-risk subjects by 75g-OGTT with the evaluation of 1h-PG. Taken together, we found that rapid blood glucose change could be a risk factor for arterial stiffness. Disclosure S. Okada: None. J. Okada: None. E. Yamada: None. T. Saito: None. M. Yamada: None.

Role of Dietary Macronutrients and Fatty Acids in Obesity and Metabolic Risk in Older Adults (P08-026-19)

ObjectivesThe aim of the study was to examine the role of dietary consumption of different types of fatty acids on metabolic risk factors and regional fat deposition in older men and women. We hypothesized that saturated fatty acid (SFA) intake, ratio of monounsaturated fatty acids (MUFA) to polyunsaturated fatty acids (PUFA), and total fat intake, as well as proportion of energy derived from fat, would be associated with markers of insulin resistance, hyperlipidemia, and ectopic fat. MethodsSedentary, obese (Body Mass Index: 29–48 kg/m2) adults (N = 20) aged 45–78 years underwent two-hour oral glucose tolerance test, blood draw, DXA scan, and CT scan of the abdomen and mid-thigh. Seven-day diet records were analyzed with NutritionistPro software and the USDA Foodapedia feature of the Supertracker program. ResultsSubjects had low fitness levels (VO2 max = 23.5 ±2.4 mL/kg/min) and high total body fat (43.5 ± 1.7%) with abdominal obesity (visceral adipose tissue area = 192.4 ± 18 cm2, subcutaneous abdominal adipose area = 465.4 ± 29 cm2) and intermuscular adipose tissue (IMAT) area in thigh (150.1 ± 17 cm2). The average macronutrient composition of the diet was high in fat (fat as a % of total kcal = 35.5) with SFA, MUFA, and PUFA were respectively represented as 33.0, 34.8, and 22.1% of total fat intake. The average MUFA to PUFA ratio was 1.66. There were no differences in fatty acid intake between subjects with normal glucose tolerance and impaired glucose tolerance subjects. The ratio of MUFA to PUFA was positively correlated with higher fasting glucose (r = 0.42, P = 0.06), glucose intolerance (r = 0.43, P = 0.06), and serum cholesterol (r = 0.48, P = 0.03). PUFA intake as a percentage of fat intake was associated with lower serum cholesterol (r = –0.44, P = 0.05). Associations between diet composition with body composition (abdominal fat, IMAT) were not found to be uniformly significant among a homogenous sample of obese, sedentary subjects with diets high in proportion of lipid. ConclusionsDietary fatty acid intake, specifically MUFA unbalanced by PUFA, was associated with glucose intolerance and increased serum cholesterol, and therefore may confer increased risk for diabetes among obese, sedentary individuals. Future investigation of food sources, or context of dietary lipids, could lead to individualized dietary recommendations to promote healthy eating habits and potentially alter metabolic risk. Funding SourcesSupported by grant awards from the Department of Veteran’s Affairs and the National Institute of Health.