Normal Glucose Tolerance Controls Research Articles

Abdominal fat depots and their association with insulin resistance in patients with type 2 diabetes

Background Asian-Indians show thin fat phenotype, characterized by predominantly central deposition of excess fat. The roles of abdominal subcutaneous fat (SAT), intra-peritoneal adipose tissue, and fat depots surrounding the vital organs (IPAT-SV) and liver fat in insulin resistance (IR), type-2 diabetes (T2D) and metabolic syndrome (MetS) in this population are sparsely investigated. Aims and objectives Assessment of liver fat, SAT and IPAT-SV by MRI in subjects with T2D and MetS; and to investigate its correlation with IR, specifically according to different quartiles of HOMA-IR. Methods Eighty T2D and the equal number of age sex-matched normal glucose tolerant controls participated in this study. Abdominal SAT, IPAT-SV and liver fat were measured using MRI. IR was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Results T2D and MetS subjects have higher quantity liver fat and IPAT-SV fat than controls (P = 9 x 10−4 and 4 x 10−4 for T2D and 10−4 and 9 x 10−3 for MetS subjects respectively). MetS subjects also have higher SAT fat mass (P = 0.012), but not the BMI adjusted SAT fat mass (P = 0.48). Higher quartiles of HOMA-IR were associated with higher BMI, W:H ratio, waist circumference, and higher liver fat mass (ANOVA Test P = 0.020, 0.030, 2 x 10−6 and 3 x 10−3 respectively with F-values 3.35, 3.04, 8.82, 4.47 respectively). In T2D and MetS subjects, HOMA-IR showed a moderately strong correlation with liver fat (r = 0.467, P < 3 x 10−5 and r = 0.493, P < 10−7), but not with SAT fat and IPAT-SV. However, in MetS subjects IPAT-SV fat mass showed borderline correlation with IR (r = 0.241, P < 0.05), but not with the BMI adjusted IPAT-SV fat mass (r = 0.13, P = 0.26). In non-T2D and non-MetS subjects, no such correlation was seen. On analyzing the correlation between the three abdominal adipose compartment fat masses and IR according to its severity, the correlation with liver fat mass becomes stronger with increasing quartiles of HOMA-IR, and the strongest correlation is seen in the highest quartile (r = 0.59, P < 10−3). On the other hand, SAT fat mass tended to show an inverse relation with IR with borderline negative correlation in the highest quartile (r = -0.284, P < 0.05). IPAT-SV fat mass did not show any statistically significant correlation with HOMA-IR, but in the highest quartile it showed borderline, but statistically insignificant positive correlation (P = 0.07). Conclusion In individuals suffering from T2D and MetS, IR shows a trend towards positive and borderline negative correlation with liver fat and SAT fat masses respectively. The positive trend with liver fat tends to become stronger with increasing quartile of IR. Therefore, these findings support the theory that possibly exhaustion of protective compartment’s capacity to store excess fat results in its pathological deposition in liver as ectopic fat.

The association of plasma pancreastatin levels with insulin resistance in patients with gestational diabetes mellitus

Introduction Gestational diabetes mellitus (GDM) occurs on the background of increased insulin resistance. We aimed to investigate the levels of plasma pancreastatin (PST) levels and its association with metabolic, demographic, and anthropometric parameters in gestational diabetic and normal glucose-tolerant pregnant women. Materials and methods A total of 165 pregnant women in the 24th–28th week of pregnancy were enrolled in this cross-sectional study. PST levels were measured using ELISA method. Results Median PST levels were similar between GDM (n = 62, 37.6%) and normal glucose-tolerant control group (n = 103, 62.4%). In the GDM group, PST level showed a significant positive correlation with fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR). In binary logistic regression analysis, PST levels did not predict the presence of GDM significantly. Conclusion Positive correlation of PST with fasting insulin and HOMA-IR suggests that PST could be associated with insulin resistance. Further studies are needed as regards to the role of PST in GDM pathogenesis.

Differential effect of gastric bypass versus sleeve gastrectomy on insulinotropic action of endogenous incretins.

Prandial hyperinsulinemia after Roux-en-Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, β-cell sensitivity to exogenous incretin is reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and β-cell response to increasing concentrations of endogenous incretins. Glucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-g oral glucose ingestion were compared between ten nondiabetic participants with GB versus nine matched individuals with SG and seven nonoperated normal glucose tolerant control individuals (CN) with and without administration of 200 mg ofsitagliptin. Fasting glucose and hormonal levels were similar among three groups. Increasing plasma concentrations of endogenous incretins by two- to three-fold diminished prandial glycemia and increased β-cell secretion in all three groups (p < 0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p < 0.05 for interaction). However, plot of the slope of ISR (from premeal to peak values) versus plasma glucagon-like peptide-1 concentration was smaller after GB compared with SG and CN. After GB, increasing incretin activity augments prandial β-cell response whereas the β-cell sensitivity to increasing plasma concentrations of endogenous incretin is diminished.

Polygenic scores of diabetes-related traits in subgroups of type 2 diabetes in India: a cohort study.

A machine-learning approach identified five subgroups of diabetes in Europeans which included severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD) with partially distinct genetic aetiologies. We previously validated four of the non-autoimmune subgroups in people with young-onset type 2 diabetes (T2D) from the Indian WellGen study. Here, we aimed to apply European-derived centroids and genetic risk scores (GRSs) to the unselected (for age) WellGen to test their applicability and investigate the genetic aetiology of the Indian T2D subgroups. We applied European derived centroids and GRSs to T2D participants of Indian ancestry (WellGen, n=2217, 821 genotyped) and compared them with normal glucose tolerant controls (Pune Maternal Nutrition Study, n=461). SIDD was the predominant subgroup followed by MOD, whereas SIRD and MARD were less frequent. Weighted-GRS for T2D, obesity and lipid-related traits associated with T2D. We replicated some of the previous associations of GRS for T2D, insulin secretion, and BMI with SIDD and MOD. Unique to Indian subgroups was the association of GRS for (a) proinsulin with MOD and MARD, (b) liver-lipids with SIDD, SIRD and MOD, and (c) opposite effect of beta-cell GRS with SIDD and MARD, obesity GRS with MARD compared to Europeans. Genetic variants of fucosyltransferases were associated with T2D and MOD in Indians but not Europeans. The similarities emphasise the applicability of some of the European-derived GRSs to T2D and its subgroups in India while the differences highlight the need for large-scale studies to identify aetiologies in diverse ancestries. The data provide robust evidence for genetically distinct aetiologies for the T2D subgroups and at least partly mirror those seen in Europeans. Vetenskapsrådet, Diabetes Wellness, and Hjärt-Lungfonden (Sweden), DST (India), Wellcome Trust, Crafoord Foundation and Albert Påhlsson Foundation.

Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans

ABSTRACT Gestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

Cancer and its predictors in Chinese adults with newly diagnosed diabetes and impaired glucose tolerance (IGT): a 30-year follow-up of the Da Qing IGT and Diabetes Study

BackgroundWe aimed to explore if hyperglycaemia and hyperinsulinemia in the diabetes and prediabetes population were associated with increased risk of cancer occurence.MethodsOverall, 1700 participants with different glycaemic statuses were screened from the 110,660 residents of Da-Qing, China, in 1985. They were followed up to 30 years to access cancer outcomes.ResultsCancer was identified in 15.2% (259/1700) of the participants. The incidence of cancer in the normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes groups was 6.06, 6.77, and 7.18 per 1000 person-years, respectively (P = 0.02). In the Fine-Gray model with all cause death as competing risk, compared with the NGT controls, both IGT and diabetes groups demonstrated significantly higher risk of cancer (for the IGT group, adjusted hazard ratio (aHR) = 1.77, 95% CI 1.38–2.27, P < 0.0001; for the diabetes, aHR = 3.34, 95% CI 2.64–4.22, P < 0.0001). Among the IGT participants, progress to diabetes (aHR = 2.28, 95%CI 1.24–4.20, P = 0.008) and insulin-area under the curve at baseline (for 1 SD increase, aHR = 1.39, P = 0.02) were also associated with the risk of cancer after adjustment of covariables.ConclusionsHyperglycaemia in patients with diabetes, hyperinsulinemia, and progression to diabetes in people with IGT is significantly associated with the long-term increased risk of cancer occurrence.

Study of Serum Adiponectin and Interleukin-1β Levels in Women with Gestational Diabetes.

Pregnancy is associated with alterations in the regulation of glucose metabolism caused by actions of various placental hormones and substances that antagonise the action of insulin leading to a state of relative insulin resistance as pregnancy progresses. Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Adiponectin is known to be synthesised by adipocytes as well as by the placenta during pregnancy. It has an insulin-sensitising and anti-atherosclerotic actions. Interleukin-1β (IL-1β) is a member of interleukin-1 cytokine family and is known to involve in immune-mediated disease and regulation of inflammation. Accumulating evidence indicates that diseases related to metabolic syndrome are characterised by abnormal cytokine production, including IL-1β. To evaluate serum adiponectin and IL-1β levels in women with GDM and correlate their levels with blood glucose level. A hospital-based case-control study was conducted in which 30 cases of GDM along with age-matched normal glucose tolerance (NGT) pregnant controls were taken. Informed consent was taken and subjects were screened at 24-28th weeks of gestation for GDM by glucose challenge test (GCT), followed by oral glucose tolerance test. Socio-demographic data and clinical evaluation were done using a pre-structured perfoma. Serum concentration of adiponectin and IL-1β was measured using enzyme-linked immunosorbent assay. The mean value of serum adiponectin level was significantly lower, 5.76 μg/ml SD ± 2.01351 in cases of GDM compared to NGT controls (14.12 μg/dl SD ± 4.99734), P < 0.05. A cutoff value of serum adiponectin level ≤8.7 μg/ml gave a sensitivity and specificity of 100% when used alone for identifying cases of GDM in the present study. Serum level of IL-1β was less than the detectable level (<6.5 pg/ml) in NGT controls. In this study, 26.7% of GDM cases showed levels >6.5 pg/ml (median 18.2 [12.8-34.62]), rest of the cases (73.3%) had levels less than 6.5 pg/ml. A significant inverse correlation was seen between serum adiponectin and HbA1c, pre-gestational BMI, and blood glucose level at GCT. There was no significant correlation of serum IL-1β level with any of the parameters. GDM is associated with low level of serum adiponectin, and serum adiponectin may be used as a biomarker for detecting cases of GDM to complement blood glucose level.

The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects

We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35–2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13–2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14–3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10–6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10–5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.

SUN-639 Secretagogin Levels Are Unrelated to Gestational Diabetes Mellitus in a Cohort of Pregnant Women

IntroductionSecretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients.1,2,3 Up to this day, no study on SCGN levels in patients with gestational diabetes mellitus (GDM) has been published.Patients and MethodsIn 138 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of GDM patients were compared to women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with an oral glucose tolerance test (oGTT) performed before 20 weeks gestation. The women with GDM (39.1%) were further divided into GDM types depending on insulin sensitivity or secretion defects defined as below the 25th percentile in the oGTT of the NGT controls.ResultsCompared to women with NGT (mean SCGN= 52.7 ng/dl), there was no statistically significant difference in SCGN in patients with GDM (mean value 53.9 ng/dl, p=0.857). After splitting into secretion defect and insulin resistance subtypes, SCGN remained unrelated to GDM in our study population. However, Secretagogin was found to be significantly higher in postpartum visits (mean= 62.9 ng/dl) than during pregnancy (mean value= 48.5 ng/dl; p= 0.047). Furthermore, SCGN was positively correlated with BMI (p=0.006) in the present analysis.ConclusionUnlike in studies conducted on type 2 diabetes,1,2,3 a relationship between GDM and Secretagogin levels could not be demonstrated in this study. However, lower levels during pregnancy point towards physiological changes in SCGN levels unrelated to (gestational) diabetes mellitus. Further research, ideally including before-pregnancy levels, is paramount to assess possible roles of SCGN during pregnancy.1. Maj M, Wagner L, Tretter V, et al. A TRPV1‐to‐secretagogin regulatory axis controls pancreatic β‐cell survival by modulating protein turnover. EMBO J. 2017;36(14):2107-2125. doi:10.15252/embj.2016953472. Yang C, Qu H, Zhao X, et al. Plasma Secretagogin is Increased in Individuals with Glucose Dysregulation. Exp Clin Endocrinol Diabetes. 2019:0-4. doi:10.1055/a-1001-22443. Maj M, Wagner L, Tretter V. 20 Years of Secretagogin: Exocytosis and Beyond. Front Mol Neurosci. 2019;12(February):1-10. doi:10.3389/fnmol.2019.00029

Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case–control study

ObjectiveTo examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM.Research design and methodsA total of 135 women...

The variation degree of coagulation function is not responsible for extra risk of hemorrhage in gestational diabetes mellitus.

BackgroundGestational diabetes mellitus (GDM) is characterized as glucose intolerance of any degree that begins or first diagnosed during pregnancy. It possesses a higher risk of haemorrhage, which may be caused by the coagulation dysfunction. However, there has been no study focus on how coagulation state changes in the progress of GDM pregnancy. Our study is aimed to assess the association of coagulation function and haemorrhage in GDM.MethodsA total of 662 subjects (273 from a population‐based study and 389 from a prospective cohort study) were selected to measure mean platelet volume (MPV), platelet distribution width (PDW), platelet (PLT), thrombocytocrit (PCT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). All pregnant individuals were divided into normal glucose tolerance (NGT) controls and GDM patients diagnosed between the 24th and 28th weeks of gestation.ResultsCompared with NGT controls, GDM females showed shortened PT, shortened APTT, and increased blood FIB levels, while the platelet parameters MPV, PDW, PLT, and PCT remained unchanged in mid‐pregnancy. By late pregnancy, the platelet parameters MPV, PDW, and PCT were increased in the GDM group compared with the NGT group, while PT and APTT were unchanged.ConclusionsThe GDM group was hypercoagulable compared with the NGT group rather than hypocoagulable as predicted, but still within the normal range. Therefore, our findings demonstrate that the variation degree of coagulation function is not responsible for extra risk of hemorrhage in GDM, and prevention of hemorrhage should focus on other causes.

Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.

BackgroundType 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers.MethodsEleven IGT- volunteers followed a 36-day placebo- and L-carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m2/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (1H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group.ResultsMetabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected.ConclusionCarnitine supplementation improves acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.

Circulating Lactate Is Elevated in Prediabetes Phenotypes Compared with Normal Glucose Tolerant Counterparts

PURPOSE: Prediabetes can be characterized as impaired fasting glucose (IFG) with or without impaired glucose tolerance (IGT; 2-hr blood glucose). IFG is depicted by impaired liver insulin sensitivity, while IFG+IGT is related to reduced liver and muscle insulin sensitivity. Lactate is a byproduct of non-oxidative glycolysis that may mediate altered glucose regulation. However, whether people with IFG and/or IFG+IGT have elevated lactate concentrations compared to normal glucose tolerant (NGT) controls is unclear. We hypothesized that individuals with IFG and IFG+IGT would have higher lactate levels than NGT controls in relation to glucose metabolism. METHODS: Forty-one obese adults (Age: 54.8±2.0yrs; BMI: 36.0±1.0kg/m2; 34F/7M) were screened for NGT, IFG, or IFG+IGT (75g OGTT, ADA criteria) following an overnight fast. Plasma lactate, glucose, and insulin were measured during a 120min 75g OGTT. The oral minimal model was used as an estimate for insulin sensitivity. Aerobic fitness (VO2peak), fasting substrate oxidation (respiratory exchange ratio (RER), indirect calorimetry) and body composition (bioelectrical impedance) were also tested. RESULTS: There were no differences in VO2peak, body fat or fasting RER across groups. Individuals with IFG+IGT had lower insulin sensitivity compared with IFG and NGT (P<0.01). However, both IFG and IFG+IGT had increased lactate tAUC compared to NGT (P<0.01 and P=0.01, respectively). Increased lactate tAUC correlated with fasting glucose (r=0.33, P=0.03) and reduced VO2peak (r=-0.34, P=0.03). Fasting lactate also related to fasting RER (r=0.31, P=0.04). CONCLUSION: Despite no differences between prediabetes phenotypes, adults with IFG and IFG+IGT have elevated lactates compared to NGT controls. Lactate tAUC directly associates with fasting glucose and fitness, but not insulin sensitivity. These data suggest that fitness may mediate lactate metabolism via the liver. Future work is warranted to determine the mechanism by which lactate influences type 2 diabetes risk.

2247-PUB: Comparative Analysis of the Thickness of Inner Retinal Layers among African Immigrants Based on Their Status of Glucose Tolerance

Inner retinal neurodegeneration was found, independent of the severity of retinopathy in persons with diabetes (DM). However, it is unknown whether the inner retinal neurodegeneration is evident in people with prediabetes (preDM) or asymptomatic people with newly diagnosed DM. In this cross-sectional study, we prospectively enrolled African immigrants who self-identified as being healthy with no prior history of diabetes. Each participant was tested for diabetes with an OGTT and underwent a comprehensive eye exam with spectral-domain optical coherence tomography and stereoscopic fundus photographs. The thickness of parafoveal (PA) retinal nerve fiber layer (RNFL), perifoveal (PE) RNFL, PA ganglion cell + inner plexiform layers (G+I), and PE G+I were measured using an automated segmentation software. A total of 211 African immigrants enrolled in the study. After excluding participants with a history or signs of glaucoma and other conditions that could affect retinal structural integrity, there were 21 DM participants (76% male, age 46 (28-61y) (mean (range))), 72 preDM participants (61.1% male, age 42.4 (23-65)), and 91 normal glucose tolerant (NGT) participants (58% male, age 36 (20-62y)). From the 91 NGT control subgroup, 52 age-sex-matched participants were selected for comparative analyses (64% male, age 43 (32-62y)). Among participants in the 3 subgroups (DM, preDM, NGT), there was no significant difference in the mean thickness of PA RNFL (24.7 (2.4) (mean (SD)), 24.9 (2.1), 24.6 (2.8), respectively, P=0.863), PE RNFL (35.9 (3.8), 36.7 (4.1), 35.4 (3.2), P=0.794), PA G+I (88.8 (5.6), 90.6 (10.3), 89.7 (7.2), P=0.415), or PE G+I (65.0 (5.0), 67.2 (5.6), 67.4 (4.2), P=0.194). With this limited sample size, we were unable to find in fircan an association of neurodegeneration in persons with PDM and NDM. Future studies with larger sample size may provide further supporting evidence for such an association. Disclosure C.K. Hwang: None. E. Agron: None. A.E. Sumner: None. S.M. Briker: None. J.Y. Aduwo: None. C. DuBose: None. E. Chew: None.

Relationship between serum osteocalcin/undercarboxylated osteocalcin and type 2 diabetes: a systematic review/meta-analysis study protocol

IntroductionThe global burden of type 2 diabetes (T2DM) is steadily increasing. Experimental studies have demonstrated that a novel hormone secreted by bone cells, osteocalcin (OC), can stimulate beta-cell proliferation and...

Expression Profile of Diabetes-Related Genes Associated with Leukocyte Sirtuin 1 Overexpression in Gestational Diabetes.

Although compelling evidence indicates that Sirtuin 1 (SIRT1) plays a prominent role in type 2 diabetes, its relationship with gestational diabetes (GDM) remains elusive. This study was aimed at identifying diabetes-related genes and cellular pathways linked to changes of leukocyte SIRT1 expression at the time of GDM diagnosis. For this purpose, 122 GDM patients were screened for leukocyte SIRT1 expression, and two subgroups were distinguished, namely GDM/SIRT1(↑) (n = 30, p < 0.05) and GDM/SIRT1(↔) (n = 92, p > 0.05), with significant and insignificant changes in leukocyte SIRT1 expression compared to a normal glucose tolerant (NGT) group (n = 41), respectively. PCR array analysis identified 11 diabetes-related genes with at least a ± 2-fold difference in expression in GDM/SIRT1(↑) patients (n = 9) vs. NGT controls (n = 7); in addition, significant differences in the expression of four of the six investigated genes were confirmed between the entire GDM/SIRT1(↑) group and the whole NGT group (p < 0.05). Interestingly, of these four genes, only ACLY expression was found to significantly differ between GDM/SIRT1(↑) and GDM/SIRT1(↔). This study demonstrates that under hyperglycemic conditions, leukocyte SIRT1 overexpression is accompanied by an over-abundance of three transcripts and an under-abundance of another; these four govern related metabolism, inflammation, and transport functions, suggesting that such alterations might represent systemic biological adaptations with a unique ACLY under-expression in GDM/SIRT1(↑) women.

Relationship between NK Cell Activity and Glucose Regulation in Type 2 Diabetes Patients

Introduction: NK cells are cytotoxic lymphocytes critical to innate immunity. The purpose of this study is to find out the difference in NK cell activity between type 2 diabetes patients and controls, and to investigate the association between NK cell activity and glucose control. Methods: 49 subjects were enrolled in this study, with 23 type 2 diabetes patients and 26 normal glucose tolerant controls. Anthropometric and biochemical parameters were assessed. Homeostatic model assessment (HOMA) was calculated for insulin resistance. NK cell activity was measured using a newly developed NK Vueⓡ Kit (ATgen, Seoul), which is a method of detecting and comparing interferon-gamma level from NK cells. Results: NK cell activity was lower in type 2 diabetes patients compared to control subjects. There was a significant inverse linear relationship between NK cell activity and fasting plasma glucose after adjusting for age and gender (r = -0.346, P = 0.045). Postprandial glucose and HbA1c showed a similar tendency with NK cell activity (r = -0.313 and -0.241, and P = 0.072 and 0.17, respectively). Regression analysis showed HbA1c, fasting glucose and postprandial glucose to be independent predictors of NK cell activity (beta = -0.303, -0.360, -0.356, and P = 0.034, 0.011, 0.033). There was no relationship between NK cell activity and HOMA-IR. Conclusions: NK cell activity was lower in type 2 diabetes compared to controls, and it was significantly related to degree of hyperglycemia. A further, larger population study is warranted to confirm the possible correlation. Disclosure J. Kim: None. K. Park: None. S. Lee: None. M. Kim: None. J. Nam: None. S. Kang: None. J. Park: None. C. Ahn: None. Y. Kim: None.

The effects of short-term continuous subcutaneous insulin infusion treatment on fasting glucagon-like peptide-1 concentrations in newly diagnosed type 2 diabetes

ObjectiveEarly short-term intensive insulin therapy in newly diagnosed type 2 diabetes patients shows benefit in glycemic control and β-cell function. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose metabolism and development of type 2 diabetes. We did a study to observe the changes of GLP-1 and β-cell function after short-term continuous subcutaneous insulin infusion (CSII) treatment. MethodsA total of 66 subjects were enrolled, including 30 normal glucose tolerance controls (NGT) and 36 patients with newly diagnosed type 2 diabetes between October 2015 and July 2016. Fasting plasma glucose (FPG), insulin, and GLP-1 were measured in each subject. The patients underwent CSII treatment for 2 weeks, and then FBG, insulin, and GLP-1 were measured. HOMA-IR and HOMA-B were then calculated. ResultsAll patients achieved target glycemic control in two weeks. HOMA-IR and HOMA-B improved significantly after intensive interventions (p < 0.05). The GLP-1 concentration increased significantly in patients after treatment (p < 0.05). When grouped according to bodyweight and age in all patients, the HOMA-IR changed significantly in overweight and old age subgroups, the HOMA-B increased significantly in normal weight, overweight and middle age subgroups, and the GLP-1 concentration also increased significantly in overweight and middle age subgroups respectively (p < 0.05). ConclusionShort-term CSII treatment can obtain glycemic control target and recover β-cell function and GLP-1 secretion in newly diagnosed type 2 diabetes patients. The overweight and middle-aged patients may get more benefit from this treatment.

Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes

Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon's action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Fasting levels of amino acids and glucagon in plasma were measured, using validated ELISAs and high-performance liquid chromatography, in obese, middle-aged individuals with I) normal glucose tolerance (NGT) and NAFLD, II) T2D and NAFLD, III) T2D without liver disease, and IV) NGT and no liver disease. Elevated levels of total amino acids were observed in participants with NAFLD and NGT compared with NGT controls (1,310 ± 235 µM vs. 937 ± 281 µM, P = 0.03) and in T2D and NAFLD compared with T2D without liver disease (1,354 ± 329 µM vs. 511 ± 235 µM, P < 0.0001). Particularly amino acids with known glucagonotropic effects (e.g., glutamine) were increased. Plasma levels of total amino acids correlated to plasma levels of glucagon also when adjusting for body mass index (BMI), glycated hemoglobin (HbA1c), and cholesterol levels (β = 0.013 ± 0.007, P = 0.024). Elevated plasma levels of total amino acids associate with hyperglucagonemia in NAFLD patients independently of glycemic control, BMI or cholesterol - supporting the potential importance of a "liver-α-cell axis" in which glucagon regulates hepatic amino acid metabolism. Fasting hyperglucagonemia as seen in T2D may therefore represent impaired hepatic glucagon action with increasing amino acids levels. NEW & NOTEWORTHY Hypersecretion of glucagon (hyperglucagonemia) has been suggested to be linked to type 2 diabetes. Here, we show that levels of amino acids correlate with levels of glucagon. Hyperglucagonemia may depend on hepatic steatosis rather than type 2 diabetes.

Assessment of insulin resistance in Chinese PCOS patients with normal glucose tolerance

The study aimed to investigate insulin resistance (IR) status in polycystic ovary syndrome (PCOS) women with normal glucose tolerance (NGT), and further to evaluate feasible diagnostic method for those patients. Three hundred and twenty-five PCOS women with NGT and ninety-five healthy age-matched controls were recruited with Rotterdam criterion and 75 g oral glucose tolerance test (OGTT). IR status was estimated following a glycemic and insulinemic OGTT (0, 30, 60, 120, and 180 min). A modified HOMA-IR formula was applied to each time-course value of glycemia and insulinemia. The predictive performance of each IR index was analyzed with the use of ROC curves. Compared with healthy controls, both non-obese and obese PCOS patients with NGT had a higher BMI, serum glucose, insulin value (p < .05). The best predictive index of IR in non-obese PCOS-NGT was a HOMA-M30 value of 20.36 or more (AUC: 0.753). In obese PCOS-NGT population, the best predictive performance was obtained by a HOMA-M60 value of 32.17 or more (AUC: 0.868). IR was common in Chinese PCOS women with NGT, and the early assessment of IR should be heeded. We recommended HOMA-M30 (Cutoff: 20.36) and HOMA-M60 (Cutoff: 32.17) as the best predictive parameters for non-obese and obese PCOS-NGT patients, respectively.