Normal Glucose Tolerance Patients Research Articles

Cost-effectiveness of prevention program for type 2 diabetes mellitus in high risk patients in the Republic of Srpska, Bosnia and Herzegovina.

The Republic of Srpska (RS), as a part of the Western Balkans (WB) region, has a higher diabetes prevalence than the EU. This study aims to assess the cost-effectiveness of early treatment of high-risk patients with pre-diabetes and undiagnosed diabetes in our setting. We designed a Markov chain Monte Carlo (MCMC) model which reflects the current International Diabetes Federation (IDF) three-step plan for the prevention of T2DM in those at increased risk. The model captures the evolution of the disease in FINDRISC high-risk patients from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and then to T2DM and its complications. We developed two MCMC models, in order to follow the progression of the disease in high-risk cases, ie, when early treatment is undertaken or when it is not undertaken. The health costs and quality adjusted life years (QALY) were discounted at an annual rate of 3%. The key model parameters were varied in one-way and probabilistic sensitivity analysis. Early treatment resulted in increased life expectancy, postponement of the onset of diabetes and increased QALY for all patients. The discounted incremental cost-effectiveness-ratios (ICER) in NGT, IFG, IGT, and T2DM patients were -289.9, 9724.03, -1478.59 and 4084.67 €. In high-risk IGT patients, ICER was the most favorable, being both a cost saving and QALY gaining, with the consistent results confirmed by the sensitivity analysis. The results recommend the acceptance of a new health policy of identifying IGT patients with the use of FINDRISC questionnaire and plasma glucose measurements; providing them with a lifestyle change program; and implementing intensive diabetes treatment, as their disease progresses. Our results are especially significant for the Western Balkan countries, since this was the first cost-effectiveness study of T2DM prevention in this region.

Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis

BackgroundPlatelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes.MethodsWe enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system.ResultsAmong groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters.ConclusionsIn the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

Association between non-dipping blood pressure pattern and different glucometabolic profile during oral glucose tolerance test

It is known that, a not physiological blood pressure (BP) circadian pattern has been associated with increased risk of organ damage and cardiovascular (CV) event. The aim of this study was to assess the association between circadian BP pattern and glucometabolic phenotypes occurring after oral glucose tolerance test (OGTT). We recruited 810 hypertensive Caucasian patients. All participants underwent to OGTT, laboratory test and 24-h ambulatory BP monitoring (ABPM). The analysis of collected data allowed classifying patients based on nocturnal BP profiles into four categories: dippers, non-dippers, extreme dippers, and reverse dippers. Considering the dipping pattern, the proportion of non-dippers in normal glucose tolerance patients with 1-h glucose ≥ 155 mg/dL (NGT ≥ 155) (36.4%) was higher than NGT < 155 (29.6%) and impaired glucose tolerance (IGT) (34.8%), but lower than type 2 diabetes group (T2DM) (52.6%) (p = 0.001). The proportion of dippers was lower in NGT ≥ 155 (47%) and T2DM (34.6%), when compared with NGT < 155 (53.8%) and IGT (51.2%) (p = 0.017). From logistic regression analysis, 1-h glucose ≥ 155 increased the risk of a pathological nocturnal drop in BP by 74%, (OR = 1.740, 95% CI 1.254–2.415, p < 0.0001). In addition, the improvement in 1 unit of Matsuda was responsible for a 3.5% risk decrease (OR = 0.965, 95% CI 0.958–0.971, p < 0.0001), while e-GFR determined a 0.9% risk reduction of nocturnal BP drop (OR = 0.991, 95% CI 0.984–0.999, p = 0.020). Our data demonstrated the existence, in newly diagnosed hypertensive patients, of an association between circadian BP profile and altered glycemic response during OGTT, in particular NGT ≥ 155 subjects are associated with a non-dipper BP pattern, this is clinically relevant because may explain, at least in part, the increased CV risk in this setting of patients.

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma.

Islet amyloid deposition and reduced β-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects. To date, the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma (PDAC) have not been specifically addressed. To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences (proximal vs distal residual pancreas) are associated with islet amyloid deposition. We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients, including 14 patients with normal glucose tolerance (NGT), 16 patients with prediabetes and 15 new-onset diabetes (NOD) patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020. Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans. Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows: (1) Hematoxylin and eosin for general histological appearance; (2) hematoxylin and insulin for the determination of fractional β-cell area (immunohistochemistry); and (3) quadruple insulin, glucagon, thioflavin T and DAPI staining for the determination of β-cell area, α-cell area and amyloid deposits. Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition, fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions, especially in the prediabetes and NOD groups. Consistent with this finding, the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group (37.35 ± 12.16 cm3 vs 69.79 ± 18.17 cm3, P < 0.001). As expected, islets that stained positive for amyloid (islet amyloid density) were found in the majority of PDAC cases. The proportion of amyloid/islet area (severity of amyloid deposition) was significantly higher in both prediabetes and NOD patients than in NGT patients (P = 0.002; P < 0.0001, respectively). We further examined the regional differences in islet amyloid deposits. Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups (3.98% ± 3.39% vs 0.50% ± 0.72%, P = 0.01; 12.03% vs 1.51%, P = 0.001, respectively). In conclusion, these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation, which may be associated with the pathogenesis of NOD secondary to PDAC.

234-OR: Succinate Potentiates Insulin Secretion through SUCNR1

Here, we examined the role of succinate, a metabolite that acts by engaging the succinate receptor 1 (SUCNR1), in regulating insulin secretion by β-cells. We found that glucose increases SUCNR1 expression in β-cells and that activating SUCNR1 with either extracellular succinate or a synthetic agonist boosts glucose-stimulated insulin secretion through the Gq and PKC signaling pathways. Also, we identified that SUCNR1 is essential for preserving insulin secretion in a diet-induced insulin-resistance model. Mice with β-cell-specific SUCNR1 deficiency had impaired glucose tolerance and reduced insulin secretion when fed a high-fat diet, without changes in β-cell mass or insulin sensitivity. To investigate the physiological significance of succinate as a secretagogue in humans, we studied the potential connection between circulating succinate levels and β-cell function in response to oral and intravenous glucose challenges in a cohort of patients with impaired glucose tolerance (IGT). These patients were characterized by presenting hyperinsulinemia during both oral and intravenous glucose tests, compared to normal glucose tolerance (NGT) individuals. Moreover, succinate levels were elevated in IGT patients in response to these challenges compared to NGT patients, whereas circulating GLP-1 levels during the tests were not different between groups. Remarkably, we found that circulating succinate levels are positively correlated with insulin secretion potentiation during intravenous glucose administration, indicating that this system is activated by high glucose levels and partially regulated by the β-cell in an autocrine fashion. These findings suggest that succinate may act as a hormone, potentiating insulin secretion in humans through SUCNR1- a compensatory mechanism particularly relevant in the hyperinsulinemia elicited by insulin resistance. Our work sheds new light on the role of the succinate-SUCNR1 axis as a potential therapeutic target for improving insulin secretion in metabolic disorders. Disclosure J.Sabadell-basallote: None. J.J.Vendrell: None. S.Fernandez-veledo: None. B.D.Astiarraga: None. M.Ejarque: None. M.Repollés-de-dalmau: None. F.X.Sureda: None. D.F.De jesus: None. C.Núñez roa: None. A.Mari: Consultant; Eli Lilly and Company. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. Funding Spanish Ministry of Science and Innovation (SAF2015-65019-R, RTI2018-093919-B-100); Instituto de Salud Carlos III (FI18/00151, CP10/00438, CPII16/00008); Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CB07708/0012); Catalan Association of Diabetes (PV21039S)

Lipid droplet accumulation in β cells in patients with type 2 diabetes is associated with insulin resistance, hyperglycemia and β cell dysfunction involving decreased insulin granules.

Background and objectivePancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in β cells; however, the pathophysiological significance, especially for β cell function, has not been elucidated. Our aim was to assess LD accumulation in β cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters.MethodsWe examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in β cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy.ResultsThe BODIPY-positive area in β cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in β cells was positively correlated with age (r = 0.45, p = 0.0097), HbA1c (r = 0.38, p = 0.0302), fasting plasma glucose (r = 0.37, p = 0.045), and homeostasis model assessment insulin resistance (r = 0.41, p = 0.049) and negatively correlated with an increase in the C-peptide immunoreactivity level by the glucagon test (r = -0.59, p = 0.018). The ratio of mature insulin granule number to total insulin granule number was reduced in the patients with rich LD accumulation in β cells (p = 0.039).ConclusionsType 2 diabetes patients had high LD accumulation in β cells, which was associated with insulin resistance, hyperglycemia, aging and β cell dysfunction involving decreased mature insulin granules.

New insights on hyperglycemia in 17-hydroxylase/17,20-lyase deficiency.

ObjectiveThe adrenal glands of patients with 17-hydroxylase/17,20-lyase deficiency (17OHD) synthesize excessive 11-deoxycorticosterone(DOC) and progesterone, and produce less amount of sex steroid production. Mineralocorticoids and sex hormones play an important role in regulating glucose homeostasis. This study aimed to describe the glucose metabolism in 17OHD patients diagnosed at Peking Union Medical College Hospital (PUMCH).Design/methodsA total of 69 patients diagnosed with 17OHD after adolescence in PUMCH from 1995 to June in 2021. Among them 23 patients underwent a 3-hours oral glucose tolerance test (3hOGTT) after being diagnosed with 17OHD. Insulin response in patients with normal glucose tolerance (NGT) were further compared between the study two groups with different kalemia status. Another 19 patients were followed up to 30 years and older. All clinical data were obtained from the hospital information system of PUMCH.Results Baseline: (1) The average body mass index(BMI) of all patients at baseline was 20.3 ± 3.7kg/m2. Twenty-three patients underwent 3hOGTT, of whom three were diagnosed with diabetes mellitus, and one with impaired glucose tolerance (IGT). Positive correlation between the ratio of progesterone to upper limit of normal range (P times) and hyperglycaemia was exist(r=0.707, P=0.005). (2) In 19 NGT patients, the insulin concentrations at 0 minute, results of the homeostasis model assessment for β-cell function and insulin resistance were lower in the hypokalaemia group than in the normal kalemia group(7.0(5.8-13.2) vs 12.4(8.9-14.9) μIU/ml, P=0.017; 115.5(88.2-240.9) vs 253.1(177.2-305.8), P=0.048; 1.54(1.17-2.61) vs 2.47(1.91-2.98), P=0.022, respectively). Follow-up: Four patients had IGT, while seven patients had diabetes mellitus. Of the 19 patients,11 had hyperglycaemia. P times was significantly higher(7.6(5.0-11.0) vs 3.75(2.2-5.3), P=0.008) in hyperglycemia group than in the normal glucose group.ConclusionsAbnormal glucose metabolism was common in 17OHD patients, which was possibly associated with hypokalaemia and high progesterone levels. Routine monitoring on glucose metabolism in 17OHD patient should be conducted.

NDRG1 Activity in Fat Depots Is Associated With Type 2 Diabetes and Impaired Incretin Profile in Patients With Morbid Obesity.

ObjectiveWe aimed to investigate insulin-, mTOR- and SGK1-dependent signaling basal states in morbidly obese patients’ fat. We analyzed the correlation between the signaling activity, carbohydrate metabolism, and incretin profiles of patients.MethodsThe omental and subcutaneous fat was obtained in patients with obesity. The omental study included 16 patients with normal glucose tolerance (NGT) and 17 patients with type 2 diabetes mellitus (T2DM); the subcutaneous study included 9 NGT patients and 12 T2DM patients. Insulin resistance was evaluated using the hyperinsulinemic euglycemic clamp test and HOMA-IR index. The oral glucose tolerance test (OGTT) for NGT patients and mixed meal tolerance test (MMTT) for T2DM patients were performed. The levels of incretins (GLP-1, GIP, oxyntomodulin) and glucagon were measured during the tests. Signaling was analyzed by Western blotting in adipose tissue biopsies.ResultsWe have shown equal levels of basal phosphorylation of insulin- and mTOR-dependent signaling in omental fat depot in NGT and T2DM obese patients. Nevertheless, pNDRG1-T346 was decreased in omental fat of T2DM patients. Correlation analysis has shown an inverse correlation of pNDRG1-T346 in omental fat and diabetic phenotype (HbA1c, impaired incretin profile (AUC GLP-1, glucagon)). Moreover, pNDRG1-T346 in subcutaneous fat correlated with impaired incretin levels among obese patients (inverse correlation with AUC glucagon and AUC GIP).ConclusionsAccording to results of the present study, we hypothesize that phosphorylation of pNDRG1-T346 can be related to impairment in incretin hormone processing. pNDRG1-T346 in adipose tissue may serve as a marker of diabetes-associated impairments of the systemic incretin profile and insulin sensitivity.

The Relationship Between Neutrophil/Lymphocyte Ratio (NLR) and Mean Platelet Volume (MPV) with Microalbuminuria in Participants with Different Glucose Tolerances

Neutrophil/lymphocyte ratio (NLR) is a simple and inexpensive marker of subclinical inflammation for chronic diseases. Mean platelet volume (MPV) is a platelet function index. This study aimed to evaluate the relationship of NLR and MPV with microalbuminuria in participants with different glucose tolerances. 951 patients (male/female=302/649) were divided into five groups according to their oral glucose tolerance test (OGTT) results: group 1=normal glucose tolerance (NGT), group 2=impaired fasting glucose (IFG), group 3=isolated impaired glucose tolerance (IGT), group 4=both IFG and IGT, and group 5=type 2 diabetes mellitus (DM). Additionally, patients were divided into three groups according to their glycated hemoglobin (HbA1c) results: group 1=NGT, group 2=prediabetes, and group 3=type 2 DM. Outcomes were compared between groups. According to the OGTT, HbA1c, and OGTT+HbA1c criteria, there was a significantly positive correlation of microalbuminuria with MPV and NLR in all DM patients (p<0.001). Additionally, according to the OGTT, HbA1c, and OGTT+HbA1c criteria, there was a significantly positive correlation between MPV and microalbuminuria in all NGT patients (p<0.001). According to the OGTT and OGTT+HbA1c criteria, there was no significant correlation between NLR and microalbuminuria in prediabetic patients (p>0.05); however, there was a significantly positive correlation between NLR and microalbuminuria in the group with HbA1c 5.7–6.49 (p<0.001). Except isolated IFG and IGT, there was a significantly positive correlation between MPV and microalbuminuria in all prediabetic patients according to the OGTT, HbA1c, and OGTT+HbA1c criteria (p<0.001). NLR and MPV levels may be reliable predictive markers for the detection of microalbuminuria in prediabetes and DM.

Combined Indeterminate and Impaired Glucose Tolerance Is a Novel Group at High Risk of Cystic Fibrosis-Related Diabetes

Indeterminate glycemia (INDET) and impaired glucose tolerance (IGT) are independently associated with cystic fibrosis-related diabetes (CFRD) risk. We determined whether patients meeting both criteria have increased risk of diabetes in 2 separate adult cohorts. The Montreal Cystic Fibrosis Cohort (MCFC; n = 293 baseline and 198 for prospective analysis excluding subjects identified with incident CFRD at baseline) and the Lyon cystic fibrosis cohort [Determination of the Predictive Factors in the Reversibility or the Aggravation in the Disorders of the Glucose Metabolism in Cystic Fibrosis Patients (DIAMUCO); n = 144/105] are prospective observational cohorts. In the MCFC and DIAMUCO cohorts, mean age was 25.5 ± 7.7 and 25.0 ± 8.6 years; body mass index, 21.7 ± 3.0 and 20.2 ± 2.2 kg/m2; percentage of forced expiratory volume expired in 1 sec, 73.2 ± 22.1 and 62.5 ± 21.9; and follow-up, 6.9 ± 3.8 and 2.4 ± 1.2 years, respectively. In the MCFC cohort, the IGT only and combined INDET and IGT (INDET + IGT) groups had greater risk of CFRD (P = 0.0109). In the DIAMUCO cohort, there was lower diabetes-free survival in the INDET + IGT group (P = 0.0105). In both cohorts, CFRD risk ranged from 17% in normal glucose tolerance patients up to 42% to 56% in patients with INDET + IGT. Patients who meet combined criteria have a higher risk of developing diabetes probably justifying closer follow-up.

1287-PUB: SGK1-NDRG1 Signal Axis as a Key Marker Associated with Insulin Resistance and Impaired Incretin Profile in Subcutaneous and Omental Fat Depots among Obese Patients

Objective: We have performed the comparative study of basal state of SGK-dependent signaling among obese patients with/without type 2 diabetes mellitus (T2DM). We have accomplished correlation analysis of glucose metabolism and incretin profile parameters against phosphorylation and expression parameters for SGK1 and its substrate NDRG1. Methods: 36 patients with long (&amp;gt;10 years) and morbid (BMI&amp;gt;35 kg/m2) obesity, 18 of which had normal glucose tolerance (NGT) and 18 had T2DM were enrolled in this study. Hyperinsulinemic-euglycemic clamp test and HOMA-IR were used to evaluate the insulin resistance. Blood samples taken at 0, 30 and 120 min of food load test were used to assess incretin profile, insulin and glucose levels. Biopsies from subcutaneous and omental fat depots were obtained during bariatric surgery for all patients and signaling states were analyzed by western blot. Results: Analysis of SGK signaling for subcutaneous fat has shown single significant intergroup difference: enhancing of pSGK-S422 phosphorylation in T2DM group, but also pNDRG-T346 level has tendency to accumulation in subcutaneous fat of NGT patients. Analysis of SGK signaling for omental fat has shown similar results: in this case accumulation of pNDRG-T346 in NGT patients was statistically significant. Correlation analysis has shown strong direct correlation of pNDRG-T346 level with BMI and AUC for GLP-1 and reverse correlation of pNDRG-T346 with Hb1Ac and AUC for glucagon. For pSGK-S422 we have observed opposite characters of correlations with the similar parameters of carbohydrate metabolism and incretin profile. Conclusions: In present work we have taken more patients and have shown critical relevance and general character of stress-dependent SGK1-NDRG1 signal axis as a marker of insulin resistance for different fat depots. Disclosure I. Stafeev: None. A. V. Vorotnikov: None. Y. V. Parfyonova: None. M. V. Shestakova: None. I. Sklyanik: None. E. Mamontova: None. S. Michurina: None. E. Shestakova: None. K. Yahyaev: None. A. Yurasov: None. E. Ratner: None. M. Menshikov: None. Funding Russian Science Foundation (17-15-01435)

Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is characterized by glycemia and insulin disorders. Bile acids (BAs) have emerged as vital signaling molecules in glucose metabolic regulation. BA change in GDM is still unclear, which exerts great significance to illustrate the change of BAs in GDM. GDM patients and normal pregnant women were enrolled during the oral glucose tolerance test (OGTT) screening period. Fasting serums were sampled for the measurement of BAs. BA metabolism profiles were analyzed in both pregnant women with GDM and those with normal glucose tolerance (NGT). Delivery characteristics, delivery gestational age, and infant birthweight were extracted from medical records. GDM patients presented distinctive features compared with NGT patients, including higher body mass index (BMI), elevated serum glucose concentration, raised insulin (both fasting and OGTT), and increased hemoglobin A1c (HbA1c) levels. Higher homeostasis model assessment of insulin resistance (HOMA-IR) and decreased β-cell compensation (i.e., oral disposition index (DIo)) were also prevalent in this group. Total BAs (TBAs) remained stable, but glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) levels declined significantly in GDM. GDCA was inversely correlated with HOMA-IR and positively correlated with DIo. No obvious differences in clinical outcome between the GDM and NGT groups were observed. However, GDM patients with high HOMA-IR and low DIo tended to have a higher cesarean delivery rate and younger delivery gestational age. In conclusion, GDCA provides a valuable biomarker to evaluate HOMA-IR and DIo, and decreased GDCA levels predict poorer clinical outcomes for GDM.

Effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome with different glucose tolerance status

To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared. Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (P<0.05), and NO was increased (P<0.05) in the two groups; FPG, 2hPG, FINS and HOMA-IR after treatment were decreased in the IGT group (P<0.05), the improvement of the above indexes in the IGT group was more significant than that in the NGT group (P<0.05). After treatment, the serum levels of ADMD, ET-1 and MDA were decreased (P<0.05), and NO was increased (P<0.05) in the obese subgroup. In the IGT group, the improvement of serum ADMD, ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). In the NGT group, the improvement of ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.

The Relationship Between the Expression of Resistin and Apoptosis Factors in Placenta and the Pathogenesis of Gestational Diabetes Mellitus

Abstract Objective: To detect the expression of caspase-3, baculoviral inhibitor of apoptosis repeat containing 5 (BIRC-5), vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), and the concentration of resistin protein in placental of patients with gestational diabetes mellitus (GDM) and normal pregnant women, and to explore its correlation with the pathogenesis of GDM and its significance. Methods: This study includes 30 pregnant women who chose cesarean section at Tongji Hospital of Tongji Medical College during May 2013 to February 2014: 15 GDM patients and 15 normal glucose tolerance patients. The expression of caspase-3, VEGF, HIF, and BIRC-5 in placenta of 15 patients with GDM (GDM group) and 15 normal late pregnancy (control group) was detected by real-time fluorescence quantitative polymerase chain reaction. The concentration of resistin protein in the placenta was detected by enzyme-linked immunosorbent assay. Results: Compared with the control group, the expression of caspase-3, HIF, VEGF, resistin in placenta of GDM group increased significantly (P &lt; 0.05); the expression of BIRC-5 in placenta of GDM group decreased significantly (P &lt; 0.05). Conclusion: The expression of caspase-3, BIRC-5, VEGF, HIF, and resistin in placenta of GDM patients and normal pregnant women are significantly different, which may be involved in the pathogenesis of GDM disease.

Circulating miR-135 May Serve as a Novel Co-biomarker of HbA1c in Type 2 Diabetes.

Hemoglobin A1c (HbA1c) is a reliable marker of insulin resistance in normal glucose tolerance patients; however, several physiological, environmental, and genetic factors may affect HbA1c and cause false results. Therefore, it is essential to use new biomarkers due to increasing diabetes predictive value. Recently, it has been indicated that microRNAs (miRNAs) are involved in the pathophysiology of diabetes, particularly, in insulin resistance pathways. Therefore, miRNAs have the potential to be introduced as new glycemic control biomarkers. The aim of this study was to investigate the association between plasma level of miRNA-135a and HbA1c in patients with prediabetes and type 2 diabetes. In this case-control study, 120 samples were enrolled (healthy individuals, people with type 2 diabetes, and prediabetes) and HbA1c and miR-135a expression level in their plasma samples were evaluated. Multinomial logistic regression and ROC curve analysis were conducted to assess the diagnostic accuracy of plasma miR-135a in T2D , prediabetes, and healthy control groups. Data analysis indicated that miR-135a was significantly elevated in both diabetes/prediabetes samples. Then, subjects were reclassified based on the calculated cutoff value of miRNA. Logistic Regression analysis showed that an increased level of miRNA positively correlated with HbA1c level in prediabetes (Adjusted OR = 1.14, p value = 0.033) and diabetic status (Adjusted OR = 1.27, p value = 0.024 ). miR-135 may provide an assistant marker for HbA1c to detect type 2 diabetes.

P4406New hypothesis of the insulin resistance development: role of adipose-derived stem cell proliferation and adipogenesis

Abstract Background Obesity, remaining a topical issue of modern medicine, leads to development of latent inflammation and insulin resistance in adipose tissue with subsequent development of type 2 diabetes mellitus (T2DM). Among patients with obesity, patients with obesity and normal glucose tolerance (NGT) are often encountered. In our study we have tested the hypothesis that low proliferative potential of adipose derived stromal cells (ADSC) associates with reduced formation of new fat depots, excess accumulation of fat in the functional adipocytes and their hypertrophy, resulting in fat inflammation and insulin resistance. Methods We screened two groups of obese patients with or without T2DM, matched for BMI, age, and duration of obesity to test the hypothesis that hypertrophy and decreased renewal of adipocytes may underlie transition from obesity to T2DM. All patients were matched for carbohydrate metabolism (fasting blood glucose level, glycated hemoglobin, HOMA-IR index and M-index). The subcutaneous and omental fat tissue biopsies were obtained during bariatric surgery from obese individuals with or without T2DM. The morphology and immunophenotype of subcutaneous and omental fat was assessed in frozen tissue sections. ADSC were isolated from both types of fat tissue biopsies and screened for morphology, proliferative potential and inflammatory status. Results The non-diabetic patients had normal carbohydratemetabolism andmoderate insulin resistancemeasured byHOMA-IR and hyperinsulinemic clamp (M-index),while T2DM patientswere extremely insulin resistant by both indexes. The average size of diabetic adipocytes was higher than that of non-diabetic in both subcutaneous and omental fat tissues, indicating adipocyte hypertrophy in T2DM. We have shown that ADSC from T2DM patients had significantly higher level of inflammation. According to measurement of p62 expression and LC3 modification we can say that ADSC from T2DM patients have less autophagy level compare with ADSC from NGT patients. Immunohistochemistry have shown that patients with T2DM have much more infiltration of CD68+-cells in subcutaneous and omental adipose tissue and immunophenotype (balance of M1-M2 macrophages) of adipose tissue at this patients shift toward inflammatory state. Conclusion These results suggest that decreased proliferation and increased hypertrophy of diabetic ADSC may lead to reduced insulin sensitivity via increased inflammation mediated by M1-macrophages and JNK1/2 pathway. Acknowledgement/Funding This work was supported by RSF grant #17-15-01435

Effects of high glucose on proliferation and function of circulating fibrocytes: Involvement of CXCR4/SDF‑1 axis.

The present study aimed to further investigate the effects of high glucose on the function of circulating fibrocytes and its underlying mechanisms. The total peripheral blood mononuclear cells were obtained from normal glucose tolerance patients and type 2 diabetic mellitus patients. Circulating fibrocytes were stimulated with different glucose concentrations for different time periods (24, 48 and 72 h). Cell proliferation was determined by Cell Counting Kit-8 assay. The expression of connective tissue growth factor (CTGF) was detected by western blotting. The expression of COL-I was detected by flow cytometry. The apoptotic bodies of cells were detected by fluorescence microscopy after Hoechst33258 staining. The invasive and migration abilities of fibrocytes were detected by Transwell chamber assay. Secretion of stromal cell-derived factor 1 (SDF-1) was measured by ELISA. The circulating fibrocytes showed a typical spindle-shape and were double-positive for cluster of differentiation 45 (green) and COL-I (red). Compared with the 5.5 mmol/l glucose group, a high glucose concentration significantly promoted the proliferation of circulating fibrocytes and showed the most significant effects at 30 mmol/l after treatment for 48 h. AMD3100 showed no effects on the proliferation of circulating fibrocytes. Flow cytometry revealed that 30 mmol/l glucose significantly promoted the expression of COL-I vs. 5.5 mmol/l glucose group (P<0.01), while AMD3100 reversed this (P<0.05). Hoechst33258 staining showed no differences in the apoptotic bodies between experimental groups (P>0.05). Western blotting revealed that the expression of CTGF was decreased significantly by AMD3100 pretreatment (P<0.01). Transwell chamber assay showed that 30 mmol/l glucose significantly promoted the invasive and transfer abilities (P<0.01) of fibrocytes when compared with the 5.5 mmol/l glucose group. While AMD3100 reversed the cell migratory effects induced by high glucose (P<0.01). In addition, the secretion of SDF-1 stimulated by 30 mmol/l glucose DMEM showed no differences compared with 5.5 mmol/l glucose DMEM (P>0.05). High glucose stimulated the expressions of CTGF and COL-I, and promoted migration of circulating fibrocytes via the CXC chemokine receptor 4/SDF-1 axis.

Adiponectin and insulin resistance are related to restenosis and overall new PCI in subjects with normal glucose tolerance: the prospective AIRE Study

BackgroundIn patients with Normal Glucose Tolerance (NGT) some causes of ischemic heart disease (IHD) were not completely investigated. The role both of metabolic milieu and adipokines in IHD progression was not fully investigated. Our aim was to assess the link between adipokines plasma levels, insulin resistance (IR) and IHD in NGT patients undergoing Percutaneous Coronary Intervention (PCI).MethodsAIRE is a single-center prospective longitudinal observational study investigating the IHD outcome of NGT subjects who underwent coronary revascularization by PCI in a third level cardiology center at A.O. dei Colli Hospital, University of Campania “Luigi Vanvitelli”. Six hundred seventy-nine subjects hospitalized in 2015 for coronary arteriography not suffering from Acute Coronary Syndrome (ACS) in the previous 4 weeks, as well as from all conditions could affect glycemic plasma levels and IR status, were assessed for eligibility. Fifty-four patients with neither history of diabetes nor Altered Fasting Glucose (AFG)/Impaired Fasting Glucose (IGT) after Oral Glucose Tolerance Test (OGTT) were finally enrolled. Primary endpoint was the assessment of the relationship of adipokines and HOMA-IR with the occurrence of restenosis in NGT subjects. As secondary endpoint we assessed the association of the same adipokines and IR with overall ACS events after PCI in NGT subjects.ResultsThe 54 NGT patients enrolled were mainly males (85%), with a median age of 60 years [IQR 58–63 years]. Only 4 patients (7.4%) experimented restenosis. Median follow-up was equal to 29.5 months [IQR 14.7–34 months]. Adiponectin levels were independently associated to restenosis (OR 0.206; 95% CI 0.053–0.796; p = 0.000). Instead HOMA-IR and adiponectin appeared independently associated both to de novo IHD (OR 9.6*1013; 95% CI 3.026–3.08*1027; p = 0.042 and OR 0.206; 95% CI 0.053–0.796; p = 0.000, respectively) and overall new PCI (OR 1.5*1011; 95% CI 2.593–8.68*1021; p = 0.042 and OR 0.206; 95% CI 0.053–0.796; p = 0.000, respectively). Moreover, we fixed a potential cut-off for adiponectin for risk of restenosis (≤ 8.5 µg/mL) and overall new PCI (≤ 9.5 µg/mL).ConclusionIR and cytokines play a role in progression of any stage of IHD also in NGT subjects. Our results in this setting of patients, though the relatively small sample size, represent a novelty. Future studies on larger populations are needed to analyze more in depth adipokines and insulin resistance role on IHD progression in non-diabetic people.

Circulating Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1): Relationship with carotid artery elasticity in patients with impaired glucose regulation (IGR)

ObjectiveTo investigate the relations of circulating adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) with carotid artery elasticity in patients with impaired glucose regulation (IGR). MethodsA total of 208 subjects were enrolled from January 2013 to March 2014. One hundred forty-eight were IGR patients, and 60 had normal glucose tolerance (NGT). Carotid intima-media thickness (IMT), carotid artery pressure-strain elasticity coefficient (Eρ), stiffness (β), arterial compliance (AC), and pulse wave velocity (PWVβ), as well as blood pressure, body mass index, blood glucose, blood lipids, insulin resistance index, VCAM-1, and ICAM-1 were measured and compared between IGR and NGT patients. ResultsEρ, β and PWVβ were significantly higher in the IGR group than in the NGT group (P<0.05), but the IMT showed no significant difference (P>0.05). VCAM-1 and ICAM-1 were significantly higher in the IGR group than in the NGT group (P<0.05). VCAM-1 and ICAM-1 were positively correlated with Eρ, β, and PWVβ and negatively correlated with AC in IGR patients. ConclusionsChanges in carotid artery elasticity and endothelial dysfunction are found in patients with IGR. Early comprehensive intervention should be performed in such IGR populations.

Analysis of PTEN expression and promoter methylation in Uyghur patients with mild type 2 diabetes mellitus.

Phosphatase and tension homolog deleted on chromosome 10 (PTEN) was considered as a promising target in type 2 diabetes mellitus (T2DM) because of its negative effects on insulin resistance. Alteration in DNA methylation is thought to play a role in the pathogenesis of T2DM. The aim of the present study was to quantitatively evaluate the promoter methylation of PTEN in Uyghur patients with mild T2DM. We evaluated methylation levels in 21 CpG sites from −2515 bp to −2186 bp relative to the translation initiation site in 55 cases of T2DM and 50 cases of normal glucose tolerance (NGT) using the MassARRAY spectrometry. In addition, PTEN mRNA and protein levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting to determine whether DNA methylation alterations were responsible for PTEN expression. Compared with NGT groups, the PTEN mRNA expression was significantly higher in Uyghur patients with mild T2DM groups. We also showed that PTEN protein expression was upregulated in Uyghur patients with mild T2DM groups, but the level of protein kinase B (AKT) was downregulated. PTEN methylation in T2DM patients was significantly lower than that in NGT groups. In addition, 2 CpG units demonstrated a significant difference between the NGT and Uyghur patients with mild T2DM groups. Furthermore, there was a negative association between promoter methylation and PTEN expression. Together, these findings suggest that epigenetic inactivation of PTEN plays an important role in Uyghur patients with mild T2DM. The aberrant methylation of CpG sites within the PTEN promoter may serve as a potential candidate biomarker for T2DM in the Uyghur population.