Euglycemic Patients Research Articles

A prospective study on urinary microalbuminuria as surrogate marker of vascular endothelial dysfunction, in patients of ischemic stroke

Background: Presence of overt proteinuria has been independently linked to greater stroke risk. The objectives of this study were to determine the relationship between the for ischemic stroke and albuminurea as a marker for vascular events. Microalbuminuria, is an early marker of both kidney disease and endothelial dysfunction, may be associated with global vascular risk, but the nature and relationship between microalbuminuria and incident ischemic stroke has not been clearly defined. The purpose of this study was to assess the association of microalbuminuria and ischemic stroke.Methods: Study enrolled 150 admitted patients of acute ischemic stroke. The patients were assessed by questionnaire, microalbuminuria, creatinine clearance after detailed history taking and thorough clinical examination.Results: The combined common risk factors were HTN (80%), diabetes (33%) and smoking (53%). The hypertensive patients had 8 times higher risk of microalbuminuria as compared to normotensive patients (95% 1.8-31.0 p<0.05). Among diabetes patients had risk of microalbuminuria 30 times higher compared to euglycemic patients (95% CL 9.6-78.8 p<0.01). The smoker patients had 8 times risk of microalbuminuria (CL 95%-1.2-22.8 p<0.16). However, the patients who had dyslipidemia had risk of microalbuminuria 1.07 times who have normal lipid level, but it was statistically insignificance (98% CL 0.8-4.1 p>0.05). The 38 patients out of 46 patients who had microalbuminuria has high normal serum creatinine with creatinine clearance (45-59 mL/min/1.73 m2. (82% versus. 4.4% 30.44 mL/min/173m2). The risk of microalbuminuria was higher in patients who had high normal serum creatinine (1.4 mg/dL) with creatinine clearance of 45-59 mL/min/1.73 m2 versus normal serum creatinine 0.8 mg/dL.Conclusions: The finding of the study, show the microalbuminuria is an independent risk factor for vascular endothelial dysfunction, in patient of diabetes early renal dysfunction and HTN, extrapolating the vascular event (ischemic stroke).

Effects of two different dialytic treatments on inflammatory markers in people with end-stage renal disease with and without type 2 diabetes mellitus

This study was aimed to evaluate the effects on some inflammatory markers of two dialytic treatments [bicarbonate dialysis (BHD) and hemodiafiltration (HDF)] in patients with severe chronic kidney disease.We evaluated: blood glucose, homeostasis model assessment insulin resistance index, homocistein (Hcs), high sensitivity C-reactive protein (hs-CRP), fibrinogen, lipoprotein (a) [Lp(a)], metalloproteinases-2, and -9 (MMP-2 and MMP-9), and soluble receptor for advanced glycation end products (sRAGE).Considering the all sample, we observed a decrease of sRAGE with BHD, but not with HDF. Fibrinogen, MMP-2, and -9, Hs-CRP decreased after HDF, but not after BHD. In diabetics, blood glucose decreased after HDF dialysis, but not after BHD. Soluble receptor for advanced glycation end products obtained with HDF were higher compared to BHD. Fibrinogen, MMP-2, MMP-9, Hcs, Hs-CRP decreased, and ADN increased after HDF, these changes did not happen after BHD. Furthermore, sRAGE, and ADN were higher, and MMP-2 lower after HDF. In euglycemic patients, instead, MMP-2, MMP-9, and Hs-CRP decreased, and ADN increased with HDF, but not with BHD.We can conclude that hemodiafiltration seems to greater reduce inflammatory markers, and it could be more suitable for people with type 2 diabetes.Registration number: ClinicalTrials.gov NCT01049152.

Assessment of atrial conduction times in prediabetic patients with coronary artery disease.

Objective:Prediabetes is a dysglycemic state and is associated with subtle myocardial injury and dysfunction. We evaluated atrial conduction times (ACTs) and atrial electromechanical delays (EMDs) in prediabetic patients with coronary artery disease (CAD).Methods:In the present study, we recruited 128 consecutive patient candidates (40 euglycemic, 48 prediabetic, and 40 diabetic patients) for coro- nary artery bypass grafting. ACTs were measured using tissue Doppler imaging (TDI). The time intervals between the beginning of the P wave in the surface electrocardiogram and the peak of the a¢ wave in TDI (PA) in the septal and lateral mitral annuli and the lateral tricuspid annulus were measured and termed as “septal PA,” “lateral PA,” and “right ventricular (RV) PA,” respectively. The differences between lateral and septal PA, septal and RV PA, and lateral and RV PA were termed as “left intra-atrial EMD,” “right intra-atrial EMD,” and “inter-atrial EMD” respectively.Results:Septal PA, lateral PA, RV PA, left and right intra-atrial EMDs, and inter-atrial EMD were not statistically different between these three groups. Furthermore, multivariable linear regression models, adjusted for potential confounders, showed that glycemic state was not associated with ACTs, left and right intra-atrial EMDs, and inter-atrial EMD.Conclusion:There were no significant differences between the euglycemic, prediabetic, and diabetic patients with CAD regarding ACTs and atrial EMDs.

A Genetic Risk Score for Insulin Resistance Identify Patients with Chronic Myeloid Leukemia, Treated with Nilotinib, Developing Diabetes

BACKGROUD: Nilotinib, a potent 2nd generation tyrosin kinase inhibitor, is efficacious in the treatment of chronic myelogenous leukemia (CML). Impaired glucose metabolism represents one of the most frequently observed adverse events and several clinical trials, reported a high diabetes incidence during treatment with this drug. The mechanism of this side effect is poorly understood, but recently has been hypothesized an increased postreceptorial insulin resistence. Moreover, "in vitro"results indicated that c-ABL is involved in the insulin receptor signaling pathway. A large number of genetic variants associated with Type 2 diabetes (T2D) are implicated in beta-cell function but the role of common genetic variants associated with insulin resistance in the etiology of T2D, remains poorly documented. Scott R. and al. (Diabetes 2014) recently identified 10 multiple single nucleotide polymorphisms (SNPs) associated with insulin resistance and created a genetic risk scores (uGRS) as complementary tool to for insulin resistance.AIM of the study was to identify whether this uGRS could be a valid prognostic tool in identifying patients developing diabetes during Nilotinib therapyPATIENTS AND METHODS:45 patients (19 males) were included in the study. Twenty-four were treated with Nilotinib in first-line and 21 as second line (10 for resistance, 8 intolerance and 3 for other reasons). None of the subjects studied had abnormal blood glucose or took any antidiabetic drug before Nilotinib treatment.We genotyped all patients with the GRS created by Scott R. including those in, or near, the IRS1, GRB14, ARL15, PPARG, PEPD, ANKRD55/MAP3K1, PDGFC, LYPLAL1, RSPO3, and FAM13A1 genes that have primary effects on subcutaneous adipocyte function. Also we added 2 new variants, one for TCF7L2 gene, associated with insulin secretion and another in FTO gene, whose effect on insulin levels is mediated by BMI. The uGRS was calculated, as previously reported, by summing the number of risk alleles across the 12 variants (0 for risk allele absent, 1 for heterozygosity and 2 for homozygosity for risk allele). A cut-off point for uGRS, maximizing predictivity and sensitivity of the score was calculated using Youden's index. Diabetes and impaired fasting Glycaemia were defined using the American Diabetes association (ADA) criteria. Data were reported as median and range,RESULTS:Age at diagnosis was 45(18-82) years, the Sokal was low in 16 (42%), intermediate in 12 (26%) and high in 17 (32%) patients. During treatment and subsequent follow up of 45(7-127) months, 28 patients remained euglycemic, 5 (2 treated in the first line) developed diabetes after 14(1-32) months and 12 (6 treated as first line) developed IFG in 6 (1-12) months. No IFG patients developed an overt diabetes in the subsequent follow-up of 60.3 (33-102) months.We calculated a cut-off point of 12 for uGRS. When the 28 euglycemic patient were compared with 5 patients becoming diabetics after Nilotinib, uGRS showed a sensibility of 100% and a specificity of 46% in predicting diabetes. Consequently, the positive predictive valuewas 25% where the negative predictive values 100%. When the 28 euglycemic patients were compared with the 12 patients developing IFG after Nilotinib, the sensibility and specificity of uGRS was low: 50% and 46% respectively.CONCLUSIONS: A Genetic risk score for insulin resistance showed high specificity and a strong negative predictive values when used to identify CML patients treated with Nilotinib developing an overt diabetes. Further studies in lager populations are needed to confirm this predictivity that can be used in clinical practice to tailor the best anti TKI therapy. DisclosuresNo relevant conflicts of interest to declare.

Impaired Left Atrial Conduit Function in Coronary Artery Disease Patients With Poorly Controlled Diabetes: Two-Dimensional Speckle-Tracking Echocardiographic Study.

The myocardium can be affected by diabetes mellitus. The effects of blood glucose control on some organs such as the kidney and eye have been previously reported. The aim of our study was to evaluate left atrial function via 2-dimensional (2D) speckle-tracking echocardiography in a group of coronary artery disease (CAD) patients with well-controlled diabetes (hemoglobin A1c [HbA1c] < 7%) and to compare it with that in a group of CAD patients with poorly controlled diabetes. This cross-sectional study included 110 CAD patients, comprising 44 euglycemic control patients, 33 patients with well-controlled diabetes (HbA1c < 7%), and 33 patients with poorly controlled diabetes. The study population thereafter underwent 2D speckle-tracking echocardiography for an evaluation of their left atrial function. Our findings showed that the absolute values of early diastolic strain and early diastolic strain rate were lower in the CAD patients with poorly controlled diabetes than in the euglycemic control patients with CAD. Moreover, early diastolic strain in the CAD patients with poorly controlled diabetes was lower than that in the CAD patients with well-controlled diabetes. Multivariable analysis revealed that poorly controlled diabetes was an independent determinant of early diastolic strain and strain rate. The conduit function of the left atrium was impaired in the CAD patients with poorly controlled diabetes compared with that in the euglycemic control patients with CAD and the CAD patients with well-controlled diabetes.

Clinical Study of Serum Homocysteine and Non-Alcoholic Fatty Liver Disease in Euglycemic Patients.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic liver disease. NAFLD includes a spectrum of hepatic pathologies: simple fatty liver, steatohepatitis and cirrhosis. Insulin resistance may contribute to NAFLD. The liver plays an important role in the production and metabolism of homocysteine (HCY), which is known to be an independent risk factor for cardiovascular disease. High HCY level can aggravate NAFLD by increasing the reactive oxygen species and activating oxidative stress. In this study, we investigated the relationship between HCY and NAFLD in euglycemic patients.Material/MethodsA total of 1143 euglycemic patients were recruited: 519 patients with non-alcoholic fatty liver disease (NAFLD) and 624 sex and age-matched controls without NAFLD.ResultsThe NAFLD group had significantly higher HCY level (13.78±5.84 vs. 11.96±3.58 mmol/L, p<0.001), as well as higher body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for beta cell function (HOMA-B), and lower high density lipoprotein cholesterol (HDL-C). HCY level was positively correlated with HOMA-IR (r=0.239, p<0.001), TG (r=0.356, p<0.001) and negatively correlated with HDL-C (r=−0.161, p<0.001). In the logistic regression analysis, BMI (beta=0.345, p<0.001), HOMA-IR (beta=0.654, p<0.01), TG (beta=0.881, p<0.001), and HCY (beta=0.04, p=0.044) were the predictors of NAFLD.ConclusionsHigher HCY level existed in NAFLD patients and was correlated with the severity of insulin resistance. HCY is an independent risk factor for NAFLD.

Small amounts of tissue preserve pancreatic function: Long-term follow-up study of middle-segment preserving pancreatectomy.

Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear.The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP.From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires.Our case series included 3 women and 2 men, with median age of 50 (37–81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250–615) min and 800 (400–5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4 preoperatively euglycemic patients. Beta-cell function parameters in this group of patients were quite comparable to those after Whipple procedure, and seemed better than those after total pancreatectomy. No symptoms of hypoglycemia were identified in any patient, although half of the patients reported symptoms of exocrine insufficiency.In conclusion, MPP is a feasible and effective procedure for middle-segment sparing multicentric lesions in the pancreas, and patients exhibit satisfied endocrine function after surgery.

Lipid and inflammatory biomarker profiles in early insulin resistance.

To analyze the serum lipid and inflammatory biomarker profile in the early insulin resistance (e-IR). Cross-sectional study of 5943 adults without diabetes, stratified into no IR group (C-peptide <third tertile and glucose <100mg/dL), e-IR group (C-peptide ≥third tertile and glucose <100mg/dL) and advanced IR group (glucose ≥100mg/dL). E-IR showed significant differences with no IR in the serum concentration of triglycerides (P<0.001), HDL cholesterol (P<0.001), LDL cholesterol (P<0.001), sCD40L (P<0.001), C-reactive protein (P<0.004), leptin (P<0.001) and adiponectin (P<0.001). Adjusting for age, gender and abdominal obesity, corroborated the association of e-IR with highest quintile of triglycerides (OR 3.88 [3.07-4.89]), HDL cholesterol (OR 0.35 [0.28-0.44]), sCD40L (OR 0.47 [0.24-0.94]), C-reactive protein (OR 2.31 [1.29-4.12]), adiponectin (OR 0.11 [0.04-0.32]), PAI-1 (OR 3.29 [1.29-8.40]) and resistin (OR 1.25 [1.01-1.54]); the same biomarkers were associated with advanced IR although resistin was a protective factor (OR 0.73 [0.58-0.93]). Euglycemic patients with e-IR present an unfavorable serum lipid and inflammatory biomarker profile. Measuring C-peptide in euglycemic patients with elevated triglycerides identifies e-IR.

Severe dyslipidemia and immune activation in HIV patients with dysglycemia

Background and Objective: Diabetes mellitus (DM) is common in human immunodeficiency virus (HIV)-infected patients. However, the relationship between dysglycemia, lipid metabolism, and immune activation in HIV patients is poorly understood.Methods: We retrospectively analyzed the clinical data of 180 HIV patients, including 153 patients undergoing highly active antiretroviral therapy (HAART) and 27 HAART-naive patients. DM was defined as fasting serum glucose levels ≥126 mg/dl, and impaired fasting glucose (IFG) was defined as serum glucose levels of 101–125 mg/dl at two different time points. Lipid metabolic indexes were measured. CD4+, CD8+, and CD8+ HLA-DR+ T cells were determined by flow cytometry.Results: IFM and DM percentages were higher in the HAART group than in the HAART-naive group (59.5% vs. 48.1% and 21.6% vs. 7.4%, respectively; p < 0.01). Additionally, DM percentage was high in patients receiving HAART containing protease inhibitors. Serum levels of triglycerides and very low-density lipoprotein cholesterol were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Serum triglyceride levels were higher in HAART-naive DM patients than in other patients (p < 0.05). CD8+ and CD8+ HLA-DR+ cell counts were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Ordinal logistic regression analysis suggested that TRIG, VLDL, CD8, and HAART were predictors of glucose metabolic disorders.Conclusion: HIV patients with hyperglycemia have severe dyslipidemia and immune activation, and HAART is an important impact factor of glucose and lipid metabolic disorders.

Gliflozin monotherapy for type 2 diabetes: a review of NICE Technology Appraisal 390

Gliflozin monotherapy for type 2 diabetes: a review of <scp>NICE</scp> Technology Appraisal 390

Postoperative hyperglycemia in nondiabetic patients after gastric surgery for cancer: perioperative outcomes.

Hyperglycemia (HG) is widely known to be associated with increased postoperative complications after colorectal surgery. Very few data on the effects of HG on patients after gastric surgery for cancer are reported in literature. The aim of this study was to evaluate the effects of postoperative HG in non-diabetic patients undergoing gastrectomy for cancer. One hundred and ninety-three consecutive gastrectomies for cancer performed between January 2010 and December 2015 were considered. Diabetic patients, and those undergoing pancreatic resections were excluded. Postoperative blood glucose levels were monitored in the first 72h after surgery. Postoperative complications, mortality, and postoperative course were analyzed in patients who experienced postoperative HG (blood glucose level; BGL>125mg/dl) compared with euglycemic patients (BGL≤125mg/dl). Differences between mild HG (BGL between 125 and 200mg/dl) and severe HG (BGL≥200mg/dl) were also analyzed. Ninety-six patients (55.5%) experienced postoperative HG. In 11 patients (6.4%), a severe postoperative HG was found. Postoperative BGL>200mg/dl was related to worse outcomes than those experienced by euglycemic patients (and even than patients who experienced mild postoperative HG). The postoperative complications rate was 24.8% (43 patients out of 173), but significantly higher in patients with postoperative severe HG compared to mild HG and normoglycemic patients (63.6, 30.6, and 13%, respectively, p<0.001). Poor postoperative glycemic control seems to be related to worse postoperative outcomes even in patients undergoing elective gastric surgery for cancer.

VGF Peptide Profiles in Type 2 Diabetic Patients' Plasma and in Obese Mice.

To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74±10 vs. 167±28, and 92±10 vs. 191±19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p<0.03). Upon a standard glucose load, a distinct response was shown for VGF C-terminus, TLQP and QQET-like (ERVW immunoreactive) peptides in euglycemic normal BMI patients, but was virtually abolished in euglycemic obese, and in T2D patients independently of BMI. High-fat diet induced obese mice showed reduced plasma VGF C-terminus, NAPPE and QQET-like (ERVW) peptide/s (3±0.2 vs. 4.6±0.3, 22±3.5 vs. 34±1.3, and 48±7 vs. 100±7 pmol/ml, mean+SEM, n = 8/group, obese vs. slim, respectively, p<0.03), with a loss of the response to glucose for all VGF peptides studied. In immunohistochemistry, TLQP and/or VGF C-terminus antibodies labelled VGF containing perikarya in mouse celiac ganglia, pancreatic islet cells and thin beaded nerve fibres in brown adipose tissues, with fewer in white adipose tissue. Upon the glucose load, tyrosine hydroxylase and VGF C-terminus immunoreactive axons became apparent in pancreatic islets of slim animals, but not in obese animals. Alltogether, a significant loss of VGF peptide immunoreactivity and/or their response to glucose was demonstrated in obese patients, with or without T2D, in parallel with a similar loss in high-fat diet induced obese mice. An involvement of VGF in metabolic regulations, including those of brown and/or white adipose tissues is underlined, and may point out specific VGF peptides as potential targets for diagnosis and/or treatment.

Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control

BackgroundAfter ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk. MethodsA newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease. ResultsBetaine concentrations in males were significantly higher than in females (42.0 vs. 35.9 μmol/L; p < 0.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980 μmol/L; p = 0.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43 μmol/L; p = 0.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho: −0.281; p < 0.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8 μmol/L; p = 0.045). ConclusionsPlasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease.

Admission glucose and in-hospital mortality in patients with acute myocardial infarction, with and without diabetes, from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective analysis

BackgroundThe relation between blood glucose concentrations on hospital admission and in-hospital mortality in patients with acute myocardial infarction, with and without diabetes, has not been well characterised in Chinese patients. MethodsUsing the China PEACE-Retrospective Acute Myocardial Infarction Study, we took a representative sample of patients with acute myocardial infarction from 2001, 2006, and 2011 and classified them according to their blood glucose concentrations on admission to hospital (<3·9, 3·9–7·8, 7·8–11·1, ≥11·1 mmol/L). We compared in-hospital mortality across these admission glucose categories, stratified by diabetes status. The central ethics committee at the China National Center for Cardiovascular Diseases approved the study, with a waiver of patients' written consent. This study is registered with www.ClinicalTrials.gov, NCT01624883. FindingsDespite an increase in the proportion of patients with diabetes admitted to hospital for acute myocardial infarction in 2001–11 (17·5% in 2001, 20·1% in 2006, and 23·1% in 2011; p=0·0001), in-hospital mortality associated with hyperglycaemia on admission did not change (p=0·2). The relation between blood glucose concentration on admission and in-hospital mortality risk in patients with acute myocardial infarction with or without recognised diabetes was consistent across different study years (p value for interaction 0·9). After adjustment for patients characteristics and clinical status, compared with euglycaemic patients (7·8–11·1 mmol/L), hyperglycaemia (≥11·1 mmol/L) was associated with an increase in mortality risk both in patients with known diabetes (odds ratio [OR] 2·49, 95% CI 1·59–3·90) and in patients without known diabetes (2·59, 2·17–3·09). By contrast, hypoglycaemia (<3·9 mmol/L) was associated with a greater risk of in-hospital mortality only in patients with known diabetes (2·93, 1·16–7·39). A U-shaped relation exists between blood glucose concentrations on admission and in-hospital mortality in patients with diabetes, but a more linear relationship exists in patients without diabetes. InterpretationIn Chinese patients with acute myocardial infarction, both hyperglycaemia and hypoglycaemia on admission to hospital are associated with an increased risk for in-hospital mortality in patients with diabetes. However, only hyperglycaemia, but not hypoglycaemia, is a predictor of increased mortality for patients without diabetes. FundingThis project was partly supported by the Research Special Fund for Public Welfare Industry of Health (201202025) from the National Health and Family Planning Commission of China, the National Key Technology R&D Program (2013BAI09B01) from the Ministry of Science and Technology of China, and grant 20131100501 from State Administration of Foreign Experts Affairs of China. HMK is supported by grant U01 HL105270-05 (Center for Cardiovascular Outcomes Research at Yale University) from the US National Heart, Lung, and Blood Institute. The sponsors had no role in the conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation or approval of the abstract.

Effect of blood-sugar limitation on intensive care mortality: Intragroup evaluation.

To evaluate the safety profile of blood sugar limits in intensive care unit (ICU) patients. Adult patients with ICU stay >36 h, more than two blood sugar measurements and antibiotic therapy concordant with locally adapted guidelines were included. For analyses, one study cohort was defined in two ways: as a narrow group, euglycaemic patients' blood sugar levels 80-150 mg/dl; as a moderate group, euglycaemic patients' blood sugar levels 80-180 mg/dl. Dysglycaemia was defined as blood sugar levels <80 mg/dl for >5% of measurements, and >150 mg/dl or >180 mg/dl (narrow or moderate groups, respectively) for >10% of measurements. The primary endpoint was ICU mortality (euglycaemia versus dysglycaemia). The study comprised 668 patients. When defined as a narrow group, ICU mortality was 3% (four of 135) euglycaemic versus 10% (54/533) dysglycaemic patients (odds ratio [OR] 3.692, 95% confidence interval [CI] 1.313, 10.382). When defined as a moderate group, ICU mortality was 6% (21/351) euglycaemic versus 12% (37/317) dysglycaemic patients (OR 2.077, 95% CI 1.188, 3.630). Frequency of severe hypoglycaemia (blood sugar <40 mg/dl) was not different between the narrow and moderate euglycaemic ranges. Euglycaemia was associated with lower ICU mortality than dysglycaemia, and incidence of hypoglycaemia was low overall in this study. Based on current published evidence, therapeutic targets should be defined according to individual patient characteristics.

Insulin resistance and outcome in bipolar disorder.

Little is known about the impact of insulin resistance on bipolar disorder. To examine the relationships between insulin resistance, type 2 diabetes and clinical course and treatment outcomes in bipolar disorder. We measured fasting glucose and insulin in 121 adults with bipolar disorder. We diagnosed type 2 diabetes and determined insulin resistance. The National Institute of Mental Health Life Chart was used to record the course of bipolar disorder and the Alda scale to establish response to prophylactic lithium treatment. Patients with bipolar disorder and type 2 diabetes or insulin resistance had three times higher odds of a chronic course of bipolar disorder compared with euglycaemic patients (50% and 48.7% respectively v. 27.3%, odds ratio (OR) = 3.07, P = 0.007), three times higher odds of rapid cycling (38.5% and 39.5% respectively v. 18.2%, OR = 3.13, P = 0.012) and were more likely to be refractory to lithium treatment (36.8% and 36.7% respectively v. 3.2%, OR = 8.40, P<0.0001). All associations remained significant after controlling for antipsychotic exposure and body mass index in sensitivity analyses. Comorbid insulin resistance may be an important factor in resistance to treatment in bipolar disorder.

Effect of admission hyperglycemia in sepsis patients with or without a history of diabetes

Introduction Hyperglycemia is common and often multifactorial in critically ill patients. The association of hyperglycemia with adverse outcome has repeatedly been established in a variety of settings. The objective of this study was to investigate whether hyperglycemia on admission to the ICU impacts presentation and outcome of sepsis patients and whether this effect is different for patients with a history of diabetes mellitus. Methods A two-center, prospective observational cohort study was conducted including all consecutive critically ill patients admitted to the ICU between January 2011 and July 2013. Sepsis patients were identified using strict clinical and diagnostic criteria. The first glucose measurement within a time window of 4 hours before up to 4 hours after ICU admission was categorized into euglycemia (71 to 140 mg/dl), mild hyperglycemia (141 to 200 mg/dl) or severe hyperglycemia (>200 mg/ dl), patients with hypoglycemia were excluded. A multivariable Cox proportional hazard model was used to determine the effect of admission hyperglycemia on mortality corrected for covariates. Results Of the 1,059 patients admitted with sepsis, 526 (55.8%) had admission glucose levels within the normal range, 270 (25.5%) had mild hyperglycemia and 202 (19.1%) severe hyperglycemia. Patients with severe hyperglycemia were older, had higher APACHE IV scores and were more often diabetics compared with euglycemic patients. Shock on admission was more common in patients admitted with euglycemia. Crude mortality increased with increased admission glucose and a Cox regression analysis showed increased risk for 30day (HR = 1.67, CI = 1.24 to 2.23), 60-day (HR = 1.42, CI = 1.08 to 1.87) and 90-day (1.31, CI = 1.02 to 1.70) mortality in patients admitted with severe hyperglycemia compared with euglycemia. The association between mortality and severe hyperglycemia on admission was only present in patients without known diabetes but not in patients with a history of diabetes (30-day mortality HR = 1.67, CI = 1.15 to 2.43 vs. 1.84, CI = 0.97 to 3.49). Severe hyperglycemia was associated with a blunted proinflammatory cytokine response (IL-6 and IL-8) on admission in patients without, but not in patients with diabetes. Conclusion Severe hyperglycemia on admission is associated with increased 30-day, 60-day and 90-day mortality in sepsis patients without a history of diabetes mellitus.

Pulmonary Artery Relaxation was Best with Increasing GLP1 than the Metabolic Improvement in Patients with Type 2 Diabetes

According to epidemiological data on type 2 diabetes (T2DM) represents about 95 % of cases of diabetes diagnosed, with projected to exceed 480 million in 2030. In addition, pulmonary arterial hypertension (PAH) has an estimated prevalence of 30 to 50 cases per million population, affects women more often than men, and PAH and T2DM are medical conditions that presents statistical correlation. The aim of this study was to evaluate the treatment in patients with diabetic that despite age, reported no episodes of hypoglycemia during the case study. Larger studies are needed to assess whether the same results are reproducible in diabetics and also euglycemic patients with PAH. Case 1, SPLM, patient 63-year-old female with a previous diagnosis of T2DM, obesity, hypertension and dyslipidemia forwarded to endocrine evaluation for better glycemic control and weight loss. Case 2, HFC,patient 74-year-old female with a previous diagnosis of T2DM about three years, obesity, hypertension, dyslipidemia osteopenia, vitamin D deficiency and pulmonary hypertension. In the present study, this is the first description in humans that use a iDDP4 may be a treatment option for patients with PAH by the presence of receptor GLP-1R in the lung. It was concluded that in the first case there was weight loss and improved glycemic level. In the second case, both the glucose level of the weight remained. In both cases, using vildagliptin, there was a decrease in systolic pressure of right ventricle pointed out that the relaxation of pulmonary artery has a more beneficial effect would be mediated by NO and activation of vascular potassium channels, further of the effect direct by increasing GLP1, since the IRS1 less inhibited increases the activation of kinases, which in turn increases the stimulus for nitric oxide production in endothelial cells, reducing pulmonary arterial pressure.

Role of diabetes mellitus on the recurrence rate of hepatocellular carcinomas after radiofrequency ablation in chronic hepatitis C patients

Aim: The aim was to assess the impact of hyperglycemia on the recurrence of hepatocellular carcinoma (HCC) as well as evaluate survival after curative ablation by radiofrequency. Methods: This study, which was conducted retrospectively on 107 chronic hepatitis C (CHC) patients with 159 HCCs, was presented to the Hepatology Unit of Internal Medicine Department at Tanta University Hospitals. All lesions were curatively treated by radiofrequency ablation (RFA) and the surveillance of HCC recurrence was evaluated radiologically every 3 months for periods between 6 and 36 months. Of 107 subjects, 70 were males and 37 were females, with mean age 50.4 ΁ 9.4 years. All patients were divided according to their glycemic state into the following three groups: Group I, which included 37 type 2 diabetic patients, with adequate maintenance of blood glucose, has 52 HCCs; Group II, which included 25 type 2 diabetic patients with inadequate maintenance of blood glucose, has 43 HCCs; and Group III, which included 45 euglycemic non-diabetic patients, has 64 HCCs. Results: Our results showed that, there was significant increase in recurrence rate in diabetic patients with inadequate maintenance of blood glucose (Group II) compared to those in Group I and Group III ( P Conclusion: Inadequate maintenance of blood glucose in diabetic patients is a significant risk factor for recurrence of HCC and for poor survival after curative RFA therapy in CHC patients.

Short-term and long-term adverse cardiovascular events across the glycaemic spectrum in patients with acute coronary syndrome

Limited data exist on the prognostic impacts of diabetes mellitus (DM) and new-onset hyperglycaemia (NOH) on cardiovascular outcomes in Middle Eastern patients with acute coronary syndrome (ACS). Here, we explored this relationship in a large contemporary Middle Eastern ACS registry: the second Gulf Registry of Acute Coronary Events (Gulf RACE-2). Our analysis included 6362 consecutive ACS patients enrolled from October 2008 to June 2009, with or without a known DM diagnosis, and with an available fasting blood sugar measurement from the index hospitalization. Baseline demographics, risk factors for atherosclerosis, medical history, investigations and therapies were registered. Adverse hospital outcomes, as well as short-term and long-term mortalities were compared. Comparisons for categorical data were performed using χ or Fisher's exact tests, whereas analysis of variance or the Kruskal-Wallis test was used for continuous variables. Multiple logistic regression models were used to estimate the odds ratio. Almost half of the ACS cohort had been diagnosed previously with DM, and 8.8% had NOH. DM patients were more frequently older, female and Arab Gulf nationals. Compared with nondiabetic patients, DM patients had higher rates of adverse in-hospital clinical events, and 30-day and 1-year mortality. NOH was an independent predictor of in-hospital mortality, major bleeding and cardiogenic shock. Patients with NOH had higher in-hospital mortality (8.29 vs. 5.37%, P=0.035), ventricular arrhythmia (4.97 vs. 1.91%, P<0.001) and cardiogenic shock rates (6.45 vs. 4.12%, P=0.019) compared with DM patients not requiring insulin. DM was very common among ACS patients in the Arab Gulf area, and ACS patients with NOH were at a higher risk compared with euglycaemic patients and diabetic patients not requiring insulin. Further studies are needed to examine the clinical impact of in-hospital intensive glycaemic control in these patients and to explore the long-term glycaemic status of ACS patients with NOH.