Reversal of Insulin Resistance in Overweight and Obese Subjects by trans-Resveratrol and Hesperetin Combination-Link to Dysglycemia, Blood Pressure, Dyslipidemia, and Low-Grade Inflammation.

The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = -0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = -0.68, p < 0.05)-a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = -0.56, p < 0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ΔAUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = -0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.

Screening for Glucose Perturbations and Risk Factor Management in Dysglycemic Patients With Coronary Artery Disease-A Persistent Challenge in Need of Substantial Improvement: A Report From ESC EORP EUROASPIRE V.

OBJECTIVE: Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects. RESEARCH DESIGN AND METHODS: The European Society of Cardiology's European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016-2017) included 8,261 CAD patients, aged 18-80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A1c. Lifestyle, risk factors, and pharmacological management were investigated. RESULTS: A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium-glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small. CONCLUSIONS: Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.

Update on Diabetes Mellitus and Glucose Metabolism Alterations in Prader-Willi Syndrome.

PURPOSE OF REVIEW: This review summarizes our current knowledge on type 2 diabetes mellitus (T2DM) and glucose metabolism alterations in Prader-Willi syndrome (PWS), the most common syndromic cause of obesity, and serves as a guide for future research and current best practice. RECENT FINDINGS: Diabetes occurs in 10-25% of PWS patients, usually in adulthood. Severe obesity is a significant risk factor for developing of T2DM in PWS. Paradoxically, despite severe obesity, a relative hypoinsulinemia, without the expected insulin resistance, is frequently observed in PWS. The majority of PWS subjects with T2DM are asymptomatic and diabetes-related complications are infrequent. Long-term growth hormone therapy does not adversely influence glucose homeostasis in all ages, if weight gain does not occur. Early intervention to prevent obesity and the regular monitoring of glucose levels are recommended in PWS subjects. However, further studies are required to better understand the physiopathological mechanisms of T2DM in these patients.

Analysis of "never events" following adult cardiac surgical procedures in the United States.

BACKGROUND: This study was conducted to determine the risk factors, nature, and outcomes of "never events" following open adult cardiac surgical procedures. Understanding of these events can reduce their occurrence, and thereby improve patient care, quality metrics, and cost reduction. METHODS: "Never events" for patients included in the Nationwide Inpatient Sample who underwent coronary artery bypass graft, heart valve repair/replacement, or thoracic aneurysm repair between 2003-2011 were documented. These events included air embolism, catheter-based urinary tract infection (UTI), pressure ulcer, falls/trauma, blood incompatibility, vascular catheter infection, poor glucose control, foreign object retention, wrong site surgery and mediastinitis. Analysis included characterization of preoperative demographics, comorbidities and outcomes for patients sustaining never events, and multivariate analysis of predictive risk factors and outcomes. RESULTS: A total of 588,417 patients meeting inclusion criteria were identified. Of these, never events occurred in 4377 cases. The majority of events were in-hospital falls, vascular catheter infections, and complications of poor glucose control. Rates of falls, catheter based UTIs, and glucose control complications increased between 2009-2011 as compared to 2003-2008. Analysis revealed increased hospital length of stay, hospital charges, and mortality in patients who suffered a never event as compared to those that did not. CONCLUSIONS: This study establishes a baseline never event rate after cardiac surgery. Adverse patient outcomes and increased resource utilization resulting from never events emphasizes the need for quality improvement surrounding them. A better understanding of individual patient characteristics for those at risk can help in developing protocols to decrease occurrence rates.

Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement.

DESCRIPTION: Update of the 2008 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for diabetes in asymptomatic adults. METHODS: The USPSTF reviewed the evidence on screening for impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes in asymptomatic, nonpregnant adults who are at average or high risk for diabetes and its complications. POPULATION: This recommendation applies to adults aged 40 to 70 years seen in primary care settings who do not have symptoms of diabetes and are overweight or obese. RECOMMENDATION: The USPSTF recommends screening for abnormal blood glucose as part of cardiovascular risk assessment in adults aged 40 to 70 years who are overweight or obese. Clinicians should offer or refer patients with abnormal blood glucose to intensive behavioral counseling interventions to promote a healthful diet and physical activity. (B recommendation).

Endocrine disorders in Fanconi anemia: recommendations for screening and treatment.

CONTEXT: Endocrine problems are common in patients with Fanconi anemia (FA). About 80% of children and adults with FA have at least one endocrine abnormality, including short stature, GH deficiency, abnormal glucose or insulin metabolism, dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired fertility. The goal of this report is to provide an overview of endocrine abnormalities and guidelines for routine screening and treatment to allow early diagnosis and timely intervention. EVIDENCE ACQUISITION: This work is based on a comprehensive literature review, including relevant articles published between 1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi Anemia Research Fund in 2013. EVIDENCE SYNTHESIS: The panel of experts collected published evidence and discussed its relevance to reflect current information about the endocrine care of children and adults with FA before the Consensus Conference and through subsequent deliberations that led to the consensus. CONCLUSIONS: Individuals with FA should be routinely screened for endocrine abnormalities, including evaluation of growth; glucose, insulin, and lipid metabolism; thyroid function; puberty; gonadal function; and bone mineral metabolism. Inclusion of an endocrinologist as part of the multidisciplinary patient care team is key to providing comprehensive care for patients with FA.

A double-edged sword: review of the interplay between physical health and mental health.

It is widely acknowledged that there is interplay between physical and mental health, with causality in both directions. A common theme across countries is the uncertainty surrounding who should act as gatekeeper for physical health matters in psychiatry. Much of the metabolic monitoring is carried out by psychiatrists who often feel ill equipped to treat medical problems such as abnormal cholesterol or disturbances of glucose metabolism. However many patients do not attend primary care on a regular basis and may not be likely to follow through on referral to primary care. This review aims to examine the interplay between co-morbid physical and mental health conditions, identify the physical health conditions particularly associated with severe affective and psychotic illness and briefly discuss interventions and recommendations in this area. As people with severe mental illness die 10-20 years younger than their peers, with much of this premature mortality due to cardiovascular disease, this topic is emerging as one of great importance amongst clinicians and policymakers internationally.

Effects of lifestyle intervention and meal replacement on glycaemic and body-weight control in Chinese subjects with impaired glucose regulation: a 1-year randomised controlled trial.

The purpose of the present study was to evaluate the impact of a lifestyle intervention programme, combined with a daily low-glycaemic index meal replacement, on body-weight and glycaemic control in subjects with impaired glucose regulation (IGR). Subjects with IGR were randomly assigned to an intervention group (n 46) and a control group (n 42). Both groups received health counselling at baseline. The intervention group also received a daily meal replacement and intensive lifestyle intervention to promote healthy eating habits during the first 3 months of the study, and follow-up visits performed monthly until the end of the 1-year study. Outcome measurements included changes in plasma glucose, glycated Hb (HbA1c), plasma lipids, body weight, blood pressure and body composition (such as body fat mass and visceral fat area). The results showed that body-weight loss after 1 year was significant in the intervention group compared with the control group (-1·8 (SEM 0·35) v. -0·6 (SEM 0·40) 2·5 kg, P<0·05). The 2 h plasma glucose concentration decreased 1·24 mmol/l in the intervention group and increased 0·85 mmol/l in the control group (P<0·05) compared with their baseline, respectively. A 5 kg body-weight loss at 1 year was associated with a decrease of 1·49 mmol/l in 2 h plasma glucose (P<0·01). The incidence of normal glucose regulation (NGR) in the two groups was significantly different (P=0·001). In conclusion, the combination of regular contact, lifestyle advice and meal replacement is beneficial in promoting IGR to NGR.

Let's prevent diabetes: study protocol for a cluster randomised controlled trial of an educational intervention in a multi-ethnic UK population with screen detected impaired glucose regulation.

BACKGROUND: The prevention of type 2 diabetes is a globally recognised health care priority, but there is a lack of rigorous research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. The aim of the study is to establish whether a pragmatic structured education programme targeting lifestyle and behaviour change in conjunction with motivational maintenance via the telephone can reduce the incidence of type 2 diabetes in people with impaired glucose regulation (a composite of impaired glucose tolerance and/or impaired fasting glucose) identified through a validated risk score screening programme in primary care. DESIGN: Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is the incidence of type 2 diabetes. Secondary outcomes include changes in HbA1c, blood glucose levels, cardiovascular risk, the presence of the Metabolic Syndrome and the cost-effectiveness of the intervention. METHODS: The study consists of screening and intervention phases within 44 general practices coordinated from a single academic research centre. Those at high risk of impaired glucose regulation or type 2 diabetes are identified using a risk score and invited for screening using a 75 g-oral glucose tolerance test. Those with screen detected impaired glucose regulation will be invited to take part in the trial. Practices will be randomised to standard care or the intensive arm. Participants from intensive arm practices will receive a structured education programme with motivational maintenance via the telephone and annual refresher sessions. The study will run from 2009-2014. DISCUSSION: This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme conducted within routine primary care in the United Kingdom. TRIAL REGISTRATION: Clinicaltrials.gov NCT00677937.

The effects of adjuvant insulin therapy among pregnant women with IGT who failed to achieve the desired glycemia levels by diet and moderate physical activity.

OBJECTIVE: Evaluation of adjuvant insulin therapy effects on glycemic control, perinatal outcome and postpuerperal glucose tolerance in impaired glucose tolerance (IGT) pregnant women who failed to achieve desired glycemic control by dietary regime. METHODS: A total of 280 participants were classified in two groups: Group A patients continued with dietary regime and Group B patients were treated with adjuvant insulin therapy. Glycemic control was assessed by laboratory and ultrasonograph means. Pregnancy outcomes were evaluated by prevalence of pregnancy induced hypertension (PIH), high birth weight, neonatal hypoglycemia and caesarean section rates. Postpuerperal glucose tolerance was assessed by oral glucose tolerance test (oGTT). RESULTS: All laboratory and ultrasound indicators of glycemic control had significantly lower values in Group B. Group A women were more likely to develop the EPH (Edema, Proteinuria, Hypertension) syndrome, 20% versus 7.86% (p = 0.003). High birth weight occurred more frequently in Group A, but the difference was not significant (p = 0.197). Higher rate of caesarean delivery was in Group A than in Group B, 16.43% versus 26.43% (p = 0.041). The difference in neonatal hypoglycemia was not significant (p = 0.478). Pathological oGTT results were observed in 73 Group A patients and in 15 Group B patients. CONCLUSION: Lower caesarean section rates and the EPH syndrome incidence are the benefits of adjuvant insulin therapy in IGT patients.

Efecto del bypass gástrico a largo plazo (7 a 10 años) en pacientes con obesidad severa y mórbida sobre el peso corporal, diabetes, dislipidemia y desarrollo de anemia / Results of gastric bypass for morbid obesity after a follow up of seven to 10 years

weight and complications of obesity, seven to 10 years after gastric bypass surgery. Material and Methods: One hundred eighteen subjects with morbid obesity, aged 15 to 66years (103 women), were followed for a mean of 94 months after surgery. Body weight, fasting blood glucose, total cholesterol, triglycerides and hemoglobin were measured before surgery and during follow up. Results: At 24 months of follow up, all patients lost weight and there was a mild weight increase at 94 months, that paralleled the preo-perative body mass index. Diabetes, hypercholesterolemia and hypertriglyceridemia subsided in 95, 87 and 94% of cases, respectively. Twenty percent of patients had mild anemia and 11% moderate or severe anemia. No patient recovered the preoperative weight. Conclusions: Weight reducing effects of gastric bypass are maintained after 94 months of follow up with the expected health benefits.

[Results of gastric bypass for morbid obesity after a follow up of seven to 10 years]. / Efecto del bypass gástrico a largo plazo (7 a 10 años) en pacientes con obesidad severa y mórbida sobre el peso corporal, diabetes, dislipidemia y desarrollo de anemia.

BACKGROUND: There is a paucity of information about the long term effects of gastric bypass for morbid obesity. AIM: To study the evolution of weight and complications of obesity, seven to 10 years after gastric bypass surgery. MATERIAL AND METHODS: One hundred eighteen subjects with morbid obesity, aged 15 to 66 years (103 women), were followed for a mean of 94 months after surgery. Body weight, fasting blood glucose, total cholesterol, triglycerides and hemoglobin were measured before surgery and during follow up. RESULTS: At 24 months of follow up, all patients lost weight and there was a mild weight increase at 94 months, that paralleled the preoperative body mass index. Diabetes, hypercholesterolemia and hypertriglyceridemia subsided in 95, 87 and 94% of cases, respectively. Twenty percent of patients had mild anemia and 11% moderate or severe anemia. No patient recovered the preoperative weight. CONCLUSIONS: Weight reducing effects of gastric bypass are maintained after 94 months of follow up with the expected health benefits.

Management of sepsis in neutropenic patients: guidelines from the infectious diseases working party of the German Society of Hematology and Oncology.

Sepsis is a leading cause of mortality in neutropenic cancer patients. Early initiation of effective causative therapy as well as intensive adjunctive therapy is mandatory to improve outcome. We give recommendations for the management of adults with neutropenia and sepsis. The guidelines are written for clinicians involved in care of cancer patients and focus on pathophysiology, diagnosis and treatment of sepsis during neutropenia.

Lifting the lid of the "black intervention box" - the systematic development of an action competence programme for people with screen-detected dysglycaemia.

BACKGROUND: The evidence gained from effective self-management interventions is often criticised for the ambiguity of its active components, and consequently the obstruction of their implementation into daily practice.Our aim is to report how an intervention development model aids the careful selection of active components in an intervention for people with dysglycaemia. METHODS: The first three phases of the UK Medical Research Council's model for developing complex interventions in primary care were used to develop a self-management intervention targeting people with screen-detected dysglycaemia. In the preclinical phase, the expected needs of the target group were assessed by review of empirical literature and theories. In phase I, a preliminary intervention was modelled and in phase II, the preliminary intervention was pilot tested. RESULTS: In the preclinical phase the achievement of health-related action competence was defined as the overall intervention goal and four learning objectives were identified: motivation, informed decision-making, action experience and social involvement. In Phase I, the educational activities were defined and the pedagogical tools tested. In phase II, the intervention was tested in two different primary healthcare settings and adjusted accordingly. The 18-hour intervention "Ready to Act" ran for 3 months and consisted of two motivational one-to-one sessions conducted by nurses and eight group meetings conducted by multidisciplinary teams. CONCLUSIONS: An intervention aimed at health-related action competence was successfully developed for people with screen-detected dysglycaemia. The systematic and transparent developmental process is expected to facilitate future clinical research. The MRC model provides the necessary steps to inform intervention development but should be prioritised according to existing evidence in order to save time.

Readiness of US health plans to manage cardiometabolic risk.

INTRODUCTION: American health plans can make a substantial contribution to the control of cardiometabolic risk (CMR), a condition associated with both adverse health outcomes and increased cost of care. Our goal was to determine health plan interest in and ability to provide CMR control services. METHODS: In January 2008, America's Health Insurance Plans, in collaboration with the HealthPartners Research Foundation, surveyed the chief medical officers of 74 member health insurance plans that offer commercial health maintenance organization, point of service, and preferred provider organization insurance. The response rate was 47%. RESULTS: The 35 responding chief medical officers reported that their plans identify members with CMR through referral from case or care management (89%), health risk assessment data (86%), claims data (82%), and pharmaceutical use data (79%). Nearly all (97%) plans currently offer interventions for tobacco use, obesity/overweight, and nutrition. Ninety-four percent of plans offer interventions to increase physical activity. All plans offer health risk appraisal or assessment with feedback and education, 91% use Web-based tools, and 85% use health coaching to help plan members lower their risk. Perceived barriers to broader implementation of risk control programs included lack of resources (79%), limited available enrollee data (74%), and lack of reporting systems (79%). Few health plan officers viewed lack of purchaser interest to be a barrier to program implementation. CONCLUSION: Health plans appear to be positioned to provide CMR control services that could improve health outcomes, reduce health care costs, and increase workplace productivity in the United States.

Perioperative management of benign hepatic tumors in patients with glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSD-Ia; von Gierke disease) is an inherited disorder caused by glucose-6-phosphatase deficiency, and there have been some reports of hepatic tumors in patients with this disease. We report two patients with benign hepatic tumors with GSD-Ia. One is a 19-year-old man who underwent segmentectomy 4 for a focal nodular hyperplasia, and the other is a 31-year-old woman who underwent segmentectomies 3, 5, and 6 for hepatic adenomas. Two significant perioperative complications, resulting from the carbohydrate metabolic disorders, hypoglycemia and metabolic acidosis, occurred in both patients. We managed the metabolic complications successfully by administering a sufficient volume of glucose intravenously. Close perioperative monitoring of blood glucose and lactate concentrations is essential in the perioperative management of patients with GSD-Ia. The intravenous administration of glucose, starting with a smaller dose and then increasing the dose, is adequate management for lactic acidosis with or without hypoglycemia during the perioperative period.

[Carbohydrate metabolism dysregulation in cirrhosis: pathophysiology, prognostic impact and therapeutic implications]. / Perturbations du métabolisme des glucides au cours de la cirrhose: pathogénie, impact pronostique et implications thérapeutiques.

The liver plays a key-role in carbohydrates metabolism. Glucose intole-rance, overt diabetes mellitus and insulin resistance are characteristic features of patients with cirrhosis. Central hyperinsulinemia and peripheral insulin-resistance are the main explanations for the high prevalence of diabetes in patients with cirrhosis. On the other hand, type 2 diabetes is associated with a wide spectrum of liver diseases ranging from nonalcoholic fatty liver to cirrhosis and hepatocellular carcinoma. Carbohydrate metabolism abnormalities are a major aggravating risk factor in cirrhosis. Diabetes is also an independent negative prognostic factor in cirrhotic patients. This leads to specific diagnostic procedures and therapeutic issues. Patients with diabetes and liver disease frequently need insulin treatment. The presence of liver disease makes the treatment of diabetes complex, and additional research is needed to determine the best treatment strategies in these patients.

Endocrine disorders in the neonate.

There is a significant amount of knowledge that has been gained in recent years in the study of endocrine disorders in the newborn. The explosion of genetic data shedding light on the origins of endocrine disease has expanded the level of diagnostic evaluation and management of these infants. This article provides a general review of endocrine disorders as they present in a newborn.

Gene therapy technology applied to disorders of glucose metabolism: promise, achievements, and prospects.

Gene transfer technology has spawned an entire realm of clinical investigation, collectively referred to as "gene therapy." The feasibility and achievements of gene therapy to prevent and treat glucose homeostasis disorders, with particular emphasis on diabetes mellitus, are evaluated in this review. While a considerable amount of effort has yielded gene delivery vectors based on adenoviral, retroviral, and herpes simplex virus DNA, the number of successful clinical applications has not been as impressive. Despite the number of successes in vitro and in animal models, preliminary safety trials in humans have not yet been attempted. The current state of this science, outlined here, underlines the necessity of marrying gene transfer technology with cell therapy. The ex vivo transfer of gene combinations into a variety of cell types will likely prove more therapeutically feasible than direct in vivo vector transfer. Current efforts aimed at assessing the future of gene therapy for diabetes must, at the very least, take into account the importance of moving successful methods into human safety trials.