Long-term Glucose Levels Research Articles

Impact of direct acting antiviral (DAA) treatment on glucose metabolism and reduction of pre-diabetes in patients with chronic hepatitis C.

With the development of direct acting antiviral agents (DAA) chronic hepatitis C virus (HCV) infection has become curable in most patients. Since HCV infection is known to have direct and/or indirect effects on glucose metabolism, successful HCV treatment may have an impact in reducing glucose level, pre-diabetes, the need of treatment for diabetes, and ultimately diabetes-associated morbidity. We investigated the association of DAA treatment and glucose metabolism in the context of development or resolution of hepatic fibrosis in a large cohort of HCV- infected patients. In this retrospective single-center observational study, we investigated 281 patients receiving all-oral DAA therapy for fasting plasma glucose, HbA1c, liver enzymes and general clinical chemistry, measured during a 52-week follow-up. In addition, elastography, FIB-4- and APRI-calculation were used to assess hepatic fibrosis non-invasively. Successful elimination of HCV through DAA treatment was associated with a significant drop in fasting glucose level and a reduced rate of impaired fasting plasma glucose (FPG). Interestingly, this metabolic change was BMI-independent. In addition, long-term glucose levels also decreased after successful DAA treatment. A significant APRI-score reduction was associated with a persistent improvement of FPG. However, DAA did not have an impact on glucose metabolism in patients suffering from liver cirrhosis. This study highlights the beneficial impact of successful HCV therapy on glucose metabolism and identifies patients with liver cirrhosis as a collective in need of intensified surveillance with regard to diabetes progression despite HCV eradication.

Stress-Induced Hyperglycemia in Diabetes: A Cross-Sectional Analysis to Explore the Definition Based on the Trauma Registry Data.

Background: The diagnosis of diabetic hyperglycemia (DH) does not preclude a diabetes patient from having a stress-induced hyperglycemic response. This study aimed to define the optimal level of elevated glucose concentration for determining the occurrence of stress-induced hyperglycemia (SIH) in patients with diabetes. Methods: This retrospective study reviewed the data of all hospitalized trauma patients, in a Level I trauma center, from 1 January 2009 to 31 December 2016. Only adult patients aged ≥20 years, with available data on serum glucose and glycated hemoglobin A1c (HbA1c) levels upon admission, were included in the study. Long-term average glucose levels, as A1c-derived average glucose (ADAG), using the equation, ADAG = ((28.7 × HbA1c) − 46.7), were calculated. Patients with high glucose levels were divided into three SIH groups with diabetes mellitus (DM), based on the following definitions: (1) same glycemic gap from ADAG; (2) same percentage of elevated glucose of ADAG, from which percentage could also be reflected by the stress hyperglycemia ratio (SHR), calculated as the admission glucose level divided by ADAG; or (3) same percentage of elevated glucose as patients with a defined SIH level, in trauma patients with and without diabetes. Patients with incomplete registered data were excluded. The primary hypothesis of this study was that SIH in patients with diabetes would present worse mortality outcomes than in those without. Detailed data of SIH in patients with diabetes were retrieved from the Trauma Registry System. Results: Among the 546 patients with DH, 332 (32.0%), 188 (18.1%), and 106 (10.2%) were assigned as diabetes patients with SIH, based on defined glucose levels, set at 250 mg/dL, 300 mg/dL, and 350 mg/dL, respectively. In patients with defined cut-off glucose levels of 250 mg/dL and 300 mg/dL, SIH was associated with a 3.5-fold (95% confidence interval (CI) 1.61–7.46; p = 0.001) and 3-fold (95% CI 1.11–8.03; p = 0.030) higher odds of mortality, adjusted by sex, age, pre-existing comorbidities, and injury severity score, than the 491 patients with diabetic normoglycemia (DN). However, in patients with a defined cut-off glucose level of 350 mg/dL, adjusted mortality in SIH in DM was insignificantly different than that in DM. According to the receiver operating characteristic (ROC) curve analysis, a blood sugar of 233 mg/dL, a glycemic gap of 79 (i.e., blood sugar of 251 mg/dL), and a SHR of 1.45 (i.e., blood sugar of 250 mg/dL) were identified as cut-offs for mortality outcomes, with AUCs of 0.622, 0.653, and 0.658, respectively. Conclusions: In this study, a cut-off glucose level of 250 mg/dL was selected to provide a better definition of SIH in DM than glucose levels of 300 mg/dL or 350 mg/dL.

Relationships of iron metabolism with insulin resistance and glucose levels in young and healthy adults

AimsSeveral biomarkers within the iron metabolism pathway have been related to the occurrence of diabetes mellitus, but underlying mechanisms are unknown. The aim of our study was to investigate the differential relationships of iron metabolism with a broad range of diabetes markers in young and healthy adults. Design2160 participants aged 25 to 41years were enrolled in a population-based study. Established cardiovascular disease, diabetes or a body mass index >35kg/m2 were exclusion criteria. Multivariable linear regression models were built to assess the associations of ferritin and transferrin saturation (TSAT) with blood levels of glucagon-like peptide-1 (GLP-1), insulin, homeostatic model assessment-insulin resistance (HOMA-IR), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). ResultsMedian (interquartile range) age was 37 (31, 40) years. In multivariable linear regression analyses, β-coefficients (95% confidence intervals) per 1-SD increase in ferritin were 0.04 (0.02; 0.07, p=0.0008) for GLP-1, 0.06 (0.04; 0.08, p<0.0001) for insulin, 0.07 (0.04; 0.09, p<0.0001) for HOMA-IR, 0.004 (−0.00; 0.01, p=0.07) for FPG and −0.003 (−0.01; −0.00, p=0.07) for HbA1c. β-coefficients (95% CI) per 1-SD increase in TSAT were −0.07 (−0.09; −0.05, p<0.0001) for GLP-1, −0.06 (−0.08; −0.04, p<0.0001) for insulin, −0.07(−0.09; −0.05, p<0.0001) for HOMA-IR, −0.01 (−0.01; −0.00, p<0.0001) for FPG and −0.01 (−0.01; −0.00, p=0.0004) for HbA1c. ConclusionsMarkers of insulin resistance are strongly related with markers of iron metabolism in healthy subjects. These relationships were inconsistent and weaker for short-term and long-term glucose levels. These results may provide insights in the relationships between iron metabolism and diabetes occurrence.

The microRNA-124-iGluR2/3 pathway regulates glucagon release from alpha cells.

Glucagon, secreted from islet alpha cells, plays an important role in regulating glucose homeostasis; however, the molecular mechanism underlying this process is not fully understood. Previous studies have demonstrated that miRNAs are involved in the function of alpha cells. Glutamate promotes glucagon secretion by mediating the opening of Ca2+ channels. In this present, iGluR2 and iGluR3 levels were significantly increased in fasting-treated mouse islets. Additional studies showed that miR-124-3p simultaneously regulates the expression of iGluR2 and iGluR3 through the direct targeting of mRNA 3’UTR of these two genes. The miR-124-iGluRs pathway also contributed to the high level of glucagon secretion through long-term high glucose levels. Thus, a novel pathway comprising miRNA, glutamate and iGluRs has been demonstrated to regulate the biological process of glucagon release.

Metformin Prevents Nonunion after Three-Cannulated-Screw Fixation in Displaced Femoral Neck Fractures: A Retrospective Study.

Patients aged from 40 to 60 with displaced fractures of the femoral neck (Garden III or IV) who received fixation with three cannulated screws from January 2005 to December 2012 were evaluated retrospectively for the development of nonunion. Plasma HbA1C, a marker for long-term plasma glucose level, anti-T2DM medication, and other potential risk factors were recorded for the purpose of this study. There were no differences between the union and nonunion groups with respect to age, gender, Garden classification, Pauwel's angle, reduction quality, and T2DM presence. There were significant differences in reduction quality and preoperative plasma HbA1C level between patients with and those without union. The odds ratio (OR) for fracture nonunion was 2.659 (95% confidence interval [CI], 1.530–4.620) in subjects with anatomical reduction compared with those without anatomical reduction, 4.797 (95% CI, 1.371–16.778), in subjects with poor blood glucose control (HbA1C > 10%). The metformin usage showed a preventive effect on nonunion development (OR: 0.193 and CI: 0.060–0.616). The nonunion rate of metformin group (6.7%, 6/89) was even much lower than that of patients without T2DM (17.4%, 80/460).

Perception of difficulty and glucose control: Effects on academic performance in youth with type I diabetes.

To investigate whether perceptions of task difficulty on neuropsychological tests predicted academic achievement after controlling for glucose levels and depression. Participants were type 1 diabetic adolescents, with a mean age = 12.5 years (23 females and 16 males), seen at a northwest suburban Chicago hospital. The sample population was free of co-morbid clinical health conditions. Subjects completed a three-part neuropsychological battery including the Digit Symbol Task, Trail Making Test, and Controlled Oral Word Association test. Following each task, individuals rated task difficulty and then completed a depression inventory. Performance on these three tests is reflective of neuropsychological status in relation to glucose control. Blood glucose levels were measured immediately prior to and after completing the neuropsychological battery using a glucose meter. HbA1c levels were obtained from medical records. Academic performance was based on self-reported grades in Math, Science, and English. Data was analyzed using multiple regression models to evaluate the associations between academic performance, perception of task difficulty, and glucose control. Perceptions of difficulty on a neuropsychological battery significantly predicted academic performance after accounting for glucose control and depression. Perceptions of difficulty on the neuropsychological tests were inversely correlated with academic performance (r = -0.48), while acute (blood glucose) and long-term glucose levels increased along with perceptions of task difficulty (r = 0.47). Additionally, higher depression scores were associated with poorer academic performance (r = -0.43). With the first regression analysis, perception of difficulty on the neuropsychological tasks contributed to 8% of the variance in academic performance after controlling for peripheral blood glucose and depression. In the second regression analysis, perception of difficulty accounted for 11% of the variance after accounting for academic performance and depression. The final regression analysis indicated that perception of difficulty increased with peripheral blood glucose, contributing to 22% of the variance. Most importantly, after controlling for perceptions of task difficulty, academic performance no longer predicted glucose levels. Finally, subjects who found the cognitive battery difficult were likely to have poor academic grades. Perceptions of difficulty on neurological tests exhibited a significant association with academic achievement, indicating that deficits in this skill may lead to academic disadvantage in diabetic patients.

Comment on Evert et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes care 2013;36:3821-3842.

I read the new nutrition therapy recommendations with great interest. However, I was disappointed that the position statement includes “low-carbohydrate” diets as an acceptable option for managing diabetes (1). Low-carbohydrate diets focus on eating foods higher in protein and fat (meat, poultry, fish, etc.) (Table 3 in ref. 1). These low-carbohydrate diets may produce short-term weight loss and glycemic control, but there is evidence of long-term elevated glucose levels and insulin resistance (2). No reference was made to the abundance of data on meat consumption and the associated risks to type 2 diabetes and obesity:

Intradermal insulin delivery: a promising future for diabetes management.

The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines.

Protein kinase C isoforms in atherosclerosis: Pro- or anti-inflammatory?

Atherosclerosis is a pathologic condition caused by chronic inflammation in response to lipid deposition in the arterial wall. There are many known contributing factors such as long-term abnormal glucose levels, smoking, hypertension, and hyperlipidemia. Under the influence of such factors, immune and non-immune effectors cells are activated and participate during the progression of atherosclerosis. Protein kinase C (PKC) family isoforms are key players in the signal transduction pathways of cellular activation and have been associated with several aspects of the atherosclerotic vascular disease. This review article summarizes the current knowledge of PKC isoforms functions during atherogenesis, and addresses differential roles and disputable observations of PKC isoforms. Among PKC isoforms, both PKCβ and PKCδ are the most attractive and potential therapeutic targets. This commentary discusses in detail the outcomes and current status of clinical trials on PKCβ and PKCδ inhibitors in atherosclerosis-associated disorders like diabetes and myocardial infarction. The risk and benefit of these inhibitors for clinical purposes will be also discussed. This review summarizes what is already being done and what else needs to be done in further targeting PKC isoforms, especially PKCβ and PKCδ, for therapy of atherosclerosis and atherosclerosis-associated vasculopathies in the future.

Circulation: Cardiovascular Interventions Editors’ Picks

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Stroke : Highlights of Selected Articles

HomeStrokeVol. 44, No. 8Stroke: Highlights of Selected Articles Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBStroke: Highlights of Selected Articles Originally published1 Aug 2013https://doi.org/10.1161/STROKEAHA.113.002626Stroke. 2013;44:2092Glycosylated Hemoglobin A1 Predicts Risk for Symptomatic Hemorrhage After Thrombolysis for Acute StrokeSymptomatic intracerebral hemorrhage after intravenous treatment with tissue-type plasminogen activator (tPA) in acute ischemic stroke is a potentially devastating event with a high mortality rate. Many factors are thought to increase the risk of hemorrhage, including damage to the microvasculature. Hemoglobin A1 (HbA1c) is a marker for long-term elevated glucose level and is used for monitoring diabetic vascular damage. In this retrospective analysis, Rocco et al investigated the predictive value of HbA1c for symptomatic intracerebral hemorrhage and clinical outcome in patients treated with intravenous tPA for acute ischemic stroke. The authors reviewed >1000 patients treated with tPA from 1998 to 2011 at the Neurological Department in Heidelberg, Germany. Any hemorrhage occurred in 222 patients (19.9%); 43 of those had symptomatic intracerebral hemorrhage (3.9%) per Safe Implementation of Treatments in Stroke definition and 95 (8.5%) per National Institute of Neurological Disorders and Stroke definition. In multivariate analysis, HbA1c was highly significantly associated with any hemorrhage and symptomatic intracerebral hemorrhage with a cut-off value of 6.5%, regardless of the definition used. By contrast, blood glucose at baseline was not statistically significantly associated with any type of hemorrhage. In multivariate analysis, age, National Institutes of Health Stroke Scale score on admission, and HbA1c were predictors of dependent outcome (modified Rankin Scale, 3–5). HbA1c is an important predictor of symptomatic intracerebral hemorrhage after thrombolysis for acute ischemic stroke. These results suggest that hemorrhage after thrombolysis may be a consequence of long-term vascular injury rather than of acute hyperglycemia. Patients should not be excluded from intravenous tPA with elevated HbA1c. However, if validated in larger prospective studies, these patients may warrant more intensive monitoring following tPA. See p 2134.Size Ratio Can Highly Predict Rupture Risk in Intracranial Small (<5 mm) AneurysmsThe decision-making process in the management of unruptured cerebral aneurysms is controversial. The risk of rupture increases with increasing aneurysm size. There are, however, a significant number of cases of subarachnoid hemorrhage from ruptured aneurysms <5 mm. Most studies use aneurysm diameter as a clinical variable when assessing risk of rupture. This study aimed to identify other parameters that highly predict the rupture risk of small (<5 mm) unruptured cerebral aneurysms. They reviewed a prospective cohort of 854 aneurysmal subarachnoid hemorrhage patients from 2003 and 2011 in Sapporo City, Japan. The size, aneurysm-to-vessel size ratio, and distribution were precisely compared between the ruptured and unruptured aneurysms. The size ratio was defined as the ratio of the maximum aneurysm diameter to the average vessel diameter. The most frequent site of ruptured aneurysm was at the anterior communicating artery, and the most frequent site of unruptured aneurysm was the middle cerebral artery. The maximal diameter and the size ratio were significantly higher in the ruptured group than unruptured. In multivariate analysis, both size and size ratio were correlated with aneurysm rupture. Specifically regarding the small aneurysms, 27% of the ruptured cerebral aneurysms were <5 mm. In multivariate analysis, only size ratio was associated with rupture in the small aneurysm group. These results should be validated in further, large prospective registries. However, based on these results, the calculation of size ratio may represent a good marker of rupture risk in small aneurysms. See p 2169.Systemic Inflammatory Response Syndrome in Tissue-Type Plasminogen Activator–Treated Patients is Associated With Worse Short-term Functional OutcomeSystemic inflammatory response (SIRS) is a generalized inflammatory state. Previous research has shown that patients with severe acute ischemic stroke have increased risk of having SIRS. In the current study, the investigators looked at the differences in outcomes in SIRS and non-SIRS tissue-type plasminogen activator–treated patients. They retrospectively reviewed their stroke database from 2008 to 2011 for patients with SIRS, excluding patients with infection. Out of 241 tissue-type plasminogen activator–treated patients included in this study, 44 had evidence of SIRS (18.2%). Patients with SIRS were more likely to be black and had lower median total cholesterol at baseline. SIRS patients were more likely to have longer length of stay and greater odds of poor functional outcome. Adjusting for baseline National Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge. SIRS was not a predictor of poor discharge disposition or in-hospital mortality. Larger prospective studies are needed to validate these results, which are limited due to the small sample size and retrospective nature. See p 2322. Previous Back to top Next FiguresReferencesRelatedDetails August 2013Vol 44, Issue 8 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.113.002626 Originally publishedAugust 1, 2013 PDF download Advertisement

An amperometric hemoglobin A1c biosensor based on immobilization of fructosyl amino acid oxidase onto zinc oxide nanoparticles–polypyrrole film

Measurement of hemoglobin A1c (HbA1c, glycated hemoglobin) level in blood provides the long-term glucose level in diabetic patients without the influence of short-term fluctuations. The existing methods for HbA1c determination, including biosensors, suffer from insufficient sensitivity, detection limit, response time, and storage stability. These problems were overcome in the current biosensor. A method is described for construction of an amperometric HbA1c biosensor by immobilizing a fructosyl amino acid oxidase (FAO) onto zinc oxide nanoparticles/polypyrrole (ZnONPs/PPy) hybrid film deposited onto gold (Au) electrode and using it as working electrode, Ag/AgCl as reference electrode, and platinum (Pt) as auxiliary electrode. The whole blood samples were hemolyzed and digested by protease before measuring their HbA1c level by the biosensor. The enzyme electrode detected fructosyl valine (FV) as low as 50μM at a signal-to-noise ratio of 3 within 2s at +0.27V versus Ag/AgCl, pH7.0, and 35°C with a linear working range of 0.1 to 3.0mM for FV and sensitivity of 38.42μAmM−1. The electrode showed only a 30% loss of its initial response over a period of 160days when stored at 4°C. The biosensor measured HbA1c in whole blood of apparently healthy individuals and diabetic patients and found it to be in the ranges of 4.0% to 5.6% and 5.7% to 12.0%, respectively.

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Glucose-induced [Ca2+]i abnormalities in human pancreatic islets: important role of overstimulation.

Chronic hyperglycemia desensitizes beta-cells to glucose. To further define the mechanisms behind desensitization and the role of overstimulation, we tested human pancreatic islets for the effects of long-term elevated glucose levels on cytoplasmic free Ca2+ concentration ([Ca2+]i) and its relationship to overstimulation. Islets were cultured for 48 h with 5.5 or 27 mmol/l glucose. Culture with 27 mmol/l glucose obliterated postculture insulin responses to 27 mmol/l glucose. This desensitization was specific for glucose versus arginine. Desensitization was accompanied by three major [Ca2+]i abnormalities: 1) elevated basal [Ca2+]i, 2) loss of a glucose-induced rise in [Ca2+]i, and 3) perturbations of oscillatory activity with a decrease in glucose-induced slow oscillations (0.2-0.5 min(-1)). Coculture with 0.3 mmol/l diazoxide was performed to probe the role of overstimulation. Neither glucose nor diazoxide affected islet glucose utilization or oxidation. Coculture with diazoxide and 27 mmol/l glucose significantly (P < 0.05) restored postculture insulin responses to glucose and lowered basal [Ca2+]i and normalized glucose-induced oscillatory activity. However, diazoxide completely failed to revive an increase in [Ca2+]i during postculture glucose stimulation. In conclusion, desensitization of glucose-induced insulin secretion in human pancreatic islets is induced in parallel with major glucose-specific [Ca2+]i abnormalities. Overstimulation is an important but not exclusive factor behind [Ca2+]i abnormalities.

Electrophoretically determined haemoglobin A1 concentrations during short-term changes in glucose concentration.

In our experience, electrophoresis on agar gel is a very satisfactory alternative to the more widely used chromatographic methods for the determination of haemoglobin A1 (HbA1). Like the chromatographic method, the electrophoretic method is unable to detect any difference between the labile intermediate form of HbA1, which changes rapidly with acute changes in blood glucose level, and the more stable end-product, which reflects long-term glucose levels. In vitro at 37 degrees C the electrophoretically determined HbA1 concentration increases with increasing glucose concentration and with time in both normal and diabetic erythrocytes, but decreases to the preincubation concentration during further incubation of the erythrocytes in a glucose-free medium at 37 degrees C. Similarly, if normal or diabetic erythrocytes are incubated with isotonic saline before the HbA1 assay, the labile fraction is eliminated. In diabetics, the decrease in HbA1 concentration correlates with both the blood glucose level and the preincubation HbA1 concentration. Thus for HbA1 to be an accurate indicator of long-term glucose control in diabetic patients saline incubation of the erythrocytes may be necessary before HbA1 assay by the electrophoretic method, otherwise the assay results will also reflect recent changes in the blood glucose level.