Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation

Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk.As a new parameter for continuously evaluating personal clinical statuses,the newly developed technique“continuous glucose monitoring”(CGM)can characterize glucose dynamics.By calculating the complexity of glucose time series index(CGI)with refined composite multi-scale entropy analysis of the CGM data,the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes(P for trend<0.01).Furthermore,CGI was significantly associated with various parameters such as insulin sensitivity/secretion(all P<0.01),and multiple linear stepwise regression showed that the disposition index,which reflectsβ-cell function after adjusting for insulin sensitivity,was the only independent factor correlated with CGI(P<0.01).Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

The correlation between serum uric acid level and early- phase insulin secretion in subjects with normal glucose regulation

Objective To investigate the correlation between serum uric acid(SUA)level and early-phase insulin secretion in subjects with normal glucose regulation(NGR).Methods Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled.

Culprits or consequences:Understanding the metabolic dysregulation of muscle in diabetes

The prevalence of type 2 diabetes(T2D)continues to rise despite the amount of research dedicated to finding the culprits of this debilitating disease.Skeletal muscle is arguably the most important contributor to glucose disposal making it a clear target in insulin resistance and T2D research.Within skeletal muscle there is a clear link to metabolic dysregulation during the progression of T2D but the determination of culprits vs consequences of the disease has been elusive.Emerging evidence in skeletal muscle implicates influential cross talk between a key anabolic regulatory protein,the mammalian target of rapamycin(mTOR)and its associated complexes(mTORC1 and mTORC2),and the well-described canonical signaling for insulin-stimulated glucose uptake.This new understanding of cellular signaling crosstalk has blurred the lines of what is a culprit and what is a consequence with regard to insulin resistance.Here,we briefly review the most recent understanding of insulin signaling in skeletal muscle,and how anabolic responses favoring anabolism directly impact cellular glucose disposal.This review highlights key cross-over interactions between protein and glucose regulatory pathways and the implications this may have for the design of new therapeutic targets for the control of glucoregulatory function in skeletal muscle.

Effects of serum containing natural cerebrolysin on glucose-regulated protein 78 and CCAAT enhancer-binding protein homologous protein expression in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress

BACKGROUND： Glucose-regulated protein 78 （GRP78）, a marker of endoplasmic reticulum stress, can prolong cell survival. Alternatively, CCAAT enhancer-binding protein homologous protein （CHOP）, a transcription factor specific for endoplasmic reticulum stress, can cause cell cycle arrest and cell apoptosis. OBJECTIVE： To study the protective effects of serum containing natural cerebrolysin on endoplasmic reticulum stress in tunicamycin-induced neuronal PC12 cells, and analyze the influence on GRP78 and CHOP expressions. DESIGN, TIME AND SETTING： A parallel controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital, Southern Medical University, between March 2006 and August 2008. MATERIALS： Adult Sprague-Dawley rats were perfused with natural Cerebrolysin aqueous extract （0.185 g/kg/d） to produce serum containing natural Cerebrolysin. Physiological saline was used to produce blank serum. PC12 cell line was provided by Shanghai Institute of Cell Biology, Chinese Academy of Science. Tunicamycin was provided by Sigma （St. Louis, USA）, and natural Cerebrolysin, containing ginseng, rhizoma gastrodiae, and gingko leaf （1：2：2）, by Shengzhen Institute of Integrated Western and Traditional Chinese Medicine. METHODS： PC12 cells were treated with DMEM culture media containing 10% blank serum （normal control group）, tunicamycin （1 μg/mL; model group）, and 5%, 10%, and 15% serum containing natural cerebrolysin and tunicamycin （1 μ g/mL; low-, moderate-, and high-dose serum containing natural cerebrotysin groups）, for 2 hours. MAIN OUTCOME MEASURES： PC12 cells were treated with tunicamycin for 48 hours after which apoptosis was measured using the TUNEL method to calculate apoptotic index. GRP78 expression was detected using immunocytochemistry. After 24 hours of treatment with tunicamycin, GRP78 and CHOP mRNA expressions were measured using RT-PCR. RESULTS： The apoptotic index and CHOP mRNA expression were in the model group and three cerebrolysin groups were significantly increased when compared to the normal control group （P 〈 0.05）. In contrast, GRP78 mRNA and protein expressions were significantly decreased （P 〈 0.05）. CONCLUSION： Serum containing natural cerebrolysin significantly reduced apoptosis in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress. These results may be related to an up-regulation of GRP78 expression and down-regulation of CHOP expression, both of which displayed dose-dependent effects.

Glycated Haemoglobin in Diagnosis of Diabetes Mellitus and Pre-diabetes among Middle-aged and Elderly Population:Shanghai Changfeng Study

Objective To investigate the optimal glycated haemoglobin （HbAlc） cut off points and evaluate the impact of HbAlc on diabetes and pre-diabetes in middle-aged and elderly population. Methods Subjects were recruited from Shanghai Changfeng Study. A total of 1 973 community-based participants （age_〉45） without known diabetes underwent oral glucose tolerance test （OG3-r） by using a 75-g oral glucose load and HbAlc was measured by using high performance liquid chromatography （HPLC）. Subjects were classified as normal glucose tolerance （NGT）, pre-diabetes（impaired glucose regulation, IGR） and new diagnosed diabetes （NDD） per 1999 WHO criteria. Two tests are compared with receiver operating characteristic curve （ROC）. Results Among 1973 subjects, 271 （13.7%） were diagnosed as NDD and 474 （24.0%） as IGR by using OGTT. HbAlc was 5.7%_＋0.7% in this population. Use of 6.5% as the HbAIC cutoff point has sensitivity of 38.7% and specificity of 98.5%. We recommend 6.0% as a better cutoff value for diagnosis of diabetes in this population （AUC 0.829, 95% CI 0.798-0.860, P〈0.001） with its sensitivity and specificity as 66.1% and 86.8%. For IGR, the results showed low sensitivity （44.9%） and specificity （66.7%） with an AUC of 0.571 for HbAlc when 5.8% was used as the cutoff point. Participants detected with HbAlc_〉6.0% were associated with nearly the same metabolic characteristics, including body mass index （BMI）, blood pressure, lipid profile and urine albumin-creatinine ratio （uACR） compared with diabetic subjects detected by OGTT. Conclusion The optimum HbAlc cutoff point for diabetes in our study population was lower than ADA criteria, and HbAlc may not be used to identify IGR.

Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca2+ and cyclic adenosine monophosphate levels through PI3K/AKT pathway

BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.

Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate

Background Recently, it has been suggested that the serum uric acid （SUA） level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate （GFR） reflected by the simplified Modification of Diet in Renal Disease （MDRD） equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.Methods This cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test （OGTT） for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.Results Multiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index （BMI）, waist/hippo ratio, systolic blood pressure （SBP） and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose （FPG） increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.Conclusion This study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.

Bioactive effects advances of natural polysaccharides

Taking into account the rising incidence of metabolic diseases,it is an urgent need for effective treatments to control human health problems.Natural polysaccharides have been found effective on metabolic diseases in more and more researches.In the context of serious side effects of drugs,natural polysaccharides will be verified in the prevention and treatment of metabolic diseases and show their advantages of low toxicity and high efficiency.This review mainly summarized the activity of polysaccharides from different sources in regulating metabolism,and laid a reference for metabolic diseases by natural polysaccharides.

Association between Genetic Variants and Characteristic Symptoms of Type 2 Diabetes:A Matched Case-Control Study

Objective： To examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus （T2DM）. Methods： A matched case-control study was performed to investigate the association between common variants in four genes （CDKAL1, GLIS3, GRK5, and TCFTL2） and symptoms of T2DM. Symptoms were examined with questionnaire for 710 subjects. Genomic DNA was extracted from peripheral blood mononuclear cell by salting-out procedure. Genotyping was carried out by direct sequencing of the unpurified polymerase chain reaction products. Result： Most of the T2DM patients pressented characteristic symptoms, such as feeling weak in limbs （P=0.0057）, hand tremor （P=0.0208）, bradymasesis （P=0.0234）, and polyuria （P=0.0051）. Some of the T2DM patients shared characteristic symptoms, such as desire for cold drinks （P=0.0304）, polyphagia （P=0.0051）, and furred tongue （P=0.028）. The impaired glucose regulation （IGR） cases took only one characteristic symptom of frequent micturition （P=0.0422）. GLIS3 rs7034200 and GRK5 rs10886471 were significantly associated with increased T2DM risk （GLIS3 rs7034200 under dominant model： P=0.0307; GRK5 rs 10886471 under recessive model： P=0.0092）. However, only the rs10886471 polymorphism in GRK5 showed a significant effect on both differentiated symptoms and T2DM risk. The C-allele was involved in both dampness-heat encumbering Pi （Spleen） syndrome （P=0.047） and qi-yin deficiency syndrome （P=0.002） via increased GRK5 expression. Conclnsions： Both T2DM and IGR exhibited its corresponding characteristic symptoms. The variants of GRK5 were involved with both qi-yin deficiency syndrome and dampness-heat encumbering Pi syndrome.