NLRP3 Inflammasome in Relation to Glucose and Lipid Metabolism, and Insulin Resistance in Diabetes and Pre-Diabetes

Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with abnormal blood glucose divided into the pre-diabetes mellitus (PDM) group (N = 46) and the type 2 diabetes mellitus (T2DM) group (N = 54). 20 normoglycemic subjects (NG, N = 20) were selected as a control group. The serum levels of glucose and lipid metabolism, IR, and the expression of NLRP3, ASC and Caspase-1 were measured. Besides, the correlations of NLRP3 inflammasome with glucose and lipid metabolism, and IR were analyzed. Results: Compared with the NG group, the levels of NLRP3, ASC, Caspase-1, FBG, HbA1C, TG, LDL-C, FINs, and HOMA-IR were higher (P β were lower (P P β were seen (P P β. Regression analysis further showed that blood glucose related indexes, FINs, and NLRP3 have made a decisive contribution to IR. Conclusions: Collectively, this evidence suggested that NLRP3 is closely related to glucose and lipid metabolism, and IR, and activated in PDM and T2DM.

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.

Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy

AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.

Increased Arterial Stiffness in Subjects with Pre-diabetes among Middle Aged Population in Beijing,China

Objective To investigate the relationship between arterial stiffness and pre-diabetes when assessed by the new glycosylated hemoglobin Ale （HbAlc） 5.7%-6.4% criterion or by impaired fasting glucose in middle aged Chinese. Methods 1122 adults aged 55 years or younger in the health examination centers for physical check-ups were enrolled in the two large-sized Tertiary Comprehensive Hospitals in Beijing from June 2011 to June 2012 after excluding those who previously had been diagnosed or treated as diabetes or cardiovascular disease. Subjects with a diagnosis of pre-diabetes according to impaired fasting glucose （IFG） （fasting plasma glucose （FPG） levels at 5.6-6.9 mmol/L）, HbA^c levels at 5.7%-6.4%, or both, were classified into four groups for observation： （1） Normoglycaemia （HbA^c〈5.7% and FPG 〈5.6 mmol/L）; （2） IFG alone （FPG levels at 5.6-6.9 mmol/L and HbA1c〈5.7% ）; （3） HbAI~ 5.7%-6.4% alone （HbA^c levels at 5.7%-6.4% and FPG 〈5.6 mmol/L）; and （4） both HbA1c 5.7%-6.4% and IFG （l-lbA1~ levels at 5.7%-6.4% and FPG levels at 5.6-6.9 mmol/L）. All subjects were measured for weight, height, waist circumference, blood pressure, fasting plasma glucose, HbA1c, lipid profile and brachial-ankle pulse wave velocity （baPWV）. Results The mean values of baPWV were 1282±8, 1311±10, 1398±30, and 1418_±27 cm/s （Mean_±SE） in Normoglycaemia, HbA~ 5.7%-6.4% alone, IFG alone and the both HbAlc 5.7%-6.4% and IFG groups, respectively. After adjusting for age, gender, blood pressure, BMI and triglyceride, baPWV was significantly higher in subjects with both HbAlc5.7%-6.4% and iFG compared among the subjects with Normoglycaemia （1350±14 vs. 1301±6 cm/s, P=0.002） and HbA1c 5.7%-6.4% alone （1350±14 vs. 1309±8 cm/s, P=0.013）.Conclusion Subjects with pre-diabetes exhibited a greater arterial stiffness.

Update on pre-diabetes: Focus on diagnostic criteria and cardiovascular risk

Pre-diabetes, which is typically defined as blood glucose concentrations higher than normal but lower than thediabetes threshold, is a high-risk state for diabetes and cardiovascular disease development. As such, it represents three groups of individuals: Those with impaired fasting glucose(IFG), those with impaired glucose tolerance(IGT) and those with a glycated haemoglobin(HbA1c) between 39-46 mmol/mol. Several clinical trials have shown the important role of IFG, IGT and HbA1c -pre-diabetes as predictive tools for the risk of developing type 2 diabetes. Moreover, with regard to cardiovascular disease, pre-diabetes is associated with more advanced vascular damage compared with normoglycaemia, independently of confounding factors. In view of these observations, diagnosis of pre-diabetes is mandatory to prevent or delay the development of the disease and its complications; however, a number of previous studies reported that the concordance between pre-diabetes diagnoses made by IFG, IGT or HbA1c is scarce and there are conflicting data as to which of these methods best predicts cardiovascular disease. This review highlights recent studies and cur-rent controversies in the field. In consideration of the expected increased use of HbA1c as a screening tool to identify individuals with alteration of glycaemic homeo-stasis, we focused on the evidence regarding the ability of HbA1c as a diagnostic tool for pre-diabetes and as a useful marker in identifying patients who have an increased risk for cardiovascular disease. Finally, we reviewed the current evidence regarding non-traditional glycaemic biomarkers and their use as alternatives to or additions to traditional ones.

Correlation of Liver Enzymes with Diabetes and Pre-diabetes in Middle-aged Rural Population in China

The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus（T2DM） and pre-diabetes（pre-DM） in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test（OGTT） was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases（ALT and GGT）, Hb A1 C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose（IFG）, impaired glucose tolerance（IGT）, impaired fasting glucose combined with impaired glucose tolerance（IFG＋IGT） and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio（WHR）, blood pressure, fasting blood glucose（FBG）, high density lipoprotein-cholesterol（HDL-C）, and liver enzymes（ALT and GGT）. Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance（IR） in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.

Prevalence rates and cardiometabolic determinants of diabetes mellitus and pre-diabetes with projected coronary heart disease at bank site of Brazzaville

Background: Aim: Congolese Bank employees are often inactive without valid information on the burden of dysglycemia and cardiometabolic risk. This study aims to assess the prevalence rates of diabetes mellitus (DM) and pre-diabetes and to identify the environmental, genetic and cardiometabolic risk factors associated with Type 2 diabetes mellitus (T2DM) and pre-diabetes among Congolese bank employees. Methods: In representative 126 bank employees from Brazzaville, Congo, Central Africa, Abdominal obesity, dyslipidemia and metabolic syndrome (MetS) were defined by IDF for Europe, NCEP-ATPIII and IDF criteria modified for Central Africa. Projected high 10-year total risk of coronary heart disease (CHD) ≥20% was calculated using Framingham scores. Results: Out of the employees, 16% and 21.4% had DM and pre-diabetes, respectively. The rate of T2DM among diabetics was estimated 90%. Aging, high total cholesterol, high LDL-cholesterol, high conicity index and longer urban residence after migration were significantly associated with pre-diabetes. Physical inactivity, smoking, excessive alcohol intake, abdominal obesity, female gender, low HDL-C, hypertension, CHD, projected high 10-year total CHD risk, age ≥ 55 years, urban residence, Southern area residence, high socioeconomic status, non married status, MetS/NCEP, MetS/IDF for Europe and MetS/IDF for Africa were significantly associated with T2DM.MetS/IDF for Africa was the only independent determinant of T2DM. Conclusion: Urgent prevention and intervention programme are needed to curb the alarming increase in DM, T2DM, pre-diabetes.

Changes before and after improvement of subjective sleep state of a man diagnosed with pre-diabetes and sleep disorder

The purpose of this case study was to examine the changes before and after improvements of the subjective sleep status of Mr A, a 40-year-old man diagnosed with pre-diabetes and a sleep disorder. Data were collected using a Holter monitor for 24 hours a day for 3 days to assess autonomic nervous activity by recording bed-time and waking time activity (activity counts: ACs). Mr. A kept a diary of activities and completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The study revealed that subjective sleeping hours correlated almost precisely with those measured by the actigraph and as described in the diary. Both the parasympathetic and sympathetic nervous system activities were imbalanced. However, no correlation was observed between the ACs and autonomic nervous activity. Subjective sleep state according to the PSQI score improved remarkably by dietary and exercise therapy from 13 to 3 points, after six months, with corresponding high level sleep satisfaction level. Significant correlations were observed between ACs and high-frequency spectral power of R-R intervals, and between ACs and the low-frequency/high frequency ratio of spectral power of R-R intervals. Although Mr. A’s sleep satisfaction level has improved, the autonomic nervous system activity remained different from that of healthy people.

Study on influencing factors of beta cell early stage dysfunction in pre-diabetes

Objective:To study the effects of obesity,blood lipids,age and other factors on early functional defects ofβcells in pre-diabetes.Methods:Thirty-seven IGR subjects who met the study conditions were randomly selected,and 42 T2DM subjects were used as the control group.General items such as BMI and TG were evaluated.Standard steamed bread test was used to evaluate the subjects'fasting,30 minutes,60 minutes,120 minutes,180 minutes of insulin,C-peptide secretion and peak time.HOMA-IR index and Matsuda index were used to evaluate insulin sensitivity.HOMA-βand AUCI/AUCG were used to evaluateβ-cell Function.Results:The results of BMI,TG,Matsuda index,HOMA-βand AUCI/AUCG in IGR group were higher than those in T2DM group,and HOMA-IR was lower than those in T2DM group(P<0.05).BMI and TG in IGR group were positively correlated with fasting and late phase secretion ofβcells,positively correlated with time of peak secretion ofβcells,positively correlated with HOMA-IR(P<0.05)and negatively correlated with Matsuda index(P<0.05),and age factor in IGR group was significantly correlated with HOMA-βand AUCI/AUCG.(P<0.05).After controlling for BMI and TG,age was still associated with HOMA-βand AUCI/AUCG.(P<0.05);BMI in IGR and T2DM groups were positively correlated withβ-cell HOMA-βand AUCI/AUCG functional indexes,(P<0.05);TG,late-phase insulin secretion value and peak time of insulin secretion andβ-cell secretion index AUCI/AUCG index in IGR obese group were higher than those in non-obese group(P<0.05),and insulin resistance index Matsuda was lower than those in the non-obese group.(P<0.05).Conclusion:The increase of BMI,TG and age are the important factors that affect the early function defect ofβcell in the stage of IGR,especially the correlation between BMI,TG and IGR is greater than that of T2DM,which should be the target of intervention,control and treatment in the early stage of diabetes.

Tale of two kinases:Protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in pre-diabetic cardiomyopathy

Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations,including insulin resistance,visceral fat accumulation,and dyslipidemias,which increase the risk for developing cardiovascular disease.Metabolic syndrome is associated with augmented sympathetic tone,which could account for the etiology of pre-diabetic cardiomyopathy.This review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustainedβ-adrenergic response in pre-diabetes,focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic cardiomyopathy.The research reviewed indicates that both protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ play important roles in functional responses mediated byβ1-adrenoceptors;therefore,alterations in the expression or function of these kinases can be deleterious.This review also outlines recent information on the role of protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in abnormal Ca^(2+)handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy.

Literature review of type 2 diabetes mellitus among minority Muslim populations in Israel

This review surveys the literature published on the characteristics and implications of pre-diabetes and type 2 diabetes mellitus(T2DM) for the Arab andBedouin populations of Israel. T2 DM is a global health problem. The rapid rise in its prevalence in the Arab and Bedouin populations in Israel is responsible for their lower life expectancy compared to Israeli Jews. The increased prevalence of T2 DM corresponds to increased rates of obesity in these populations. A major risk group is adult Arab women aged 55-64 years. In this group obesity reaches 70%. There are several genetic and nutritional explanations for this increase. We found high hospitalization rates for micro and macrovascular complications among diabetic patients of Arab and Bedouin origin. Despite the high prevalence of diabetes and its negative health implications, there is evidence that care and counseling relating to nutrition, physical activity and self-examination of the feet are unsatisfactory. Economic difficulties are frequently cited as the reason for inadequate medical care. Other proposed reasons include faith in traditional therapy and misconceptions about drugs and their side effects. In Israel, the quality indicators program is based on one of the world's leading information systems and deals with the management of chronic diseases such as diabetes. The program's baseline data pointed to health inequality between minority populations and the general population in several areas, including monitoring and control of diabetes. Based on these data, a pilot intervention program was planned, aimed at minority populations. This program led to a decrease in inequality and served as the basis for a broader, more comprehensive intervention that has entered the implementation stage. Interventions that were shown to be effective in other Arabic countries may serve as models for diabetes management in the Arab and Bedouin populations in Israel.

Prevalence and Correlates of Prediabetes and Diabetes Results-I: A Screening Plan in a Selected Military Community in Central Saudi Arabia

Background: Diabetes is a chronic disease of a genetic and environmental background. If it is not diagnosed and controlled early, it can have devastating complications. Aim: Measure and analyze the prevalence and risks of prediabetes and diabetes among recruits enlisted in the Wadi Al-Dawasir (WD) military zone, central Saudi Arabia. The influence of some demographic criteria, weight, and blood pressure upon blood glucose level would be evaluated. Methods: A cross sectional design was utilized, whereas predesigned questionnaire and clinical interview were used to screen the study population. Results: The participants’ median age was 33.7 (IQR 11.9), mean body mass index (BMI) was 27.6 ± 5.4 kg/m2. Out of 531 recruits screened, almost two-thirds were either overweight (34.7%) or obese (29.9%). The mean waist circumference (WC) was 94.7 ± 13.3 cm;and 27.9% had central obesity (WC ≥102 cm). Random plasma glucose (RPG) median accounted 106 mg/dl (IQR 21). The participants’ RPG levels significantly increased by age (U = 19697.0), by BMI [H(df 5) = 59.6], and by WC (U = 25,670.5), (p rho(df 503) = 0.241, p U 3515, p 25 to ≥40 kg/m2) more than normal subjects [46 (87%) vs. 5 (0.9%)], [χ2(df 5) = 18.8, p Conclusions: Prediabetes and uncontrolled diabetes are relatively prevalent among Saudi recruits’ community. An insufficient influence of obesity for developing diabetes symptoms in the study population may well be attributed to time factor separating the two variables. A preventive approach to revert the predisposition of prediabetes in WD recruits population is quite promising.

Comparison of the fatty acid composition of the serum phospholipids of controls, prediabetics and adults with type 2 diabetes

Objective: Although abnormalities in the fatty acid composition of serum and red cell membrane phospholipids of patients with type 2 diabetes are well-documented, lacking are studies of this issue in prediabetic individuals. Materials/Methods: For this cross-sectional study, we recruited 180 subjects (30 - 80 years), 56 of whom were normal with regard to glucose control (HbA1c, 6.5%). Serum phospholipids were isolated and analyzed for fatty acids. Results: Most importantly, the fatty acid compositions of the controls and prediabetic subjects were not different for 19 fatty acids. However, the fatty acid profile of the phospholipids of the patients with diabetes differed from the other two groups;the 14 to 18-carbon saturated fatty acids were decreased by 12% - 26% whereas the unsaturated fatty acids 16:1n-7, 18:1n-9, 18:2n-6, 20:3n-6 and 20:4n-6 were increased by 45% - 64%. Of note, the docosahexaenoic acid (DHA) status of individuals in all three study groups was remarkably low compared with international values, as indicated by DHA proportions in the 1.62% - 2.07% range, and there were no differences between groups. The mean melting point of the phospholipid fatty acids of the diabetic patients (32.2℃) was significantly lower (p < 0.001) than that of the prediabetic subjects (38.1℃) and the controls (39.9℃) which were not different from each other. Conclusion: These observations indicate that the fatty acid changes associated with type 2 diabetes follow the onset of the disease as opposed to being a causative factor of poor glucose control and insulin insensitivity.

A diabetic hypertension treatment program for the underserved in rural Dominican Republic

Background: Worldwide, diabetes and hypertension are leading causes of preventable end-organ disease. The prevalence of these diseases in the Dominican Republic is high and the end stage complications common. A treatment program utilizing modern protocols often thought too complex for the rural poor was initiated. Methods: With local government permission, a pilot study utilized Dominican physicians and local healthcare advocates (cooperadores) to obtain medical histories and physical exams as well as to determine healthcare needs specifically for type 2 diabetes and hypertension. A glycosylated hemoglobin (A1c) was used to identify and stratify diabetes patients. Blood pressure parameters per established standards were used to identify patients with hypertension. As indicated, pharmacotherapy was initiated (see treatment protocols), multiple forms of education and awareness building utilized, and a protocol-driven follow-up program maintained under weekly review. Results: In fifteen months, 1405 patients were screened, 229 type 2 diabetes patients, 59 pre-diabetes patients, and 98 hypertension patients were identified and enrolled for education, treatment, and follow-up. Normalization of blood pressure in hypertensives at 6 month follow-up was 78% and reduction of A1c values to <7.0 was 79.8%. Conclusion: Utilizing a best practice approach per internationally agreed-upon parameters has been shown here to be not only relevant but capable of improving outcomes in a developing world setting. A model incorporating standard of care, education, and integration of local resources as established suggests that further study is warranted to evaluate the long-term benefits as well as secondary outcomes of this approach to local populations.

Cost effectiveness of nonpharmacological prevention programs for diabetes:A systematic review of trial-based studies

Trial-based economic value of prevention programs for diabetes is inexplicit.We aimed to review the cost-effectiveness of nonpharmacological interventions to prevent type-2 diabetes mellitus(T2DM)for high-risk people.Six electronic databases were searched up to March 2022.Studies assessing both the cost and health outcomes of nonpharmacological interventions for people at high-risk of T2DM were included.The quality of the study was assessed by the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist.The primary outcome for synthesis was incremental cost-effectiveness ratios(ICER)for quality-adjusted life years(QALYs),and costs were standardized in 2022 US dollars.Narrative synthesis was performed,considering different types and delivery methods of interventions.Sixteen studies included five based on the US diabetes prevention program(DPP),six on non-DPP-based lifestyle interventions,four on health education,and one on screening plus lifestyle intervention.Compared with usual care,lifestyle interventions showed higher potential of cost-effectiveness than educational interventions.Among lifestyle interventions,DPP-based programs were less cost-effective(median of ICERs:$27,077/QALY)than non-DPP-based programs(median of ICERs:$1395/QALY)from healthcare perspectives,but with larger decreases in diabetes incidence.Besides,the cost-effectiveness of interventions was more possibly realized through the combination of different delivery methods.Different interventions to prevent T2DM in high-risk populations are both cost-effective and feasible in various settings.Nevertheless,economic evidence from low-and middle-income countries is still lacking,and interventions delivered by trained laypersons and combined with peer support sessions or mobile technologies could be potentially a cost-effective solution in such settings with limited resources.

The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice

Jin-tang-ning(JTN), a Chinese patent medicine, mainly comprised of Bombyx mori L., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2 DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate(MSG)-induced obese mice,suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance(IGT) to T2 DM. In this study, we evaluated the effect of JTN on the progression of T2 DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment,blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp.Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones(insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase(GCK), pyruvate carboxylase(PCB) and pancreas duodenum homeobox-1(PDX-1), while down-regulating C/EBP homologous protein(Chop)expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum(ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2 DM.

Total pancreatectomy with islet autotransplantation in diabetic and pre-diabetic patients with intractable chronic pancreatitis

Total pancreatectomy with islet autotransplantation(TPIAT)is an effective treatment option for non-diabetic patients with intractable chronic pancreatitis.The outcome and potential benefits for pre-diabetic and diabetic patients are less well established.Thirty-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control:diabetes mellitus(DM)(n=5,15%),pre-DM(n=11,32%)and non-DM(n=18,54%).Pre-operative fasting c-peptide was detectable and similar in all 3 groups.Islet yield in the DM group was comparable to pre-DM and non-DM groups(median islet equivalents[IEQ]was 191,800,111,800,and 232,000 IEQ,respectively).Patients received islet mass of over the target level of 2000 IEQ/kg in pre-DM and DM at lower but clinically meaningful rates compared to the non-DM group:45%(5/11)and 60%(3/5)for a combined 50%(8/16)rate,respectively,compared to 83%(15/18)for the non-DM group.At 1 year,fasting c-peptide and HbA1c did not differ between DM and pre-DM groups but c-peptide was significantly higher in non-DM.Islet transplantation failed(negative c-peptide)only in 1 patient.Preoperatively,all patients experienced pancreatic pain with daily opioid dependence in 60%to 70%.Pancreatic-type pain gradually subsided completely in all groups with no differences in other painful somatic symptoms.Diabetic patients with measurable pre-operative c-peptide can achieve similar benefit from TPIAT,with comparable outcomes to pre-diabetic and non-diabetic patients including pain relief and the metabolic benefit of transplanted islets.Not surprisingly,endocrine outcomes for diabetic and prediabetics patients are substantially worse than in those with normal pre-operative glucose control.

Prognostic significance of the hemoglobin A1c level in non-diabetic patients undergoing percutaneous coronary intervention: a meta-analysis

Background:The predictive value of hemoglobin A1c(HbA1c)levels in non-diabetic patients with myocardial infarction undergoing percutaneous coronary intervention(PCI)is still controversial.This study aimed to evaluate whether HbA1c levels were independently associated with adverse clinical outcomes in non-diabetic patients with coronary artery disease(CAD)who had undergone PCI by performing a meta-analysis of cohort studies.Methods:This meta-analysis included non-diabetic patients with CAD who had undergone PCI.A systematic search for publications listed in the PubMed,Embase,and Cochrane Library databases from commencement to December 2018 was conducted.Studies evaluating the adverse clinical outcomes according to abnormal HbA1c levels in non-diabetic patients diagnosed with CAD who had undergone PCI were eligible.The primary outcomes were long-term all-cause deaths and long-term major adverse cardiac events,and the secondary outcome was short-term all-cause deaths.The meta-analysis was conducted with RevMan 5.3 and Stata software 14.0.Odds ratios(ORs)were pooled using a random or fixed-effects model,depending on the heterogeneity of the included studies.Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity,when necessary.Results:Six prospective cohort studies involving 10,721 patients met the inclusion criteria.From the pooled analysis,abnormal HbA1c levels were associated with increased risk for long-term all-cause death(OR 1.39,95%confidence interval[CI]1.16-1.68,P=0.001,I2=45%).Sub-group analysis suggested that abnormal HbA1c levels between 6.0%and 6.5%predicted higher long-term major adverse cardiac event(including all-cause deaths,non-fatal myocardial infarction,target lesion revascularization,target vessel revascularization,recurrent acute myocardial infarction,heart failure requiring hospitalization,and stent thrombosis)risk(OR 2.05,95%CI 1.46-2.87,P<0.001,I2=0).Contrarily,elevated HbA1c levels were not associated with increased risk of short-term all-cause death(OR 1.16,95%CI 0.88-1.54,P=0.300,I2=0).Conclusions:An abnormal HbA1c level is an independent risk factor for long-term adverse clinical events in non-diabetic patients with CAD after PCI.Strict control of HbA1c levels may improve patient survival.Further studies in different countries and prospective cohort studies with a large sample size are required to verify the association.