The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus： the Desheng Diabetic Eye Study

AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

Hippocampal insulin resistance and the Sirtuin 1 signaling pathway in diabetes-induced cognitive dysfunction

In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes mellitus were generated by a single injection of streptozotocin.At 8 weeks after streptozotocin injection,the Morris water maze test and western blot assays confirmed that the diabetic model rats had learning and memory deficits,insulin resistance,and Sirtuin 1 expression could be detected in the hippocampus.Insulin and the insulin receptor inhibitor S961 were intranasally administered to investigate the regulatory effects of insulin signaling on Sirtuin 1.The results showed that insulin administration improved the impaired cognitive function of diabetic model rats and increased the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1 in the hippocampus.Conversely,S961 administration resulted in more severe cognitive dysfunction and reduced the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1.The Sirtuin 1 activator SRT2104 and the inhibitor Sirtinol were injected into the lateral ventricle,which revealed that the activation of Sirtuin 1 increased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor.Hippocampal dendritic length and spine density also increased in response to Sirtuin 1 activation.In contrast,Sirtinol decreased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor and damaged the dendritic structure.These findings suggest that the Sirtuin 1 signaling pathway plays an important role in the development of insulin resistance-related cognitive deficits in diabetic rats.This study was approved by the Animal Ethics Welfare Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine(approval No.ZYFY201811207)in November 2018.

Functional microbiomics reveals branched-chain amino acids depletion for alleviation of insulin resistance by berberine

Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.

Cognitive Functioning and Insulin Regulation in Obese Youth

Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms associated with cognitive function in obese youth. The objective of the present study was to assess the associations among cognitive functioning and insulin regulation in a sample of obese youth. Methods: The sample consisted of 30 obese, non-diabetic youth (BMI > 95th percentile) ages 6-16 years (mean age = 12.60 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated Scale of Intelligence (WASI) and Wide Range Assessment of Memory and Learning (WRAML-2). Results: Verbal memory, attention/concentration, and intelligence scores were similar across obese youth with elevated insulin levels and normal insulin levels. Obese youth with elevated insulin levels had lower scores in visual memory, with a medium effect (effect size = 0.51). Fasting insulin levels were not associated with any of the four cognitive domains in the multiple linear regression analysis (P > 0.05). Conclusions: These data provide preliminary evidence that visual memory may be impacted in obese youth with insulin resistance. Longitudinal studies examining insulin regulation, cognitive functioning, and weight status over time are needed.

Improved <i>β</i>-cell function rather than increased insulin sensitivity is associated with reduction in hemoglobin A1c in newly diagnosed Type 2 diabetic patients treated with metformin

β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line oral agent in the treatment of Type 2 diabetes. However, the relative contributions of improved β-cell function and increased insulin sensitivity to reduction in hemoglobin A1c (HbA1c) are unclear in newly diagnosed Type 2 diabetic patients treated with metformin. We investigated β-cell function and insulin sensitivity in relation to reduction in HbA1c in 20 newly diagnosed Type 2 diabetic patients (17 men and 3 women, mean age 49.1 ± 10.1 years, mean body mass index 26.4 ± 5.2 kg/m2) treated with metformin for 16 weeks. We used homeostasis model assessment (HOMA) 2%B and HOMA2%S as estimates of β-cell function and insulin sensitivity, respectively. Median HOMA2%B and HOMA2%S significantly increased from 38.8 to 68.8 (p p = 0.004), respectively. In univariate regression analysis, reduction in HbA1c was highly correlated with change in HOMA2%B (r = -0.866, p < 0.001), but not with that in HOMA2%S (r = -0.264, p = 0.260). Furthermore, multivariate regression analysis with reduction in HbA1c as a dependent variable showed that increase in HOMA2%B but not that in HOMA2%S was a significant dependent variable (β = -0.847, p β-cell function rather than increased insulin sensitivity is associated with reduction in HbA1c. These results suggest that metformin reduces HbA1c chiefly through improved β-cell function rather than increased insulin sensitivity in patients with newly diagnosed Type 2 diabetes.

Association of point in range withβ-cell function and insulin sensitivity of type 2 diabetes mellitus in cold areas

Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.

Effects of intensive insulin therapy on immune function, inflammatory markers, matrix metalloproteinase and stress response in patients with severe pneumonia

Objective:To explore the effects of intensive insulin therapy on immune function, inflammatory markers, matrix metalloproteinase and stress response in patients with severe pneumonia.Methods: From January 2016 to December 2017, 80 cases of severe pneumonia in ICU of our hospital were selected as the subjects of this study, according to the principle of randomization, they were divided into control group (40 cases) and observation group (40 cases). The control group was given routine insulin + routine treatment, and the observation group was given insulin intensification + routine treatment. The changes of immune function, inflammation index, matrix metalloproteinase and stress level were compared between the two groups before and after treatment.Results: After treatment, the levels of IgA, IgG and IgM in the two groups were significantly higher than those before treatment, and the levels of IgA, IgG and IgM in the observation group were significantly higher than those in the control group;the levels of TNF-α, sTREM1 and CRP in the two groups were significantly lower than those before treatment, and the levels of TNF-α, sTREM1 and CRP in the observation group were significantly lower than those in the control group;the levels of TIMP-1, MMP-9 and MMP-9/TIMP-1 in the two groups were significantly lower than those before treatment, and the levels of TIMP-1, MMP-9 and MMP-9/TIMP-1 in the observation group were significantly lower than those in the control group;the levels of SF and LPO in the two groups were significantly lower than those before treatment, while the levels of SOD in the observation group were significantly higher than those before treatment, and the levels of SF and LPO in the observation group were significantly lower than those in the control group, while the levels of SOD in the observation group were significantly higher than those in the control group. Conclusions:Intensive insulin therapy can effectively improve the immune function of severe pneumonia patients, reduce their inflammatory reaction, matrix metalloproteinase levels and oxidative stress injury.

Effect of exenatide combined with metformin therapy on insulin resistance,liver function and inflammatory response in patients with type 2 diabetes mellitus combined with NAFLD

Objective: To study the effect of exenatide combined with metformin therapy on insulin resistance, liver function and inflammatory response in patients with type 2 diabetes mellitus combined with NAFLD. Methods: A total of 98 patients with type 2 diabetes mellitus combined with NAFLD who were treated in the hospital between February 2015 and January 2017 were divided into control group and observation group by random number table, each with 49 cases. Control group received metformin therapy, and observation group received exenatide combined with metformin therapy. Serum levels of insulin resistance indexes, liver function indexes and inflammatory factors of two groups of patients were detected before treatment and after 12 weeks of treatment. Results: Before treatment, serum levels of insulin resistance indexes, liver function indexes and inflammatory factors were not significantly different between the two groups of patients;after 12 weeks of treatment, serum INS and HOMA-IR levels as well as AST, ALT, GGT, ALP, hs-CRP, IL-1β and IL-6 contents of observation group were lower than those of control group. Conclusion: Exenatide combined with metformin therapy can effectively reduce insulin resistance, reduce liver function injury and inhibit systemic inflammatory response in patients with type 2 diabetes mellitus combined with NAFLD.

Functional foods-based diet as a novel dietary approach for management of type 2 diabetes and its complications: A review

Type 2 diabetes is a complicated metabolic disorder with both short- and long-term undesirable complications. In recent years, there has been growing evidence that functional foods and their bioactive compounds, due to their biological properties, may be used as complementary treatment for type 2 diabetes mellitus. In this review, we have highlighted various functional foods as missing part of medical nutrition therapy in diabetic patients. Several in vitro, animal models and some human studies, have demonstrated that functional foods and nutraceuticals may improve postprandial hyperglycemia and adipose tissue metabolism modulatecarbohydrate and lipid metabolism. Functional foods may also improve dyslipidemia and insulin resistance, and attenuate oxidative stress and inflammatory processes and subsequently could prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. In conclusion available data indicate that a functional foods-based diet may be a novel and comprehensive dietary approach for management of type 2 diabetes.

Hyperinsulinemia,Insulin Resistance and Cognitive Decline in Older Cohort

Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and insulin （IR） in the development of AD are still controversial. This study was designed to evaluate or IR influenced the cognitive functions of older cohort. Methods The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose （FBG） and fasting insulin （FINS） were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. Results In our study, there were 180 participants with HI and 148 without HI, and 192 with iR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model I adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. Conclusion HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.

Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction(HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue(VAT), pancreatic fat fraction(PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance(HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index(WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either:(1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/d L to < 126 mg/d L;(2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/d L and < 200 mg/d L; or(3) hemoglobin A1 c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index(BMI)-SD score, and VAT. In multiple regression analysis withWBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI(standardized coefficient B,-0.398; P = 0.001) as well as HOMA-IR(0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes(OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.

interrelationships between ghrelin, insulin and glucose homeostasis: physiological relevance

Ghrelin is a 28 amino acid peptide mainly derived from the oxyntic gland of the stomach. Both acylated(AG) and unacylated(UAG) forms of ghrelin are found in the circulation. Initially, AG was considered as the only bioactive form of ghrelin. However, recent advances indicate that both AG and UAG exert distinct and common effects in organisms. Soon after its discovery, ghrelin was shown to promote appetite and adiposity in animal and human models. In response to these anabolic effects, an impressive number of elements have suggested the influence of ghrelin on the regulation of metabolic functions and the development of obesityrelated disorders. However, due to the complexity ofits biochemical nature and the physiological processes it governs, some of the effects of ghrelin are still debated in the literature. Evidence suggests that ghrelin influences glucose homeostasis through the modulation of insulin secretion and insulin receptor signaling. On the other hand, insulin was also shown to influence circulating levels of ghrelin. Here, we review the relationship between ghrelin and insulin and we describe the impact of this interaction on the modulation of glucose homeostasis.

Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes

Background:Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,the potential associations of insulin resistance(IR)and beta-cell function(BCF)with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood.Methods:A cross-sectional survey of 15,928 participants was conducted.Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF.A restricted cubic spline(RCS)nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids.Results:High triglyceride(TG),low high-density lipoprotein cholesterol,and high low-density lipoprotein cholesterol(LDL-C)accounted for 49.7%,47.8%,and 59.2%of the participants,respectively.In multivariable analysis,high IR was associated with an increased risk of high TGs(P for trend<0.001)in T1DM and is associated with an elevated risk of high TG and low HDL-C(all P for trend<0.01)in T2DM.Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders.Conclusion:High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients,suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.

The hypoglycemic potential of phenolics from functional foods and their mechanisms

Long-term postprandial hyperglycemia is a primary risk factor for developing chronic metabolic diseases such as obesity,type 2 diabetes,and cardiovascular disease.Chronic hyperglycemia induces the glycation of proteins,oxidative stress,inflammation and increases plasma insulin and lipid concentrations.Insulin resistance is the primary cause of postprandial excursions of blood glucose and lipids.Hyperglycemia can be treated by lowering dietary carbohydrates intake,digestion,and absorption.Various functional foods improve glucose metabolism by increasing insulin sensitivity and inhibitingα-glucosidase in the small intestine.Natural phytochemicals,especially active phenolics are good antioxidants and show anti-inflammatory action and regulate blood glucose.This review aimed to report on hypoglycemic properties of active phenolics from functional foods and their proposed anti-diabetic mechanisms.Nevertheless,further clinical trials are required to confirm the bioavailability,safety,and efficacy of phenolics,especially the dosage and duration of treatment,to avoid adverse effects and give better dietary recommendations.

The Influence of the Pro12Ala Mutation of PPARγ2 Receptor Gene on β-cells Restoration and Insulin Resistance in Type 2 Diabetes with Hypertension

The aim of this investigation was to determine whether a PPAR72 Prol2Ala polymorphism was associated with insulin resistance, β-cellfunction and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes （HbAC1〈6.0） were investigated, including 132 hypertensive diabetic （HTD） subjects, 157 normotensive diabetic （NTD） subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test （OGTT）. Biochemical measurements （high-density lipoprotein （HDL） and low-density lipoprotein-cholesterol （LDL）, triglycerides） and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group （3. 03 %） than in the non-hypertension group （5.7 %） （P〈0.05） after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level （P=0. 0127）, and better glucose tolerance 60 min after oral glucose （P=0. 0361）. Moreover, plasma insulin concentrations at 60 min was lower than those without A variant （P = 0. 0275）, and both hypertensive Ala/Pro in HOMA-β （P ： 0. 0455） and AUC for insulin （P=0. 0473） were higher, and HOMA-IR was lower （P=0. 0375） as compared with hypertensive Pro/Pro subjects. No association was observed between Prol2Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPARγ2 on glucose homeostasis and insulin resistance.

Association of insulin resistance with serum ferritin and aminotransferases-iron hypothesis

AIM: To investigate the relationship of iron indices with diabetes mellitus(DM) in those without hemochromatosis.METHODS: This cross-sectional study examined data collected during the Third National Health and Nutrition Examination Survey(NHANES III). Only those who fasted properly and were not anemic with transferrin saturation < 45% were included(n = 6849). Insulin sensitivity and beta cell function were calculated from fasting glucose and insulin concentrations. Indices of iron metabolism were examined in the presence or absence of DM. We examined the relationship of insulin sensitivity and beta cell function with serum ferritin concentration. The influence of C-reactive protein and liver enzymes was also investigated.RESULTS: Serum ferritin concentration was significantly higher in diabetic subjects(P = 0.0001 to< 0.000001). The difference remained significant after adjustment for age, body mass index, alcohol consumption, and mineral/iron supplement(P = 0.03 to< 0.000001). In those who did not take insulin, serum ferritin concentration was negatively associated with insulin sensitivity(P = 0.05 to 0.00001), but not with beta cell function. The alanine aminotransferase was correlated with serum ferritin concentration(P = 0.02 to< 0.000001) but not with insulin sensitivity, suggesting the role of the liver in iron-associated insulin resistance.CONCLUSION: As most of diabetes is type 2 diabetes and insulin resistance is a cardinal feature of type 2diabetes, disordered iron metabolism could play a role in the pathogenesis of insulin resistance and type 2diabetes through its effect on liver function.

Adult neural stem cell dysfunction in the subventricular zone of the lateral ventricle leads to diabetic olfactory defects

Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.