A cross-sectional study to assess beta-cell function in individuals with recently diagnosed young-onset type 2 diabetes mellitus and its’ complications / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications.@*Methodology@#A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels.@*Results@#113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C–peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C–peptide levels.@*Conclusion@#Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Tres versiones del "Ogtt Squeezer", un programa para evaluar de un vistazo la información metabólica de la curva de tolerancia a la glucosa / Three versions of the "Ogtt Squeezer", a program to evaluate ataglance the metabolic information of the oral glucose tolerance test

El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.

Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.

Effect of Shenqi Compound on Islet β-cell Function in Type 2 Diabetic GK Rats / 中国实验方剂学杂志

Objective:To explore the effect of Shenqi compound on islet β-cell function in type 2 diabetic GK rats. The whole genome expression profile chip technology is used to explore the molecular mechanism of Shenqi compound regulating pancreatic islet cell function and provide theoretical basis for the prevention and treatment of type 2 diabetes with traditional Chinese medicine. Method:GK rats were fed with high-fat diet daily for 4 weeks. Rats were randomly selected from GK rats to detect random blood glucose and verified the success of type 2 diabetes model. Rats were divided into 4 groups， Wistar group， model group， Shenqi compound（1.44 g∙kg-1） group and west glenn（16 mg∙kg-1） group. After 8 weeks of gavage， the serum insulin（INS） levels were detected by enzyme-linked immunosorbent assay（ELISA）. The apoptosis of islet β cells was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling（TUNEL）fluorescence method. Differential gene detection uses whole-genome expression profiling chip technology in each group of rat pancreatic tissues， the mRNA transcription level of key differential genes is detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with blank group， before gavage， 4 weeks， 8 weeks， GK rats have higher blood sugar in each group （P<0.01）.Gavage for 4 weeks and gavage for 8 weeks， compared with model group， the blood sugar of rats in each drug intervention group was lower （P<0.01）. Gavage for 8 weeks， compared with blank group， the INS level of model group was lower （P<0.01）. Compared with model group， the Shenqi compound group had a higher INS level， and the sitagliptin group had a higher INS level （P<0.01）. After gavage for 8 weeks， compared with the blank group， the number of pancreatic islet β-cell apoptosis in the model group was higher （P<0.05）. Compared with model group， the number of pancreatic islet β cell apoptosis in the Shenqi compound group and sitagliptin group was lower （P<0.05，P<0.01）. Gene chip and Real-time PCR tests both showed that phosphatidylinositol 3-kinase receptor 1（PIK3R1） was up-regulated in the Shenqi compound group/model group， and down-regulated in the sitagliptin group/model group， model group/blank group. Protein kinase B1（Akt1） was expressed in the Shenqi compound group/model The expression was up-regulated in the group， sitagliptin group/model group， and down-regulated in the model group/blank group. Conclusion:Shenqi compound which has the function of supplenmenting Qi and Yin and promoting the blood circulation， can inhibit the islet β cell apoptosis， improve islet β cell function， regulate insulin secretion， and prevent T2DM by up-regulating the expression of genes PIK3R1 and Akt1.

Clinical characteristics, residual beta-cell function and pancreatic auto-antibodies in Thai people with long-standing type 1 diabetes mellitus / Journal of the ASEAN Federation of Endocrine Societies

@#Objectives. To describe the characteristics of long-standing T1DM in Thai patients and assess residual beta-cell function with status of pancreatic autoantibodies. Methodology. This is a cross-sectional study of Thai subjects with T1DM and disease duration ≥ 25 years seen at the Theptarin Hospital. Random plasma C-peptide and pancreatic auto-antibodies (Anti-GAD, Anti-IA2, and Anti-ZnT8) were measured. Patients who developed complications were compared with those who remained free of complications. Results. A total of 20 patients (males 65%, mean age 49.4±12.0 years, BMI 22.5±3.1 kg/m2, A1C 7.9±1.6%) with diabetes duration of 31.9±5.1 years were studied. Half of the participants remained free from any diabetic complications while the proportions reporting retinopathy, nephropathy, and neuropathy were 40%, 30%, and 15%, respectively. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy but not in those who were free from other complications. The prevalence rates of anti-GAD, anti- IA2, and anti-ZnT8 were 65%, 20%, and 10%, respectively. None of the patients who tested negative for both anti-GAD and anti-IA2 was positive for anti-ZnT8. Residual beta-cell function based on detectable random plasma C-peptide (≥ 0.1 ng/mL) and MMTT was found in only 3 patients (15%). There was no relationship between residual beta-cell function and protective effects of diabetic complications. Conclusion. Endogenous insulin secretion persists in some patients with long-standing T1DM and half of longstanding T1DM in Thai patients showed no diabetic complications. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy

Insulin resistance and β-Cell function of lean versus overweight or obese Filipino patients with newly diagnosed Type 2 Diabetes Mellitus / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#To compare the level of insulin resistance and β-cell function between lean and overweight/obese Filipino patients with newly diagnosed type 2 diabetes mellitus (T2DM).@*Methodology@#This was a cross-sectional analytical study including newly diagnosed T2DM Filipino patients from St. Luke’s Medical Center - Quezon City. The patients were classified as either lean or overweight/obese. Age, sex, smoking history, anthropometric measures and blood pressure were obtained. Insulin resistance and β-cell function were determined using the homeostasis model assessment (HOMA). The original model (HOMA1) and the updated model (HOMA2) were used. @*Results@#A total of 80 subjects were included. There were 40 subjects in each group. The overweight/obese subjects had significantly higher mean insulin resistance (HOMA1-IR 9.8±11.7, HOMA2-IR 3.0±2.0) compared to the lean group (HOMA1-IR 2.9±1.5, HOMA2-IR 1.3±0.5). This was consistent in both HOMA1 and HOMA2 (p-values=0.001 and <0.001, respectively). The mean β-cell function of the overweight/obese patients was significantly higher than the lean subjects when using HOMA1 (lean=57.8±35.5, overweight/obese=93.6±66.4, p-value=0.003), but not in HOMA2 (lean=57.6±30.5, overweight/obese=74.8±45.7, p-value=0.051). Overweight/obesity increased HOMA1-IR by 4.0 and HOMA1-B by 46.1 (p-values= 0.002 and <0.001, respectively). Through the use of HOMA2, overweight/obesity increased HOMA2-IR by 1.4 and HOMA2-B by 29.1 (p-values<0.001). Being overweight/obese was also associated with significantly higher odds for developing greater insulin resistance (HOMA1-IR adjOR = 5.6, 95%CI= 1.7-19.2, p-value=0.005; HOMA2-IR adjOR=10.9, 95%CI=3.4-34.9, p-value<0.001) and lower odds for a decreased β-cell function (HOMA1-B adjOR = 0.2, 95%CI = 0.05-0.9, p-value=0.033; HOMA2-B adjOR=0.2, 95%CI=0.04-0.9, p-value=0.043) compared to being lean. @*Conclusion@#Newly diagnosed overweight/obese T2DM had higher mean insulin resistance and β-cell function compared to lean T2DM. Overweight/obesity was also associated with higher odds of developing insulin resistance and lower odds for a decreased β-cell function compared to being lean. The overweight/obese T2DM group also had worse metabolic profile manifested by higher FPG, HbA1c, SGPT and blood pressures compared to the lean T2DM group.

Prevalence of pancreatic autoantibodies in non-diabetic patients with autoimmune thyroid disease and its relation to insulin secretion and glucose tolerance

ABSTRACT Objective We evaluated the prevalence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase-protein antibodies (IA2A), their titers and their relation to first phase insulin response (FPIR) and glucose tolerance in autoimmune thyroid diseases (ATDs) patients. Subjects and methods Graves' disease (GD; n = 181) and Hashimoto's thyroiditis (HT; n = 143) patients in addition to healthy controls (n = 93) were studied. Secondly, FPIR and oral glucose tolerance tests (OGTT) were performed in 11 anti-pancreatic islet-cell (+) and in 20 anti-pancreatic-cell (-) patients. Results There was a non significant trend for higher prevalence of GADA positivity in GD vs HT (7.2% vs 2% p = 0.06), but the GADA titers were higher in HT. We also did not find a significant difference in IA2 prevalence (0.7% vs 0.0%) between these two groups or compared to the control group. In the subsequent analysis, low FPIR was found in 10% of these patients but without statistical difference for OGTT between pancreatic antibody-positive and -negative patients. Conclusion A trend for greater prevalence of GADA was observed for GD patients than for HT or control. However, the titers of these autoantibodies were higher in HT patients, but there was no significant relation to insulin secretion and glucose tolerance at that moment and stage of autoimmune diseases.

Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased beta-Cell Function Similar to Impaired Glucose Tolerance

BACKGROUND: Subjects with normal glucose tolerance (NGT) who have a high 1-hour postload plasma glucose level (> or =155 mg/dL; NGT 1 hour-high) have been shown to be at higher risk for type 2 diabetes than subjects with NGT 1 hour-low postload plasma glucose level (<155 mg/dL). We compared beta-cell function in subjects with NGT 1 hour-high, NGT 1 hour-low, and impaired glucose tolerance (IGT). METHODS: We classified subjects into NGT 1 hour-low (n=149), NGT 1 hour-high (n=43), and IGT (n=52). The beta-cell function was assessed based on insulinogenic index (IGI), oral disposition index (DI), and insulin secretion-sensitivity index-2 (ISSI-2). RESULTS: Insulin sensitivity was comparable between the subjects with NGT 1 hour-high and NGT 1 hour-low. The beta-cell function with/without adjusting insulin sensitivity was significantly different among the three groups. The IGI (pmol/mmol) was 116.8+/-107.3 vs. 64.8+/-47.8 vs. 65.8+/-80.6 (P=0.141), oral DI was 3.5+/-4.2 vs. 1.8+/-1.4 vs. 1.8+/-3.1 (P<0.001), and ISSI-2 was 301.2+/-113.7 vs. 213.2+/-67.3 vs. 172.5+/-87.5 (P<0.001) in NGT 1 hour-low, NGT 1 hour-high, and IGT, respectively. Post hoc analyses revealed that oral DI and ISSI-2 were significantly different between NGT 1 hour-low and NGT 1 hour-high but comparable between NGT 1 hour-high and IGT. CONCLUSION: Among Korean subjects with NGT, those who have a higher 1-hour postload glucose level have a compromised insulin-sensitivity adjusted beta-cell function to a similar degree as IGT subjects.

INITIATE STUDY: Insulin versus oral hypoglycemic agent as Initial therapy for newly diagnosed diabetes mellitus Type 2: A systematic review and meta-analysis / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#This study aims to evaluate the effectiveness of initial insulin therapy versus oral hypoglycemic agents in glucose control among newly diagnosed Type 2 diabetes patients. @*Methodology@#This is a systematic review and meta-analysis of RCTs with quality grade B searched using the medical subject headings (MeSH): diabetes mellitus type 2, insulin, oral hypoglycemic agent, with adults newly diagnosed with type 2 DM as subjects and given insulin (± metformin) vs. OHA. Results were summarized as graphs and forest plots using the random effects due to foreseen sources of heterogeneity using Review Manager version 5.1. @*Results@#Presence of substantial heterogeneity prevents us from making a conclusion. All four studies showed lower post treatment BMI among participants in the insulin treatment arm. An opposite finding was expected as insulin is known to cause weight gain. Main adverse effect was hypoglycemia. @*Conclusion@#Among newly diagnosed type 2 DM patients, there is insufficient evidence for or against the use of insulin compared to oral hypoglycemic agents as initial management in terms of improvement in glycemic control, decrease in insulin resistance, and improvement in beta cell function.

Effect of short-term continuous subcutaneous insulin infusion treatment on beta-cell function, blood fat and C-reactive protein of newly diagnosed type 2 diabetes mellitus patients / 中国综合临床

Objective To investigate the effect on short-term continuous subcutaneous insulin infusion (CSII) treatment on beta-cell function,serum triglyceride(TG),C-reactive protein(CRP) and serum insulin like growth factor-1 (IGF-1) of newly diagnosed type 2 diabetes mellitus(T2DM) patients.Methods Thirty-two newly diagnosed T2DM patients with fasting plasma glucose(FPG) ＞ 11.1 mmol/L were treated with CSII for 2 weeks.FPG,2 h postprandial blood glucose (2hPG),fasting insulin (FINS),2 h postprandial insulin (PINS),fasting C peptide (FC-P),2 h postprandial C peptide (PC-P),glycosylated hemoglobin (HbA1 c),Homa-β,Homa-R,TG,CRP and IGF-1 were measured and compared before and after CSII.Results (1) Compared with that of before treatment,the levels of FPG,2hPG,HbA1c,PINS and PC-P in patients after treatment were dramatically improved(t =12.04,11.57,7.61,20.77,6.16; P ＜ 0.05),and Homa-β increased from (23.0 ±16.2) to (71.0±23.8)(t=9.46,P＜0.05),while Homa-IR significantly decreased from (6.8 ±2.1) to (3.9 ± 2.6) (t =4.81,P ＜ 0.05).(2) The levels of TG and CRP significantly decreased from (1.50 ± 0.32) mmol/L,(3.14±1.14) to (1.29±0.31) mmol/L,(1.95 ±0.52) mg/L(t =26.73,23.62;P ＜0.05).The levels of IGF-1 significantly increased from (341 ± 16) μg/L to (471 ± 17) μg/L (t =8.65,P ＜ 0.05).Conclusion The excellent glycemic control,improvement of lipid metabolism,anti-inflammatory and improvement of beta-cell function can be achieved with short-term CSII intensive therapy in newly diagnosed T2DM patients with severe hyperglycemia.

Therapeutic Approaches for Preserving or Restoring Pancreatic beta-Cell Function and Mass

The goal for the treatment of patients with diabetes has today shifted from merely reducing glucose concentrations to preventing the natural decline in beta-cell function and delay the progression of disease. Pancreatic beta-cell dysfunction and decreased beta-cell mass are crucial in the development of diabetes. The beta-cell defects are the main pathogenesis in patients with type 1 diabetes and are associated with type 2 diabetes as the disease progresses. Recent studies suggest that human pancreatic beta-cells have a capacity for increased proliferation according to increased demands for insulin. In humans, beta-cell mass has been shown to increase in patients showing insulin-resistance states such as obesity or in pregnancy. This capacity might be useful for identifying new therapeutic strategies to reestablish a functional beta-cell mass. In this context, therapeutic approaches designed to increase beta-cell mass might prove a significant way to manage diabetes and prevent its progression. This review describes the various beta-cell defects that appear in patients with diabetes and outline the mechanisms of beta-cell failure. We also review common methods for assessing beta-cell function and mass and methodological limitations in vivo. Finally, we discuss the current therapeutic approaches to improve beta-cell function and increase beta-cell mass.

Moderate diet-induced weight loss is associated with improved insulin sensitivity in middle-aged healthy obese Korean women

BACKGROUND/OBJECTIVE: The goal of the present study was to investigate the effects of moderate caloric restriction on beta-cell function and insulin sensitivity in middle-aged obese Korean women. SUBJECTS/METHODS: Fifty-seven obese pre-menopausal Korean women participated in a 12-week calorie restriction program. Data on total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and fasting serum levels of glucose, insulin, C-peptide, blood pressure, leptin and anthropometrics were collected. A dietary intake assessment was based on three days of food recording. Additionally, beta-cell function [homeostasis model assessment of beta-cell (HOMA-beta), insulinogenic index (ISI), C-peptide:glucose ratio, and area under curve insulin/glucose (AUCins/glu)] and insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR), Quantitative insulin-sensitivity check index (QUICKI) and Matsuda index (MI)] were recorded. RESULTS: When calories were reduced by an average of 422 kcal/day for 12 weeks, BMI (-2.7%), body fat mass (-10.2%), and waist circumference (-5%) all decreased significantly (P < 0.05). After calorie restriction, weight, body fat percentage, hip circumference, BP, TC, HDL-C, LDL-C, plasma glucose at fasting, insulin at fasting and 120 min, AUCglu and the insulin area under the curve all decreased significantly (all P < 0.05), while insulin sensitivity (HOMA-IR, QUICKI and Matsuda index) measured by OGTT improved significantly (P < 0.01). CONCLUSIONS: Moderate weight loss due to caloric restriction with reduction in insulin resistance improves glucose tolerance and insulin sensitivity in middle-aged obese women and thereby may help prevent the development of type 2 diabetes mellitus.

Beta cell function, insulin resistance and low grade systemic inflammation in Myanmar adults with different categories of glucose tolerance / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The aim of the study was to evaluate the beta cell function, insulin sensitivity and low grade systemic inflammation in different categories of glucose tolerance in Myanmar. @*Methodology@#A cross-sectional study was conducted on 202 Myanmar subjects of both sexes, aged between 45-65 years old. Fasting blood glucose, insulin, C-peptide and hs-CRP levels were measured. A 75g oral glucose tolerance test was performed. Insulin resistance and beta cell function were assessed by homeostasis-model-assessment (HOMA). @*Results@#The subjects were categorized as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM) according to WHO-2006 criteria. Fasting serum insulin, C-peptide and hs-CRP levels and insulin resistance index (HOMA-IR) progressively increased from NGT through prediabetes (IFG, IGT) to DM (p<0.01). Beta-cell function did not change significantly in any other group as compared to normal group. @*Conclusion@#After multivariate analysis, increases in fasting C-peptide, hs-CRP and HOMA-IR index were significantly associated with diabetes. It was also found that insulin resistance was a predominant feature in deterioration of the glucose tolerance in Myanmar subjects.

Influence of combination therapy of epalrestat and insulin on islet beta cell function in newly diagnosed type 2 diabetic patients / 中国基层医药

Objective To observe the influence of epalrestat combined with insulin therapy on islet beta cell function in newly diagnosed type 2 diabetic patients.Methods 45 newly diagnosed type 2 diabetic patients were randomly treated with 4 times of subcutaneous insulin therapy(RI group) or epalrestat plus 4 times of subcutaneous insulin therapy(RI + EP group).Patients were followed up for 3 months.The fasting blood-glucose (FPG),the 2 hour postprandial blood glucose (2 h PG),fasting insulin (FINS),the 2 hour postprandial blood insulin (2 h INS),glycated hemoglobin (HbA1 C),superoxide dismutase (SOD),malondialdehyde (MDA),insulin resistance index (HOMA-IR) and insulin release index(HOMA-β) were observed at 3th month after the initiation of therapy.Results Follow-up evaluation of 22 cases in RI group,23 cases in group RI + EP were completed 3 months of treatment.After treatment,FPG,2 h PG,HbA1 C,MDA and HOMA-IR in the two groups were decreased than those before treatment,the serum FINS,2 h INS,SOD and HOMA-β were higher than those before treatment,the differences were statistically significant (all P ＜0.05).After treatment,FINS,2 h INS,SOD and HOMA-β of RI + EP group were higher than those in RI group,MDA was lower than that of RI group,the differences were statistically significant (t =3.228,2.536,3.021,2.343,2.122,all P ＜ 0.05).FPG,2 h PG,HbA1 C,HOMA-IR between the two groups had no significant differences (all P ＞ 0.05).Linear regression analysis showed that HOMA-β was positively correlated with SOD level (r =0.888,r2 =0.783,all P ＜ 0.01).Conclusion The results suggest that epalrestat combined with insulin therapy can inhibit oxidative stress,and improve islet beta cell function in newly diagnosed type 2 diabetic patients,and its clinical effect is better than monotherapy with insulin.

Association of TNF-α with insulin resistance in type 2 diabetes mellitus.

Background & objectives: TNF-α is an adipocytokine that has been implicated in the development of insulin resistance. Dysregulation of TNF-α production has been implicated in a variety of human diseases including type 2 diabetes mellitus. We aimed to find out the association of TNF-α levels with insulin resistance, body mass index and waist hip ratio; and to elicit its role with respect to duration of the disease, if any. Methods: 50 type-2 diabetic patients attending Narayana Medical Hospital, Nellore, were studied. Body mass index and Waist hip ratio were calculated. Homeostasis model assessment method was used to calculate insulin resistance (HOMA IR) and per cent β cell function (HOMA B) . Insulin was estimated by chemiluminescence method and TNF-α by ELISA method. The subjects were arbitrarily categorized into three groups based on duration of diabetes. Group 1 included subjects with diabetes of less than 5 yr duration, group 2 included diabetics of 6-10 yr duration and group 3 greater than 10 yr duration. Results: Our study revealed a significant correlation between TNF-α levels and BMI (P=0.006), the correlation being stronger in males when compared to females. A significant correlation was found between per cent β cell function and TNF-α (P=0.008). TNF-α correlated significantly with HOMA IR, HOMA B and insulin, in group 2 diabetes. Interpretation & conclusions: Our results suggest the possible role of TNF-α in the pathogenesis of type-2 diabetes mellitus and the importance of reducing obesity to prevent elevated levels of the cytokine and related complications.

The Relationship between beta-cell Function and Nutrient Intakes in Korean Adult: Using 4th Korea National Health and Nutrition Examination Survey 2009 / 대한지역사회영양학회지

The purpose of this study was to evaluate pancreatic beta-cell function of Korean adult and to examine the associations between beta-cell function and nutrient intakes. Data were analyzed for 1,917 male and 2,885 female subjects older than 30 years using 'The Forth Korean National Health and Nutrition Survey in 2009'. We calculated HOMA beta-cell (The homeostasis model assessment of beta-cell function) using fasting glucose and fasting insulin for assessing beta-cell function. Subjects were divided into HHG (High HOMA beta-cell Group) or LHG (Low HOMA beta-cell Group) according to median of HOMA beta-cell, and then nutrient intakes were compared between two groups. In the entire study population, HHG showed lower percent of carbohydrate intakes (p or = 23 kg/m2 (over-weight and obese). Significant differences of some nutrients intakes and correlations with HOMA beta-cell were observed only in under- and normal weight subjects, but not in over-weight and obese subjects. In conclusion, high carbohydrate, lower fat and lower vitamin intakes may be related with pancreatic beta-cell dysfunction in under- and normal-weight Korean.

The Changes of Blood Glucose Control and Lipid Profiles after Short-Term Smoking Cessation in Healthy Males

OBJECTIVE: Our aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males. METHODS: Smoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the beta-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: The data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA beta-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively). CONCLUSION: During the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.

Parameters Measuring Beta-Cell Function Are Only Valuable in Diabetic Subjects with Low Body Mass Index, High Blood Glucose Level, or Long-Standing Diabetes

PURPOSE: The aim of this study was to identify the most precise and clinically practicable parameters that predict future oral hypoglycemic agent (OHA) failure in patients with type 2 diabetes, and to determine whether these parameters are valuable in various subgroups. MATERIALS AND METHODS: We took fasting blood samples from 231 patients for laboratory data and standard breakfast tests for evaluation of pancreatic beta-cell function. Hemoglobin A1c (HbA1c) levels were tested, and we collected data related to hypoglycemic medications one year from the start date of the study. RESULTS: Fasting C-peptide, postprandial insulin and C-peptide, the difference between fasting and postprandial insulin, fasting beta-cell responsiveness (M0), postprandial beta-cell responsiveness (M1), and homeostasis model assessment-beta (HOMA-B) levels were significantly higher in those with OHA response than in those with OHA failure. The area under the curve (AUC) of the receiver operating characteristic (ROC) measured with postprandial C-peptide to predict future OHA failure was 0.720, and the predictive power for future OHA failure was the highest of the variable parameters. Fasting and postprandial C-peptide, M0, and M1 levels were the only differences between those with OHA response and those with OHA failure among diabetic subjects with low body mass index, high blood glucose level, or long-standing diabetes. CONCLUSION: In conclusion, postprandial C-peptide was most useful in predicting future OHA failure in type 2 diabetic subjects. However, these parameters measuring beta-cell function are only valuable in diabetic subjects with low body mass index, high blood glucose level, or long-standing diabetes.

The relation of early time secretion function of Beta cell in newly diagnosed type 2 diabetic patient and body weight changes following intensification therapy of insulin / 中国综合临床

Objective To explore the relation of early time secretion function of Beta cell in newly diag-nosed type 2 diabetic patient and the changes of body weight following intensification therapy of insulin. Methods 237 newly diagnosed type 2 diabetic patients were divided into 1 kg lower group, the 1-5 kg group, the 5 kg above group. The maximum body weight and waist circumference were recorded. The present body weight and waist circum-ference were measured according to OGTT study, meanwhile,30 minuets blood sugars, the insulin and the C-peptide (C-P) level and the blood pressure(BP) and the insulin resistance index (HOMA-IR), the early insulin secretion index (△I30/△G30) was calculated. All cases were treated for 14 days. Results Early time secretion function of Beta cell in the group keeping above lose weight 5 kg was the worst, after treatment insulin secretion level were in-creased 1.12 times and 1.86 times in 1 kg lower group than in the 1-5 kg group and above 5 kg group. Conclusions Early time secretion function of Beta cell in newly diagnosed type 2 diabetic patient is correlated with the maxi-mum body weight decrease.

Effects of Cydosponne A on Qucose Metabolism and Beta-Cell Functions in Rats / 第二军医大学学报

The effects of cyclosporine A (CsA) on glucose metabolism and betancell functions in vivo in rats were investigated. CsA (20mg/kg, 2/d) was given to Spraguer-Dawley rats for 14d. After a 1.5g/kg body weight glucose load by gavage the plasma glucose at 1 h and the area under curve (AUC) of plasma glucose were higher in the CsA-treated group than in the control (P