Glucose Tolerance Subjects Research Articles

Polymorphisms in the SOCS7 gene and glucose homeostasis traits

BackgroundSOCS7 is a member of the suppressor of cytokine signaling family of proteins and is expressed in skeletal muscle and islets. SOCS7 deficient mice develop islet hyperplasia in the setting of increased insulin sensitivity and normal glucose tolerance. The objective of this study was to determine if variants in SOCS7 play a role in variation of glucose and insulin levels and the development of type 2 diabetes (T2DM).ResultsFive SOCS7 tagging SNPs were genotyped in diabetic and nondiabetic Old Order Amish. A case–control study was performed in T2DM (n = 145) and normal glucose tolerant (n = 358) subjects. Nominal associations were observed with T2DM and the minor alleles for rs8068600 (P = 0.01) and rs8074124 (P = 0.04); however, only rs8068600 remained significant after Bonferroni adjustment for multiple comparisons (P = 0.01). Among nondiabetic Amish (n = 765), no significant associations with glucose or insulin traits including fasting or 2 hour glucose and insulin from the oral glucose tolerance test, insulin or glucose area under the curve, Matsuda Index or HOMA-IR were found for any of the SNPs.ConclusionIn conclusion, genetic variants in the SOCS7 gene do not impact variation in glucose homeostasis traits and only minimally impact risk of T2DM in the Old Order Amish. Our study was not able to address whether rare variants that potentially impact gene function might influence T2DM risk.

GLP-1 Action and Glucose Tolerance in Subjects With Remission of Type 2 Diabetes After Gastric Bypass Surgery

OBJECTIVEGlucagon like peptide-1 (GLP-1) has been suggested as a major factor for the improved glucose tolerance ensuing after Roux-en-Y gastric bypass (RYGBP) surgery. We examined the effect of blocking endogenous GLP-1 action on glucose tolerance in subjects with sustained remission of type 2 diabetes mellitus (T2DM) present before RYGBP.RESEARCH DESIGN AND METHODSBlood glucose, insulin, C-peptide, glucagon, GLP-1, and glucose-dependent insulinotropic peptide levels were measured after a meal challenge with either exendin-(9–39) (a GLP-1r antagonist) or saline infusion in eight subjects with sustained remission of T2DM after RYGBP and seven healthy controls.RESULTSInfusion of exendin-(9–39) resulted in marginal deterioration of the 2-h plasma glucose after meal intake in RYGBP subjects [saline 78.4 ± 15.1 mg/dL compared with exendin-(9–39) 116.5 ± 22.3 mg/dL; P < 0.001]. Furthermore, glucose response to meal intake was similarly enlarged in the two study groups [percent change in the area under the curve of glucose exendin-(9–39) infusion versus saline infusion: controls 10.84 ± 8.8% versus RYGBP 9.94 ± 8.4%; P = 0.884]. In the RYGBP group, the blockade of the enlarged GLP-1 response to meal intake resulted in reduced insulin (P = 0.001) and C-peptide (P < 0.001), but no change in glucagon (P = 0.258) responses.CONCLUSIONSThe limited deterioration of glucose tolerance on blockade of GLP-1 action in our study suggests the resolution of T2DM after RYGBP may be explained by mechanisms beyond enhancement of GLP-1 action.

Letter by Wang et al Regarding Article, “Childhood Air Pollutant Exposure and Carotid Artery Intima–Media Thickness in Young Adults”

HomeCirculationVol. 127, No. 22Letter by Wang et al Regarding Article, “Childhood Air Pollutant Exposure and Carotid Artery Intima–Media Thickness in Young Adults” Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBLetter by Wang et al Regarding Article, “Childhood Air Pollutant Exposure and Carotid Artery Intima–Media Thickness in Young Adults” Xi-Mei Wang, PhD, Yue-Jin Yang, MD, PhD and Yong-Jian Wu, MD, PhD Xi-Mei WangXi-Mei Wang Department of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of China Search for more papers by this author , Yue-Jin YangYue-Jin Yang Department of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of China Search for more papers by this author and Yong-Jian WuYong-Jian Wu Department of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of China Search for more papers by this author Originally published4 Jun 2013https://doi.org/10.1161/CIRCULATIONAHA.112.141564Circulation. 2013;127:e658To the Editor:We read with great interest the recently published article by Breton et al1 regarding childhood air pollutant exposure and carotid artery intima–media thickness (CIMT) in young adults. The authors report that childhood exposure to O3 is a novel risk factor for CIMT in a healthy population of college students. Given the study’s findings, we acknowledge that exposure to O3 may play an important role in the development of CIMT. However, based on the data provided in this study, we think that the authors should consider additional clinically relevant information that might help make the conclusion more convincing. It is well known that the risk factors associated with atherogenesis later in life are already present and observable in college-aged young adults, such as dietary pattern composition, blood pressure (BP) status during adolescence period, abnormal glucose metabolism, and so on. Now we will introduce the problems existing in this article in detail. First, the study did not analyze the information about the participants’ diet corresponding to the elementary school years (separately for ages 0–5 and 6–12 years) and lifetime exposure (from birth to date of CIMT measurement). Of note, the evidence has shown that subtle differences in dietary pattern composition affect the process of subclinical atherosclerosis.2 And dietary saturated fat is positively associated with artery calcium, whereas fiber and whole-grain intake can reduce progression of CIMT. Second, BP status during adolescence period of the participants is not taken into account. Because elevated BP at adolescence and a relative increase in BP from adolescence to adulthood unfavorably affect CIMT,3 these data should not be ignored in the analysis. Third, the most important deficit, however, is the lack of information on glucose metabolism of the participants. Previous studies have indicated that impaired glucose regulation categories increased vascular disease risk, as indicated by carotid/femoral intima–media thickness.4 Furthermore, even if normal glucose tolerance subjects with a 1-h postload glucose ≥155 mg/dL also have an atherogenic effects which is similar to impaired glucose tolerance individuals.5 Therefore, if all the participants have oral glucose tolerance test, it will be helpful in identification of the subjects who are at increased risk for CIMT. Nevertheless, the above important issues, which may limit the power to conclude an effect of childhood air pollutant on CIMT, were not discussed in this article. Finally, we believe that the applicative value of the result will be more instructive in real-world settings if the above information has been adjusted.Xi-Mei Wang, PhDYue-Jin Yang, MD, PhDYong-Jian Wu, MD, PhDDepartment of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of ChinaDisclosuresNone.

Nutrient infusion bypassing duodenum-jejunum improves insulin sensitivity in glucose-tolerant and diabetic obese subjects

The mechanisms of type 2 diabetes remission after bariatric surgery is still not fully elucidated. In the present study, we tried to simulate the Roux-en-Y gastric bypass with a canonical or longer biliary limb by infusing a liquid formula diet into different intestinal sections. Nutrients (Nutrison Energy) were infused into mid- or proximal jejunum and duodenum during three successive days in 10 diabetic and 10 normal glucose-tolerant subjects. Plasma glucose, insulin, C-peptide, glucagon, incretins, and nonesterified fatty acids (NEFA) were measured before and up to 360 min following. Glucose rate of appearance (Ra) and insulin sensitivity (SI), secretion rate (ISR), and clearance were assessed by mathematical models. SI increased when nutrients were delivered in mid-jejunum vs. duodenum (SI × 10⁴ min⁻¹·pM⁻¹: 1.11 ± 0.44 vs. 0.62 ± 0.22, P < 0.015, in controls and 0.79 ± 0.34 vs. 0.40 ± 0.20, P < 0.05, in diabetic subjects), whereas glucose Ra was not affected. In controls, Sensitivity of NEFA production was doubled in mid-jejunum vs. duodenum (2.80 ± 1.36 vs. 1.13 ± 0.78 × 10⁶, P < 0.005) and insulin clearance increased in mid-jejunum vs. duodenum (2.05 ± 1.05 vs. 1.09 ± 0.38 l/min, P < 0.03). Bypass of duodenum and proximal jejunum by nutrients enhances insulin sensitivity, inhibits lipolysis, and increases insulin clearance. These results may further our knowledge of the effects of bariatric surgery on both insulin resistance and diabetes.

Effects of Different Proportion of Carbohydrate in Breakfast on Postprandial Glucose Excursion in Normal Glucose Tolerance and Impaired Glucose Regulation Subjects

The variability of postprandial plasma glucose is an independent risk factor for diabetes. The type and amount of carbohydrate may be important determinants of glycemic control. The aim of the study was to compare the effects of different proportions of carbohydrate in breakfast on postprandial blood glucose fluctuations in impaired glucose regulation (IGR) and normal glucose tolerance (NGT) subjects. This is a cross-sectional study of two groups including 55 subjects with IGR and 78 individuals with NGT. Their recorded breakfast was sorted into low-carbohydrate (LC) (carbohydrate <45%), medium-carbohydrate (MC) (carbohydrate 45-65%), and high-carbohydrate (HC) (carbohydrate >65%) meals according to the proportion of carbohydrate. Glucose concentrations were continuously measured with a continuous glucose monitoring system, and parameters such as the incremental area under the curve (iAUC) of glucose and postprandial glucose excursion (PPGE) were calculated to evaluate postprandial glucose fluctuations. The postprandial fluctuations of glucose increased gradually with increased proportions of carbohydrate in breakfast in both IGR and NGT subjects. For the MC and HC meals, iAUC, PPGE, postprandial glucose spike (PGS), and mean blood glucose were significantly greater than those in the NGT group (P<0.05), respectively. The median time to PGS and the time period in which glucose concentrations decreased to baseline after the MC and HC meals in the IGR group were significantly longer than those in the NGT group (P<0.01), respectively. Compared with the NGT subjects for the HC meal, the IGR subjects consuming the MC meal had greater PGS, range of glucose concentrations, SD, and PPGE (P<0.05). The proportion of carbohydrate in breakfast contributes to glucose excursions in the NGT and IGR subjects. In the IGR subjects, a HC meal should be avoided and a LC meal should be recommended to prevent development of diabetes.

The Dysfunction of NK Cells in Patients with Type 2 Diabetes and Colon Cancer

Glucose metabolism disorders influence anticarcinogenic function of natural killer (NK) cells. The aim of this study was to evaluate the number and cytotoxic activity of NK cells in type 2 diabetic (T2D) patients with negative family history of cancer, type 2 diabetic subjects with newly diagnosed untreated colon cancer (T2DCC) and patients without type 2 diabetes with newly diagnosed, untreated colon cancer (CC). Incubation tests were performed in 18 T2D patients, treated with diet and oral antidiabetic agents, 16 T2DCC; cT1-4N0M0 (c-clinical diagnosis based on computed tomography, colonoscopy and histopathology) treated with diet and oral antidiabetic agents and 16 normoglycemic CC; cT1-4N0M0. Control group included 18 metabolically healthy (with normal fasting glucose and normal glucose tolerance) subjects (HS) with negative family history of cancer, matched by age, BMI and waist circumference. Peripheral blood mononuclear cells were isolated by means of gradient centrifugation. The K562 human erythroleukemia cell line served as the standard target for human NK cytotoxicity assay. The T2D revealed an increased number of NK cells (13.56 ± 5.9 vs 9.50 ± 4.8 %; p < 0.05) when compared with HS, yet these cells had a decreased activity (3.3 ± 2.5 vs 9.4 ± 3.6 %; p < 0.01). The CC demonstrated a decreased activity (2.9 ± 1.8 %; p < 0.01) but a similar number (8.82 ± 3.7 %; not significant) of NK cells when compared to HS. The T2DCC NK cells were characterized by trace cytotoxic activity (1.1 ± 0.7 %; p < 0.01) and nearly three times greater amount (21.24 ± 7.5 %; p < 0.01) when compared to T2D. Type 2 diabetes and CC are associated with disadvantageous alterations of NK cells, leading to impairment in their cytotoxic activity. The impaired activity of NK cells in T2D can be involved in the increased carcinogenic risk and can promote a higher incidence of CC.

Prevention of the metabolic syndrome in IGT subjects in a lifestyle intervention: Results from the SLIM study

Background and aimsThe Study on Lifestyle intervention and Impaired glucose tolerance Maastricht (SLIM), a randomized controlled trial, directed at diet and physical activity in impaired glucose tolerant subjects was effective to improve glucose tolerance and prevent type 2 diabetes. The aim of this study was to determine the effects of the SLIM lifestyle intervention on the incidence and prevalence of the metabolic syndrome (MetS) during the active intervention and four years thereafter. Methods and resultsMetS was diagnosed according to the NCEP ATP III criteria. At baseline, 66.4% of all participants (n = 146, age 57 ± 7 years, BMI 29.7 ± 3.6, 51.3% female) fulfilled the criteria for MetS. No significant difference in MetS prevalence was observed between the intervention (63.9%) and control group (68.9%). At the end of active intervention (average duration 4.2 ± 2.0 years), prevalence of MetS was significantly lower in the intervention group (52.6%, n = 57) compared to the control group (74.6%, n = 59) (p = 0.014).Furthermore, in participants without MetS at baseline, cumulative incidence of MetS was 18.2% in the intervention group at the end of active intervention, compared to 73.7% in the control group (Log-rank test, p = 0.011). Four years after stopping active intervention, the reduced incidence of MetS was maintained (Log-rank test, p = 0.002). ConclusionIn conclusion, a combined diet-and-exercise intervention to improve glucose tolerance, not only prevented type 2 diabetes, but also reduced the prevalence of MetS and prevented MetS development, showing the long-term impact of lifestyle intervention on cardiovascular risk reduction.Clinical trial registration number: NCT 00381186 (www.clincialtrials.gov).

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance

To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Altered Response of Skeletal Muscle to IL-6 in Type 2 Diabetic Patients

Interleukin-6 (IL-6) has a dual role in modulating insulin sensitivity, with evidence for this cytokine as both an enhancer and inhibitor of insulin action. We determined the effect of IL-6 exposure on glucose and lipid metabolism in cultured myotubes established from people with normal glucose tolerance or type 2 diabetes. Acute IL-6 exposure increased glycogen synthesis, glucose uptake, and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cultured myotubes from normal glucose tolerant subjects. However, in type 2 diabetic patients, IL-6 was without effect on glucose metabolism and STAT3 signaling, concomitant with increased suppressor of cytokine signaling 3 (SOCS3) expression. IL-6 increased fatty acid oxidation in myotubes from type 2 diabetic and normal glucose tolerant subjects. Expression of IL-6, IL-6 receptor (IL-6R), or glycoprotein 130, as well as IL-6 secretion, was unaltered between cultured myotubes from normal glucose tolerant or type 2 diabetic subjects. Circulating serum IL-6 concentration was unaltered between normal glucose tolerant and type 2 diabetic subjects. In summary, skeletal muscle cells from type 2 diabetic patients display selective IL-6 resistance for glucose rather than lipid metabolism. In conclusion, IL-6 appears to play a differential role in regulating metabolism in type 2 diabetic patients compared with normal glucose tolerant subjects.

Effects of Roux-en-Y Gastric Bypass on Fasting and Postprandial Levels of the Inflammatory Markers YKL-40 and MCP-1 in Patients with Type 2 Diabetes and Glucose Tolerant Subjects

Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states, following Roux-en-Y gastric bypass (RYGB) in subjects with type 2 diabetes (T2D) and normal glucose tolerance (NGT). Methods. Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year) RYGB. Results. Fasting state MCP-1 levels decreased after RYGB in both groups (P values < 0.0001) whereas fasting YKL-40 levels were unchanged (P values ≥ 0.120). Postprandial MCP-1 levels showed a tendency towards a decrease on most study days; however, the changes were only significant at 1 week (P = 0.001) and 1 yr (P < 0.0001) in the T2D group and at 3 mo after RYGB in the NGT group (P = 0.009). YKL-40 levels showed a slight, postprandial suppression on all study days in the T2D group (all P values ≤ 0.021). Conclusions. Fasting MCP-1 levels, but not YKL-40 levels, decrease after RYGB in subjects with T2D and NGT. Postprandial changes of inflammatory markers are discrete and inconsistent.

A Study of Snack Consumption, Night-Eating Habits, and Nutrient Intake in Gestational Diabetes Mellitus

This study was performed to identify dietary behavior such as snack consumption, night-eating and nutrients intake associated with gestational diabetes mellitus (GDM). The study was conducted on 219 normal glucose tolerance (NGT) subjects and 44 GDM subjects by using a questionnaire including dietary behavior, food frequency and 3-day food record. The mean age, OGTT, and delivery weight of GDM subjects were statistically higher than those in NGT. A larger proportion of NGT subjects consumed black coffee (49.8%) while the majority of GDM subjects (61.4%) drank mixed coffee with sugar and cream. Dairy products were the most frequently consumed snack item in NGT subjects (40.7%), while fruits were most frequently consumed food item in GDM subjects (34.4%). Many of NGT subjects (49.8%) answered that they hardly took night-eating snacks whereas most of GDM subjects (61.4%) took night-eating snacks more than once a week. For change of taste preference, the proportion of NGT subjects who showed less preference for salty taste (33.3%) or greasy taste (16.9%) was higher than that of GDM subjects (11.4%). Nutrient intakes of energy, fat, cholesterol, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), carbohydrate, vitamin B1, vitamin B2, vitamin C, and vitamin E in GDM group were significantly higher than those in NGT group. Nutrient densities of SFA and vitamin C in GDM group were higher and nutrient density of calcium was lower than those in NGT group. Taken together, it is recommended to reduce night-eating snack and choose less salty and fatty foods, black-coffee rather than coffee with cream and sugar, and more dairy products to prevent GDM.

Association of amylin in the development of impaired fasting glucose and impaired glucose tolerance

Objective: The present study was planned to explore the role of amylin in the pathogenesis of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) subjects. Subjects and Methods: In this study, 20 IFG and 25 IGT subjects along with 30 healthy subjects were included. Plasma glucose (fasting and 2 h after 75 g glucose) was measured by glucose oxidase method, serum triglyceride and total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) by enzymatic method. Serum insulin and amylin were measured by the enzyme-linked immunosorbent assay method. B-cell secretory capacity (Homeostasis model assessment [HOMA] %B) and insulin sensitivity (HOMA %S) were estimated by HOMA-CIGMA software. Results: Age and body mass index were matched among control and the hyperglycemic groups (IFG, IGT). Fasting total cholesterol, HDL and LDL was significantly higher in IGT subjects compared with control and IFG subjects. Plasma insulin was significantly higher in IFG and IGT compared with control subjects (median [range], pmol/l; control, 38 [28-55]; IFG, 49 [40-56] and IGT, 60 [20-91]). HOMA %B was significantly lower in IFG and significantly higher in IGT subjects compared with the controls (median [range], %; control, 81 [53-156]; IFG, 52 [40-63] and IGT, 95 [33-195]). HOMA %S was significantly decreased in IGT and also in IFG compared to controls (median (range), %; control, 137 [95-187]; IFG, 104 [88-127] and IGT, 86 [57-255]). Plasma amylin was significantly raised in IFG and IGT compared to control subjects (mean ± standard deviation, pmol/l; control, 5.0 ± 0.63; IFG, 6.43 ± 0.67 and IGT, 8.0 ± 1.18). In binary logistic regression analysis, it has been found that plasma amylin concentration is positively associated with impaired glucose regulation and in bivariate correlation analysis it has been found that plasma amylin is positively associated with HOMA %B and negatively associated with fasting glucose. Conclusion: The present data suggested that increased amylin concentration may be contributed to the development of pre-diabetic condition or vice versa.

The rs1142345 in TPMT Affects the Therapeutic Effect of Traditional Hypoglycemic Herbs in Prediabetes.

Therapeutic interventions in prediabetes are important in the primary prevention of type 2 diabetes (T2D) and its chronic complications. However, little is known about the pharmacogenetic effect of traditional herbs on prediabetes treatment. A total of 194 impaired glucose tolerance (IGT) subjects were treated with traditional hypoglycemic herbs (Tianqi Jiangtang) for 12 months in this study. DNA samples were genotyped for 184 mutations in 34 genes involved in drug metabolism or transportation. Multinomial logistic regression analysis indicated that rs1142345 (A > G) in the thiopurine S-methyltransferase (TPMT) gene was significantly associated with the hypoglycemic effect of the drug (P = 0.001, FDR P = 0.043). The “G” allele frequencies of rs1142345 in the healthy (subjects reverted from IGT to normal glucose tolerance), maintenance (subjects still had IGT), and deterioration (subjects progressed from IGT to T2D) groups were 0.094, 0.214, and 0.542, respectively. Binary logistic regression analysis indicated that rs1142345 was also significantly associated with the hypoglycemic effect of the drug between the healthy and maintenance groups (P = 0.027, OR = 4.828) and between the healthy and deterioration groups (P = 0.001, OR = 7.811). Therefore, rs1142345 was associated with the clinical effect of traditional hypoglycemic herbs. Results also suggested that TPMT was probably involved in the pharmacological mechanisms of T2D.

Plasma Progranulin Concentrations Are Increased in Patients with Type 2 Diabetes and Obesity and Correlated with Insulin Resistance

Insulin resistance (IR) is considered to be one of the most important pathogenesis of glycolipid metabolism disorders. However, the molecular mechanism responsible for IR is not fully understood. Recently, the chronic inflammation has been proposed to be involved in the pathogenesis of IR. In this study, we aim to investigate the concentrations of plasma progranulin in Chinese patients with obesity (OB) and type 2 diabetes mellitus (T2DM), and its relationship to IR. Plasma progranulin concentrations were significantly higher in the T2DM patients than in the normal glucose tolerant (NGT) subjects (P < 0.01). Within the T2DM and the NGT patients, the concentrations of progranulin were significantly higher in obese subjects than that in the normal weight subjects (225.22 ± 34.39 ng/mL versus 195.59 ± 50.47 ng/mL and 183.79 ± 61.63 ng/mL versus 148.69 ± 55.27 ng/mL, P < 0.05). Plasma progranulin concentrations correlated positively with weight, waist circumferences, BMI, HbA1c, TG, IL-6, FINS and HOMA-IR (P < 0.05), while correlated negatively with HOMA-β (P < 0.05). Multiple linear regression analysis showed that BMI, HbA1c, IL-6 and TG correlated independently with circulating progranulin concentrations (P < 0.05). These results suggested that Plasma progranulin concentrations were higher in Chinese patients with type 2 diabetes and obesity and correlated closely with glycolipid metabolism, chronic inflammation and IR.

Transcriptomic analysis of visceral adipose from healthy and diabetic obese subjects

Understanding the role of visceral fat accumulation in the occurrence and progression of metabolic syndrome is of considerable interest. In order to understand the difference between visceral tissue biology of healthy and unhealthy obese individuals, we have used microarray profiling to compare genome-wide expression differences between visceral adipose tissue biopsies obtained from obese diabetics, and those from age and body mass index (BMI) matched normal glucose tolerance subjects. Whereas genes upregulated in diabetics showed enrichment of natural killer cell mediated cytotoxicity, the downregulated genes showed enrichment of biosynthesis of unsaturated fatty acids. Given the known inhibitory effect of unsaturated fatty acids on inflammation and natural killer cell number or activity, our results suggest that visceral inflammation resulting from decreased levels of unsaturated fatty acids may underlie progression of diabetes in obese individuals.

Early metabolic defects in Arab subjects with strong family history of Type 2 diabetes.

It is widely accepted that the genetic make-up of the subject plays a pivotal role in the development of insulin resistance and β cell failure. The objective of this study was to examine whether the same or distinct genetic backgrounds contribute to the development of insulin resistance and β cell failure. We examined insulin sensitivity and β cell function in lean normal glucose tolerance subjects from 3 multigeneration Arab families. Families 1 and 2 had strong history of Type 2 diabetes (T2DM), while no member of family 3 had T2DM. Subjects in family 1 manifested increased basal plasma free fatty acid (FFA) concentration and impaired suppression of plasma FFA during the OGTT compared to subjects in family 3. Subjects in family 2 had comparable fasting plasma FFA and suppression of plasma FFA during the OGTT to family 3. Both the absolute plasma glucose concentrations, and incremental area under the plasma glucose curve (ΔG0-120) during the OGTT were comparable in subjects of families 1 and 2, and were decreased in subjects of family 3. Whole body and muscle insulin sensitivity were comparable in subjects from families 2 and 3, and both were significantly decreased in subjects of family 1. Beta cell function was comparable in subjects of families 1 and 3 and was significantly decreased in subjects of family 2. These results demonstrate that distinct genetic background contributes to the development of insulin resistance and β cell dysfunction in Arab individuals.

Examining the Effects of Hyperglycemia on Pancreatic Endocrine Function in Humans: Evidence forin VivoGlucotoxicity

Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease. The objective of the study was to test the hypothesis that experimental hyperglycemia impairs insulin and glucagon secretion. A randomized, crossover in healthy controls, compared with type 2 diabetic patients. The study was conducted at a university hospital. Normal glucose-tolerant subjects (n = 10) and patients with type 2 diabetes (n = 10), individually matched by age, sex, and body mass index. Normal glucose-tolerant subjects underwent 24 h of experimental hyperglycemia (+5.4 mm above basal). Subjects with type 2 diabetes did not undergo an intervention. Insulin secretion, glucagon secretion, insulin sensitivity, disposition index, and endogenous glucose production (via [6,6-(2)H(2)]glucose infusion) were measured during hyperglycemic clamps combined with infusion of glucagon-like peptide (GLP)-1(7-36) (0.5 pmol/kg · min) and injection of arginine (5 g). Insulin secretion was correlated with glucagon suppression in subjects with normal glucose tolerance only. Individuals with type 2 diabetes had lower insulin sensitivity (-33 ± 11%) and insulin secretory responses to glucose, GLP-1, and arginine (-40 ± 11, -58 ± 7, and -36 ± 13%, respectively) and higher plasma glucagon and endogenous glucose production compared with normal glucose-tolerant subjects (all P < 0.05). After 24 h of experimental hyperglycemia, insulin sensitivity (-29 ± 10%), disposition index (-24 ± 16%), and GLP-1- (-19 ± 7%) and arginine-stimulated (-15 ± 10%) insulin secretion were decreased in normal glucose-tolerant subjects (all P < 0.05). However, plasma glucagon responses were not affected. Furthermore, experimental hyperglycemia abolished the correlation between insulin secretion and glucagon suppression. Experimental hyperglycemia impaired pancreatic β-cell function but did not acutely impair α-cell glucagon secretion in normal glucose-tolerant subjects.

EZSCAN SCREENING OF IMPAIRED GLUCOSE TOLERANCE AND DIABETES IN A CHINESE POPULATION

ObjectivesEZSCAN (Impeto Medical, Paris, France), a non-invasive technology that evaluates sweat gland dysfunction through electrochemical skin conductance (ESC) measurement, is a promising new approach for detecting and quantitating impaired glucose...

Prevalence of metabolic syndrome (MetS) in Chinese subjects gradually increased with impaired glucose homeostasis: a multicenter, clinical based, cross-sectional study

BackgroundMetabolic Syndrome (MetS) is a high risk factor for Cardiovascular Diseases (CVD). We estimated to investigate how MetS prevalence by glucose homeostasis varies across different age and gender groups.MethodsWe studied 9257 Chinese subjects over the age of 15 years in two cross-sectional surveys in 2006. With oral glucose tolerance test (OGTT) test, 2341 subjects were normal glucose tolerance (NGT), and 5448 were diagnosed as having type 2 diabetes (T2D). All other 1468 subjects were considered to be impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) subjects. Diabetes was diagnosis by WHO99 criteria. We used modified NCEP-III criteria for the diagnosis of MetS.ResultsThe prevalences of MetS in the male NGT, IFG/IGT and T2D groups were 25.9% (404/1559), 65.6% (769/1172), and 73.5% (2483/3376), respectively. The prevalences of MetS in the female NGT, IFG/IGT and T2D groups were 13.4% (105/782), 51.0% (151/296), and 75.4% (1563/2072), respectively. The prevalence of MetS in the male IFG/IGT group gradually decreased from 73.26% to 41.08% in subjects over the age of 30 years. The prevalence of MetS in the female IFG/IGT group gradually increased from 30% to 75% with aging.ConclusionsThe prevalence of MetS in subjects with different glucose tolerances in China was high and gradually increased with impaired glucose homeostasis both in males and females.

Plasma 25-Hydroxyvitamin D Levels Are Favorably Associated With β-Cell Function

The association of hypovitaminosis D with type 2 diabetes is well recognized. Although hypovitaminosis D is associated with insulin resistance, there is much less information about its impact on β-cell function in humans. We enrolled 150 healthy, glucose-tolerant subjects for the assessment of β-cell function (acute insulin response) and insulin sensitivity index (ISI) using a hyperglycemic clamp. Adjusted β-cell function (ABCF) was defined as the product of acute insulin response and ISI. The relations of plasma 25-hydroxyvitamin D [25(OH)D] level with insulin sensitivity and ABCF were examined. Plasma 25(OH)D levels were positively associated with ABCF (P = 0.00004) and ISI (P < 0.00001). The associations remained significant after adjustment for age, sex, body mass index, physical activity, ethnicity, and season of study. Plasma 25(OH)D levels are positively association with both β-cell function and insulin sensitivity. Our observations suggest the roles of vitamin D deficiency in the dual defect of type 2 diabetes.