Plasma C-peptide Levels Research Articles

Effect of Anthocyanin-Rich Tart Cherry Extract on Inflammatory Mediators and Adipokines Involved in Type 2 Diabetes in a High Fat Diet Induced Obesity Mouse Model.

Male C57BL/6J mice were used to determine the possible therapeutic effects of our previously described tart cherry extract in a chronic obesity mouse model on metabolic parameters, glucose tolerance, inflammatory mediators, and antioxidant capacity. The control group received standard mouse chow, and the high fat control group was switched to a high fat diet and tap water supplemented with 5% sucrose. The high fat + anthocyanin group received the high fat and sucrose diet, but received the anthocyanin-rich tart cherry extract dissolved in their drinking water. After six weeks, an oral glucose tolerance test was performed, and the water-soluble antioxidant capacity (ACW), superoxide dismutase (SOD) activity, and the plasma levels of insulin, C-peptide, leptin, IL-6, MCP-1, adiponectin and resistin were measured. The high fat diet increased body weight, reduced glucose tolerance, and caused an elevation in leptin, IL-6, MCP-1, and resistin levels. Furthermore, antioxidant capacity was decreased with a significant elevation of SOD activity. Anthocyanin treatment failed to reverse the effects of the high fat diet on body weight and glucose tolerance, but significantly reduced the leptin and IL-6 levels. The tart cherry extract also made a significant enhancement in antioxidant capacity and SOD activity. Our results show that chronic anthocyanin intake has a potential to enhance redox status and alleviate inflammation associated with obesity.

The role of Leu260Phe polymorphism of the receptor gene to GLP-1 incretin in the pathogenesis of diabetes type 2 diabetes with obesity

BACKGROUND: Glucagon-like peptide-1 (GLP-1) stimulates the proliferation of β-cells, enhances their resistance to apoptosis and increases glucose-dependent insulin secretion. AIMS: Study of the relationship of Leu260Phe polymorphism (rs1042044) of the GLP-1R gene with postprandial hormone production (C-peptide, insulin, ghrelin, GLP-1) in obese patients with type 2 diabetes. MATERIALS AND METHODS: A total of 174 patients, 82 patients with obesity with type 2 diabetes (BMI=40.4±14.3 kg/m 2 )and 92 conditionally healthy donors (BMI=22.6±2.7 kg/m 2 ) were studied. The material for the study was venous blood taken on an empty stomach and 60 minutes after the test breakfast. Genotyping was performed by PCR using the sets for determining polymorphism (rs1042044) of the GLP-1R gene (Sintol) and the amplificator (CFX96 BioRad, USA). Plasma hormone levels were evaluated by flow fluorimetry (Bio-PlexProteinAssaySystem, Bio-Rad, USA) using commercial test systems (Bio-PlexProHumanDiabetes 10-Plex Assay, Bio-Rad, USA). Statistical analysis and graphs were obtained at R Statistical Software. RESULTS: A violation of postprandial production of GLP-1 and ghrelin after a test breakfast in obese patients with type 2 diabetes was found. A postprandial increase in C-peptide levels of 3.25[1.83;4.16] ng/ml and insulin 3048 [1978;4972] ng/ml in carriers of the CC genotype compared with carriers of the CA genotype in the group of patients with obesity with type 2 diabetes type In carriers of the CA genotype, there was a decrease in the C-peptide level of 2.21 [1.8;2.49] ng/ml and insulin 1462 [1146; 2304] ng/ml with a constant concentration of GLP-1. The postprandial level of ghrelin in carriers of the CA genotype of the Leu260Phe polymorphism increased to 118[96.1;157] ng/ml compared to carriers of the AA 98 genotype [86; 109] ng/ml. CONCLUSION: The presence of the CC genotype of the Leu260Phe polymorphism of the GLP-1 receptor gene is associated with an increase in postprandial plasma levels of C-peptide and insulin in obese patients with type 2 diabetes, and the CA genotype with a decrease in these indicators and an increase in ghrelin content.

The role of Leu260Phe polymorphism of the receptor gene to GLP-1 incretin in the pathogenesis of diabetes type 2 diabetes with obesity

BACKGROUND: Glucagon-like peptide-1 (GLP-1) stimulates the proliferation of -cells, enhances their resistance to apoptosis and increases glucose-dependent insulin secretion.
 AIMS: Study of the relationship of Leu260Phe polymorphism (rs1042044) of the GLP-1R gene with postprandial hormone production (C-peptide, insulin, ghrelin, GLP-1) in obese patients with type 2 diabetes.
 MATERIALS AND METHODS: A total of 174 patients, 82 patients with obesity with type 2 diabetes (BMI=40.414.3 kg/m2)and 92 conditionally healthy donors (BMI=22.62.7 kg/m2) were studied. The material for the study was venous blood taken on an empty stomach and 60 minutes after the test breakfast. Genotyping was performed by PCR using the sets for determining polymorphism (rs1042044) of the GLP-1R gene (Sintol) and the amplificator (CFX96 BioRad, USA). Plasma hormone levels were evaluated by flow fluorimetry (Bio-PlexProteinAssaySystem, Bio-Rad, USA) using commercial test systems (Bio-PlexProHumanDiabetes 10-Plex Assay, Bio-Rad, USA). Statistical analysis and graphs were obtained at R Statistical Software.
 RESULTS: A violation of postprandial production of GLP-1 and ghrelin after a test breakfast in obese patients with type 2 diabetes was found. A postprandial increase in C-peptide levels of 3.25[1.83;4.16] ng/ml and insulin 3048 [1978;4972] ng/ml in carriers of the CC genotype compared with carriers of the CA genotype in the group of patients with obesity with type 2 diabetes type In carriers of the CA genotype, there was a decrease in the C-peptide level of 2.21 [1.8;2.49] ng/ml and insulin 1462 [1146; 2304] ng/ml with a constant concentration of GLP-1. The postprandial level of ghrelin in carriers of the CA genotype of the Leu260Phe polymorphism increased to 118[96.1;157] ng/ml compared to carriers of the AA 98 genotype [86; 109] ng/ml.
 CONCLUSION: The presence of the CC genotype of the Leu260Phe polymorphism of the GLP-1 receptor gene is associated with an increase in postprandial plasma levels of C-peptide and insulin in obese patients with type 2 diabetes, and the CA genotype with a decrease in these indicators and an increase in ghrelin content.

Metabolic hormones and breast cancer risk among Mexican American Women in the Mano a Mano Cohort Study

C-peptide, insulin, leptin, and other metabolic hormones are assumed to play roles in breast cancer development; though, results are inconsistent. In this prospective case-control study nested within the Mano a Mano Cohort Study, we assessed the risk of breast cancer with regard to plasma levels of c-peptide, gastric inhibitory polypeptide, insulin, leptin, monocyte chemoattractant protein-1, pancreatic polypeptide, and peptide YY. Among women followed for a median of 8.5 years, 109 breast cancer cases were identified and frequency-matched to 327 controls at a ratio of 1:3. Overall, only c-peptide was observed significantly associated with breast cancer risk. High c-peptide levels (≥ the median level of controls) were significantly associated with increased breast cancer risk (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.01, 2.44). In an analysis of participants stratified by age, the significant association between c-peptide levels and breast cancer risk was evident in only women age ≥51 years (OR = 1.53, 95% CI: 1.02, 3.27). Among women age <51 years, high leptin levels were significantly associated with decreased breast cancer risk (OR = 0.49, 95% CI: 0.24, 0.82). Our findings suggest that selected metabolic hormones are associated with breast cancer development in Mexican American women.

Effects of Cinnamon Spice on Postprandial Plasma Levels of Glucose and Insulin in Healthy Participant with Normal Weight (FS15-04-19)

ObjectivesThe objective of this study is to investigate the effect of one time intake of cinnamon spice on the postprandial glucose tolerance and insulin secretion following consumption of a high glycemic index meal in normal weight and glucose tolerance individuals. MethodsSixteen healthy controls (BMI = 18.5–24.9 kg/m2 and fasting blood glucose (BG) < 100 mg/dL) aging 20–50 years, who typically consume a low fiber/polyphenol diet (beige diet) were recruited for this study. Recruitment of overweight/obese, prediabetic participants is not completed (no data presented). Participants consume a typical American breakfast containing 50 g of carbohydrates (1/3 cup of oatmeal and 1 cup 2% milk) with or without cinnamon (6 g) followed by 1-week washout and crossover to the opposite intervention. The blood samples were taken at fasting state and at 30, 60, 90, 120, 150 and 180 minutes after the meal. The main outcome measures included BG and insulin. The secondary outcome measures were C-peptide and glucagon. Cinnamon spice (Indonesia) was purchased at the local grocery store (McCormick®) and contains 3.9% proanthocyanin. The statistical significance was set at P < 0.05 using SPSS. ResultsConsumingcinnamon spice with the oatmeal significantly decreased the rate of glucose change from fasting state at 60 and 90 minutes after the meal by 37% and 31%, respectively. The peak postprandial BG and the areas under the curve (AUC) of glucose were also lowered by cinnamon compared to oatmeal alone but did not reach the significant levels. There was a trend towards significant decrease (21%, P = 0.08) in plasma insulin concentrations and a significant decrease in plasma C-peptide levels 30 minutes after ingestion of the meal with cinnamon. Cinnamon ingestion compared to oatmeal alone also significantly decreased plasma glucagon levels at 90 minutes after the meal test. ConclusionsOur results suggest that one time intake of cinnamon spice lowers the mean rate of glucose change following a high glycemic index meal in healthy individuals. Cinnamon also decreased plasma levels of insulin, C-peptide, and glucagon. Funding SourcesUCLA Center for Human Nutrition.

1723-P: Genetic Risk Scores Predict Glycemic Traits and Response to Glipizide Treatment in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)

Whether genetics can help predict response to type 2 diabetes (T2D) drugs is unknown. We set out to examine whether genetic risk scores (GRSs) composed of single nucleotide polymorphisms (SNPs) known to be associated with glycemic traits and T2D are associated with glycemic traits and the acute response to metformin and glipizide in SUGAR-MGH. We measured plasma glucose, insulin, glucagon, proinsulin, c-peptide, GLP-1, and GIP levels in 1,000 participants naïve to antidiabetes medications at 0, 30, 60, 90, 120, 180, and 240 minutes following administration of 5 mg glipizide (Visit 1, day 1), and during a 75-g oral glucose tolerance test following a short metformin course (Visit 2, day 8). We constructed a T2D, fasting glucose (FG), and fasting insulin (FI) GRS (with 65, 43 and 13 SNPs respectively) by summing the number of risk alleles carried by each person based on known genome-wide significant associations. Linear regression tested for associations between GRSs and glycemic traits as well as pharmacodynamic endpoints, adjusting for age, sex, race, and BMI. The FG GRS predicted FG in our cohort (β=0.46 increase in FG in mg/dL*allele, P&amp;lt;0.001). The FI GRS predicted fasting insulin (β=0.02 increase in ln FI in µU/mL*allele, P=0.04). A higher T2D GRS was associated with a shorter time to insulin peak, greater glucose area over the curve, shorter time to glucose trough, and steeper slope to glucose trough (P&amp;lt;0.05) after glipizide administration, indicating a stronger response. When we set a more stringent P-value of 0.008 to correct for multiple comparisons, the FG GRS remained associated with FG and the T2D GRS remained associated with the insulin-based endpoint. We conclude that established genetic determinants of glycemic traits predict FG and FI in our cohort of individuals free of overt diabetes; moreover, T2D risk alleles may predispose individuals to a greater insulin response to glipizide treatment. Disclosure J.H. Li: None. L. Szczerbinski: None. V. Kaur: None. J. Todd: None. J.C. Florez: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK-088214, R03DK-077675, P30-DK-036836); Joslin Clinical Research Center; Harvard Catalyst; National Center for Research Resources/National Center for Advancing Translational Sciences (M01-RR-01066, 1UL1-RR-025758-04, 88UL1-TR-000170-05; Harvard University

Identification of inflammatory and vascular markers associated with mild cognitive impairment.

Biochemical processes have been associated with the pathogenesis of mild cognitive impairment (MCI) and dementia, including chronic inflammation, dysregulation of membrane lipids and disruption of neurotransmitter pathways. However, research investigating biomarkers of these processes in MCI remained sparse and inconsistent. To collect fresh evidence, we evaluated the performance of several potential markers in a cohort of 57 MCI patients and 57 cognitively healthy controls. MCI patients showed obviously increased levels of plasma TNF-α (p = 0.045) and C-peptide (p = 0.004) as well as decreased levels of VEGF-A (p = 0.042) and PAI-1 (p = 0.019), compared with controls. In addition, our study detected significant correlations of plasma sTNFR-1 (MCI + Control: B = -6.529, p = 0.020; MCI: B = -9.865, p = 0.011) and sIL-2Rα (MCI + Control: B = -7.010, p = 0.007; MCI: B = -11.834, p = 0.003) levels with MoCA scores in the whole cohort and the MCI group. These findings corroborate the inflammatory and vascular hypothesis for dementia. Future studies are warranted to determine their potential as early biomarkers for cognitive deficits and explore the related mechanisms.

Probiotic Lactobacillus gasseri SBT2055 improves insulin secretion in a diabetic rat model

The probiotic Lactobacillus gasseri SBT2055 (LG2055) has a protective effect against metabolic syndrome in rats and humans. Metabolic syndrome increases the risk of type 2 diabetes mellitus. In this study, Goto-Kakizaki rats were used as a diabetic model and fed diets containing LG2055-fermented or nonfermented skim milk for 4 wk. Indices of diabetes such as blood glucose levels, serum glucagon levels, plasma levels of insulin, C-peptide, and glucagon-like peptide-1, tissue glycogen contents, and pancreatic mRNA levels were measured. The plasma C-peptide levels and pancreatic mRNA levels of insulin genes (Ins1 and Ins2) and Pdx1 (a transcriptional factor of insulin genes) were increased in LG2055 diet-fed rats. The increase in insulin secretion corresponded to an improvement in serum and pancreatic inflammatory status, associated with decreases in serum levels of serum amyloid P and pancreatic levels of granulocyte colony-stimulating factor. Insulin resistance in Goto-Kakizaki rats was ameliorated by increased glycogen storage in the liver and quadriceps femoris muscles and decreased serum free fatty acid levels. This improvement may be related to the increased cecal production of short-chain fatty acids. In conclusion, dietary LG2055 improved insulin secretion in diabetic rats by improving the inflammatory status in the pancreas and serum.

Purinergic receptor Y2 (P2Y2)- dependent VCAM-1 expression promotes immune cell infiltration in metabolic syndrome.

Sterile inflammation of visceral fat, provoked by dying adipocytes, links the metabolic syndrome to cardiovascular disease. Danger-associated molecular patterns, such as adenosine triphosphate (ATP), are released by activated or dying cells and orchestrate leukocyte infiltration and inflammation via the purinergic receptor P2Y2. The gene expression of ATP receptor P2Y2 did not change in several tissues in the course of obesity, but was increased within epididymal fat. Adipose tissue from P2Y 2-/- mice consuming high-fat diet (HFD) contained less crown-like structures with a reduced frequency of adipose tissue macrophages (ATMs). This was likely due to decreased leukocyte migration because of missing VCAM-1 exposition on P2Y2 deficient hypertrophic adipose tissue endothelial cells. Accordingly, P2Y 2-/- mice showed blunted traits of the metabolic syndrome: they gained less weight compared to P2Y 2+/+ controls, while intake of food and movement behaviour remained unchanged. Liver and adipose tissue were smaller in P2Y 2-/- animals. Insulin tolerance testing (ITT) performed in obese P2Y 2-/- mice revealed a better insulin sensitivity as well as lower plasma C-peptide and cholesterol levels. We demonstrate that interfering with somatic P2Y2 signalling prevents excessive immune cell deposition in diet-induced obesity (DIO), both attenuating adipose tissue inflammation and ameliorating the metabolic phenotype. Thus, blocking the P2Y2 cascade may be a promising strategy to limit metabolic disease and its sequelae.

Effect of low carbohydrate high fat diet on LDL cholesterol and gene expression in normal-weight, young adults: A randomized controlled study

Background and aimsThe effects of a low carbohydrate/high fat (LCHF) diet on health are debated. This study aims to explore the effects of a diet with less than 20 g carbohydrates per day (LCHF) on plasma low density lipoprotein cholesterol (LDL-C) in young and healthy adults. The secondary aim is the assessment of lipid profile and peripheral blood mononuclear cells (PBMC) gene expression. MethodsThis was a randomized controlled parallel-designed intervention study. Participants were either assigned to a three-week LCHF diet or a control group continuing habitual diet ad libitum, in both groups. ResultsIn total, 30 healthy normal weight participants completed the study. Nine subjects did not complete it due to adverse events or withdrawn consent. In the LCHF diet group (n = 15), plasma LDL-C increased from (mean ± SD) 2.2 ± 0.4 mmol/l before intervention to 3.1 ± 0.8 after, while in the control group (n = 15), LDL-C remained unchanged: 2.5 ± 0.8 mmol/l (p < 0.001 between groups). There was a significant increase in apolipoprotein B, total cholesterol, high-density lipoprotein cholesterol, free fatty acids, uric acid and urea in the LCHF group versus controls. Plasma levels of triglycerides, lipoprotein (a), glucose, C-peptide or C-reactive protein (CRP), blood pressure, body weight or body composition did not differ between the groups. PBMC gene expression of sterol regulator element binding protein 1 (SREBP-1) was increased in the LCHF group versus controls (p ≤ 0.01). The individual increase in LDL-C from baseline varied between 5 and 107% in the LCHF group. ConclusionsAn LCHF diet for three weeks increased LDL-C with 44% versus controls. The individual response on LCHF varied profoundly.

Effects of oral supplementation with FOS and GOS prebiotics in women with adult acne: the "S.O. Sweet" study: a proof-of-concept pilot trial.

BackgroundWe evaluated the effects of 3-month prebiotic oral supplementation with fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) on glucose and lipid metabolic parameters in women with adult acne (female adult acne).MethodsTwelve women, mean age 35 years, with mild to moderate acne were enrolled. Exclusion criteria were severe acne, body mass index (BMI) >25, history of diabetes mellitus, polycystic ovary syndrome, regular intake of prebiotics or probiotics, and history of inflammatory intestinal diseases. At baseline visit (T0), at month 1 (T1), and at month 3 (T2) fasting glucose, blood insulin, glycated hemoglobin (HbA1c), C-peptide, triglycerides, total cholesterol levels, and BMI were measured. Subjects were treated with a food supplement containing FOS (100 mg) and GOS (500 mg), one sachet daily, for 3 months. Subjects were instructed to follow their regular diet, and no dietary restrictions were suggested.ResultsAt baseline, the BMI, mean ± SD, was 23±0.7. No modification of BMI was observed during the study. At baseline, fasting blood glucose levels were 92±7 mg/dL. A significant (P=0.02) reduction was observed at month 1 (86±5 mg/dL) and at month 3 (85±7 mg/dL) (–10%). Total cholesterol levels were reduced significantly (P=0.018) from 184±19 to 161±10 mg/dL (–13%) at the end of the study. Triglycerides at baseline were 51 mg/dL and were reduced to 46 mg/dL (P=0.05). Insulin and C-peptide plasma levels showed a nonsignificant reduction trend from baseline to the end of the study. In subjects with baseline insulin level >6 µUI/mL (n=6) the FOS/GOS supplementation induced a significant (P=0.03) reduction from 7.8 to 4.3 µUI/mL at day 90 (–45%). C-peptide was reduced from 2.1 to 1.6 ng/mL (month 3). HbA1c at baseline was 35 mg/dL and 32 mg/dL at the end of the study (NS).ConclusionIn adult female acne, supplementation with prebiotic FOS and GOS was associated with positive effects on glycemic and lipid metabolic parameters.

Optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram syndrome.

The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus is a heterogeneous metabolic disease characterized by destruction of the pancreatic beta cells resulting in an absolute deficiency of insulin secretion with subsequent hyperglycemia. This review details the definition and classification, epidemiology, pathophysiology, pathogenesis, prevention, diagnosis, and management of type 1 diabetes mellitus. Figures show the opposing actions of insulin and glucagon, particularly within the liver, on substrate flow and plasma levels; plasma glucose, insulin and C-peptide levels; the structure of human proinsulin; the cellular actions of insulin; measurement of insulin levels after the administration of glucose; the pathways that lead from insulin deficiency to the major clinical manifestations of type 1 diabetes mellitus; the pathogenesis of type 1 autoimmune diabetes mellitus; the relationship between hemoglobin A1C and calculated average glucose level; basal-bolus and insulin pump regimens; and management of diabetic ketoacidosis. Tables list the etiologic classification of diabetes mellitus, criteria for the diagnosis of diabetes, American Diabetes Association standards for glycemic control in diabetes mellitus, insulin preparations, potential advantages of continuous subcutaneous insulin infusion compared with multiple daily injections, cardiovascular risk factor screening and treatment, and typical admission laboratory findings and monitoring in diabetic ketoacidosis. This review contains 10 highly rendered figures, 7 tables, and 66 references.

PCSK9 deficiency reduces insulin secretion and promotes glucose intolerance: the role of the low-density lipoprotein receptor.

PCSK9 loss of function genetic variants are associated with lower low-density lipoprotein cholesterol but also with higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Here, we investigated the molecular mechanisms underlying this association. Pcsk9 KO, WT, Pcsk9/Ldlr double KO (DKO), Ldlr KO, albumin AlbCre+/Pcsk9LoxP/LoxP (liver-selective Pcsk9 knock-out mice), and AlbCre-/Pcsk9LoxP/LoxP mice were used. GTT, ITT, insulin and C-peptide plasma levels, pancreas morphology, and cholesterol accumulation in pancreatic islets were studied in the different animal models. Glucose clearance was significantly impaired in Pcsk9 KO mice fed with a standard or a high-fat diet for 20 weeks compared with WT animals; insulin sensitivity, however, was not affected. A detailed analysis of pancreas morphology of Pcsk9 KO mice vs. controls revealed larger islets with increased accumulation of cholesteryl esters, paralleled by increased insulin intracellular levels and decreased plasma insulin, and C-peptide levels. This phenotype was completely reverted in Pcsk9/Ldlr DKO mice implying the low-density lipoprotein receptor (LDLR) as the proprotein convertase subtilisin/kexin Type 9 (PCSK9) target responsible for the phenotype observed. Further studies in albumin AlbCre+/Pcsk9LoxP/LoxP mice, which lack detectable circulating PCSK9, also showed a complete recovery of the phenotype, thus indicating that circulating, liver-derived PCSK9, the principal target of monoclonal antibodies, does not impact beta-cell function and insulin secretion. PCSK9 critically controls LDLR expression in pancreas perhaps contributing to the maintenance of a proper physiological balance to limit cholesterol overload in beta cells. This effect is independent of circulating PCSK9 and is probably related to locally produced PCSK9.

Effect of High ß-Glucan Barley on Postprandial Plasma Glucose Levels in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes

Increasing evidence supports a more prominent role for postprandial glucose (PPG) regulation in the management of type 2 diabetes. Viscous dietary fibers including oat and barley β-glucan are one of the most effective classes of functional food ingredients for reducing PPG. We investigated the effect of high β-glucan barley on postprandial plasma glucose and C-peptide levels using a meal tolerance test and continuous glucose monitoring (CGM) in 15 subjects with normal glucose tolerance (NGT) and 29 type 2 diabetic patients. A 500-kcal meal tolerance test, using white rice alone (white rice) or white rice mixed with 50% of barley (Kirari-mochi®) containing 1.5-times β-glucan higher than usual barley (barley), was performed, and plasma glucose and C-peptide levels were measured every 30 minutes for 180 minutes. Daily glucose variability was measured using CGM over two days, while subjects consumed 1600-kcal or 1800-kcal test meals consisting of white rice or barley. Subsequently, a meal tolerance test with identical carbohydrate quantity (52g carbohydrate) with or without 1.8g of β-glucan, was performed in 7 diabetic patients. In NGT subjects and diabetic patients, the incremental area under the curve (AUC) of plasma glucose and C-peptide levels for 180 minutes after the meal tolerance test were significantly decreased following the consumption of barley compared to the consumption of white rice alone. The studies using CGM have demonstrated that the consumption of barley lead to a significant decrease in the 24-h standard deviation of blood glucose (24-h SDBG) and mean amplitude of glycemic excursion (MAGE) in diabetic patients. Similar results were obtained in subsequent tests with identical carbohydrate quantity but with β-glucan. In conclusion, these results suggest that high-β-glucan barley may contribute to decreased PPG levels and endogenous insulin secretion in both patients with type 2 diabetes and the subjects with NGT. Disclosure M. Higa: None. A. Hashimoto: None. M. Hayasaka: None. M. Hijikata: None. A. Ueda: None. K. Oda: None. D. Kato: None. K. Yamashita: None. T. Ichijo: None.

Canagliflozin Improves Glycemic Control and Beta-Cell Mass in the TallyHo Polygenic Model of Type 2 Diabetes

SGLT2 inhibitors reduce insulin resistance and may improve beta-cell function in humans with T2D. We studied the effects of Canagliflozin (Cana) on glucose homeostasis, islet architecture and endocrine cell fate in male TallyHO/JngJ (TH) mice, a new model of T2D, which mimics many aspects of polygenic T2D in humans. By 8 weeks of age, all TH mice developed moderate obesity and hyperglycemia compared to control SWR/J mice; ∼60% of TH mice converted quickly to overt diabetes, characterized by elevated BG values (&amp;gt;400mg/dL) (HG mice), while the remaining cohort maintained lower BG values (250-400mg/dL) until the end of the study (LG mice). Mice from both groups (HG, LG) were then randomized to receive Chow or Chow-containing Cana (100ppm) diet for 10 weeks, prior to sacrifice. Cana treatment significantly decreased the fasting BG levels only in the HG mice (HG/Cana) compared with untreated HG/Chow mice (207.7±34.6 vs. 452.2±163.4mg/dL, p&amp;lt;0.0001), improved glucose and insulin excursion curves during an ipGTT (p&amp;lt;0.0001 for AUC values) and decreased HbA1c values (4.3±0.7 vs. 6.2±0.93%, p&amp;lt;0.0001). Non-fasting plasma insulin and C-peptide levels, pancreatic insulin content and HOMA-B index were all significantly higher in HG/Cana than in HG/Chow mice, suggesting improved beta-cell function by Cana. Immunofluorescence staining for islet hormones showed that, compared to untreated animals, Cana reestablished the islet area and the beta-cell number/islet in HG mice (possibly due to reduced apoptosis of beta-cells), in addition to decreased number of alpha- and delta-cells/islet. In HG/Cana mice, the majority of Ins+ cells expressed the glucose transporter Glut2, while its expression was undetectable in Ins+ cells of the HG/Chow mice, further suggesting an improvement in glucose sensing capability of beta-cells with Cana treatment. Our study shows that Cana has beneficial effects on preserving beta-cell mass, identity and function in a model of early onset T2D. Disclosure I. Popescu: None. G.M. Mussman: None. C.B. Hughes: None. T.J. Janes: None. P. Ray: None. R. Bunn: None. J. Fowlkes: None. K.M. Thrailkill: None.

Protection from Severe Periodontal Disease among People with Type 1 Diabetes with Duration of 50 Years or Longer

Periodontal disease (PD) is more common and severe in people with diabetes than the general population. The presence of severe PD is correlated with decreased survival, since it can potentially affect glycemic control and severity of complications in people with diabetes. We have reported that Medalists (people with T1DM of 50 years or longer duration) may have endogenous protective factors for the development of diabetic nephropathy (DN) and retinopathy (DR). This study assessed the prevalence of PD in the Medalist cohort and correlated it to the known risk factors of PD and diabetic complications. Severity of PD was defined in a subset (n=170) of Medalists with comparable characteristics of the whole cohort, according to the AAP criteria. The prevalence of severe PD was dramatically decreased in Medalists (13.5%) compared with other studies of people with diabetes of similar age, approximately 33%. Clinical parameters, such as male gender, chronological age, age at diagnosis, and total insulin dose were correlated positively with severity of PD (p=0.04, 0.01, 0.03, and 0.02, respectively), while duration of disease, hemoglobin A1c, BMI, and lipid profiles did not exhibit any correlation. Interestingly, detectible plasma C-peptide levels correlated inversely with severity of PD (p=0.04). Systemic inflammatory markers, such as plasma IL-6, clearly correlated positively with the severity of PD (p=0.01). Serum antibody titer against Porphyromonas gingivalis (Pg), a known pathogen of PD, trended with severity of PD (p=0.08). Amongst the various complications, only the prevalence of CVD correlated positively with severity of PD (p=0.02). These results suggest that Medalists are protected from severe PD even with hyperglycemia. The endogenous protective factors for PD could be similar to those for CVD, possibly related to endogenously produced insulin to neutralize the chronic inflammation caused by residual infection with Pg in the gingival tissues. Disclosure T. Shinjo: None. A. Ishikado: Employee; Self; Sunstar Inc.. Employee; Spouse/Partner; Sunstar Inc.. H. Hasturk: None. L.J. Tinsley: None. D.M. Pober: None. I. Wu: None. T.E. Van Dyke: None. R.J. Genco: None. G.L. King: Research Support; Self; Sanofi-Aventis.

Impact of chronic and low cadmium exposure of rats: sex specific disruption of glucose metabolism

BackgroundSeveral epidemiological and animal studies suggest a positive association between cadmium (Cd) exposure and incidence of type 2 diabetes, but the association remains controversial. Besides, the experimental data have mainly been obtained with relatively high levels of Cd, over various periods of time, and with artificial routes of administration. ObjectivesDo environmental exposures to Cd induce significant disruption of glucose metabolism? MethodsAdults Wistar rats were exposed for three months to 0, 5, 50 or 500 μg.kg−1.d−1 of CdCl2 in drinking water. Relevant parameters of glucose homeostasis were measured. ResultsCd accumulated in plasma, kidney and liver of rats exposed to 50 and 500 μg.kg−1.d−1, without inducing signs of organ failure. In rats drinking 5 μg.kg−1.d−1 for 3 months, Cd exposure did not lead to any significant increase of Cd in these organs. At 50 and 500 μg.kg−1.d−1 of Cd, glucose and insulin tolerance were unchanged in both sexes. However, females exhibited a significant increase of both fasting and glucose-stimulated plasma insulin that was assigned to impaired hepatic insulin extraction as indicated by unaltered fasting C-peptide plasma levels. ConclusionsGlucose homeostasis is sensitive to chronic Cd exposure in a gender-specific way. Moreover, this study proves that an environmental pollutant such as Cd can have, at low concentrations, an impact on the glucose homeostatic system and it highlights the importance of a closer scrutiny of the underlying environmental causes to understand the increased incidence of type 2 diabetes.

TCF7L2 correlation in both insulin secretion and postprandial insulin sensitivity

BackgroundThe TCF7L2 rs7903146 variant is strongly associated with type 2 diabetes mellitus (T2DM). However, the mechanisms involved in this association remain unknown and may include extrapancreatic effects. The aim of this study was to perform a metabolic characterization of T2DM patients with and without the TCF7L2 rs7903146 risk T allele and analyze some influences of the TCF7L2 genotype on glucose metabolism.MethodsPatients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism. Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C, HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon. Additional secondary assessments included determination of insulinogenic index (IGI30), and insulin sensitivity (%S) and resistance (IR) by Homeostatic model assessment (HOMA).ResultsPatients with the CT/TT genotype showed lower baseline plasma concentrations of C-peptide when compared with those with the CC genotype. Of the 56 individuals who participated in the mixed-meal test, 26 and 30 had the CC and CT/TT genotypes, respectively. CT/TT subjects, compared with CC individuals, had higher post prandial plasma levels of insulin and C-peptide at 30–120 min (p < 0.05) and proinsulin at 45–240 min (p < 0.05). Interestingly CT/TT individuals presented at baseline higher %S (p = 0.021), and lower IR (p = 0.020) than CC individuals. No significant differences in IGI30 values were observed between groups.ConclusionsThe T2DM individuals carrying the rs7903146 T allele of the TCF7L2 gene presented higher IR pattern in response to a mix-meal test, different of beta cell function at baseline assessed by C-peptide levels which was lower, and Homa-IR was lower when comparing with non-carriers.

Diabetes after pancreaticoduodenectomy: can we predict it?

BackgroundThere is limited literature about the perioperative factors which can predict endocrine insufficiency after pancreaticoduodenectomy (PD). The primary aim was to correlate percentage pancreatic remnant volume (%RV) after PD in nondiabetic patients with the development of new-onset impaired glucose tolerance/diabetes mellitus (IGT/DM). The secondary aim was to identify the risk factors for new-onset IGT/DM. MethodsIn this prospective study, all consecutive patients with resectable periampullary carcinoma and without IGT/DM were evaluated with fasting and postprandial plasma glucose, HbA1c, insulin, and C-peptide levels preoperatively and at 3 mo postoperatively. After that, all patients were followed up with fasting and postprandial plasma glucose level assessed at 3-mo intervals for 24 mo or till death, whichever occurred earlier. The %RV was determined from computed tomography measurements preoperatively. ResultsOf the 50 patients, 11 (22%) patients developed IGT/DM after median follow-up of 32 mo. The patients' with/without IGT/DM were similar in demographic/perioperative variables. The %RV was found to be an independent factor associated with new-onset IGT/DM. A %RV of <48.8% was found to be a predictor of new-onset IGT/DM (sensitivity, 89.7%; specificity, 73.6%). Plasma sugar and glycosylated hemoglobin levels were significantly higher postoperatively after PD than the preoperative levels. Insulin and C-peptide levels were significantly lower after PD, irrespective of new-onset IGT/DM. ConclusionsThe incidence of IGT/DM after PD was 22%, and %RV < 48.8% was found to be a significant risk factor for new-onset IGT/DM. (CTRI/2013/12/004233).