Glucose Tolerance Test Insulin Research Articles

The deuterated glucose insulin tolerance test: a new tool to delineate insulin-stimulated glucose uptake from suppression of endogenous glucose production

The deuterated glucose insulin tolerance test: a new tool to delineate insulin-stimulated glucose uptake from suppression of endogenous glucose production

Investigation of glucagon-like peptide-1 response to six oral carbohydrates in ponies

Glucagon-like peptide-1 (GLP-1), the principal incretin in horses, may play a role in the pathophysiology of insulin dysregulation (ID). This study aimed to describe its concentration in response to three preserved forages and four dynamic tests for ID in ponies. Twelve adult ponies of mixed ID status were given a meal of hay, soaked hay or haylage, an in-feed oral glucose test (OGT), oral sugar test (OST), an oral test using a proprietary breakfast cereal (WEET) or a combined glucose-insulin tolerance test (CGIT) weekly in a randomised cross-over study. Glucose, insulin and GLP-1 concentrations were measured before and following each intervention. Ponies were designated ID or non-ID and insulin resistant (IR) or non-IR according to OGT and CGIT results, respectively.All interventions apart from the CGIT provoked a GLP-1 response within 30 min. The OGT and WEET interventions, (containing the greatest dose of non-structural carbohydrate, 1.06 and 1 g/kg BW, respectively), resulted in a greater area under the curve (AUC) for GLP-1 compared to all other interventions (P < 0.001). No difference in GLP-1 response was detected according to ID or IR status, despite there being strong positive correlations (rs [95 % CI]) between GLP-1 and insulin concentrations measured at individual time points (0.67 [0.62 – 0.71]; P < 0.001) and as AUC (0.66 [0.49–0.79], P < 0.001). These data do not support of the use of GLP-1 as an adjunctive diagnostic test for ID or IR, as defined by conventional intravenous or oral dynamic tests.

Comparison of one novel and four established diagnostic tests for insulin dysregulation in ponies

Several tests have been advocated for diagnosis of insulin dysregulation (ID). Tests using simple sugars may not reflect the response to naturally ingested carbohydrates. This study aimed to evaluate agreement between the oral glucose test (OGT), the oral sugar test (OST), a novel oral test using a proprietary cereal (WEET), the IV combined glucose-insulin tolerance test (CGIT) and fasted basal insulin (FI) for diagnosis of ID. Each of the five tests above was performed on a group of six normal and six insulin dysregulated mixed-breed ponies in a randomised crossover study. Area under the curve (AUC) and maximum concentration of insulin from OGT, OST and WEET showed strong to very strong bivariate correlations (r = 0.85–0.94, and r = 0.87–0.92, respectively; P ≤ 0.001) and were significantly different between tests (associated with dose of carbohydrate) and between CGIT-positive and -negative ponies. Dichotomous results showed substantial agreement between OST and both WEET (κ = 0.65; P = 0.02) and OGT (κ = 0.67; P = 0.01) and between CGIT and both OST (κ = 0.63; P = 0.03) and OGT (κ = 0.67; P = 0.01), and no agreement between FI, which had low sensitivity, and all other tests (κ = 0.15 – 0.31; P > 0. 05). Palatability of WEET was variable, resulting in one pony being excluded for analysis of WEET data. Further work on development of an oral test using a more palatable feedstuff and appropriate cut-offs or diagnostic thresholds for tests of ID is warranted.

At any Level of Adiposity, Relatively Elevated Leptin Concentrations Are Associated With Decreased Insulin Sensitivity.

The impact of obesity on glucose homeostasis has high interindividual variability, which may be partially explained by different adipokine concentrations. Leptin regulates energy balance and metabolism, and although its plasma levels are proportional to fat mass, they vary significantly across individuals with the same level of adiposity. We tested whether glucose homeostasis differs in subjects with similar degrees of adiposity but different leptin levels. We analyzed 1290 healthy adults from the Relationship Between Insulin Sensitivity and Cardiovascular Disease study cohort (30-60 years; male/female, 577/713; body mass index [BMI], 25 ± 3 kg/m2) characterized for body composition and metabolic variables with a 75-g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp, β-cell function, and lipidomics. Individuals were divided into relatively high and low leptin (RHL and RLL) if they were above or below the sex-specific leptin-fat mass (%) regression. Despite similar glucose tolerance, RHL showed markedly higher fasting and oral glucose tolerance test insulin concentration (+30% and +29%, respectively; P < .0001) and secretion (+17% and +11%, respectively; P < .0001). Regardless of BMI, RHL individuals had lower whole-body (-17-23%, P < .0001) and adipose tissue insulin sensitivity (-24%, P < .0001) compared with RLL. Notably, lean RHL individuals showed similar insulin sensitivity and β-cell function to RLL individuals with overweight/obesity. Subjects with leptin levels that are inappropriately elevated for their fat mass show whole-body/adipose tissue insulin resistance and hyperinsulinemia, regardless of BMI.

17 Can a yeast-derived prebiotic improve insulin response in aged horses?

Research has shown aged horses to be disproportionately affected by insulin dysregulation. Therefore, the objective of this study was to test the hypothesis that feeding ActivAge® (AA), a unique yeast-derived prebiotic purported to improve metabolic health, would lower insulin response in aged horses. Ten Quarter Horse geldings (19 ± 0.6 yr; 587.5 ± 22 kg) were utilized in a randomized design, with a 42d feeding period, followed by a 28d washout, then a crossover 42d feeding period. All horses received 0.36 kg/45.5 kg BW/d Purina® Equine Senior® (ES) paired with either 0.45 kg/d of a pelleted supplement containing AA (TRT) or no supplement (CON). All horses were offered 1.25% BW/d Timothy hay. All hay and concentrate feedings were split into 2 equal feedings at 0700 and 1430. Horses were housed in stalls with individual drylot turnouts. The glucose-insulin response to feeding (GIRF) was recorded on d28, and horses underwent a combined glucose-insulin tolerance test (CGIT) on d35 in each feeding period. For both tests, horses were catheterized for blood samples and no hay was fed before or during the sampling periods. For GIRF, horses were offered their AM meal and serial (every 30 min) blood samples were obtained from −30 through 360 min. For the CGIT, horses were administered IV dextrose (150mg/kg) and insulin (0.1U/kg) and serial blood samples were taken at −30, 0, 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 min. Serum was analyzedfor glucose and plasma was analyzed for insulin via colorimetric ELISA (Mercodia). Additionally, serum samples were collected via venipuncture every 2 wk, 2 h post AM meal, and analyzed for glucagon-like protein 1 (GLP-1) via an equine specific ELISA (MyBioSource). Data were analyzed via ANOVA using the MIXED procedure (SAS 9.4). Horses in both CON and TRT had similar glucose responses to feeding. No differences were observed in peak glucose response or area under the curve (AUC) for glucose. The insulin response during the GIRF was impacted by treatment with a trend for TRT having a lower insulin level (P = 0.07) and a decreased AUC (P = 0.02) compared with CON. For the CGIT, CON and TRT had similar glucose curves during the test, however there was a trend for the AUC for insulin in TRT to be lower compared with CON (P = 0.10). Horses in both the CON and TRT had similar starting levels of GLP-1 at d 0 but with time, GLP-1 levels rose in CON while they stayed lower in TRT over each 42-d feeding period (P < 0.001). In conclusion, feeding horses ActivAge® appears to affect insulin, but not glucose response, in standardized testing. Changes to GLP-1 secretion by enterocytes may be a mechanism behind this phenomenon.

Long-term Outcome of Body Composition, Ectopic Lipid, and Insulin Resistance Changes With Surgical Treatment of Acromegaly.

Acromegaly presents a unique pattern of lower adiposity and insulin resistance in active disease but reduction in insulin resistance despite a rise in adiposity after surgery. Depot-specific adipose tissue masses and ectopic lipid are important predictors of insulin resistance in other populations, but whether they are in acromegaly is unknown. Long-term persistence of body composition changes after surgery is unknown. To determine how depot-specific body composition and ectopic lipid relate to insulin resistance in active acromegaly and whether their changes with surgery are sustained long-term. Cross-sectional study in patients with active acromegaly and longitudinal study in newly diagnosed patients studied before and in long-term follow-up, 3 (1-8) years (median, range), after surgery. Seventy-one patients with active acromegaly studied cross-sectionally and 28 with newly diagnosed acromegaly studied longitudinally. Main outcome measures were visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue masses by whole-body magnetic resonance imaging; intrahepatic lipid (IHL) by proton magnetic resonance spectroscopy; insulin resistance measures derived from fasting; and oral glucose tolerance test insulin and glucose levels. SAT and insulin-like growth factor 1 level, but not VAT or IHL, were independent predictors of insulin resistance in active acromegaly. VAT, SAT, and IHL gains were sustained long-term after surgery. VAT mass rise with surgery correlated inversely with rise in QUICKI while SAT rise correlated with fall in the Homeostatic Model Assessment score. SAT and disease activity are important predictors of insulin resistance in active acromegaly. Adiposity gains are sustained long-term after surgical treatment and impact on the accompanying improvement in insulin resistance.

Oncometabolic surgery in gastric cancer patients with type 2 diabetes

The rates of early gastric cancer and type 2 diabetes mellitus(T2DM) are sharply increasing in Korea. Oncometabolic surgery in which metabolic surgery is conducted along with cancer surgery is a method used to treat gastric cancer and T2DM in one-stage operation. From 2011 to 2019, a total of 48 patients underwent long-limb Roux-en-Y gastrectomy (LRYG) in Inha University Hospital, and all data were reviewed retrospectively. A 75 g oral glucose tolerance test and serum insulin level test were performed before and 1 week and 1 year after surgery. One year after LRYG operation, 25 of 48 patients showed complete or partial remission and 23 patients showed non-remission of T2DM. The preoperative HbA1c level was significantly lower and the change in HbA1c was significantly greater in the T2DM remission group. Insulin secretion indices(insulinogenic index and disposition index) were increased significantly in the T2DM remission group. In contrast, the insulin resistance indices (homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda index) changed minimal. In the case of LRYG in T2DM patients, remnant β cell function is an important predictor of favorable glycemic control.

Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses.

The objectives of the study were to study the effects of the synthetic ergot alkaloid (EA), bromocriptine, on glucose and lipid metabolism in insulin dysregulated (ID, n = 7) and non-ID (n = 8) mares. Horses were individually housed and fed timothy grass hay and two daily concentrate meals so that the total diet provided 120% of daily DE requirements for maintenance. All horses were given intramuscular bromocriptine injections (0.1 mg/kg BW) every 3 days for 14 days. Before and after 14 days of treatment horses underwent a combined glucose-insulin tolerance test (CGIT) to assess insulin sensitivity and a feed challenge (1 g starch/kg BW from whole oats) to evaluate postprandial glycemic and insulinemic responses. ID horses had higher basal plasma concentrations of insulin (P = 0.01) and triglycerides (P = 0.02), and lower concentrations of adiponectin (P = 0.05) compared with non-ID horses. The CGIT response curve showed that ID horses had slower glucose clearance rates (P = 0.02) resulting in a longer time in positive phase (P = 0.03) and had higher insulin concentrations at 75 min (P = 0.0002) compared with non-ID horses. Glucose (P = 0.02) and insulin (P = 0.04) responses to the feeding challenge were lower in non-ID compared to ID horses. Regardless of insulin status, bromocriptine administration increased hay intake (P = 0.03) and decreased grain (P < 0.0001) and total DE (P = 0.0002) intake. Bromocriptine treatment decreased plasma prolactin (P = 0.0002) and cholesterol (P = 0.10) and increased (P = 0.02) adiponectin concentrations in all horses. Moreover, in both groups of horses, bromocriptine decreased glucose clearance rates (P = 0.02), increased time in positive phase (P = 0.04) of the CGIT and increased insulin concentrations at 75 min (P = 0.001). The postprandial glycemic (P = 0.01) and insulinemic (P = 0.001) response following the oats meal was lower after bromocriptine treatment in all horses. In conclusion, in contrast to data in humans and rodents, bromocriptine treatment reduced insulin sensitivity in all horses, regardless of their insulin status. These results indicate that the physiological effects of EA might be different in horses compared to other species. Moreover, because bromocriptine shares a high degree of homology with natural EA, further investigation is warranted in horses grazing endophyte-infected grasses.

STUDY OF SPECIFIC ANTIDIABETIC EFFECT OF PERSPECTIVE SIRTUIN-1 ACTIVATOR PYRABENTIN ON THE MODEL OF METABOLIC MEMORY IN RATS

Pharmacological activation of sirtuin-1 (SIRT1), which can mimic calorie restriction, reduce fat deposition along with stimulating its utilization, and possibly erase "metabolic memory", is a promising goal for the prevention and treatment of obesity and type 2 diabetes. The aim of the study was to evaluate the specific antidiabetic effect of the original heterocyclic compound with the proprietary name pyrabentin with in situ proven ability to activate human sirtuin-1 on the experimental model of "metabolic memory" in rats.&#x0D; The study was conducted on adult male Wistar rats (n=24), which were kept on a high-fat diet (HFD) for 5 months, control sex- and age-matched animals (n=6) were received standard diet (StD). At the end of the 5-mo HFD-period, the animals were randomized for the study over the next two months into 4 groups as follows: HFD/HFD+placebo, HFD/StD+placebo, HFD/StD+pyrabentin (PB), HFD/StD+metformin (MF). PB was administered orally at 50 mg/kg body weight as an aqueous suspension with Tween-80 daily, the reference drug metformin was administered in a similar way at 100 mg/kg body weight, the control group received a placebo. Glucose tolerance test and short insulin test were performed, body weight, abdominal adipose tissue weight by fraction and blood pressure were assessed. Shapiro-Wilk test, paired and unpaired Student’s t-test, and Mann-Whitney U-test were used.&#x0D; It was found that 60-day administration of pyrabentin to rats with a model of "metabolic memory", insulin resistance and obesity, was realized in a statistically significant decrease in basal glycemia, glucose intolerance, body weight and weight of abdominal adipose tissue fractions with comparable efficacy to the reference drug. This was accompanied by improved insulin sensitivity and blood pressure.

Association of glucose metabolism and retinopathy signs in non-diabetic individuals in midlife-The Northern Finland Birth Cohort 1966 study.

Diabetic retinopathy is a microvascular complication of hyperglycaemia. Little is known about the association of glucose metabolism and retinopathy signs in the non-diabetic middle-aged population. We studied prevalence of retinopathy in a subsample of Northern Finland Birth Cohort study (NFBC1966) of 1809 subjects, at 47 years of age, without previously diagnosed type 2 diabetes and/or blood pressure-lowering medication. All participants underwent clinical evaluations including an oral glucose tolerance test (glucose and insulin values measured at 0, 30, 60 and 120 min) and HbA1c. The retinopathy signs were diagnosed by fundus photographs and classified according to the Eurodiab classification scheme. The overall prevalence of newly diagnosed retinopathy was 1.4%. The retinopathy signs were significantly associated with increased 30 min, 1-h and 2-h glucose levels and 2-h insulin level in an OGTT. After adjustment with systolic blood pressure, only 30 min glucose, 1-h glucose and 2-h insulin levels were associated with retinopathy signs. Our findings show the potential role of 30 min and 1-h post-load glucose and 2-h insulin levels as risk factors for retinopathy lesions among the participants without previously diagnosed diabetes or hypertensive medication.

Long-term efficacy and safety of two doses of Norditropin® (somatropin) in Noonan syndrome: a 4-year randomized, double-blind, multicenter trial in Japanese patients.

This 4-year randomized, double-blind, multicenter trial (NCT01927861) investigated the long-term efficacy and safety of Norditropin® (NN-220; somatropin) in Japanese children with short stature due to Noonan syndrome. Pre-pubertal children with Noonan syndrome were randomized 1:1 to receive 0.033 mg/kg/day (n = 25, mean age 6.57 years) or 0.066 mg/kg/day (n = 26, mean age 6.06 years) GH. Height standard deviation score (SDS) change after 208 weeks from baseline was evaluated using an analysis of covariance model. Height SDS improved from -3.24 at baseline with a significantly greater increase (estimated mean [95% confidence interval]) with 0.066 vs. 0.033 mg/kg/day GH (1.84 [1.58; 2.10] vs. 0.85 [0.59; 1.12]; estimated mean difference 0.99 [0.62; 1.36]; p < 0.0001). The majority of treatment-emergent adverse events (TEAEs) were non-serious, mild and assessed as unlikely treatment-related. TEAE rates and frequencies of serious TEAEs were similar between groups. Three patients receiving 0.066 mg/kg/day were withdrawn; two due to TEAEs at days 1,041 and 1,289. Mean insulin-like growth factor-I SDS increased from -1.71 to -0.75 (0.033 mg/kg/day) and 0.57 (0.066 mg/kg/day) (statistically significant difference). In both groups, there were only minor glycosylated hemoglobin changes, similar oral glucose tolerance test insulin response increases and no clinically relevant changes in oral glucose tolerance test blood glucose, vital signs, electrocardiogram or transthoracic echocardiography. In conclusion, treatment with 0.033 and 0.066 mg/kg/day GH for 208 weeks improved height SDS in Japanese children with short stature due to Noonan syndrome with a significantly greater increase with 0.066 vs. 0.033 mg/kg/day GH and was well tolerated, with no new safety concerns.

Serum magnesium and high-sensitivity C-reactive protein as a predictor for gestational diabetes mellitus in Sudanese pregnant women

BackgroundGestational diabetes mellitus (GDM) is a big health problem that adversely affects both the maternal and perinatal outcomes. We aimed to predict the development of GDM in the first trimester using high sensitivity C-reactive protein (hs-CRP) and serum magnesium.MethodsThe study conducted in the antenatal care clinic of Saad Abualila Hospital (Khartoum, Sudan). Pregnant women were enrolled in this longitudinal cohort study during first trimester ≤14 weeks of gestation. Serum hs-CRP and magnesium concentrations were measured between weeks 11 and 14 of gestation. Glucose tolerance test and fasting plasma insulin (FPI) measurement were performed between 24 and 28 weeks gestational age. To assess insulin sensitivity and β-cell function, Homeostatic Model Assessment Insulin Resistance (HOMA-IR), HOMA-β indices and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated and used.ResultsOut of the 126 who completed the study 19 (15%) were diagnosed as GDM. The median (interquartile) of FBG was significantly higher in women with GDM [81 (70–95) vs. 67(60–75) mg/dl; P = < 0.001] compared to women without GDM. There was no significant difference in hs-CRP, serum magnesium, HOMA-IR, QUICKI and HOMA- β between women with GDM and women without GDM. No correlation was observed between body mass index (BMI), serum magnesium, hs-CRP, FBG and insulin levels.ConclusionsFirst trimester hs-CRP and serum magnesium levels were not correlated with the later development of gestational diabetes in this setting.

2127-P: Reduced Islet Parasympathetic Nerve Density Correlates with Decrease in Beta-Cell Volume of Islet in Lean Type 2 Diabetic Goto-Kakizaki Rat

Pancreatic branch of vagus nerve (pvn) signaling plays a pivotal role in the maintenance of islet β cell volume density (Vβ). In type 2 diabetes (T2D), small fibers in the epidermis is decreased by diabetic insult. It is not still uncovered yet, however, that the reduction of terminal pvn fibers is associated with Vβ in T2DM. Herein, we explored the association between islet pvn fiber density and Vβ. We recruited non-obese spontaneous T2D Goto-Kakizaki (GK) rats and control Wistar rats (W) at 5 weeks of age. GK was divided into DPP-4 inhibitor (DPi)-treated group (GTe) (10mg/kg teneligliptine), SGLT2 inhibitor (SGi)-treated group (GCa) (10mg/kg canagliflozin) and both treated group (GTeCa). During experimental period, 2g/kg oral glucose tolerance test (OGTT) and glucose-stimulated insulin secretion test (GSIS) was performed. At end, pancreata were underwent for the pathological evaluation. OGTT in GK was attenuated (p&amp;lt;0.01 vs. W). Although DPi and SGi in each significantly improved OGTT compared to GK, the effect was the most robust in GTeCa. Low GSIS in GK (p&amp;lt;0.01 vs. W) was significantly improved in GTe and GCaTe (p&amp;lt;0.05 and p&amp;lt;0.01 vs. GK, respectively), although it was comparable between GK and GCa. Pathological evaluation disclosed a significant decrease in Vβ in GK (p&amp;lt;0.01 vs. W). Vβ was the most well-preserved in GCaTe (p&amp;lt;0.05 vs. GTe), followed by GTe (p&amp;lt;0.05 vs. GK), while it was comparable between GK and GCa. The density of pvn fibers labeled by the antibody for vesicular acetylcholine transporter (VachT) were significantly decreased in the islet of GK (p&amp;lt;0.01 vs. W). It was significantly improved in GCa, GTe and GCaTe compared to GK (p&amp;lt;0.05 vs. GCa and GTe; p&amp;lt;0.01 GCaTe, respectively). pvn fiber density in the islets significantly correlated with Vβ (r=0.53, p&amp;lt;0.01). Our results shed light on the association between terminal fiber density of pvn in the islet and Vβ, and the maintenance of the fibers may be beneficial for the prevention from Vβ loss in T2D. Disclosure H. Mizukami: None. D. Guo: None. K. Takahashi: None. S. Osonoi: None. K. Kudo: None. S. Yagihashi: None.

Serum magnesium status and its correlation with insulin resistance in newly diagnosed patients with type 2 diabetes mellitus

Hypomagnesaemia has been reported in type 2 diabetes mellitus (T2DM) and an association of low serum magnesium (Mg) with insulin resistance has been observed. In this cross-sectional study, 65 new T2DM patients and 65 healthy controls were investigated to assess the Mg status and see the association between Mg level and insulin resistance. Oral glucose tolerance test, HbA1c, serum Mg, and fasting insulin were measured and the level of insulin resistance was calculated by using the homeostasis model assessment for insulin resistance (HOMA-IR). Serum Mg level was similar in T2DM and control groups; a higher frequency of hypomagnesemia was observed in the T2DM than control group (26.2% vs. 12.3%) though it was not statistically significant (p= 0.074). Level of insulin resistance (HOMA-IR) was higher in the T2DM group and a higher frequency of subjects had insulin resistance in this group compared to controls. No significant differences in age, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), fasting plasma glucose (FPG), HbA1c, fasting insulin level and HOMA-IR were observed between normomagnesaemic and hypomagnesaemic T2DM subjects. In the T2DM group, age, BMI, WC, WHR, FPG, fasting insulin and HOMA-IR correlated with serum Mg level though in the control group Mg had significant inverse correlations with BMI and fasting insulin. New T2DM subjects and healthy controls had similar Mg status although the frequency of hypomagnesemia was higher (not significant) in the T2DM group and serum Mg level had no correlation with glycemic status, fasting insulin and HOMA-IR in T2DM patients.

Insulin Resistance as a Result of Body Condition Categorized as Thin, Moderate, and Obese in Domesticated U.S. Donkeys (Equus asinus)

Donkeys are often kept, especially in industrialized countries, as companion animals. Donkeys have greater digestive efficiency and tend to expend less energy than horses or ponies, which contributes to obesity in nonworking donkeys. Obesity in all equine species increases risk of chronic health conditions such as laminitis and insulin resistance. Previous studies in horses and ponies have documented obesity's potential effects on glucose-insulin dynamics with lower insulin sensitivity and higher insulin responses to glucose. However, limited studies on obesity and its health impacts in donkeys exist, so these effects on glucose-insulin dynamics have not been fully studied. Twenty-four donkeys were selected according to initial body condition score (BCS) and divided into three categories with eight donkeys in each: thin, moderate, and obese. A frequently sampled glucose-insulin tolerance test was performed with subsequent MINMOD analysis to determine the effects of BCS on glucose-insulin dynamics. Basal insulin was highest in obese donkeys when compared with moderate and thin donkeys (P = .02 and P = .01, respectively). There was an overall trend across groups for BCS to lower insulin sensitivity (P = .06). No other effect was found. Body condition score seems to affect donkeys in a similar manner to horses and ponies as higher BCS was associated with higher basal insulin and may lower insulin sensitivity. Higher basal insulin concentrations in obese donkeys could negatively influence health and contribute to serious, chronic conditions.

Effect of vitamin D deficiency on the 75 g oral glucose tolerance test screening and insulin resistance

Gestational diabetes mellitus (GDM), is the most common medical complications of pregnancy. This study aimed to clarify the effect of second-trimester vitamin D deficiency on the 75 g oral glucose tolerance test (OGTT) screening and insulin resistance. A total of 120 pregnant women with a singleton pregnancy at a gestational age of 26–28 weeks were analyzed. Participants were divided into two groups according to 25-hydroxyvitamin D levels; vitamin D deficiency, and control groups. For GDM scan, 75 g OGTT was preferred. GDM prevalence was 17.5% in vitamin D deficiency group and 13.75% in control group, there is no significant difference in GDM prevalence (p = 0.149). Fasting plasma glucose and 1-h plasma glucose levels were significantly higher in the vitamin D deficiency group than in the control group (p < .001 and p < .001, respectively). No significant differences were observed between 2-hour plasma glucose levels (p = .266). The HOMA-IR level was significantly higher in the vitamin D deficiency group than in the control group (p < .001). The findings of the present study suggested that vitamin D deficiency in the second trimester was inversely correlated with fasting and 1-h plasma glucose after 75 g glucose challenge test; also, low 25 OHD3 levels were associated with insulin resistance.

The revascular and transplanted effects of vascular endothelial cells on islets grafts

Objective To investigate the revascular and transplanted effects of islet grafts after co-transplantation with vascular endothelial cells (ECs) in diabetic rats. Methods The rat ECs and islet cells were isolated and purified, then subcutaneously co-transplanted to the inbred SD male rats with diabetes mellitus, the group of islets transplanted alone, group of phosphate buffered solution, and group of normal rats served as control. Islet grafts revascularization degree, islet cells activity and apoptosis were observed by immunohistochemical double staining of CD31, insulin and factor associated suicide (Fas) antibody. The results of intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT), the blood glucose and insulin levels of the rats and the survival time of the islet grafts were compared. Results The blood glucose concentrations of IPGTT and IPITT, the blood glucose and insulin levels of rats analyzed by multivariate analysis in the ECs and islets transplantation group were better than those in the islets transplantation alone group (P<0.05). The islet grafts mean survival time of the ECs and islets transplantation group was longer than that of the islets transplantation alone group (P<0.05). On the 7th day after transplantation, mean microvascular density of islet grafts per square millimeter in the ECs and islets transplantation group was 26.4±6.1, significantly greater than that in the islets transplantation alone group 18.3±5.7 (P<0.05). In the ECs and islets transplantation group, insulin staining intensity was higher than that in the islets transplantation alone group (P<0.05), while factor associated suicide(Fas) staining intensity was lower than that in the islets transplantation alone group (P<0.05). Conclusion Co-transplantation with ECs could promote the revascularization of islet grafts and improve the effect of islet transplantation. (Chin J Endocrinol Metab, 2018, 34: 516-521) Key words: Islet transplantation; Endothelial cells; Revascularization; Diabetes mellitus

Optimal Cut-off Points of Fasting and Post-Glucose Stimulus Surrogates of Insulin Resistance as Predictors of Metabolic Syndrome in Adolescents According to Several Definitions

Objective:The aim of this study was to determine optimal cut-off points for fasting and post-glucose stimulus surrogates of insulin resistance to predict metabolic syndrome in adolescents according to several definitions.Methods:One hundred fifty-five adolescents living in Mexico City were enrolled during 2011 and 2012. Waist circumference and blood pressure were recorded. Subjects received an oral glucose load of 1.75 g per kg up to a maximum dose of 75 g. Blood samples were drawn at baseline and 120 minutes. Concentrations of plasma glucose, triglycerides, high-density lipoprotein cholesterol and insulin were determined.Results:The frequency of metabolic syndrome showed a large variability when using a variety of published definitions; in contrast, the optimal cut-off points for fasting insulin, homeostatic model assessment of insulin resistance and two-hour oral glucose tolerance test insulin were very similar in almost all the definitions considered and had adequate diagnostic performance: area under the curve >0.869, sensitivity >0.835 and specificity >0.755. Insulin resistance surrogates had substantial agreements with Ford, Cook and Salas definitions (Kappa~0.62; agreement~82%); moderate agreement was observed for International Diabetes Federation, Cruz and Ferranti definitions (Kappa~0.41–0.59; agreement~77%).Conclusions:Insulin resistance surrogates may be a better approach for metabolic syndrome assessment in an adolescent population because of reduced variability and a higher predictive value.

Coadministration of Intranasally Delivered Insulin and Proinsulin C-Peptide to Rats with Types 1 and 2 Diabetes Mellitus Restores Their Metabolic Parameters

The C-peptide, the product of proinsulin proteolysis, not only is a signal molecule, but also, forming a complex with insulin, is able to modulate the signaling functions of insulin. The signaling systems sensitive to insulin in the hypothalamus and other brain areas are among the targets of insulin. We hypothesized that in systemic deficiency of insulin and C-peptide in the type 1 diabetes mellitus (DM) and in severe forms of the type 2 DM, the increase in the level of C-peptide in the CNS will improve central effects of insulin, including its influence on peripheral metabolism. To verify this, the influence of separate and co-administration of intranasal insulin (II) and C-peptide (IP) on their metabolic parameters and sensitivity to insulin in rats with acute and mild type 1 DM induced by the treatment with streptozotocin at the doses of 60 and 35 mg/kg and in rats with neonatal type 2 DM corresponding to severe long-term form of type 2 DM in human was studied. The treatment of animals with II and IP was carried out for 7 days in the daily doses of 20 and 10 μg/rat, respectively. The co-administration of II and IP leading to an increase of insulin and C-peptide levels in the brain was most effective. In rats with type 1 DM treated with the combination of II plus IP, hyperglycemia was decreased and weight loss was prevented. In rats with type 2 DM, co-administration of II and IP led to the normalization of glucose homeostasis and the increase in insulin sensitivity, as shown by glucose-tolerance and insulin-glucose tolerance tests, and to improvement of lipid metabolism, as demonstrated by the decrease in the atherogenic index. The effectiveness of monotherapy with II was lower than in the case of a combination of II+IP, while monotherapy with C-peptide had little effect on the indicators studied. Thus, the simultaneous increase of insulin and C-peptide levels in the brain in the conditions of their deficiency in diabetic pathology can be considered as one of the promising approaches to restore the central insulin-dependent regulation of peripheral metabolism and to improve the utilization of glucose in different forms of DM.

Use of First-phase Insulin Secretion in Early Diagnosis of Thyroid Diabetes and Type 2 Diabetes Mellitus.

Background:A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM.Methods:In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-β, modified β-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTT from the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0′~10′, and AUCins-IVGTT from the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion.Results:In the OGTT, the HOMA-β values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P < 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P < 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P < 0.05). In the IVGTT, insulin secretion peaked for all groups at 2–4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P < 0.05). The Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P < 0.05). Compared with the other five groups, the Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the T2DM group were significantly decreased (all P < 0.05). The Ip/I0 and AUCins-IVGTT values of the TNGT group were higher than those of the NGT group (all P < 0.05).Conclusions:β-cell function in TDM patients is superior to that in T2DM patients. First-phase insulin secretion could be used as an early diagnostic marker to differentiate TDM and T2DM.