Search

Efficient and accurate methods to estimate insulin sensitivity (SI) and b-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk. [ABSTRACT FROM AUTHOR]

Introduction: Maternal overweight is a risk factor for gestational diabetes mellitus (GDM). However, emerging evidence suggests that an increased maternal body mass index (BMI) promotes the development of perinatal complications even in women who do not develop GDM. This study aims to assess physiological glucometabolic changes associated with increased BMI. Methods: Twenty-one women with overweight and 21 normal weight controls received a metabolic assessment at 13 weeks of gestation, including a 60-min frequently sampled intravenous glucose tolerance test. A further investigation was performed between 24 and 28 weeks in women who remained normal glucose tolerant. Results: At baseline, mothers with overweight showed impaired insulin action, whereby the calculated insulin sensitivity index (CSI) was lower as compared to normal weight controls (3.5 vs. 6.7 10-4 min-1 [microU/mL]-1, p = 0.025). After excluding women who developed GDM, mothers with overweight showed higher average glucose during the oral glucose tolerance test (OGTT) at the third trimester. Moreover, early pregnancy insulin resistance and secretion were associated with increased placental weight in normal glucose-tolerant women. Conclusion: Mothers with overweight or obesity show an unfavorable metabolic environment already at the early stage of pregnancy, possibly associated with perinatal complications in women who remain normal glucose tolerant. [ABSTRACT FROM AUTHOR]

Aim: To determine whether glucose volume of distribution (VdGLUCOSE) affects the diagnosis of impaired insulin sensitivity (IS) when using an intravenous glucose tolerance test (IVGTT). Methods: Individuals with distinct levels of IS underwent IVGTT after an overnight fast. The prediabetic group (Prediab; n = 33) differed from the healthy group (Healthy; n = 14) in their larger glycosylated hemoglobin (HbA1c of 5.9 ± 0.3 vs. 5.4 ± 0.1%; 41 ± 4 vs. 36 ± 1 mmol/mol; p < 0.001), percent body fat (37 ± 6 vs. 24 ± 3%; p < 0.001) and cardiovascular fitness level (VO2MAX 22 ± 5 vs. 44 ± 5 mL of O2·kg−1·min−1; p < 0.001). Ten minutes after intravenous infusion of the glucose bolus (i.e., 35 g in a 30% solution), VdGLUCOSE was assessed from the increases in plasma glucose concentration. IS was calculated during the next 50 min using the slope of glucose disappearance and the insulin time‐response curve. Results: VdGLUCOSE was higher in Healthy than in Prediab (230 ± 49 vs. 185 ± 21 mL·kg−1; p < 0.001). VdGLUCOSE was a strong predictor of IS (β standardized coefficient 0.362; p = 0.004). VO2MAX was associated with VdGLUCOSE and IS (Pearson r = 0.582 and 0.704, respectively; p < 0.001). However, body fat was inversely associated with VdGLUCOSE and IS (r = −0.548 and −0.555, respectively; p < 0.001). Conclusions: Since fat mass is inversely related to VdGLUCOSE and in turn, VdGLUCOSE affects the calculations of IS, the IV glucose bolus dose should be calculated based on fat‐free mass rather than body weight for a more accurate diagnosis of impaired IS. [ABSTRACT FROM AUTHOR]

Energy partitioning in lactating cows affects milk production, f eed efficiency, and body reserves, with the latter having health implications for the transition into the following lactation. One molecule likely involved in the regulation of en ergy partitioning is serotonin. The objective of this experiment was to explore how increasing circulating serotonin, by intravenous infusion of the serotonin precursor 5-hydroxytryptophan (5-HTP), affects metabolic responses to a glucose challenge in m idlactation cows as a means to manipulate energy partitioning. We intravenously infused Holstein cows with 5-HTP (1 mg/kg bodyweight dissolved in saline, n = 11) or saline alone as control (n = 9) over 1 h/day for 3 days. Cows were fasted overnight on day 2. On day 3, fasted cows were given an intravenous bolus of glucose (0.092 g/kg bodyweig ht). Blood samples were collected for the following 120 min for metabolic and hormonal analysis. Infusion of 5-HTP elevated circulating concentrations of serotonin and free fatty acids, reduced the concentration of insulin and amino acids, and did not affect the concentration of glucose and glucagon before the glucose challenge. Surrogate insulin sensitivity indices indicated improved insulin sensitivity in 5-HTP cows, but due to the unique metabolism of lactating ruminants, these index changes may instead reflect effects in ins ulin-independent glucose disposal, like milk synthesis. Challenging 5-HTP-treated cows with a glucose bolus reduced the insulin spike and blunted the decrease in fre e fatty acids, compared to saline cows, without changing glucose dynamics. Overall, these results suggest that serotonin stimulates insulin-independent glucose disposal, requiring less insulin to maintain normoglycemia. [ABSTRACT FROM AUTHOR]

The objective of this experiment was to determine if supplying additional propionate to the rumen alters dry matter intake (DMI), feeding behavior, glucose metabolism, and rumen fluid metabolites in steers fed a finishing diet. Ruminally cannulated steers (n = 6) were fed a finishing diet ad libitum. Steers were randomly assigned to one of three treatments in a 3 × 6 Latin rectangle design with three 15 d periods. Treatments of no Ca propionate (Control), 100 g/d (Low), or 300 g/d (High) were ruminally dosed twice daily. Individual intake was measured using an Insentec feeding system. Pre-feeding blood samples were collected on day 7 and rumen fluid samples were collected on day 13. An intravenous glucose tolerance test (IVGTT) was conducted on day 14 and liver biopsies were collected on day 15. Liver samples were analyzed for expression of genes involved in gluconeogenesis. Data were analyzed using a mixed model with period, treatment, day, and their interaction included, with day and minute within period as a repeated measure and steer as a random effect. Meal size (P = 0.049), meal frequency (P = 0.046), and DMI (P < 0.001) were decreased in High steers. Day 7 plasma glucose (P = 0.23) and lactate (P = 0.47) were not affected by treatment, but insulin was decreased (P = 0.008) and non-esterified fatty acids were increased (P = 0.044) in the High treatment compared with the Control. Rumen fluid lactate was decreased (P = 0.015) in the High treatment compared with the Low treatment. Total VFA concentrations did not differ (P = 0.88) between treatments. There was treatment × time interaction for proportions of acetate and propionate (P < 0.001) and the acetate:propionate ratio (P = 0.005). The effect on acetate was due to a decrease in the High treatment 2 h after dosing the treatment. Propionate proportions were greater in the High treatment than the Control at all time points and differed from the Low except at 0 h. Propionate treatments had no major effects on the glucose and insulin parameters observed in the IVGTT other than a tendency (P = 0.09) for an increased insulin time to peak. These data indicate that exogenous propionate decreases DMI but the decrease in propionate from fermentation due to reduced DMI might negate the supply of exogenous propionate in VFA supply to the animal. Mechanisms other than hepatic oxidation of propionate might be responsible for DMI regulation. [ABSTRACT FROM AUTHOR]

BackgroundType 2 resistant starch (RS2) has been shown to improve glycemic control and some cardiovascular endpoints in rodent and human studies.ObjectiveThe aim of this study was to perform one of the first randomized clinical trials in adults with prediabetes and one of the longest trials to test whether RS2 can improve cardiometabolic health.Design68 overweight [body mass index (BMI) ≥27 kg/m2] adults aged 35-75 y with prediabetes were randomized to consume 45 g/d of high-amylose maize (RS2) or an isocaloric amount of the rapidly digestible starch amylopectin (control) for 12 wk. At baseline and postintervention, ectopic fat depots (visceral adipose tissue, intrahepatic lipids, and intramyocellular lipids) were measured by magnetic resonance imaging/spectroscopy, energy metabolism by respiratory chamber, and carbohydrate metabolism by glycated hemoglobin (HbA1c), an intravenous glucose tolerance test, and a meal tolerance test. Cardiovascular risk factors-serum lipids, blood pressure, heart rate, and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, and tumor necrosis factor [TNF]-α)-were also measured. The primary endpoints were insulin sensitivity, insulin secretion, ectopic fat, and markers of inflammation. Data were primarily analyzed as treatment effects via a linear mixed model both with and without the addition of covariates.ResultsRelative to the control group, RS2 lowered HbA1c by a clinically insignificant 0.1 ± 0.2% (Δ = -1 ± 2 mmol/mol; P = 0.05) but did not affect insulin secretion, insulin sensitivity, the disposition index, or glucose or insulin areas under the curve relative to baseline (P ≥ 0.23). RS2 decreased heart rate by 5 ± 9 beats/min (P = 0.02) and TNF-α concentrations by 2.1 ± 2.7 pg/mL (P = 0.004), relative to the control group. Ectopic fat, energy expenditure, substrate oxidation, and all other cardiovascular risk factors were unaffected (P ≥ 0.06).Conclusions12 wk of supplementation with resistant starch reduced the inflammatory marker TNF-α and heart rate, but it did not significantly improve glycemic control and other cardiovascular disease risk factors, in adults with prediabetes. This trial was registered at clinicaltrials.gov as NCT01708694.

Context: Muscle fiber composition is associated with peripheral insulin action. Objective: We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia. Methods: Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group 1 (n = 11), area occupied by type I muscle fibers = 61.0 ± 11.8%, and group 2 (n = 8), type I area = 36.0 ± 4.9% (P < 0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition, and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity, and secretion were determined. Results: Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group 2 vs group 1 (P = 0.019). First-phase insulin release (area under the insulin curve during 10 minutes after glucose infusion) was increased by almost 4-fold in group 2 vs group 1 (P = 0.01). Whole-body insulin sensitivity was correlated with percentage area occupied by type I fibers (r = 0.54; P = 0.018) and capillary density in muscle (r = 0.61; P = 0.005) but not with mitochondrial respiration. Insulin release was strongly related to percentage area occupied by type II fibers (r = 0.93; P < 0.001). Conclusions: Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose-stimulated insulin secretion prior to onset of clinical manifestations. [ABSTRACT FROM AUTHOR]

Background: The possible existence of an acini-islet-acinar (AIA) reflex, involving mutual amylase and insulin interactions, was investigated in the current acute experiment on pigs., Aim: To confirm the existence of an AIA reflex and justify the placement of the exocrine and endocrine pancreatic components within the same organ., Methods: The study was performed on six pigs under general anesthesia. An intravenous glucose tolerance test was performed, with a bolus infusion of 50% glucose to the jugular vein, while amylase (5000 U/kg) or vehicle intrapancreatic infusions were administered via the pancreaticoduodenalis cranialis artery during 30 min with a 1 mL/min flow rate., Results: The amylase infusion to pancreatic arterial circulation inhibited and delayed the insulin release peak which is usually associated with the highest value of blood glucose and is typically observed at 15 min after glucose infusion, for > 1 h. The intrapancreatic infusion of the vehicle (saline) did not have any effect on the time frame of insulin release. Infusion of 1% bovine serum albumin changed the insulin release curve dramatically and prolonged the high range of insulin secretion, far beyond the glucose peak., Conclusion: Intrapancreatic arterial infusion of amylase interrupted the integrated glucose-insulin interactions. This confirms an AIA reflex and justifies placement of the exocrine and endocrine pancreatic components within the same organ., Competing Interests: Conflict-of-interest statement: The authors of this manuscript have the following competing interests: Stefan Pierzynowski and Kateryna Pierzynowska are the owners of Anara AB, Sweden. Piotr Wychowański is the owner of MED Sp. z o.o., Poland. Stefan Pierzynowski is the owner of Vitanano Sp. z o.o., Poland. Kamil Zaworski received funding from National Science Centre, Poland (Preludium, 2021/41/N/NZ9/01722). All other authors declare no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse. Aims: This study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM). Methods: A total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity. Results: Age, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 (p for linear trend <0.05), and the differences between G1 and G2 were also statistically significant (p < 0.05). Glucose peak of most participants in G1 converged at 5 min, and the curves shape of insulin and C-peptide in G2 were the sharpest among three groups. There was no significant difference in all IVGTT-based indices between G1 and G2, but AUCIns, AUCIns/AUCGlu, and △Ins3/△Glu3 in G2 were the highest, and the p- value for linear trend of those indices among three groups were statistically significant (p < 0.05). Conclusions: Two patterns of FPIS were in subjects with NGT, while subjects with later time to glucose peak during FPIS might be less likely to develop T2DM in the future. [ABSTRACT FROM AUTHOR]

BackgroundThe increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse.AimsThis study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM).MethodsA total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity.ResultsAge, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 (p for linear trend

Abstract Aim The aim of the present study was to assess beta cell function based on an oral glucose tolerance test (OGTT) in participants with single islet autoantibody or an intravenous glucose tolerance test (IvGTT) in participants with multiple islet autoantibodies. Materials and methods Healthy participants in Sweden and Finland, between 2 and 49.99 years of age previously identified as positive for a single (n = 30) autoantibody to either insulin, glutamic acid decarboxylase, islet antigen‐2, zinc transporter 8 or islet cell antibodies or multiple autoantibodies (n = 46), were included. Participants positive for a single autoantibody underwent a 6‐point OGTT while participants positive for multiple autoantibodies underwent an IvGTT. Glucose, insulin and C‐peptide were measured from OGTT and IvGTT samples. Results All participants positive for a single autoantibody had a normal glucose tolerance test with 120 minutes glucose below 7.70 mmol/L and HbA1c values within the normal range (

Aim: The aim of the present study was to assess beta cell function based on an oral glucose tolerance test (OGTT) in participants with single islet autoantibody or an intravenous glucose tolerance test (IvGTT) in participants with multiple islet autoantibodies. Materials and methods: Healthy participants in Sweden and Finland, between 2 and 49.99 years of age previously identified as positive for a single (n = 30) autoantibody to either insulin, glutamic acid decarboxylase, islet antigen‐2, zinc transporter 8 or islet cell antibodies or multiple autoantibodies (n = 46), were included. Participants positive for a single autoantibody underwent a 6‐point OGTT while participants positive for multiple autoantibodies underwent an IvGTT. Glucose, insulin and C‐peptide were measured from OGTT and IvGTT samples. Results: All participants positive for a single autoantibody had a normal glucose tolerance test with 120 minutes glucose below 7.70 mmol/L and HbA1c values within the normal range (<42 mmol/mol). Insulin responses to the glucose challenge on OGTT ranged between 13.0 and 143 mIU/L after 120 minutes with C‐peptide values between 0.74 and 4.60 nmol/L. In Swedish participants, the first‐phase insulin response (FPIR) on IvGTT was lower in those positive for three or more autoantibodies (n = 13; median 83.0 mIU/L; range 20.0‐343) compared to those with two autoantibodies (n = 15; median 146 mIU/L; range 19.0‐545; P =.0330). Conclusion: Participants positive for a single autoantibody appeared to have a normal beta cell function. Participants positive for three or more autoantibodies had a lower FPIR as compared to participants with two autoantibodies, supporting the view that their beta cell function had deteriorated. [ABSTRACT FROM AUTHOR]

Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous glucose tolerance test data from subjects with type 2 diabetes (T2D, n=154) and non-diabetic (ND) subjects (n=343). A hierarchical statistical analysis was performed, which provided a formal mechanism for pooling the data from all study subjects, to yield a single composite population model that quantifies the role of subject specific characteristics such as weight, height, age, sex, and glucose tolerance. Based on the resulting composite population model, GEZI was reduced from 0.021 min–1 (standard error – 0.00078 min–1) in the ND population to 0.011 min–1 (standard error – 0.00045 min–1) in T2D. The resulting model was also employed to calculate the proportion of the non–insulin-dependent net glucose uptake in each subject receiving an intravenous glucose load. Based on individual parameter estimates, the fraction of total glucose disposal independent of insulin was 72.8% ± 12.0% in the 238 ND subjects over the course of the experiment, indicating the major contribution to the whole-body glucose clearance under non-diabetic conditions. This fraction was significantly reduced to 48.8% ± 16.9% in the 30 T2D subjects, although still accounting for approximately half of the total in the T2D population based on our modeling analysis. Given the potential application of glucose effectiveness as a predictor of glucose intolerance and as a potential therapeutic target for treating diabetes, more investigations of glucose effectiveness in other disease conditions can be conducted using the hierarchical modeling framework reported herein.

Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous glucose tolerance test data from subjects with type 2 diabetes (T2D, n=154) and non-diabetic (ND) subjects (n=343). A hierarchical statistical analysis was performed, which provided a formal mechanism for pooling the data from all study subjects, to yield a single composite population model that quantifies the role of subject specific characteristics such as weight, height, age, sex, and glucose tolerance. Based on the resulting composite population model, GEZI was reduced from 0.021 min–1 (standard error – 0.00078 min–1) in the ND population to 0.011 min–1 (standard error – 0.00045 min–1) in T2D. The resulting model was also employed to calculate the proportion of the non–insulin-dependent net glucose uptake in each subject receiving an intravenous glucose load. Based on individual parameter estimates, the fraction of total glucose disposal independent of insulin was 72.8% ± 12.0% in the 238 ND subjects over the course of the experiment, indicating the major contribution to the whole-body glucose clearance under non-diabetic conditions. This fraction was significantly reduced to 48.8% ± 16.9% in the 30 T2D subjects, although still accounting for approximately half of the total in the T2D population based on our modeling analysis. Given the potential application of glucose effectiveness as a predictor of glucose intolerance and as a potential therapeutic target for treating diabetes, more investigations of glucose effectiveness in other disease conditions can be conducted using the hierarchical modeling framework reported herein. [ABSTRACT FROM AUTHOR]

Objective: To study the endocrine pancreas' function in transfusion-dependent ß-thalassemia (ß-TDT) patients with a normal glucose tolerance test (NGT) and hypoinsulinemia. In addition, the prospective long-term follow-up using an annual oral glucose tolerance test (OGTT) to detect any abnormality of glucose metabolism. Patients and methods: Seven ß-TDT patients (mean age 22.4 ± 4.2 years) with NGT and inadequate insulin response (hypoinsulinemia) to OGTT were referred for a second opinion to an Italian Centre. Results: The first-phase insulin response (FPIR), expressed as the sum of 1 and 3 minutes insulin, to intravenous glucose tolerance test (IVGTT), was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in five. The results were not associated with ß-cell autoimmunity. After 43 ± 26 months (range 11 - 80 months) of follow-up, two patients developed impaired glucose tolerance (IGT), three both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline, the lowest value of the insulinogenic index (IGI: 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at the diagnosis of IFG, IGT, and DM. There was a significant inverse correlation between ISSI-2 and area under the curve plasma glucose (AUC-PG). Conclusions: These data demonstrated, for the first time, progressive deterioration in glucose homeostasis in ß-TDT subjects with NGT and hypoinsulinemia and that the ISSI-2 index may be a valuable parameter to identify patients at high risk for developing glucose dysregulation. [ABSTRACT FROM AUTHOR]

Efficient and accurate methods to estimate insulin sensitivity ( S I ) and β-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived S I and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk. NEW & NOTEWORTHY The pathogenesis of type 2 diabetes (T2D) is determined by a balance between insulin sensitivity ( S I ) and β-cell function (BCF), which can be determined by gold standard direct measurements or estimated by fitting differential equation models to oral glucose tolerance tests (OGTTs). We propose and validate a new differential equation model that is simpler to use than current models and requires less data while maintaining good correlation and agreement with gold standards. Matlab and Python code is freely available.

Background and Aims: Insulin clearance is a relevant process in glucose homeostasis. In this observational study, we aimed to assess insulin clearance (ClINS) in women with former gestational diabetes (fGDM) both early after delivery and after a follow-up.Methods and Results: We analysed 59 fGDM women, and 16 women not developing GDM (CNT). All women underwent an oral glucose tolerance test (OGTT) yearly, and an insulin-modified intravenous glucose tolerance test (IVGTT) at baseline and at follow-up end (until 7 years). Both IVGTT and OGTT ClINS was assessed as insulin secretion to plasma insulin ratio. We also defined IVGTT first (0-10 min) and second phase (10-180 min) ClINS. We found that 14 fGDM women progressed to type 2 diabetes (PROG), whereas 45 women remained diabetes-free (NONPROG). At baseline, IVGTT ClINS showed alterations in PROG, especially in second phase (0.88 ± 0.10 l·min-1 in PROG, 0.60 ± 0.06 in NONPROG, 0.54 ± 0.07 in CNT, p ≤ 0.03). Differences in ClINS were not found from OGTT. Cox regression analysis showed second phase ClINS as significant type 2 diabetes predictor (hazard ratio = 1.90, 95% confidence interval 1.09-3.30, p = 0.02).Conclusion: This study showed that insulin clearance derived from an insulin-modified IVGTT is notably altered in women with history of GDM progressing towards type 2 diabetes. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate glucose-induced insulin response in cows exposed to different temperature-humidity index. Twenty early lactating Holstein-Friesian cows were divided into 2 equal groups based on season, as summer (SU) and spring (SP). SP cows were not exposed to heat stress, while SU cows were exposed to moderate or severe heat stress. Milk production was recorded daily. Starting from day 30 of lactation, intravenous glucose tolerance test (IVGTT) was carried out three times at 30-day intervals. Blood samples were taken before (basal) and after glucose infusion, and glucose and insulin were measured at each sample point. The homeostatic model assessment (HOMA) index was calculated. Milk yield from days 30 to 40 and 64 to 90 of lactation were higher in SP cows than in SU cows. Basal glucose did not differ on days 30 and 60 of lactation, while basal insulin and HOMA were lower in SU compared to SP cows. On day 90 of lactation, SU cows had higher basal glucose, whereas basal insulin and HOMA did not differ. IVGTT results revealed that glucose tolerance was affected by heat stress such that SU cows had higher glucose clearance. Insulin responses to IVGTT did not differ on days 30 and 60 of lactation. Heat stress had a marked effect on insulin secretion on day 90 of lactation, illustrated by higher increments, peak concentrations and area under the curve for insulin in SU cows. Overall, season differences in glucose tolerance depend not only on heat stress and milk production but also on the stage of lactation.

Metabolic P (MP) systems are a part of the infobiotics research field. The intravenous glucose tolerance test (IVGTT) MP system models glucose-insulin interactions. MP system implementation in software is well researched, although there is a lack of techniques for hardware implementation, specifically with field programmable gate arrays. In this article the existing techniques are examined first, including combinative, single digital signal processor element, and pipelined. Then the specifics of six different IVGTT MP systems are analyzed. Having in mind these specifics, a new unified combinative IVGTT MP system implementation in field programmable gate arrays is proposed. Carried out experimental investigation results confirm, that the proposed unified system in comparison with single IVGTT MP systems, uses 36% less digital signal processor and 49% less look-up table resources of the field programmable gate arrays. Santrauka Metabolinė P (MP) sistema yra naujos infobiotikos mokslo srities dalis. Intraveninio gliukozės tolerancijos testo (IVGTT) MP sistema modeliuojama gliukozės ir insulino sąveika. MP sistemų įgyvendinimas programinėmis priemonėmis yra gerai ištirtas, tačiau trūksta MP sistemoms įgyvendinti aparatinėje įrangoje, konkrečiai – lauku programuojamose loginėse matricose (LPLM), skirtų metodų. Šiame straipsnyje iš pradžių aptariami taikytini žinomi įgyvendinimo būdai: kombinacinis, vieno skaitmeninio signalų apdorojimo elemento ir srautinis. Vėliau nagrinėjamos šešios skirtingos IVGTT MP sistemos ir nustatomi jų ypatumai. Atsižvelgiant į bendras IVGTT MP sistemų savybes, pasiūlomas naujas apibendrintas kombinacinis IVGTT MP sistemų įgyvendinimo būdas, kuris sujungia visas minėtas sistemas vienoje LPLM. Palyginus apibendrintą sistemą su atskiromis IVGTT MP sistemomis, nustatyta, kad apibendrinta sistema naudoja 36 % mažiau skaitmeninių signalų apdorojimo elementų ir 49 % mažiau peržvalgos lentelių visoms šešioms žinomoms IVGTT MP sistemoms apskaičiuoti. Reikšminiai žodžiai: lauku programuojama loginė matrica, metabolinė P sistema, infobiotika, intraveninis gliukozės tolerancijos testas, lygiagretieji skaičiavimai, fiksuoto kablelio aritmetika

Background: Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. Results: Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). Conclusions: The models are used to investigate how different degrees of pax'tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted. [ABSTRACT FROM AUTHOR]

Few studies have compared individual variability of an intravenous glucose tolerance test (ivGTT) obtained daily in young cattle. The objective of this study was to evaluate the repeatability of glucose traits and insulin responses derived from ivGTT during 3 consecutive days in Holstein-Friesian cattle (bulls: n = 4, steers: n = 3, heifers: n = 3). Blood collections were performed from min 0 (basal concentrations) to min 63 (last measurement). Additional estimates included maximal concentration for glucose and insulin, glucose half-life time (GHLT), and glucose and insulin area under the curve. Glucose traits showed higher repeatability when compared with insulin responses. On average, the glucose trait and insulin response with the lowest coefficient of variation was GHLT (0.7%) and insulin area under the curve (21.3%), respectively. In addition, a general linear model with repeated measures was used to test for significant differences in glucose and insulin concentrations over time at different trial days. Both glucose and insulin concentrations were influenced by time point but not by trial day or time point × trial day. The results from this study showed that individual insulin responses were more variable than glucose traits. The high repeatability of GHLT evidenced the strict regulatory glucose disposal mechanisms occurring in young Holstein-Friesian cattle, whereas insulin responses showed high variability despite controlled management and nutritional practices. [ABSTRACT FROM AUTHOR]

Background/Objective: Impaired fasting glycemia (IFG) reflects an intermediate hyperglycemia in the fasting state. Which fasting glucose level that actually is associated with impaired insulin‐glucose homeostasis in children and adolescents with obesity is unknown. The aim of this study was to investigate how insulin and glucose homeostasis in children and adolescents with obesity in Sweden varies within different fasting glucose levels in the non‐diabetic range. Subjects: The subjects, n = 333, were divided into three groups based on their fasting glucose level. Normoglycemic range: up to 5.5 mmol/L (n = 268); the exclusive range the American Diabetes Association (ADA) has for IFG diagnosis: 5.6‐6.0 mmol/L (n = 44); and IFG according to World Health Organization: 6.1‐6.9 mmol/L (n = 21). The three groups were of similar age, degree of obesity, fasting insulin levels, sex, and migrant background distribution. Methods: We used an insulin‐modified frequent sample intravenous glucose tolerance test to study acute insulin response (AIR), insulin sensitivity (SI), and disposition index (DI) in children and adolescents with obesity. The main outcome measures were AIR, SI, and DI in three groups based on fasting glucose level. Results: Fasting glucose levels ranging from 5.6 to 6.0 mmol/L were not associated with a lower AIR, SI, or DI compared with the normoglycemic range. However, glucose levels ranging from 6.1 to 6.9 mmol/L were associated with lower AIR and lower DI, but no statistical differences in SI were present. Conclusions: IFG in the exclusive ADA range was not associated with disturbed glucose metabolism. This suggests that IFG contributes to adverse metabolic profile in children differently to what has been described previously in adult obese populations. [ABSTRACT FROM AUTHOR]

Background: Management of diabetes remains a major health and economic challenge, demanding test systems in which to develop new therapies. These studies assessed different methodologies for determining glucose tolerance in green monkeys. Methods: Twenty‐eight African green monkeys between 4 and 24 years old underwent single or repeat intravenous glucose tolerance testing (IVGTT), oral glucose tolerance testing (OGTT), and/or graded glucose infusion testing. Results: Geriatric monkeys exhibited glucose intolerance with impaired glucose‐stimulated insulin secretion following IVGTT. Repeat IVGTT and OGTT assessments were inconsistent. Monkeys with low glucose‐stimulated insulin secretion after graded glucose infusion exhibited elevated blood glucose levels. Conclusion: IVGTT and graded glucose infusion protocols revealed differences in glucose tolerance among green monkeys at single time points, including age‐dependent differences suggestive of shifts in pancreatic beta‐cell functional capacity, but care should be applied to study design and the interpretation of data in the setting of longitudinal studies. [ABSTRACT FROM AUTHOR]

Metabolic P (MP) systems are a part of the infobiotics research field. The intravenous glucose tolerance test (IVGTT) MP system models glucose-insulin interactions. MP system implementation in software is well researched, although there is a lack of techniques for hardware implementation, specifically with field programmable gate arrays. In this article the existing techniques are examined first, including combinative, single digital signal processor element, and pipelined. Then the specifics of six different IVGTT MP systems are analyzed. Having in mind these specifics, a new unified combinative IVGTT MP system implementation in field programmable gate arrays is proposed. Carried out experimental investigation results confirm, that the proposed unified system in comparison with single IVGTT MP systems, uses 36% less digital signal processor and 49% less look-up table resources of the field programmable gate arrays. [ABSTRACT FROM AUTHOR]

Background: Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. Objective: The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. Design: We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group). Methods: The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous glucose-tolerance test before and after the intervention period. Results: Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (−29.3% to −1.0%) in comparison to −2.8% (−30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1 · min (350–1040mU· L-1 · min) to 671mU· L-1 · min (376–1010mU· L-1 · min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence. Conclusions: Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (DM) is the most common form of DM in cats and humans. The intravenous glucose tolerance test is the recommended method for evaluating glucose homeostasis in cats. However, the requirements for anesthesia and hospitalization have prevented the clinical application of this test. To evaluate the clinical applicability of the simplified intravenous glucose tolerance test (SIVGTT) with minor modifications for client-owned cats, 38 client-owned cats with variable body weight were collected. The cats were divided into obese and lean groups based on body weight and feline body mass index (FBMI). All the cats were fasted for 12h. The owners accompanied the cats for catheter placement and during the entire duration of the test. The cats were covered with towels, and their blood was drawn via an extension of a winged infusion set. Glucose and insulin concentrations were measured before glucose injection (1.0g/kg) and at 5, 10, 15, 30, 45, 60, 90 and 120 min after glucose administration for the modified SIVGGT. A complete evaluation was achieved in 32 of the 38 cats (84%) using the modified SIVGTT, and significant differences between obese and lean cats were detected. The results are, in similar to previous reports in which the cats were hospitalized and anesthetized. In addition, three glucose-intolerant cats were identified by the test. Taken together, the modified SIVGTT was proven to bed clinically applicable, and it could be recommended in the future for the evaluation of glucose homeostasis in cats. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary Aims To examine circulating betatrophin concentrations in subjects with different glucose tolerance status and to investigate the relationship between serum betatrophin levels and first-phase of glucose-stimulated insulin secretion. Methods Serum betatrophin concentrations were measured in 110 age- and sex-matched subjects: 47 newly diagnosed type 2 diabetes mellitus (T2DM), 29 impaired glucose tolerance (IGT) and 34 normal glucose tolerance (NGT). Oral glucose tolerance test and intravenous glucose tolerance test were performed to assess glucose tolerance and first-phase of glucose-stimulated insulin secretion. Results Serum betatrophin levels were significantly higher in the T2DM and IGT group than in the NGT group (2.10 ± 1.16 ng/mL vs 0.77 ± 0.44 ng/mL, 1.73 ± 1.28 ng/mL vs 0.77 ± 0.44 ng/mL; P < 0.01). The AIR and AUC among the three groups showed a progressive decrease from the NGT to IGT group with the lowest value in the T2DM group ( P < 0.01). Betatrophin were found to be positively correlated with BMI, waist circumference (WC), homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride (TG), and inversely associated with HDL-c (all P < 0.01), but not significantly correlated with 0–10 min insulin the area under the curve (AUC) and acute insulin response (AIR) ( P > 0.05). Stepwise multiple regression analysis showed that HOMA-IR and TG were independently related to betatrophin ( P < 0.05). Conclusion Serum betatrophin concentrations were higher in T2DM and IGT, and were closely related to glucolipid disorder, insulin resistance, but not related to the first-phase of glucose-stimulated insulin secretion. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the correlation between different surrogate indices and parameters of the intravenous glucose tolerance test (IVGTT) in dairy cows at the start of their lactation. Ten dairy cows underwent IVGTT on Days 3 to 7 after calving. Areas under the curve during the 90 min after infusion, peak and nadir concentrations, elimination rates, and times to reach half-maximal and basal concentrations for glucose, insulin, nonesterified fatty acids, and β-hydroxybutyrate were calculated. Surrogate indices were computed using the average of the IVGTT basal samples, and their correlation with the IVGTT parameters studied through the Spearman's rank test. No statistically significant or strong correlation coefficients ( P > 0.05; | ρ | < 0.50) were observed between the insulin sensitivity measures derived from the IVGTT and any of the surrogate indices. Therefore, these results support that the assessment of insulin sensitivity in early lactation cattle cannot rely on the calculation of surrogate indices in just a blood sample, and the more laborious tests (ie, hyperinsulinemic euglycemic clamp test or IVGTT) should be employed to predict the sensitivity of the peripheral tissues to insulin accurately. [ABSTRACT FROM AUTHOR]

Background: Liver cirrhosis is frequently complicated by portal hypertension leading to increased mortality from variceal bleeding and hepatic decompensation. Noncardioselective β-blockers not only reduce portal hypertension and prevent variceal bleeding in cirrhosis but also impair glucose tolerance and insulin sensitivity in other settings. This study aimed to determine whether nonselective β-blockade with nadolol impairs glucose metabolism in liver cirrhosis.Methods: A randomized, double-blind, placebo-controlled crossover trial of nadolol in cirrhotic patients examined insulin sensitivity, disposition index, and glucose tolerance. Stable cirrhotic patients of mixed etiology underwent an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp for the measurement of insulin secretion and insulin sensitivity (n = 16) and a 75-g oral glucose tolerance test (n = 17). These measurements were conducted twice (after 3 months of treatment with nadolol or placebo and, after a 1-month washout period, after 3 months on the alternative treatment). Total body fat and plasma catecholamines were measured at the end of each 3-month treatment.Results: Compared with placebo, nadolol treatment reduced insulin sensitivity (79.7 ± 10.1 vs 99.6 ± 10.3 μL/kg fat-free mass·min-1 ·(mU/L)-1 , P = .005). Insulin secretion was unchanged (P = .24), yielding a lower disposition index with nadolol (6083 ± 2007 vs 8692 ± 2036, P = .050). There was no change in total body fat or plasma catecholamines. A 2-hour plasma glucose concentration from the oral glucose tolerance test was higher on nadolol than placebo (10.8 ± 0.9 vs 9.9 ± 0.9 mmol/L, P = .035).Conclusions: Nadolol significantly worsened insulin sensitivity, glycemia, and disposition index in patients with liver cirrhosis. These findings may have significant clinical implications because cirrhosis is already associated with an increased prevalence of diabetes. [ABSTRACT FROM AUTHOR]

Aim. To characterize leptin secretion in fasting state and upon intravenous glucose administration in patients with type 2 diabetes mel- litus (T2DM), prediabetes and obesity. Materials and methods. 59 female patients took part in this study: 12 had no signs of glycemic disorder, 18 were diagnosed with prediabetes and 30 ? with newly diagnosed T2DM. Median age was 54 [48.6?60] years, median BMI ? 33.2 [29.0?37.2] kg/m2. All participants were tested for fasting leptin, fasting insulin and blood glucose levels. Prediabetic and diabetic subjects also received a bolus intravenous injection of 40% glucose solution (0.75 g/kg of body mass) with subsequent additional measurement of insulin levels at 2, 70 and 120 min upon injection, and leptin levels ? at 120 min. Results. Median fasting leptin in obese and patients with weight excess was 42.0 [22?60] ng/mL, which is about 2 times higher than normal reference maximum (27.6 ng/mL). Subjects with prediabetes and T2DM showed significantly lower median fasting leptin levels of 29.1 ng/mL [13.5?45.7] and 21.3 [14.3?42.2], respectively (p

Cows exposed to heat stress exhibit a decreased ability to mobilize lipids due to increased sensitivity to insulin, which is expressed in a decreased concentration of NEFA. However, certain cows can preserve the level of lipid mobilization after adapting to heat stress. We assumed that cows that have a preserved ability to mobilize lipids are less sensitive to insulin and that they have a lower tolerance for glucose. The aim of this work was to compare the results of an intravenous glucose tolerance test in cows that exhibited, in prolonged heat stress, a decreased (NEFA0.30 mmol/l) ability for lipid mobilization. Glucose concentration and NEFA concentration were measured following intravenous application of glucose. The mean glycaemic index value did not differ statistically significantly between the two groups of cows at 10, 15 and 20 minutes after glucose application (p>0.05), but there was a tendency at 10 and 15 minutes for the glycaemia to be higher in cows with preserved lipomobilization (p