scholarly journals Determining insulin sensitivity from glucose tolerance tests in Iberian and landrace pigs

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11014
Author(s):  
José Miguel Rodríguez-López ◽  
Manuel Lachica ◽  
Lucrecia González-Valero ◽  
Ignacio Fernández-Fígares
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Early Stage ◽  
Insulin Response ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Glucose Infusion ◽  
Sensitivity Index ◽  
Post Infusion

As insulin sensitivity may help to explain divergences in growth and body composition between native and modern breeds, metabolic responses to glucose infusion were measured using an intra-arterial glucose tolerance test (IAGTT). Iberian (n = 4) and Landrace (n = 5) barrows (47.0 ± 1.2 kg body weight (BW)), fitted with a permanent carotid artery catheter were injected with glucose (500 mg/kg BW) and blood samples collected at -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120 and 180 min following glucose infusion. Plasma samples were analysed for insulin, glucose, lactate, triglycerides, cholesterol, creatinine, albumin and urea. Insulin sensitivity indices were calculated and analysed. Mean plasma glucose, creatinine and cholesterol concentrations were lower (P < 0.01) in Iberian (14, 68 and 22%, respectively) than in Landrace pigs during the IAGTT. However, mean plasma insulin, lactate, triglycerides and urea concentrations were greater (P < 0.001) in Iberian (50, 35, 18 and 23%, respectively) than in Landrace pigs. Iberian pigs had larger area under the curve (AUC) of insulin (P < 0.05) or tended to a greater AUC of lactate (P < 0.10), and a smaller (P < 0.05) AUC for glucose 0-60 min compared with Landrace pigs. Indices for estimating insulin sensitivity in fasting conditions indicated improved β-cell function in Iberian compared with Landrace pigs, but no difference (P > 0.10) in calculated insulin sensitivity index was found after IAGTT between breeds. A time response (P < 0.05) was obtained for insulin, glucose and lactate so that maximum concentration was achieved at 10 and 15 min post-infusion for insulin (Iberian and Landrace pigs, respectively), immediately post-infusion for glucose, and 20 min post-infusion for lactate, decreasing thereafter until basal levels. There was no time effect for the rest of metabolites evaluated. In conclusion, growing Iberian pigs challenged with an IAGTT showed changes in biochemical parameters and insulin response that may indicate an early stage of insulin resistance.

scholarly journals Determining insulin sensitivity from glucose tolerance tests in Iberian and Landrace pigs

2019 ◽  
Author(s):  
JM Rodríguez-López ◽  
M Lachica ◽  
L González-Valero ◽  
I Fernández-Fígares
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Early Stage ◽  
Insulin Response ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Glucose Infusion ◽  
Sensitivity Index ◽  
Post Infusion

ABSTRACTAs insulin sensitivity may help to explain divergences in growth and body composition between native and modern breeds, metabolic responses to glucose infusion were measured using an intra-arterial glucose tolerance test (IAGTT). Iberian (n = 4) and Landrace (n = 5) barrows (47.0 ± 1.2 kg BW), fitted with a permanent carotid artery catheter were injected with glucose (500 mg/kg BW) and blood samples collected at −10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120 and 180 min following glucose infusion. Plasma samples were analysed for insulin, glucose, lactate, triglycerides, cholesterol, creatinine, albumin and urea. Insulin sensitivity indices were calculated and analyed. Mean plasma glucose, creatinine and cholesterol concentrations were lower (P < 0.01) in Iberian (14, 68 and 22%, respectively) compared with Landrace pigs during the IAGTT. However, mean plasma insulin, lactate, triglycerides and urea concentrations were greater (P < 0.001) in Iberian (50, 35, 18 and 23%, respectively) than in Landrace pigs. Iberian pigs had larger area under the curve (AUC) of insulin (P < 0.05) and lactate (P < 0.1), and smaller (P < 0.05) AUC for glucose 0-60 min compared with Landrace pigs. Indices for estimating insulin sensitivity in fasting conditions indicated improved β-cell function in Iberian compared with Landrace pigs, but no difference (P > 0.10) in calculated insulin sensitivity index was found after IAGTT between breeds. A time response (P < 0.05) was obtained for insulin, glucose and lactate so that maximum concentration was achieved 10 and 15 min post-infusion for insulin (Iberian and Landrace pigs, respectively), immediately post-infusion for glucose, and 20 min post-infusion for lactate, decreasing thereafter until basal levels. There was no time effect for the rest of metabolites evaluated. In conclusion, growing Iberian pigs challenged with an IAGTT showed changes in biochemical parameters and insulin response that may indicate an early stage of insulin resistance.

Estimation of β-cell function from the data of the oral glucose tolerance test

2007 ◽  
Vol 292 (6) ◽  
pp. E1575-E1580 ◽  
Author(s):  
Shinji Sakaue ◽  
Shinji Ishimaru ◽  
Daisuke Ikeda ◽  
Yoshinori Ohtsuka ◽  
Toshiro Honda ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Β Cell ◽  
Β Cell Function ◽  
The Relationship

Although a hyperbolic relationship between insulin secretion and insulin sensitivity has been shown, the relationship has been often questioned. We examined the relationship using oral glucose tolerance test (OGTT)-derived indexes. A total of 374 Japanese subjects who had never been given a diagnosis of diabetes underwent a 75-g OGTT. In subjects with normal glucose tolerance (NGT), the ln [insulinogenic index (IGI)] was described by a linear function of ln ( x) ( x, insulin sensitivity index) in regression analysis when the reciprocal of the insulin resistance index in homeostasis model assessment, Matsuda's index, and oral glucose insulin sensitivity index were used as x. Because the 95% confidence interval of the slope of the regression line did not necessarily include −1, the relationships between IGI and x were not always hyperbolic, but power functions IGI × xα = a constant. We thought that IGI × xα was an appropriate β-cell function estimate adjusted by insulin sensitivity and referred to it as β-cell function index (BI). When Matsuda's index was employed as x, the BI values were decreased in subjects without NGT. Log BI had a better correlation with fasting plasma glucose (PG; FPG) and 2-h PG in non-NGT subjects than in NGT subjects. In subjects with any glucose tolerance, log BI was linearly correlated with 1-h PG and glucose spike (the difference between maximum PG and FPG). In conclusion, the relationship between insulin secretion and insulin sensitivity was not always hyperbolic. The BI is a useful tool in the estimation of β-cell function with a mathematical basis.

scholarly journals First-phase insulin response (FPIR) to intravenous glucose tolerance test (IVGTT), insulin sensitivity and long-term follow-up in ?- transfusion-dependent thalassemia (TDT) normoglycemic patients with reduced insulin secretion to oral glucose tolerance t

2021 ◽  
Vol 13 (1) ◽  
pp. e2021021
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Intravenous Glucose

Summary. Objective: To  study the function of the endocrine pancreas in transfusion-dependent ?-thalassemia (?-TDT) patients with normal oral glucose tolerance test (OGTT) and hypoinsulinemia. Patients and methods: Seven ?-TDT patients  (mean age 22.4 ± 4.2 years) with normal glucose tolerance test (NGT) and poor insulin response (hypoinsulinemia) to OGTT,  not associated with ?-cell autoimmunity, were referred for a second opinion to an Italian Centre, part of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). In this pilot study,  the first-phase insulin response (FPIR), expressed as the sum of 1 and  3 minutes insulin, of ?-TDT patients to intravenous glucose tolerance test (IVGTT), was tested. Moreover, the long-term natural history was followed prospectively using an annual OGTT, with the aim of detecting any abnormality of glucose metabolism. Results: The FPIR value  was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in  five. After 43 ± 26 months (range 11 - 80 months) of follow-up, 2 patients developed impaired glucose tolerance (IGT), 3 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 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 diagnosis of IFG, IGT and DM. There was a significant inverse correlation between ISSI-2 and area under the curve of plasma glucose (AUC-PG). Conclusions: These data demonstrated, for the first time, a progressive deterioration in glucose homeostasis in ?-TDT subjects with NGT and hypoinsulinemia.  Thus, we consider that variations of insulin sensitivity could possibly have an impact on glucose tolerance in adult patients with TDT. Further investigations should focus on factors that might positively influence insulin sensitivity, including nutrition, drugs and physical activity.  

scholarly journals Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults1

1998 ◽  
Vol 83 (6) ◽  
pp. 1911-1915 ◽  
Author(s):  
Ramin Alemzadeh ◽  
Gina Langley ◽  
Lori Upchurch ◽  
Pam Smith ◽  
Alfred E. Slonim
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Zucker Rats ◽  
Significant Difference

Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) &gt; 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean ± se for age and BMI, 31 ± 1 and 40 ± 2, respectively) received DZ (2 mg/kg BW·day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean± se for age and BMI, 28 ± 1 and 43 ± 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P &lt; 0.001), greater decrease in body fat (P &lt; 0.01), greater increase in fat-free mass to body fat ratio (P &lt; 0.01), and greater attenuation of acute insulin response to glucose (P &lt; 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified iv glucose tolerance test (Bergman’s minimal model) and no significant difference in glycohemoglobin values. Conclusion: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

scholarly journals Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1–Mediated Mechanism

2019 ◽  
Vol 104 (8) ◽  
pp. 3481-3490 ◽  
Author(s):  
Alfonso Galderisi ◽  
Cosimo Giannini ◽  
Michelle Van Name ◽  
Sonia Caprio
Keyword(s):  
Glucose Tolerance ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Cell Function ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Double Blind ◽  
Obesity And Diabetes ◽  
Glucose Ingestion

Abstract Context The consumption of high-fructose beverages is associated with a higher risk for obesity and diabetes. Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect. Objective We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity. Design We studied 14 lean adolescents [four females; 15.9 ± 1.6 years of age; body mass index (BMI), 21.8 ± 2.2 kg/m2] and 23 adolescents with obesity (five females; 15.1 ± 1.6 years of age; BMI, 34.5 ± 4.6 kg/m2). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and β-cell function [oral disposition index (oDIcpep)]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDIcpep was evaluated by regression analysis. Results Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P &lt; 0.001) and GLP-1 (P &lt; 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P &lt; 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDIcpep (r2 = 0.22, P = 0.009). Conclusion Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1–mediated mechanism.

scholarly journals Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Carolina Bravo ◽  
Luis Rodrigo Cataldo ◽  
José Galgani ◽  
Javier Parada ◽  
José Luis Santos
Keyword(s):  
Molecular Weight ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
High Molecular Weight ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Sensitivity Index ◽  
High Molecular Weight Adiponectin ◽  
Intravenous Glucose ◽  
Negatively Associated

Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m2). LAR was negatively associated with HOMA-S (r=−0.49; p<0.0001), Matsuda-ISICOMP (r=−0.54; p<0.0001), and the calculated sensitivity index (CSi) derived from IVGTT (r=−0.38; p=0.007). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit (r2) nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regression). The discriminatory capacity of both ratios to classify insulin-resistant versus insulin-sensitive subjects was similar for HOMA-S (p=0.84), Matsuda-ISICOMP (p=0.43), or CSi (p=0.50). In conclusion, LAR showed consistent negative associations with different systemic insulin sensitivity indexes. The use of HMWA to generate leptin/HMWA ratio did not show any advantage over LAR as a biomarker of systemic insulin sensitivity in normoglycemic women.

scholarly journals Validation of Insulin Sensitivity Indices from Oral Glucose Tolerance Test Parameters in Obese Children and Adolescents

2004 ◽  
Vol 89 (3) ◽  
pp. 1096-1101 ◽  
Author(s):  
Catherine W. Yeckel ◽  
Ram Weiss ◽  
James Dziura ◽  
Sara E. Taksali ◽  
Sylvie Dufour ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Intramyocellular Lipid ◽  
Insulin Sensitivity Index ◽  
Obese Youth ◽  
Intramyocellular Lipid Content

Abstract Given the extreme increase in prediabetes, type 2 diabetes, and the potential for metabolic syndrome in obese youth, identifying simplified indexes for assessing stimulated insulin sensitivity is critical. The purpose of this study was validation of two surrogate indexes of insulin sensitivity determined from the oral glucose tolerance test (OGTT): the composite whole body insulin sensitivity index (WBISI) and the insulin sensitivity index (ISI). An obese population (aged 8–18 yr) of normal and impaired glucose tolerance individuals was studied. One group (n = 38) performed both the euglycemic-hyperinsulinemic clamp and OGTT for comparison of insulin sensitivity measurements as well as 1H-magnetic resonance spectroscopy estimates of intramyocellular lipid content. Another larger (n = 368) cohort participated only in an OGTT. Both the WBISI and ISI represented good estimates (r = 0.78 and 0.74; P &lt; 0.0005) for clamp-derived insulin sensitivity (glucose disposed, M-value), respectively. In the large cohort, the surrogate indexes demonstrated the shift toward poorer function and increased risk profile as a function of insulin resistance. Additionally, the WBISI and ISI correlated with intramyocellular lipid content (r = −0.74 and −0.71; P &lt; 0.0001), a tissue marker for insulin resistance. Insulin sensitivity can be estimated using plasma glucose and insulin responses derived from the OGTT in obese youth with normal and impaired glucose tolerance.

Association between Genetic Polymorphisms of β-Cell Differentiation Genes and Insulin Resistance (β-Cell Dysfunction) in Childhood Acute Lymphoblastic Leukemia (ALL) Survivors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4281-4281
Author(s):  
Pacharapan Surapolchai ◽  
Suradej Hongeng ◽  
Samart Pakakasama ◽  
Pat Mahachoklertwattana ◽  
Angkana Winaichatsak ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Sensitivity Index ◽  
Insulin Sensitivity Index ◽  
Β Cell ◽  
Childhood All ◽  
Cell Dysfunction ◽  
Β Cell Function

Abstract Background: The purposes of the study were to determine β-cell function and insulin sensitivity after ALL therapy cessation and the association between genetic polymorphisms of β-cell differentiation genes, TCF7L2 and PAX4, with insulin resistance (β-cell dysfunction) in childhood ALL survivors. Methods: Childhood ALL patients diagnosed during 1997–2004 finished the treatment for at least 6 months. The oral glucose tolerance test and lipid screening were performed. Impaired glucose tolerance and diabetes mellitus (DM) were defined according to WHO criteria. β-cell function was estimated by homeostasis model assessment β-cell (HOMA β-cell) and insulinogenic index (IGI) and insulin sensitivity was estimated by whole body insulin sensitivity index (WBISI). The polymorphisms of TCF7L2 (rs12255372 and rs7903146) and PAX4 (A1186C) were genotyped and assessed for the association between these polymorphisms and the β-cell function and the insulin sensitivity. Results: 126 patients were studied (52 females, 74 males and age at the time of study; 4–20 yrs). 116 patients (92%) had normal glucose tolerance (NGT) while the others 10 patients (8%) had impaired glucose tolerance (IGT). Comparing between IGT and NGT groups respectively, we found statistically significant differences in age at the diagnosis (7.5 and 5.2 yrs, p=0.041), age at the study (14 and 10.3 yrs, p=0.001), the duration of post ALL therapy cessation (43 and 26 months, p=0.015), and insulin sensitivity index (WBISI) (5.75 and 9.52, p<0.001). HOMA β-cell and IGI were not different between NGT and IGT group (190.8 and 139.5, p=0.332; 23.6 and 15.8, p=0.310, respectively). Moreover, 32 of 126 patients (25%) had insulin resistance (modified from the criteria of WBISI in obese children and adolescents). These 32 patients who had insulin resistance demonstrated significant pictures of metabolic syndrome i.e. hypertriglyceridemia (116.6 and 85.4 mg/dL, p=0.036), low HDL-C (43.0 and 48.3 mg/dL, p=0.015), obesity (BMI SDS 1.03 and 0.38, p=0.044) and were also older age at the study (12.8 and 9.9 yrs, p<0.001). The genotype frequencies and allele frequencies of polymorphisms of TCF7L2 and PAX4 genes between IGT and NGT groups and between insulin resistance and nonresistance were not difference (p>0.05). Conclusion: The childhood ALL survivors who had IGT were associated with the longer duration of ALL therapy cessation, the older age at diagnosis and at the time of study, and insulin resistance while β-cell function was still relatively preserved. Long-term childhood ALL survivors have potential risks of IGT, insulin resistance and metabolic syndrome. Our findings with such small representatives are not yet applicable to associate TCF7L2 and PAX4 polymorphisms with the insulin resistance (β-cell dysfunction) in the childhood ALL survivors.

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