Glucose Metabolism, Insulin Sensitivity and β-Cell Function in Type A Insulin Resistance Syndrome Around Puberty: A 9-Year Follow-up

2013 ◽  
Vol 46 (01) ◽  
pp. 65-72 ◽  
Author(s):  
Z. Huang ◽  
J. Liu ◽  
L. Ma ◽  
X. Wan ◽  
X. He ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Cell Function ◽  
Insulin Resistance Syndrome ◽  
Type A ◽  
Β Cell ◽  
Β Cell Function ◽  
Type A Insulin Resistance

scholarly journals Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4568-4568
Author(s):  
Ampaiwan Chuansumrit ◽  
Pimprae Pengpis ◽  
Pat Mahachoklertwattana ◽  
Nongnuch Sirachainan ◽  
Preamrudee Poomthavorn ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Cell Function ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Β Cell ◽  
Β Cell Function

Abstract Background: Increased intestinal iron absorption has been shown in non-transfusion-dependent thalassemia (NTDT) and thus results in mild to moderate iron excess. Therefore, these patients should theoretically have increased risks of pre-diabetes and diabetes. However, there have been no studies addressing insulin and glucose metabolism in these patients. We, therefore, hypothesize that NTDT with iron excess may have impaired β-cell function and reduced insulin sensitivity and their improvements may occur following iron chelation therapy. Objective: To assess insulin sensitivity and β-cell function in NTDT with iron excess pre- and post-iron chelation therapy. Study design: non-randomized open-labelled prospective cohort study Patients: Inclusion criteria: NTDT patients, aged older than 10 years who have had serum ferritin >300 ng/mL and/or transferrin saturation ≥70% and/or liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight. Exclusion criteria: Known case of type I or type II DM and taking medications affecting glucose metabolism or iron chelation therapy within one month prior to study. Methods: The complete patient histories were obtained and physical examinations were performed initially and at 3- and 6-month follow-up. Deferasirox at the dose of 10 mg/kg was prescribed daily to the studied patients for 6 months. Iron status indicators including serum ferritin, serum iron, total iron biding capacity (TIBC), transferrin saturation, non-transferrin-binding iron (NTBI) and hepcidin were determined pre- and 6-month post-chelation. For assessment of glucose metabolism, an oral glucose tolerance test (OGTT) and serum adiponectin were determined pre- and 6-month post-chelation. During an OGTT, serum insulin and plasma glucose at 0, 30, 60, 90 and 120 min were obtained. Insulin resistance, insulin sensitivity and β-cell function indices including homeostatic model assessment-insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI) and disposition index (WBISI x insulinogenic index), were calculated. Also, MRI of the heart, liver and pancreas were monitored pre- and 6-month post-chelation. Results: Ten patients (7 males) with a median age of 17.4 years enrolled in the study. Seven patients were b-thalassemia /Hb E disease of either b0 or b+ thalassemia genes and three patients were non-deletion type of Hb H disease with Hb Constant Spring or Hb Pakse. One of these three patients had additional Hb E resulting in AE Bart's disease. The severity of the thalassemia diseases was classified using a scoring system for b-thal/HbE revealing severe (n=1), moderate (n=6) and mild (n=3) degrees. For iron status indicators, the median pre-chelation serum ferritin was significantly higher than that of post-chelation (551.4 vs. 486.1 ng/mL, p=0.049). Also, the median pre-chelation TIBC was significantly lower than that of post-chelation (211.5 vs. 233.5 µg/dL, p=0.006). The median pre-chelation NTBI was higher than that of post-chelation (6.2 vs 4.0 µM, p =0.068) but no statistical significance. Also, the median pre-chelation hepcidin was lower than that of post-chelation but no statistical significance. For glucose metabolism, the median pre-chelation serum adiponectin was not different from that of post-chelation (46.41 vs. 48.77 ng/mL, p=0.508). All patients had normal glucose tolerance both pre- and post-chelation with no significant changes of body mass index during the 6-month period. However, there was a significant reduction of fasting plasma glucose after iron chelation (85.0 vs.79.5 mg/dL, p =0.045). In comparison between pre- and post-chelation, there were trends towards decreasing insulin resistance index expressed as HOMA-IR (0.8 vs. 0.2, p =0.219) and increasing insulin sensitivity indices expressed as WBISI (11.5 vs. 19.8, p =0.105). Also, there was a trend towards improving β-cell function expressed as disposition index (5.1 vs. 6.2, p=0.064). MRI revealed no significant changes of iron accumulation in liver, pancreas and myocardium following 6-month iron chelation therapy. No adverse effects following oral iron chelation therapy were detected. Conclusions: There was a trend towards improving insulin sensitivity and β-cell function following 6-month iron chelation therapy. Longer term of iron chelating agent treatment may demonstrate a significant beneficial effect on glucose metabolism. Disclosures No relevant conflicts of interest to declare.

scholarly journals Maternal taurine supplementation in rats partially prevents the adverse effects of early-life protein deprivation on β-cell function and insulin sensitivity

Reproduction ◽  
2013 ◽  
Vol 145 (6) ◽  
pp. 609-620 ◽  
Author(s):  
Christine Tang ◽  
Kelly Marchand ◽  
Loretta Lam ◽  
Victoria Lux-Lantos ◽  
Sandra M Thyssen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Control Diet ◽  
Adult Offspring ◽  
Β Cell ◽  
Rat Offspring ◽  
Β Cell Function

Dietary protein restriction during pregnancy and lactation in rats impairs β-cell function and mass in neonates and leads to glucose intolerance in adult offspring. Maternal taurine (Tau) supplementation during pregnancy in rats restores β-cell function and mass in neonates, but its long-term effects are unclear. The prevention of postnatal catch-up growth has been suggested to improve glucose tolerance in adult offspring of low-protein (LP)-fed mothers. The objective of this study was to examine the relative contribution of β-cell dysfunction and insulin resistance to impaired glucose tolerance in 130-day-old rat offspring of LP-fed mothers and the effects of maternal Tau supplementation on β-cell function and insulin resistance in these offspring. Pregnant rats were fed i) control, ii) LP, and iii) LP+Tau diets during gestation and lactation. Offspring were given a control diet following weaning. A fourth group consisting of offspring of LP-fed mothers, maintained on a LP diet following weaning, was also studied (LP-all life). Insulin sensitivity in the offspring of LP-fed mothers was reduced in females but not in males. In both genders, LP exposure decreased β-cell function. Tau supplementation improved insulin sensitivity in females and β-cell function in males. The LP-all life diet improved β-cell function in males. We conclude that i) maternal Tau supplementation has persistent effects on improving glucose metabolism (β-cell function and insulin sensitivity) in adult rat offspring of LP-fed mothers and ii) increasing the amount of protein in the diet of offspring adapted to a LP diet after weaning may impair glucose metabolism (β-cell function) in a gender-specific manner.

scholarly journals Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Tyg Index ◽  
Β Cell Function

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

scholarly journals Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients

2011 ◽  
Vol 106 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Pál Brasnyó ◽  
Gergő A. Molnár ◽  
Márton Mohás ◽  
Lajos Markó ◽  
Boglárka Laczy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Type 2 Diabetic Patients ◽  
Β Cell Function ◽  
Type 2 Diabetic

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.

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.

scholarly journals Antidepressant medication use and trajectories of fasting plasma glucose, glycated haemoglobin, β-cell function and insulin sensitivity: a 9-year longitudinal study of the D.E.S.I.R. cohort

2015 ◽  
Vol 44 (6) ◽  
pp. 1927-1940 ◽  
Author(s):  
Marine Azevedo Da Silva ◽  
Aline Dugravot ◽  
Beverley Balkau ◽  
Ronan Roussel ◽  
Frédéric Fumeron ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Cell Function ◽  
Glycated Haemoglobin ◽  
Β Cell ◽  
Fasting Plasma ◽  
Β Cell Function ◽  
Antidepressant Use

Abstract Background : Use of antidepressants is seen to be a risk factor for type 2 diabetes, even though the underlying mechanisms remain unclear. We examined whether antidepressant use was associated with change in fasting plasma glucose, glycated haemoglobin (HbA1c), β-cell function (HOMA2-%B) and insulin sensitivity (HOMA2-%S) over time. Methods : Participants in the French D.E.S.I.R. cohort study included over 4700 men (48.1%) and women, free of diabetes, aged 30–65 years at baseline in 1994–96 (D.E.S.I.R. 0), who were followed for 9 years at 3-yearly intervals (D.E.S.I.R. 3, 1997–99; 6, 2000–02; 9, 2003–05). Antidepressant use, fasting plasma glucose, HbA1c, HOMA2-%B and HOMA2-%S were assessed concurrently at four medical examinations. Linear mixed models were used to examine the cross-sectional and longitudinal associations of time-dependent antidepressant use with changes in these four biological parameters. Results : Mean fasting plasma glucose and HbA1c increased whereas HOMA2-%B and HOMA2-%S decreased over the follow-up. In a fully adjusted model, there were no differences in: mean fasting plasma glucose ( β  = 0.01 mmol/l, P  = 0.702); HbA1c ( β  = 0.01 %, P  = 0.738); HOMA2-%B ( β  = 0.00, P  = 0.812); or HOMA2-%S ( β  =−0.01, P  = 0.791) at baseline (1994–96) between antidepressant users and non-users. The interaction term with time also suggested no differences in the annual change in: fasting plasma glucose ( β  = 0.00 mmol/l, P  = 0.322); HbA1c ( β  = 0.00 %, P  = 0.496); HOMA2-%B ( β  = 0.00, P  = 0.609); or HOMA2-%S ( β  = 0.00, P  = 0.332) between antidepressant users and non-users. Similar associations were observed in analyses of type and cumulative use of antidepressants over follow-up. Conclusion : Our longitudinal data show that use of antidepressants is not associated with altered glucose metabolism, suggesting that the association between antidepressant use and diabetes reported by previous studies may not be causal. Detection bias or clinical ascertainment bias may account for much of this apparent association.

scholarly journals Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell Function

2020 ◽  
Vol 105 (7) ◽  
pp. e2408-e2420
Author(s):  
Uche Ezeh ◽  
Ida Y-D Chen ◽  
Yen-Hao Chen ◽  
Ricardo Azziz
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Dynamic State ◽  
Whole Body ◽  
Sensitivity Index ◽  
Β Cell ◽  
Nonesterified Fatty Acids ◽  
Glut 4 ◽  
Β Cell Function

Abstract Context Impaired sensitivity to the antilipolytic action of insulin in adipose tissue (AT) may play a role in determining metabolic dysfunction in polycystic ovary syndrome (PCOS). Objectives To test the hypothesis that insulin resistance (IR) in AT is associated with whole-body insulin sensitivity and β-cell function in PCOS. Research Design and Setting Prospective cross-sectional study. Methods Eighteen participants with PCOS and 18-matched control participants underwent a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT); subgroups underwent single-slice computed tomography scans determining AT distribution and adipocyte glucose transporter type 4 (GLUT-4) expression. Main Outcome Measures IR in AT in basal (by the adipose insulin resistance index [Adipo-IR]) and dynamic (mFSIVGTT-derived indices of insulin-mediated nonesterified fatty acids [NEFA] suppression [NEFAnadir, TIMEnadir, and %NEFAsupp]) states; whole-body insulin-mediated glucose uptake and insulin secretion in basal (by homeostatic model assessment [HOMA]-IR and HOMA-β%) and dynamic (mFSIVGTT-derived insulin sensitivity index [Si], acute insulin response to glucose [AIRg], and disposition index [Di]) states. Results Participants with PCOS had higher HOMA-IR and HOMA-β%, lower Si and Di, higher longer TIMEnadir, higher Adipo-IR and NEFAnadir, and a trend toward lower GLUT-4, than the control group participants. Adipo-IR was associated with dynamic state IR in AT (NEFAnadir TIMEnadir, and %NEFAsupp), but only in PCOS, and with HOMA-IR and HOMA-β% in both groups. NEFAnadir and TIMEnadir were negatively and %NEFAsupp positively associated with Si only in PCOS, but not with AIRg and Di, or GLUT-4 expression. Conclusion Women with PCOS demonstrated increased IR in AT, which is closely associated with whole-body IR but not with dynamic state β-cell function or adipocyte GLUT-4 gene expression.

scholarly journals Agreement and Reliability of Fasted and Oral Glucose Tolerance Test-Derived Indices of Insulin Sensitivity and Beta Cell Function in Boys

2017 ◽  
Vol 38 (06) ◽  
pp. 411-417 ◽  
Author(s):  
Emma Cockcroft ◽  
Craig Williams ◽  
Sarah Jackman ◽  
Neil Armstrong ◽  
Alan Barker
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function ◽  
Method Agreement

AbstractAssessment of plasma insulin and glucose outcomes is important in paediatric studies aimed at reducing future risk of type 2 diabetes and cardiovascular disease. The aims of this study are to determine the between-method agreement and the day-to-day reliability of fasting and oral glucose tolerance test (OGTT)-derived estimates of insulin sensitivity and β-cell function in healthy boys. Fasting and OGTT assesments of insulin resistance and β-cell function were performed on 28 boys (12.3±2.9 years). Measurements were repeated after 1 week (fasting, n=28) and 1 day (OGTT, n=8). Agreement between estimates of insulin resistance and β-cell function was examined using Pearson’s correlation coefficient. Reliability was assessed using change in the mean, Pearson’s correlation coefficient, and typical error expressed as a coefficient of variation (CV). The Matsuda index was positively related with QUICKI (r=0.88, P<0.001) and negatively related to HOMA-IR (r=−0.76, P<0.001). The Cederholm index was not significantly related with fasting estimates of insulin resistance (all r<0.40, P>0.05). For reliability, QUICKI had the lowest CV% for the fasting (4.7%) and the Cederholm index for the OGTT (6.4%) estimates. The largest CV% was observed in fasting insulin (30.8%) and insulinogenic index 30’ (62.5%). This study highlights differences in between-method agreement and day-to-day reliability for estimates of insulin resistance in youth. The low CV supports the use of the FGIR (fasting) and Cederholm (OGTT) indices in this population.

scholarly journals Early Detection of Insulin Sensitivity and β-Cell Function with Simple Tests Indicates Future Derangements in Late Pregnancy

2008 ◽  
Vol 93 (3) ◽  
pp. 876-880 ◽  
Author(s):  
A. Lapolla ◽  
M. G. Dalfrà ◽  
G. Mello ◽  
E. Parretti ◽  
R. Cioni ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Early Pregnancy ◽  
Cell Function ◽  
Late Pregnancy ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Β Cell ◽  
Β Cell Function

Abstract Objective: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). Research Design and Methods: The oral glucose tolerance test (OGTT) was performed in 903 women at 16–20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26–30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and β-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. Results: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower β-cell function than ND. During the late visit, GDM2 also showed impaired β-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. Conclusions: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. β-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.

Sign in / Sign up

Export Citation Format

Share Document