Genetic Polymorphisms of β-Cell Differentiation Confer Risk of Alterations of Glucose Metabolism in Survivors of Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1908-1908
Author(s):  
Pacharapan Surapolchai ◽  
Suradej Hongeng ◽  
Pat Mahachoklertwattana ◽  
Samart Pakakasama ◽  
Angkana Winaichatsak ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Lymphoblastic Leukemia ◽  
Β Cell ◽  
Childhood All ◽  
Β Cell Function

Abstract Purpose: Long-term survivors of acute lymphoblastic leukemia (ALL) seem to be at risk of insulin resistance, impaired glucose tolerance and may develop typical signs of metabolic syndrome with disturbances in lipid metabolism. The aim of the present study was to study the prevalence of alterations in glucose metabolism and the predisposing factors of these disturbances in survivors of childhood ALL. Furthermore, we intended to identify the role of such genetic polymorphisms affecting β-cell function and glucose metabolism and possibly to develop them as markers for monitoring β-cell dysfunction following treatment for ALL in the future. Patients and methods: In 131 ALL survivors after cessation of therapy, an oral glucose tolerance test was performed to determine β-cell function/insulin sensitivity. Six single-nucleotide polymorphisms of PAX4 and TCF7L2 genes were genotyped in order to evaluate the association between these polymorphisms and β-cell function/insulin sensitivity. Results: Ten out of 131 (7.6%) survivors had impaired glucose tolerance (IGT) while 40 out of 131 (30.5%) had insulin resistance (IR) and demonstrated characteristics of metabolic syndrome (hyperinsulinemia, hypertriglyceridemia, low HDL-C). In the logistic regression analysis, the most important factor predicting IGT and IR was older current age (p= 0.010 and <0.001, respectively) while the PAX4 R192H mutation (rs2233580) was significant associated only to IGT after adjusted for age (p=0.043) (adjusted OR 5.28, 95%CI 1.06–26.40). Conclusion: Our findings suggest that older age of childhood ALL survivors is the most important risk factor of IGT and IR, underlining the need to continue regular and long-term screening till adulthood. Moreover, after adjusted for age, the PAX4 R192H variant (rs2233580) seemed to be associated with IGT. If this association is confirmed, institution of lifestyle and therapeutic measures may be needed to reduce metabolic risk and diabetes.

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 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 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.

scholarly journals The Normal Glucose Tolerance Continuum in Obese Youth: Evidence for Impairment in β-Cell Function Independent of Insulin Resistance

2005 ◽  
Vol 90 (2) ◽  
pp. 747-754 ◽  
Author(s):  
Catherine W. Yeckel ◽  
Sara E. Taksali ◽  
James Dziura ◽  
Ram Weiss ◽  
Tania S. Burgert ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Normal Glucose Tolerance ◽  
Β Cell ◽  
Obese Youth ◽  
Normal Glucose ◽  
Β Cell Function
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