scholarly journals Impaired Insulin Secretion in the Turner Metabolic Syndrome

2004 ◽  
Vol 89 (7) ◽  
pp. 3516-3520 ◽  
Author(s):  
Vladimir K. Bakalov ◽  
Margaret M. Cooley ◽  
Michael J. Quon ◽  
Mei Lin Luo ◽  
Jack A. Yanovski ◽  
...  

Abstract An increased prevalence of impaired glucose homeostasis (IGH) and diabetes mellitus is reported in monosomy X, or Turner syndrome (TS). To determine whether IGH is an intrinsic feature of this syndrome, independent of obesity or hypogonadism, we compared results of a standard oral glucose challenge in age- and body mass index-matched women with TS and with karyotypically normal premature ovarian failure (POF). Fasting glucose levels were normal in both groups, but glucose values after oral glucose challenge were higher in TS [2-h glucose, 135 ± 36 mg/dl (7.5 ± 2.0 mmol/liter) in TS and 97 ± 18 mg/dl (5.4 ± 1.0 mmol/liter) in POF; P < 0.0001]. Glucose-stimulated insulin secretion was lower in TS; e.g. the initial insulin response (ΔI/ΔG30) was decreased by 60% compared with POF (P < 0.0001). We also compared responses to a standard iv glucose tolerance test in women with TS and in age- and body mass index-matched normal women and found that the insulin area under the curve was 50% lower in women with TS (P = 0.003). Insulin sensitivity measured by the quantitative insulin sensitivity check index was higher in women with TS compared with both control groups. Thus, IGH is not secondary to obesity or hypogonadism in TS, but it is a distinct entity characterized by decreased insulin secretion, suggesting that haploinsufficiency for X-chromosome gene(s) impairs β-cell function and predisposes to diabetes mellitus in TS.

Diabetes Care ◽  
2022 ◽  
Author(s):  
Marta Garaulet ◽  
Jesus Lopez-Minguez ◽  
Hassan S. Dashti ◽  
Céline Vetter ◽  
Antonio Miguel Hernández-Martínez ◽  
...  

OBJECTIVE We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes–associated G allele in the melatonin receptor-1b gene (MTNR1B). RESEARCH DESIGN AND METHODS In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime (“early dinner timing”) and a late condition scheduled 1 h prior to habitual bedtime (“late dinner timing”), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responsesbetween early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method. RESULTS Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. In the late condition, MTNR1B G-allele carriers had lower glucose tolerance than noncarriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint Disposition Index = 0.018). CONCLUSIONS Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects.


2020 ◽  
Vol 7 (2) ◽  
pp. 218
Author(s):  
Sambit Das ◽  
Mahesh Rath ◽  
Lipsa Das ◽  
Kasturi Bharadwaj

Background: Gestational Diabetes Mellitus (GDM) is usually diagnosed between 24th and 28th gestational week using the 75-g Oral Glucose Tolerance Test (OGTT). It is controversial that if FPG ≥92 mg/dL before 24th gestational week should be intervened or not. The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy Body Mass Index (BMI).Methods: This was a hospital based retrospective cohort study done at CHC Balipatna, Khurdha, Odisha. Women who had a singleton live birth between June 20, 2016 and June 30, 2019, resided in Balipatna block area and received prenatal care in the Community Health Centre, were included in this study. Pre-pregnancy BMI, FPG before the 24th gestational week, and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical records and analyzed. The pregnant women were classified into four groups based on pre-pregnancy BMI: Group A (underweight), Group B (normal), Group C (overweight) and Group D (obesity). Statistical analysis using independent sample t-test, Analysis of Variance (ANOVA) and Pearson Chi-square test was done.Results: The prevalence of GDM was 20.0% (68/341) in the study population. FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. The incidence of GDM in women with FPG ≥92 mg/dL in the 19th to 24th gestational weeks and pre-pregnancy overweight or obesity was significantly higher than that in women with FPG ≥92 mg/dL and pre-pregnancy BMI <24.0 kg/m2.Conclusions: FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. Pre-pregnancy overweight or obesity was associated with an increased FPG value before the 24th gestational week. FPG ≥92 mg/dL between 19 and 24 gestational weeks should be treated as GDM in women with pre-pregnancy overweight and obesity.


2008 ◽  
Vol 158 (5) ◽  
pp. 711-719 ◽  
Author(s):  
S Cupisti ◽  
N Kajaia ◽  
R Dittrich ◽  
H Duezenli ◽  
M W Beckmann ◽  
...  

BackgroundThe aim of this study was to evaluate associations of clinical features, such as hirsutism, polycystic ovaries (PCOs), ovulatory dysfunction, and body mass index (BMI) ≥25 kg/m2, with metabolic abnormalities in hyperandrogenic women.MethodsHirsutism was based on the modified Ferriman–Gallwey score. Ovulatory function was classified as eumenorrhea, oligomenorrhea and amenorrhea, and PCOs were assessed using the ultrasound criteria recommended in the Rotterdam definition. An oral glucose tolerance test was performed. Different insulin resistance (IR) indices were calculated.ResultsHirsute women had significantly higher BMI, DHEA sulfate (DHEAS) and free androgen index (FAI), and significantly lower values for sex hormone-binding globulin (SHBG). Women with amenorrhea were younger in comparison to women with eumenorrhea and had significantly higher values for fasting insulin (FI) and 1- and 2-h insulin levels; lower values for glucose to insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and SHBG. Women with PCO had significantly higher levels of LH and low-density lipoprotein (LDL), whereas high-density lipoprotein (HDL) levels were significantly lower. Women with a BMI ≥25 kg/m2 had significantly higher values for age, fasting plasma glucose, FI, and 1- and 2-h glucose and insulin levels, homeostatic model for assessment of IR (HOMA-IR), homeostatic model for assessment of B-cell function (HOMA-B), and FAI, whereas their GIR, insulin sensitivity index, QUICKI, SHBG, and HDL were significantly lower.ConclusionsIn women with hyperandrogenic syndrome, BMI≥25 kg/m2 and amenorrhea appear to be associated with severe endocrine and metabolic abnormalities.


2000 ◽  
Vol 278 (4) ◽  
pp. E700-E706 ◽  
Author(s):  
Daniel E. Flanagan ◽  
Vivienne M. Moore ◽  
Ian F. Godsland ◽  
Richard A. Cockington ◽  
Jeffrey S. Robinson ◽  
...  

Although there is now substantial evidence linking low birthweight with impaired glucose tolerance and type 2 diabetes in adult life, the extent to which reduced fetal growth is associated with impaired insulin sensitivity, defective insulin secretion, or a combination of both factors is not clear. We have therefore examined the relationships between birth size and both insulin sensitivity and insulin secretion as assessed by an intravenous glucose tolerance test with minimal model analysis in 163 men and women, aged 20 yr, born at term in Adelaide, South Australia. Birth size did not correlate with body mass index or fat distribution in men or women. Men who were lighter or shorter as babies were less insulin sensitive ( P = 0.03 and P = 0.01, respectively), independently of their body mass index or body fat distribution. They also had higher insulin secretion ( P = 0.007 and P = 0.006) and increased glucose effectiveness ( P = 0.003 and P = 0.003). Overall glucose tolerance, however, did not correlate with birth size, suggesting that the reduced insulin sensitivity was being compensated for by an increase in insulin secretion and insulin-independent glucose disposal. There were no relationships between birth size and insulin sensitivity or insulin secretion in women. These results show that small size at birth is associated with increased insulin resistance and hyperinsulinemia in young adult life but that these relationships are restricted to the male gender in this age group.


2014 ◽  
Vol 307 (9) ◽  
pp. E784-E792 ◽  
Author(s):  
Torsten P. ◽  
Benedikt A. Aulinger ◽  
Eric P. Smith ◽  
Deborah L. Drazen ◽  
Yve Ulrich-Lai ◽  
...  

Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. We hypothesized that enhanced activity of the enteroinsular axis mediates glucose homeostasis during MF. Cohorts of rats were allocated to MF or ad libitum (AL) regimens for 2–4 wk. Insulin secretion and glucose tolerance were determined after oral carbohydrate and intraperitoneal (ip) and intravenous (iv) glucose. MF rats ate less than AL in the first week but maintained a comparable weight trajectory thereafter. MF rats had decreased glucose excursions after a liquid mixed meal (AUC: MF 75 ± 7, AL 461 ± 28 mmol·l−1·min, P < 0.001), with left-shifted insulin secretion (AUC0–15: MF 31.0 ± 4.9, AL 9.6 ± 4.4 pM·min, P < 0.02), which peaked before a significant rise in blood glucose. Both groups had comparable fasting glucagon levels, but postprandial responses were lower with MF. However, neither intestinal expression of proGIP and proglucagon mRNA nor plasma incretin levels differed between MF and AL groups. There were no differences in the insulin response to ip or iv glucose between MF and AL rats. These findings demonstrate that MF improves oral glucose tolerance and is associated with significant changes in postprandial islet hormone secretion. Because MF enhanced β-cell function during oral but not parenteral carbohydrate administration, and was not accounted for by changes in circulating incretins, these results support a neural mechanism of adaptive insulin secretion.


2006 ◽  
Vol 91 (11) ◽  
pp. 4645-4649 ◽  
Author(s):  
Germán Iñiguez ◽  
Ken Ong ◽  
Rodrigo Bazaes ◽  
Alejandra Avila ◽  
Teresa Salazar ◽  
...  

Abstract Introduction: Insulin resistance (IR) develops as early as age 1 to 3 yr in small for gestational age (SGA) infants who show rapid catch-up postnatal weight gain. In contrast, greater insulin secretion is related to infancy height gains. We hypothesized that IGF-I levels could be differentially related to gains in length and weight and also differentially related to IR and insulin secretion. Methods: In a prospective study of 50 SGA (birth weight &lt; 5th percentile) and 14 normal birth weight [appropriate for gestational age (AGA)] newborns, we measured serum IGF-I levels at birth, 1 yr, and 3 yr. IR (by homeostasis model assessment) and insulin secretion (by short iv glucose tolerance test) were also measured at 1 yr and 3 yr. Results: SGA infants had similar mean length and weight at 3 yr compared with AGA infants. SGA infants had lower IGF-I levels at birth (P &lt; 0.0001), but conversely they had higher IGF-I levels at 3 yr (P = 0.003) than AGA infants. Within the SGA group, at 1 yr IGF-I was associated with length gain from birth and insulin secretion (P &lt; 0.0001); in contrast at 3 yr IGF-I was positively related to weight, body mass index, and IR. Conclusions: IGF-I levels increased rapidly from birth in SGA, but not AGA children. During the key first-year growth period, IGF-I levels were related to β-cell function and longitudinal growth. In contrast, by 3 yr, when catch-up growth was completed, IGF-I levels were related to body mass index and IR, and these higher IGF-I levels in SGA infants might indicate the presence of relative IGF-I resistance.


2007 ◽  
Vol 135 (7-8) ◽  
pp. 440-446 ◽  
Author(s):  
Biljana Beleslin ◽  
Jasmina Ciric ◽  
Milos Zarkovic ◽  
Zorana Penezic ◽  
Svetlana Vujovic ◽  
...  

Introduction Obesity is often accompanied by a number of complications including diabetes mellitus and cardiovascular diseases. Elevated blood pressure and lipids, as well as deterioration of glucoregulation are attributed, as the most significant factors, to development of diabetes mellitus and cardiovascular complications in obese patients. Objective The aim of our study was to evaluate the effects of a fasting diet on blood pressure, lipid profile and glucoregulatory parameters. Method We included 110 patients (33 male and 77 female; mean age 35?1 years, body weight 131.7?2.6 kg, body mass index 45.4?0.8 kg/m2) who were hospitalized for three weeks for the treatment of extreme obesity with the fasting diet. At the beginning, during, and at the end of this period, we evaluated changes in blood pressure, lipid profile, as well as parameters of glucoregulation including glycaemia, insulinaemia, and insulin sensitivity by HOMA. Oral glucose tolerance test (OGTT) was performed in all patients at the beginning and at the end of the fasting diet. Results During the fasting diet, the body weight decreased from 131.7?2.6 kg to 117.7?2.4 kg (p<0.001), the body mass index decreased from 45.4?0.8 kg/m2 to 40.8?0.8 kg/m2 (p<0.001), and both systolic and diastolic blood pressure significantly declined (143?2 vs. 132?2 mm Hg, p<0.001; 92?2 vs. 85?2 mm Hg, p<0.001). In addition, the fasting diet produced a significant decrease in total cholesterol, LDL cholesterol, triglycerides, as well as basal glycaemia and insulinaemia (p<0.001) Before the fasting diet, OGTT was normal in 76% of patients, whereas 21% of patients showed glucose intolerance, and 4% of patients diabetes mellitus. After the fasting diet, OGTT was normal in 88% of patients, whereas 12% of patients still had signs of glucose intolerance (p<0.05). In addition, insulin resistance significantly (p<0.05) increased from 54?6% to 89?13% after the fasting diet. Conclusion The three-week fasting diet in extremely obese patients produced a significant decrease and normalization of blood pressure, decrease in lipids, and improvement in glucoregulation including the increase in insulin sensitivity.


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