scholarly journals Syndromic Obesity and Diabetes: Changes in Body Composition with Age and Mutation Analysis of ALMS1 in 12 United Kingdom Kindreds with Alström Syndrome

2006 ◽  
Vol 91 (8) ◽  
pp. 3110-3116 ◽  
Author(s):  
J. A. L. Minton ◽  
K. R. Owen ◽  
C. J. Ricketts ◽  
N. Crabtree ◽  
G. Shaikh ◽  
...  

Abstract Context: Alström syndrome (AS) is a monogenic form of infancy-onset obesity and insulin resistance, caused by ALMS1 mutations. The natural history of the insulin resistance is unknown, in particular how this relates to changes in body composition. It is also unclear how ALMS1 mutations relate to the characteristic phenotype. Objectives: Our objectives were to characterize body composition and metabolic parameters, to establish ALMS1 mutation spectrum of United Kingdom AS patients, and to determine whether a genotype-phenotype correlation exists. Design and Patients: We conducted a cross-sectional cohort study of 12 unrelated subjects with AS. Age-standardized body composition was assessed by anthropometry and dual-energy x-ray absorptiometry and insulin sensitivity by homeostasis model assessment. The exons and intron-exon boundaries of ALMS1 were directly sequenced. Setting: The study was performed during the annual Alström Syndrome UK multidisciplinary screening clinic. Results: AS patients have early-onset obesity, but body mass index, waist circumference, and body fat from dual-energy x-ray absorptiometry were negatively correlated with age (r = −0.37, P = 0.2; r = −0.84, P = 0.002; and r = −0.6, P = 0.05). Despite this, insulin resistance increased, demonstrated by raised fasting insulin and fall in homeostasis model assessment insulin sensitivity with age (r = −0.64, P = 0.02). ALMS1 mutations were identified in 10 of 12 patients, with a potential founder mutation in exon 16 present in five [np 10775del (C); Del3592fs/ter3597]. No genotype-phenotype correlation was observed. Conclusions: We identified mutations in ALMS1 in more than 80% of patients with no genotype-phenotype correlation. In AS, severe childhood obesity, waist circumference, and body fat decrease with age, whereas insulin resistance increases. The abdominal obesity, insulin resistance, diabetes, hypertriglyceridemia, and hypertension suggest that AS could represent a monogenic model for the metabolic syndrome.

2007 ◽  
Vol 92 (11) ◽  
pp. 4230-4235 ◽  
Author(s):  
Lana M. Bell ◽  
Katie Watts ◽  
Aris Siafarikas ◽  
Alisha Thompson ◽  
Nirubasini Ratnam ◽  
...  

Abstract Context: The number of obese children with insulin resistance and type 2 diabetes is increasing, but the best management strategy is not clear. Objective: The objective of this study was to assess the effect of a structured 8-wk exercise training program on insulin resistance and changes in body composition in obese children. Design: The study was 8 wk of structured supervised exercise intervention with outcome measures before and after the exercise period. Subjects: Fourteen obese children (12.70 ± 2.32 yr; eight male, six female) with high fasting insulin levels were enrolled into the study. Intervention: Intervention consisted of 8 wk of supervised circuit-based exercise training, composed of three fully supervised 1-h sessions per week. Outcome Measures: Outcome measures were assessed pretraining program and posttraining program and included insulin sensitivity (euglycemic-hyperinsulinemic clamp studies), fasting insulin and glucose levels, body composition using dual energy x-ray absorptiometry scan, lipid profile, and liver function tests. Results: Insulin sensitivity improved significantly after 8 wk of training (Mlbm 8.20 ± 3.44 to 10.03 ± 4.33 mg/kg·min, P < 0.05). Submaximal exercise heart rate responses were significantly lower following the training (P < 0.05), indicating an improvement in cardiorespiratory fitness. Dual energy x-ray absorptiometry scans revealed no differences in lean body mass or abdominal fat mass. Conclusion: An 8-wk exercise training program increases insulin sensitivity in obese children, and this improvement occurred in the presence of increased cardiorespiratory fitness but is independent of measurable changes in body composition.


2021 ◽  
pp. 1-9
Author(s):  
Narges Ghorbani Bavani ◽  
Parvane Saneei ◽  
Ammar Hassanzadeh Keshteli ◽  
Ahmadreza Yazdannik ◽  
Ebrahim Falahi ◽  
...  

Abstract Objective: We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women. Design: A cross-sectional study. Setting: Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI). Participants: Iranian female nurses (n 345) selected by a multistage cluster random sampling method. Results: The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers. Conclusions: Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.


2012 ◽  
Vol 51 (16) ◽  
pp. 2119-2124 ◽  
Author(s):  
Fumihiko Kamezaki ◽  
Shinjo Sonoda ◽  
Sei Nakata ◽  
Kuninobu Kashiyama ◽  
Yoshitaka Muraoka ◽  
...  

2013 ◽  
Vol 60 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Kohei Okita ◽  
Hiromi Iwahashi ◽  
Junji Kozawa ◽  
Yukiyoshi Okauchi ◽  
Tohru Funahashi ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
pp. 41
Author(s):  
Hwi Seung Kim ◽  
Yun Kyung Cho ◽  
Eun Hee Kim ◽  
Min Jung Lee ◽  
Chang Hee Jung ◽  
...  

The triglyceride glucose (TyG) index has been suggested as a marker for insulin resistance; however, few studies have investigated the clinical implications of markers that combine obesity markers with the TyG index. This study aimed to investigate the associations between non-alcoholic fatty liver disease (NAFLD) and TyG-related markers in healthy subjects in Korea. We enrolled 21,001 asymptomatic participants who underwent hepatic ultrasonography. The homeostasis model assessment of insulin resistance (HOMA-IR), TyG index, TyG-body mass index, and TyG-waist circumference (WC) were subsequently analyzed. NAFLD was diagnosed using hepatic ultrasonography. A multiple logistic regression analysis was performed to evaluate the associations between the quartiles of each parameter and the risk of NAFLD. The increase in the NAFLD risk was most evident when the TyG-WC quartiles were applied; the multivariate-adjusted odds ratios for NAFLD were 4.72 (3.65–6.10), 13.28 (10.23–17.24), and 41.57 (31.66–54.59) in the 2nd, 3rd, and 4th TyG-WC quartiles, respectively, when compared with the lowest quartile. The predictability of the TyG-WC for NAFLD was better than that of the HOMA-IR using the area under the curve. The TyG-WC index was superior to the HOMA-IR for identifying NAFLD in healthy Korean adults, especially in the non-obese population.


2006 ◽  
Vol 91 (9) ◽  
pp. 3287-3295 ◽  
Author(s):  
Richard M. Martin ◽  
Jeff M. P. Holly ◽  
George Davey Smith ◽  
David Gunnell

Abstract Context: One metabolic pathway through which adiposity influences disease risk may be via alterations in insulin and IGF metabolism. Objective: Our objective was to investigate associations of adiposity at different stages of life with insulin and the IGF system. Design, Setting, and Participants: The study was a 65-yr follow-up of 728 Boyd Orr cohort participants (mean age, 71 yr) originally surveyed between 1937 and 1939. Main Outcomes: Outcomes included homeostasis model assessment of insulin resistance, total IGF-I and IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood. Results: Childhood body mass index (BMI) was weakly inversely related to adult IGF-I (coefficient per BMI sd, −3.4 ng/ml; 95% confidence interval, −7.3 to 0.5; P = 0.09). IGF-II (but not IGF-I) increased with higher current fat mass index (coefficient, 26.1 ng/ml; 95% confidence interval, 4.6 to 47.6; P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4 to 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2 to 24.9; P < 0.001), and homeostasis model assessment of insulin resistance increased by 38.8% (28.9 to 49.6; P < 0.001) per sd higher adult BMI. Among thin adults (BMI tertiles 1 and 2), IGFBP-2 was positively, and insulin resistance was inversely, associated with childhood BMI. Conclusion: There was only weak evidence that associations of childhood BMI with chronic disease risk may be mediated by adult IGF-I levels. Circulating IGFBP-2 in adulthood, a marker for insulin sensitivity, was inversely associated with current adiposity, but overweight children who became relatively lean adults were more insulin sensitive than thinner children. The findings may indicate programming of later insulin sensitivity and consequently IGFBP-2 levels in response to childhood adiposity. The role of IGF-II in obesity-related chronic diseases warrants additional investigation.


2020 ◽  
Vol 9 (6) ◽  
pp. 1732
Author(s):  
Francisco Campillo-Sánchez ◽  
Ricardo Usategui-Martín ◽  
Ángela Ruiz -de Temiño ◽  
Judith Gil ◽  
Marta Ruiz-Mambrilla ◽  
...  

Background: Insulin may play a key role in bone metabolism, where the anabolic effect predominates. This study aims to analyze the relationship between insulin resistance and bone quality using the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in non-diabetic postmenopausal women by determining cortical and trabecular compartments. Methods: A cross-sectional study was conducted in non-diabetic postmenopausal women with suspected or diagnosed osteoporosis. The inclusion criteria were no menstruation for more than 12 months and low bone mass or osteoporosis as defined by DXA. Glucose was calculated using a Hitachi 917 auto-analyzer. Insulin was determined using an enzyme-linked immunosorbent assay (EIA). Insulin resistance was estimated using a homeostasis model assessment of insulin resistance (HOMA-IR). DXA, 3D-DXA, and TBS were thus collected. Moreover, we examined bone parameters according to quartile of insulin, hemoglobin A1C (HbA1c), and HOMA-IR. Results: In this study, we included 381 postmenopausal women. Women located in quartile 4 (Q4) of HOMA-IR had higher values of volumetric bone mineral density (vBMD) but not TBS. The increase was higher in the trabecular compartment (16.4%) than in the cortical compartment (6.4%). Similar results were obtained for insulin. Analysis of the quartiles by HbA1c showed no differences in densitometry values, however women in Q4 had lower levels of TBS. After adjusting for BMI, statistical significance was maintained for TBS, insulin, HOMA-IR, and HbA1c. Conclusions: In non-diabetic postmenopausal women there was a direct relationship between insulin resistance and vBMD, whose effect is directly related to greater weight. TBS had an inverse relationship with HbA1c, insulin, and insulin resistance unrelated to weight. This might be explained by the formation of advanced glycosylation products (AGEs) in the bone matrix, which reduces bone deformation capacity and resistance, as well as increases fragility.


2007 ◽  
Vol 92 (5) ◽  
pp. 1843-1847 ◽  
Author(s):  
Dalit Modan-Moses ◽  
Daniel Stein ◽  
Clara Pariente ◽  
Amit Yaroslavsky ◽  
Anka Ram ◽  
...  

Abstract Context: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. Objective: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters. Design, Setting, and Participants: We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight). Main Outcome Measures: Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured. Results: At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T4 or cortisol levels. Conclusions: Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 350-351
Author(s):  
Hector H Salgado ◽  
Aline Remus ◽  
Marie-Pierre Letourneau-Montminy ◽  
Candido Pomar

Abstract Growing pigs’ body composition variation can be associated with differences in insulin sensitivity given the insulin anabolic effect on protein and lipid synthesis. The objective of this study was to elucidate this association by relating the individual insulin response to the oral glucose tolerance test (OGTT) with the body composition of growing pigs. Thirty 95 kg jugular vein catheterized pigs received an oral dose of 1.75 g of glucose/kg of BW after 18 hours of fasting. Blood samples were collected at -20, -10, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300 and 360 min following glucose ingestion. Insulin sensitivity indexes were calculated and analyzed. Body lipids (LB, %) and protein (PB, %) composition were estimated by dual X-ray densitometry. Association between body composition and insulin sensitivity were studied by using partial least squares and correlations. Average LB and PB were 19.7% (CV = 7.6 %) and 16.2% (CV = 2.2%), respectively. Basal insulin blood concentration and area-under-the-curve (AUC) CV (51.9 % and 26.9 %, respectively) were larger than those for basal glucose and AUC (5.52 and 5.48 %, respectively). Additionally, insulin sensitivity (%S), steady-state beta cell function (%B), and insulin resistance (HOMA-IR) estimated with the Homeostasis Model Assessment (HOMA 2) and whole-body insulin sensitivity index (ISI) were highly variable between pigs which CV ranged from 30.1 % to 54.5 %. These results can indicate an early stage of insulin resistance in an important part of the studied pig population. LB and PB were affected by insulin sensitivity indexes (P < 0.05) which accounted, respectively, for 48% and 44% of the observed variation. In conclusion, lower insulin sensitivity was associated with higher body fat in growing pigs raised under similar conditions.


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