Analysis of candidate genes in Polish families with obesity

2004 ◽  
Vol 42 (5) ◽  
Author(s):  
Malgorzata Malczewska-Malec ◽  
Iwona Wybranska ◽  
Iwona Leszczynska-Golabek ◽  
Lukasz Partyka ◽  
Jadwiga Hartwich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Tolerance Test ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
The Metabolic Syndrome

AbstractThis study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γThe 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated.The single gene mutations such as CWe conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

scholarly journals PSVIII-40 Late-Breaking Abstract: Variability in body composition is associated with insulin sensitivity in growing-finishing pigs

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 350-351
Author(s):  
Hector H Salgado ◽  
Aline Remus ◽  
Marie-Pierre Letourneau-Montminy ◽  
Candido Pomar
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Growing Pigs ◽  
The Body ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Glucose Ingestion

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.

scholarly journals Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function

2020 ◽  
Vol 318 (3) ◽  
pp. E381-E391 ◽  
Author(s):  
Julie Lacombe ◽  
Omar Al Rifai ◽  
Lorraine Loter ◽  
Thomas Moran ◽  
Anne-Frédérique Turcotte ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Cell Function ◽  
Fasting Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Β Cell

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes ( n = 132), ucOCN correlated negatively with fasting glucose (r = −0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = −0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity ( n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = −0.50, P = 0.046) and glycated hemoglobin (r = −0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp ( P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and β-cell dysfunction in humans.

scholarly journals Modification and Validation of the Triglyceride-to–HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE)

2016 ◽  
Vol 62 (9) ◽  
pp. 1211-1219 ◽  
Author(s):  
Katharina Paulmichl ◽  
Mensud Hatunic ◽  
Kurt Højlund ◽  
Aleksandra Jotic ◽  
Michael Krebs ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Single Point ◽  
Hdl Cholesterol ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Blood Draw ◽  
Sensitivity Indices

Abstract BACKGROUND The triglyceride-to–HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ2 test. RESULTS The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C0.185/(TG0.2 × BMI1.338), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m2). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg−1 · min−1 (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment–insulin resistance) when calculated with M-values. CONCLUSIONS The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults.

scholarly journals A Chinese Herbal Decoction, Dang Gui Bu Xue Tang, Prepared from Radix Astragali and RadixAngelicae sinensis, Ameliorates Insulin Resistance Induced by A High-Fructose Diet in Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
I-Min Liu ◽  
Thing-Fong Tzeng ◽  
Shorong-Shii Liou
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Oral Administration ◽  
Glucose Transporter ◽  
Plasma Lipid ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Radix Astragali

Dang Gui Bu Xue Tang (DBT), a Chinese medicinal decoction contains RadixAngelicae sinensis(Danggui) and Radix Astragali (Huangqi) at a ratio of 1 : 5, is used commonly for treating women's ailments. This study was conducted to explore the effects of this preparation on insulin resistance in rats fed with 6-week diet containing 60% fructose. Similar to the action of rosiglitazone (4 mg kg-1per day by an oral administration), repeated oral administration of DBT (2.5 g kg-1per day) for 14 days was found to significantly alleviate the hyperglycemia but made no influence on plasma lipid profiles nor weight gain in fructose chow-fed rats. Also, the higher degree of insulin resistance as measured by homeostasis model assessment of basal insulin resistance in fructose chow-fed rats was significantly decreased by repeated DBT treatment. DBT displays the characteristic of rosiglitazone by increasing the whole-body insulin sensitivity in fructose chow-fed rats after 2-week treatment, as evidenced by the marked elevation of composite whole-body insulin sensitivity index during the oral glucose tolerance test. DBT improves insulin sensitivity through increased post-receptor insulin signaling mediated by enhancements in insulin receptor substrate-1-associated phosphatidylinositol 3-kinase step and glucose transporter subtype 4 translocation in soleus muscles of animals exhibiting insulin resistance. DBT is therefore proposed as potentially useful adjuvant therapy for patients with insulin resistance and/or the patients who wish to increase insulin sensitivity.

Sex-dependent nutritional programming: fish oil intake during early pregnancy in rats reduces age-dependent insulin resistance in male, but not female, offspring

2013 ◽  
Vol 304 (4) ◽  
pp. R313-R320 ◽  
Author(s):  
Fatima L. C. Sardinha ◽  
Flavia S. Fernandes ◽  
Maria G. Tavares do Carmo ◽  
Emilio Herrera
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Early Pregnancy ◽  
Adult Life ◽  
Male Offspring ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Standard Diet ◽  
Model Assessment

Prenatal and early postnatal nutritional status may predispose offspring to impaired glucose tolerance and changes in insulin sensitivity in adult life. The long-term consequences of changes in maternal dietary fatty acid composition were determined in rats. From day 1 until day 12 of pregnancy, rats were given isocaloric diets containing 9% nonvitamin fat based on soybean, olive, fish (FO), linseed, or palm oil. Thereafter, they were maintained on the standard diet; offspring were studied at different ages. Body weight at 4, 8, and 12 mo and lumbar adipose tissue and liver weights at 12 mo did not differ between females on the different diets, whereas in males the corresponding values were all lower in the offspring from the FO group compared with the other dietary groups. Plasma glucose concentrations (both basal and after an oral glucose load) did not change with sex or dietary group, but plasma insulin concentrations were lower in females than in males and, in males, were lowest in the FO group. Similar relations were found with both the homeostasis model assessment of insulin resistance and insulin sensitivity index. In conclusion, the intake of more n–3 fatty acids (FO diet) during early pregnancy reduced both fat accretion and age-related decline in insulin sensitivity in male offspring but not in females. It is proposed that the lower adiposity caused by the increased n–3 fatty acids during the intrauterine life was responsible of the lower insulin resistance in male offspring.

scholarly journals Circulating obestatin levels and the ghrelin/obestatin ratio in obese women

2007 ◽  
Vol 157 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Valentina Vicennati ◽  
Silvia Genghini ◽  
Rosaria De Iasio ◽  
Francesca Pasqui ◽  
Uberto Pagotto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tolerance Test ◽  
Normal Weight ◽  
Metabolic Parameters ◽  
Blood Levels ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Obese Women ◽  
Glucose Levels

Objective: We measured blood levels of obestatin, total ghrelin, and the ghrelin/obestatin ratio and their relationship with anthropometric and metabolic parameters, adiponectin and insulin resistance, in overweight/obese and normal-weight women. Design: Outpatients Unit of Endocrinology of the S Orsola-Malpighi Hospital of Bologna, Italy. Methods: Fasting obestatin, ghrelin, adiponectin and lipid levels, fasting and glucose-stimulated oral glucose tolerance test insulin, and glucose levels were measured in 20 overweight/obese and 12 controls. The fasting ghrelin/obestatin ratio was calculated; the homeostasis model assessment-IR (HOMA-IR) and insulin sensitivity index (ISIcomposite) were calculated as indices of insulin resistance. Results: Obese women had higher obestatin and lower ghrelin blood levels, and a lower ghrelin/obestatin ratio compared with controls. In all subjects, obestatin was significantly and positively correlated with total cholesterol and triglycerides, but not with ghrelin, anthropometric, and metabolic parameters. In the obese women, however, obestatin and ghrelin concentrations were positively correlated. By contrast, the ghrelin/obestatin ratio was significantly and negatively correlated with body mass index, waist, waist-to-hip ratio, fasting insulin, and HOMA-IR, and positively with ISIcomposite but not with adiponectin. None of these parameters were correlated with the ghrelin/obestatin ratio in the obese. Conclusions: Increased obestatin, decreased ghrelin levels, and a decreased ghrelin/obestatin ratio characterize obesity in women. This supports the hypothesis that the imbalance of ghrelin and obestatin may have a role in the pathophysiology of obesity. On the other hand, some relevant differences between our data on circulating levels of obestatin and the ghrelin/obestatin ratio in obese subjects and those reported in the few studies published so far imply that further research is needed.

scholarly journals Significance and role of homeostatic model assessment in the evaluation of glucose regulation mechanisms

2017 ◽  
Vol 70 (5-6) ◽  
pp. 155-161
Author(s):  
Stanislava Nikolic ◽  
Nikola Curic ◽  
Romana Mijovic ◽  
Branislava Ilincic ◽  
Damir Benc
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Glucose Regulation ◽  
Oral Glucose ◽  
Model Assessment ◽  
Oral Glucose Tolerance ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model

Introduction. Mathematical formulas, such as homeostatic model assessment indexes, proved to be useful for the estimation of insulin resistance. Nevertheless, numerous published results point to a considerable variability of their reference values. The aim of this study was to use homeostatic model assessment indexes and evaluate levels of insulin resistance in nondiabetic patients. Material and Methods. The study included 486 individuals (mean age 36.84 ? 12.86; 17% of males and 83% of females). Blood sampling was performed in order to determine glucose and insulin plasma levels, at the 0th and 120th minute of the oral glucose tolerance test. The indexes were calculated by the use of homeostatic model assessment 2 calculator, homeostatic model assessment of insulin resistance, homeostatic model assessment of insulin sensitivity, and homeostatic model assessment of ?-cells function. The results were statistically analyzed using a Data Analysis programme. Results. In the examined population, the average glycemic values of the oral glucose tolerance test were within the euglycemic scope (Gluc 0 = 4.76 ? 0.45 mmol/L; Gluc 120 = 5.24 ? 1.17 mmol/L), while the average values of calculated homeostatic model assessment indexes were: insulin resistance - 1.41 ? 0.82; ?-cells function - 131.54 ? 49.41%, and insulin sensitivity - 91.94 ? 47.32%. According to study cut-off values, homeostatic model assessment of insulin resistance was less than 2. We found 84 (17.28%) individuals with increased insulin resistance. Also, we set the lowest reference value for homeostatic model assessment of insulin sensitivity at less than 50%. With the probability of 66.67% (x? ? 1SD), basal insulin level under 11.9 mIU/L can be considered to correspond to physiologic level of insulin resistance. Conclusion. The follow-up of increased insulin resistance and altered secretion of pancreatic ?-cells, at early stages of glucose regulation disturbances, may be useful in assessing dynamics and level of glucose regulation disturbances and their appropriate treatment. <br><br><font color="red"><b> This article has been corrected. Link to the correction <u><a href="http://dx.doi.org/10.2298/MPNS1708202E">10.2298/MPNS1708202E</a><u></b></font>

scholarly journals The biochemical assessment of insulin resistance

2007 ◽  
Vol 44 (4) ◽  
pp. 324-342 ◽  
Author(s):  
Anwar Borai ◽  
Callum Livingstone ◽  
Gordon A A Ferns
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Model Assessment ◽  
Intravenous Glucose ◽  
Gold Standard Method ◽  
The Metabolic Syndrome ◽  
Increased Risk

Insulin resistance is a common condition, recognized to be a central feature of the metabolic syndrome, and strongly associated with an increased risk of cardiovascular disease and diabetes. The quantitative assessment of insulin sensitivity is not used for routine clinical purposes, but the emerging importance of insulin resistance has led to its wider application to research studies that have examined its pathogenesis, aetiology and consequences. The gold standard method for the determination of insulin sensitivity is the euglycaemic hyperinsulinaemic clamp from which indices of insulin sensitivity can be derived. The clamp technique is both expensive and complex to undertake and has prompted the use of surrogate methods, notably the insulin tolerance test and frequently sampled intravenous glucose tolerance test. Indices may be derived from these methods and correlate well with those derived from clamp studies. Indices can also be derived from measurements made during a standard oral glucose tolerance test and from one-off fasting specimens (e.g. homeostasis model assessment and quantitative insulin sensitivity check index). These indices lend themselves for use in large population studies where a relatively simple, inexpensive assessment is necessary. However, these tests all suffer from important limitations, including poor precision. Insulin resistance is increasingly being assessed in clinical situations, where relatively simple markers are required. Insulin-like growth factor binding protein-1 is an emerging marker which may be useful in this context.

scholarly journals Adiponectin may mediate the association between omentin, circulating lipids and insulin sensitivity: results from the KORA F4 study

2015 ◽  
Vol 172 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Christian Herder ◽  
D Margriet Ouwens ◽  
Maren Carstensen ◽  
Bernd Kowall ◽  
Cornelia Huth ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Large Population ◽  
Serum Levels ◽  
Population Based ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Related Factors

ObjectiveReduced circulating omentin levels have been reported in obesity and type 2 diabetes, but data were mostly derived from univariate analyses in small study samples. This study aimed to investigate the relationship between omentin, abnormal glucose tolerance and related metabolic factors in a large population-based cross-sectional study.Design and methodsSerum omentin was measured by ELISA in 1092 participants of the German KORA F4 survey (2006–2008). Associations between omentin serum levels, glucose tolerance (assessed with an oral glucose tolerance test) and diabetes-related factors were estimated using logistic and linear regression models respectively.ResultsSerum levels of omentin were not related to categories of glucose tolerance. However, serum omentin was positively associated with whole-body insulin sensitivity index (ISI (composite)) and HDL cholesterol and showed inverse associations with 2-h post-load glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance, BMI and triglycerides (all P≤0.03 after adjustment for age, sex and lifestyle factors). Further adjustment for BMI and/or serum lipids attenuated the associations with parameters of glucose metabolism, whereas adjustment for serum adiponectin virtually abolished all aforementioned associations. In contrast, adjustment for omentin had no effect on the positive association between adiponectin levels and ISI (composite).ConclusionsThe data from this large population-based cohort show that circulating omentin levels are associated with insulin sensitivity. Our observations further suggest that omentin acts via upregulation of adiponectin, which in turn affects lipid metabolism and thereby also indirectly enhances insulin sensitivity, but mechanistic studies are required to corroborate this hypothesis.

scholarly journals Carbohydrate-induced manipulation of insulin sensitivity independently of intramyocellular lipids

2003 ◽  
Vol 89 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Louise M. Goff ◽  
Gary S. Frost ◽  
Gavin Hamilton ◽  
E. Louise Thomas ◽  
Waljit S. Dhillo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Healthy Volunteers ◽  
Dietary Intervention ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Resonance Spectroscopy ◽  
Sensitivity Index ◽  
Intramyocellular Lipids ◽  
Post Intervention

Subjects with insulin resistance have been shown to have higher storage levels of intramyocellular lipid (IMCL) than their insulin-sensitive counterparts. It has been proposed that elevated IMCL stores may be the main cause of insulin resistance. The aim of the present study was to ascertain whether there is a causal relationship between IMCL storage and insulin resistance. IMCL storage was assessed using magnetic resonance spectroscopy and insulin sensitivity was assessed by performing an oral glucose tolerance test. A 4-week intervention of reduction of dietary glycaemic index was used to manipulate insulin sensitivity in a cohort of healthy volunteers; the effects of this intervention on IMCL were measured after 4 weeks of intervention. Significant improvements in the insulin sensitivity index occurred following the dietary intervention (baseline 7·8 (sem 1·11) v. post-intervention 9·7 (sem 1·11), P=0·02). However, there were no changes in IMCL storage levels, suggesting that insulin sensitivity can be manipulated independently of IMCL. This suggests that in healthy volunteers, insulin sensitivity is independent of IMCL storage and the high storage levels that have been found in insulin-resistant subjects may occur as a consequence rather than a cause of insulin resistance.

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