Higher Homeostasis Model Assessment Insulin Research Articles

How close are children with obesity to becoming an adult with chronic illnesses?

Childhood obesity has become a global threat due to its serious negative consequences. We aimed to determine the patterns of metabolic syndrome and cardio-metabolic risk factors in Turkish children with obesity. We examined 169 schoolchildren with obesity in April and May 2019 in Samsun, Turkey. After clinical evaluation and anthropometric measurements, fasting blood samples were collected to measure total cholesterol, low and high-density lipoprotein, fasting blood glucose, triglycerides, and insulin levels. The proportion of those who met the metabolic syndrome criteria in boys was 14.3%, but it was twice as high in girls (28.2%). The most prevalent component of cardio-metabolic risk factor was increased waist circumference (96.4%) followed by a high homeostasis model assessment insulin resistance index (74.6%) and high blood pressure (29.0%). While the average high-density lipoprotein was higher in boys than in girls, on the contrary, insulin, HbA1c, and homeostasis model assessment insulin resistance concentrations were higher in girls. The prevalence of dyslipidemia was also higher in girls (67.1%) than in boys (47.6%), as were all impaired metabolic syndrome components. One in five children with obesity was at risk of metabolic syndrome. For early intervention and prevention, children with obesity should be monitored in terms of cardio-metabolic risk factors, but obese girls are more prioritized.

Association between Gestational Weight Gain, Gestational Diabetes Risk, and Obstetric Outcomes: A Randomized Controlled Trial Post Hoc Analysis.

Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). Lifestyle trials have not achieved much GWG limitation, and have largely failed to prevent GDM. We compared the effect of substantial GWG limitation on maternal GDM risk. Pregnant women with a body mass index (BMI) ≥29 kg/m2 <20 weeks gestation without GDM (n = 436) were randomized, in a multicenter trial, to usual care (UC), healthy eating (HE), physical activity (PA), or HE and PA lifestyle interventions. GWG over the median was associated with higher homeostasis model assessment insulin resistance (HOMA-IR) and insulin secretion (Stumvoll phases 1 and 2), a higher fasting plasma glucose (FPG) at 24–28 weeks (4.66 ± 0.43 vs. 4.61 ± 0.40 mmol/L, p < 0.01), and a higher rate of caesarean section (38% vs. 27% p < 0.05). The GWG over the median at 35–37 weeks was associated with a higher rate of macrosomia (25% vs. 16%, p < 0.05). A post hoc comparison among women from the five sites with a GWG difference >3 kg showed no significance difference in glycaemia or insulin resistance between HE and PA, and UC. We conclude that preventing even substantial increases in GWG after the first trimester has little effect on maternal glycaemia. We recommend randomized controlled trials of effective lifestyle interventions, starting in or before the first trimester.

Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring.

Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring: maternal non-transgenic control and maternal transgenic offspring, and paternal control and paternal transgenic offspring. Plasma triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG) and fasting insulin (FINS) were measured. ApoCIII overexpression caused severe hypertriglyceridemia, but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups. The 4 groups of offspring had similar birth weight and growth rate. The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice, but there was no difference in plasma TG between maternal and paternal transgenic offspring. Although the FPG of the 4 groups of animals had no difference, the maternal transgenic mice showed impaired glucose tolerance, increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups. In conclusion, maternally inherited hypertriglyceridemia in ApoCIII transgenic mice displayed impaired glucose tolerance, hyperinsulinemia and increased HOMA-R, while paternally inherited hypertriglyceridemia did not have such impacts.

Does Homeostasis Model Assessment Insulin Resistance Have a Predictive Value for Post-Coronary Artery Bypass Grafting Surgery Outcomes?

ObjectiveThis study aims to investigate whether pre-operative Homeostasis Model Assessment Insulin Resistance (HOMA-IR) value is a predictor in non-diabetic coronary artery bypass grafting patients in combination with hemoglobin A1c, fasting blood glucose and insulin levels.MethodsEighty one patients who were admitted to Cardiovascular Surgery Clinic at our hospital between August 2012 and January 2013 with a coronary artery bypass grafting indication were included. Patients were non-diabetic with <6.3% hemoglobin A1c and were divided into two groups including treatment and control groups according to normal insulin resistance (HOMA-IR<2.5, Group A; n=41) and high insulin resistance (HOMA-IR>2.5, Group B; n=40), respectively. Pre-operative fasting blood glucose and insulin were measured and serum chemistry tests were performed. The Homeostasis Model Assessment Insulin Resistance values were calculated. Statistical analysis was performed.ResultsThere was a statistically significant difference in fasting blood glucose and HOMA-IR values between the groups. Cross-clamping time, and cardiopulmonary bypass time were longer in Group B, compared to Group A (P=0.043 and P=0.031, respectively). Logistic regression analysis revealed that hemoglobin A1c was not a reliable determinant factor alone for pre-operative glucometabolic evaluation of non-diabetic patients. The risk factors of fasting blood glucose and cardiopulmonary bypass time were more associated with high Homeostasis Model Assessment Insulin Resistance levels.ConclusionOur study results suggest that preoperative screening of non-diabetic patients with Homeostasis Model Assessment Insulin Resistance may improve both follow-up visit schedule and short-term outcomes, and may be useful in risk stratification of the high-risk population for impending health problems.

Serum Osteocalcin Is Not Associated with Glucose but Is Inversely Associated with Leptin across Generations of Nondiabetic Women

The skeleton is recognized as an important player in energy metabolism through its interactions with other tissues. Whether the association of osteocalcin with glucose metabolism is age dependent has not been fully addressed. The objective of the study was to examine the age-specific association between different forms of osteocalcin and glucose and adipokines. This was a family-based study across three generations. The study was conducted at a university laboratory. Sixty-four daughter-premenopausal mother-maternal grandmother trios participated in the study. Fasting plasma glucose and insulin concentrations, serum total (tOC), carboxylated (cOC), and uncarboxylated (ucOC = tOC - cOC) osteocalcin, leptin, and adiponectin levels, and fat masses were assessed. Generalized estimating equations (GEE) model was used to assess the associations of bone biomarkers with glucose metabolism variables and adipokines. No significant difference in insulin was found between generations, whereas glucose and leptin increased with age. Levels of tOC, cOC, and ucOC were highest in girls and lowest in mothers (P < 0.01). Grandmothers had higher leptin and adiponectin than mothers and girls. Despite the differences in insulin and glucose between the low and high homeostasis model assessment insulin resistance index (HOMA-IR) groups within generations, no significant differences in tOC, cOC, and ucOC were found. Compared with their low HOMA-IR counterparts, the high HOMA-IR group had significantly higher leptin and lower adiponectin in mothers and grandmothers. The tOC, cOC, and ucOC levels did not correlate with HOMA-IR, leptin, or adiponectin when the three generations were evaluated together, but when separated by generation, leptin was inversely correlated with tOC (P = 0.003) and cOC (P = 0.047) in mothers and with ucOC in grandmothers (P = 0.042). Osteocalcin, glucose, and adipokines change with age but in a noncommensurate manner. We infer that the association between osteocalcin and glucose metabolism is minor and age specific in nondiabetic women. Leptin, however, strongly correlated with insulin resistance independently of fat masses, suggesting that obesity, as a metabolic disorder risk factor, affects glucose metabolism, partly through the role of leptin.

Upregulation of Hepatic 11β-Hydroxysteroid Dehydrogenase-1 Expression in Calcium-Deficient Rats

Background: Many epidemiologic studies have reported a link between calcium (Ca) deficiency and metabolic syndrome. In this study, we examine Ca deficiency in rats and whether changes in glucocorticoid metabolism are induced. Methods: Twelve-week-old female Wistar rats were weaned onto a very-low-Ca diet (low-Ca group) or a control diet (control group) for 2 weeks. Quantitative real-time PCR was used to assess mRNA for 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1), 11β-HSD2, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor-α, and glucocorticoid receptor in the liver. Concentrations of adiponectin, leptin, corticosterone, intact parathyroid hormone, asymmetrical dimethylarginine and insulin in fasting serum were determined using a rat-specific enzyme-linked immunosorbent assay. Glucose concentrations were measured using a glucose oxidase system. Serum ionized Ca levels were measured with an automatic ion-selective electrode analyzer. Serum nitrite/nitrate levels were measured using a colorimetric assay kit. Results: After 2 weeks, no differences in serum glucose, corticosterone or insulin levels were observed. The low-Ca group rats showed higher homeostasis model assessment insulin resistance, lower adiponectin and higher intact parathyroid hormone levels. Serum nitrite/nitrate and asymmetrical dimethylarginine were significantly higher in the low-Ca group than in the control group. The expression of hepatic 11β-HSD1 mRNA was upregulated, while hepatic phosphoenolpyruvate carboxykinase expression was downregulated in the low-Ca group. Glucocorticoid receptor, peroxisome proliferator-activated receptor-α and 11β-HSD2 expression levels showed a similar tendency. Conclusion: A low-Ca diet alters glucocorticoid metabolism, which leads to hepatic upregulation of 11β-HSD1, and is possibly a key mechanism inducing the metabolic complications of Ca deficiency.

β-cell function of subjects with 1-hour hyperglycemia in oral glucose tolerance test

Based on the results of oral glucose tolerance test( OGTT )and the levels of 1-h plasma glucose ( 1 hPG),793 subjects were classified into three groups:583 with NGTN ( normal 1 hPG in OGTT),127 with NGT1 H( higher 1 hPG in OGTT) and 83 with IGT( impaired glucose tolerance).NGT1H group had large waist circumference,higher body mass index,fasting plasma glucose( FPG),triglyceride,and lower high density lipoprotein-cholesterol than those of NGTN group.NGT1 H group had higher homeostasis model assessment insulin index ( 1.2 ± 0.6),lower homeostasis model assessment β3 ( HOMA-β ) (4.5 ± 0.7 ) and insulinogenic index (2.1 ±0.7) than those of NGTN group(0.5 ±0.6,4.8 ±0.7,2.7 ±0.9,respectively,all P ＜0.05 ).HOMA-β of NGT1 H group was higher than that of IGT group(4.5 ±0.7 vs.4.4 ±0.6,P ＜0.05 ).The results indicate that 1 hPG in OGTT may identify a condition of glucose metabolic abnormalities characterized by insulin resistance and reduced β-cell function. Key words: Glucose metabolism disorders;  pancreatic β-cell function

Expression levels of haem oxygenase-1 in the omental adipose tissue and peripheral blood mononuclear cells of women with polycystic ovary syndrome

Haem oxygenase (HO)-1, an enzyme that degrades haem, plays a key role in the regulation of the inflammatory response and insulin resistance. The aim of this study was to evaluate the role of HO-1 in the regulation of insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS). Omental adipose tissue and human peripheral blood mononuclear cells (PBMCs) from seven women with PCOS and five healthy controls, matched for BMI and age, were analysed using western blotting and the real-time PCR. Women with PCOS were found to have significantly higher fasting and 2-h insulin levels, a significantly higher homeostasis model assessment insulin resistance index and a lower fasting glucose-to-insulin ratio (G(0)/I(0)) than the controls. The level of HO-1 protein in omental fat (P = 0.002), and the expression of HO-1 mRNA in omental fat and PBMCs from the women with PCOS were significantly lower (P = 0.002 and 0.05, respectively) than those of the controls. The expression of adiponectin mRNA in omental fat was also significantly lower (P = 0.02) in the women with PCOS than in the controls. However, there were no significant differences in the expression of tumour necrosis factor-α or interleukin-6 between the two groups. The level of HO-1 protein showed a significant positive correlation with the expression of HO-1 mRNA (r(2) = 0.786, P = 0.037) and adiponectin mRNA (r(2) = 0.7276, P <0.05). Serum insulin and glucose levels and BMI showed a significant negative correlation with the level of HO-1 (P< 0.05). Our results suggest that the HO-1-adiponectin axis may be associated with the regulation of insulin resistance and glucose intolerance in women with PCOS.

Association of the fatty acid‐binding protein 2 gene Ala54Thr polymorphism with insulin resistance and blood glucose: a meta‐analysis in 13451 subjects

The results from the published studies on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with insulin resistance and blood glucose are conflicting. In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with insulin resistance and blood glucose. We collected data on fasting blood glucose and fasting insulin, 2-h blood glucose (2-h BG) and 2-h insulin (2-h insulin), and homeostasis model assessment insulin resistance index. A dominant model was used for this meta-analysis. Thirty-one studies with 13 451 subjects were included in this meta-analysis. The carriers of Thr54 allele have significantly higher homeostasis model assessment insulin resistance index and marginally higher fasting insulin than the non-carriers: standardized mean difference (SMD) = 0.07, 95% confidence interval (CI, 0.02, 0.12), p = 0.007, p(heterogeneity) = 0.19 and SMD = 0.08, 95% CI (-0.01, 0.17), p = 0.07, p(heterogeneity) < 0.00001, respectively. A borderline significant association between the FABP2 Ala54Thr polymorphism and an increased 2-h BG was also detected under the dominant model: SMD = 0.10, 95% CI (0.00, 0.20), p = 0.05, p(heterogeneity) = 0.09. In addition, a borderline association between this polymorphism and an increased fasting blood glucose in populations of other ethnic origins was detected under the dominant model: SMD = 0.11, 95% CI (-0.00, 0.23), p = 0.06, p(heterogeneity) = 0.03. Our meta-analysis suggests that the Thr54 allele of the FABP2 Ala54Thr is weakly associated with a higher degree of insulin resistance, higher level of fasting insulin and higher level of 2-h BG. Our meta-analysis also suggests a weak association between this polymorphism and an increased fasting blood glucose in populations of other ethnic origins under the dominant model.

Impact of metabolic syndrome on elevated serum alanine aminotransferase levels in the Japanese population

Measurement of the serum alanine aminotransferase (ALT) level is used as an initial test for detection of liver diseases, and recent studies have also highlighted its potential value as a measure of overall health and survival as a marker of an increased risk of metabolic disorder. This study was designed to clarify the prevalence of elevated ALT levels in the Japanese population and to assess factors associated with ALT elevation. The subjects were 2165 individuals aged 40 to 85 years who participated in a Japanese community-based study referred to as the Takahata Study. Serum ALT levels and factors associated with ALT elevation were investigated. Among 2087 subjects who were negative for hepatitis B and C, the rates of elevated ALT greater than 30 U/L in men and greater than 25 U/L in women were 217 (22.7%) of 957 and 239 (21.2%) of 1130, respectively. These ALT cutoff levels had a specificity of more than 80% for exclusion of subjects with none or 1 of 3 metabolic risk factors: hypertension, lipid metabolism abnormality, and hyperglycemia. Multivariate analysis revealed 5 factors with a significant association with ALT elevation in men (n = 957): high γ-glutamyltranspeptidase, low adiponectin, high low-density lipoprotein cholesterol, high body mass index, and high homeostasis model assessment insulin resistance index. Similarly, 4 factors were significantly associated with ALT elevation in women (n = 1130): high γ-glutamyltranspeptidase, low adiponectin, high body mass index, and high homeostasis model assessment insulin resistance index. These results suggest that elevated ALT levels in the Japanese population older than 40 years have a strong association with metabolic syndrome–related features including obesity and insulin resistance.

Insulin resistance and acute coronary syndrome in the young Japanese population have a strong association

There are few data regarding acute coronary syndrome (ACS) in young Japanese patients. We examined the risk factors for ACS in young Japanese patients, especially impaired glucose metabolism. From a database of 789 consecutive patients admitted to our hospital with ACS between 2000 and 2005, we compared risk factors of patients divided into two age categories: < or =45 years (group Y, n = 41) and > or =46 years (group O, n = 748). All patients in group Y were male. Overt diabetes, hypertension, and a family history of ischemic heart disease were not so important to group Y. Higher triglyceride (160.5 +/- 86.0 vs 133.9 +/- 75.2 mg/dl, P = 0.0296) and lower high-density lipoprotein cholesterol (43.9 +/- 12.1 vs 48.7 +/- 13.5 mg/dl, P = 0.027) concentrations were present in group Y. We obtained data concerning insulin resistance in 326 of 789 patients. Although the incidence of impaired glucose tolerance was similar between the groups (31% vs 31%, not significant), a higher homeostasis model assessment insulin resistance index (2.26 +/- 2.03), indicating insulin resistance, was present in group Y. Insulin resistance might be correlated with the development of ACS in the young adult Japanese population.

Birthweight of offspring and paternal insulin resistance and paternal diabetes in late adulthood: cross sectional survey.

It has been proposed that genetic factors involved in insulin action could explain part of the link between low birthweight and risk of cardiovascular disease and diabetes in adulthood. To confirm this we examined the association between offspring birthweight and paternal insulin resistance and diabetes in late adulthood. We did a cross-sectional survey of 4252 men who were 60 to 79 years of age and from 24 British towns. Of these, 2788 men provided details of their offsprings' birthweight and sex. Offspring birthweight was inversely associated with paternal insulin resistance defined by the homeostasis model assessment (HOMA) score and with Type 2 diabetes in late adulthood. Fathers of offspring in the highest quartile of sex-standardised birthweight SD scores had a 34% reduction in odds of having a high HOMA insulin resistance score (OR=0.66, 95% CI: 0.47 to 0.92) compared with fathers of offspring in the lowest quartile after adjustment for potential confounders. A stronger inverse association was seen between offspring birthweight and risk of paternal diabetes (adjusted OR=0.59, 95% CI: 0.39 to 0.88 top quartile vs lowest quartile). For each increase of offspring-birthweight SD score the odds of high HOMA scores decreased by 13% (OR=0.87, 95% CI: 0.78 to 0.98) and the odds for diabetes by 17% (OR=0.83, 95% CI: 0.72 to 0.95), after full adjustment. Offspring birthweight is inversely associated with paternal insulin resistance and diabetes in late adulthood, supporting the hypothesis that genetic factors related to insulin action contribute to the association between birthweight and adult cardiovascular disease and diabetes risk.