The Relationship between Circulating Acetate and Human Insulin Resistance before and after Weight Loss in the DiOGenes Study

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (stdβ 0.130, p = 0.033) in women, but not in men (stdβ −0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

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Melatonin Treatment Improves Insulin Resistance and Pigmentation in Obese Patients with Acanthosis Nigricans

International Journal of Endocrinology ◽

10.1155/2018/2304746 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Hang Sun ◽

Xingchun Wang ◽

Jiaqi Chen ◽

Aaron M. Gusdon ◽

Kexiu Song ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Acanthosis Nigricans ◽

Resistance Index ◽

Inflammatory Factors ◽

Model Assessment ◽

Obese Patients ◽

Inflammatory Status ◽

Before And After ◽

Matsuda Index

Objective. This study aimed to determine the effects of melatonin on insulin resistance in obese patients with acanthosis nigricans (AN). Methods. A total of 17 obese patients with acanthosis nigricans were recruited in a 12-week pilot open trial. Insulin sensitivity, glucose metabolism, inflammatory factors, and other biochemical parameters before and after the administration of melatonin were measured. Results. After 12 weeks of treatment with melatonin (3 mg/day), homeostasis model assessment insulin resistance index (HOMA-IR) (8.99 ± 5.10 versus 7.77 ± 5.21, p<0.05) and fasting insulin (37.09 5 ± 20.26 μU/ml versus 32.10 ± 20.29 μU/ml, p<0.05) were significantly decreased. Matsuda index (2.82 ± 1.54 versus 3.74 ± 2.02, p<0.05) was significantly increased. There were also statistically significant declines in the AN scores of the neck and axilla, body weight, body mass index, body fat, visceral index, neck circumference, waist circumference, and inflammatory markers. Conclusions. It was concluded that melatonin could improve cutaneous symptoms in obese patients with acanthosis nigricans by improving insulin sensitivity and inflammatory status. This trial is registered with ClinicalTrials.gov NCT02604095.

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Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals

Journal of Investigative Medicine ◽

10.1136/jim-2017-000681 ◽

2018 ◽

Vol 66 (6) ◽

pp. 1019-1022 ◽

Cited By ~ 19

Author(s):

Luis Rodrigo Cataldo ◽

Rodrigo Fernández-Verdejo ◽

José Luis Santos ◽

Jose Eduardo Galgani

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

High Energy ◽

12S Rrna ◽

Model Assessment ◽

Metabolic Homeostasis ◽

Reading Frame ◽

Homeostatic Model Assessment ◽

Matsuda Index ◽

Insight Into

Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide that attenuates weight gain and hyperinsulinemia when administered to high fat-fed mice. MOTS-c is therefore a potential regulator of metabolic homeostasis under conditions of high-energy supply. However, the effect of insulin resistance and obesity on plasma MOTS-c concentration in humans is unknown. To gain insight into MOTS-c regulation, we measured plasma MOTS-c concentration and analyzed its relationship with insulin sensitivity surrogates, in lean and obese humans (n=10 per group). Obese individuals had impaired insulin sensitivity as indicated by low Matsuda and high Homeostatic Model Assessment (HOMA) indexes. Although plasma MOTS-c concentration was similar in lean and obese individuals (0.48±0.16 and 0.52±0.15 ng/mL; p=0.60), it was correlated with HOMA (r=0.53; p<0.05) and Matsuda index (r=−0.46; p<0.05). Notably, when the groups were analyzed separately, the associations remained only in lean individuals. We conclude that plasma MOTS-c concentration is unaltered in human obesity. However, MOTS-c associates positively with insulin resistance mostly in lean individuals, indicating that plasma MOTS-c concentration depends on the metabolic status in this population. Such dependence seems altered when obesity settles. The implications of plasma MOTS-c for human metabolic homeostasis deserve future examination.

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The Relationship between Insulin Resistance and the Cardiovascular Biomarker Growth Differentiation Factor-15 in Obese Patients

Clinical Chemistry ◽

10.1373/clinchem.2010.153726 ◽

2011 ◽

Vol 57 (2) ◽

pp. 309-316 ◽

Cited By ~ 73

Author(s):

Greisa Vila ◽

Michaela Riedl ◽

Christian Anderwald ◽

Michael Resl ◽

Ammon Handisurya ◽

...

Keyword(s):

Insulin Resistance ◽

Gastric Bypass ◽

Insulin Sensitivity ◽

Oral Glucose ◽

Model Assessment ◽

Obese Patients ◽

Growth Differentiation Factor 15 ◽

Homeostatic Model Assessment ◽

Homeostatic Model ◽

The Relationship

BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

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

Medicinski pregled ◽

10.2298/mpns1706155n ◽

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. This article has been corrected. Link to the correction <a href="http://dx.doi.org/10.2298/MPNS1708202E">10.2298/MPNS1708202E</a>

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The Insulin Sensitivity Mcauley Index (Mcai) is Associated with 40-Year Cancer Mortality in a Cohort of Men and Women Free of Diabetes at Baseline

10.21203/rs.3.rs-1011207/v1 ◽

2021 ◽

Author(s):

Yonatan Moshkovits ◽

David Rott ◽

Angela Chetrit ◽

Rachel Dankner

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Cancer Mortality ◽

Model Assessment ◽

Cancer Death ◽

Men And Women ◽

Adult Men ◽

Sensitivity Indices ◽

Increased Risk ◽

Homeostatic Model Assessment

Abstract Background:The association between insulin resistance and cancer mortality is not fully explored. We investigated the association between several insulin sensitivity indices (ISIs) and cancer mortality in a cohort of adult men and women free of diabetes. We hypothesized that higher insulin resistance (Q1 of the Mcauley index (MCAi), calculated by fasting insulin and triglycerides, and Q4 of the Homeostatic Model Assessment (HOMA), calculated by fasting plasma glucose and insulin) will be associated with greater cancer mortality risk.Methods: A cohort of 1612 men and women free of diabetes during baseline were followed since 1979 through 2016 for cause specific mortality as part of the Israel study on Glucose Intolerance, Obesity and Hypertension (GOH). Results: Mean age at baseline was 51.5 ± 8.0 years, 804 (49.9%) were males, and 871 (54.0%) had prediabetes. Mean follow-up was 36.7±0.2 years and 47,191 person years were accrued. Cumulative incidence analysis using Cox proportional hazard model and competing risks analysis adjusted for age, sex, country of origin, BMI, blood pressure, total cholesterol, smoking and glycemic status (table 2), revealed an increased risk for cancer death, sub-distribution HR=1.4 (95% CI: 1.1-1.9, p=0.02) for individuals in the lower quartile of MCAi (Q1), denoting higher insulin resistance, compared with the upper quartiles (Q2-4). No statistically significant association was observed between the other insulin resistance surrogates and cancer death.Conclusion: The MCAi was found to independently associate with an increased risk for cancer mortality in adult men and women free of diabetes. The MCAi may be considered as a long-term prognostic biomarker in diabetes-free adults.

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Vitamin D status and parathyroid hormone in obese children before and after weight loss

Acta Endocrinologica ◽

10.1530/eje-07-0188 ◽

2007 ◽

Vol 157 (2) ◽

pp. 225-232 ◽

Cited By ~ 123

Author(s):

Thomas Reinehr ◽

Gideon de Sousa ◽

Ute Alexy ◽

M Kersting ◽

Werner Andler

Keyword(s):

Vitamin D ◽

Weight Loss ◽

Parathyroid Hormone ◽

Insulin Sensitivity ◽

Weight Status ◽

Intervention Program ◽

Model Assessment ◽

Obese Children ◽

Percentage Body Fat ◽

Before And After

Objective: The roles of vitamin D and parathyroid hormone (PTH) are discussed controversially in obesity, and studies of these hormones in obese children are limited. Therefore, we studied the relationships between PTH, 1,25-dihydroxy-vitamin D (1,25-OH Vit D), 25-hydroxy-vitamin D (25-OH Vit D), weight status, and insulin sensitivity before and after weight loss in obese children. Methods: Fasting serum PTH, 1,25-OH Vit D, 25-OH Vit D, inorganic phosphate, calcium, alkaline phosphatase (AP), insulin, glucose, and weight status (SDS–BMI and percentage body fat) were determined in 133 obese children (median age 12.1 years) and compared with 23 non-obese children. Furthermore, these parameters were analyzed in 67 obese children before and after participating in a 1-year obesity intervention program. Results: Obese children had significantly (P < 0.001) higher PTH and lower 25-OH Vit D concentrations compared with non-obese children, while calcium, phosphate, AP, and 1,25-OH Vit D did not differ significantly. Changes of PTH (r = 0.23, P = 0.031) and 25-OH Vit D (r = −0.27, P = 0.013) correlated significantly with changes of SDS–BMI, but not with changes of insulin sensitivity (homeostasis model assessment; HOMA-B%). Reduction of overweight in 35 children led to a significant (P < 0.01) decrease of PTH concentrations and an increase in 25-OH Vit D levels. Conclusions: PTH levels were positively and 25-OH Vit D concentrations were negatively related to weight status. Since these alterations normalized after weight loss, these changes are consequences rather than causes of overweight. A relationship between PTH, vitamin D, and insulin sensitivity based on the HOMA index was not found in obese children. Further longitudinal clamp studies are neccessary to study the relationship between vitamin D and insulin sensitivity.

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Is Insulin Resistance at Baseline a Predictor of Weight Loss After Bariatric Surgery?

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.034 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A18-A19

Author(s):

Marta Borges-Canha ◽

João Sérgio Neves ◽

Fernando Mendonça ◽

Maria Manuel Silva ◽

Cláudia Costa ◽

...

Keyword(s):

Insulin Resistance ◽

Bariatric Surgery ◽

Morbid Obesity ◽

Weight Loss ◽

Cell Function ◽

First Year ◽

Model Assessment ◽

Post Surgery ◽

Homeostatic Model Assessment ◽

Homeostatic Model

Abstract Background: Obesity is a multifactorial disease that is strongly associated to other metabolic disorders, such as insulin resistance and type 2 diabetes. Bariatric surgery is nowadays considered the most effective treatment of morbid obesity. The role of insulin resistance (IR) in weight loss after bariatric surgery is highly unknown. Aim: To evaluate the association between Insulin Resistance (IR) and percentage of excess weight loss (EWL%) one, two, three and four years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our centre between January 2010 and July 2018 were included. Patients were excluded if they had diabetes. We evaluated baseline Homeostatic Model Assessment of IR (HOMA-IR), Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index (QUICKI) and Matsuda and DeFronzo index, and performed a linear regression concerning each year’s EWL%. Results: After applying the exclusion criteria, 1723 patients were included in this analysis. The logarithm of HOMA-beta was negatively associated with EWL% at second-, third- and fourth-years post-surgery (β=-1.04 [-1.82 to -0.26], p<0.01; β=-1.16 [-2.13 to -0.19], p=0.02; β=-1.29 [-2.64 to 0.06], p=0.061, respectively), adjusting for age, sex, body mass index and type of surgery. This was not observed in the first-year post-surgery nor for the other indexes. Glycaemia at baseline was also positively associated to EWL% at second- and third-years post-surgery. Conclusion: IR at baseline seems to be associated to long term weight loss, explicitly after the first year post bariatric surgery.

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Metabolomic profiling identifies complex lipid species associated with response to weight loss interventions

10.1101/2020.10.05.326025 ◽

2020 ◽

Author(s):

Nathan A. Bihlmeyer ◽

Lydia Coulter Kwee ◽

Clary B. Clish ◽

Amy Anderson Deik ◽

Robert E. Gerszten ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Metabolic Pathways ◽

Model Assessment ◽

Metabolomic Profiling ◽

Lipid Species ◽

Complex Lipid ◽

Homeostatic Model Assessment ◽

Homeostatic Model ◽

Weight Loss Interventions

AbstractObesity is an epidemic internationally. While weight loss interventions are efficacious, they are compounded by heterogeneity with regards to clinically relevant metabolic responses. Thus, we sought to identify metabolic pathways and biomarkers that distinguish individuals with obesity who would most benefit from a given type of intervention. Liquid chromatography mass spectrometry-based profiling was used to measure 765 metabolites in baseline plasma from three different weight loss studies: WLM (behavioral intervention, N=443), STRRIDE-PD (exercise trial, N=163), and CBD (surgical cohort, N=125). The primary outcome was percent change in insulin resistance (as measured by the Homeostatic Model Assessment of Insulin Resistance [%ΔHOMA-IR]) over the intervention. Overall, 92 individual metabolites were associated with %ΔHOMA-IR after adjustment for multiple comparisons. Concordantly, the most significant metabolites were triacylglycerols (TAGs; p=2.3e-5) and diacylglycerols (DAGs; p=1.6e-4), with higher TAG and DAG levels associated with a greater improvement in HOMA-IR. In tests of heterogeneity, 50 metabolites changed differently between weight loss interventions; we found amino acids, peptides, and their analogues to be most significant (4.7e-3) in this category. Our results highlight novel metabolic pathways associated with heterogeneity in response to weight loss interventions, and related biomarkers which could be used in future studies of personalized approaches to weight loss interventions.

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Obesity is associated with increased basal and postprandial β-cell insulin secretion even in the absence of insulin resistance

10.2337/figshare.12601082.v1 ◽

2020 ◽

Author(s):

Ada Admin ◽

Stephan van Vliet ◽

Han-Chow E. Koh ◽

Bruce W. Patterson ◽

Mihoko Yoshino ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Production ◽

Compensatory Response ◽

Insulin Kinetics ◽

Positron Emission ◽

Glucose Ingestion ◽

Before And After

We tested the hypothesis that obesity, independent of insulin resistance, is associated with increased insulin secretion. We compared insulin kinetics before and after glucose ingestion in lean healthy people and people with obesity who were matched on multi-organ insulin sensitivity (inhibition of adipose tissue lipolysis and glucose production and stimulation of muscle glucose uptake), assessed by using a two-stage hyperinsulinemic-euglycemic pancreatic clamp procedure in conjunction with glucose and palmitate tracer infusions and positron emission tomography. We also evaluated the effect of diet-induced weight loss on insulin secretion in people with obesity who did not improve insulin sensitivity despite marked (~20%) weight loss. Basal and postprandial insulin secretion rates were more than 50% greater in people with obesity than lean people even though insulin sensitivity was not different between groups. Weight loss in people with obesity decreased insulin secretion by 35% even though insulin sensitivity did not change. These results demonstrate that increased insulin secretion in people with obesity is associated with excess adiposity itself and is not simply a compensatory response to insulin resistance. These findings have important implications regarding the pathogenesis of diabetes, because hyperinsulinemia causes insulin resistance and insulin hypersecretion is an independent risk factor for developing diabetes.

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Comparison of Various Indices in Identifying Insulin Resistance and Diabetes in Chronic Spinal Cord Injury

Journal of Clinical Medicine ◽

10.3390/jcm10235591 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5591

Author(s):

Gary J. Farkas ◽

Phillip S. Gordon ◽

Nareka Trewick ◽

Ashraf S. Gorgey ◽

David R. Dolbow ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Metabolism ◽

Diagnostic Study ◽

Model Assessment ◽

Linear Regression Models ◽

Post Injury ◽

Intravenous Glucose ◽

Cord Injury ◽

Matsuda Index

The purpose of this screening and diagnostic study was to examine the accord among indices of glucose metabolism, including the Homeostatic Model Assessment for Insulin Resistance (HOMA), HOMA2, Matsuda Index, Quantitative Insulin-sensitivity Check Index (QUICKI), hemoglobin A1C (HbA1C), and fasting plasma glucose (FPG) against intravenous glucose tolerance test-measured insulin sensitivity (Si) in individuals with chronic motor complete SCI. Persons with chronic (≥12-months post-injury) SCI (n = 29; 79% men; age 42.2 ± 11.4; body mass index 28.6 ± 6.4 kg/m2; C4-T10) were included. Measures were compared using adjusted R2 from linear regression models with Akaike information criterion (AIC, a measure of error). QUCKI had the greatest agreement with Si (adjusted R2 = 0.463, AIC = 91.1, p = 0.0001), followed by HOMA (adjusted R2 = 0.378, AIC = 95.4, p = 0.0008), HOMA2 (adjusted R2 = 0.256, AIC = 99.7, p = 0.0030), and the Matsuda Index (adjusted R2 = 0.356, AIC = 95.5, p = 0.0004). FPG (adjusted R2 = 0.056, AIC = 107.5, p = 0.1799) and HbA1C (adjusted R2 = 0.1, AIC = 106.1, p = 0.0975) had poor agreement with Si. While HbA1C and FPG are commonly used for evaluating disorders of glucose metabolism, QUICKI demonstrates the best accord with Si compared to the other measures.

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