Quantile-Dependent Heritability of Glucose, Insulin, Proinsulin, Insulin Resistance, and Glycated Hemoglobin

Lifestyle Genomics ◽

10.1159/000519382 ◽

2021 ◽

pp. 1-25

Author(s):

Paul T. Williams

Keyword(s):

Insulin Resistance ◽

Fasting Glucose ◽

Tolerance Test ◽

Alternative Interpretation ◽

Model Assessment ◽

Gene Environment ◽

Heart Study ◽

Glucose Ratio ◽

Homeostatic Model Assessment ◽

Regression Slopes

Background: “Quantile-dependent expressivity” is a dependence of genetic effects on whether the phenotype (e.g., insulin resistance) is high or low relative to its distribution. Methods: Quantile-specific offspring-parent regression slopes (βOP) were estimated by quantile regression for fasting glucose concentrations in 6,453 offspring-parent pairs from the Framingham Heart Study. Results: Quantile-specific heritability (h2), estimated by 2βOP/(1 + rspouse), increased 0.0045 ± 0.0007 (p = 8.8 × 10−14) for each 1% increment in the fasting glucose distribution, that is, h2 ± SE were 0.057 ± 0.021, 0.095 ± 0.024, 0.146 ± 0.019, 0.293 ± 0.038, and 0.456 ± 0.061 at the 10th, 25th, 50th, 75th, and 90th percentiles of the fasting glucose distribution, respectively. Significant increases in quantile-specific heritability were also suggested for fasting insulin (p = 1.2 × 10−6), homeostatic model assessment of insulin resistance (HOMA-IR, p = 5.3 × 10−5), insulin/glucose ratio (p = 3.9 × 10−5), proinsulin (p = 1.4 × 10−6), proinsulin/insulin ratio (p = 2.7 × 10−5), and glucose concentrations during a glucose tolerance test (p = 0.001), and their logarithmically transformed values. Discussion/Conclusion: These findings suggest alternative interpretations to precision medicine and gene-environment interactions, including alternative interpretation of reported synergisms between ACE, ADRB3, PPAR-γ2, and TNF-α polymorphisms and being born small for gestational age on adult insulin resistance (fetal origin theory), and gene-adiposity (APOE, ENPP1, GCKR, IGF2BP2, IL-6, IRS-1, KIAA0280, LEPR, MFHAS1, RETN, TCF7L2), gene-exercise (INS), gene-diet (ACSL1, ELOVL6, IRS-1, PLIN, S100A9), and gene-socioeconomic interactions.

Download Full-text

The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

International Journal of Endocrinology ◽

10.1155/2015/836941 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Alexis Elias Malavazos ◽

Emanuele Cereda ◽

Federica Ermetici ◽

Riccardo Caccialanza ◽

Silvia Briganti ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Lipid Accumulation ◽

Fasting Glucose ◽

Tolerance Test ◽

Continuous Variable ◽

Oral Glucose ◽

Model Assessment ◽

Lipid Accumulation Product ◽

Adult Age

“Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006andP=0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

Download Full-text

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>

Download Full-text

Sex differences in the link between blood cobalt concentrations and insulin resistance in adults without diabetes

Environmental Health and Preventive Medicine ◽

10.1186/s12199-021-00966-w ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Yong Chen ◽

Haobin Huang ◽

Xiaowei He ◽

Weiwei Duan ◽

Xuming Mo

Keyword(s):

Insulin Resistance ◽

Linear Regression ◽

Linear Models ◽

Fasting Glucose ◽

Adult Population ◽

Linear Regression Analysis ◽

Cobalt Concentration ◽

Model Assessment ◽

Homeostatic Model Assessment ◽

Cobalt Exposure

Abstract Background Little is known about the effects of environmental cobalt exposure on insulin resistance (IR) in the general adult population. We investigated the association between cobalt concentration and IR. Methods A total of 1281 subjects aged more than 20 years with complete blood cobalt data were identified from the National Health and Nutrition Examination Survey (NHANES) 2015–2016 cycle. Blood cobalt levels were analyzed for their association with IR among all populations and subgroups by sex. Regression coefficients and 95% confidence intervals (CIs) of blood cobalt concentrations in association with fasting glucose, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were estimated using multivariate linear regression after adjusting for age, sex, ethnicity, alcohol consumption, body mass index, education level, and household income. A multivariate generalized linear regression analysis was further carried out to explore the association between cobalt exposure and IR. Results A negative association between blood cobalt concentration (coefficient = − 0.125, 95% CI − 0.234, − 0.015; P = 0.026) and HOMA-IR in female adults in the age- and sex-adjusted model was observed. However, no associations with HOMA-IR, fasting glucose, or insulin were found in the overall population. In the generalized linear models, participants with the lowest cobalt levels had a 2.74% (95% CI 0.04%, 5.50%) increase in HOMA-IR (P for trend = 0.031) compared with subjects with the highest cobalt levels. Restricted cubic spline regression suggested that a non-linear relationship may exist between blood cobalt and HOMA-IR. Conclusions These results provide epidemiological evidence that low levels of blood cobalt are negatively associated with HOMA-IR in female adults.

Download Full-text

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00321.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. E381-E391 ◽

Cited By ~ 7

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.

Download Full-text

Insulin resistance in children with familial hyperlipidemia

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0337 ◽

2018 ◽

Vol 31 (12) ◽

pp. 1349-1354 ◽

Cited By ~ 1

Author(s):

Semiha Terlemez ◽

Erkin Bozdemir ◽

Sema Kalkan Uçar ◽

Ceyda Kabaroğlu ◽

Sara Habif ◽

...

Keyword(s):

Insulin Resistance ◽

Tolerance Test ◽

The Body ◽

Oral Glucose ◽

Model Assessment ◽

Apo B ◽

Factors Affecting ◽

Homeostatic Model Assessment ◽

Method Of Evaluation ◽

Familial Hyperlipidemia

Abstract Background The aim of the study was to investigate whether there is insulin resistance in children with familial hyperlipidemia (FHL) and to determine the factors affecting insulin resistance. Methods Hyperlipidemic children aged between 4 and 18 years and followed up with an FHL diagnosis were included in the study. The children of adults followed up with an FHL diagnosis were also recruited after the screening period. The scanned children were divided into two groups as hyperlipidemic and normolipidemic. A total of 77 patients of whom 52 were hyperlipidemic and 25 were normolipidemic were assessed in the study. Insulin resistance was evaluated (homeostatic model assessment of insulin resistance [HOMA-IR]) by performing the oral glucose tolerance test (OGTT). Results Of the patients, 36 were male and 41 were female; the average age was 11.6±3.9 years, and the body mass index (BMI) was established to be 20.3±4.4. In hyperlipidemic and normolipidemic patients, the following were determined: fasting insulin: 10.6 (±0.89) μU/mL, 4.9 (±0.45) μU/mL (p=0.000); 2-h insulin: 28.7 (±12.7) μU/mL, 18.9 (±10.5) μU/mL (p=0.000); and HOMA-IR: 1.9 (±0.17), 0.86 (±0.7) (p=0.000). No relationship was identified between lipid profiles and insulin resistance. Nevertheless, there was a positive correlation between insulin resistance and apolipoprotein B (Apo B) levels (0.52), and a negative correlation was determined in carnitine levels (−0.64). Conclusions Insulin resistance was established to be higher in children with FHL compared to normolipidemic children. Insulin resistance was not related to lipid phenotypes, but to Apo B levels and carnitine levels. Insulin resistance should be a routine method of evaluation in the follow-up of children with FHL.

Download Full-text

Association of Serum Levels of Zinc, Copper, and Iron with Risk of Metabolic Syndrome

Nutrients ◽

10.3390/nu13020548 ◽

2021 ◽

Vol 13 (2) ◽

pp. 548

Author(s):

Chia-Wen Lu ◽

Yi-Chen Lee ◽

Chia-Sheng Kuo ◽

Chien-Hsieh Chiang ◽

Hao-Hsiang Chang ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Linear Models ◽

Serum Zinc ◽

Serum Levels ◽

Least Square ◽

Model Assessment ◽

Serum Concentrations ◽

Metabolic Factors ◽

Homeostatic Model Assessment

The association between serum concentrations of zinc, copper, or iron and the risk of metabolic syndrome are inconclusive. Therefore, we conduct a case-control study to explore the relationship between serum levels of zinc, copper, or iron and metabolic syndrome as well as each metabolic factor and insulin resistance. We enrolled 1165 adults, aged ≥ 40 (65.8 ± 10) years in a hospital-based population to compare the serum levels of zinc, copper, and iron between subjects with and without metabolic syndrome by using multivariate logistic regression analyses. The least square means were computed by general linear models to compare serum concentrations of zinc, copper, and iron in relation to the number of metabolic factors. The mean serum concentrations of zinc, copper, and iron were 941.91 ± 333.63 μg/L, 1043.45 ± 306.36 μg/L, and 1246.83 ± 538.13 μg/L, respectively. The odds ratios (ORs) of metabolic syndrome for the highest versus the lowest quartile were 5.83 (95% CI: 3.35–10.12; p for trend < 0.001) for zinc, 2.02 (95% CI: 1.25–3.25; p for trend: 0.013) for copper, and 2.11 (95% CI: 1.24–3.62; p for trend: 0.021) for iron after adjusting for age, sex, personal habits, body mass index, and homeostatic model assessment insulin resistance. Additionally, the serum zinc, copper, and iron concentrations increased as the number of metabolic factors rose (p for trend < 0.001). This was the first study to clearly demonstrate that higher serum levels of zinc, copper, and iron were associated with the risk of metabolic syndrome and the number of metabolic factors independent of BMI and insulin resistance.

Download Full-text

Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

European Journal of Pediatrics ◽

10.1007/s00431-020-03924-w ◽

2021 ◽

Author(s):

Francesca Caroppo ◽

Alfonso Galderisi ◽

Laura Ventura ◽

Anna Belloni Fortina

Keyword(s):

Metabolic Disease ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Model Assessment ◽

Limited Data ◽

Single Center ◽

Increased Risk ◽

High Prevalence ◽

Homeostatic Model Assessment ◽

Homeostatic Model

AbstractPsoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3–10 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was ≥ 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance.Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis. What is Known:• Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.• Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis. What is New:• This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.• In children with psoriasis metabolic syndrome risk factors should be assessed.

Download Full-text

P1279INSULIN RESISTANCE IN HEMODIALYSIS PATIENS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1279 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Pavel Filinyuk ◽

Aleksander Rumyantsev

Keyword(s):

Insulin Resistance ◽

Systemic Inflammation ◽

Clinical Manifestations ◽

Biological Response ◽

Fold Increase ◽

Atherogenic Dyslipidemia ◽

Model Assessment ◽

Peripheral Tissues ◽

Reactive Protein ◽

Homeostatic Model Assessment

Abstract Background and Aims insulin resistance (IR) is a decrease in the biological response of sensitive tissues to insulin. IR is known as an adverse risk factor in cardiovascular disease, which largely determines the prognosis of patients receiving hemodialysis (HD). But this issue is not well understood. For the screening of IR, special indices have been developed that characterize the sensitivity of tissues to insulin. The aim of the study was to compare the methods of screening for IR in patients receiving HD in relation to the markers of systemic inflammation and atherogenic dyslipidemia (AtD). Method 124 patients receiving HD for 75.4 ± 44.5 months were examined including 66 men and 58 women aged 57.6 ± 13.6 years. For IR screening, the Homeostatic Model Assessment-1 and 2 indices (HOMA-1 and HOMA-2), the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides / glucose (Tri/G) were used. Patients were examined in accordance with the recommendations of KDIGO. Data analysis was carried out using “STATISTICA 10.0”. Results fasting insulin levels were elevated in 19% of patients. But, the calculated indices were consistent with the idea that IR is much more common. So, the IR index in the HOMA -1 model was increased in 47%, in the HOMA -2 model - in 33%, in the QUICKI model - in 36%, the TriH indicator - in 91%. The sensitivity of peripheral tissues in the HOMA-1 and HOMA-2 models was equally reduced by 35-40%. The results of the correlation analysis between indicators of IR and plasma concentration of C-reactive protein and lipid profile are presented in table 1. Informativeness of IR indicators depending on the presence of obesity is presented in table 2 We were also interested in whether insulin resistance affects the development of clinical manifestations of atherosclerosis, cardiac arrhythmias, and heart failure. An analysis of this relationship did not reveal. Only the IR index in the HOMA-1 model with a value of more than 2.7 units was associated with a 4.5-fold increase in the risk of developing clinical manifestations of atherosclerotic lesions (χ2 = 4.582 p = 0.032). Statistically significant it was only in men. Given our data, perhaps IR is one of the reasons for the higher morbidity and mortality of men at HD. Conclusion a comparison of IR models allows us to distinguish HOMA-2 as the most accurate index. The highest correlation with systemic inflammation and AtD was in the HOMA-1 and HOMA-2 indices.

Download Full-text

Pharyngeal collapsibility during sleep is elevated in insulin-resistant females with morbid obesity

European Respiratory Journal ◽

10.1183/13993003.00918-2015 ◽

2016 ◽

Vol 47 (6) ◽

pp. 1718-1726 ◽

Cited By ~ 1

Author(s):

Oscar L. Llanos ◽

Panagis Galiatsatos ◽

Edmarie Guzmán-Vélez ◽

Susheel P. Patil ◽

Philip L. Smith ◽

...

Keyword(s):

Insulin Resistance ◽

Fasting Glucose ◽

Sleep Apnoea ◽

Model Assessment ◽

Rapid Eye Movement Sleep ◽

Homeostasis Model Assessment ◽

Tonsillar Hypertrophy ◽

Insulin Resistant ◽

Bariatric Patients ◽

Respiratory Disturbance

Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10 events·h−1, diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp.Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104–0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196–0.835; p=0.021).Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.

Download Full-text

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.

Download Full-text