Serum angiopoietin-like 3 levels are elevated in obese non diabetic men but are unaffected during an oral glucose tolerance test.
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ABSTRACT:
SUBMITTER: Garces MF
PROVIDER: S-EPMC7713064 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Serum angiopoietin-like 3 levels are elevated in obese non diabetic men but are unaffected during an oral glucose tolerance test.
Garcés Maria Fernanda MF Buell-Acosta Julieth Daniela JD Rodríguez-Navarro Haiver Antonio HA Pulido-Sánchez Estefania E Rincon-Ramírez Juan José JJ Moreno-Ordóñez Diana Carolina DC Franco-Vega Roberto R Roncancio-Muñoz Jhoan Sebastian JS Burgos-Cardenas Alvaro Javier AJ Lacunza Ezequiel E Castaño Justo P JP Diéguez Carlos C Nogueiras Rubén R Sanchez Elizabeth E Caminos Jorge Eduardo JE
Scientific reports 20201203 1
This study aimed to determine ANGPTL3 serum levels in healthy young lean and obese non-diabetic men during an oral glucose tolerance test (OGTT) and correlate them with anthropometric, biochemical and hormonal parameters. A case-control study was carried out and 30 young obese non-diabetic (23.90 ± 3.84 years and BMI 37.92 ± 4.85 kg/m<sup>2</sup>) and 28 age-matched healthy lean (24.56 ± 3.50 years and BMI of 22.10 ± 1.72 kg/m<sup>2</sup>) men were included in this study. The primary outcome mea ...[more]
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Project description:Impaired glucose tolerance (IGT) is diagnosed by a standardized oral glucose tolerance test (OGTT). However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state.Given a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA), proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1?year.The most accurate prediction of IGT was reached with the recursive partitioning method (accuracy?=?0.78). For all classifiers, mean accuracy was 0.73?±?0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77.Machine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a subsequent OGTT.
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Project description:BackgroundAlternate methods for characterizing oral glucose tolerance tests (OGTT) have emerged as superior to the 2-hour glucose in identifying individuals at risk for type 2 diabetes. The significance of these methods in cystic fibrosis (CF) is unclear. We compared 3 OGTT classifications in youth with CF: 1. curve shape (biphasic vs. monophasic), 2. time to glucose peak (≤30minutes vs. >30minutes), 3. 1-hour glucose (1hG) <155 mg/dL vs. ≥155 mg/dL to traditional OGTT criteria to determine which best identifies lower oral disposition index (oDI), pulmonary function, and body mass index (BMI).MethodsYouth 10-18 years with CF, not on insulin, underwent 2-hour OGTT. Glucoses were classified by traditional criteria and 3 alternate methods as normal (biphasic curve, glucose peak ≤30minutes, and/or 1hG <155 mg/dL) or abnormal (monophasic curve, glucose peak >30minutes, and/or 1hG ≥155 mg/dL). oDI was calculated [1/fasting insulin*(ΔInsulin0-30 min/ΔGlucose0-30 min)]. Mean oDI, BMI, forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) were compared by OGTT classification.ResultsFifty-two youth with CF participated (mean±SD age 13±4years; 37% male; BMI z-score 0.0±0.8; FEV1 88±16.3%; FVC 97±14.8%). Late time to peak glucose and 1hG ≥155 mg/dL identified individuals with lower oDI (p=0.01); traditional OGTT criteria for prediabetes did not. No OGTT classification identified individuals with worse BMI nor pulmonary function. oDI was not associated with BMI, FEV1, or FVC.ConclusionsAlternate OGTT measures including time to peak glucose and 1hG better identify oDI abnormalities than traditional criteria. Further studies are required to determine whether these alternate methods identify individuals with CF at risk for future clinical decline.
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Project description:IntroductionThe Oral Minimal Model (OMM), a differential-equations based mathematical model of glucose-insulin dynamics, utilizes data from a frequently sampled oral glucose tolerance test (OGTT) to quantify insulin sensitivity ( SI ). OMM-based estimates of SI can detect differences in insulin resistance (IR) across population groups and quantify effects of clinical or behavioral interventions. These estimates of SI have been validated in healthy adults using data from OGTTs with durations from 2 to 7 h. However, data demonstrating how protocol duration affects SI estimates in highly IR populations such as adolescents with obesity are limited.MethodsA 6-h frequently sampled OGTT was performed in adolescent females with obesity. Two, 3-, and 4- hour implementations of OMM assuming an exponentially-decaying rate of glucose appearance beyond measured glucose concentrations were compared to the 6-h implementation. A 4- hour OMM implementation with truncated data (4h Tr) was also considered.ResultsData from 68 participants were included (age 15.8 ± 1.2 years, BMI 35.4 ± 5.6 kg/m2). Although SI values were highly correlated for all implementations, they varied with protocol duration (2h: 2.86 ± 3.31, 3h: 2.55 ± 2.62, 4h: 2.81 ± 2.59, 4h tr: 3.13 ± 3.14, 6h: 3.06 ± 2.85 x 10-4 dl/kg/min per U/ml). SI estimates based on 2 or 3 h of data underestimated SI values, whereas 4-h SI estimates more closely approximated 6-h SI values.DiscussionThese results suggest that OGTT protocol duration should be considered when implementing OMM to estimate SI in adolescents with obesity and other IR populations.
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Project description:Objective Approximately 50% of obese Black patients with unprovoked diabetic ketoacidosis (DKA) or severe hyperglycemia (SH) at new-onset diabetes achieve near-normoglycemia remission with intensive insulin treatment. Despite the initial near-normoglycemia remission, most DKA/SH individuals develop hyperglycemia relapse after insulin discontinuation. Traditional biomarkers such as normal glucose tolerance at the time of remission were not predictive of hyperglycemia relapse. We tested whether 1-h plasma glucose (1-h PG) at remission predicts hyperglycemia relapse in Black patients with DKA/SH. Methods Secondary analysis was performed of two prospective randomized controlled trials in 73 patients with DKA/SH at the safety net hospital with a median follow-up of 408 days. Patients with DKA/SH underwent a 5-point, 2-h 75-g oral glucose tolerance test after hyperglycemia remission. Hyperglycemia relapse is defined by fasting blood glucose (FBG) > 130 mg/dl, random blood glucose (BG) >180 mg/dl, or HbA1c > 7%. Results During the median 408 (interquartile range: 110–602) days of follow-up, hyperglycemia relapse occurred in 28 (38.4%) participants. One-hour PG value ≥199 mg/dl discriminates hyperglycemia relapse (sensitivity: 64%; specificity: 71%). Elevated levels of 1-h PG (≥199 mg/dl) were independently associated with hyperglycemia relapse (adjusted hazard ratio: 2.40 [95% CI: 1.04, 5.56]). In a multivariable model with FBG, adding 1-h PG level enhanced the prediction of hyperglycemia relapse, with significant improvements in C-index (Δ: +0.05; p = 0.04), net reclassification improvement (NRI: 48.7%; p = 0.04), and integrated discrimination improvement (IDI: 7.8%; p = 0.02) as compared with the addition of 2-h PG (NRI: 20.2%; p = 0.42; IDI: 1.32%; p = 0.41) or HbA1c (NRI: 35.2%; p = 0.143; IDI: 5.8%; p = 0.04). Conclusion One-hour PG at the time of remission is a better predictor of hyperglycemia relapse than traditional glycemic markers among obese Black patients presenting with DKA/SH. Testing 1-h PG at insulin discontinuation identifies individuals at high risk of developing hyperglycemia relapse.
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Project description:BackgroundOral glucose tolerance test (OGTT) is a traditional diagnostic tool for diabetes. Hemoglobin A1c (HbA1c) is an alternative method used in adults; however, its application in youths has been controversial. We evaluated the diagnostic performance of HbA1c and determined optimal cutoff points for detecting prediabetes and diabetes in youth.MethodsThis retrospective study included 389 obese children (217 boys, 55.8%) who had undergone simultaneous OGTT and HbA1c testing at six hospitals, Korea, between 2010 and 2016. Subjects were diagnosed with diabetes (fasting glucose ≥ 7.0 mmol/L; 2-hour glucose ≥ 11.1 mmol/L) or prediabetes (fasting glucose 5.6-6.9 mmol/L; 2-hour glucose 7.8-11.0 mmol/L). The diagnostic performance of HbA1c for prediabetes and diabetes was determined using the area under the receiver operating characteristic curve (AUC).ResultsAt diagnosis, 197 (50.6%) subjects had normoglycemia, 121 (31.1%) had prediabetes, and 71 (18.3%) had diabetes. The kappa coefficient for agreement between OGTT and HbA1c was 0.464. The optimal HbA1c cutoff points were 5.8% (AUC, 0.795; a sensitivity of 64.1% and a specificity of 83.8%) for prediabetes and 6.2% (AUC, 0.972; a sensitivity of 91.5% and a specificity of 93.7%) for diabetes. When HbA1c (≥ 6.2%) and 2-hour glucose level were used to diagnose diabetes, 100% were detected.ConclusionPediatric criteria for HbA1c remain unclear, therefore, we recommend the combination of fasting and 2-hour glucose levels, in addition to HbA1c, in the diagnosis of childhood prediabetes and diabetes.
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Project description:Aims/hypothesisImpaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men.MethodsEleven NGT men and nine long-term diagnosed type 2 diabetic men (7 ± 1 years), matched for age (58 ± 2 vs 62 ± 2 years), BMI (31.4 ± 0.6 vs 30.5 ± 0.6 kg/m(2)) and [Formula: see text] (28.9 ± 1.5 vs 29.5 ± 2.4 ml kg(-1) min(-1)) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic-euglycaemic clamp (8, 20 and 40 mU m(-2) min(-1)). AT and SM biopsies were collected to investigate underlying mechanisms.ResultsHyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (-7 ± 6%, -13 ± 9% and -27 ± 9%) compared with men with NGT (-21 ± 7%, -38 ± 8% and -53 ± 8%) (p = 0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8 ± 3.1 vs 30.5 ± 2.0 μmol kg body weight(-1) min(-1); p < 0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups.Conclusions/interpretationOur results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes.Trial registrationClinicalTrials.gov NCT01680133.
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Project description:ObjectiveThe objective of the present study was to compare 24-hour glycemic levels between obese pregnant women with normal glucose tolerance and non-obese pregnant women.MethodsIn the present observational, longitudinal study, continuous glucose monitoring was performed in obese pregnant women with normal oral glucose tolerance test with 75 g of glucose between the 24th and the 28th gestational weeks. The control group (CG) consisted of pregnant women with normal weight who were selected by matching the maternal age and parity with the same characteristics of the obese group (OG). Glucose measurements were obtained during 72 hours.ResultsBoth the groups were balanced in terms of baseline characteristics (age: 33.5 [28.7-36.0] vs. 32.0 [26.0-34.5] years, p = 0.5 and length of pregnancy: 25.0 [24.0-25.0] vs. 25.5 [24.0-28.0] weeks, p = 0.6 in the CG and in the OG, respectively). Pre-breakfast glycemic levels were 77.77 ± 10.55 mg/dL in the CG and 82.02 ± 11.06 mg/dL in the OG (p<0.01). Glycemic levels at 2 hours after breakfast were 87.31 ± 13.10 mg/dL in the CG and 93.48 ± 18.74 mg/dL in the OG (p<0.001). Daytime blood glucose levels were 87.6 ± 15.4 vs. 93.1 ± 18.3 mg/dL (p<0.001) and nighttime blood glucose levels were 79.3 ± 15.8 vs. 84.7 ± 16.3 mg/dL (p<0.001) in the CG and in the OG, respectively. The 24-hour, daytime, and nighttime values of the area under the curve were higher in the OG when compared with the CG (85.1 ± 0.16 vs. 87.9 ± 0.12, 65.6 ± 0.14 vs. 67.5 ± 0.10, 19.5 ± 0.07 vs. 20.4 ± 0.05, respectively; p<0.001).ConclusionThe results of the present study showed that obesity in pregnancy was associated with higher glycemic levels even in the presence of normal findings on glucose tolerance test.
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Project description:ContextMorphological characteristics of the glucose curve during an oral glucose tolerance test (OGTT) (time to peak and shape) may reflect different phenotypes of insulin secretion and action, but their ability to predict diabetes risk is uncertain.ObjectiveTo compare the ability of time to glucose peak and curve shape to detect prediabetes and β-cell function.Design and participantsIn a cross-sectional evaluation using an OGTT, 145 adults without diabetes (age 42±9 years (mean±SD), range 24-62 years, BMI 29.2±5.3 kg/m2 , range 19.9-45.2 kg/m2 ) were characterized by peak (30 minutes vs >30 minutes) and shape (biphasic vs monophasic).Main outcome measuresPrediabetes and disposition index (DI)-a marker of β-cell function.ResultsPrediabetes was diagnosed in 36% (52/145) of participants. Peak>30 minutes, not monophasic curve, was associated with increased odds of prediabetes (OR: 4.0 vs 1.1; P<.001). Both monophasic curve and peak>30 minutes were associated with lower DI (P≤.01). Time to glucose peak and glucose area under the curves (AUC) were independent predictors of DI (adjR2 =0.45, P<.001).ConclusionGlucose peak >30 minutes was a stronger independent indicator of prediabetes and β-cell function than the monophasic curve. Time to glucose peak may be an important tool that could enhance prediabetes risk stratification.
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