scholarly journals Fasting insulin reflects heterogeneous physiological processes: role of insulin clearance

2011 ◽  
Vol 301 (2) ◽  
pp. E402-E408 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Jinrui Cui ◽  
Yii-Der I. Chen ◽  
Willa A. Hsueh ◽  
Xiuqing Guo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Waist Circumference ◽  
Mexican Americans ◽  
Fasting Glucose ◽  
Insulin Clearance ◽  
Oral Glucose ◽  
Metabolic Clearance ◽  
Insulinogenic Index ◽  
Fasting Insulin

Several processes contribute to variation in fasting insulin concentration, including fasting glucose, insulin resistance, insulin secretion, and insulin clearance. Our goal was to determine the relative contribution of each of these insulin-related traits, plus anthropometric parameters, to fasting insulin among 470 Mexican Americans. The euglycemic hyperinsulinemic clamp yielded insulin sensitivity (M value) and metabolic clearance rate of insulin (MCRI). Acute insulin secretion was estimated by the insulinogenic index (IGI30) from the oral glucose tolerance test. Regression (univariate) and generalized estimating equations (multivariate) were used to describe the relationship of insulin-related traits to fasting insulin. Univarate analyses were used to select which traits to include in the multivariate model. In multivariate analysis, MCRI, M, BMI, waist circumference, and fasting glucose were independently associated with fasting insulin. Decreasing M and MCRI were associated with increasing fasting insulin, whereas increasing BMI, waist circumference, and fasting glucose were associated with increasing fasting insulin. Standardized coefficients allowed determination of the relative strength of each trait's association with fasting insulin in the entire cohort (strongest to weakest): MCRI (−0.35, P < 0.0001), M (−0.24, P < 0.0001), BMI (0.20, P = 0.0011), waist circumference (0.16, P = 0.021), and fasting glucose (0.11, P = 0.014). Fasting insulin is a complex phenotype influenced by several independent processes, each of which might have its own environmental and genetic determinants. One of the most associated traits was insulin clearance, which has implications for studies that have used fasting insulin as a surrogate for insulin resistance.

scholarly journals Sustained Decrease of Early-Phase Insulin Secretion in Japanese Women with Gestational Diabetes Mellitus who Developed Impaired Glucose Tolerance and Impaired Fasting Glucose Postpartum

2015 ◽  
Vol 6 ◽  
pp. JCM.S32743 ◽  
Author(s):  
Hiroko Katayama ◽  
Daisuke Tachibana ◽  
Akihiro Hamuro ◽  
Takuya Misugi ◽  
Koka Motoyama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Plasma Glucose Level ◽  
Fasting Glucose ◽  
Japanese Women ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Homeostasis Model Assessment

Objective The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design. Patients and Methods Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors. Results Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. Conclusions Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves.

Waist circumference and cardiorespiratory fitness are independently associated with glucose tolerance and insulin resistance in obese women

2014 ◽  
Vol 39 (3) ◽  
pp. 358-362 ◽  
Author(s):  
Einat Shalev-Goldman ◽  
K. Ashlee McGuire ◽  
Robert Ross
Keyword(s):  
Insulin Resistance ◽  
Waist Circumference ◽  
Glucose Tolerance ◽  
Cardiorespiratory Fitness ◽  
Fasting Glucose ◽  
Tolerance Test ◽  
Fasting Insulin ◽  
Obese Women ◽  
Insulin Metabolism ◽  
The Relationship

The purpose of this study was to determine the independent associations between physical activity (PA), cardiorespiratory fitness (CRF), abdominal obesity and insulin action in obese women. We studied 141 abdominally obese women (waist circumference (WC): 106.4 ± 10.2 cm). PA duration (min/day) and intensity (counts/min) were obtained by accelerometry. CRF was measured using a treadmill. WC was measured at the iliac crest; abdominal adiposity was measured by magnetic resonance imaging. Glucose and insulin measures were obtained during a 75-g, 2-h glucose tolerance test. The homeostasis model of assessment iHOMA2-IS was used to estimate insulin sensitivity. PA duration and intensity were not associated with glucose or insulin metabolism (p > 0.05). However, moderate-to-vigorous PA (MVPA) duration was associated with fasting insulin and iHOMA2-IS (p < 0.01). CRF was associated with fasting insulin and iHOMA2-IS (r = 0.27, p ≤ 0.01), whereas WC was associated with fasting insulin (r = 0.50, p < 0.01) and iHOMA2-IS (r = –0.52, p ≤ 0.01). Following adjustment for CRF, MVPA, and age, WC remained associated with fasting glucose, insulin, 2-h glucose and iHOMA2-IS (r = –0.44, p ≤ 0.01). CRF was associated with fasting glucose as well as 1- and 2-h glucose (r = 0.24, p < 0.01) after adjusting for WC, MVPA, and age. MVPA was not associated with glucose or insulin measures after control for CRF and WC (p > 0.05). Mediation analysis revealed that CRF and WC combined mediated the relationship between MVPA and both glucose tolerance and insulin resistance (p < 0.05). In conclusion, among abdominally obese women, WC and CRF are independently associated with measures of glucose tolerance and insulin resistance and mediate the association between MVPA and insulin resistance.

scholarly journals Low-density lipoprotein cholesterol is associated with insulin secretion

2021 ◽  
Author(s):  
Corinna Dannecker ◽  
Robert Wagner ◽  
Andreas Peter ◽  
Julia Hummel ◽  
Andreas Vosseler ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Insulin Clearance ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Glucose Load ◽  
Cholesterol Lowering ◽  
C Peptide ◽  
Increased Risk

Abstract Objective Pharmacological lowering of LDL cholesterol potently reduces cardiovascular risk while concurrently increasing type 2 diabetes risk. The aim of this study was to investigate the relationship between LDL cholesterol concentrations and insulin secretion and glucagon levels. Methods 3,039 subjects without cholesterol lowering therapy, but with increased risk for diabetes, underwent routine blood tests and a 5-point oral glucose tolerance test (OGTT). Glucagon concentrations, insulin secretion and insulin clearance indices were derived from the OGTT. Results There was no association between LDL cholesterol and fasting glucagon (p=0.7, ß=-0.01) or post glucose load glucagon levels (p=0.7, ß=-0.07), but we detected significant positive associations of LDL cholesterol and C-peptide-based indices of insulin secretion (AUCC-Peptide(0-30min)/AUCGlucose(0-30min): p=0.0001, ß=0.06; AUCC-Peptide(0-120min)/AUCGlucose(0-120min): p&lt;0.0001, ß=-0.08). In contrast we found a negative association of insulin-based insulin secretion indices with LDL concentrations (Insulinogenic index: p=0.014, ß=-0.04; disposition index: p=0.0005, ß=-0.06). Though, LDL cholesterol levels were positively associated with insulin clearance assessed from C-peptide and insulin concentrations, both in the fasting state and post glucose load (p&lt;0.0001, ß=0.09 and p&lt;0.0001, ß=0.06, respectively). Conclusion As C-peptide based indices reflect insulin secretion independent of hepatic clearance, our results indicate lower insulin secretion in case of lesser LDL cholesterol. This could explain deteriorating glycemic control in response to cholesterol lowering drugs.

Abstract P133: Added Sugar Intake Is Associated With Greater 2-hour Glucose And Lower Muscle Quality In Adults Free Of Diabetes: Coronary Artery Risk Development In Young Adults Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
So-Yun Yi ◽  
Lyn M Steffen ◽  
James G Terry ◽  
Daniel A Duprez ◽  
Brian Steffen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Energy Intake ◽  
Fasting Glucose ◽  
Dietary Guidelines ◽  
Muscle Quality ◽  
Oral Glucose ◽  
Fasting Insulin ◽  
Blood Draw ◽  
Added Sugar

Background: - Excess added sugar (AS) intake was shown to promote insulin resistance in skeletal muscle in animal studies, while sugar sweetened beverage (SSB) intake was associated with insulin resistance and lipids in skeletal muscle in humans. However, SSBs account for only 40% of AS intake. US adults consume excessive AS from foods and beverages relative to the 2015-2020 Dietary Guidelines recommendation which limit AS intake to <10% of energy intake per day. We evaluated the hypothesis that AS intake is adversely associated with glucose metabolism, insulin, and lean muscle attenuation (MA) in Black and white men and women aged 18-30 years at baseline (Y0). Methods: - After exclusions for diabetes defined as MD diagnosis, insulin or oral agent use, fasting glucose ≥126 mg/dL, or HbA1c ≥6.5%, outlying energy intake, and missing 2-hour glucose, 2,016 adults were included in the analyses. Dietary intake was assessed by Diet History at Y0, Y7 and Y20. At Y25 follow-up, participants free of diabetes underwent a fasting blood draw for glucose, insulin, and triglycerides, an oral glucose tolerance test for 2-hour post-challenge glucose, and an abdominal CT scan for lean MA (an indicator of muscle quality). AS intake was averaged across Y0, Y7, and Y20 and divided into tertiles. General linear regression models estimated the associations across tertiles of AS intake with 2-hour glucose, fasting glucose, insulin, and triglycerides, and lean MA adjusted for potential confounders. Results: - AS intake (Table) was positively associated with 2-hour glucose and fasting insulin and triglycerides (p trend =0.004, 0.04, and 0.01, respectively) and inversely associated with lean MA (p trend =0.02). AS intake was not associated with fasting glucose (p trend =0.57). Conclusions: - Among adults free of diabetes, greater long-term AS intake was associated with higher 2-hour glucose and fasting insulin and triglycerides, and lower muscle quality. Our findings are consistent with the US Dietary Guidelines for Americans recommendation to limit AS intake.

scholarly journals Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity

2008 ◽  
Vol 159 (5) ◽  
pp. 577-583 ◽  
Author(s):  
Lovisa E Johansson ◽  
Ulf Lindblad ◽  
Charlotte A Larsson ◽  
Lennart Råstam ◽  
Martin Ridderstråle
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Cell Function ◽  
Leisure Time Physical Activity ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Β Cell Function

ObjectiveThe insulin responsive adiponutrin or patatin-like phospholipase 3 (PNPLA3, previously ADPN) gene shows association with obesity and in vitro adipocyte lipolysis. This study aimed to replicate the association between PNPLA3 variants and obesity, and to investigate their effect on insulin resistance and β-cell function.Methodsrs738409 (Met148Ile) and rs2072907 (C to G) were genotyped using TaqMan allelic discrimination assay in a Swedish population-based sample (n=1811). Oral glucose tolerance test (OGTT) with data from three time points (0, 30, and 120 min) were available from individuals under the age of 50 years (n=973).ResultsBoth variant alleles were associated with decreased prevalence of obesity (P<0.05); odds ratio 0.75 (0.61–0.93) per carried Ile-allele for rs738409 and 0.80 (0.64–1.00) per carried G-allele for rs2072907. For obesity as a quantitative trait, there was no association in the whole population, but in obese subjects body mass index (BMI; P=0.023) and waist (P=0.0098) were higher in carriers of the Ile-allele. The Ile-carriers also displayed decreased insulin secretion in response to OGTT (30 min insulin; P=0.007, insulinogenic index; P=0.0051) with no significant differences in fasting plasma glucose (P=0.31), β-cell function (disposition index; P=0.17) or homeostasis model of assessment insulin resistance (HOMA-IR; P=0.063). The correlation between BMI and HOMA-IR differed (Met/X versus Ile/Ile, P=0.028), Met-allele carriers were seemingly more insulin resistant at a lower BMI. The rs2072907 variant shows similar results for insulin secretion. The significance of this finding remained after adjusting for age, gender, and level of self-reported leisure-time physical activity.ConclusionWe confirm the association between PNPLA3 and obesity. In addition, the rs738409 variant was associated with insulin secretion. There seems to be a differential effect of the Ile-allele depending on the degree of obesity, possibly as a consequence of insulin resistance.

scholarly journals The Use of Biochemical Parameters Instead of MRI for the Prediction of Pancreatic Iron Loading Among Patients with β-Thalassemia Major

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1356-1356
Author(s):  
Munevver Bas ◽  
Fatma Gumruk ◽  
Tuncay Hazirolan ◽  
A. Murat Tuncer ◽  
Mualla Cetin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Iron Overload ◽  
Fasting Glucose ◽  
Thalassemia Major ◽  
Iron Accumulation ◽  
Oral Glucose ◽  
Iron Loading ◽  
Fasting Insulin ◽  
Normal Range ◽  
Cardiac Iron

Abstract Patients with β-thalassemia major (BTM) are prone to morbidities and mortalities of iron accumulation as a consequence of transfusional iron overload and increased intestinal iron absorption. The use of cardiac and hepatic T2* measurements to pr edict the amount of iron accumulation in these organs have been studied extensively and was suggested to be used reliably. However, although the use of MRI for the assessment of iron status in other organs such as pancreas is possible, it may not be practical to screen all organs with MRI related to economical issues and also the prolonged imaging durations. Herein, we studied fasting glucose, fasting insulin, HOMA-IR, HOMA-B and oral glucose tolerance results among patients with BTM, to detect the correlations of these measurements with pancreas, cardiac and hepatic T2* or R2* MRI values. Patients with BTM from a single center were included in the study between February 2013 and January 2014. All patients were above seven years of age, and were on regular erythrocyte transfusion programme. Only the patients who were compliant to iron chelation treatments were included in the study. Patients with hepatitis B or C, and/or cirrhosis were excluded. The study included a total of 37 patients who fulfilled the inclusion and exclusion criteria. Cardiac, hepatic T2* and pancreas T2* and R2* MRI was applied with 1.5 T (Siemens, Symphony, Erlangen, Germany) device. Simultaneous to MRI, fasting glucose, fasting insulin, HOMA-IR, HOMA-B and oral glucose tolerance results were obtained. HOMA-B was calculated as: insulin (μU/ml) x 20/glucose (mg/dl) - 3.5 and the normal range is 130-400. HOMA-IR was calculated as: insulin (μU/ml) x glucose (mg/dl) / 22,5 and the normal range is 0.8-1.6. Insulin resistance is defined as HOMA-IR value above 1.6. Two patients had a diagnosis of diabetes mellitus. The mean age of patients participating in the study was 20.8 ± 6.3 years (7.1-36.8). Of the study group, 43.3 % was above 20 years of age. According to BMI assessments, 32 (86.5%) of the patients had normal BMI, whereas 5 (13.5%) were underweight. Insulin resistance was found in 7.4% of the patients. Fasting blood glucose has been shown to increase with decreases of pancreatic T2* values, which was indicative of increase in fasting glucose levels in parallel to increased pancreatic iron accumulation (r= -0,55, p=0.016). Also there was a statistically significant positive correlation between fasting insulin and pancreatic R2* values. (r= 0.59, p= 0.01). A positive correlation was found between fasting insulin levels and pancreas R2* measeures, indicating increase in fasting insulin levels, paralleling the pancreatic iron accumulation. Correlation analysis was perfromed for cardiac and hepatic T2*, pancreas T2*, R2* and simultaneously calculated HOMA-IR and HOMA-B values and a negative correlation was found between liver T2* and HOMA-IR values (r=-0.54, p=0.004). A negative correlation was found between pancreas R2* ile cardiac T2* (r=-0.67, p=0.02), indicating increased pancreatic iron loading in parallel with cardiac iron accumulation. In centers where T2*/R2* MRI fascilities are unavailable, fasting insulin, fasting glucose, HOMA-IR measurements may be used to predict pancreatic iron overload. Since hepatic iron loading correlated with insulin resistance development, the insulin resistance among patients with BTM may partially be explained with decreased hepatic insulin clearance from heavily iron loaded liver. Additionally, disorders of glucose metabolism should be taken as a sign for the need to exercise caution in terms of cardiac iron overload and just vice versa patients with cardiac iron loading should be examined thoroughly for consequences of pancreatic iron loading. These biochemical tests may be used dynamically and more frequently throughout the control visits, whereas MRI is ordered at most once or twice a year which may cause a delay for the earlier diagnosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals The efficiency of dapagliflozin as add-on therapy in obese patients with resistant hypertension and chronic kidney disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Obertynska
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Insulin Secretion ◽  
Waist Circumference ◽  
Antihypertensive Effect ◽  
Fasting Glucose ◽  
Fluid Retention ◽  
Obese Patients

Abstract Background Obesity, insulin resistance, renal dysfunction, hyperuricemia are some of the most common causes of resistant hypertension (RH). A close relationship exists between RH and fluid retention. Currently, there is no consensus regarding pathogenetic therapy of RH and there are no studies on the effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors in obese patients with RH and chronic kidney disease (CKD). The aim was to evaluate the effects of dapagliflozin (D) in obese P with RH and CKD stages 3a. Methods 45 obese P (mean body mass index (BMI) 34.2 kg/m2, waist circumference (WC) 104 cm) with true RH and CKD 3a (eGFR 45–59 mL/min/1.73m2) were included in the study under conventional therapy full doses of appropriate combinations (mean 3.7 antihypertensive drugs). The D at daily doses of 10 mg was added to previous treatment. The blood pressure (BP) was measured in the office and by ambulatory BP monitoring. Anthropometry, metabolic profile, including oral glucose tolerance test with insulin, homeostatic model assessment HOMA-R, hematocrit (Hct), uric acid, potassium (K), serum creatinine, calculated GFR were performed at baseline and after 12 weeks treatment. Results At baseline were excellent correlations between BMI and SBP (r=0.45, P&lt;0.01), eGFR and DBP (r=−0.33, P&lt;0.05), eGFR and Hct (r=0.31, P&lt;0.05), BMI and HOMA-R (r=0.34, P&lt;0.05). At baseline mean HOMA-R was 2,8±0.7, eGFR 53.50±3.26 ml/min/1.73 m2, uric acid 469±23 nmol/L, K 4,9±0.9 mmol/L. The asymptomatic hyperuricemia was observed in 57%, impaired glucose tolerance in the 37%. After 12 weeks administration of D, the mean 24 h ambulatory BP effectively decreased (−7.6/−4.3 mmHg; P&lt;0.05 for both; respectively. Also, there were significant decreases in BMI (−2,1 kg/m2, P&lt;0.01), WC (−4,8 cm, P&lt;0.01), fasting glucose (−0,8 mmol/L, P&lt;0.01) and uric acid (−42 nmol/L, P&lt;0.01) without changes in insulin secretion and not significant improvement in HOMA-R (2,8±0.7 versus 2.4±0.4). Mean eGFR and K on D remained unchanged, however, the albumin/creatinine ratio decreased significantly (P&lt;0.05). Also, the Hct significantly increased after start of D (P&lt;0.01). By linear regression analysis, the independent associated factor for the change SBP was baseline BMI (P&lt;0.05) and for the change DBP baseline eGFR (P&lt;0.05). Conclusion Dapagliflozin shows an additional antihypertensive effect when added to the prior combination therapy in obese patients with RH and CKD 3a without risk of hyperkalemia. Dapagliflozin increase hematocrit, possibly due to its diuretic effects and hemoconcentration. So, positive antihypertensive effect D is due to natriuretic effect and decrease fluid retention. Furthermore, there is also a strong indication that the BP effect is also influenced by weight loss and dapagliflozin administration decreased body mass index, waist circumference, fasting glucose and uric acid, with a tendency to decrease the insulin resistance without changes in insulin secretion. FUNDunding Acknowledgement Type of funding sources: None.

Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans

Diabetes ◽  
1995 ◽  
Vol 44 (12) ◽  
pp. 1386-1391 ◽  
Author(s):  
S. M. Haffner ◽  
H. Miettinen ◽  
S. P. Gaskill ◽  
M. P. Stern
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Mexican Americans

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

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