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  • 1
    In: The American Journal of Human Genetics, Elsevier BV, Vol. 100, No. 2 ( 2017-02), p. 343-351
    Type of Medium: Online Resource
    ISSN: 0002-9297
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1473813-2
    SSG: 12
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  • 2
    In: Clinical Endocrinology, Wiley, Vol. 93, No. 5 ( 2020-11), p. 579-589
    Abstract: The effects of dietary macronutrients on orexigenic and anorexigenic hormones in children are poorly understood. Objective To explore effects of varying dietary macronutrients on appetite‐regulating hormones [acyl ghrelin (AG) and desacyl ghrelin (DAG), glucagon‐like peptide 1 (GLP‐1), peptide tyrosine tyrosine (PYY) and insulin] in children with PWS and healthy children (HC). Design Randomized, cross‐over experiments compared two test diets [high protein‐low carbohydrate (HP‐LC) and high protein‐low fat ( HP‐LF) ] to a STANDARD meal (55% carbohydrate, 30% fat, 15% protein). Experiment 1 included ten children with PWS (median age 6.63 years; BMI z 1.05); experiment 2 had seven HC (median age 12.54 years; BMI z 0.95). Blood samples were collected at baseline and at 60‐minute intervals for 4 hours. Independent linear mixed models were adjusted for age, sex and BMI z ‐score. Results Fasting and post‐prandial AG and DAG concentrations are elevated in PWS children; the ratio of AG/DAG is normal. Food consumption reduced AG and DAG concentrations in both PWS and HC. GLP‐1 levels were higher in PWS after the HP‐LC and HP‐LF meals than the STANDARD meal ( P  = .02‐0.04). The fasting proinsulin to insulin ratio (0.08 vs 0.05) was higher in children with PWS ( P  = .05) than in HC. Average appetite scores in HC declined after all three meals ( P  = .02) but were lower after the HP‐LC and HP‐LF meals than the STANDARD meal. Conclusion Altered processing of proinsulin and increased GLP‐1 secretion in children with PWS after a high protein meal intake might enhance satiety and reduce energy intake.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2004597-9
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  • 3
    In: Clinical Endocrinology, Wiley, Vol. 69, No. 6 ( 2008-12), p. 911-920
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 2004597-9
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  • 4
    In: Clinical Endocrinology, Wiley, Vol. 90, No. 4 ( 2019-04), p. 553-561
    Abstract: Macronutrient regulation of hyperphagia and adiposity in Prader‐Willi syndrome (PWS) is poorly understood. We compared fasting and postprandial concentrations of hormones and metabolites in eight PWS children (age 9‐18 years) fed, in random order, low carbohydrate, high‐fat (LC, 15% carb; 65% fat; 20% protein) and low‐fat, high carbohydrate (LF, 65% carb, 15% fat, 20% protein) diets matched for calories and protein. Methods Participants were randomized to consume either the LC or LF diet during a first hospital admission and the second diet during a subsequent admission. Blood samples were obtained after overnight fasting and 1 hour after a mixed meal. Results Relative to subjects consuming the LF diet, subjects consuming the LC diet had: lower postprandial insulin concentrations ( P  = 0.02); higher fasting GLP‐1 AND GIP concentrations and increased postprandial GLP‐1 ( P   〈  0.02); reduced ratio of fasting ghrelin to GLP‐1 ( P  = 0.0078); increased FFA and fatty acid oxidation, as assessed by concentrations of even‐chain acylcarnitines ( P   〈  0.001); lower fasting TG and TG/HDL ratio ( P   〈  0.01); and higher concentrations of branch chain amino acids ( P   〈  0.01). There were no changes in glucose, PYY, or adiponectin. CRP, AST and ALT were all higher ( P   〈  0.01) on the LC diet. Conclusions Increases in GLP‐1 with low carbohydrate feeding and reductions in the ratio of ghrelin to GLP‐1 might limit food intake and improve glycaemic control in PWS. Other potential benefits of carbohydrate restriction may include fat mobilization and oxidation and reductions in the TG/HDL ratio, a marker of insulin resistance. However, increases in CRP, AST and ALT necessitate longer‐term studies of low carbohydrate efficacy and safety.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 5
    In: Clinical Endocrinology, Wiley, Vol. 67, No. 6 ( 2007-12), p. 944-951
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2007
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  • 6
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 6, No. Supplement_1 ( 2022-11-01), p. A636-A636
    Abstract: Type 1 diabetes (T1D) is associated with decreased skeletal muscle mass (SMM) and impaired muscle function in adults. Despite the importance of skeletal muscle in insulin action and metabolic homeostasis, our understanding of skeletal muscle health in children with T1D is very limited. Here we used a novel, non-invasive methodology to compare muscle mass (MM) in children with T1D and sex and age-matched healthy children without diabetes. Objectives We hypothesized that: (a) children with T1D have lower MM than age, sex, and BMI-matched children without T1D; (b) MM in children with T1D correlates with insulin sensitivity and glycemic control. Methods Weight (BW), height, BMI%, body fat% (BF%), daily insulin requirement, CGM data, HbA1c, and total and HMW adiponectin were measured in 24 young children (15 females, 9 males; age 6-11 years) with T1D. BF% and fat-free-mass (FFM) was measured by bioelectrical impedance. Insulin sensitivity was assessed by total and HMW-adiponectin and daily insulin requirements. Glycemic control was assessed by glucose time in range, mean blood glucose, and HbA1c. MM was measured using the D3creatine dilution method in 22 of the children with T1D (14 females, 8 males) and, in a separate study, in 34 children without T1D (17 females and 17 males). This method involves an oral 10 mg dose of deuterated creatine (methyl-d3, D3Cr). Creatine is converted in vivo to creatinine, including D3Cr to D3creatinine, in muscle by an irreversible, nonenzymatic reaction and then excreted. A single fasting urine sample is collected to determine D3creatinine enrichment. MM/BW (%) was calculated to normalize for body weight. Results There were strong positive associations between MM and body weight (r=0.85, p & lt;0.0001), BMI (r=0.61, p=0.0028), and FFM (r=0.72, p=0.0040). Although children with T1D were slightly older (9.2 ±1.3 vs 8.1± 1.2 yo, p=0.003) and had higher BMI (18± 2.3 vs16.0 ±2.0, p=0.001) than controls, they had lower %MM/BW than children without diabetes (37.8± 4.6 vs 43.1±4.5%, p & lt;0.0001). The lower %MM/BW in T1D compared to controls was confirmed in sub-cohorts matched for age and in males and females analyzed separately. Mean daily insulin requirement and HbA1c in the children with T1D were 0.76±0.15 IU/kg/day and 7.1±1.1%, respectively. MM, FFM, %BF, FM, %MM/BW did not correlate with metrics of insulin sensitivity or glycemic control. Conclusions This is the first study to quantitate MM directly in young children with T1D. Our results demonstrate a lower %MM in 6–11-year-old pre-pubertal children with T1D with stable and reasonable glycemic control. The cause for the lower % MM in T1D is not clear; however future studies could examine the rates of muscle protein and fat synthesis and breakdown in healthy and diabetic children along with their relations to insulin administration, metabolic control, growth, and pubertal development. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
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  • 7
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. 2 ( 2022-12-15)
    Abstract: Blood pressure and plasma catecholamines normally decline during sleep and rapidly increase in early morning. This is blunted in adults with type 2 diabetes (T2D). Objective We hypothesize that increased sympatho-adrenal activity during sleep differentiates youth with T2D from nondiabetic obese youth and lean youth. Methods Fasting spot morning and 24-hour urines were collected in obese adolescents with and without T2D, and normal-weight controls. Fractionated free urine catecholamines (epinephrine, norepinephrine, and dopamine) were measured, and the ratio of fasting spot morning to 24-hour catecholamines was calculated. Results Urinary 24-hour catecholamine levels were comparable across the 3 groups. Fasting morning epinephrine and the ratio of fasting morning/24-hour epinephrine were higher in youth with T2D (P = 0.004 and P = 0.035, respectively). In males, the ratio of fasting morning/24-hour epinephrine was also higher in youth with T2D (P = 0.005). In females, fasting morning norepinephrine and the ratio of fasting morning/24-hour dopamine were lower in obese youth with and without T2D (P = 0.013 and P = 0.005, respectively) compared with lean youth. Systolic blood pressure was higher in diabetic participants than other groups; males trended higher than females. Conclusion Circadian rhythm in catecholamines is disrupted in youth-onset T2D, with a blunted overnight fall in urinary epinephrine in males. Conversely, fasting morning norepinephrine and dopamine levels were lower in obese females with or without T2D. Higher nocturnal catecholamines in males with T2D might associate with, or predispose to, hypertension and cardiovascular complications. Lower catecholamine excretion in females with obesity might serve an adaptive, protective role.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
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  • 8
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 6, No. Supplement_1 ( 2022-11-01), p. A613-A614
    Abstract: In healthy, normal - weight adults there is a circadian rhythm in blood pressure (BP) and plasma catecholamines (epinephrine and norepinephrine): BP and the levels of norepinephrine and epinephrine decline during sleep, followed by a rapid increase during the early morning hours. Studies in adults with Type 2 diabetes (T2D) show blunted reductions in BP and plasma catecholamine levels during sleep that are associated with increased risks for heart failure, stroke, myocardial infarction, and sudden death. In this study, we explored if the circadian rhythm in catecholamines is disrupted in youth-onset T2D. We hypothesized that increased sympatho-adrenal activity during sleep differentiates youth with T2D from non-diabetic overweight/obese and lean youth of comparable age, pubertal status, and ethnicity. To that end, we measured urine catecholamines in fasting – morning-spot urines and 24-hour urine samples. Methods 56 non-diabetic adolescents with overweight/obesity ("obese"), 42 adolescents with T2D ("T2D"), and 43 normal-weight controls ("lean"); aged 12-21 years, were studied. None was diagnosed with hypertension, and none was on antihypertensive treatment. Weight, height, BMI, BMI%, and BP were extracted from medical charts. Body fat percent (BF%) was measured by TANITA. Stress levels were assessed using PHQ-2 and PHQ-9 questionnaires. Fractionated free urine catecholamines (epinephrine, norepinephrine, and dopamine) were analyzed by liquid chromatography/tandem mass spectrometry (LC/MS-MS) in both spot and 24-hour urines, normalized to urinary creatinine. The ratio of fasting morning urine catecholamines to 24-hour urine catecholamines was calculated to assess circadian variation in catecholamines. Group differences were assessed by Kruskal-Wallis or ANOVA. Results Groups were comparable for age (obese 14.8 +/- 1.9; T2D 15.7 +/- 2.1 and lean 14.9 +/- 1.9-yr), pubertal status, and ethnicity. Obese youth with and without T2D were predominantly female (T2D, 28 F, 14 M; obese 33 F, 23 M; lean, 17 F, 26 M); those with T2D had highest BF% (obese 37.3 +/- 9.5; T2D 42.9 +/- 9.9; lean 20.1 +/- 6.3%; p=2.58e-22) and systolic blood pressure (obese 115.36 +/- 11.54; T2D 127.83 +/- 12.08 and lean 111.65 +/- 9.13 mmHg; p=5.49e-10). Fractionated free urine catecholamines (epinephrine, norepinephrine and dopamine) were comparable across groups in 24-hour urines. However, fasting morning epinephrine levels and the ratio of fasting morning/24-hour epinephrine were higher in T2D (p=0.0035, and p=0.035, respectively) than in either lean or nondiabetic youth with obesity. There were no differences in morning urine catecholamines between lean controls and non-diabetic youth with obesity. Conclusions Our results suggest a disrupted circadian rhythm in catecholamines in youth-onset T2D, with a blunted overnight fall in epinephrine levels. Higher levels of epinephrine levels at night in youth with T2D might be associated with, or predispose to, hypertension and long-term cardiovascular complications. Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45 a.m.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
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  • 9
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 6, No. Supplement_1 ( 2022-11-01), p. A614-A615
    Abstract: We have previously demonstrated that insulin resistance (IR) in youth is associated with elevated levels of branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids (AAA) including tryptophan, the precursor of serotonin, for uptake into β-cells and other tissues via the large neutral amino acid transporter. Serotonin has been reported to increase β-cell mass and glucose-dependent insulin secretion. In this study we have explored how BCAA, tryptophan (one of the AAA), and a subset of their metabolites are modulated in youth-onset T2D. Based on our prior studies in neuronal BCAA metabolism, we hypothesized that elevated BCAA could induce diversion of tryptophan metabolism towards production of kynurenine rather than serotonin in youth with T2D. To test this, we analyzed 24-hour urine samples and compared levels of byproducts of BCAAs and tryptophan metabolism in obese youth with T2D with those in non-diabetic obese and lean youth of comparable age, pubertal status and ethnicity. Methods 56 non-diabetic adolescents with overweight/obesity ("obese"), 42 adolescents with T2D ("T2D"), and 43 normal weight controls ("lean"), ages 12-21 years-old were studied. Weight, height, BMI, BMI% were extracted from medical charts. Body fat percent (BF%) was measured by TANITA. We also measured metabolites derived from BCAA catabolism, including the branched-chain ketoacids (BCKAs), and tryptophan metabolism, including intermediates of the serotonergic and kynurenine pathways, in spot and 24-hour urine samples by liquid chromatography/tandem-mass spectrometry (LC/MS-MS). Levels were normalized to urine creatinine. Group differences were assessed by Kruskal Wallis or ANOVA. Results Groups were comparable for age (obese 14.8 +/- 1.9; T2D 15.7 +/- 2.1 and lean 14.9 +/- 1.9-yr), pubertal status, and ethnicity. Youth with T2D were predominantly female (T2D, 28 F, 14 M; obese 33 F, 23 M and lean, 17 F, 26 M), and had highest BF% (obese 37.3 +/- 9.5; T2D 42.9 +/- 9.9; lean 20.1 +/- 6.3%; p=2.58e-22). In 24-hour urine samples, BCKAs, tryptophan, and kynurenine levels were higher in T2D (p=0.0002, p= 0.0045 and p= 0.00009 respectively) than in either lean controls or nondiabetic youth with obesity; in contrast, there were no differences between lean controls and non-diabetic youth with obesity. The levels of 5-HIAA, the principal metabolite of serotonin, were comparable across groups; however, the ratio of kynurenine/tryptophan was higher (p= 0.0112) in youth with T2D and the ratios of 5-HIAA/ tryptophan (p=0.027) and 5-HIAA/Kynurenine (p=0.0067) were lower compared to the other two groups. Those ratios were comparable between lean controls and non-diabetic youth with obesity. Conclusions Increased BCKAs are accompanied by diversion of tryptophan metabolism from the serotonin pathway to the kynurenine pathway, suggesting perturbations in both BCAA and AAA metabolism in youth-onset T2D. These alterations could contribute to development of beta-cell dysfunction and progression to T2D in youth. Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
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  • 10
    In: The American Journal of Human Genetics, Elsevier BV, Vol. 99, No. 4 ( 2016-10), p. 991-999
    Type of Medium: Online Resource
    ISSN: 0002-9297
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 1473813-2
    SSG: 12
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