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Article: Editorial: Hereditary and acquired disorders of calcium homeostasis.

Sanjad, Sami A / Tfayli, Hala / Aoun, Bilal

2022 Volume 13, Page(s) 1124762

MeSH term(s)	Humans ; Calcium ; Parathyroid Hormone ; Hypocalcemia ; Homeostasis/genetics
Chemical Substances	Calcium (SY7Q814VUP) ; Parathyroid Hormone
Language	English
Publishing date	2022-12-29
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.1124762
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Article ; Online: The Shape of the Oral Glucose Tolerance Test-Glucose Response Curve in Islet Cell Antibody-Positive vs. -Negative Obese Youth Clinically Diagnosed with Type 2 Diabetes.

Kim, Joon Young / Tfayli, Hala / Bacha, Fida / Arslanian, Silva

Journal of obesity & metabolic syndrome

2019 Volume 30, Issue 2, Page(s) 178–183

Abstract: Background: The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and β-cell function, being worse in the former and superior in the latter. Here, we examined if ... ...

Abstract	Background: The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and β-cell function, being worse in the former and superior in the latter. Here, we examined if the OGTT-GRC pattern is worse in obese antibody (glutamic acid decarboxylase 65-kDa [GAD65] and insulinoma-associated protein-2 [IA-2])-positive (Ab Methods: Forty-seven obese youth, 15 Ab Results: Incessant increase OGTT-GRC is the most frequent curve type and is three-fold higher in Ab Conclusion: Severe insulin deficiency, a characteristic of type 1 diabetes, seems to be related to higher prevalence of incessant increase in Ab
Language	English
Publishing date	2019-10-07
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	3021984-X
ISSN	2508-7576 ; 2508-6235
ISSN (online)	2508-7576
ISSN	2508-6235
DOI	10.7570/jomes20088
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Article ; Online: β-cell impairment and clinically meaningful alterations in glycemia in obese youth across the glucose tolerance spectrum.

Kim, Joon Young / Tfayli, Hala / Bacha, Fida / Lee, SoJung / Gebara, Nour / Arslanian, Silva

Metabolism: clinical and experimental

2020 Volume 112, Page(s) 154346

Abstract: Background/aims: In obese youth, it is not clear what degree of β-cell impairment translates to glucose dysregulation commensurate with shifts from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes. We aimed to ... ...

Abstract	Background/aims: In obese youth, it is not clear what degree of β-cell impairment translates to glucose dysregulation commensurate with shifts from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes. We aimed to investigate the quantitative relationship between β-cell (clamp-measured disposition index [DI]) and OGTT glucose area under the curve (G-AUC) in obese youth across the spectrum of glucose tolerance. Methods: Data from 152 youth (58 African-American [AA] and 94 American-White [AW]; 73 NGT, 48 IGT, and 31 type 2 diabetes) who completed a 3-h hyperinsulinemic (80 mu/m Results: In IGT vs. NGT, 36% lower DI corresponded to 27% higher G-AUC; in type 2 diabetes vs. IGT, 65% lower DI related to 25% higher G-AUC, and in type 2 diabetes vs. NGT, 78% lower DI paralleled 59% higher G-AUC. Although AA vs. AW youth had larger decrements in DI, from NGT to IGT and from NGT to type 2 diabetes, they displayed comparable increments in G-AUC. Conclusion: At least ~35-50% recovery in β-cell function might be needed to have clinically meaningful improvement in G-AUC commensurate with conversion to better glucose tolerance. Mechanism(s) protective against dysglycemia might be operative in AA vs. AW youth despite greater declines in DI. Treatments aiming to improve β-cell function should focus on degree of change in DI commensurate with clinically meaningful changes in glycemia, reflective of restoration of glucose tolerance.
MeSH term(s)	African Americans ; Blood Glucose/metabolism ; Child ; Diabetes Mellitus, Type 2/metabolism ; Fasting/blood ; Female ; Glucose Clamp Technique ; Glucose Tolerance Test ; Humans ; Insulin/blood ; Insulin Resistance/physiology ; Insulin-Secreting Cells/metabolism ; Male ; Pediatric Obesity/metabolism ; Whites ; Young Adult
Chemical Substances	Blood Glucose ; Insulin
Language	English
Publishing date	2020-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80230-x
ISSN	1532-8600 ; 0026-0495
ISSN (online)	1532-8600
ISSN	0026-0495
DOI	10.1016/j.metabol.2020.154346
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Article ; Online: Impaired Lipolysis, Diminished Fat Oxidation, and Metabolic Inflexibility in Obese Girls With Polycystic Ovary Syndrome.

Kim, Joon Young / Tfayli, Hala / Michaliszyn, Sara F / Arslanian, Silva

The Journal of clinical endocrinology and metabolism

2017 Volume 103, Issue 2, Page(s) 546–554

Abstract: Context: Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation manifested in increased respiratory quotient (RQ). Little is known about adipose tissue metabolism and metabolic flexibility in ...

Abstract	Context: Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation manifested in increased respiratory quotient (RQ). Little is known about adipose tissue metabolism and metabolic flexibility in adolescent girls with polycystic ovary syndrome (PCOS). Objective: We investigated whole-body lipolysis, substrate oxidation, and metabolic flexibility in obese girls with PCOS vs obese girls without PCOS. Patients/design: Twenty-one obese girls with PCOS and 21 obese girls without PCOS were pair-matched for age and race. Body composition, abdominal visceral adipose tissue (VAT), sex hormones, lipid profile, and adiponectin were measured. Whole-body lipolysis ([2H5]glycerol turnover), RQ, and substrate oxidation (indirect calorimetry) were evaluated during fasting and a hyperinsulinemic-euglycemic clamp together with assessment of insulin sensitivity (IS). Results: Despite similar body mass index and percent body fat, girls with PCOS vs girls without PCOS had lower fasting lipolysis and fat oxidation, less increase in RQ during hyperinsulinemia with impaired suppression in lipolysis and lipid oxidation, and lower IS. In multiple regression, the best predictors of metabolic flexibility were [using clinical parameters: adiponectin, fasting triglycerides, and insulin (R2 = 0.618, P < 0.0001); using research parameters: IS, VAT, and baseline RQ (R2 = 0.756, P < 0.0001)]. Conclusions: Obese girls with PCOS vs obese girls without PCOS have decreased lipid mobilization, diminished fat oxidation, and metabolic inflexibility. Whether this metabolic phenotype of adipose tissue dysfunction, which is conducive to fat accretion, plays a role in the induction and maintenance of obesity in adolescent girls with PCOS remains to be determined.
MeSH term(s)	Abdominal Fat/metabolism ; Abdominal Fat/pathology ; Adolescent ; Body Composition ; Case-Control Studies ; Child ; Female ; Humans ; Insulin Resistance/physiology ; Lipid Metabolism/physiology ; Lipolysis/physiology ; Oxidation-Reduction ; Pediatric Obesity/complications ; Pediatric Obesity/metabolism ; Polycystic Ovary Syndrome/complications ; Polycystic Ovary Syndrome/metabolism
Language	English
Publishing date	2017-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2017-01958
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Article ; Online: Higher Incidence Rates of Hypothyroidism and Late TSH Rise in Preterm Very-Low-Birth-Weight Infants at a Tertiary Care Center.

Tfayli, Hala / Charafeddine, Lama / Tamim, Hani / Saade, Joanne / Daher, Rose T / Yunis, Khalid

Hormone research in paediatrics

2018 Volume 89, Issue 4, Page(s) 224–232

Abstract: Background/aims: Preterm newborns with a very low birth weight (VLBW) of < 1,500 g have an atypical form of hypothyroidism with a delayed rise in TSH, necessitating a second newborn screening specimen collection. The aims of this study were to survey ... ...

Abstract	Background/aims: Preterm newborns with a very low birth weight (VLBW) of < 1,500 g have an atypical form of hypothyroidism with a delayed rise in TSH, necessitating a second newborn screening specimen collection. The aims of this study were to survey the compliance with second newborn screening to detect delayed TSH rise in VLBW preterm infants at a tertiary care center, and to determine the rate of atypical hypothyroidism. Methods: Retrospective review of the records of 104 preterm VLBW infants. Late TSH rise was defined as an increase in TSH concentration after 14 days of age in the presence of a normal initial screen. Results: The compliance rate was 92% for the second screening. High rates of hypothyroidism (16.3%) and of late TSH rise (4.8%) were detected. Patients with hypothyroidism had a significantly lower birth weight (p = 0.01) and longer hospital stay (p = 0.004). Patients with late versus those with early TSH rise had a significantly lower mean birth weight (851 ± 302 vs. 1,191 ± 121 g, p = 0.004). Conclusion: The rates of early and late TSH rise in this VLBW population were higher than those in the literature and could be due to the use of povidone-iodine disinfectants. The yield of a second TSH screening in this study was high indicating the need for vigilance in screening VLBW preterm infants.
MeSH term(s)	Female ; Humans ; Hypothyroidism/blood ; Hypothyroidism/epidemiology ; Hypothyroidism/therapy ; Incidence ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Length of Stay ; Male ; Retrospective Studies ; Thyrotropin/blood
Chemical Substances	Thyrotropin (9002-71-5)
Language	English
Publishing date	2018-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2537278-6
ISSN	1663-2826 ; 1663-2818
ISSN (online)	1663-2826
ISSN	1663-2818
DOI	10.1159/000487637
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Article ; Online: Adipose Tissue Insulin Resistance in Youth on the Spectrum From Normal Weight to Obese and From Normal Glucose Tolerance to Impaired Glucose Tolerance to Type 2 Diabetes.

Kim, Joon Young / Bacha, Fida / Tfayli, Hala / Michaliszyn, Sara F / Yousuf, Shahwar / Arslanian, Silva

Diabetes care

2018 Volume 42, Issue 2, Page(s) 265–272

Abstract: Objective: Adipose tissue insulin resistance is one of the pathophysiological components of type 2 diabetes. Herein we investigated: : Research design and methods: A total of 205 youth had fasting glucose, insulin, FFA, Adipose-IR, body composition, ... ...

Abstract	Objective: Adipose tissue insulin resistance is one of the pathophysiological components of type 2 diabetes. Herein we investigated: Research design and methods: A total of 205 youth had fasting glucose, insulin, FFA, Adipose-IR, body composition, visceral adipose tissue (VAT), leptin, and adiponectin evaluated. Results: Adipose-IR was 2.2-fold higher in obese NGT, 4.3-fold higher in IGT, and 4.6-fold higher in type 2 diabetes compared with that in normal-weight peers (all Conclusions: Adipose-IR is a simple surrogate estimate that reflects pathophysiological alterations in adipose tissue insulin sensitivity in youth, with progressive deterioration from normal weight to obese and from NGT to IGT to type 2 diabetes. Adipose-IR can be applied in large-scale epidemiological/observational studies of the natural history of youth-onset type 2 diabetes and its progression or reversal with intervention strategies.
MeSH term(s)	Adipose Tissue/metabolism ; Adiposity/physiology ; Adolescent ; Blood Glucose/metabolism ; Child ; Cohort Studies ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/metabolism ; Female ; Glucose/metabolism ; Glucose Intolerance/complications ; Glucose Intolerance/epidemiology ; Glucose Intolerance/metabolism ; Glucose Tolerance Test ; Humans ; Ideal Body Weight/physiology ; Insulin/metabolism ; Insulin Resistance/physiology ; Male ; Pediatric Obesity/complications ; Pediatric Obesity/epidemiology ; Pediatric Obesity/metabolism ; Young Adult
Chemical Substances	Blood Glucose ; Insulin ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2018-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc18-1178
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Article ; Online: Increased Lipolysis, Diminished Adipose Tissue Insulin Sensitivity, and Impaired β-Cell Function Relative to Adipose Tissue Insulin Sensitivity in Obese Youth With Impaired Glucose Tolerance.

Kim, Joon Young / Nasr, Alexis / Tfayli, Hala / Bacha, Fida / Michaliszyn, Sara F / Arslanian, Silva

Diabetes

2017 Volume 66, Issue 12, Page(s) 3085–3090

Abstract: Despite evidence of insulin resistance and β-cell dysfunction in glucose metabolism in youth with prediabetes, the relationship between adipose tissue insulin sensitivity (ATIS) and β-cell function remains unknown. We investigated whole-body lipolysis, ... ...

Abstract	Despite evidence of insulin resistance and β-cell dysfunction in glucose metabolism in youth with prediabetes, the relationship between adipose tissue insulin sensitivity (ATIS) and β-cell function remains unknown. We investigated whole-body lipolysis, ATIS, and β-cell function relative to ATIS (adipose disposition index [DI]) in obese youth with impaired glucose tolerance (IGT) versus normal glucose tolerance (NGT). Whole-body lipolysis (glycerol appearance rate [GlyRa], [
MeSH term(s)	Adipose Tissue/metabolism ; Adolescent ; Female ; Glucose/metabolism ; Glucose Intolerance/metabolism ; Humans ; Insulin Resistance ; Insulin-Secreting Cells/physiology ; Lipolysis ; Male ; Obesity/metabolism
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2017-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db17-0551
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Article ; Online: β-cell function, incretin response, and insulin sensitivity of glucose and fat metabolism in obese youth: Relationship to OGTT-time-to-glucose-peak.

Kim, Joon Young / Tfayli, Hala / Bacha, Fida / Lee, SoJung / Michaliszyn, Sara F / Yousuf, Shahwar / Gebara, Nour / Arslanian, Silva

Pediatric diabetes

2019 Volume 21, Issue 1, Page(s) 18–27

Abstract: Background: In adults, the time-to-glucose-peak at or after 30 minutes during an oral glucose tolerance test (OGTT) identifies physiologically distinct groups with differences in insulin sensitivity, β-cell function and risk for type 2 diabetes. In ... ...

Abstract	Background: In adults, the time-to-glucose-peak at or after 30 minutes during an oral glucose tolerance test (OGTT) identifies physiologically distinct groups with differences in insulin sensitivity, β-cell function and risk for type 2 diabetes. In obese non-diabetic adolescents, we investigated if the OGTT-time-to-glucose-peak also reflects incretin and free fatty acid (FFA) responses besides insulin sensitivity and β-cell function, measured by the clamp. Methods: Obese adolescents (n = 278) were categorized according to their OGTT-time-to-glucose-peak by Early-peak (at 30 minutes) vs Late-peak (>30 minutes) groups. Body composition, visceral adipose tissue, oral disposition index and OGTT-area under the curve (AUC) were examined. A subset of 102 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β-cell function relative to insulin sensitivity. Results: Compared with the Early-peak group, the Late-peak group had impaired β-cell function relative to insulin sensitivity, lower glucose-dependent insulinotropic polypeptide-AUC, and higher FFA-AUC despite higher insulin- and C-peptide-AUC. They also had lower hepatic and peripheral insulin sensitivity despite similar percent body fat and visceral adipose tissue, and had higher prevalence of impaired glucose tolerance (all P < .05). Conclusions: In obese non-diabetic youth, those with a Late-peak vs an Early-peak glucose during an OGTT showed diminished β-cell function, blunted incretin secretion, and lower insulin sensitivity of glucose and FFA metabolism. It remains to be determined if Late-peak glucose predicts the future development of type 2 diabetes in these high-risk youth.
MeSH term(s)	Adolescent ; Biomarkers/metabolism ; Body Mass Index ; Child ; Diabetes Mellitus, Type 2/etiology ; Diabetes Mellitus, Type 2/metabolism ; Fatty Acids, Nonesterified/metabolism ; Female ; Glucose Tolerance Test ; Humans ; Incretins/metabolism ; Insulin Resistance/physiology ; Insulin Secretion/physiology ; Insulin-Secreting Cells/physiology ; Male ; Obesity/complications ; Obesity/metabolism ; Risk Factors ; Time Factors
Chemical Substances	Biomarkers ; Fatty Acids, Nonesterified ; Incretins
Language	English
Publishing date	2019-11-14
Publishing country	Denmark
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1502504-4
ISSN	1399-5448 ; 1745-1426 ; 1399-543X
ISSN (online)	1399-5448
ISSN	1745-1426 ; 1399-543X
DOI	10.1111/pedi.12940
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Article ; Online: Anti-Müllerian Hormone in Obese Adolescent Girls With Polycystic Ovary Syndrome.

Kim, Joon Young / Tfayli, Hala / Michaliszyn, Sara F / Lee, SoJung / Nasr, Alexis / Arslanian, Silva

The Journal of adolescent health : official publication of the Society for Adolescent Medicine

2016 Volume 60, Issue 3, Page(s) 333–339

Abstract: Purpose: Anti-Müllerian hormone (AMH) is proposed as a biomarker of polycystic ovary syndrome (PCOS). This study investigated: (1) AMH concentrations in obese adolescents with PCOS versus without PCOS; (2) the relationship of AMH to sex steroid hormones, ...

Abstract	Purpose: Anti-Müllerian hormone (AMH) is proposed as a biomarker of polycystic ovary syndrome (PCOS). This study investigated: (1) AMH concentrations in obese adolescents with PCOS versus without PCOS; (2) the relationship of AMH to sex steroid hormones, adiposity, and insulin resistance; and (3) the optimal AMH value and the multivariable prediction model to determine PCOS in obese adolescents. Methods: AMH levels were measured in 46 obese PCOS girls and 43 obese non-PCOS girls. Sex steroid hormones, clamp-measured insulin sensitivity and secretion, body composition, and abdominal adiposity were evaluated. Logistic regression and receiver-operating characteristic curve analyses were used, and multivariate prediction models were developed to test the utility of AMH for the diagnosis of PCOS. Results: AMH levels were higher in obese PCOS versus non-PCOS girls (8.3 ± .6 vs. 4.3 ± .4 ng/mL, p < .0001), of comparable age and puberty. AMH concentrations correlated positively with age in both groups, total and free testosterone in PCOS girls only, abdominal adipose tissue in non-PCOS girls, with no correlation to in vivo insulin sensitivity and secretion in either groups. A multivariate model including AMH (cutoff 6.26 ng/mL, area under the curve .788) together with sex hormone-binding globulin and total testosterone exhibited 93.4% predictive power for diagnosing PCOS. Conclusions: AMH may be a useful biomarker for the diagnosis of PCOS in obese adolescent girls.
MeSH term(s)	Adolescent ; Anti-Mullerian Hormone/blood ; Biomarkers/blood ; Cross-Sectional Studies ; Female ; Humans ; Pediatric Obesity/blood ; Pediatric Obesity/complications ; Polycystic Ovary Syndrome/blood ; Polycystic Ovary Syndrome/complications
Chemical Substances	Biomarkers ; Anti-Mullerian Hormone (80497-65-0)
Language	English
Publishing date	2016-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1063374-1
ISSN	1879-1972 ; 1054-139X
ISSN (online)	1879-1972
ISSN	1054-139X
DOI	10.1016/j.jadohealth.2016.10.015
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Article: Menstrual health and the metabolic syndrome in adolescents.

Tfayli, Hala / Arslanian, Silva

Annals of the New York Academy of Sciences

2008 Volume 1135, Page(s) 85–94

Abstract: The metabolic syndrome, a constellation of interrelated risk factors for cardiovascular disease and type 2 diabetes mellitus, has become a major public health concern against the backdrop of increasing rates of obesity. Insulin resistance plays a pivotal ...

Abstract	The metabolic syndrome, a constellation of interrelated risk factors for cardiovascular disease and type 2 diabetes mellitus, has become a major public health concern against the backdrop of increasing rates of obesity. Insulin resistance plays a pivotal role as the underlying pathophysiological linchpin of the various components of the syndrome. The metabolic syndrome is well recognized in adults, and there is convincing evidence that it starts in childhood, with progressive clustering of the various components over time and tracking through adulthood. Adult women and adolescents with polycystic ovary syndrome (PCOS) have higher prevalence rates of the metabolic syndrome compared with the general population. Several anthropometric (obesity, particularly abdominal obesity), metabolic (insulin resistance/hyperinsulinemia, dyslipidemia) and hormonal (low IGFBP1, IGFBP2 and low sex hormone binding globulin) features of adolescents with PCOS are also features of the metabolic syndrome. Insulin resistance, believed to be a key pathogenic factor in both PCOS and the metabolic syndrome, may be the thread that links the two conditions. Menstrual health in adolescents could be viewed as yet another component in the evaluation of the metabolic syndrome. Careful assessment of menstrual history and appropriate laboratory work-up could reveal the presence of PCOS in obese at-risk adolescent girls with a family history of the metabolic syndrome.
MeSH term(s)	Adolescent ; Adult ; Female ; Health ; Humans ; Insulin Resistance ; Menstruation ; Metabolic Syndrome/complications ; Polycystic Ovary Syndrome/complications ; Risk Factors
Language	English
Publishing date	2008-06-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1196/annals.1429.024
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