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Article ; Online: Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome.

Chen-Patterson, Angie / Bernier, Angelina / Burgert, Tania / Davis, Vanessa / Khan, Tazeena / Geller, David / Paprocki, Emily / Shah, Rachana / Witchel, Selma F / Pereira-Eshraghi, Camila / Sopher, Aviva B / Cree, Melanie G / Torchen, Laura C

Journal of the Endocrine Society

2024 Volume 8, Issue 2, Page(s) bvad169

Abstract: ... who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis.: Methods: Data were ... < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th ... percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G.: Results ...

Abstract	Introduction: Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis. Methods: Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G. Results: Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans. Conclusion: LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvad169
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Article ; Online: Comprehensive transition of care for polycystic ovary syndrome from adolescence to adulthood.

Simon, Stacey L / Phimphasone-Brady, Phoutdavone / McKenney, Kathryn M / Gulley, Lauren D / Bonny, Andrea E / Moore, Jaime M / Torres-Zegarra, Carla / Cree, Melanie G

The Lancet. Child & adolescent health

2024

Abstract: Polycystic ovary syndrome (PCOS) is a lifelong chronic condition that affects one in ten females and can be diagnosed in adolescence. As adolescents with PCOS transition to adulthood, counselling for lifestyle management and mental health concerns often ... ...

Abstract	Polycystic ovary syndrome (PCOS) is a lifelong chronic condition that affects one in ten females and can be diagnosed in adolescence. As adolescents with PCOS transition to adulthood, counselling for lifestyle management and mental health concerns often transition from involving the family unit to increasingly individual-focused approaches. PCOS is associated with a large range of comorbidities affecting reproductive, metabolic, dermatological, and psychological health. The diagnosis and comorbidities of PCOS are influenced by pubertal hormones and need to be reassessed continuously to ensure that treatment remains appropriate for age and development. As young patients grow up, personal concerns often change, especially in relation to reproductive management. In this Review, we present prevalence rates, screening tools, and treatment recommendations for PCOS-related conditions, and we consider the diagnostic and clinical elements of optimal transition of care models that ensure continuity of comprehensive care for adolescents moving from the paediatric health-care system to the adult health-care system.
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Journal Article ; Review
ISSN	2352-4650
ISSN (online)	2352-4650
DOI	10.1016/S2352-4642(24)00019-1
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Article ; Online: Prediction of resting energy expenditure for adolescents with severe obesity: A multi-centre analysis.

Rydin, Amy A / Severn, Cameron / Pyle, Laura / Morelli, Nazeen / Shoemaker, Ashley H / Chung, Stephanie T / Yanovski, Jack A / Han, Joan C / Higgins, Janine A / Nadeau, Kristen J / Fox, Claudia / Kelly, Aaron S / Cree, Melanie G

Pediatric obesity

2024 , Page(s) e13123

Abstract: Background and objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive ... ...

Abstract	Background and objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations. Methods: Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites. Data were randomly divided into development (N = 438) and validation (N = 118) cohorts. A predictive equation was developed using Elastic Net regression, using sex, race, ethnicity, weight, height, BMI percent of the 95th%ile (BMIp95), waist circumference, hip circumference, waist/hip ratio, age, Tanner stage, fat and fat-free mass. This equation was verified in the validation cohort and compared with 11 prior equations. Results: Data from the total cohort (n = 556, age 15 ± 1.7 years, 77% female, BMIp95 3.3 ± 0.94) were utilized. The best fit equation was REE = -2048 + 18.17 × (Height in cm) - 2.57 × (Weight in kg) + 7.88 × (BMIp95) + 189 × (1 = male, 0 = female), R Conclusion: This new equation provides an updated REE prediction that accounts for severe obesity and metabolic complications frequently observed in contemporary youth.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2655527-X
ISSN	2047-6310 ; 2047-6302
ISSN (online)	2047-6310
ISSN	2047-6302
DOI	10.1111/ijpo.13123
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Article: Estimating Insulin Sensitivity and Beta-Cell Function from the Oral Glucose Tolerance Test: Validation of a new Insulin Sensitivity and Secretion (ISS) Model.

Ha, Joon / Chung, Stephanie T / Springer, Max / Kim, Joon Young / Chen, Phil / Cree, Melanie G / Behn, Cecilia Diniz / Sumner, Anne E / Arslanian, Silva / Sherman, Arthur S

bioRxiv : the preprint server for biology

2023

Abstract: Efficient and accurate methods to estimate insulin sensitivity ( ... ...

Abstract	Efficient and accurate methods to estimate insulin sensitivity (S
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.16.545377
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Article ; Online: Estimating insulin sensitivity and β-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model.

Ha, Joon / Chung, Stephanie T / Springer, Max / Kim, Joon Young / Chen, Phil / Chhabra, Aaryan / Cree, Melanie G / Diniz Behn, Cecilia / Sumner, Anne E / Arslanian, Silva A / Sherman, Arthur S

American journal of physiology. Endocrinology and metabolism

2023 Volume 326, Issue 4, Page(s) E454–E471

Abstract: Efficient and accurate methods to estimate insulin sensitivity ( ...

Abstract	Efficient and accurate methods to estimate insulin sensitivity (
MeSH term(s)	Humans ; Glucose Tolerance Test ; Insulin Resistance/physiology ; Insulin Secretion ; Diabetes Mellitus, Type 2/diagnosis ; Blood Glucose ; Insulin/metabolism ; Glucose ; Glucose Clamp Technique
Chemical Substances	Blood Glucose ; Insulin ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00189.2023
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Article ; Online: Metabolic effects of an essential amino acid supplement in adolescents with PCOS and obesity.

Fordham, Talyia M / Morelli, Nazeen S / Garcia-Reyes, Yesenia / Ware, Meredith A / Rahat, Haseeb / Sundararajan, Divya / Fuller, Kelly N Z / Severn, Cameron / Pyle, Laura / Malloy, Craig R / Jin, Eunsook S / Parks, Elizabeth J / Wolfe, Robert R / Cree, Melanie G

Obesity (Silver Spring, Md.)

2024 Volume 32, Issue 4, Page(s) 678–690

Abstract: Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study' ...

Abstract	Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS. Methods: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.3 ± 6.5 kg/m Results: Compared to placebo, EAA was associated with no difference in body weight (p = 0.673). Two markers of liver health improved: HS was lower (-0.8% absolute, -7.5% relative reduction, p = 0.013), as was plasma aspartate aminotransferase (AST) (-8%, p = 0.004). Plasma TG (-9%, p = 0.015) and VLDL-TG (-21%, p = 0.031) were reduced as well. VLDL-TG palmitate derived from lipogenesis was not different between the phases, nor was insulin sensitivity (p > 0.400 for both). Surprisingly, during the EAA phase, participants reported consuming fewer carbohydrates (p = 0.038) and total sugars (p = 0.046). Conclusions: Similar to studies in older adults, short-term EAA supplementation in adolescents resulted in significantly lower liver fat, AST, and plasma lipids and thus may prove to be an effective treatment in this population. Additional research is needed to elucidate the mechanisms for these effects.
MeSH term(s)	Adolescent ; Female ; Humans ; Fatty Liver ; Hyperandrogenism/complications ; Insulin ; Insulin Resistance ; Lipoproteins, VLDL ; Obesity/complications ; Polycystic Ovary Syndrome/drug therapy ; Polycystic Ovary Syndrome/complications
Chemical Substances	Insulin ; Lipoproteins, VLDL
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.23988
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Article ; Online: Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

Jin, Eunsook S / Malloy, Craig R / Sharma, Gaurav / Finn, Erin / Fuller, Kelly N Z / Reyes, Yesenia Garcia / Lovell, Mark A / Derderian, Sarkis C / Schoen, Jonathan A / Inge, Thomas H / Cree, Melanie G

Redox biology

2023 Volume 63, Page(s) 102749

Abstract: Background: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components ... ...

Abstract	Background: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. Methods: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U- Results: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14-19]; BMI 47.4 kg/m Conclusions: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a compensatory mechanism to increase glutathione in the setting of excess glycerol delivery to the liver.
MeSH term(s)	Humans ; Liver/metabolism ; Glutathione/metabolism ; Glycerol/metabolism ; Male ; Female ; Adolescent ; Young Adult ; Magnetic Resonance Spectroscopy
Chemical Substances	Glutathione (GAN16C9B8O) ; Glycerol (PDC6A3C0OX)
Language	English
Publishing date	2023-05-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2023.102749
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Article ; Online: Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver

Eunsook S. Jin / Craig R. Malloy / Gaurav Sharma / Erin Finn / Kelly N.Z. Fuller / Yesenia Garcia Reyes / Mark A. Lovell / Sarkis C. Derderian / Jonathan A. Schoen / Thomas H. Inge / Melanie G. Cree

Redox Biology, Vol 63, Iss , Pp 102749- (2023)

2023

Abstract	Background: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. Methods: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U–13C3]glycerol (50 mg/kg) prior to surgery and liver tissue (0.2–0.7g) was obtained during surgery. Glutathione, amino acids, and other water-soluble metabolites were extracted from the liver tissue and isotopomers were quantified with nuclear magnetic resonance spectroscopy. Results: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14–19]; BMI 47.4 kg/m2 [range 41.3–63.3]). The concentrations of free glutamate, cysteine, and glycine were similar among participants, and so were the fractions of 13C-labeled glutamate and glycine derived from [U–13C3]glycerol. The signals from all component amino acids of glutathione - glutamate, cysteine and glycine - were strong and analyzed to obtain the relative concentrations of the antioxidant in the liver. The signals from glutathione containing [13C2]glycine or [13C2]glutamate derived from the [U–13C3]glycerol drink were readily detected, and 13C-labelling patterns in the moieties were consistent with the patterns in corresponding free amino acids from the de novo glutathione synthesis pathway. The newly synthesized glutathione with [U–13C3]glycerol trended to be lower in obese adolescents with liver pathology. Conclusions: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a ...
Keywords	Glycerol ; Glycine ; Glutamate ; Cysteine ; Liver ; Glutathione ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	500
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Youth-onset type 2 diabetes mellitus: an urgent challenge.

Bjornstad, Petter / Chao, Lily C / Cree-Green, Melanie / Dart, Allison B / King, Malcolm / Looker, Helen C / Magliano, Dianna J / Nadeau, Kristen J / Pinhas-Hamiel, Orit / Shah, Amy S / van Raalte, Daniel H / Pavkov, Meda E / Nelson, Robert G

Nature reviews. Nephrology

2022 Volume 19, Issue 3, Page(s) 168–184

Abstract: The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are ... ...

Abstract	The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus. Moreover, the available treatment options for children and adolescents with T2DM are more limited than for adult patients. Intermediate complications of youth-onset T2DM, such as increased albuminuria, often develop in late childhood or early adulthood, and end-stage complications, including kidney failure, develop in mid-life. The increasing frequency, earlier onset and greater severity of childhood obesity in the past 50 years together with increasingly sedentary lifestyles and an increasing frequency of intrauterine exposure to diabetes are important drivers of the epidemic of youth-onset T2DM. The particularly high risk of the disease in historically disadvantaged populations suggests an important contribution of social and environmental factors, including limited access to high-quality health care, healthy food choices and opportunities for physical activity as well as exposure to stressors including systemic racism and environmental pollutants. Understanding the mechanisms that underlie the development and aggressive clinical course of youth-onset T2DM is key to identifying successful prevention and management strategies.
MeSH term(s)	Adult ; Humans ; Child ; Adolescent ; Diabetes Mellitus, Type 2/complications ; Pediatric Obesity/complications ; Diabetes Mellitus, Type 1/complications ; Exercise ; Disease Progression
Language	English
Publishing date	2022-10-31
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/s41581-022-00645-1
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Zs.A 6334: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Impact of Obesity on Measures of Cardiovascular and Kidney Health in Youth With Type 1 Diabetes as Compared With Youth With Type 2 Diabetes.

Tommerdahl, Kalie L / Baumgartner, Karl / Schäfer, Michal / Bjornstad, Petter / Melena, Isabella / Hegemann, Shannon / Baumgartner, Amy D / Pyle, Laura / Cree-Green, Melanie / Truong, Uyen / Browne, Lorna / Regensteiner, Judith G / Reusch, Jane E B / Nadeau, Kristen J

Diabetes care

2021 Volume 44, Issue 3, Page(s) 795–803

Abstract: Objective: Insulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and ...

Abstract	Objective: Insulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and kidney outcomes in youth with T1D versus control youth with normal weight or obesity and youth with type 2 diabetes (T2D). Research design and methods: Pubertal youth ( Results: In adolescents with T1D, RHR, SBP, DBP, mean arterial pressure, leptin, hs-CRP, and hypertension prevalence were significantly higher, and BAD, descending aorta pulse wave velocity, and VO Conclusions: Obesity, now increasingly prevalent in people with T1D, correlates with a less favorable cardiovascular and kidney risk profile, nearly approximating the phenotype of youth with T2D. Focused lifestyle management in youth-onset T1D is critically needed to reduce cardiovascular risk.
MeSH term(s)	Adolescent ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 2/complications ; Humans ; Kidney ; Obesity/complications ; Pulse Wave Analysis ; Risk Factors
Language	English
Publishing date	2021-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc20-1879
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