Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.

PURPOSE OF REVIEW: Chronic pain affects a significant portion of the population globally, making it a leading cause of disability. Understanding the multifaceted nature of chronic pain, its various types, and the intricate relationship it shares with risk factors, comorbidities, and mental health issues like depression and anxiety is critical for comprehensive patient care. Factors such as socioeconomic status (SES), age, gender, and obesity collectively add layers of complexity to chronic pain experiences and pose management challenges. RECENT FINDINGS: Low SES presents barriers to effective pain care, while gender differences and the prevalence of chronic pain in aging adults emphasize the need for tailored approaches. The association between chronic pain and physical comorbidities like cardiovascular disease, chronic obstructive pulmonary disease (COPD), and diabetes mellitus reveals shared risk factors and further highlights the importance of integrated treatment strategies. Chronic pain and mental health are intricately linked through biochemical mechanisms, profoundly affecting overall quality of life. This review explores pharmacologic treatment for chronic pain, particularly opioid analgesia, with attention to the risk of substance misuse and the ongoing opioid epidemic. We discuss the potential role of medical cannabis as an alternative treatment with a nuanced perspective on its impact on opioid use. Addressing the totality and complexity of pain states is crucial to individualizing chronic pain management. With different types of pain having different underlying mechanisms, considerations should be made when approaching their treatment. Moreover, the synergistic relationship that pain states can have with other comorbidities further complicates chronic pain conditions.

The effect of animated Sci-Fi characters' racial presentation on narrative engagement, wishful identification, and physical activity intention among children.

Characters play an integral role in animated narratives, but their visual racial presentation has received limited attention. A diverse group of U.S. children watched a 15-min physical activity-promoting animated Sci-Fi narrative. They were randomly assigned to one of three conditions, which varied the lead characters' racial presentation: realistic racially unambiguous (Original: White children, Black mother), realistic racially ambiguous (Ambiguous: All with brown skin without specified race/ethnicity), and fantastical racially ambiguous (Fantastical: All with brown skin with fantastical hair-and-eye color schemes). We assessed narrative engagement, wishful identification, and physical activity intention. Controlling for social desirability and multigroup ethnic identity, children who watched Fantastical characters showed significantly higher narrative engagement than those who watched Original characters, but they did not statistically differ from those who watched Ambiguous characters. Structural equation modeling indicated that narrative engagement and wishful identification fully mediated the racial representation effect (Fantastical vs. Original) on physical activity intention.

Lived experience of participants who engaged in the co-creation of initiatives to improve children's health in a rural Australian community.

OBJECTIVE: To describe participants' lived experience of co-creating and implementing initiatives to improve children's health. DESIGN: This manuscript reports an embedded case study design, which aims to describe participants' lived experiences of co-creating community-based initiatives. Information was gathered from an online survey and two focus groups. The two transcribed discussions from the focus groups were analysed using a 6-step phenomenological process. SETTING: Mansfield, Australia, population 4787, is one of ten local government areas (LGA) participating in the Reflexive Evidence and Systems Interventions to Prevent Obesity and Non-communicable Disease (RESPOND) project. PARTICIPANTS: Participants were purposively selected from established community groups previously engaged by RESPOND using a co-creation approach. The recruitment for the focus groups was a convenient sampling from participants that provided their email addresses in the online survey. RESULTS: Eleven participants completed the online survey. A total of ten participants attended the two focus groups of 1-h duration: five participants in each. Participants reported feeling empowered to create unique, locally relevant and readily adaptable community-wide change. They were supported by a strong partnership that mobilised funding for a part-time health promotion employee. Strengthened social connections were an unexpected though highly valued outcome. CONCLUSION: Co-creation processes may assist stakeholders in delivering prevention strategies in ways that are empowering for them, responsive to the changing needs of the community, strengthen organisational partnerships and enhance community participation, social inclusion and engagement.

Reproducibility of Glycemic Measures Among Dysglycemic Youth and Adults in the RISE Study.

AIMS: Previous work found poor reproducibility for measures of glycemia in individuals at risk for dysglycemia. Differences between youth and adults have not been assessed. Using youth and adults in the Restoring Insulin Secretion Study, we tested variability and classification concordance for hemoglobin A1C (HbA1c), fasting and 2-hour glucose from oral glucose tolerance tests (OGTTs). METHODS: HbA1c and glucose on repeated samples obtained ∼6 weeks apart were compared in 66 youth (mean age 14.2 years) and 354 adults (52.7 years). Changes, coefficient of variation (CV), and concordance of diagnostic categories between the 2 visits were compared. RESULTS: Mean difference between the 2 visits in HbA1c was higher in youth than adults (P < .001), while fasting glucose was similar and 2-hour glucose was lower in youth (P = .051). CV was smallest for HbA1c compared to fasting and 2-hour glucose. For HbA1c, youth had higher CV (P < .001); whereas CV for 2-hour glucose was lower for youth (P = .041). Classification concordance by HbA1c was lower in youth (P = .004). Using OGTT or HbA1c for classification, intervisit variability produced discordant classification in 20% of youth and 28% of adults. Using both fasting glucose and HbA1c, intervisit variability reduced discordant classification to 16% of adults while not improving classification in youth. CONCLUSIONS: Poor reproducibility and lack of classification concordance highlight the limitations of one-time testing, with important implications for assessing eligibility in clinical trials. Consideration should be given to using more than a single parameter for screening and diagnosis, especially when classification category is important.

Effectiveness of one dose of MVA-BN smallpox vaccine against mpox in England using the case-coverage method: an observational study.

BACKGROUND: The UK experienced a national outbreak of mpox (formerly known as monkeypox) disease that started in May, 2022, as did many other countries worldwide, with case numbers rising rapidly, mainly among gay, bisexual, and other men who have sex with men (GBMSM). To control the outbreak, Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN), an attenuated smallpox vaccine, was offered to at-risk GBMSM. We aimed to assess the effectiveness of a single MVA-BN dose against symptomatic mpox disease in at-risk GBMSM. METHODS: In this case-coverage study, mpox cases in England were sent questionnaires collecting information on demographics, vaccination history, symptoms, and sexual orientation. Returned questionnaires were linked to laboratory data and a public health case management system (HP Zone) to obtain additional information on symptom onset and specimen date. Cases with a rash onset date (or alternative proxy) between July 4 and Oct 9, 2022, were included. Females, heterosexual men, and those with missing vaccination information were excluded. Vaccine effectiveness was calculated using the case-coverage method in which vaccine coverage among cases is compared with coverage in the eligible population, estimated from doses given to GBMSM and the estimated size of at-risk GBMSM. Sensitivity analyses included an increase and decrease of 20% differences in the estimated high-risk GBMSM population size. FINDINGS: By Nov 3, 2022, 1102 people had responded to questionnaires, of which 739 were excluded (52 females or self-declared male heterosexuals, 590 with an index date outside of the study period, and 97 missing a vaccination date). 363 cases were included in the analyses. Vaccine uptake among eligible GBMSM increased steadily from July, 2022, reaching 47% by Oct 9, 2022. Of the 363 confirmed cases, eight cases either did occur or were likely to have occurred at least 14 days after vaccination, 32 within 0-13 days after vaccination, and the rest were unvaccinated. The estimated vaccine effectiveness against symptomatic mpox at least 14 days after a single dose was 78% (95% CI 54 to 89) ranging from 71 to 85 in sensitivity analyses. Vaccine effectiveness within 0-13 days after vaccination was -4% (95% CI -50 to 29). INTERPRETATION: A single MVA-BN dose was highly protective against symptomatic mpox disease among at-risk GBMSM, making it a useful tool for mpox outbreak control when rapid protection is needed. For cases in which numbers at highest risk of infection exceed vaccine supply, there might be benefit in prioritising delivery of first doses. FUNDING: UK Health Security Agency.

Reducing COVID-19 vaccine hesitancy among African Americans: the effects of narratives, character's self-persuasion, and trust in science.

This research examines the efficacy of self-persuasion narratives (i.e., narratives that describe how a character has changed their mind about the COVID-19 vaccines) in encouraging vaccine uptake among unvaccinated African Americans. A five-condition experiment (N = 394) was conducted in June 2021. Participants viewed one of the three pro-vaccine messages (a self-persuasion narrative, a narrative without self-persuasion, or a non-narrative message) or an irrelevant message or completed a self-persuasion task. Findings supported the persuasive benefits of the self-persuasion narrative compared to the narrative without self-persuasion, actual self-persuasion, and the irrelevant message. Its advantage over the narrative without self-persuasion was mediated by increased self-referencing, affective empathy, and perceived similarity with the character. Moreover, its psychological effects were moderated by participants' trust in science. Unexpectedly, the non-narrative showed persuasive benefits compared to other intervention strategies. The theoretical implications for narrative persuasion and practical implications for vaccine promotion were discussed.

11-Oxygenated Androgen Metabolite Concentrations Are Affected by Pubertal Progression and Obesity.

INTRODUCTION: 11-oxygenated C19 steroids (11-oxyandrogens) have been shown to rise during adrenarche and remain higher throughout adulthood than in early childhood. The patterns of circulating 11-oxyandrogens throughout normal puberty have not yet been described. METHODS: We conducted a secondary analysis of healthy youth participants, both males and females, enrolled in six prior endocrine studies (N = 249). Participants were classified according to Tanner stage and body mass index (BMI). Concentrations of three adrenal-specific 11-oxygenated androgens, 11ß-hydroxyandrostenedione (11OHA4), 11ß-hydroxytestosterone (11OHT), and 11-ketotestosterone (11KT), were measured in fasting serum samples. RESULTS: 11OHA4 and 11OHT increased modestly between early and late puberty in youth with normal weight (p < 0.05), whereas increases in 11KT did not reach statistical significance (p < 0.06). 11KT levels differed between sexes throughout puberty (p < 0.01), and changes in 11-oxyandrogens were small compared to the marked increases for estradiol in girls or testosterone in boys. The trajectories of 11KT and 11OHA4 changes throughout puberty differed by BMI category (p < 0.05). CONCLUSION: Beyond adrenarche, 11-oxyandrogens continue to rise during pubertal development. The differences in 11KT trajectories in males and females are small compared to changes in testosterone for males and estradiol for females during puberty. Obesity appears to influence the trajectories of 11-oxyandrogens during puberty.

How much did it cost to develop and implement an eHealth intervention for a minority children population that overlapped with the COVID-19 pandemic?

BACKGROUND: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions. OBJECTIVES: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19. METHODS: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs. RESULTS: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant completing the RCT (79 participants/237 visits) was $24,403 (Direct: $15,543; Indirect: $8860). Due to no-shows and cancellations (198 visits) and dropouts before study completion (61 visits; 56 participants), 496 visits had to be scheduled to ensure complete data collection on 79 participants. If all 496 visits were from participants completing the three-visit protocol, that would correspond to 165 participants, bringing the average cost per participant down to $11,684 (Direct: $7442; Indirect: $4242). Of the subcategories, intervention material development accounted for the largest portion, followed by personnel salaries. While the direct COVID-19-specific cost constituted <1% of the entire budget, the indirect effects were much larger and significantly impacted the trial. CONCLUSION: RCTs typically involve significant resources, even more so during a pandemic. Future eHealth intervention investigators should budget and plan accordingly to prepare for unexpected costs such as recruitment challenges to increase flexibility while maximizing the intervention efficacy.

Youth-onset type 2 diabetes mellitus: an urgent challenge.

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.

Using imaginary worlds for real social benefits.

We argue that imaginary worlds gain much of their appeal because they fulfill the fundamental need of human beings to feel connected to other humans. Immersion into story worlds provides a sense of social connection to the characters and groups represented in the world. By fulfilling the need to belong, imaginary worlds provide a buffer against rejection and loneliness.

Quantifying the inflammatory secretome of human intermuscular adipose tissue.

Adipose tissue secretes an abundance of lipid and protein mediators, and this secretome is depot-specific, with local and systemic effects on metabolic regulation. Intermuscular adipose tissue (IMAT) accumulates within the skeletal muscle compartment in obesity, and is associated with insulin resistance and metabolic disease. While the human IMAT secretome decreases insulin sensitivity in vitro, its composition is entirely unknown. The current study was conducted to investigate the composition of the human IMAT secretome, compared to that of the subcutaneous (SAT) and visceral adipose tissue (VAT) depots. IMAT, SAT, and VAT explants from individuals with obesity were used to generate conditioned media. Proteomics analysis of conditioned media was performed using multiplex proximity extension assays, and eicosanoid analysis using liquid chromatography-tandem mass spectrometry. Compared to SAT and/or VAT, IMAT secreted significantly more cytokines (IL2, IL5, IL10, IL13, IL27, FGF23, IFNγ and CSF1) and chemokines (MCP1, IL8, CCL11, CCL20, CCL25 and CCL27). Adipokines hepatocyte growth factor and resistin were secreted significantly more by IMAT than SAT or VAT. IMAT secreted significantly more eicosanoids (PGE2, TXB2 , 5-HETE, and 12-HETE) compared to SAT and/or VAT. In the context of obesity, IMAT is a distinct adipose tissue with a highly immunogenic and inflammatory secretome, and given its proximity to skeletal muscle, may be critical to glucose regulation and insulin resistance.

Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity.

Under healthy conditions, the pancreas responds to a glucose challenge by releasing insulin. Insulin suppresses lipolysis in adipose tissue, thereby decreasing plasma glycerol concentration, and it regulates plasma glucose concentration through action in muscle and liver. Insulin resistance (IR) occurs when more insulin is required to achieve the same effects, and IR may be tissue-specific. IR emerges during puberty as a result of high concentrations of growth hormone and is worsened by youth-onset obesity. Adipose, liver, and muscle tissue exhibit distinct dose-dependent responses to insulin in multi-phase hyperinsulinemic-euglycemic (HE) clamps, but the HE clamp protocol does not address potential differences in the dynamics of tissue-specific insulin responses. Changes to the dynamics of insulin responses would alter glycemic control in response to a glucose challenge. To investigate the dynamics of insulin acting on adipose tissue, we developed a novel differential-equations based model that describes the coupled dynamics of glycerol concentrations and insulin action during an oral glucose tolerance test in female adolescents with obesity and IR. We compared these dynamics to the dynamics of insulin acting on muscle and liver as assessed with the oral minimal model applied to glucose and insulin data collected under the same protocol. We found that the action of insulin on glycerol peaks approximately 67 min earlier (p < 0.001) and follows the dynamics of plasma insulin more closely compared to insulin action on glucose as assessed by the parameters representing the time constants for insulin action on glucose and glycerol (p < 0.001). These findings suggest that the dynamics of insulin action show tissue-specific differences in our IR adolescent population, with adipose tissue responding to insulin more quickly compared to muscle and liver. Improved understanding of the tissue-specific dynamics of insulin action may provide novel insights into the progression of metabolic disease in patient populations with diverse metabolic phenotypes.

Combined Oral Contraceptive Treatment Does Not Alter the Gut Microbiome but Affects Amino Acid Metabolism in Sera of Obese Girls With Polycystic Ovary Syndrome.

Background: The gut microbiome is altered in obese adolescents with polycystic ovary syndrome (PCOS), and is associated with free testosterone, metabolic markers, and insulin resistance. Combined oral contraceptives (OCP) are a primary treatment for PCOS and decrease testosterone, but the effect on the serum metabolome or gut microbiome in obese adolescents with PCOS is unknown. Objective: Contrast gut microbiome profiles, targeted serum metabolomics, hormone levels, and metabolic measures in adolescents with PCOS and obesity with and without OCP treatment. Methods: Adolescent girls with obesity and PCOS underwent stool and fasting blood collection and MRI for hepatic fat fraction. Fecal bacteria were profiled by high-throughput 16S rRNA gene sequencing and fasting serum metabolomics performed with high resolution mass spectrometry. Groups were contrasted using t-tests and principle least squares discrimination analysis (PLS-DA). Associations between bacterial taxa, baseline metabolic measures, hormone levels and the metabolome were conducted using Spearman analysis. Analyses were adjusted for false discovery rate. Results: 29 adolescents with obesity [Untreated N = 21, 16 ± 1.2 years, BMI%ile 36.5 ± 3.0; OCP N = 8, 15.5 ± 0.9 years, BMI%ile 32.5 ± 3.9] participated. Of the untreated adolescents, N = 14 contributed serum for metabolomic analysis. Participants on OCP therapy had lower free testosterone and free androgen index (p < 0.001) and higher sex hormone binding globulin. There was no difference in measures of fasting glucose, insulin, lipids or HOMA-IR between groups. PLS-DA of serum metabolomics showed discrimination between the groups, secondary amino acid changes. Untreated and OCP had similar stool microbiome α-diversity based on evenness (p = 0.28), richness (p = 0.39), and Shannon diversity (p = 0.24) and global microbial composition (ß-diversity, p = 0.56). There were no differences in % relative abundance at any level. Bacterial α-diversity was negatively associated with serum long chain fatty acids and branched chain amino acids. A higher %relative abundance of family Ruminococcaceae was significantly associated with serum bile acids and HOMA-IR. Conclusion: Despite hormone and serum amino acid differences, girls treated with OCP had similar metabolic and gut microbiome profiles compared to the untreated PCOS group. The association between bacterial α-diversity, Ruminococcaceae, clinical markers and long chain fatty acids suggests a potential role of the gut microbiome in the pathogenesis of the metabolic comorbidities in PCOS.

11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome.

Context: Polycystic ovary syndrome (PCOS) is common and diagnosis requires an elevated testosterone. The clinical importance of adrenal 11-oxyandrogens in PCOS is unclear. Objective: We sought to determine if 11-oxyandrogens 1) better identify PCOS diagnosis compared to testosterone, 2) predict clinical comorbidities of PCOS, and 3) are altered with an combined oral contraceptive pill (COCP) or metformin therapy. Methods: Data from 200 adolescent female participants aged 12 to 21 years, most with obesity, enrolled across 6 studies in pediatric endocrinology were included: 70 non-PCOS controls, 115 untreated PCOS, 9 PCOS + obesity treated with COCP, and 6 PCOS + obesity treated with metformin. 11-Hydroxyandrostenedione (11-OHA4), 11-hydroxytestosterone (1-OHT), 11-ketotestosterone (11-KT), and testosterone were measured with liquid chromatography-tandem mass spectrometry. Data between 1) untreated PCOS and controls and 2) untreated PCOS and the 2 treatment groups were compared. Results: Untreated girls with PCOS had higher 11-OHA4 (P = .003) and 11-OHT (P = .005) compared to controls, but not 11-KT (P = .745). Elevated 11-OHA4 remained statistically significant after controlling for obesity. Testosterone better predicted PCOS status compared to 11-oxyandrogens (receiver operating characteristic curve analysis: 11-OHA4 area under the curve [AUC] = 0.620, 11-OHT AUC = 0.638; testosterone AUC = 0.840). Among untreated PCOS patients, all 3 11-oxyandrogens correlated with hirsutism severity. 11-KT (P = .039) and testosterone (P < .006) were lower in those on COCP treatment compared to untreated PCOS. Metformin treatment had no effect on 11-oxyandrogens, although testosterone was lower (P = .01). Conclusion: Although 11-oxyandrogens do not aid in the diagnosis of PCOS, they relate to excess hair growth. COCP treatment may related to 11-KT; however, further work is needed to determine causality, relationship with metabolic outcomes, and the clinical utility of measuring these androgens in PCOS.

The Interaction of Obesity and Reproductive Function in Adolescents.

Obesity is increasing worldwide, including in pediatrics. Adequate nutrition is required for initiation of menses, and there is a clear secular trend toward earlier pubertal onset and menarche in females in countries around the globe. Similar findings of earlier pubertal start are suggested in males. However, as individuals and populations have crossed into over-nutritional states including overweight and obesity, the effect of excess weight on disrupting reproductive function has become apparent. Hypothalamic hypogonadism and polycystic ovary syndrome are two conditions where reproductive function appears to directly relate to excess weight. Clinical findings in individuals with certain polygenic and monogenic obesity syndromes, which also have reproductive disruptions, have helped elucidate neurologic pathways that are common to both. Clinical endocrinopathies such as hypothyroidism or panhypopituitarism also aide in the understanding of the role of the endocrine system in weight gain. Understanding the intersection of obesity and reproductive function may lead to future therapies which can treat both conditions.

Single-leg exercise training augments in vivo skeletal muscle oxidative flux and vascular content and function in adults with type 2 diabetes.

KEY POINTS: People with type 2 diabetes (T2D) have impaired skeletal muscle oxidative flux due to limited oxygen delivery. In the current study, this impairment in oxidative flux in people with T2D was abrogated with a single-leg exercise training protocol. Additionally, single-leg exercise training increased skeletal muscle CD31 content, calf blood flow and state 4 mitochondrial respiration in all participants. ABSTRACT: Cardiorespiratory fitness is impaired in type 2 diabetes (T2D), conferring significant cardiovascular risk in this population; interventions are needed. Previously, we reported that a T2D-associated decrement in skeletal muscle oxidative flux is ameliorated with acute use of supplemental oxygen, suggesting that skeletal muscle oxygenation is rate-limiting to in vivo mitochondrial oxidative flux during exercise in T2D. We hypothesized that single-leg exercise training (SLET) would improve the T2D-specific impairment in in vivo mitochondrial oxidative flux during exercise. Adults with (n = 19) and without T2D (n = 22) with similar body mass indexes and levels of physical activity participated in two weeks of SLET. Following SLET, in vivo oxidative flux measured by 31 P-MRS increased in participants with T2D, but not people without T2D, measured by the increase in initial phosphocreatine synthesis (P = 0.0455 for the group × exercise interaction) and maximum rate of oxidative ATP synthesis (P = 0.0286 for the interaction). Additionally, oxidative phosphorylation increased in all participants with SLET (P = 0.0209). After SLET, there was no effect of supplemental oxygen on any of the in vivo oxidative flux measurements in either group (P > 0.02), consistent with resolution of the T2D-associated oxygen limitation previously observed at baseline in subjects with T2D. State 4 mitochondrial respiration also improved in muscle fibres ex vivo. Skeletal muscle vasculature content and calf blood flow increased in all participants with SLET (P < 0.0040); oxygen extraction in the calf increased only in T2D (P = 0.0461). SLET resolves the T2D-associated impairment of skeletal muscle in vivo mitochondrial oxidative flux potentially through improved effective blood flow/oxygen delivery.

In-vivo skeletal muscle mitochondrial function in Klinefelter syndrome.

Klinefelter syndrome (XXY) occurs in 1 in 600 males, resulting in testosterone deficiency and a high prevalence of insulin resistance. Testosterone deficiency in men is a known cause of insulin resistance, and mitochondrial dysfunction is hypothesized to mediate this relationship. The aim of this cross-sectional study was to evaluate muscle mitochondrial function in XXY compared with male controls. Twenty-seven boys with XXY (age 14.7±1.8 years) were compared with 87 controls (age 16.9±0.9). In-vivo calf muscle mitochondrial function was assessed via phosphorus magnetic resonance spectroscopy (31P-MRS) following 90 s of isometric 70% maximal exercise. Multiple linear regression was used to compare 31P-MRS outcomes (ADP and phosphocreatine (PCr) time constants, rate of oxidative phosphorylation (Oxphos), and Qmax or the maximal mitochondrial function relative to mitochondrial density) between groups after adjusting for age differences. There were no statistically significant differences in the mitochondrial outcomes of ADP, Oxphos, PCr, and Qmax between the groups. There were also no differences in a sensitivity analysis within the XXY group by testosterone treatment status. In this study, in-vivo postexercise skeletal muscle mitochondrial function does not appear to be impaired in adolescents with XXY compared with controls and is not significantly different by testosterone treatment status in XXY.

Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity.

OBJECTIVE: Adolescents with polycystic ovary syndrome (PCOS) and obesity can have insulin resistance, dysglycemia, and hepatic steatosis. Excess pancreatic fat may disturb insulin secretion and relate to hepatic fat. Associations between pancreatic fat fraction (PFF) and metabolic measures in PCOS were unknown. METHODS: This secondary analysis included 113 sedentary, nondiabetic adolescent girls (age = 15.4 [1.9] years), with or without PCOS and BMI ≥ 90th percentile. Participants underwent fasting labs, oral glucose tolerance tests, and magnetic resonance imaging for hepatic fat fraction (HFF) and PFF. Groups were categorized by PFF (above or below the median of 2.18%) and compared. RESULTS: Visceral fat and HFF were elevated in individuals with PCOS versus control individuals, but PFF was similar. PFF did not correlate with serum androgens. Higher and lower PFF groups had similar HFF, with no correlation between PFF and HFF, although hepatic steatosis was more common in those with higher PFF (≥5.0% HFF; 60% vs. 36%; p = 0.014). The higher PFF group had higher fasting insulin (p = 0.026), fasting insulin resistance (homeostatic model assessment of insulin resistance, p = 0.032; 1/fasting insulin, p = 0.028), free fatty acids (p = 0.034), and triglycerides (p = 0.004) compared with those with lower PFF. ß-Cell function and insulin sensitivity were similar between groups. CONCLUSIONS: Neither PCOS status nor androgens related to PFF. However, fasting insulin and postprandial lipids were worse with higher PFF.