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INTRODUCTION: Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM. METHODS: Case-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer MRI) were assessed. RESULTS: Participants included 11 individuals with FRDA (4 female), median age 27y (IQR 23, 39), BMI 26.9kg/m2 (24.1, 29.4), and 24 controls (11 female), 29y (26, 39), 24.4kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA (91 vs. 83mg/dL (5.0 vs. 4.6mmol/L), p<0.05). Individuals with FRDA had lower insulin sensitivity (WBISI 2.8 vs. 5.3, p<0.01), higher post-prandial insulin secretion (insulin secretory rate iAUC 30-180 minutes, 24,652 vs. 17,858, p<0.05), and more suppressed post-prandial endogenous glucose production (-0.9% vs. 26.9% of fasting EGP, p<0.05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different. CONCLUSIONS: Lower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory, and when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.
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OBJECTIVE: Measure 18F-FDG uptake in digital tissues of healthy horses subjected to different ambulatory conditions between the time of injection and positron emission tomography (PET) scan acquisition. ANIMALS: 8 healthy adult horses. METHODS: Horses were walked (AMB) or tied in stalls (NONAMB) immediately after injection with â¼1.5 MBq/kg 18F-FDG until scan acquisition using a randomized crossover design. Steps were quantified using accelerometers. Standardized uptake values (SUV; mean and maximum) in digital tissues including the dorsal lamellae (proximal, middle, and distal), quarter lamellae (medial and lateral), and coronary band were analyzed using a mixed-effects linear regression model. RESULTS: Mean (95% CI) step count for AMB (569[484-653]) was higher than NONAMB (88[24-152]) P = <.001. The SUVmax (but not SUVmean) was increased in AMB compared with NONAMB in the proximal (2.74[2.52-2.98] vs 2.42[2.05-2.78]; P = .04) and middle (2.74[2.37-3.11] vs 2.36[2.05-2.68]; P = .03) dorsal lamellae but was not different in the distal lamellae or coronary band. In the medial quarter lamellae, both SUVmax (2.53[1.58-3.48] vs 2.07[0.81-3.33]; P = .01) and SUVmean (1.90[1.55-2.25] vs 1.49[0.91-2.06]; P = .007) were increased in AMB compared with NONAMB. The medial quarter lamellae also had lower SUVmax (P = .002) and SUVmean (P = .04) compared with the lateral quarter and lower SUVmax compared with the mid-dorsal lamellae (P = .01). CLINICAL RELEVANCE: Lamellar 18F-FDG uptake was affected by ambulatory activity mostly in the medial quarter; however, this effect was relatively small and unlikely to interfere with clinical detection of laminitis.
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Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Animais , Cavalos , Tomografia por Emissão de Pósitrons/veterinária , Tomografia por Emissão de Pósitrons/métodos , Cintilografia , Caminhada , Estudos Cross-OverRESUMO
OBJECTIVE: The American Academy of Pediatrics recommends routine sleep problem screenings during child well-visits. However, studies suggest a discrepancy between caregiver- and clinician-reported child sleep problems. The present study examines whether caregiver-reported child sleep problems (ie, habitual snoring, insomnia symptoms, poor sleep health) and clinician-documented child sleep problems and management are congruent. METHODS: The sample included 170 caregiver-child dyads (child Mage = 3.3 years, range = 2-5 years; 56.5% girls; 64.1% Black, 20.0% non-Latinx White, and 4.1% Latinx; 86.5% maternal caregiver reporter). Caregivers' questionnaire-based reports of habitual snoring, insomnia symptoms, and sleep health behaviors (nighttime electronics, caffeine intake, insufficient sleep) were compared with clinician documentation in the electronic health record. RESULTS: About 92.3% of children had at least 1 caregiver-reported sleep problem (66% insomnia symptoms, 64% electronics, 38% insufficient sleep, 21% caffeine, 17% snoring). In contrast, a substantially lower percent of children had a clinician documented sleep problem (20% overall; 10% insomnia symptoms, 7% electronics, 0% insufficient sleep, 3% caffeine, 4% snoring), sleep-related referral (1% overall; 0.6% Otolaryngology, 0.6% polysomnogram, 0% sleep clinic), or recommendation (12% overall; 8% insomnia symptoms, 4% electronics, 0% insufficient sleep, 1% caffeine). CONCLUSIONS: There is a vast discrepancy between caregiver-reported child sleep problems and clinician-documented sleep problems and management, with a higher proportion of caregiver reports. To benefit overall child health and well-being, future research and quality improvement initiatives should focus on enhancing screening tools and educational opportunities to improve clinician documentation and enhance family conversations about early childhood sleep problems.
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Cuidadores , Distúrbios do Início e da Manutenção do Sono , Feminino , Criança , Humanos , Pré-Escolar , Estados Unidos , Masculino , Ronco , Privação do Sono , Cafeína , Encaminhamento e ConsultaRESUMO
Impaired insulin and incretin secretion underlie abnormal glucose tolerance (AGT) in pancreatic insufficient cystic fibrosis (PI-CF). Whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can enhance pancreatic islet function in cystic fibrosis (CF) is not known. We studied 32 adults with PI-CF and AGT randomized to receive either GLP-1 (n = 16) or GIP (n = 16) during glucose-potentiated arginine (GPA) testing of islet function on two occasions, with either incretin or placebo infused, in a randomized, double-blind, cross-over fashion. Another four adults with PI-CF and normal glucose tolerance (NGT) and four matched control participants without CF underwent similar assessment with GIP. In PI-CF with AGT, GLP-1 substantially augmented second-phase insulin secretion but without effect on the acute insulin response to GPA or the proinsulin secretory ratio (PISR), while GIP infusion did not enhance second-phase or GPA-induced insulin secretion but increased the PISR. GIP also did not enhance second-phase insulin in PI-CF with NGT but did so markedly in control participants without CF controls. These data indicate that GLP-1, but not GIP, augments glucose-dependent insulin secretion in PI-CF, supporting the likelihood that GLP-1 agonists could have therapeutic benefit in this population. Understanding loss of GIP's insulinotropic action in PI-CF may lead to novel insights into diabetes pathogenesis.
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Fibrose Cística , Peptídeo 1 Semelhante ao Glucagon , Adulto , Arginina , Glicemia , Polipeptídeo Inibidor Gástrico/farmacologia , Glucagon , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Glucose/farmacologia , Humanos , Incretinas , Insulina , ProinsulinaRESUMO
OBJECTIVE: The aim of this study was to assess whether exendin-(9-39) will increase fasting and postprandial plasma glucose and decrease the incidence of hypoglycemia in children with hyperinsulinism (HI). RESEARCH DESIGN AND METHODS: This was an open-label, four-period crossover study. In periods 1 and 2, the effect of three different dosing regimens of exendin-(9-39) (group 1, 0.28 mg/kg; group 2, 0.44 mg/kg; group 3, 0.6 mg/kg) versus vehicle on fasting glucose was assessed in 16 children with HI. In periods 3 and 4, a subset of eight subjects received either vehicle or exendin-(9-39) (0.6 mg/kg) during a mixed-meal tolerance test (MMTT) and an oral protein tolerance test (OPTT). RESULTS: Treatment group 2 showed 20% (P = 0.037) increase in the area under the curve (AUC) of fasting glucose. A significant increase in AUC of glucose was also observed during the MMTT and OPTT; treatment with exendin-(9-39) resulted in 28% (P ≤ 0.001) and 30% (P = 0.01) increase in AUC of glucose, respectively. Fasting AUC of insulin decreased by 57% (P = 0.009) in group 3. In contrast, AUC of insulin was unchanged during the MMTT and almost twofold higher (P = 0.004) during the OPTT with exendin-(9-39) treatment. In comparison with vehicle, infusion of exendin-(9-39) resulted in significant reduction in likelihood of hypoglycemia in group 2, by 76% (P = 0.009), and in group 3, by 84% (P = 0.014). Administration of exendin-(9-39) during the OPTT resulted in 82% (P = 0.007) reduction in the likelihood of hypoglycemia. CONCLUSIONS: These results support a therapeutic potential of exendin-(9-39) to prevent fasting and protein-induced hypoglycemia in children with HI.
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Hiperinsulinismo Congênito , Hiperinsulinismo , Glicemia/metabolismo , Criança , Hiperinsulinismo Congênito/tratamento farmacológico , Estudos Cross-Over , Jejum , Glucose/uso terapêutico , Humanos , Insulina , Insulina Regular Humana/uso terapêutico , Fragmentos de Peptídeos , Período Pós-PrandialRESUMO
Anecdotal accounts correlate equine colic onset to changing weather conditions; however, atmospheric effects on colic have not been studied extensively. We hypothesized that changes in barometric pressure would increase the likelihood of a colic diagnosis compared with other noncolic sick events. Multivariable logistic regression analysis was used to look for associations between colic diagnosis and barometric pressure. The University of Pennsylvania Field Service electronic medical records were searched by identifiable examination type via billing procedure codes collecting 3,108 emergent and nonemergent medical events along with corresponding weather data from the National Weather Service from January 1, 2005, through January 1, 2017. Barometric pressure values and changes were not found to be statistically associated with a diagnosis of colic (P = .1). Horses that did not survive were almost 12 times more likely to have a diagnosis of colic (odds ratio [OR]: 11.97; P < .0001). Horses with disease recurrence were 30% more likely to have a diagnosis of colic (OR: 1.29; P = .006). The likelihood of colic diagnosis increased with increasing latitude (OR: 2.43; P = .04). Horses were more likely to be diagnosed with colic in the fall (OR: 1.72; P < .0001), spring (OR: 1.29; P = .04), and summer (OR: 1.85; P < .0001), compared with winter. Stallions were 48% less likely to colic compared with mares (OR: 0.52; P = .016) and Quarter Horses were 32% less likely to colic compared with Thoroughbreds and Arabians (OR: 0.68; P = .047). This study provided evidence that changes in barometric pressure were not a contributing risk factor for colic, although seasons with changing weather and latitude may play a role.
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Cólica , Doenças dos Cavalos , Animais , Pressão Atmosférica , Cólica/epidemiologia , Cólica/veterinária , Feminino , Doenças dos Cavalos/epidemiologia , Cavalos , Incidência , Masculino , Tempo (Meteorologia)RESUMO
BACKGROUND: Sleep-disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. However, data on whether SDB alters the metabolism of free fatty acids (FFAs) are lacking. RESEARCH QUESTION: The primary objective of the current study was to characterize alterations in FFA metabolism across the spectrum of SDB severity. STUDY DESIGN AND METHODS: The study sample included 118 participants with and without SDB who underwent full-montage polysomnography, the frequently sampled IV glucose tolerance test (FSIGTT), and body composition measurements including determination of percent body fat. Parameters of lipolysis suppression, time to FFA nadir, and FFA rebound after an IV glucose challenge were derived using a mathematical model. Multivariable regression analyses were used to characterize the independent associations between SDB severity and parameters of FFA metabolism. RESULTS: SDB severity, as assessed by the apnea-hypopnea index, was associated with adipocyte insulin resistance, a decrease in the glucose- and insulin-mediated suppression of lipolysis, a longer duration to reach a nadir in FFA levels during the FSIGTT, and a sluggish rebound in FFA levels after suppression. Severity of SDB-related hypoxemia was independently associated with adipocyte insulin resistance and the time to reach the FFA nadir during the FSIGTT. Finally, a higher percentage of stage N3 sleep was positively associated with greater suppression of lipolysis and a faster rebound in the FFA levels during the FSIGTT. INTERPRETATION: Independent of adiposity, SDB is associated with impairments in FFA metabolism, which may contribute to the development of glucose intolerance and type 2 diabetes in SDB.
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Ácidos Graxos não Esterificados/sangue , Resistência à Insulina/fisiologia , Síndromes da Apneia do Sono/sangue , Sono/fisiologia , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Fatores de Risco , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologiaRESUMO
OBJECTIVE: To evaluate survival and associated risk factors when utilizing an outpatient treatment protocol for treatment of canine parvovirus (CPV) performed in a shelter-based low-cost urban clinic. DESIGN: Retrospective study. SETTING: Pennsylvania Society for the Prevention of Cruelty to Animals. ANIMALS: Ninety-five CPV positive dogs presented between June 1 and July 31, 2016. Owners elected for outpatient care when inpatient care was not financially feasible and the dog was considered medically stable for outpatient care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 95 CPV positive dogs, 79 (83%) survived treatment. Logistic regression indicated that an increasing number of days with clinical signs prior to treatment and an increase in percent body weight during treatment were significantly associated with survival (odds ratio [OR], 3.15, P = 0.020; and OR, 1.29, P = 0.027, respectively). Hypothermia upon presentation (T < 37â) was negatively associated with survival (OR, 0.002; P = 0.002). CONCLUSIONS AND CLINICAL RELEVANCE: The survival rate of this clinic suggests that an outpatient program may be a potential alternative treatment to inpatient care. Longer duration of clinical signs prior to treatment and an increase in percent body weight during treatment appear to be associated with increased survival outcomes, while hypothermia on presentation appears to be associated with decreased survival outcomes.
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Doenças do Cão/terapia , Infecções por Parvoviridae/veterinária , Parvovirus Canino , Animais , Cães , Modelos Logísticos , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/terapia , Pennsylvania/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined ß-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced ß-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF.
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Fibrose Cística/metabolismo , Fibrose Cística/patologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Adolescente , Adulto , Peptídeo C/metabolismo , Insuficiência Pancreática Exócrina/metabolismo , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Incretinas/metabolismo , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Proinsulina/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To determine the association between altitude and obesity in a nationally representative sample of the Peruvian adult population. METHODS: This is a cross-sectional analysis of publicly available data from the Food and Nutrition National Center (CENAN, Peru), period 2009-2010. The Prevalence ratio of obesity and abdominal obesity was determined as a measure of association. Obesity and abdominal obesity were diagnosed based on direct anthropometric measurements. RESULTS: The final data set consisted of 31,549 individuals ≥20 years old. The prevalence ratio of obesity was as follows: 1.00 between 0 and 499 m (reference category), 1.00 (95% confidence interval 0.87-1.16) between 500-1,499 m, 0.74 (0.63-0.86) between 1,500-2,999 m, and 0.54 (0.45-0.64) at ≥3,000 m, adjusting for age, sex, self-reported physical activity, out-migration rate, urbanization, poverty, education, and geographical latitude and longitude. In the same order, the adjusted prevalence ratio of abdominal obesity was 1.00, 1.01 (0.94-1.07), 0.93 (0.87-0.99), and 0.89 (0.82-0.95), respectively. We found an interaction between altitude and sex and between altitude and age (P < 0.001, for both interactions) on the association with obesity and abdominal obesity. CONCLUSIONS: Among Peruvian adult individuals, we found an inverse association between altitude and obesity, adjusting for multiple covariates. This adjusted association varied by sex and age.