Assuntos
Eritrócitos , Testosterona , Humanos , Testosterona/uso terapêutico , Estudos LongitudinaisRESUMO
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 (n = 284) aged 12-21 years underwent assessments of resting heart rate (RHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), leptin, hs-CRP, adiponectin, ratio of urine albumin to creatinine, and estimated glomerular filtration rate. Participants with T1D underwent bicycle ergometry for VO2peak, monitoring for peripheral brachial artery distensibility (BAD), endothelial function testing for reactive hyperemic index, and aortic MRI for central arterial stiffness or shear. 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 VO2peak lower with an obese versus normal BMI. Although hypertension prevalence and RHR were highest in obese adolescents with T1D and adiponectin lowest in youth with T2D, other measures were similar between obese adolescents with T1D and those with T2D. 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.
Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adolescente , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Humanos , Rim , Obesidade/complicações , Análise de Onda de Pulso , Fatores de RiscoRESUMO
STUDY OBJECTIVE: To identify why adolescents with polycystic ovary syndrome (PCOS) chose the etonogestrel (ENG) contraceptive implant, to determine the 12-month continuation rate, and to characterize factors related to discontinuation. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review of adolescents seen at a tertiary care children's hospital between July 1, 2008, and August 30, 2019, with PCOS diagnosis confirmed per National Institutes of Health criteria and ≥12-month ENG follow-up. INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic characteristics, reasons for ENG insertion and removal, and information on other hormonal/contraceptive therapies were collected. Patients were categorized as ENG continuers (use ≥12 months) or discontinuers (removal at <12 months), and groups were compared. RESULTS: A total of 96 patients met inclusion criteria (age 17.7 ± 2.2 years, body mass index 34.8 ± 8 kg/m2). Reasons for ENG were documented in 74% (51% contraception, 32% ease of use, 15% other, 13% estrogen avoidance). In all, 27% had never been sexually active, and 67% had had prior sexual activity. Treatments prior to ENG placement included 74% combined hormonal contraception, 20% medroxyprogesterone acetate withdrawal, and 17% depot medroxyprogesterone. A total of 77% continued ENG at 12 months. The main reasons for discontinuation were bleeding (41%), concern about weight gain (23%), and mood changes (18%). No preimplantation characteristics were independently predictive of continuation, although 100% of patients with type 2 diabetes (n = 11) continued. Patients who sought additional care, including telephone calls (41% vs 12%, P = .006) and clinic visits (64% vs 20%, P < .001) were more likely to discontinue. CONCLUSIONS: The ENG implant was well tolerated in adolescents with PCOS and similar to published 12-month continuation rates.
Assuntos
Contraceptivos Hormonais/administração & dosagem , Tomada de Decisões , Desogestrel/administração & dosagem , Adolescente , Adulto , Estudos de Casos e Controles , Contraceptivos Hormonais/efeitos adversos , Dispositivos Anticoncepcionais Femininos/efeitos adversos , Desogestrel/efeitos adversos , Remoção de Dispositivo/psicologia , Remoção de Dispositivo/estatística & dados numéricos , Implantes de Medicamento/administração & dosagem , Implantes de Medicamento/efeitos adversos , Feminino , Humanos , Síndrome do Ovário Policístico/psicologia , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE/BACKGROUND: Rates of overweight/obesity and insufficient/delayed sleep are high among adolescents and are also unique risk factors for mood/behavior difficulties. This study aimed to evaluate relationships between sleep/circadian health and mood/behavior in a cohort of adolescents with overweight/obesity. PARTICIPANTS: Twenty-two adolescents (16.4 ± 1.1 years) with overweight/obesity attending high school completed in the study. METHODS: Participants completed one week of home sleep monitoring (actigraphy), questionnaires assessing chronotype (diurnal preference; Morningness/Eveningness Scale for Children) and mood/behavior (Strengths & Difficulties Questionnaire), and had in-laboratory salivary melatonin sampling on a Thursday or Friday during the academic year. RESULTS: Linear regressions revealed later weekday bedtime and shorter weekday time in bed and sleep duration were associated with worse mood/behavior scores. Shorter duration of melatonin secretion and greater "eveningness" were also associated with worse mood/behavior scores. CONCLUSIONS: Short and late sleep, shorter melatonin secretion, and eveningness chronotype are associated with worse mood/behavior symptoms in a cohort of adolescents with overweight/obesity. Clinicians should assess for both sleep and mood/behavior symptoms and further research is needed to evaluate the impact of improved sleep on mood/behavior in adolescents with overweight/obesity.
Assuntos
Afeto , Comportamento Infantil/psicologia , Ritmo Circadiano/fisiologia , Obesidade/complicações , Sobrepeso/complicações , Transtornos do Sono-Vigília/etiologia , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
OBJECTIVES: To examine the relationship between insulin resistance (IR) and sleep/circadian health in overweight/obese adolescents. We hypothesized that insufficient and delayed sleep would be associated with IR in this population. STUDY DESIGN: Thirty-one adolescents (mean age, 16.0 ± 1.4 years; 77% female) with body mass index ≥90th percentile for age/sex were recruited from outpatient clinics at a children's hospital. Participants underwent 1 week of objective home sleep monitoring with wrist actigraphy during the academic year. A 3-hour oral glucose tolerance test was conducted, followed by in-laboratory salivary dim-light melatonin sampling every 30-60 minutes from 5 p.m. to noon the next day. Regression analyses between sleep and circadian variables with IR were examined. RESULTS: Longer sleep time and time in bed on weekends and weekdays and earlier weekday bedtime were significantly associated with better insulin sensitivity. Participants who obtained less than the median duration of sleep per night (6.6 hours) had evidence of IR with compensatory insulin secretion compared with those obtaining ≥6.6 hours of sleep. A wider phase angle between bedtime and melatonin onset, indicating a later circadian timing of sleep onset, was significantly associated with IR. CONCLUSIONS: Short sleep duration, later weekday bedtime, and later circadian timing of sleep were associated with IR in a cohort of adolescents with overweight/obesity during the school year. Further research is needed to better understand the physiology underlying these observations and to evaluate the impact of improved sleep and circadian health on metabolic health in this at-risk population.
Assuntos
Ritmo Circadiano/fisiologia , Resistência à Insulina/fisiologia , Insulina/sangue , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Instituições Acadêmicas , Sono/fisiologia , Actigrafia , Adolescente , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Masculino , Melatonina/sangue , Obesidade/sangue , Sobrepeso/sangue , Estudos Retrospectivos , Fatores de TempoRESUMO
Type 2 diabetes is associated with impaired exercise capacity. Alterations in both muscle perfusion and mitochondrial function can contribute to exercise impairment. We hypothesized that impaired muscle mitochondrial function in type 2 diabetes is mediated, in part, by decreased tissue oxygen delivery and would improve with oxygen supplementation. Ex vivo muscle mitochondrial content and respiration assessed from biopsy samples demonstrated expected differences in obese individuals with (n = 18) and without (n = 17) diabetes. Similarly, in vivo mitochondrial oxidative phosphorylation capacity measured in the gastrocnemius muscle via 31P-MRS indicated an impairment in the rate of ADP depletion with rest (27 ± 6 s [diabetes], 21 ± 7 s [control subjects]; P = 0.008) and oxidative phosphorylation (P = 0.046) in type 2 diabetes after isometric calf exercise compared with control subjects. Importantly, the in vivo impairment in oxidative capacity resolved with oxygen supplementation in adults with diabetes (ADP depletion rate 5.0 s faster, P = 0.012; oxidative phosphorylation 0.046 ± 0.079 mmol/L/s faster, P = 0.027). Multiple in vivo mitochondrial measures related to HbA1c These data suggest that oxygen availability is rate limiting for in vivo mitochondrial oxidative exercise recovery measured with 31P-MRS in individuals with uncomplicated diabetes. Targeting muscle oxygenation could improve exercise function in type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Mitocôndrias Musculares/efeitos dos fármacos , Obesidade/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Oxigênio/administração & dosagem , Adulto , Idoso , Respiração Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Obesidade/complicações , Obesidade/terapia , Oxigênio/farmacologia , Consumo de Oxigênio/fisiologia , Comportamento SedentárioRESUMO
BACKGROUND: Myocardial mechanics are altered in adults with obesity and type 2 diabetes (T2D); insulin resistance and adipokines have been implicated as important risk factors for cardiovascular disease, but these relationships are poorly described in adolescents. We hypothesized that obese adolescents and adolescents with T2D would have abnormal cardiac function compared to lean adolescents. In addition, we hypothesized that insulin sensitivity (IS), adiposity, and adipokines would be associated with altered cardiac strain and cardiopulmonary fitness in adolescents with T2D. METHODS AND RESULTS: Adolescents (15±2 years) with T2D (n=37), obesity without diabetes (n=41), and lean controls (n=31) of similar age and pubertal stage underwent echocardiography with speckle tracking, assessment of IS by hyperinsulinemic-euglycemic clamp, body composition by dual-energy x-ray absorptiometry, peak oxygen consumption (VO2peak) by cycle ergometry, adiponectin, and leptin. Compared to lean and to obese controls, adolescents with T2D had significantly lower cardiac circumferential strain (CS) (-18.9±4.6 [T2D] versus -21.5±3.5 [obese] versus -22.0±4.2% [lean], P=0.04) and VO2peak (37.6±7.5 [T2D] versus 43.4±8.2 [obese] versus 47.6±8.6 mL/lean kg/min [lean], P<0.0001). In T2D youth, VO2peak was associated with CS, and the association remained significant after adjusting for age, sex, and IS (ß±SE: -0.73±0.26, P=0.02). Among adolescents with T2D, CS was also associated with adiponectin, longitudinal strain with leptin, and VO2peak with adiponectin and IS. CONCLUSIONS: Adolescents with T2D had abnormal CS and reduced VO2peak compared to obese and lean controls, which may represent the earliest evidence of cardiac functional impairment in T2D. Low adiponectin, rather than conventional risk factors and IS, correlated with CS, while both adiponectin and IS related to cardiopulmonary fitness.
Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/etiologia , Obesidade Infantil/complicações , Função Ventricular Esquerda , Absorciometria de Fóton , Adiposidade , Adolescente , Biomarcadores/sangue , Fenômenos Biomecânicos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/fisiopatologia , Ecocardiografia Doppler , Teste de Esforço , Tolerância ao Exercício , Feminino , Humanos , Resistência à Insulina , Masculino , Consumo de Oxigênio , Obesidade Infantil/sangue , Obesidade Infantil/diagnóstico , Obesidade Infantil/fisiopatologia , Estresse MecânicoRESUMO
OBJECTIVE: Diabetic nephropathy and cardiovascular disease are strongly related in adults with type 1 diabetes, yet little is known about this relationship in adolescents prior to the onset of detectable clinical disease. We hypothesized that cardiopulmonary fitness would be directly associated with albumin-to-creatinine ratio (ACR) and inversely related to estimated glomerular filtration rate (eGFR) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Sixty-nine adolescents with type 1 diabetes and 13 nondiabetic control subjects of similar pubertal stage and BMI had insulin sensitivity (glucose infusion rate [GIR]), measured by hyperinsulinemic-euglycemic clamp, and lean body mass, measured by DEXA. Cardiopulmonary fitness was measured by cycle ergometry to obtain peak volume of oxygen (VO2peak), and renal function was measured by eGFR using the Bouvet equation (measuring creatinine and cystatin C levels) and ACR. RESULTS: Adolescents (15.5 ± 2.2 years of age) with type 1 diabetes (6.3 ± 3.8 years diabetes duration) had reduced VO2peak (31.5 ± 6.3 vs. 36.2 ± 7.9 mL/kg â min, P = 0.046) and VO2peak/lean kg (43.7 ± 7.0 vs. 51.0 ± 8.6 mL/lean kg â min, P = 0.007) compared with nondiabetic control subjects. eGFR was inversely associated with VO2peak and VO2peak/lean kg after adjusting for sex, Tanner stage, GIR, HbA1c level, systolic blood pressure, and LDL cholesterol level (ß ± SE, VO2peak: -0.19 ± 0.07, P = 0.02; VO2peak/lean kg: -0.19 ± 0.09, P = 0.048). Moreover, participants in the highest tertile for eGFR had significantly lower sex- and Tanner-adjusted VO2peak and VO2peak/lean kg compared with participants in the lowest tertile. CONCLUSIONS: Adolescents with type 1 diabetes had reduced exercise capacity, which was strongly associated with renal health, independent of insulin sensitivity. Future studies should examine the underlying interrelated pathophysiology in order to identify probable targets for treatment to reduce cardiovascular and renal complications.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Tolerância ao Exercício , Rim/fisiopatologia , Adolescente , Glicemia/metabolismo , Pressão Sanguínea , Composição Corporal , Estudos de Casos e Controles , Criança , LDL-Colesterol/sangue , Creatinina/urina , Cistatina C/urina , Feminino , Taxa de Filtração Glomerular , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina , Modelos Lineares , Masculino , Análise Multivariada , Adulto JovemRESUMO
Insulin resistance (IR) increases cardiovascular morbidity and is associated with mitochondrial dysfunction. IR is now recognized to be present in type 1 diabetes; however, its relationship with mitochondrial function is unknown. We determined the relationship between IR and muscle mitochondrial function in type 1 diabetes using the hyperinsulinemic-euglycemic clamp and (31)P-MRS before, during, and after near-maximal isometric calf exercise. Volunteers included 21 nonobese adolescents with type 1 diabetes and 17 nondiabetic control subjects with similar age, sex, BMI, Tanner stage, and activity levels. We found that youths with type 1 diabetes were more insulin resistant (median glucose infusion rate 10.1 vs. 18.9 mg/kglean/min; P < 0.0001) and had a longer time constant of the curve of ADP conversion to ATP (23.4 ± 5.3 vs. 18.8 ± 3.9 s, P < 0.001) and a lower rate of oxidative phosphorylation (median 0.09 vs. 0.21 mmol/L/s, P < 0.001). The ADP time constant (ß = -0.36, P = 0.026) and oxidative phosphorylation (ß = 0.02, P < 0.038) were related to IR but not HbA1c. Normal-weight youths with type 1 diabetes demonstrated slowed postexercise ATP resynthesis and were more insulin resistant than control subjects. The correlation between skeletal muscle mitochondrial dysfunction in type 1 diabetes and IR suggests a relationship between mitochondrial dysfunction and IR in type 1 diabetes.
Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Resistência à Insulina/fisiologia , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease and is a major cause of mortality in type 2 diabetes. Insulin sensitivity is an important determinant of renal health in adults with type 2 diabetes, but limited data exist in adolescents. We hypothesized that measured insulin sensitivity (glucose infusion rate [GIR]) would be associated with early markers of DN reflected by estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in adolescents with type 2 diabetes. RESEARCH DESIGN AND METHODS: Type 2 diabetic (n = 46), obese (n = 29), and lean (n = 19) adolescents (15.1 ± 2.2 years) had GIR measured by hyperinsulinemic-euglycemic clamps. ACR was measured and GFR was estimated by the Bouvet equation (combined creatinine and cystatin C). RESULTS: Adolescents with type 2 diabetes had significantly lower GIR, and higher eGFR and ACR than obese or lean adolescents. Moreover, 34% of type 2 diabetic adolescents had albuminuria (ACR ≥30 mg/g), and 24% had hyperfiltration (≥135 mL/min/1.73 m2). Stratifying ACR and eGFR into tertiles, adolescents with type 2 diabetes in the highest tertiles of ACR and eGFR had respectively lower GIR than those in the mid and low tertiles, after adjusting for age, sex, Tanner stage, BMI, and HbA1c (P = 0.02 and P = 0.04). GIR, but not HbA1c, LDL, or systolic blood pressure, was also associated with eGFR after adjusting for sex and Tanner stage (ß ± SE: -2.23 ± 0.87; P = 0.02). CONCLUSIONS: A significant proportion of adolescents with type 2 diabetes showed evidence of early DN, and insulin sensitivity, rather than HbA1c, blood pressure, or lipid control, was the strongest determinant of renal health.