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In this narrative review, we describe the epidemiology (prevalence, incidence, temporal trends, and projections) of type 2 diabetes among children and adolescents (<20 years), focusing on data from the U.S. and reporting global estimates where available. Secondarily, we discuss the clinical course of youth-onset type 2 diabetes, from prediabetes to complications and comorbidities, drawing comparisons with youth type 1 diabetes to highlight the aggressive course of this condition, which, only recently, has become recognized as a pediatric disease by health care providers. Finally, we end with an overview of emerging topics in type 2 diabetes research that have potential to inform strategies for effective preventive action at the community and individual levels.
Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Criança , Humanos , Adolescente , Diabetes Mellitus Tipo 2/epidemiologia , Estado Pré-Diabético/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Comorbidade , IncidênciaRESUMO
OBJECTIVE: To identify correlates of hemoglobin A1c (HbA1c) testing frequency and associations with HbA1c levels and microvascular complications in youth-onset diabetes. RESEARCH DESIGN AND METHODS: The SEARCH for Diabetes in Youth study collected data from individuals diagnosed with diabetes before age 20 at 8 years (n=1,885 type 1, n=230 type 2) and 13 years (n=649 type 1, n = 84 type 2) diabetes duration. We identified correlates of reporting ≥3 HbA1c tests/year using logistic regression. We examined associations of HbA1c testing with HbA1c levels and microvascular complications (retinopathy, neuropathy, or nephropathy) using sequentially adjusted linear and logistic regression. RESULTS: For type 1 diabetes, odds of reporting ≥3 HbA1c tests/year at 8 and 13 years diabetes duration decreased with older age at diagnosis (odds ratio [OR] 0.91 [95% CI 0.88-0.95]), longer duration of diabetes (OR 0.90 [0.82-0.99]), not having a personal doctor (OR 0.44 [0.30-0.65]), and lapses in health insurance (OR 0.51 [0.27-0.96]). HbA1c testing ≥3 times/year over time was associated with lower HbA1c levels (OR -0.36% [-0.65 to -0.06]) and lower odds of microvascular complications (OR 0.64 [0.43-0.97]) at 13 years duration, but associations were attenuated after adjustment for HbA1c testing correlates (OR -0.17 [-0.46 to 0.13] and 0.70 [0.46-1.07], respectively). For type 2 diabetes, not seeing an endocrinologist decreased the odds of reporting ≥3 HbA1c tests/year over time (OR 0.19 [0.06-0.63]), but HbA1c testing frequency was not associated with HbA1c levels or microvascular complications. CONCLUSIONS: We observed disparities in HbA1c testing frequency predominately by health care-related factors, which were associated with diabetes outcomes in type 1 diabetes.
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OBJECTIVE: The metabolic phenotype of youth-onset type 2 diabetes (T2D) differs from that of adult-onset T2D, but little is known about genetic contributions. We aimed to evaluate the association between a T2D genetic risk score (GRS) and traits related to glucose-insulin homeostasis among healthy youth. RESEARCH DESIGN AND METHODS: We used data from 356 youth (mean age 16.7 years; 50% female) in the Exploring Perinatal Outcomes Among Children (EPOCH) cohort to calculate a standardized weighted GRS based on 271 single nucleotide polymorphisms associated with T2D in adults. We used linear regression to assess associations of the GRS with log-transformed fasting glucose, 2-h glucose, HOMA of insulin resistance (HOMA-IR), oral disposition index, and insulinogenic index adjusted for age, sex, BMI z score, in utero exposure to maternal diabetes, and genetic principal components. We also evaluated effect modification by BMI z score, in utero exposure to maternal diabetes, and ethnicity. RESULTS: Higher weighted GRS was associated with lower oral disposition index (ß = -0.11; 95% CI -0.19, -0.02) and insulinogenic index (ß = -0.08; 95% CI -0.17, -0.001), but not with fasting glucose (ß = 0.01; 95% CI -0.01, 0.02), 2-h glucose (ß = 0.03; 95% CI -0.0004, 0.06), or HOMA-IR (ß = 0.02; 95% CI -0.04, 0.07). BMI z score and in utero exposure to maternal diabetes increased the effect of the GRS on glucose levels. CONCLUSIONS: Our results suggest that T2D genetic risk factors established in adults are relevant to glucose-insulin homeostasis in youth and that maintaining a healthy weight may be particularly important for youth with high genetic risk of T2D.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adolescente , Glicemia , Criança , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Glucose , Homeostase , Humanos , Insulina , Resistência à Insulina/genética , Masculino , Fenótipo , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE: To examine associations of dietary changes from childhood to adolescence with adolescent hepatic fat and whether the PNPLA3 rs738409 risk allele, a strong genetic risk factor for hepatic fat, modifies associations. STUDY DESIGN: Data were from 358 participants in the Exploring Perinatal Outcomes among CHildren (EPOCH) study, a longitudinal cohort in Colorado. Diet was assessed by food frequency questionnaire in childhood (approximately 10 years of age) and adolescence (approximately 16 years of age) and converted to nutrient densities. Hepatic fat was assessed in adolescence by magnetic resonance imaging. Linear regression was used to test associations of dietary changes from childhood to adolescence with adolescent hepatic fat. RESULTS: Increases in fiber, vegetable protein, and polyunsaturated fat intake from childhood to adolescence were associated with lower adolescent hepatic fat, and increases in animal protein were associated with higher hepatic fat (ß per 5-unit increase on log-hepatic fat: -0.12 [95% CI, -0.21 to -0.02] for âµfiber; -0.26 [95% CI, -0.45 to -0.07] for âµvegetable protein; -0.18 [95% CI, -0.35 to -0.02] for âµpolyunsaturated fat; 0.13 [95% CI, 0.04-0.22] for âµanimal protein). There was evidence of effect modification by PNPLA3 variant, whereby inverse associations of âµfiber and âµvegetable protein and positive associations of âµsaturated fat with adolescent hepatic fat were stronger in risk allele carriers. Most conclusions were similar after adjusting for obesity in adolescence, but associations of âµsaturated fat with hepatic fat were attenuated toward the null. CONCLUSIONS: Our results suggest that nutrient intake changes between childhood and adolescence, particularly decreases in fiber and vegetable protein and increases in saturated fat intake, interact with the PNPLA3 variant to predict higher hepatic fat in adolescence, and may be targets for reducing hepatic fat in high-risk youth.
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Dieta/efeitos adversos , Fígado Gorduroso/etiologia , Adolescente , Comportamento do Adolescente , Criança , Comportamento Infantil , Dieta/psicologia , Inquéritos sobre Dietas , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/genética , Fígado Gorduroso/psicologia , Feminino , Interação Gene-Ambiente , Marcadores Genéticos , Predisposição Genética para Doença , Comportamentos Relacionados com a Saúde , Humanos , Modelos Lineares , Lipase/genética , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana/genética , Estudos Prospectivos , Fatores de Risco , AutorrelatoRESUMO
OBJECTIVE: Poor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D (n = 1,095) or T2D (n = 285). RESEARCH DESIGN AND METHODS: Cognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition. RESULTS: Having T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model (P < 0.01 for all, respectively). CONCLUSIONS: These data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.
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Diabetes Mellitus Tipo 2 , Adolescente , Criança , Cognição , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Obesidade , Pais , Adulto JovemRESUMO
OBJECTIVES: To characterize prevalence of ideal cardiovascular health (ICVH) during early childhood (4-7 years of age), and to identify pre- and perinatal biological, sociodemographic, metabolic, and behavioral correlates of ICVH. STUDY DESIGN: Among 350 mother-child pairs in the Healthy Start Study, we defined ICVH as no exposure to second hand smoke; ≥1 hour/day of moderate-to-vigorous physical activity; body mass index ≤85th percentile; systolic and diastolic blood pressure <90th percentile; cholesterol <170 mg/dL, fasting glucose <100 mg/dL; and healthy diet, per the American Heart Association. Pre- and perinatal characteristics were obtained from questionnaires, medical records, and in-person visits. Because of low prevalence of ICVH, we focused on prevalence of meeting ≥6 metrics in the analysis. We examined bivariate associations of each characteristic with % meeting ≥6 metrics and included those that were significant (P < .05) in a multivariable logistic regression model. RESULTS: ICVH prevalence at mean ± SD age 4.7±0.6 years was 6.9%; boys had twice the prevalence as girls (9% vs 4.4%). Most (>85%) children met criteria for second hand smoke, body mass index, blood pressure, cholesterol, and glucose, and only one-third met criteria for physical activity (31.4%) and diet (35.1%). In multivariable analyses, key correlates of ICVH were maternal weight status (ORoverweight/obese vs nonoverweight/obese = 0.41 [0.23, 0.73]) and offspring sex (ORmale vs female = 2.14 [1.22, 3.65]). CONCLUSIONS: At age 4-7 years, ICVH prevalence is already low, with diet and adequate physical activity being the limiting factors. Healthy maternal weight prior to pregnancy and male sex are potential determinants of childhood ICVH. Additional work is required to explore associations of early-life ICVH with future health outcomes.
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Doenças Cardiovasculares/prevenção & controle , Saúde da Criança/estatística & dados numéricos , Nível de Saúde , Fatores de Risco de Doenças Cardíacas , Efeitos Tardios da Exposição Pré-Natal , Adulto , Doenças Cardiovasculares/etiologia , Criança , Pré-Escolar , Dieta Saudável/estatística & dados numéricos , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Gravidez , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Poluição por Fumaça de Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/estatística & dados numéricosRESUMO
An adverse intrauterine environment is associated with the future risk of obesity and type 2 diabetes. Changes in placental function may underpin the intrauterine origins of adult disease, but longitudinal studies linking placental function with childhood outcomes are rare. Here, we determined the abundance and phosphorylation of protein intermediates involved in insulin signaling, inflammation, cortisol metabolism, protein glycosylation, and mitochondrial biogenesis in placental villus samples from healthy mothers from the Healthy Start cohort. Using MANOVA, we tested the association between placental proteins and offspring adiposity (fat mass percentage) at birth (n = 109) and infancy (4-6 months, n = 104), and adiposity, skinfold thickness, triglycerides, and insulin in children (4-6 years, n = 66). Placental IGF-1 receptor protein was positively associated with serum triglycerides in children. GSK3ß phosphorylation at serine 9, a readout of insulin and growth factor signaling, and the ratio of phosphorylated to total JNK2 were both positively associated with midthigh skinfold thickness in children. Moreover, peroxisome proliferator-activated receptor γ coactivator (PGC)-1α abundance was positively associated with insulin in children. In conclusion, placental insulin/IGF-1 signaling, PGC-1α, and inflammation pathways were positively associated with metabolic outcomes in 4- to 6-year-old children, identifying a novel link between placental function and long-term metabolic outcomes.
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11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Placenta/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Técnicas In Vitro , Lactente , Proteína Quinase 9 Ativada por Mitógeno/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Fosforilação , Gravidez , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
OBJECTIVE: To assess the importance of genetic and nongenetic risk factors contributing to hepatic fat accumulation in a multiethnic population of youth. STUDY DESIGN: We investigated the relationship between genetic factors and hepatic fat fraction (HFF) in 347 children aged 12.5-19.5 years. We examined 5 single nucleotide polymorphisms previously associated with HFF and a weighted genetic risk score (GRS) and examined how these associations varied with ethnicity (Hispanic vs non-Hispanic white) and body mass index (BMI) category. We also compared how much variation in HFF was explained by genetic factors vs cardiometabolic factors (BMI z-score and the Homeostasis Model of Insulin Resistance) or diet. RESULTS: PNPLA3 rs738409 and the GRS were each associated with HFF among Hispanic (ß = 0.39; 95% CI, 0.16-0.62; P = .001; and ß = 0.20; 95% CI, 0.05-0.34; P = .007, respectively) but not non-Hispanic white (ß = 0.04; 95% CI, -0.18 to 0.26; P = .696; and ß = 0.03; 95% CI, -0.09 to 0.14; P = .651, respectively) youth. Cardiometabolic risk factors explained more of the variation in HFF than genetic risk factors among non-lean Hispanic individuals (27.2% for cardiometabolic markers vs 6.4% for rs738409 and 4.3% for the GRS), and genetic risk factors were more important among lean individuals (2.7% for cardiometabolic markers vs 12.6% for rs738409 and 4.4% for the GRS). CONCLUSIONS: Poor cardiometabolic health may be more important than genetic factors when predicting HFF in overweight and obese young populations. Genetic risk is an important contributor to pediatric HFF among lean Hispanics, but further studies are necessary to elucidate the strength of the association between genetic risk and HFF in non-Hispanic white youth.
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Fígado Gorduroso/epidemiologia , Fígado Gorduroso/genética , Tecido Adiposo/anatomia & histologia , Adolescente , Índice de Massa Corporal , Criança , Estudos de Coortes , Feminino , Hispânico ou Latino , Humanos , Fígado/anatomia & histologia , Masculino , Polimorfismo de Nucleotídeo Único , Medição de Risco , População Branca , Adulto JovemRESUMO
OBJECTIVE: To explore the associations between prenatal exposure to tobacco and neurocognitive development, in the absence of prematurity or low birth weight. STUDY DESIGN: We followed mother-child pairs within Healthy Start through 6 years of age. Children were born at ≥37 weeks of gestation with a birth weight of ≥2500 g. Parents completed the Third Edition Ages and Stages Questionnaire (n = 246) and children completed a subset of the National Institutes of Health Toolbox Cognition Battery (n = 200). The Ages and Stages Questionnaire domains were dichotomized as fail/monitor and pass. Maternal urinary cotinine was measured at approximately 27 weeks of gestation. Separate logistic regression models estimated associations between prenatal exposure to tobacco (cotinine below vs above the limit of detection) and the Ages and Stages Questionnaire domains. Separate linear regression models estimated associations between prenatal exposure to tobacco and fully corrected T-scores for inhibitory control, cognitive flexibility, and receptive language, as assessed by the National Institutes of Health Toolbox. A priori covariates included sex, maternal age, maternal education, daily caloric intake during pregnancy, race/ethnicity, household income, maternal psychiatric disorders, and, in secondary models, postnatal exposure to tobacco. RESULTS: Compared with unexposed offspring, exposed offspring were more likely to receive a fail/monitor score for fine motor skills (OR, 3.9; 95% CI, 1.5-10.3) and decreased inhibitory control (B: -3.0; 95% CI, -6.1 to -0.7). After adjusting for postnatal exposure, only the association with fine motor skills persisted. CONCLUSIONS: Prenatal and postnatal exposures to tobacco may influence neurocognitive development, in the absence of preterm delivery or low birth weight. Increased developmental screening may be warranted for exposed children.