Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 152
Filtrar
1.
Pediatr Diabetes ; 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981196

RESUMO

BACKGROUND: Although surveillance for diabetes in youth relies on provider-assigned diabetes type from medical records, its accuracy compared to an etiologic definition is unknown. METHODS: Using the SEARCH for Diabetes in Youth Registry, we evaluated the validity and accuracy of provider-assigned diabetes type abstracted from medical records against etiologic criteria that included the presence of diabetes autoantibodies (DAA) and insulin sensitivity. Youth who were incident for diabetes in 2002-2006, 2008, or 2012 and had complete data on key analysis variables were included (n = 4001, 85% provider diagnosed type 1). The etiologic definition for type 1 diabetes was ≥1 positive DAA titer(s) or negative DAA titers in the presence of insulin sensitivity and for type 2 diabetes was negative DAA titers in the presence of insulin resistance. RESULTS: Provider diagnosed diabetes type correctly agreed with the etiologic definition of type for 89.9% of cases. Provider diagnosed type 1 diabetes was 96.9% sensitive, 82.8% specific, had a positive predictive value (PPV) of 97.0% and a negative predictive value (NPV) of 82.7%. Provider diagnosed type 2 diabetes was 82.8% sensitive, 96.9% specific, had a PPV and NPV of 82.7% and 97.0%, respectively. CONCLUSION: Provider diagnosis of diabetes type agreed with etiologic criteria for 90% of the cases. While the sensitivity and PPV were high for youth with type 1 diabetes, the lower sensitivity and PPV for type 2 diabetes highlights the value of DAA testing and assessment of insulin sensitivity status to ensure estimates are not biased by misclassification.

2.
Am J Nephrol ; 51(9): 695-704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866949

RESUMO

BACKGROUND: Apolipoprotein L1 gene (APOL1) G1 and G2 kidney-risk variants (KRVs) cause CKD in African Americans, inducing mitochondrial dysfunction. Modifying factors are required, because a minority of individuals with APOL1 high-risk genotypes develop nephropathy. Given that APOL1 function is pH-sensitive and the pH of the kidney interstitium is <7, we hypothesized the acidic kidney interstitium may facilitate APOL1 KRV-induced mitochondrial dysfunction. METHODS: Human embryonic kidney (HEK293) cells conditionally expressing empty vector (EV), APOL1-reference G0, and G1 or G2 KRVs were incubated in media pH 6.8 or 7.4 for 4, 6, or 8 h. Genotype-specific pH effects on mitochondrial length (µm) were assessed using confocal microscopy in live cells and Fiji derivative of ImageJ software with MiNA plug-in. Lower mitochondrial length indicated fragmentation and early dysfunction. RESULTS: After 6 h doxycycline (Dox) induction in pH 6.8 media, G2-expressing cells had shorter mitochondria (6.54 ± 0.40) than cells expressing EV (7.65 ± 0.72, p = 0.02) or G0 (7.46 ± 0.31, p = 0.003). After 8 h Dox induction in pH 6.8 media, both G1- (6.21 ± 0.26) and G2-expressing cells had shorter mitochondria (6.46 ± 0.34) than cells expressing EV (7.13 ± 0.32, p = 0.002 and p = 0.008, respectively) or G0 (7.22 ± 0.45, p = 0.003 and p = 0.01, respectively). Mitochondrial length in cells incubated in pH 7.4 media were comparable after 8 h Dox induction regardless of genotype. APOL1 mRNA expression and cell viability were comparable regardless of pH or genotype after 8 h Dox induction. CONCLUSION: Acidic pH facilitates early mitochondrial dysfunction induced by APOL1 G1 and G2 KRVs in HEK293 cells. We propose that the acidic kidney interstitium may play a role in APOL1-mediated mitochondrial pathophysiology and nephropathy.

3.
Diabetes Care ; 43(10): 2418-2425, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737140

RESUMO

OBJECTIVE: Diabetes surveillance often requires manual medical chart reviews to confirm status and type. This project aimed to create an electronic health record (EHR)-based procedure for improving surveillance efficiency through automation of case identification. RESEARCH DESIGN AND METHODS: Youth (<20 years old) with potential evidence of diabetes (N = 8,682) were identified from EHRs at three children's hospitals participating in the SEARCH for Diabetes in Youth Study. True diabetes status/type was determined by manual chart reviews. Multinomial regression was compared with an ICD-10 rule-based algorithm in the ability to correctly identify diabetes status and type. Subsequently, the investigators evaluated a scenario of combining the rule-based algorithm with targeted chart reviews where the algorithm performed poorly. RESULTS: The sample included 5,308 true cases (89.2% type 1 diabetes). The rule-based algorithm outperformed regression for overall accuracy (0.955 vs. 0.936). Type 1 diabetes was classified well by both methods: sensitivity (Se) (>0.95), specificity (Sp) (>0.96), and positive predictive value (PPV) (>0.97). In contrast, the PPVs for type 2 diabetes were 0.642 and 0.778 for the rule-based algorithm and the multinomial regression, respectively. Combination of the rule-based method with chart reviews (n = 695, 7.9%) of persons predicted to have non-type 1 diabetes resulted in perfect PPV for the cases reviewed while increasing overall accuracy (0.983). The Se, Sp, and PPV for type 2 diabetes using the combined method were ≥0.91. CONCLUSIONS: An ICD-10 algorithm combined with targeted chart reviews accurately identified diabetes status/type and could be an attractive option for diabetes surveillance in youth.

4.
J Diabetes Complications ; 34(10): 107676, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32713707

RESUMO

AIMS: To evaluate cardiovascular risk factors and heart rate variability (HRV) in young adults with type 2 diabetes and arterial stiffness and to explore the relationship between HRV and arterial stiffness. METHODS: We studied 185 young adults with youth-onset T2D enrolled in the SEARCH for Diabetes in Youth Study. Cardiovascular risk factors and HRV were compared between individuals with and without type 2 diabetes and arterial stiffness (defined as a pulse wave velocity greater than the 90th percentile of healthy controls, >6.767 m/s). Semiparametric regression evaluated the independent relationship between HRV and PWV. RESULTS: Participants with T2D and arterial stiffness were more likely to be older, non-Hispanic Black, have higher systolic and diastolic blood pressure, greater adiposity and obesity-related dyslipidemia (higher triglycerides and lower HDLC). Participants with T2D and arterial stiffness also had lower overall HRV (lower SDNN) with parasympathetic loss (lower RMSSD and PNN50), p < 0.05. Lower HRV tended to be but was not significantly associated with arterial stiffness after adjustment for age, race/ethnicity, sex and cardiovascular risk factors (beta coefficient = -1.11, p = 0.08). CONCLUSIONS: Youth with T2D and arterial stiffness have a worse cardiovascular risk profile, specifically risk factors related to the metabolic syndrome and lower HRV.

5.
Mol Psychiatry ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32372009

RESUMO

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

6.
MMWR Morb Mortal Wkly Rep ; 69(6): 161-165, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32053581

RESUMO

Diabetes is one of the most common chronic diseases among persons aged <20 years (1). Onset of diabetes in childhood and adolescence is associated with numerous complications, including diabetic kidney disease, retinopathy, and peripheral neuropathy, and has a substantial impact on public health resources (2,3). From 2002 to 2012, type 1 and type 2 diabetes incidence increased 1.4% and 7.1%, respectively, among U.S. youths (4). To assess recent trends in incidence of diabetes in youths (defined for this report as persons aged <20 years), researchers analyzed 2002-2015 data from the SEARCH for Diabetes in Youth Study (SEARCH), a U.S. population-based registry study with clinical sites located in five states. The incidence of both type 1 and type 2 diabetes in U.S. youths continued to rise at constant rates throughout this period. Among all youths, the incidence of type 1 diabetes increased from 19.5 per 100,000 in 2002-2003 to 22.3 in 2014-2015 (annual percent change [APC] = 1.9%). Among persons aged 10-19 years, type 2 diabetes incidence increased from 9.0 per 100,000 in 2002-2003 to 13.8 in 2014-2015 (APC = 4.8%). For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites. These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/etnologia , Diabetes Mellitus Tipo 2/etnologia , Feminino , Humanos , Incidência , Índios Norte-Americanos/estatística & dados numéricos , Lactente , Recém-Nascido , Masculino , Estados Unidos/epidemiologia , Adulto Jovem
7.
Clin Transplant ; 34(6): e13827, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32080893

RESUMO

Two renal-risk variants in the apolipoprotein L1 gene (APOL1) in African American (AA) deceased donors (DD) are associated with shorter renal allograft survival after transplantation. To identify additional genes contributing to allograft survival, a genome-wide association study was performed in 532 AA DDs. Phenotypic data were obtained from the Scientific Registry of Transplant Recipients. Association and single-nucleotide polymorphism (SNP)-by-APOL1 interaction tests were conducted using death-censored renal allograft survival accounting for relevant covariates. Replication and inverse-variance-weighted meta-analysis were performed using data from 250 AA DD in the Genomics of Transplantation study. Accounting for APOL1, multiple SNPs near the Nudix Hydrolase 7 gene (NUDT7) showed strong independent effects (P = 1.6 × 10-8 -2.2 × 10-8 ). Several SNPs in the Translocation protein SEC63 homolog (SEC63; P = 2 × 10-9 -3.7 × 10-8 ) and plasmacytoma variant translocation 1 (PVT1) genes (P = 4.0 × 10-8 -7 × 10-8 ) modified the effect of APOL1 on allograft survival. SEC63 is expressed in human renal tubule cells and glomeruli, and PVT1 is associated with diabetic kidney disease. Overall, associations were detected for 41 SNPs (P = 2 × 10-9 -5 × 10-8 ) contributing independently or interacting with APOL1 to impact renal allograft survival after transplantation from AA DD. Given the small sample size of the discovery and replication sets, independent validations and functional genomic efforts are needed to validate these results.

8.
Am J Clin Nutr ; 111(3): 719-727, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31990972

RESUMO

BACKGROUND: "Energy drinks" are heavily marketed to the general public, across the age spectrum. The efficacy of decaffeinated energy drinks in enhancing subjective feelings of energy (s-energy) is controversial. OBJECTIVE: The authors sought to test the efficacy of the caffeine-free version of a popular energy drink compared with a placebo drink. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial in 223 healthy men and women aged 18-70 y with intention-to-treat and completers analysis. Participants were randomly assigned to consumption of either the decaffeinated energy drink or a placebo drink on testing day 1, and the other drink a week later. A battery of computer-based mood and cognitive tests to assess s-energy was conducted at baseline and at 0.5, 2.5, and 5 h post-ingestion. The main outcome measures were 1) mood, which was assessed by using a General Status Check Scale and the Profile of Mood States 2nd edition brief form, and 2) cognitive measures, including the N-back task (reaction time and accuracy), Reaction Time test, Flanker task (distraction avoidance), and Rapid Visual Information Processing test. RESULTS: No statistically significant or meaningful benefits were observed for any outcome measure, including mood and cognitive measures. Analyses of mean differences, slopes, and median differences were consistent. CONCLUSIONS: No differences were detected across a range of mood/cognitive/behavioral/s-energy-level tests after consumption of the energy drink compared with a placebo drink in this diverse sample of adults. Thus, we found strong evidence that the energy drink is not efficacious in enhancing s-energy levels, nor any related cognitive or behavioral variables measured. In light of federal regulations, these findings suggest that labeling and marketing of some products which claim to provide these benefits may be unsubstantiated. This trial was registered at www.clinicaltrials.gov as NCT02727920.


Assuntos
Cognição , Bebidas Energéticas/análise , Adulto , Afeto , Idoso , Cafeína/análise , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Tempo de Reação , Adulto Jovem
10.
Ann Epidemiol ; 37: 37-42, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31383511

RESUMO

PURPOSE: Most surveillance efforts in childhood diabetes have focused on incidence, whereas prevalence is rarely reported. This study aimed to assess whether a mathematical illness-death model accurately estimated future prevalence from baseline prevalence and incidence rates in children. METHODS: SEARCH for Diabetes in Youth is an ongoing population-based surveillance study of prevalence and incidence of diabetes and its complications among youth in the United States. We used age-, sex-, and race/ethnicity-specific SEARCH estimates of the prevalence of type I and type II diabetes in 2001 and incidence from 2002 to 2008. These data were used in a partial differential equation to estimate prevalence in 2009 with 95% bootstrap confidence intervals. Model-based prevalence was compared with the observed prevalence in 2009. RESULTS: Most confidence intervals for the difference between estimated and observed prevalence included zero, indicating no evidence for a difference between the two methods. The width of confidence intervals indicated high precision for the estimated prevalence when considering all races/ethnicities. In strata with few cases, precision was reduced. CONCLUSIONS: Future prevalence of type I and type II diabetes in youth may be accurately estimated from baseline prevalence and incidence. Diabetes surveillance could benefit from potential cost savings of this method.

11.
J Am Soc Nephrol ; 30(10): 2027-2036, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31383730

RESUMO

BACKGROUND: Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. METHODS: We conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts. RESULTS: Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index. CONCLUSIONS: In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.

12.
Pediatr Diabetes ; 20(7): 815-820, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31260152

RESUMO

AIM: SEARCH has recently reported that both prevalence and incidence of youth onset type 2 diabetes (YT2D) increased among most US race/ethnic groups in the early 2000s. This study reports on the incidence (2002-2013) and prevalence (2001, 2009) of YT2D in the Navajo Nation among youth age < 20 years from 2001 to 2013. METHODS: SEARCH sought to identify prevalent YT2D cases in 2001 (N = 75) and 2009 (N = 70) and all incident YT2D cases in three periods: 2002 to 2005 (N = 53), 2006 to 2009 (N = 68), and 2010 2013 (N = 90) in Navajo Nation. Denominators were based on the active Indian Health Service user population for eligible health care facilities. Prevalence (per 100 000) and period-specific incidence rates (per 100 000 person-years) were computed for youth aged 10 to 19 years. Changes in prevalence were tested with a two-sided skew-corrected inverted score test, while changes in incidence were tested with Poisson regression. RESULTS: YT2D prevalence was high but stable in 2001 and 2009, overall [146.6 (116.8, 184.0) vs 141.5 (112.0, 178.8), P = .65) and in all subgroups. In contrast, incidence rates increased particularly between the second and third periods overall and in most subgroups by age and by sex. CONCLUSIONS: These data confirm the high burden of YT2D among Navajo youth and suggest an increasing risk in more recent years. However, recent improvements in obesity reduction in this population demonstrate optimism for potential reductions in YT2D in Navajo Nation.

13.
J Lipid Res ; 60(8): 1425-1431, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31133557

RESUMO

apoM is a minor HDL apolipoprotein and carrier for sphingosine-1-phosphate (S1P). HDL apoM and S1P concentrations are inversely associated with atherosclerosis progression in rodents. We evaluated associations between plasma concentrations of S1P, plasma concentrations of apoM, and HDL apoM levels with prevalent subclinical atherosclerosis and mortality in the African American-Diabetes Heart Study participants (N = 545). Associations between plasma S1P, plasma apoM, and HDL apoM with subclinical atherosclerosis and mortality were assessed using multivariate parametric, nonparametric, and Cox proportional hazards models. At baseline, participants' median (25th percentile, 75th percentile) age was 55 (49, 62) years old and their coronary artery calcium (CAC) mass score was 26.5 (0.0, 346.5). Plasma S1P, plasma apoM, and HDL apoM were not associated with CAC. After 64 (57.6, 70.3) months of follow-up, 81 deaths were recorded. Higher concentrations of plasma S1P [odds ratio (OR) = 0.14, P = 0.01] and plasma apoM (OR = 0.10, P = 0.02), but not HDL apoM (P = 0.89), were associated with lower mortality after adjusting for age, sex, statin use, CAC, kidney function, and albuminuria. We conclude that plasma S1P and apoM concentrations are inversely and independently associated with mortality, but not CAC, in African Americans with type 2 diabetes after accounting for conventional risk factors.

14.
Hum Mol Genet ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31127295

RESUMO

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

16.
Endocrinol Diabetes Metab ; 2(2): e00057, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31008365

RESUMO

Objective: Although severe hypoglycaemia (SH) can lead to adverse health outcomes, little is known about its occurrence and re-occurrence among youth with type 1 or type 2 diabetes. Methods: This study included 2740 participants aged <20 years at diabetes diagnosis and 5-14 years diabetes duration from the SEARCH for Diabetes in Youth Cohort Study. Participants reported SH events in the past 6 months. Differences in SH events by demographic and clinical factors were tested using logistic regression models. Results: Severe hypoglycaemia in the past 6 months was more common among youth with type 1 (7.0%, 168 of 2399) than with type 2 diabetes (2.6%, nine of 341) (P < 0.002). The median number of SH events per youth who had at least one SH event in the past 6 months was 1 for both type 1 type 2 diabetes. For youth with type 1 diabetes, those who reported SH events were older, were more likely to have obesity or to be physically active, and had lower HbA1c. After adjustments, one unit increase in HbA1c was associated with 16% lower likelihood (OR 0.84, 95% CI 0.75, 0.94) and being physically active was associated with an 87% higher likelihood (OR 1.87, 95% CI 1.23, 2.86) of reporting a SH event. There were too few SH events among youth with type 2 diabetes to analyse further. Conclusions: In youth with diabetes, SH was common even within a short 6-month window. Better understanding the causes of SH may help prevent them from occurring.

17.
Contemp Clin Trials Commun ; 14: 100357, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31016270

RESUMO

Timely placement of an arteriovenous (AV) vascular access (native AV fistula [AVF] or prosthetic AV graft [AVG]) is necessary to limit the use of tunneled central venous catheters (TCVC) in patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD). National guidelines recommend placement of AVF as the AV access of first choice in all patients to improve patient survival. The benefits of AVF over AVG are less certain in the older adults, as age-related biological changes independently modulate patient outcomes. This manuscript describes the rationale, study design and protocol for a randomized controlled pilot study of the feasibility and effects of AVG-first access placement in older adults with no prior AV access surgery. Fifty patients age ≥65 years, with incident ESKD on HD via TCVC or advanced kidney disease facing imminent HD initiation, and suitable upper extremity vasculature for initial placement of an AVF or AVG, will be randomly assigned to receive either an upper extremity AVG-first (intervention) or AVF-first (comparator) access. The study will establish feasibility of randomizing older adults to the two types of AV access surgery, evaluate relationships between measurements of preoperative physical function and vascular access development, compare vascular access outcomes between groups, and gather longitudinal assessments of upper extremity muscle strength, gait speed, performance of activities of daily living, and patient satisfaction with their vascular access and quality of life. Results will assist with the planning of a larger, multicenter trial assessing patient-centered outcomes.

18.
Int J Obes (Lond) ; 43(10): 1940-1950, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30926953

RESUMO

BACKGROUND/OBJECTIVES: The waist-to-height ratio (WHtR) estimates cardiometabolic risk in youth without need for growth charts by sex and age. Questions remain about whether waist circumference measured per protocol of the National Health and Nutrition Examination Survey (WNHAHtR) or World Health Organization (WWHOHtR) can better predict blood pressures and lipid parameters in youth. PARTICIPANTS/METHODS: WHtR was measured under both anthropometric protocols among participants in the SEARCH Study, who were recently diagnosed with diabetes (ages 5-19 years; N = 2 773). Biomarkers were documented concurrently with baseline anthropometry and again ~7 years later (ages 10-30 years; N = 1 712). For prediction of continuous biomarker outcomes, baseline WNHAHtR or WWHOHtR entered semiparametric regression models employing restricted cubic splines. To predict binary biomarkers (high-risk group defined as the most adverse quartile) linear WNHAHtR or WWHOHtR terms entered logistic models. Model covariates included demographic characteristics, pertinent medication use, and (for prospective predictions) the follow-up time since baseline. We used measures of model fit, including the adjusted-R2 and the area under the receiver operator curves (AUC) to compare WNHAHtR and WWHOHtR. RESULTS: For the concurrent biomarkers, the proportion of variation in each outcome explained by full regression models ranged from 23 to 46%; for the prospective biomarkers, the proportions varied from 11 to 30%. Nonlinear relationships were recognized with the lipid outcomes, both at baseline and at follow-up. In full logistic models, the AUCs ranged from 0.75 (diastolic pressure) to 0.85 (systolic pressure) at baseline, and from 0.69 (triglycerides) to 0.78 (systolic pressure) at the prospective follow-up. To predict baseline elevations of the triglycerides/HDL cholesterol ratio, the AUC was 0.816 for WWHOHtR compared with 0.810 for WNHAHtR (p = 0.003), but otherwise comparisons between alternative WHtR protocols were not significantly different. CONCLUSIONS: Among youth with recently diagnosed diabetes, measurements of WHtR by either waist circumference protocol similarly helped estimate current and prospective cardiometabolic risk biomarkers.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Síndrome Metabólica/sangue , Obesidade Pediátrica/sangue , Razão Cintura-Estatura , Adolescente , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Criança , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Inquéritos Nutricionais , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/fisiopatologia , Valor Preditivo dos Testes , Estados Unidos/epidemiologia , Circunferência da Cintura , Adulto Jovem
19.
Nat Genet ; 51(4): 636-648, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926973

RESUMO

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.


Assuntos
Lipídeos/sangue , Lipídeos/genética , Fumar/sangue , Fumar/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Estilo de Vida , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Pediatr Diabetes ; 20(6): 693-701, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30903717

RESUMO

BACKGROUND: Given diabetes is an important risk factor for cardiovascular disease (CVD), we examined temporal trends in CVD risk factors by comparing youth recently diagnosed with type 1 diabetes (T1D) and type 2 diabetes (T2D) from 2002 through 2012. METHODS: The SEARCH for Diabetes in Youth Study identified youth with diagnosed T1D (n = 3954) and T2D (n = 706) from 2002 to 2012. CVD risk factors were defined using the modified Adult Treatment Panel III criteria for metabolic syndrome: (a) hypertension; (b) high-density lipoprotein cholesterol ≤40 mg/dL; (c) triglycerides ≥110 mg/dL; and (d) waist circumference (WC) >90th percentile. Prevalence of CVD risk factors, stratified by diagnosis year and diabetes type, was reported. Univariate and multivariate logistic models and Poisson regression were fit to estimate the prevalence trends for CVD risk factors individually and in clusters (≥2 risk factors). RESULTS: The prevalence of ≥2 CVD risk factors was higher in youth with T2D than with T1D at each incident year, but the prevalence of ≥2 risk factors did not change across diagnosis years among T1D or T2D participants. The number of CVD risk factors did not change significantly in T1D participants, but increased at an annual rate of 1.38% in T2D participants. The prevalence of hypertension decreased in T1D participants, and high WC increased in T2D participants. CONCLUSION: The increase in number of CVD risk factors including large WC among youth with T2D suggests a need for early intervention to address these CVD risk factors. Further study is needed to examine longitudinal associations between diabetes and CVD.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/etiologia , Adolescente , Fatores Etários , Idade de Início , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Progressão da Doença , Feminino , Humanos , Índios Norte-Americanos/estatística & dados numéricos , Masculino , Prevalência , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA