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1.
BMC Med Res Methodol ; 21(1): 210, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629073

RESUMO

BACKGROUND: Disease surveillance of diabetes among youth has relied mainly upon manual chart review. However, increasingly available structured electronic health record (EHR) data have been shown to yield accurate determinations of diabetes status and type. Validated algorithms to determine date of diabetes diagnosis are lacking. The objective of this work is to validate two EHR-based algorithms to determine date of diagnosis of diabetes. METHODS: A rule-based ICD-10 algorithm identified youth with diabetes from structured EHR data over the period of 2009 through 2017 within three children's hospitals that participate in the SEARCH for Diabetes in Youth Study: Cincinnati Children's Hospital, Cincinnati, OH, Seattle Children's Hospital, Seattle, WA, and Children's Hospital Colorado, Denver, CO. Previous research and a multidisciplinary team informed the creation of two algorithms based upon structured EHR data to determine date of diagnosis among diabetes cases. An ICD-code algorithm was defined by the year of occurrence of a second ICD-9 or ICD-10 diabetes code. A multiple-criteria algorithm consisted of the year of first occurrence of any of the following: diabetes-related ICD code, elevated glucose, elevated HbA1c, or diabetes medication. We assessed algorithm performance by percent agreement with a gold standard date of diagnosis determined by chart review. RESULTS: Among 3777 cases, both algorithms demonstrated high agreement with true diagnosis year and differed in classification (p = 0.006): 86.5% agreement for the ICD code algorithm and 85.9% agreement for the multiple-criteria algorithm. Agreement was high for both type 1 and type 2 cases for the ICD code algorithm. Performance improved over time. CONCLUSIONS: Year of occurrence of the second ICD diabetes-related code in the EHR yields an accurate diagnosis date within these pediatric hospital systems. This may lead to increased efficiency and sustainability of surveillance methods for incidence of diabetes among youth.

2.
Diabetes Care ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607833

RESUMO

OBJECTIVE: To examine short-term mortality and cause of death among youth and young adults (YYAs) with youth-onset diabetes. RESEARCH DESIGN AND METHODS: We included 19,717 YYAs newly diagnosed with diabetes before 20 years of age from 1 January 2002 to 31 December 2015 enrolled in the SEARCH for Diabetes in Youth Study. Of these, 14,721 had type 1; 4,141 type 2; and 551 secondary and 304 other/unknown diabetes type. Cases were linked with the National Death Index through 31 December 2017. We calculated standardized mortality ratios (SMRs) and 95% CIs based on age, sex, and race/ethnicity for state and county population areas and examined underlying causes of death. RESULTS: During 170,148 person-years (PY) (median follow-up 8.5 years), 283 individuals died: 133 with type 1 (103.0/100,000 PY), 55 with type 2 (161.5/100,000 PY), 87 with secondary (1,952/100,000 PY), and 8 with other/unknown diabetes type (312.3/100,000 PY). SMRs (95% CI) for the first three groups were 1.5 (1.2-1.8), 2.3 (1.7-3.0), and 28.0 (22.4-34.6), respectively. Diabetes was the underlying cause of death for 42.1%, 9.1%, and 4.6% of deaths, respectively. The SMR was greater for type 2 than for type 1 diabetes (P < 0.001). SMRs were significantly higher for individuals with type 1 diabetes who were <20 years of age, non-Hispanic White and Hispanic, and female and for individuals with type 2 diabetes who were <25 years of age, from all race/ethnic minority groups, and from both sexes. CONCLUSION: Excess mortality was observed among YYAs for each type of diabetes with differences in risk associated with diabetes type, age, race/ethnicity, and sex. The root causes of excess mortality among YYAs with diabetes merit further study.

3.
J Am Med Dir Assoc ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34648760

RESUMO

OBJECTIVE: To describe the experience of COVID-19 disease among chronically ventilated and nonventilated nursing home patients living in 3 separate nursing homes. DESIGN: Observational study of death, respiratory illness and COVID-19 polymerase chain reaction (PCR) results among residents and staff during nursing home outbreaks in 2020. SETTING AND PARTICIPANTS: 93 chronically ventilated nursing home patients and 1151 nonventilated patients living among 3 separate nursing homes on Long Island, New York, as of March 15, 2020. Illness, PCR results, and antibody studies among staff are also reported. MEASUREMENTS: Data were collected on death rate among chronically ventilated and nonventilated patients between March 15 and May 15, 2020, compared to the same time in 2019; prevalence of PCR positivity among ventilated and nonventilated patients in 2020; reported illness, PCR positivity, and antibody among staff. RESULTS: Total numbers of deaths among chronically ventilated nursing home patients during this time frame were similar to the analogous period 1 year earlier (9 of 93 in 2020 vs 8 of 100 in 2019, P = .8), whereas deaths among nonventilated patients were greatly increased (214 of 1151 in 2020 vs 55 of 1189 in 2019, P < .001). No ventilated patient deaths were clinically judged to be COVID-19 related. No clusters of COVID-19 illness could be demonstrated among ventilated patients. Surveillance PCR testing of ventilator patients failed to reveal COVID-19 positivity (none of 84 ventilator patients vs 81 of 971 nonventilator patients, P < .002). Illness and evidence of COVID-19 infection was demonstrated among staff working both in nonventilator and in ventilator units. CONCLUSIONS AND IMPLICATIONS: COVID-19 infection resulted in illness and death among nonventilated nursing home residents as well as among staff. This was not observed among chronically ventilated patients. The mechanics of chronic ventilation appears to protect chronically ventilated patients from COVID-19 disease.

4.
Diabetes Care ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362814

RESUMO

OBJECTIVE: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. RESULTS: Of 3,333 participants, 93 (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs. 13.6 ± 2.3 years, P = 0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs. 4.7 ± 3.5 ng/mL, P < 0.0001). Youth with MODY were less likely to have hypertension (6.9% vs. 19.5%, P = 0.007) and had higher HDL cholesterol (43.8 vs. 39.7 mg/dL, P = 0.006). CONCLUSIONS: By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n = 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing.

5.
JAMA ; 326(8): 717-727, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427600

RESUMO

Importance: Changes in the prevalence of youth-onset diabetes have previously been observed. Objective: To estimate changes in prevalence of type 1 and type 2 diabetes in youths in the US from 2001 to 2017. Design, Setting, and Participants: In this cross-sectional observational study, individuals younger than 20 years with physician-diagnosed diabetes were enumerated from 6 areas in the US (4 geographic areas, 1 health plan, and select American Indian reservations) for 2001, 2009, and 2017. Exposures: Calendar year. Main Outcomes and Measures: Estimated prevalence of physician-diagnosed type 1 and type 2 diabetes overall and by race and ethnicity, age, and sex. Results: Among youths 19 years or younger, 4958 of 3.35 million had type 1 diabetes in 2001, 6672 of 3.46 million had type 1 diabetes in 2009, and 7759 of 3.61 million had type 1 diabetes in 2017; among those aged 10 to 19 years, 588 of 1.73 million had type 2 diabetes in 2001, 814 of 1.85 million had type 2 diabetes in 2009, and 1230 of 1.85 million had type 2 diabetes in 2017. The estimated type 1 diabetes prevalence per 1000 youths for those 19 years or younger increased significantly from 1.48 (95% CI, 1.44-1.52) in 2001 to 1.93 (95% CI, 1.88-1.98) in 2009 to 2.15 (95% CI, 2.10-2.20) in 2017, an absolute increase of 0.67 per 1000 youths (95%, CI, 0.64-0.70) and a 45.1% (95% CI, 40.0%-50.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic White (0.93 per 1000 youths [95% CI, 0.88-0.98]) and non-Hispanic Black (0.89 per 1000 youths [95% CI, 0.88-0.98]) youths. The estimated type 2 diabetes prevalence per 1000 youths aged 10 to 19 years increased significantly from 0.34 (95% CI, 0.31-0.37) in 2001 to 0.46 (95% CI, 0.43-0.49) in 2009 to 0.67 (95% CI, 0.63-0.70) in 2017, an absolute increase of 0.32 per 1000 youths (95% CI, 0.30-0.35) and a 95.3% (95% CI, 77.0%-115.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic Black (0.85 per 1000 youths [95% CI, 0.74-0.97]) and Hispanic (0.57 per 1000 youths [95% CI, 0.51-0.64]) youths. Conclusions and Relevance: In 6 areas of the US from 2001 to 2017, the estimated prevalence of diabetes among children and adolescents increased for both type 1 and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus Tipo 1/etnologia , Diabetes Mellitus Tipo 2/etnologia , Feminino , Humanos , Masculino , Prevalência , Estados Unidos/epidemiologia , Adulto Jovem
6.
Nat Genet ; 53(7): 962-971, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34127860

RESUMO

We report the largest and most diverse genetic study of type 1 diabetes (T1D) to date (61,427 participants), yielding 78 genome-wide-significant (P < 5 × 10-8) regions, including 36 that are new. We define credible sets of T1D-associated variants and show that they are enriched in immune-cell accessible chromatin, particularly CD4+ effector T cells. Using chromatin-accessibility profiling of CD4+ T cells from 115 individuals, we map chromatin-accessibility quantitative trait loci and identify five regions where T1D risk variants co-localize with chromatin-accessibility quantitative trait loci. We highlight rs72928038 in BACH2 as a candidate causal T1D variant leading to decreased enhancer accessibility and BACH2 expression in T cells. Finally, we prioritize potential drug targets by integrating genetic evidence, functional genomic maps and immune protein-protein interactions, identifying 12 genes implicated in T1D that have been targeted in clinical trials for autoimmune diseases. These findings provide an expanded genomic landscape for T1D.


Assuntos
Alelos , Mapeamento Cromossômico , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Variação Genética , Genômica , Autoimunidade/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Descoberta de Drogas , Expressão Gênica , Genômica/métodos , Humanos , Terapia de Alvo Molecular , Mapeamento de Interação de Proteínas
7.
Ann Pharmacother ; : 10600280211028882, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34180274

RESUMO

BACKGROUND: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES: The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE: Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

8.
Am J Phys Anthropol ; 175(4): 905-919, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34008864

RESUMO

OBJECTIVES: Gullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West-Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah. MATERIALS AND METHODS: We leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, African populations from Sierra Leone, and population reference panels from Africa and Europe to infer population structure, ancestry proportions, and global estimates of admixture. RESULTS: Relative to non-Gullah African Americans from the Southeast US, the Gullah exhibited higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and increased male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to populations from Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations. DISCUSSION: This study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities.

9.
PLoS One ; 16(5): e0251423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34014961

RESUMO

Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (ß = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (ß = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; ß = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; ß = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; ß = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.

10.
J Psychiatr Res ; 138: 311-318, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33892269

RESUMO

The purpose of this study was to examine factors that influence a person's choice of cognitive-behavioral therapy (CBT) or yoga, the stability of these preferences, and the impact of preference on engagement and process measures. We conducted a randomized preference trial of CBT and yoga in 500 adults ≥60 years with symptoms of worry. Participants reported their intervention preference, strength of preference, and factors impacting preference. Engagement in the intervention (session completion and dropout rates) was assessed. Process measures included satisfaction with the intervention, therapeutic alliance, and intervention expectancy. Neither intervention preference (48% and 52% chose CBT and yoga, respectively) nor strength of preference differed significantly between the two preference trial groups. Intervention expectancies at baseline among those in the preference trial were approximately 4.5 units (40-point scale) higher for their preferred intervention (p < .0001 within each group). A principal component analysis of factors influencing preference identified three constructs. Using logistic regression, components focused on attitudes about CBT or yoga were predictive of ultimate preference (odds ratio = 11.5, 95% C.I.6.3-21.0 per 1SD difference in component 1 for choosing CBT; odds ratio = 7.8, 95% CI4.3-13.9 per 1SD difference in component 2 for choosing yoga). There were no significant differences between the randomized and preference trials on intervention adherence, completion of assessments, intervention satisfaction, or working alliance. Receiving a preferred treatment had no significant effects on intervention outcomes through participant engagement or process measures. When options are limited, providers may have confidence in offering the most readily available non-pharmacological treatments.


Assuntos
Terapia Cognitivo-Comportamental , Ioga , Idoso , Ansiedade , Transtornos de Ansiedade , Humanos , Pessoa de Meia-Idade
11.
J Am Soc Nephrol ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853887

RESUMO

BACKGROUND: APOL1 variants contribute to the markedly higher incidence of ESKD in Blacks compared with Whites. Genetic testing for these variants in patients with African ancestry who have nephropathy is uncommon, and no specific treatment or management protocol for APOL1-associated nephropathy currently exists. METHODS: A multidisciplinary, racially diverse group of 14 experts and patient advocates participated in a Delphi consensus process to establish practical guidance for clinicians caring for patients who may have APOL1-associated nephropathy. Consensus group members took part in three anonymous voting rounds to develop consensus statements relating to the following: (1) counseling, genotyping, and diagnosis; (2) disease awareness and education; and (3) a vision for management of APOL1-associated nephropathy in a future when treatment is available. A systematic literature search of the MEDLINE and Embase databases was conducted to identify relevant evidence published from January 1, 2009 to July 14, 2020. RESULTS: The consensus group agreed on 55 consensus statements covering such topics as demographic and clinical factors that suggest a patient has APOL1-associated nephropathy, as well as key considerations for counseling, testing, and diagnosis in current clinical practice. They achieved consensus on the need to increase awareness among key stakeholders of racial health disparities in kidney disease and of APOL1-associated nephropathy and on features of a successful education program to raise awareness among the patient community. The group also highlighted the unmet need for a specific treatment and agreed on best practice for management of these patients should a treatment become available. CONCLUSIONS: A multidisciplinary group of experts and patient advocates defined consensus-based guidance on the care of patients who may have APOL1-associated nephropathy.

12.
Lupus Sci Med ; 8(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33461980

RESUMO

OBJECTIVE: Two apolipoprotein L1 (APOL1) risk variants (RV) are enriched in sub-Saharan African populations due to conferred resistance to Trypanosoma brucei. These variants associate with adverse renal outcomes by multiple causes including SLE. Despite emerging reports that SLE is common in Ghana, where APOL1 variant allelic frequencies are high, the regional contribution to SLE outcomes has not been described. Accordingly, this prospective longitudinal cohort study tested the associations between APOL1 high-risk genotypes and kidney outcomes, organ damage accrual and death in 100 Ghanaian patients with SLE. METHODS: This was a prospective cohort study of 100 SLE outpatients who sought care at Korle bu Teaching Hospital in Accra, Ghana. Adult patients who met 4 American College of Rheumatology criteria for SLE were genotyped for APOL1 and followed longitudinally for SLE activity as measured by the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) hybrid and organ injury as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at baseline and every 6 months for 1 year. Outcomes of interest were kidney function, SDI and case fatality. RESULTS: Assuming a recessive inheritance, the APOL1 high-risk genotype (2RV) associated with end-stage renal disease (ESRD) at an OR of 14 (p=0.008). These patients accrued more SDI points particularly in renal and neurological domains. The SDI was 81.3% higher in 2RV patients compared with 0RV or 1RV patients despite no difference in SLE activity (p=0.01). After a 12-month period of observation, 3/12 (25%) of the 2RV patients died compared with 2/88 (2.3%) of the 0RV or 1RV carriers (OR=13.6, p=0.01). Deaths were due to end-stage kidney disease and heart failure. CONCLUSION: APOL1 RVs were heritable risk factors for morbidity and mortality in this Ghanaian SLE cohort. Despite no appreciable differences in SLE activity, APOL1 high-risk patients exhibited progressive renal disease, organ damage accrual and a 13-fold higher case fatality.


Assuntos
Apolipoproteína L1/genética , Lúpus Eritematoso Sistêmico , Adulto , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Feminino , Genótipo , Gana , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/genética , Masculino , Estudos Prospectivos , Estados Unidos
13.
Diabetes ; 70(4): 996-1005, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33479058

RESUMO

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multiethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth case subjects with type 2 diabetes (mean age 15.1 ± 2.9 years) and 6,061 diabetes-free adult control subjects (mean age 54.2 ± 12.4 years). After stratifying by principal component-clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified seven genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P = 3.2 × 10-8; odds ratio [OR] = 1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P = 8.0 × 10-20; OR 1.58), rs72982988 near MC4R (P = 4.4 × 10-14; OR 1.53), rs200893788 in CDC123 (P = 1.1 × 10-12; OR 1.32), rs2237892 in KCNQ1 (P = 4.8 × 10-11; OR 1.59), rs937589119 in IGF2BP2 (P = 3.1 × 10-9; OR 1.34), and rs113748381 in SLC16A11 (P = 4.1 × 10-8; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in CPEB2 (P = 3.2 × 10-8; OR 2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome-wide association study of youth-onset type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/genética , Adulto , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Proteínas de Homeodomínio/genética , Humanos , Canal de Potássio KCNQ1/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 4 de Melanocortina/genética
14.
J Diabetes Complications ; 35(2): 107768, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33168393

RESUMO

AIMS: We sought to characterize the direction and associated factors of eGFR change following diagnosis of youth-onset type 1 and type 2 diabetes. METHODS: We assessed the direction of eGFR change at two visits (mean 6.6 years apart) in SEARCH, a longitudinal cohort study of youth-onset type 1 and type 2 diabetes. We used the CKiDCr-CysC equation to estimate GFR and categorized 'rising' and 'declining' eGFR as an annual change of ≥3 ml/min/1.73 m2 in either direction. Multivariable logistic regression evaluated factors associated with directional change in eGFR. RESULTS: Estimated GFR declined in 23.8% and rose in 2.8% of participants with type 1 diabetes (N = 1225; baseline age 11.4 years), and declined in 18.1% and rose in 15.6% of participants with type 2 diabetes (N = 160; baseline age 15.0 years). Factors associated with rising and declining eGFR (versus stable) in both type 1 and type 2 diabetes included sex, age at diagnosis, baseline eGFR and difference in fasting glucose between study visits. Additional factors in type 1 diabetes included time from baseline visit, HbA1c and body mass index. CONCLUSIONS: Over the first decade of diabetes, eGFR decline is more common in type 1 diabetes whereas eGFR rise is more common in type 2 diabetes.

16.
Depress Anxiety ; 37(12): 1194-1207, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33107666

RESUMO

BACKGROUND: The purpose of this study was to compare the effects of cognitive-behavioral therapy (CBT) and yoga on late-life worry, anxiety, and sleep; and examine preference and selection effects on these outcomes. METHODS: A randomized preference trial of CBT and yoga was conducted in community-dwelling adults 60 years or older, who scored 26 or above on the Penn State Worry Questionnaire-Abbreviated (PSWQ-A). CBT consisted of 10 weekly telephone sessions. Yoga consisted of 20 biweekly group yoga classes. The primary outcome was worry (PSWQ-A); the secondary outcomes were anxiety (PROMIS-Anxiety) and sleep (Insomnia Severity Index [ISI]). We examined both preference effects (average effect for those who received their preferred intervention [regardless of whether it was CBT or yoga] minus the average for those who did not receive their preferred intervention [regardless of the intervention]) and selection effect (which addresses the question of whether there is a benefit to getting to select one intervention over the other, and measures the effect on outcomes of self-selection to a specific intervention). RESULTS: Five hundred older adults were randomized to the randomized trial (125 each in CBT and yoga) or the preference trial (120 chose CBT; 130 chose yoga). In the randomized trial, the intervention effect of yoga compared with CBT adjusted for baseline psychotropic medication use, gender, and race was 1.6 (-0.2, 3.3), p = .08 for the PSWQ-A. Similar results were observed with PROMIS-Anxiety (adjusted intervention effect: 0.3 [-1.5, 2.2], p = .71). Participants randomized to CBT experienced a greater reduction in the ISI compared with yoga (adjusted intervention effect: 2.4 [1.2, 3.7], p < .01]). Estimated in the combined data set (N = 500), the preference and selection effects were not significant for the PSWQ-A, PROMIS-Anxiety, and ISI. Of the 52 adverse events, only two were possibly related to the intervention. None of the 26 serious adverse events were related to the study interventions. CONCLUSIONS: CBT and yoga were both effective at reducing late-life worry and anxiety. However, a greater impact was seen for CBT compared with yoga for improving sleep. Neither preference nor selection effects was found.


Assuntos
Terapia Cognitivo-Comportamental , Ioga , Idoso , Ansiedade/terapia , Transtornos de Ansiedade/terapia , Cognição , Humanos , Resultado do Tratamento
17.
Pediatr Diabetes ; 21(8): 1403-1411, 2020 12.
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.

18.
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.

19.
Kidney Int Rep ; 5(9): 1472-1485, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954071

RESUMO

Introduction: Autosomal dominant tubulo-interstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). The minor allele of rs4293393, located in the promoter of the UMOD gene, is present in 19% of the population and downregulates uromodulin production by approximately 50% and might affect the age of ESKD. The goal of this study was to better understand the genetic and clinical characteristics of ADTKD-UMOD and to perform a Mendelian randomization study to determine if the minor allele of rs4293393 was associated with better kidney survival. Methods: An international group of collaborators collected clinical and genetic data on 722 affected individuals from 249 families with 125 mutations, including 28 new mutations. The median age of ESKD was 47 years. Men were at a much higher risk of progression to ESKD (hazard ratio 1.78, P < 0.001). Results: The allele frequency of the minor rs4293393 allele was only 11.6% versus the 19% expected (P < 0.01), resulting in Hardy-Weinberg disequilibrium and precluding a Mendelian randomization experiment. An in vitro score reflecting the severity of the trafficking defect of uromodulin mutants was found to be a promising predictor of the age of ESKD. Conclusion: We report the clinical characteristics associated with 125 UMOD mutations. Male gender and a new in vitro score predict age of ESKD.

20.
Diabetes Care ; 43(10): 2418-2425, 2020 10.
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.


Assuntos
Diabetes Mellitus/diagnóstico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Programas de Rastreamento/métodos , Adolescente , Adulto , Idade de Início , Algoritmos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estados Unidos/epidemiologia , Adulto Jovem
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