Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Pediatr Diabetes ; 20242024.
Artículo en Inglés | MEDLINE | ID: mdl-38765897

RESUMEN

Background: A-ß+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved ß-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A-ß+ KPD within this cohort. Methods: We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A-ß+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results: Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A-ß+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions: In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A-ß+ KPD. They manifest the key characteristics of obesity, preserved ß-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A-ß+ KPD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Humanos , Femenino , Masculino , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/etiología , Niño , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Adolescente , Prevalencia , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/fisiología , Células Secretoras de Insulina/metabolismo , Estudios Retrospectivos
2.
Genet Med ; 25(4): 100019, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36681871

RESUMEN

PURPOSE: Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic diabetes. Despite its autosomal dominant inheritance, many MODY participants in the University of Chicago Monogenic Diabetes Registry have no family members enrolled. We aimed to gather data on the Registry participants' experiences in (1) receipt of an accurate diagnosis, (2) decisions regarding disclosure of their MODY genetic test results with biological relatives, and (3) recommendations toward our Registry's processes and outreach. METHODS: We conducted 20 one-on-one semistructured interviews with adult Registry participants. RESULTS: All participants found navigating the health care system challenging because of the providers' unfamiliarity with MODY and dismissal of its importance post diagnosis. All had shared their results with at least 1 relative, however many found their relatives resistant to engaging with their providers. Participants wanted to receive targeted information on their condition and connect with other participants who have faced similar diagnostic and treatment challenges. CONCLUSION: Our results demonstrate that our probands faced resistance to reclassification of their diabetes from both health care providers and relatives. In an effort to improve cascade testing, the Registry is designing a portal to facilitate participant-research team communication and provide additional supports for participants to involve family members in testing.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Pruebas Genéticas , Familia , Sistema de Registros , Mutación
3.
Curr Diab Rep ; 19(5): 23, 2019 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-30919097

RESUMEN

PURPOSE OF REVIEW: Monogenic diabetes is an uncommon but important form of diabetes, with the most common causes benefitting from management that accounts for the genetic mutation. This often results in decreased costs and treatment burden for affected individuals. Misdiagnosis as type 1 and type 2 diabetes is common. Given the significant burden of diabetes costs to the healthcare system, it is important to assess the economic impact of incorporating genetic testing for monogenic diabetes into clinical care through formal cost-effectiveness analyses (CEAs). This article briefly summarizes the barriers to timely monogenic diabetes diagnosis and then summarizes findings from CEAs on genetic testing for monogenic diabetes. RECENT FINDINGS: CEAs have shown that routine genetic testing of all patients with a clinical diagnosis of type 1 diabetes can be cost-saving when applied to the scenarios of neonatal diabetes or in a pediatric population. Routine screening has not been shown to be cost-effective in adult populations. However, next-generation sequencing strategies and applying biomarkers to identify and limit genetic testing to people most likely to have monogenic diabetes are promising ways to make testing strategies cost-effective. CEAs have shown that genetic testing for monogenic diabetes diagnosis can be cost-effective or cost-saving and should guide insurers to consider broader coverage of these tests, which would lead to accurate and timely diagnosis and impact treatment and clinical outcomes.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación
4.
Ann Intern Med ; 168(3): 170-178, 2018 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-29230472

RESUMEN

Background: Intensive glycemic control in type 2 diabetes (glycated hemoglobin [HbA1c] level <7%) is an established, cost-effective standard of care. However, guidelines recommend individualizing goals on the basis of age, comorbidity, diabetes duration, and complications. Objective: To estimate the cost-effectiveness of individualized control versus uniform intensive control (HbA1c level <7%) for the U.S. population with type 2 diabetes. Design: Patient-level Monte Carlo-based Markov model. Data Sources: National Health and Nutrition Examination Survey 2011-2012. Target Population: The approximately 17.3 million persons in the United States with diabetes diagnosed at age 30 years or older. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Individualized versus uniform intensive glycemic control. Outcome Measures: Average lifetime costs, life-years, and quality-adjusted life-years (QALYs). Results of Base-Case Analysis: Individualized control saved $13 547 per patient compared with uniform intensive control ($105 307 vs. $118 854), primarily due to lower medication costs ($34 521 vs. $48 763). Individualized control decreased life expectancy (20.63 vs. 20.73 years) due to an increase in complications but produced more QALYs (16.68 vs. 16.58) due to fewer hypoglycemic events and fewer medications. Results of Sensitivity Analysis: Individualized control was cost-saving and generated more QALYs compared with uniform intensive control, except in analyses where the disutility associated with receiving diabetes medications was decreased by at least 60%. Limitation: The model did not account for effects of early versus later intensive glycemic control. Conclusion: Health policies and clinical programs that encourage an individualized approach to glycemic control for U.S. adults with type 2 diabetes reduce costs and increase quality of life compared with uniform intensive control. Additional research is needed to confirm the risks and benefits of this strategy. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economía , Hipoglucemiantes/economía , Hipoglucemiantes/uso terapéutico , Adulto , Anciano , Ahorro de Costo , Análisis Costo-Beneficio , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Esperanza de Vida , Masculino , Cadenas de Markov , Persona de Mediana Edad , Método de Montecarlo , Encuestas Nutricionales , Años de Vida Ajustados por Calidad de Vida , Estados Unidos
5.
Curr Diab Rep ; 18(3): 12, 2018 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-29450745

RESUMEN

PURPOSE OF REVIEW: Monogenic diabetes accounts for 1-2% of all diabetes cases, but is frequently misdiagnosed as type 1, type 2, or gestational diabetes. Accurate genetic diagnosis directs management, such as no pharmacologic treatment for GCK-MODY, low-dose sulfonylureas for HNF1A-MODY and HNF4A-MODY, and high-dose sulfonylureas for KATP channel-related diabetes. While diabetes treatment is defined for the most common causes of monogenic diabetes, pregnancy poses a challenge to management. Here, we discuss the key issues in pregnancy affected by monogenic diabetes. RECENT FINDINGS: General recommendations for pregnancy affected by GCK-MODY determine need for maternal insulin treatment based on fetal mutation status. However, a recent study suggests macrosomia and miscarriage rates may be increased with this strategy. Recent demonstration of transplacental transfer of sulfonylureas also raises questions as to when insulin should be initiated in sulfonylurea-responsive forms of monogenic diabetes. Pregnancy represents a challenge in management of monogenic diabetes, where factors of maternal glycemic control, fetal mutation status, and transplacental transfer of medication must all be taken into consideration. Guidelines for pregnancy affected by monogenic diabetes will benefit from large, prospective studies to better define the need for and timing of initiation of insulin treatment.


Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Embarazo en Diabéticas/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Glucoquinasa/genética , Factores Nucleares del Hepatocito/genética , Humanos , Mutación , Canales de Potasio/genética , Embarazo , Embarazo en Diabéticas/diagnóstico , Embarazo en Diabéticas/genética , Embarazo en Diabéticas/fisiopatología
6.
Curr Diab Rep ; 18(8): 58, 2018 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-29931562

RESUMEN

PURPOSE OF REVIEW: We provide a review of monogenic diabetes in young children and adolescents with a focus on recognition, management, and pharmacological treatment. RECENT FINDINGS: Monogenic forms of diabetes account for approximately 1-2% of diabetes in children and adolescents, and its incidence has increased in recent years due to greater awareness and wider availability of genetic testing. Monogenic diabetes is due to single gene defects that primarily affect beta cell function with more than 30 different genes reported. Children with antibody-negative, C-peptide-positive diabetes should be evaluated and genetically tested for monogenic diabetes. Accurate genetic diagnosis impacts treatment in the most common types of monogenic diabetes, including the use of sulfonylureas in place of insulin or other glucose-lowering agents or discontinuing pharmacologic treatment altogether. Diagnosis of monogenic diabetes can significantly improve patient care by enabling prediction of the disease course and guiding appropriate management and treatment.


Asunto(s)
Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Adolescente , Niño , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Pruebas Genéticas , Humanos , Mutación/genética , Prevalencia
7.
Pediatr Diabetes ; 19(3): 393-397, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29205704

RESUMEN

BACKGROUND: Neonatal diabetes mellitus (NDM) caused by mutations in KCNJ11 can be successfully treated with high dose oral sulfonylureas; however, little data is available on the risk of hypoglycemia. OBJECTIVE: To determine the frequency, severity, and clinical significance of hypoglycemia in KCNJ11-related NDM. METHODS: Utilizing the University of Chicago Monogenic Diabetes Registry, parents completed an online questionnaire addressing hypoglycemia. Continuous glucose monitoring (CGM) data was available for 7 subjects. RESULTS: Thirty subjects with KCNJ11-related permanent NDM (166 patient-years on sulfonylurea) had median sulfonylurea dose of 0.39 mg/kg/day (0.24-0.88 IQR, interquartile range) with median HbA1c 5.7% (39 mmol/mol) (5.5-6.1 IQR, 37-43 mmol/mol). Hypoglycemia (<70 mg/dL) was reported monthly once or less frequently in 89.3% of individuals, but 3 (10.7%) reported once weekly or more. Of all hypoglycemic episodes reported, none involved seizures or unconsciousness and thus did not meet the current ISPAD definition of severe hypoglycemia. Seven individuals wore a CGM for a total of 912 hours with blood sugars falling below 70 mg/dL for 5.8% of the time recorded, similar to ranges reported for people without diabetes. CONCLUSIONS: In our cohort of KCNJ11-related permanent NDM, hypoglycemia is infrequent and mild despite the high doses of sulfonylurea used and near-normal level of glycemic control. Long-term follow-up on larger numbers will be required to clarify the incidence and determinants of hypoglycemia in this unique population.


Asunto(s)
Diabetes Mellitus/genética , Hipoglucemia/inducido químicamente , Canales de Potasio de Rectificación Interna/genética , Sistema de Registros , Compuestos de Sulfonilurea/uso terapéutico , Adolescente , Niño , Preescolar , Diabetes Mellitus/tratamiento farmacológico , Femenino , Humanos , Masculino
8.
Diabetologia ; 58(7): 1430-5, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25877689

RESUMEN

AIMS/HYPOTHESIS: Individuals with heterozygous activating mutations of the KCNJ11 gene encoding a subunit of the ATP-sensitive potassium channel (KATP) can usually be treated with oral sulfonylurea (SU) pills in lieu of insulin injections. The aim of this study was to test our hypothesis that younger age at the time of initiation of SU therapy is correlated with lower required doses of SU therapy, shorter transition time and decreased likelihood of requiring additional diabetes medications. METHODS: We performed a retrospective cohort study using data on 58 individuals with neonatal diabetes due to KCNJ11 mutations identified through the University of Chicago Monogenic Diabetes Registry ( http://monogenicdiabetes.uchicago.edu/registry ). We assessed the influence of age at initiation of SU therapy on treatment outcomes. RESULTS: HbA1c fell from an average of 8.5% (69 mmol/mol) before transition to 6.2% (44 mmol/mol) after SU therapy (p < 0.001). Age of initiation of SU correlated with the dose (mg kg(-1) day(-1)) of SU required at follow-up (r = 0.80, p < 0.001). Similar associations were observed across mutation subtypes. Ten participants required additional glucose-lowering medications and all had initiated SU at age 13 years or older. No serious adverse events were reported. CONCLUSIONS/INTERPRETATION: Earlier age at initiation of SU treatment is associated with improved response to SU therapy. Declining sensitivity to SU may be due to loss of beta cell mass over time in those treated with insulin. Our data support the need for early genetic diagnosis and appropriate personalised treatment in all cases of neonatal diabetes.


Asunto(s)
Diabetes Mellitus/congénito , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Canales de Potasio de Rectificación Interna/genética , Compuestos de Sulfonilurea/uso terapéutico , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Gliburida/uso terapéutico , Hemoglobina Glucada/análisis , Humanos , Lactante , Recién Nacido , Masculino , Mutación/genética , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
9.
Popul Med ; 62024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38681897

RESUMEN

INTRODUCTION: Maturity-Onset Diabetes of the Young (MODY) is an unusual type of diabetes often missed in clinical practice, especially in Africa. Treatment decisions for MODY depend on a precise diagnosis, only made by genetic testing. We aimed to determine MODY knowledge among Nigerian healthcare professionals (HCPs), their perceptions, and barriers to the implementation of genetic testing in diabetes patients. METHODS: A cross-sectional survey was conducted among doctors and nurses in three levels of public and private healthcare institutions in Ibadan, Nigeria, from December 2018 to June 2019. In all, 70% and 30% of a total 415 participants were recruited from public and private centers, respectively. HCPs were recruited in a 60:40% ratio, respectively. A 51-item instrument was used to assess MODY knowledge, perceptions of HCPs, and barriers to the implementation of genetic testing in diabetes patients. RESULTS: In the survey, 43.4% self-rated their current MODY knowledge to be at least moderate. About 68%, 73% and 86%, respectively, correctly answered 3 of 5 questions on basic genetics' knowledge. However, only 1 of 7 MODY-specific questions was answered correctly by 72.7% of the respondents. The mean basic genetics and MODY-specific knowledge scores were 2.6/5 (SD=1.0) and 1.8/9 (SD=1.3), respectively. Multiple linear regression showed higher mean scores among those aged 30-49 years, those with degrees and fellowships (except PhD), and general practitioners; 360 (80.0%) perceived that genetic testing plays a central role in diabetes care. Barriers to genetic testing were lack of access to testing facilities, guidance on the use of and updates/educational materials on genetic testing (82.7%, 62.1% and 50.3%, respectively). CONCLUSIONS: The level of MODY awareness and knowledge among Nigerian HCPs is unacceptably low with a lack of access to genetic testing facilities. These can hinder the implementation of precision diabetes medicine. Increased awareness, provision of decision support aids, and genetic testing facilities are urgently needed.

10.
Commun Med (Lond) ; 4(1): 145, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025920

RESUMEN

BACKGROUND: Beta-cell monogenic forms of diabetes have strong support for precision medicine. We systematically analyzed evidence for precision treatments for GCK-related hyperglycemia, HNF1A-, HNF4A- and HNF1B-diabetes, and mitochondrial diabetes (MD) due to m.3243 A > G variant, 6q24-transient neonatal diabetes mellitus (TND) and SLC19A2-diabetes. METHODS: The search of PubMed, MEDLINE, and Embase for individual and group level data for glycemic outcomes using inclusion (English, original articles written after 1992) and exclusion (VUS, multiple diabetes types, absent/aggregated treatment effect measures) criteria. The risk of bias was assessed using NHLBI study-quality assessment tools. Data extracted from Covidence were summarized and presented as descriptive statistics in tables and text. RESULTS: There are 146 studies included, with only six being experimental studies. For GCK-related hyperglycemia, the six studies (35 individuals) assessing therapy discontinuation show no HbA1c deterioration. A randomized trial (18 individuals per group) shows that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes. Cohort and case studies support SU's effectiveness in lowering HbA1c. Two cross-over trials (each with 15-16 individuals) suggest glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes is limited. Most reported patients with HNF1B-diabetes (N = 293) and MD (N = 233) are on insulin without treatment studies. Limited data support oral agents after relapse in 6q24-TND and for thiamine improving glycemic control and reducing/eliminating insulin requirement in SLC19A2-diabetes. CONCLUSION: There is limited evidence, and with moderate or serious risk of bias, to guide monogenic diabetes treatment. Further evidence is needed to examine the optimum treatment in monogenic subtypes.


Monogenic diabetes is a type of diabetes caused by changes in genes that affect how the body makes or responds to insulin. Precision medicine (where knowledge of the gene change directs the selection of treatment) is available for some forms of monogenic diabetes. This study evaluated the published literature for several forms of monogenic diabetes to assess the level of evidence supporting specific precision treatments. Among the 146 small studies that we reviewed, only six compared different treatments. However, we found evidence supporting oral medications for some types of monogenic diabetes, and evidence that treatment is not needed for one particular type. Based on our results, we provide treatment recommendations for certain forms of monogenic diabetes and identify future directions for research to help us optimize precision medicine in monogenic diabetes.

11.
J Clin Transl Sci ; 7(1): e260, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38229892

RESUMEN

Objectives/Goals: The Rare and Atypical DIAbetes NeTwork (RADIANT) aims to discover the underlying pathoetiology of atypical diabetes by conducting both genotyping and non-genetic deep phenotyping. While the return of genetic test results in research settings has been investigated, the return of non-genetic results (RoR-NG) has received less attention. We explore the RoR-NG with RADIANT investigators and participants. Methods/Study Population: We conducted one-on-one interviews with 10 adult RADIANT participants and 10 RADIANT investigators. Participants also completed two health literacy screening tools and a survey on perspectives regarding return of results (RoR). Investigators completed one survey on experience and confidence in explaining clinical tests utilized in the RADIANT study and another survey on perspectives regarding RoR. Results: Most participants were non-Hispanic White. All participants had high scores on health literacy screens. Both RADIANT participants and investigators expressed strong support for RoR-NG. RADIANT participants and investigators acknowledged the different roles and responsibilities between research and clinical care for interpreting and acting on non-genetic results. However, the lines between clinical care and research in returning and acting on results were often blurred by both participants and investigators. Discussion/Significance: Our study provides important insight into how both investigators and participants simultaneously distinguish and blur clinical and research roles and responsibilities when discussing non-genetic research results and the return of these results. Further study should engage individuals from diverse racial and ethnic backgrounds and with varying levels of health literacy to understand how best to support all participants when returning research results.

12.
Diabetes Care ; 46(3): 608-612, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36637968

RESUMEN

OBJECTIVE: To examine sleep patterns in adults with maturity-onset diabetes of the young (MODY). RESEARCH DESIGN AND METHODS: Adults with glucokinase (GCK)-MODY and transcription factor (TF)-related MODY (HNF1A, HNF1B, HNF4A) were recruited (n = 24; age 46.0 years, 79% women, BMI 24.7 kg/m2) from The University of Chicago's Monogenic Diabetes Registry. Sleep patterns were assessed by 2-week wrist actigraphy (total 315 nights), one night of a home sleep apnea test, and validated surveys. RESULTS: Overall, compared with established criteria, 29% of participants had sleep latency ≥15 min, 38% had sleep efficiency ≤85%, 46% had wake after sleep onset >40 min, all indicating poor objective sleep quality. Among all participants, 54% had a sleep duration below the recommended minimum of 7 h, 88% reported poor sleep quality, 58% had obstructive sleep apnea, and 71% reported insomnia. Compared with GCK-MODY, participants with TF-related MODY had poorer objective sleep quality and increased night-to-night variability in sleep patterns. CONCLUSIONS: Sleep disturbances appear to be common in adults with MODY despite absent traditional risk factors for sleep disorders. Future research investigating the sleep-diabetes relationship is warranted in this population.


Asunto(s)
Diabetes Mellitus Tipo 2 , Trastornos Intrínsecos del Sueño , Sueño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Glucoquinasa/genética , Factor Nuclear 1-alfa del Hepatocito/genética , Mutación , Factores de Riesgo , Trastornos Intrínsecos del Sueño/etiología
13.
J Clin Transl Sci ; 7(1): e47, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36845305

RESUMEN

Introduction: Diabetes mellitus in underrepresented racial and ethnic groups (URG) is rapidly increasing in incidence and has worse outcomes than diabetes in non-Hispanic White individuals. Rare and Atypical Diabetes Network (RADIANT) established recruitment targets based on the racial and ethnic distribution of the USA to enroll a diverse study population. We examined participation of URG across RADIANT study stages and described strategies to enhance recruitment and retention of URG. Materials and Methods: RADIANT is a multicenter NIH-funded study of people with uncharacterized forms of atypical diabetes. RADIANT participants consent online and progress through three sequential study stages, as eligible. Results: We enrolled 601 participants with mean age 44 ± 16.8 years, 64.4% female. At Stage 1, 80.6% were White, 7.2% African American (AA), 12.2% other/more than one race, and 8.4% Hispanic. Enrollment of URG was significantly below preset targets across most stages. Referral sources differed by race (p < 0.001) but not ethnicity (p = 0.15). Most AA participants were referred by RADIANT investigators (58.5% vs. 24.5% in Whites), whereas flyers, news, social media, and family or friends were more frequent referral sources for White individuals (26.4% vs. 12.2% in AA). Ongoing initiatives to increase enrollment of URG in RADIANT include engaging with clinics/hospitals serving URG, screening electronic medical records, and providing culturally competent study coordination and targeted advertisement. Conclusions: There is low participation of URG in RADIANT, potentially limiting the generalizability of its discoveries. Investigations into barriers and facilitators for recruitment and retention of URG in RADIANT, with implications for other studies, are ongoing.

14.
medRxiv ; 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37214872

RESUMEN

Background: Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for precision medicine. We reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A-HNF4A- and HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes. Methods: Systematic reviews with data from PubMed, MEDLINE and Embase were performed for the different subtypes. Individual and group level data was extracted for glycemic outcomes in individuals with genetically confirmed monogenic diabetes. Results: 147 studies met inclusion criteria with only six experimental studies and the rest being single case reports or cohort studies. Most studies had moderate or serious risk of bias.For GCK-related hyperglycemia, six studies (N=35) showed no deterioration in HbA1c on discontinuing glucose lowering therapy. A randomized trial (n=18 per group) showed that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes, and cohort and case studies supported SU effectiveness in lowering HbA1c. Two crossover trials (n=15 and n=16) suggested glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes was limited. While some patients with HNF1B-diabetes (n=301) and MD (n=250) were treated with oral agents, most were on insulin. There was some support for the use of oral agents after relapse in 6q24-TND, and for thiamine improving glycemic control and reducing insulin requirement in SLC19A2-diabetes (less than half achieved insulin-independency). Conclusion: There is limited evidence to guide the treatment in monogenic diabetes with most studies being non-randomized and small. The data supports: no treatment in GCK-related hyperglycemia; SU for HNF1A-diabetes. Further evidence is needed to examine the optimum treatment in monogenic subtypes.

15.
Nat Med ; 29(10): 2438-2457, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37794253

RESUMEN

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.


Asunto(s)
Diabetes Mellitus , Medicina de Precisión , Humanos , Consenso , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Medicina Basada en la Evidencia
16.
Clin Endocrinol (Oxf) ; 75(4): 422-6, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21521318

RESUMEN

Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of monogenic disorders characterized by autosomal dominant inheritance of young-onset, non-insulin-dependent diabetes. The genes involved are important in beta cell development, function and regulation and lead to disorders in glucose sensing and insulin secretion. Heterozygous GCK mutations cause impaired glucokinase activity resulting in stable, mild hyperglycaemia that rarely requires treatment. HNF1A mutations cause a progressive insulin secretory defect that is sensitive to sulphonylureas, most often resulting in improved glycaemic control compared with other diabetes treatment. MODY owing to mutations in the HNF4A gene results in a similar phenotype, including sensitivity to sulphonylurea treatment. HNF1B mutations most frequently cause developmental renal disease (particularly renal cysts) but may also cause MODY in isolation or may cause the renal cysts and diabetes syndrome (RCAD syndrome). Mutations in NEUROD1, PDX1 (IPF1), CEL and INS are rare causes of MODY. MODY is often misdiagnosed as type 1 or type 2 diabetes. However, a correct genetic diagnosis impacts treatment and identifies at-risk family members. Thus, it is important to consider a diagnosis of MODY in appropriate individuals and to pursue genetic testing to establish a molecular diagnosis.


Asunto(s)
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Pruebas Genéticas , Femenino , Quinasas del Centro Germinal , Factor Nuclear 1-alfa del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/genética , Proteínas de Homeodominio/genética , Humanos , Masculino , Mutación , Proteínas Serina-Treonina Quinasas/genética , Transactivadores/genética
17.
Curr Diab Rep ; 11(6): 519-32, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21993633

RESUMEN

There has been major progress in recent years uncovering the genetic causes of diabetes presenting in the first year of life. Twenty genes have been identified to date. The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (K(ATP)), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24. Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections. This compelling example of personalized genetic medicine leading to improved glucose regulation and quality of life may-with continued research-be repeated for other forms of neonatal diabetes in the future.


Asunto(s)
Diabetes Mellitus/genética , Enfermedades del Recién Nacido/genética , Transportadoras de Casetes de Unión a ATP/genética , Diabetes Mellitus/tratamiento farmacológico , Humanos , Hipoglucemiantes/uso terapéutico , Recién Nacido , Enfermedades del Recién Nacido/tratamiento farmacológico , Mutación , Canales de Potasio de Rectificación Interna/genética , Receptores de Droga/genética , Compuestos de Sulfonilurea/uso terapéutico , Receptores de Sulfonilureas
18.
Pediatr Ann ; 50(7): e304-e307, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34264792

RESUMEN

A growing number of people with diabetes are turning to self-built systems to dose and deliver insulin. These do-it-yourself artificial pancreas systems (DIY-APS) use commercially available insulin pumps and continuous glucose monitors and add an algorithm that independently modulates insulin dosing. Frustrated by the pace of diabetes technology development, a group of patients and diabetes advocates developed this technology without formal safety studies and without approval by the US Food and Drug Administration (FDA). Loop, OpenAPS, and AndroidAPS are the three available platforms, and patients worldwide are choosing them over other options. Patients generally report positive outcomes, but in May 2019, the FDA publicly warned against the use of such systems. Endocrinology providers are, therefore, faced with a difficult decision of whether to support patients interested in using a DIY-APS. This article describes the current state of DIY-APS, regulatory considerations, and our recommendations for endocrinology providers regarding this technology. [Pediatr Ann. 2021;50(7):e304-e307.].


Asunto(s)
Diabetes Mellitus Tipo 1 , Sistemas de Infusión de Insulina , Páncreas Artificial , Automanejo/métodos , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Humanos , Insulina/uso terapéutico , Estados Unidos , United States Food and Drug Administration
19.
Artículo en Inglés | MEDLINE | ID: mdl-36330312

RESUMEN

Monogenic diabetes is a category of diabetes mellitus caused by a single gene mutation or chromosomal abnormality, usually sub-classified as either neonatal diabetes or maturity-onset diabetes of the young (MODY). Although monogenic diabetes affects up to 3.5% of all patients with diabetes diagnosed before age 30, misdiagnosis and/or improper treatment occurs frequently. The University of Chicago Monogenic Diabetes Registry, established in 2008, offers insight into the diagnosis, treatment, and natural history of individuals known or suspected to have monogenic diabetes. Those interested in participating in the Registry begin by completing a secure web-based registration form found on our website (http://monogenicdiabetes.uchicago.edu/registry/). Participants are then screened for eligibility and consented either by phone, video call, or in person. Relevant medical and family history is collected at baseline and then annually via surveys through our secure Research Electronic Data Capture (REDCap) database. The University of Chicago Monogenic Diabetes Registry has enrolled over 3800 participants from over 2000 families. Participants represent all 50 states and more than 20 different countries. To date, over 1100 participants have a known genetic cause of diabetes. While many Registry participants reported being referred through their diabetes care provider (54%), a large portion also learned about the Registry through web searching (24%), friends/family (18%), or other sources (13%). Around two-thirds of those with a known genetic cause had research-based genetic testing completed rather than clinical testing due to insurance coverage difficulties. Of those who were found to have monogenic diabetes, significant delays in diagnosis were identified, which highlights the need for increased access to clinical genetic testing covered by insurance companies specifically within the United States. Among genes that cause a MODY phenotype, GCK mutations were the most common (59%) followed by HNF1A mutations (28%), while mutations in KCNJ11 were the most common among genes that cause neonatal diabetes (35%) followed by INS (16%). Over the last decade, improvements in data collection for the University of Chicago Monogenic Diabetes Registry have resulted in increased knowledge of the natural history of monogenic diabetes, as well as a better understanding of the most effective treatments. The University of Chicago Monogenic Diabetes Registry serves as a valuable resource that will continue to provide evidence to support improved clinical care and patient outcomes in monogenic diabetes.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA