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OBJECTIVE: The transition from pediatric to adult care for young adults with diabetes represents an important but often challenging time characterized by a shift from a family-centered care model of pediatrics to a patient-centered care model of adult medicine. We developed a structured transition program based on an adult receivership model at a large academic medical center to improve care coordination and patient satisfaction with the transition process. METHODS: From 2016 to 2020, we implemented a series of quality improvement efforts for young adults aged 18 to 23 years with diabetes by incorporating best practices from the American Diabetes Association guidelines on care for emerging adults. We measured transition orientation attendance, patient satisfaction, hemoglobin A1c (HbA1c) pre- and post-transfer, and care gaps to determine the impact of the program. RESULTS: In this study, 307 individuals with type 1 diabetes and 16 individuals with type 2 diabetes were taken care of by the adult endocrinology department at the University of Michigan between January 1, 2016 and October 31, 2020. We observed high attendance rates (86% among internal transfers) and favorable patient satisfaction scores for the transition orientation session. Despite the glycemic challenges posed during the transition, HbA1c modestly yet significantly improved 1-year after transfer (-0.4%, P < .01). CONCLUSION: We successfully established and maintained a young adult diabetes transition program using a quality improvement approach. Future work will focus on reducing care gaps at the time of transfer, assessing long-term retention rates, and enhancing care coordination for patients referred from outside the health network.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Transição para Assistência do Adulto , Humanos , Adulto Jovem , Criança , Hemoglobinas Glicadas , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 1/terapia , Satisfação do PacienteRESUMO
PURPOSE OF REVIEW: When the Supreme Court handed down its decision in Dobbs v Jackson Women's Health Organization in June 2022, the constitutional right to abortion was no longer protected by Roe v Wade. Fifteen states now have total or near-total bans on abortion care or no clinics providing abortion services. We review how these restrictions affect the medical care of people with pregestational diabetes. RECENT FINDINGS: Of the ten states with the highest percent of adult women living with diabetes, eight currently have complete or 6-week abortion bans. People with diabetes are at high risk of diabetes-related pregnancy complications and pregnancy-related diabetes complications and are disproportionately burdened by abortion bans. Abortion is an essential part of comprehensive, evidence-based diabetes care, yet no medical society has published guidelines on pregestational diabetes that explicitly discuss the importance and role of safe abortion care. Medical societies enacting standards for diabetes care and clinicians providing diabetes care must advocate for access to abortion to reduce pregnancy-related morbidity and mortality for pregnant people with diabetes.
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Diabetes Mellitus , Decisões da Suprema Corte , Gravidez , Feminino , Humanos , Estados Unidos/epidemiologia , Aborto LegalRESUMO
PURPOSE OF REVIEW: Machine learning (ML) is increasingly being studied for the screening, diagnosis, and management of diabetes and its complications. Although various models of ML have been developed, most have not led to practical solutions for real-world problems. There has been a disconnect between ML developers, regulatory bodies, health services researchers, clinicians, and patients in their efforts. Our aim is to review the current status of ML in various aspects of diabetes care and identify key challenges that must be overcome to leverage ML to its full potential. RECENT FINDINGS: ML has led to impressive progress in development of automated insulin delivery systems and diabetic retinopathy screening tools. Compared with these, use of ML in other aspects of diabetes is still at an early stage. The Food & Drug Administration (FDA) is adopting some innovative models to help bring technologies to the market in an expeditious and safe manner. ML has great potential in managing diabetes and the future is in furthering the partnership of regulatory bodies with health service researchers, clinicians, developers, and patients to improve the outcomes of populations and individual patients with diabetes.
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Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Política de Saúde/legislação & jurisprudência , Aprendizado de Máquina/legislação & jurisprudência , Inteligência Artificial/legislação & jurisprudência , Humanos , Programas de Rastreamento/legislação & jurisprudência , Estados Unidos , United States Food and Drug AdministrationRESUMO
Objective: To determine predictors of prolonged length of stay (LOS), 30-day readmission, and 30-day mortality in a multihospital health system. Methods: We performed a retrospective review of 531 adults admitted with diabetic ketoacidosis (DKA) to a multihospital health system between November 2015 and December 2016. Demographic and clinical data were collected. Linear regression was used to calculate odds ratios (ORs) for predictors and their association with prolonged LOS (3.2 days), 30-day readmission, and 30-day mortality. Results: Significant predictors for prolonged LOS included: intensive care unit (ICU) admission (OR, 2.12; 95% confidence interval [CI], 1.38 to 3.27), disease duration (nonlinear) (OR, 1.28; 95% CI, 1.10 to 1.49), non-white race (OR, 1.73; 95% CI, 1.15 to 2.60), age at admission (OR, 1.03; 95% CI, 1.01 to 1.04), and Elixhauser index (EI) (OR, 1.21; 95% CI, 1.13 to 1.29). Shorter time to consult after admission (median [Q1, Q3] of 11.3 [3.9, 20.7] vs. 14.8 [7.4, 37.3] hours, P<.001) was associated with a shorter LOS. Significant 30-day readmission predictors included: Medicare insurance (OR, 2.35; 95% CI, 1.13 to 4.86) and EI (OR, 1.31; 95% CI, 1.21 to 1.41). Endocrine consultation was associated with reduced 30-day readmission (OR, 0.51; 95% CI, 0.28 to 0.92). A predictive model for mortality was not generated because of low event rates. Conclusion: EI, non-white race, disease duration, age, Medicare, and ICU admission were associated with adverse outcomes. Endocrinology consultation was associated with lower 30-day readmission, and earlier consultation resulted in a shorter LOS. Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EI = Elixhauser index; HbA1c = hemoglobin A1c; ICD = International Classification of Diseases; ICU = intensive care unit; LOS = length of stay; OR = odds ratio; Q = quartile.
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Cetoacidose Diabética , Adulto , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Medicare , Readmissão do Paciente , Estudos Retrospectivos , Estados UnidosRESUMO
In this review, we have highlighted work that has clearly demonstrated that mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a negative regulator of MAPKs, is an important signaling mediator in bone, muscle, and fat tissue homeostasis and differentiation. Further, we examined recent studies with particular focus on MKP-1 overexpression or deletion and its impact on tissues connected to bone. We also summarized regulation of MKP-1 by known skeletal regulators like parathyroid hormone (PTH)/PTH-related peptide (PTHrP) and bone morphogenic proteins. MKP-1's integration into the pathophysiological state of osteoporosis, osteoarthritis, rheumatoid arthritis, obesity, and muscular dystrophy are examined to emphasize possible involvement of MKP-1 both at the molecular level and in disease complications such as sarcopenia- or diabetes-related osteoporosis. We predict that understanding the mechanism of MKP-1-mediated signaling in bone-muscle-fat crosstalk will be a key in coordinating their activities and developing therapeutics to improve clinical outcomes for diseases associated with advanced age.
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Osso e Ossos/enzimologia , Fosfatase 1 de Especificidade Dupla/metabolismo , Especificidade de Órgãos , Animais , Humanos , Modelos Biológicos , Osteócitos/enzimologia , Proteína Relacionada ao Hormônio Paratireóideo/metabolismoRESUMO
Differentiation of adipocytes from preadipocytes contributes to adipose tissue expansion in obesity. Impaired adipogenesis may underlie the development of metabolic diseases such as insulin resistance and type 2 diabetes. Mechanistically, a well defined transcriptional network coordinates adipocyte differentiation. The family of paired-related homeobox transcription factors, which includes Prrx1a, Prrx1b, and Prrx2, is implicated with regulation of mesenchymal cell fate, including myogenesis and skeletogenesis; however, whether these proteins impact adipogenesis remains to be addressed. In this study, we identify Prrx1a and Prrx1b as negative regulators of adipogenesis. We show that Prrx1a and Prrx1b are down-regulated during adipogenesis in vitro and in vivo. Stable knockdown of Prrx1a/b enhances adipogenesis, with increased expression of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α and FABP4 and increased secretion of the adipokines adiponectin and chemerin. Although stable low-level expression of Prrx1a, Prrx1b, or Prrx2 does not affect 3T3-L1 adipogenesis, transient overexpression of Prrx1a or Prrx1b inhibits peroxisome proliferator-activated receptor-γ activity. Prrx1 knockdown decreases expression of Tgfb2 and Tgfb3, and inhibition of TGFß signaling during adipogenesis mimics the effects of Prrx1 knockdown. These data support the hypothesis that endogenous Prrx1 restrains adipogenesis by regulating expression of TGFß ligands and thereby activating TGFß signaling. Finally, we find that expression of Prrx1a or Prrx1b in adipose tissue increases during obesity and strongly correlates with Tgfb3 expression in BL6 mice. These observations suggest that increased Prrx1 expression may promote TGFß activity in adipose tissue and thereby contribute to aberrant adipocyte function during obesity.
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Adipogenia , Proteínas de Homeodomínio/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/genética , Humanos , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Especificidade da Espécie , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta3/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Proteína Wnt3A/metabolismoRESUMO
OBJECTIVE: Glucagon-like peptide 1 receptor agonists (GLP-1RA) are widely used for the management of diabetes mellitus (DM), but their efficacy in familial partial lipodystrophy (FPLD) is unknown. In this retrospective study, we evaluated the effect of GLP-1RA in patients with FPLD. RESEARCH DESIGN AND METHODS: We analyzed data, reported with SDs, from 14 patients with FPLD (aged 58 ± 12 years; 76.47% female) and 14 patients with type 2 DM (aged 58 ± 13 years; 71% female) before and 6 months after starting GLP-1RA. RESULTS: We observed reduction in weight (95 ± 23 to 91 ± 22 kg; P = 0.002), BMI (33 ± 6 to 31 ± 6 kg/m2; P = 0.001), HbA1c (8.2% ± 1.4% to 7.7% ± 1.4%; P = 0.02), and fasting glucose (186 ± 64 to 166 ± 53 mg/dL; P = 0.04) in patients with FPLD. The change in triglycerides after treatment was greater in the FPLD group compared with the DM group (P = 0.02). We noted acute pancreatitis in two case subjects with FPLD with longer therapy. CONCLUSIONS: Our study demonstrates the relative safety and effectiveness of GLP-1RA in patients with FPLD.
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Diabetes Mellitus Tipo 2 , Lipodistrofia Parcial Familiar , Pancreatite , Humanos , Feminino , Masculino , Hipoglicemiantes/efeitos adversos , Estudos Retrospectivos , Glicemia , Lipodistrofia Parcial Familiar/tratamento farmacológico , Lipodistrofia Parcial Familiar/genética , Doença Aguda , Hemoglobinas Glicadas , Pancreatite/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistasRESUMO
OBJECTIVE: The coexistence of insulinoma and insulin antibodies is extremely rare. The aim of this novel case report is to inform physicians of the possibility of an insulinoma with concomitant insulin antibodies. METHODS: In this report, we describe a patient with symptomatic hypoglycemia confirmed with a 72-hour fast, who was subsequently found to have an insulinoma with concomitant elevation in his immunoglobulin G insulin antibody titer. RESULTS: The patient presented with initial symptoms of diaphoresis, confusion, and disorientation and was found unresponsive by a bystander. He had a fingerstick blood glucose of 36 mg/dL (reference 74-99 mg/dL), without exogenous insulin or sulfonylurea use. His symptoms resolved with administration of glucose. He was subsequently admitted for a 72-hour fast in which he developed neuroglycopenic symptoms 4 hours into the fast with fingerstick glucose of 47 mg/dL and serum glucose of 44 mg/dL (reference 74-99 mg/dL), C-peptide of 10.8 ng/mL (reference 0.5-2.7 ng/mL), insulin level of 106 µIU/mL (reference <25 µIU/mL), and a proinsulin level of 675 pmol/mL (reference <22 pmol/mL). His insulin-to-C-peptide ratio was 0.20, in which a ratio <1 is indicative of an insulinoma. Endoscopic ultrasound demonstrated a 16 x 11 mm biopsy-proven neuroendocrine tumor. He was found to have a high titer insulin antibody titer at 2.4 U/mL (reference <0.4 U/mL), was started on prednisone, and underwent successful radiofrequency ablation. He was able to be successfully tapered off steroids without recurrence. CONCLUSION: The coexistence of insulinoma with insulin antibodies is novel, and to our knowledge, has never been published.
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Maturity-onset diabetes of the young, or MODY-monogenic diabetes, is a not-so-rare collection of inherited disorders of non-autoimmune diabetes mellitus that remains insufficiently diagnosed despite increasing awareness. These cases are important to efficiently and accurately diagnose, given the clinical implications of syndromic features, cost-effective treatment regimen, and the potential impact on multiple family members. Proper recognition of the clinical manifestations, family history, and cost-effective lab and genetic testing provide the diagnosis. All patients must undergo a thorough history, physical examination, multigenerational family history, lab evaluation (glycated hemoglobin A1c [HbA1c], glutamic acid decarboxylase antibodies [GADA], islet antigen 2 antibodies [IA-2A], and zinc transporter 8 [ZnT8] antibodies). The presence of clinical features with 3 (or more) negative antibodies may be indicative of MODY-monogenic diabetes, and is followed by genetic testing. Molecular genetic testing should be performed before attempting specific treatments in most cases. Additional testing that is helpful in determining the risk of MODY-monogenic diabetes is the MODY clinical risk calculator (>25% post-test probability in patients not treated with insulin within 6 months of diagnosis should trigger genetic testing) and 2-hour postprandial (after largest meal of day) urinary C-peptide to creatinine ratio (with a ≥0.2 nmol/mmol to distinguish HNF1A- or 4A-MODY from type 1 diabetes). Treatment, as well as monitoring for microvascular and macrovascular complications, is determined by the specific variant that is identified. In addition to the diagnostic approach, this article will highlight recent therapeutic advancements when patients no longer respond to first-line therapy (historically sulfonylurea treatment in many variants). LEARNING OBJECTIVES: Upon completion of this educational activity, participants should be able to. TARGET AUDIENCE: This continuing medical education activity should be of substantial interest to endocrinologists and all health care professionals who care for people with diabetes mellitus.
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Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Testes Genéticos , Humanos , Hipoglicemiantes/classificação , Hipoglicemiantes/uso terapêutico , Masculino , Assistência Centrada no Paciente , Adulto JovemRESUMO
CONTEXT: Preoperative imaging is performed routinely to guide surgical management in primary hyperparathyroidism, but the optimal imaging modalities are debated. OBJECTIVE: Our objectives were to evaluate which imaging modalities are associated with improved cure rate and higher concordance rates with intraoperative findings. A secondary aim was to determine whether additive imaging is associated with higher cure rate. DESIGN, SETTING, AND PATIENTS: This is a retrospective cohort review of 1485 adult patients during a 14-year period (2004-2017) at an academic tertiary referral center that presented for initial parathyroidectomy for de novo primary hyperparathyroidism. MAIN OUTCOME MEASURES: Surgical cure rate, concordance of imaging with operative findings, and imaging performance. RESULTS: The overall cure rate was 94.1% (95% confidence interval, 0.93-0.95). Cure rate was significantly improved if sestamibi/single-photon emission computed tomography (SPECT) was concordant with operative findings (95.9% vs. 92.5%, Pâ =â 0.010). Adding a third imaging modality did not improve cure rate (1 imaging type 91.8% vs. 2 imaging types 94.4% vs. 3 imaging types 87.2%, Pâ =â 0.59). Despite having a low number of cases (nâ =â 28), 4-dimensional (4D) CT scan outperformed (higher sensitivity, specificity, positive predictive value, negative predictive value) all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas. CONCLUSIONS: Preoperative ultrasound combined with sestamibi/SPECT were associated with the highest cure and concordance rates. If pathology was not found on ultrasound and sestamibi/SPECT, additional imaging did not improve the cure rate or concordance. 4D CT scan outperformed all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas, but these findings were underpowered.
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Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/cirurgia , Cuidados Pré-Operatórios , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/cirurgia , Adulto , Idoso , Estudos de Coortes , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/estatística & dados numéricos , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Hiperparatireoidismo Primário/epidemiologia , Hiperparatireoidismo Primário/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/epidemiologia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Prognóstico , Indução de Remissão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Ultrassonografia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To identify novel prognostic risk factors and compare them with other known prognostic risk factors in follicular-cell-derived thyroid carcinoma (FDTC) with distant metastases. METHODS: A retrospective review was conducted of adult patients with metastatic FDTC seen at a tertiary care center between January 1990 and December 2010. A 15-year Kaplan-Meier survival estimate was created for overall survival (OS) and cancer-specific survival (CSS). Hazard ratios (HR) and P values from Cox proportional hazard models were used with a 95% CI. RESULTS: There were 143 patients (60.1% male, 39.9% female), of whom 104 (72.7%) patients had papillary, 30 (21.0%) had follicular, 5 (3.5%) had poorly differentiated, and 4 (2.8%) had Hürthle cell cancers. Median length of follow-up was 80.0 months (range 1.0-564.0). The 15-year mortality rate was 32.2% and cancer-specific mortality was 25.2%, with OS and CSS having the same risk factors. Lung was the most common site of metastases in 53 patients (37.1%), and patients with pleural effusions had significantly lower CSS (HR = 5.21, CI = 1.79-15.12). Additional risk factors for a decreased CSS included: older age upon diagnosis (>45 years, HR = 4.15, CI = 1.43-12.02), multiple metastatic locations (HR = 3.75, CI = 1.32-10.67), and incomplete/unknown tumor resection (HR = 2.35, CI = 1.18-4.67). CONCLUSION: This study is the first to demonstrate that pleural effusion is a poor prognostic sign in patients with FDTC with distant metastases and compare this risk with other accepted prognostic variables.
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Tetratricopeptide repeat domain-7A (TTC7A) deficiency causing combined immunodeficiency with inflammatory bowel disease (IBD) is rare. This case report alerts physicians to the possibility of TTC7A deficiency causing combined immunodeficiency with IBD and also highlights some of the current treatment options. We describe a 19-year-old patient with a compound heterozygote TTC7A mutation causing combined immunodeficiency, IBD, and multiple intestinal atresia. Compound heterozygote TTC7A mutations are known to cause combined immunodeficiency and IBD. Although rare, clinicians should be alerted to this variant and should understand the general approach to treatment.
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Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Fator 1-alfa Nuclear de Hepatócito , Fator 4 Nuclear de Hepatócito , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Fator 4 Nuclear de Hepatócito/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Masculino , Adulto , Feminino , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/genética , Polipeptídeo Inibidor GástricoAssuntos
Diabetes Mellitus Tipo 2 , Infarto do Miocárdio , Inibidores do Transportador 2 de Sódio-Glicose , Acidente Vascular Cerebral , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Hipoglicemiantes , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
The adipocyte-derived hormone adiponectin promotes metabolic and cardiovascular health. Circulating adiponectin increases in lean states such as caloric restriction (CR), but the reasons for this paradox remain unclear. Unlike white adipose tissue (WAT), bone marrow adipose tissue (MAT) increases during CR, and both MAT and serum adiponectin increase in many other clinical conditions. Thus, we investigated whether MAT contributes to circulating adiponectin. We find that adiponectin secretion is greater from MAT than WAT. Notably, specific inhibition of MAT formation in mice results in decreased circulating adiponectin during CR despite unaltered adiponectin expression in WAT. Inhibiting MAT formation also alters skeletal muscle adaptation to CR, suggesting that MAT exerts systemic effects. Finally, we reveal that both MAT and serum adiponectin increase during cancer therapy in humans. These observations identify MAT as an endocrine organ that contributes significantly to increased serum adiponectin during CR and perhaps in other adverse states.