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Ji X, Zou W, Fan L, Zhou Z, Zhu X, Li X. Insulin resistance-related features are associated with cognitive decline: a cross-sectional study in adult patients with type 1 diabetes. Diabetol Metab Syndr 2024; 16:13. [PMID: 38212850 PMCID: PMC10782534 DOI: 10.1186/s13098-023-01249-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 12/29/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND To investigate the associations between insulin resistance (IR)-related features and cognitive function in type 1 diabetes (T1D). METHODS A total of 117 adult patients with T1D were recruited in this cross-sectional study. IR-related features include overweight/obesity/central obesity, hypertension, atherogenic dyslipidemia, and decreased estimated insulin sensitivity (eIS). The Wechsler Memory Scale-Chinese Revision, Wisconsin Card Sorting Test, and Sustained Attention to Response Task was used to assess memory, executive function and sustained attention, respectively. A z-score was generated from each test, and a composite measure of global cognitive performance was calculated by averaging the z-scores of all tests. Cognitive differences were measured between T1D patients with and without IR-related features. The associations between IR-related features and and cognitive performance were analyzed using: logistic regression, partial correlation, and multivariate linear regression analysis. RESULTS A total of 53 (45.3%) T1D patients were defined as having IR-related features. Individuals with IR-related features displayed worse overall cognitive scores compared to those without and had a 4-fold increase in the risk for having global cognitive z-score < 0. Among the IR-related features, higher triglyceride (TG) and lower eIS showed linear correlation with lower global cognitive performance. And the subsequent regression analysis identified eIS as the factor independently associated with global cognitive performance. CONCLUSIONS We have provided evidence linking IR-related features to deteriorated cognitive function in adult patients with T1D. And eIS showed an independent positive correlation with global cognitive performance. Although no causal relationship can be drawn, IR emerges as an important factor reflecting cognitive function. TRIAL REGISTRATION ClinicalTrials.gov NCT03610984.
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Affiliation(s)
- Xiaolin Ji
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Wenjing Zou
- National Clinical Research Center for Mental Disorders, Medical Psychological Center, Medical Psychological Institute of Central South University, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
- Department of Radiology, The First Affiliated Hospital of Zhejiang University School of Medicine, 310000, Hangzhou, China
| | - Li Fan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Xiongzhao Zhu
- National Clinical Research Center for Mental Disorders, Medical Psychological Center, Medical Psychological Institute of Central South University, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.
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ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Stanton RC, Gabbay RA. 14. Children and Adolescents: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S258-S281. [PMID: 38078582 PMCID: PMC10725814 DOI: 10.2337/dc24-s014] [Citation(s) in RCA: 42] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Robertson ND, Deacon E, Botha K. A critical review of the relationship between type 1 diabetes mellitus, inhibition, and behavioral management. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2023; 3:1080415. [PMID: 36992790 PMCID: PMC10012078 DOI: 10.3389/fcdhc.2022.1080415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 12/30/2022] [Indexed: 02/22/2023]
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic and lifelong condition that requires adequate behavior management in order to meet desired health outcomes. The effects of T1DM on the neurocognitive functioning of affected individuals raise concerns about how the disease may influence executive functioning. Inhibition is a core component of executive functioning, and plays a vital role in self-regulation and the restriction of impulsive behaviors. Inhibition may thus play a vital role in the behavior management of people with T1DM. The aim of this study was to identify current gaps in existing knowledge regarding the relationship between T1DM, inhibition, and behavior management. This study employed a critical review design to analyze and synthesize the current scientific literature. Twelve studies were identified through an appraisal process, and the data extracted were thematically analyzed and integrated. The findings of this study indicate that a possible cycle arises between these three constructs, in which T1DM affects inhibition, inhibition affects behavior management, and poor behavior management affects inhibition. It is recommended that future research should focus more specifically on this relationship.
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Affiliation(s)
- Neville Dean Robertson
- School of Psychosocial Health, Community Psychosocial Research (COMPRES), North-West University, Potchefstroom, South Africa
| | - Elmari Deacon
- School of Psychosocial Health, Community Psychosocial Research (COMPRES), North-West University, Potchefstroom, South Africa
- OPTENTIA, North-West University, Vanderbijlpark, South Africa
| | - Karel Botha
- School of Psychosocial Health, Community Psychosocial Research (COMPRES), North-West University, Potchefstroom, South Africa
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The Advanced Diabetes Technologies for Reduction of the Frequency of Hypoglycemia and Minimizing the Occurrence of Severe Hypoglycemia in Children and Adolescents with Type 1 Diabetes. J Clin Med 2023; 12:jcm12030781. [PMID: 36769430 PMCID: PMC9917934 DOI: 10.3390/jcm12030781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/09/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Hypoglycemia is an often-observed acute complication in the management of children and adolescents with type 1 diabetes. It causes inappropriate glycemic outcomes and may impair the quality of life in the patients. Severe hypoglycemia with cognitive impairment, such as a convulsion and coma, is a lethal condition and is associated with later-onset cognitive impairment and brain-structural abnormalities, especially in young children. Therefore, reducing the frequency of hypoglycemia and minimizing the occurrence of severe hypoglycemia are critical issues in the management of children and adolescents with type 1 diabetes. Advanced diabetes technologies, including continuous glucose monitoring and sensor-augmented insulin pumps with low-glucose suspension systems, can reduce the frequency of hypoglycemia and the occurrence of severe hypoglycemia without aggravating glycemic control. The hybrid closed-loop system, an automated insulin delivery system, must be the most promising means to achieve appropriate glycemic control with preventing severe hypoglycemia. The use of these advanced diabetes technologies could improve glycemic outcomes and the quality of life in children and adolescents with type 1 diabetes.
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Ibrahim BA, Hussein SA, Abdullah WH. COGNITIVE FUNCTIONS IN CHILDREN WITH TYPE I DIABETES. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2023; 76:944-950. [PMID: 37326074 DOI: 10.36740/wlek202305108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
OBJECTIVE The aim: To assess the patterns and severity of cognitive impairment in children with type 1 diabetes as well as its association with disease onset and poor glycemic control. PATIENTS AND METHODS Materials and methods: We assessed higher mental function and screened for psychosocial functioning in 60 children with type 1 DM and 60 age-matched control using the Modified Mini-Mental State examination and Pediatric Symptoms Checklist and its relation with age, gender, socioeconomic status, age at the onset of disease, duration of disease, HbA1c level, frequency of diabetic ketoacidosis and hypoglycemic attacks and type of treatment. RESULTS Results: Diabetic patients demonstrated a lower Modified Mini-Mental State examination score than controls (25.12±4.58 versus 30.08±2.95) with a highly significant difference. Furthermore, the mean Pediatric symptoms checklist score in patients was 39.08±8.18 which was much lower than that of controls 54.42±6.0 with a highly significant difference. CONCLUSION Conclusions: There is neurocognitive impairment in diabetic children compared to non-diabetics, and poor glycemic control whether hyper or hypoglycemia could affect their cognition and mental health.
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6
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ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 14. Children and Adolescents: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S230-S253. [PMID: 36507640 PMCID: PMC9810473 DOI: 10.2337/dc23-s014] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Monzani A, Savastio S, Manzo A, Scalogna A, Pozzi E, Sainaghi PP, Della Corte F, Rabbone I. Not only for caregivers: intranasal glucagon for severe hypoglycaemia in a simulation study. Acta Diabetol 2022; 59:1479-1484. [PMID: 35951133 DOI: 10.1007/s00592-022-01952-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 07/27/2022] [Indexed: 11/01/2022]
Abstract
AIMS To evaluate: (i) the propensity of paediatrics and emergency medicine residents to select different therapeutic options and (ii) the speed and administration success in a high-fidelity simulation of severe hypoglycaemia in a child with type 1 diabetes (T1DM). METHODS In this single-centre high-fidelity simulation study, 51 paediatrics or emergency medicine residents were exposed to a scenario of severe hypoglycaemia in a T1DM child attending an ambulatory setting, before and after a training on the preparation and administration of both injectable and IN glucagon. Time for drug delivery and its effectiveness were collected. RESULTS Before training, 45.1% of participants chose to administer injectable glucagon, 43.1% intravenous glucose solution, 5.9% intranasal (IN) glucagon, and 5.9% took no action. Administration was successful in 74% of injectable glucagon, 33.3% intravenous glucose solution, and 22.7% IN glucagon. After training, 58.8% of participants chose IN and 41.2% injectable glucagon, with 100% of successful administrations for IN glucagon and 90.5% for injectable glucagon. Time to successful administration was shorter for IN than injectable glucagon (23 ± 10 vs. 38 ± 7 s, p < 0.0001). CONCLUSIONS IN glucagon is an easy and effective option for severe hypoglycaemia treatment, with an almost zero possibility of failure provided that adequate training is imparted.
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Affiliation(s)
- A Monzani
- Division of Paediatrics, Department of Health Sciences, University of Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy
| | - S Savastio
- Division of Paediatrics, Department of Health Sciences, University of Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy
| | - A Manzo
- Division of Paediatrics, Department of Health Sciences, University of Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy
| | - A Scalogna
- SIMNOVA Interdepartmental Centre for Innovative Learning and Simulation in Medicine and Allied Health Professions, University of Piemonte Orientale, via Lanino 1, 28100, Novara, Italy
| | - E Pozzi
- Division of Paediatrics, Department of Health Sciences, University of Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy
| | - P P Sainaghi
- Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy
| | - F Della Corte
- SIMNOVA Interdepartmental Centre for Innovative Learning and Simulation in Medicine and Allied Health Professions, University of Piemonte Orientale, via Lanino 1, 28100, Novara, Italy
- Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy
| | - I Rabbone
- Division of Paediatrics, Department of Health Sciences, University of Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy.
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Marissal-Arvy N, Moisan MP. Diabetes and associated cognitive disorders: Role of the Hypothalamic-Pituitary Adrenal axis. Metabol Open 2022; 15:100202. [PMID: 35958117 PMCID: PMC9357829 DOI: 10.1016/j.metop.2022.100202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/18/2022] [Accepted: 07/20/2022] [Indexed: 11/12/2022] Open
Abstract
Both diabetes types, types 1 and 2, are associated with cognitive impairments. Each period of life is concerned, and this is an increasing public health problem. Animal models have been developed to investigate the biological actors involved in such impairments. Many levels of the brain function (structure, volume, neurogenesis, neurotransmission, behavior) are involved. In this review, we detailed the part potentially played by the Hypothalamic-Pituitary Adrenal axis in these dysfunctions. Notably, regulating glucocorticoid levels, their receptors and their bioavailability appear to be relevant for future research studies, and treatment development.
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Affiliation(s)
- Nathalie Marissal-Arvy
- INRAE, Laboratoire de Nutrition et Neurobiologie Intégrée, UMR 1286, UFR de Pharmacie, 146 Rue Léo Saignat, 33076, Bordeaux Cedex, France
| | - Marie-Pierre Moisan
- University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000, Bordeaux, France
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9
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Altered gray matter volume in children with newly diagnosed type 1 diabetes mellitus. Pediatr Res 2022; 93:1342-1347. [PMID: 35918400 DOI: 10.1038/s41390-022-02227-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/29/2022] [Accepted: 07/08/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) affects the development of cognitive function in children, which may be due to deficits in brain structures or functions. It is unclear whether children with T1DM experience alterations in the gray matter (GM) structure at the initial stages of the disease. This study investigated GM structure alterations in children with newly diagnosed T1DM. METHODS Based on 3D T1-weighted MR images, we investigated the gray matter volume (GMV) of 35 newly diagnosed T1DM children and 35 age- and sex-matched healthy controls using voxel-based morphometry. The brain regions with significant differences in GMV between the newly diagnosed T1DM children and the controls were extracted and the correlation with clinical data was assessed. RESULTS Compared with the control group, children with newly diagnosed T1DM had a lower GMV in the right inferior and middle temporal gyri, right lingual gyrus, and left superior frontal gyrus. In T1DM subjects, the GMV of the right middle temporal gyrus was positively correlated with IQ but was negatively correlated with HbA1c. CONCLUSIONS Our findings provide compelling evidence that GM abnormalities occur during early disease stages in T1DM children, which may be a potential neurobiological mechanism underlying cognitive deficits. IMPACT Using an efficient method to analyze gray matter changes in T1DM is very important. The anterior, posterior, and temporal brain regions are susceptible to T1DM in children. Recent glucose variability may affect regional gray matter volume in children with newly diagnosed T1DM. Structural changes were documented in the gray matter of the brain even at the early stages of the disease in children with T1DM.
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Erichsen JM, Fadel JR, Reagan LP. Peripheral versus central insulin and leptin resistance: Role in metabolic disorders, cognition, and neuropsychiatric diseases. Neuropharmacology 2022; 203:108877. [PMID: 34762922 PMCID: PMC8642294 DOI: 10.1016/j.neuropharm.2021.108877] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 10/14/2021] [Accepted: 11/04/2021] [Indexed: 02/06/2023]
Abstract
Insulin and leptin are classically regarded as peptide hormones that play key roles in metabolism. In actuality, they serve several functions in both the periphery and central nervous system (CNS). Likewise, insulin and leptin resistance can occur both peripherally and centrally. Metabolic disorders such as diabetes and obesity share several key features including insulin and leptin resistance. While the peripheral effects of these disorders are well-known (i.e. cardiovascular disease, hypertension, stroke, dyslipidemia, etc.), the CNS complications of leptin and insulin resistance have come into sharper focus. Both preclinical and clinical findings have indicated that insulin and leptin resistance are associated with cognitive deficits and neuropsychiatric diseases such as depression. Importantly, these studies also suggest that these deficits in neuroplasticity can be reversed by restoration of insulin and leptin sensitivity. In view of these observations, this review will describe, in detail, the peripheral and central functions of insulin and leptin and explain the role of insulin and leptin resistance in various metabolic disorders, cognition, and neuropsychiatric diseases.
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Affiliation(s)
- Jennifer M Erichsen
- University of South Carolina School of Medicine, Department of Pharmacology, Physiology, and Neuroscience, Columbia, SC, 29208, USA.
| | - Jim R Fadel
- University of South Carolina School of Medicine, Department of Pharmacology, Physiology, and Neuroscience, Columbia, SC, 29208, USA
| | - Lawrence P Reagan
- University of South Carolina School of Medicine, Department of Pharmacology, Physiology, and Neuroscience, Columbia, SC, 29208, USA; Columbia VA Health Care System, Columbia, SC, 29208, USA
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Nevo-Shenker M, Shalitin S. The Impact of Hypo- and Hyperglycemia on Cognition and Brain Development in Young Children with Type 1 Diabetes. Horm Res Paediatr 2022; 94:115-123. [PMID: 34247158 DOI: 10.1159/000517352] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 05/21/2021] [Indexed: 11/19/2022] Open
Abstract
Human and experimental animal data suggest both hyperglycemia and hypoglycemia can lead to altered brain structure and neurocognitive function in type 1 diabetes (T1D). Young children with T1D are prone to extreme fluctuations in glucose levels. The overlap of these potential dysglycemic insults to the brain during the time of most active brain and cognitive development may cause cellular and structural injuries that appear to persist into adult life. Brain structure and cognition in persons with T1D are influenced by age of onset, exposure to glycemic extremes such as severe hypoglycemic episodes, history of diabetic ketoacidosis, persistent hyperglycemia, and glucose variability. Studies using brain imaging techniques have shown brain changes that appear to be influenced by metabolic abnormalities characteristic of diabetes, changes apparent at diagnosis and persistent throughout adulthood. Some evidence suggests that brain injury might also directly contribute to psychological and mental health outcomes. Neurocognitive deficits manifest across multiple cognitive domains. Moreover, impaired executive function and mental health can affect patients' adherence to treatment. This review summarizes the current data on the impact of glycemic extremes on brain structure and cognitive function in youth with T1D and the use of new diabetes technologies that may reduce these complications.
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Affiliation(s)
- Michal Nevo-Shenker
- Jesse Z. and Lea Shafer Institute of Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Shlomit Shalitin
- Jesse Z. and Lea Shafer Institute of Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Monitoring Glucose Concentrations in Children with Epilepsy on a Ketogenic Diet. Healthcare (Basel) 2022; 10:healthcare10020245. [PMID: 35206860 PMCID: PMC8872244 DOI: 10.3390/healthcare10020245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/16/2022] [Accepted: 01/24/2022] [Indexed: 12/04/2022] Open
Abstract
Ketogenic diet (KD) and pulsatile dexamethasone therapy (PDT) are commonly used in the treatment of children with drug resistant epilepsy. Potential side effects of the KD are hypoglycemia, whereas PDT might lead to hyperglycemia. One practical option to measure glucose concentrations regularly is the flash glucose monitoring system (FGM). In this single-center study in Germany, two pediatric patients with epilepsy (age: 6.0 and 6.8 years) received FGM from the beginning of the KD over six months, in the year 2020, and one patient (9.8 years) was observed for one month on PDT and switched to the KD thereafter. Glucose concentrations were measured by using an FGM system and capillary blood measurement. Seizure frequency, changes in cognition, motor performance, social behavior, and sleep quality were evaluated. The mean hypoglycemia rate per day (65 mg/dL and lower) declined significantly in patient 1 and 2 after three months. Patient 3 showed in total seven hyperglycemic events during PDT. Patient 1 became seizure free. Improvement of attention and memory performance were reported. FGM during the KD as a treatment for drug resistant epilepsies in childhood is a practical option to explore and to avoid hypoglycemia during the KD and hyperglycemia during PDT.
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Cacciatore M, Grasso EA, Tripodi R, Chiarelli F. Impact of glucose metabolism on the developing brain. Front Endocrinol (Lausanne) 2022; 13:1047545. [PMID: 36619556 PMCID: PMC9816389 DOI: 10.3389/fendo.2022.1047545] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022] Open
Abstract
Glucose is the most important substrate for proper brain functioning and development, with an increased glucose consumption in relation to the need of creating new brain structures and connections. Therefore, alterations in glucose homeostasis will inevitably be associated with changes in the development of the Nervous System. Several studies demonstrated how the alteration of glucose homeostasis - both hyper and hypoglycemia- may interfere with the development of brain structures and cognitivity, including deficits in intelligence quotient, anomalies in learning and memory, as well as differences in the executive functions. Importantly, differences in brain structure and functionality were found after a single episode of diabetic ketoacidosis suggesting the importance of glycemic control and stressing the need of screening programs for type 1 diabetes to protect children from this dramatic condition. The exciting progresses of the neuroimaging techniques such as diffusion tensor imaging, has helped to improve the understanding of the effects, outcomes and mechanisms underlying brain changes following dysglycemia, and will lead to more insights on the physio-pathological mechanisms and related neurological consequences about hyper and hypoglycemia.
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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15
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Body fat, cardiovascular risk factors and brain structure in school-age children. Int J Obes (Lond) 2021; 45:2425-2431. [PMID: 34267324 DOI: 10.1038/s41366-021-00913-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 06/17/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND In adults, cardiovascular risk factors are known to be associated with brain health. We hypothesized that these associations are already present at school-age. We examined the associations of adverse body fat measures and cardiovascular risk factors with brain structure, including volumetric measures and white matter microstructure, in 10-year-old children. METHODS We performed a cross-sectional analysis in a population-based prospective cohort study in Rotterdam, the Netherlands. Analyses were based on 3098 children aged 10 years with neuroimaging data and at least one measurement of body fat and cardiovascular risk factors. Body fat measures included body mass index (BMI), fat mass index and android fat mass percentage obtained by Dual-energy X-ray absorptiometry. Cardiovascular risk factors included blood pressure, and serum glucose, insulin and lipids blood concentrations. Structural neuroimaging, including global and regional brain volumes, was quantified by magnetic resonance imaging. DTI was used to assess white matter microstructure, including global fractional anisotropy (FA) and mean diffusivity (MD). RESULTS As compared to children with a normal weight, those with underweight had a smaller total brain and white matter volumes (differences -18.10 (95% Confidence Interval (CI) -30.97,-5.22) cm3, -10.64 (95% CI -16.82,-4.47) cm3, respectively). In contrast, one SDS (Standard Deviation Score) increase in fat mass index was associated with a smaller gray matter volume (differences -3.48 (95% CI -16.82, -4.47) cm3). Also, one SDS increase in android fat mass percentage was associated with lower white matter diffusivity (difference -0.06 (95% CI -0.10, -0.02) SDS). None of the other cardiovascular risk factors were associated with any of the brain outcomes. CONCLUSIONS Body fat measures, but not other cardiovascular risk factors, were associated with structural neuroimaging outcomes in school-aged children. Prospective studies are needed to assess causality, direction and long-term consequences of the associations.
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Yu KKK, Cheing GLY, Cheung C, Kranz GS, Cheung AKK. Gray Matter Abnormalities in Type 1 and Type 2 Diabetes: A Dual Disorder ALE Quantification. Front Neurosci 2021; 15:638861. [PMID: 34163319 PMCID: PMC8215122 DOI: 10.3389/fnins.2021.638861] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 05/07/2021] [Indexed: 12/06/2022] Open
Abstract
Aims/hypothesis: Diabetes mellitus (DM) is associated with comorbid brain disorders. Neuroimaging studies in DM revealed neuronal degeneration in several cortical and subcortical brain regions. Previous studies indicate more pronounced brain alterations in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM). However, a comparison of both types of DM in a single analysis has not been done so far. The aim of this meta-analysis was to conduct an unbiased objective investigation of neuroanatomical differences in DM by combining voxel-based morphometry (VBM) studies of T1DM and T2DM using dual disorder anatomical likelihood estimation (ALE) quantification. Methods: PubMed, Web of Science and Medline were systematically searched for publications until June 15, 2020. VBM studies comparing gray matter volume (GMV) differences between DM patients and controls at the whole-brain level were included. Study coordinates were entered into the ALE meta-analysis to investigate the extent to which T1DM, T2DM, or both conditions contribute to gray matter volume differences compared to controls. Results: Twenty studies (comprising of 1,175 patients matched with 1,013 controls) were included, with seven studies on GMV alterations in T1DM and 13 studies on GMV alterations in T2DM. ALE analysis revealed seven clusters of significantly lower GMV in T1DM and T2DM patients relative to controls across studies. Both DM subtypes showed GMV reductions in the left caudate, right superior temporal lobe, and left cuneus. Conversely, GMV reductions associated exclusively with T2DM (>99% contribution) were found in the left cingulate, right posterior lobe, right caudate and left occipital lobe. Meta-regression revealed no significant influence of study size, disease duration, and HbA1c values. Conclusions/interpretation: Our findings suggest a more pronounced gray matter atrophy in T2DM compared to T1DM. The increased risk of microvascular or macrovascular complications, as well as the disease-specific pathology of T2DM may contribute to observed GMV reductions. Systematic Review Registration: [PROSPERO], identifier [CRD42020142525].
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Affiliation(s)
- Kevin K K Yu
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.,University Research Facility in Behavioral and Systems Neuroscience (UBSN), The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Gladys L Y Cheing
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.,University Research Facility in Behavioral and Systems Neuroscience (UBSN), The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Charlton Cheung
- Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong
| | - Georg S Kranz
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.,The State Key Laboratory for Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong.,Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Alex Kwok-Kuen Cheung
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong
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17
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Mauras N, Buckingham B, White NH, Tsalikian E, Weinzimer SA, Jo B, Cato A, Fox LA, Aye T, Arbelaez AM, Hershey T, Tansey M, Tamborlane W, Foland-Ross LC, Shen H, Englert K, Mazaika P, Marzelli M, Reiss AL. Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study. Diabetes Care 2021; 44:983-992. [PMID: 33568403 PMCID: PMC7985430 DOI: 10.2337/dc20-2125] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 01/05/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia. RESEARCH DESIGN AND METHODS One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.7 years, 46% female) had unsedated MRI and cognitive testing up to four times over 6.4 ± 0.4 (range 5.3-7.8) years; HbA1c and continuous glucose monitoring were done quarterly. FreeSurfer-derived brain volumes and cognitive metrics assessed longitudinally were compared between groups using mixed-effects models at 6, 8, 10, and 12 years. Correlations with glycemia were performed. RESULTS Total brain, gray, and white matter volumes and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at 6, 8, 10, and 12 years, with estimated group differences in full-scale IQ of -4.15, -3.81, -3.46, and -3.11, respectively (P < 0.05), and total brain volume differences of -15,410, -21,159, -25,548, and -28,577 mm3 at 6, 8, 10, and 12 years, respectively (P < 0.05). Differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a life-long HbA1c index and higher sensor glucose in diabetes. CONCLUSIONS Detectable changes in brain volumes and cognitive scores persist over time in children with early-onset type 1 diabetes followed longitudinally; these differences are associated with metrics of hyperglycemia. Whether these changes can be reversed with scrupulous diabetes control requires further study. These longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children.
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Affiliation(s)
- Nelly Mauras
- Division of Endocrinology, Diabetes & Metabolism, Department of Pediatrics, Nemours Children's Health System, Jacksonville, FL
| | - Bruce Buckingham
- Division of Endocrinology and Diabetes, Department of Pediatrics, Stanford University, Stanford, CA
| | - Neil H White
- Division of Endocrinology and Diabetes, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO
| | - Eva Tsalikian
- Division of Endocrinology and Diabetes, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA
| | | | - Booil Jo
- Center for Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA
| | - Allison Cato
- Division of Neurology, Nemours Children's Health System, Jacksonville, FL
| | - Larry A Fox
- Division of Endocrinology, Diabetes & Metabolism, Department of Pediatrics, Nemours Children's Health System, Jacksonville, FL
| | - Tandy Aye
- Division of Endocrinology and Diabetes, Department of Pediatrics, Stanford University, Stanford, CA
| | - Ana Maria Arbelaez
- Division of Endocrinology and Diabetes, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO
| | - Tamara Hershey
- Departments of Radiology and Psychiatry, Washington University in St. Louis, St. Louis, MO
| | - Michael Tansey
- Division of Endocrinology and Diabetes, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA
| | | | - Lara C Foland-Ross
- Center for Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA
| | - Hanyang Shen
- Center for Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA
| | - Kimberly Englert
- Division of Endocrinology, Diabetes & Metabolism, Department of Pediatrics, Nemours Children's Health System, Jacksonville, FL
| | - Paul Mazaika
- Center for Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA
| | - Matthew Marzelli
- Center for Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA
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18
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Ogugua CF, Chikani UN, Okiche CY, Ibekwe UM. Sociodemographic determinants of glycaemic control among children with type 1 diabetes in South Eastern Nigeria. Pan Afr Med J 2021; 38:250. [PMID: 34104298 PMCID: PMC8164434 DOI: 10.11604/pamj.2021.38.250.19790] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 02/12/2021] [Indexed: 12/27/2022] Open
Abstract
INTRODUCTION diabetic complications have been identified as the major causes of morbidity and mortality in persons with type 1 diabetes mellitus (T1DM). Lack of appropriate glycaemic control is a significant risk factor for the onset and progression of long term complications of diabetes. Identifying the determinants of good glycaemic control is therefore imperative. METHODS this was a cross-sectional, hospital-based study of children aged 3-18 years with T1DM. Subjects were consecutively enrolled after obtaining consent from their parents and assent from children aged ≥7 years. A questionnaire was completed recording their clinical history and sociodemographic variables. Their HbA1c was estimated and values ≤7.5% was defined as the cut-off for optimal glycaemic control. RESULTS seventy-one children with T1DM were enrolled for the study. Thirty-eight (53.5%) of them were males. Mean age (years) was 13.7±4. Mean age at onset of diabetes was 11.6 years (range: 3-16 years), mean duration of diabetes was 24.4 months (range: 4-84 months), mean HbA1c value was 10.5% (range: 6.4%-14%); a multivariate logistic regression analysis was performed to identify determinants of optimal glycaemic control. Only caregivers' involvement in diabetes management P<0.016, odd ratio 13.03 (95% CI: 1.60-105.95) was identified as determinant of good glycaemic control. CONCLUSION our data suggest that of all the sociodemographic factors studied, caregivers' involvement in diabetes management was the only strong determinant for optimal glycaemic control.
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Affiliation(s)
- Chinwe Flora Ogugua
- Paediatric Endocrinology Unit, Department of Paediatrics, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Nigeria
| | - Ugo Nnenna Chikani
- Paediatric Endocrinology Unit, Department of Paediatrics, University of Nigeria, Ituku Ozalla Campus, Enugu, Nigeria
| | - Chikosolu Yvonne Okiche
- Paediatric Endocrinology Unit, Department of Paediatrics, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Nigeria
| | - Ugochi Maryann Ibekwe
- Paediatric Endocrinology Unit, Department of Paediatrics, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Nigeria
- Department of Paediatrics, Ebonyi State University, Abakaliki, Ebonyi, Nigeria
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19
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Redondo MJ, Libman I, Maahs DM, Lyons SK, Saraco M, Reusch J, Rodriguez H, DiMeglio LA. The Evolution of Hemoglobin A 1c Targets for Youth With Type 1 Diabetes: Rationale and Supporting Evidence. Diabetes Care 2021; 44:301-312. [PMID: 33431422 PMCID: PMC7818324 DOI: 10.2337/dc20-1978] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 11/08/2020] [Indexed: 02/03/2023]
Abstract
The American Diabetes Association 2020 Standards of Medical Care in Diabetes (Standards of Care) recommends a hemoglobin A1c (A1C) of <7% (53 mmol/mol) for many children with type 1 diabetes (T1D), with an emphasis on target personalization. A higher A1C target of <7.5% may be more suitable for youth who cannot articulate symptoms of hypoglycemia or have hypoglycemia unawareness and for those who do not have access to analog insulins or advanced diabetes technologies or who cannot monitor blood glucose regularly. Even less stringent A1C targets (e.g., <8%) may be warranted for children with a history of severe hypoglycemia, severe morbidities, or short life expectancy. During the "honeymoon" period and in situations where lower mean glycemia is achievable without excessive hypoglycemia or reduced quality of life, an A1C <6.5% may be safe and effective. Here, we provide a historical perspective of A1C targets in pediatrics and highlight evidence demonstrating detrimental effects of hyperglycemia in children and adolescents, including increased likelihood of brain structure and neurocognitive abnormalities, microvascular and macrovascular complications, long-term effects, and increased mortality. We also review data supporting a decrease over time in overall severe hypoglycemia risk for youth with T1D, partly associated with the use of newer insulins and devices, and weakened association between lower A1C and severe hypoglycemia risk. We present common barriers to achieving glycemic targets in pediatric diabetes and discuss some strategies to address them. We aim to raise awareness within the community on Standards of Care updates that impact this crucial goal in pediatric diabetes management.
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Affiliation(s)
- Maria J Redondo
- Texas Children's Hospital, Baylor College of Medicine, Houston, TX
| | - Ingrid Libman
- Division of Pediatric Endocrinology, Diabetes and Metabolism, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - David M Maahs
- Division of Pediatric Endocrinology and Diabetes, Stanford University, Stanford, CA
- Stanford Diabetes Research Center, Stanford University, Stanford, CA
- Health Research and Policy (Epidemiology), Stanford University, Stanford, CA
| | - Sarah K Lyons
- Texas Children's Hospital, Baylor College of Medicine, Houston, TX
| | | | - Jane Reusch
- University of Colorado and Rocky Mountain Regional VA Medical Center, Aurora, CO
| | - Henry Rodriguez
- USF Diabetes and Endocrinology Section, University of South Florida, Tampa, FL
| | - Linda A DiMeglio
- Division of Pediatric Endocrinology and Diabetology and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN
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20
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc21-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc21-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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21
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Diabetes Mellitus-Related Dysfunction of the Motor System. Int J Mol Sci 2020; 21:ijms21207485. [PMID: 33050583 PMCID: PMC7589125 DOI: 10.3390/ijms21207485] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 10/08/2020] [Accepted: 10/08/2020] [Indexed: 12/20/2022] Open
Abstract
Although motor deficits in humans with diabetic neuropathy have been extensively researched, its effect on the motor system is thought to be lesser than that on the sensory system. Therefore, motor deficits are considered to be only due to sensory and muscle impairment. However, recent clinical and experimental studies have revealed that the brain and spinal cord, which are involved in the motor control of voluntary movement, are also affected by diabetes. This review focuses on the most important systems for voluntary motor control, mainly the cortico-muscular pathways, such as corticospinal tract and spinal motor neuron abnormalities. Specifically, axonal damage characterized by the proximodistal phenotype occurs in the corticospinal tract and motor neurons with long axons, and the transmission of motor commands from the brain to the muscles is impaired. These findings provide a new perspective to explain motor deficits in humans with diabetes. Finally, pharmacological and non-pharmacological treatment strategies for these disorders are presented.
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22
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Black KJ, Kim S, Schlaggar BL, Greene DJ. The New Tics study: A Novel Approach to Pathophysiology and Cause of Tic Disorders. JOURNAL OF PSYCHIATRY AND BRAIN SCIENCE 2020; 5:e200012. [PMID: 32587895 PMCID: PMC7316401 DOI: 10.20900/jpbs.20200012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
We report on the ongoing project "The New Tics Study: A Novel Approach to Pathophysiology and Cause of Tic Disorders," describing the work completed to date, ongoing studies and long-term goals. The overall goals of this research are to study the pathophysiology of Provisional Tic Disorder, and to study tic remission (or improvement) in a prospective fashion. Preliminary data collection for the project began almost 10 years ago. The current study is nearing completion of its third year, and has already reported several novel and important results. First, surprisingly, at least 90% of children who had experienced tics for only a mean of 3 months still had tics at the 12-month anniversary of their first tic, though in some cases tics were seen only with remote video observation of the child sitting alone. Thus almost all of them now had a DSM-5 diagnosis of Tourette's Disorder or Persistent (Chronic) Tic Disorder. Baseline clinical features that predicted 12-month outcome included tic severity, subsyndromal autism spectrum symptoms, an anxiety disorder, and a history of 3 or more phonic tics. Second, we found that poorer tic suppression ability when immediately rewarded for suppression predicted greater tic severity at follow-up. Third, striatal volumes did not predict outcome as hypothesized, but a larger hippocampus at baseline predicted worse severity at follow-up. Enrollment and data collection continue, including functional connectivity MRI (fcMRI) imaging, and additional analyses are planned once the full sample is enrolled.
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Affiliation(s)
- Kevin J. Black
- Departments of Psychiatry, Neurology, Radiology and Neuroscience, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Soyoung Kim
- Departments of Psychiatry and Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Bradley L. Schlaggar
- Kennedy Krieger Institute, Baltimore, MD 21205; and Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Deanna J. Greene
- Departments of Psychiatry and Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
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23
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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24
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Urakami T. Severe Hypoglycemia: Is It Still a Threat for Children and Adolescents With Type 1 Diabetes? Front Endocrinol (Lausanne) 2020; 11:609. [PMID: 33042005 PMCID: PMC7523511 DOI: 10.3389/fendo.2020.00609] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 07/27/2020] [Indexed: 12/13/2022] Open
Abstract
Severe hypoglycemia is defined as a condition with serious cognitive dysfunction, such as a convulsion and coma, requiring external help from other persons. This condition is still lethal and is reported to be the cause of death in 4-10% in children and adolescents with type 1 diabetes. The incidence of severe hypoglycemia in the pediatric population was previously reported as high as more than 50-100 patient-years; however, there was a decline in the frequency of severe hypoglycemia during the past decades, and relationship with glycemic control became weaker than previously reported. A lot of studies have shown the neurological sequelae with severe hypoglycemia as cognitive dysfunction and abnormalities in brain structure. This serious condition also provides negative psychosocial outcomes and undesirable compensatory behaviors. Various possible factors, such as younger age, recurrent hypoglycemia, nocturnal hypoglycemia, and impaired awareness of hypoglycemia, are possible risk factors for developing severe hypoglycemia. A low HbA1c level is not a predictable value for severe hypoglycemia. Prevention of severe hypoglycemia remains one of the most critical issues in the management of pediatric patients with type 1 diabetes. Advanced technologies, such as continuous glucose monitoring (CGM), intermittently scanned CGM, and sensor-augmented pump therapy with low-glucose suspend system, potentially minimize the occurrence of severe hypoglycemia without worsening overall glycemic control. Hybrid closed-loop system must be the most promising tool for achieving optimal glycemic control with preventing the occurrence of severe hypoglycemia in pediatric patients with type 1 diabetes.
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25
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Liu J, Fan W, Jia Y, Su X, Wu W, Long X, Sun X, Liu J, Sun W, Zhang T, Gong Q, Shi H, Zhu Q, Wang J. Altered Gray Matter Volume in Patients With Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne) 2020; 11:45. [PMID: 32117070 PMCID: PMC7031205 DOI: 10.3389/fendo.2020.00045] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 01/24/2020] [Indexed: 02/05/2023] Open
Abstract
Background and Purpose: Many imaging studies have reported structure alterations in patients with type 1 diabetes mellitus (T1DM) by using voxel-based morphometry (VBM). Nevertheless, the results reported were inconsistent and had not been reviewed quantitatively. Accordingly, the quantitative meta-analysis which including VBM studies of patients with T1DM was conducted. Materials and Methods: The gray matter volume alterations in patients with T1DM was estimated by using the software seed-based d mapping. Meantime, the meta-regression was applied to detect the effects of some demographics and clinical characteristics. Results: Six studies were finally included, which with 6 datasets comprising 414 T1DM patients and 216 healthy controls. The pooled meta-analyses detected that patients with T1DM showed robustly increased gray matter volume in the left dorsolateral superior frontal gyrus and middle frontal gyrus and a decreased gray matter volume in the right lingual gyrus, cerebellum, precuneus, the left inferior temporal gyrus, and middle temporal gyrus. The meta-regression showed that the mean age, the female patient's ratio, duration of illness and HbAlc% for T1DM patients were not linearly related with gray matter alterations. Conclusion: This meta-analysis demonstrates that gray matter volume decreases in T1DM patients were mainly locates in the cortical regions and cerebellum.
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Affiliation(s)
- Jia Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Wenliang Fan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yuxi Jia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xiaoyun Su
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Wenjun Wu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xi Long
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xin Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Jie Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Wengang Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | | | - Qiyong Gong
- Department of Radiology, Huaxi MR Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Haojun Shi
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
- *Correspondence: Haojun Shi
| | - Qing Zhu
- Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
- Qing Zhu
| | - Jing Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
- Jing Wang
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26
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Voxel-based morphometry reveals regional reductions of gray matter volume in school-aged children with short-term type 1 diabetes mellitus. Neuroreport 2019; 30:516-521. [PMID: 30913134 DOI: 10.1097/wnr.0000000000001238] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Follow-up observation is needed for type 1 diabetes mellitus (T1DM) children due to the potential injury to the brain. However, the effect of short-term T1DM on gray matter in school-aged children is still unclear. This study aimed to evaluate gray matter volume (GMV) changes and their relationships with clinical variables in school-aged children with short-term T1DM. Twenty-one school-aged T1DM children were compared with 21 control patients, matched for sex and age. T1-weighted gradient echo three-dimensional MRI was performed using a 3.0-Tesla scanner and the resulting images were processed with FSL software to assess the difference in GMV between the two groups. The children with T1DM presented with decreased GMV in the left middle temporal gyrus (LMTG), the right postcentral gyrus, and the left triangular part of the frontal inferior gyrus (LTP-FIG). No significant changes in intelligence quotient (IQ) were found between the T1DM and control groups. In T1DM patients, there was a significant positive correlation between the GMV of LMTG and full-scale IQ or linguistic IQ. In addition, an increased glycosylated hemoglobin level was negatively correlated with reduced GMV in the LMTG and LTP-FIG in the T1DM group. These findings suggest that short-term T1DM could lead to regional structural brain deficits in school-aged children. The GMV of the LMTG may affect IQ, and poor recent glycemic control may have an adverse effect on GMV in the LMTG and LTP-FIG in T1DM children.Video abstract: http://links.lww.com/WNR/A506.
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27
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Hawks Z, Hood AM, Lerman-Sinkoff DB, Shimony JS, Rutlin J, Lagoni D, Grange DK, White DA. White and gray matter brain development in children and young adults with phenylketonuria. NEUROIMAGE-CLINICAL 2019; 23:101916. [PMID: 31491833 PMCID: PMC6627563 DOI: 10.1016/j.nicl.2019.101916] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 05/09/2019] [Accepted: 06/29/2019] [Indexed: 12/27/2022]
Abstract
Phenylketonuria (PKU) is a recessive disorder characterized by disruption in the metabolism of the amino acid phenylalanine (Phe). Prior research indicates that individuals with PKU have substantial white matter (WM) compromise. Much less is known about gray matter (GM) in PKU, but a small body of research suggests volumetric differences compared to controls. To date, developmental trajectories of GM structure in individuals with PKU have not been examined, nor have trajectories of WM and GM been examined within a single study. To address this gap in the literature, we compared longitudinal brain development over a three-year period in individuals with PKU (n = 35; 18 male) and typically-developing controls (n = 71; 35 male) aged 7–21 years. Using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI), we observed whole-brain and regional WM differences between individuals with PKU and controls, which were often exacerbated with increasing age. In marked contrast with trajectories of WM development, trajectories of GM development did not differ between individuals with PKU and controls, indicating that neuropathology in PKU is more prominent in WM than GM. Within individuals with PKU, mediation analyses revealed that whole-brain mean diffusivity (MD) and regional MD in the corpus callosum and centrum semiovale mediated the relationship between dietary treatment compliance (i.e., Phe control) and executive abilities, suggesting a plausible neurobiological mechanism by which Phe control may influence cognitive outcomes. Our findings clarify the specificity, timing, and cognitive consequences of whole-brain and regional WM pathology, with implications for treatment and research in PKU.
Individuals with PKU exhibited widespread, age-related white matter compromise. Developmental trajectories of gray matter were comparable for PKU and controls. Within PKU, white matter compromise influenced cognitive outcomes.
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Affiliation(s)
- Zoë Hawks
- Department of Psychological & Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO, United States.
| | - Anna M Hood
- Department of Psychological & Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO, United States.
| | - Dov B Lerman-Sinkoff
- Department of Psychological & Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO, United States; Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
| | - Joshua S Shimony
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Jerrel Rutlin
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Daniel Lagoni
- Department of Psychological & Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO, United States
| | - Dorothy K Grange
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
| | - Desirée A White
- Department of Psychological & Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO, United States; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
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Kahkoska AR, Crandell J, Driscoll KA, Kichler JC, Seid M, Mayer-Davis EJ, Maahs DM. Dysglycemia among youth with type 1 diabetes and suboptimal glycemic control in the Flexible Lifestyle Empowering Change trial. Pediatr Diabetes 2019; 20:180-188. [PMID: 30536572 PMCID: PMC6367932 DOI: 10.1111/pedi.12805] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 11/30/2018] [Accepted: 12/04/2018] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To examine the prevalence and correlates of non-severe hypoglycemia among adolescents with type 1 diabetes and suboptimal glycemic control, an understudied topic in this group. METHODS Seven days of blinded continuous glucose monitor data were analyzed in 233 adolescents at baseline of the Flexible Lifestyle Empowering Change trial (13-16 years, type 1 diabetes duration >1 year, and hemoglobin A1c [HbA1c] 8-13% [64-119 mmol]). Incidence of clinical hypoglycemia (54-69 mg/dL) and clinically serious hypoglycemia (<54 mg/dL) was defined as number of episodes ≥15 minutes. Logistic regression modeling was used to determine the correlates of long duration of hypoglycemia, categorized by median split among those who experienced hypoglycemia. RESULTS The sample was 76.1% non-Hispanic white, 49.8% female, age = 14.9 ± 1.1 years, diabetes duration = 6.4 ± 3.7 years, and HbA1c = 9.6 ± 1.2% (81 ± 13 mmol/mol). Over 7 days, 79.4% of youth experienced ≥1 hypoglycemic episodes of <70 mg/dL, and 55.4% of youth experienced ≥1 hypoglycemic episodes of <54 mg/dL. Among all adolescents, the median duration of clinical hypoglycemia and clinically serious hypoglycemia was 21.9 (range 0-250.2) and 4.3 (range 0-209.7) minutes/day, respectively. Long duration of clinical hypoglycemia (range 1.8-17.4% time overall) and clinically serious hypoglycemia (range 1.2-14.6% time overall) was associated with older age and decreasing HbA1c. Long duration of clinically serious hypoglycemia also was associated with insulin pump use. CONCLUSIONS Almost 80% of adolescents with elevated HbA1c had an episode of clinical hypoglycemia, and >50% had clinically serious hypoglycemia in a week. Increased education alongside access to emerging diabetes technologies may help to prevent hypoglycemia while improving glycemic control.
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Affiliation(s)
- Anna R. Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Jamie Crandell
- School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Kimberly A. Driscoll
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045
| | - Jessica C. Kichler
- Cincinnati Children’s Hospital Medical Center, University of Cincinnati Medical School, Cincinnati, OH
45229
| | - Michael Seid
- Cincinnati Children’s Hospital Medical Center, University of Cincinnati Medical School, Cincinnati, OH
45229
| | - Elizabeth J. Mayer-Davis
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - David M. Maahs
- Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA 94305
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29
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He J, Li S, Liu F, Zheng H, Yan X, Xie Y, Li X, Zhou Z, Zhu X. Glycemic control is related to cognitive dysfunction in Chinese children with type 1 diabetes mellitus. J Diabetes 2018; 10:948-957. [PMID: 29671962 DOI: 10.1111/1753-0407.12775] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 03/12/2018] [Accepted: 04/15/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) is considered a risk factor for the development of cognitive difficulties. The present study examined whether the cognitive performance of Chinese children with T1DM differs from that of healthy control (HC) children, and whether cognitive dysfunction is related to glycemic control. METHODS Using a cross-sectional design, cognitive tests were administered, including general intelligence tests, to pediatric T1DM patients (n = 105) and HCs (n = 90). The effects of specific diabetes-related variables, including an earlier diabetes onset (<7 years of age), severe hypoglycemia, chronic hyperglycemia, and diabetic ketoacidosis (DKA), on cognitive outcomes were examined. RESULTS The T1DM group had lower IQ (P = 0.001) and attention (P = 0.018) scores than the HC group. Among T1DM patients, a younger age of diabetes onset was related to poorer performance on the visuospatial perception test (P = 0.017) and delayed logical memory (P = 0.012). Greater exposure to hyperglycemia over time was associated with lower visuospatial perception (P = 0.029), and DKA had a negative effect on the IQ score (P = 0.024). Compared with the late severe hypoglycemia subgroup, the early severe hypoglycemia subgroup (<7 years old) performed worse on both immediate (P = 0.001) and delayed (P = 0.049) visual memory tests. CONCLUSIONS Chinese children with T1DM showed deficits in IQ and attention. Earlier age of diabetes onset, chronic hyperglycemia, and DKA affected particular cognitive domains. Early exposure to severe hypoglycemia had negative effects on visual memory.
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Affiliation(s)
- Jing He
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute of Central South University, Changsha, China
| | - Shichen Li
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute of Central South University, Changsha, China
| | - Fang Liu
- Division of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Hong Zheng
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute of Central South University, Changsha, China
| | - Xiang Yan
- Institute of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yuting Xie
- Institute of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xia Li
- Institute of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Zhiguang Zhou
- Institute of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiongzhao Zhu
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute of Central South University, Changsha, China
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30
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Abraham MB, Jones TW, Naranjo D, Karges B, Oduwole A, Tauschmann M, Maahs DM. ISPAD Clinical Practice Consensus Guidelines 2018: Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatr Diabetes 2018; 19 Suppl 27:178-192. [PMID: 29869358 DOI: 10.1111/pedi.12698] [Citation(s) in RCA: 145] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/28/2018] [Indexed: 12/23/2022] Open
Affiliation(s)
- Mary B Abraham
- Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Australia.,Children's Diabetes Centre, Telethon Kids Institute, The University of Western Australia, Perth, Australia.,Division of Paediatrics, Medical School, The University of Western Australia, Perth, Australia
| | - Timothy W Jones
- Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Australia.,Children's Diabetes Centre, Telethon Kids Institute, The University of Western Australia, Perth, Australia.,Division of Paediatrics, Medical School, The University of Western Australia, Perth, Australia
| | - Diana Naranjo
- Division of Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California
| | - Beate Karges
- Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | | | - Martin Tauschmann
- Wellcome Trust-MRC Institute of Metabolic Science, Department of Paediatrics, University of Cambridge, Cambridge, UK
| | - David M Maahs
- Division of Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California
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31
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Bratina N, Forsander G, Annan F, Wysocki T, Pierce J, Calliari LE, Pacaud D, Adolfsson P, Dovč K, Middlehurst A, Goss P, Goss J, Janson S, Acerini CL. ISPAD Clinical Practice Consensus Guidelines 2018: Management and support of children and adolescents with type 1 diabetes in school. Pediatr Diabetes 2018; 19 Suppl 27:287-301. [PMID: 30084519 DOI: 10.1111/pedi.12743] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 07/27/2018] [Indexed: 12/13/2022] Open
Affiliation(s)
- Natasa Bratina
- Department of Endocrinology, Diabetes & Metabolism, University Children's Hospital, Ljubljana, Slovenia
| | - Gun Forsander
- The Queen Silvia Children's Hospital and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Tim Wysocki
- Center for Healthcare Delivery Science, Nemours Children Health System, Orlando, Florida
| | - Jessica Pierce
- Center for Healthcare Delivery Science, Nemours Children Health System, Orlando, Florida
| | - Luis E Calliari
- Department of Pediatrics, Santa Casa de Sao Paulo School of Medical Sciences, Brazil
| | - Danièle Pacaud
- Division of Diabetes and Endocrinology, Alberta Children's Hospital, Department of Paediatrics, University of Calgary, Calgary, Canada
| | - Peter Adolfsson
- Department of Pediatrics, The Hospital of Halland, Kungsbacka and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Klemen Dovč
- Department of Endocrinology, Diabetes & Metabolism, University Children's Hospital, Ljubljana, Slovenia
| | - Angie Middlehurst
- International Diabetes Federation Life for a Child Program, Sydney, Australia
| | - Peter Goss
- Team Diabetes, Geelong, Victoria, Australia
| | | | - Staffan Janson
- Department of Women´s and Children´s Health, Uppsala University, Uppsala, Sweden
| | - Carlo L Acerini
- Department of Paediatrics, University of Cambridge, Cambridge, UK
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32
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DiMeglio LA, Acerini CL, Codner E, Craig ME, Hofer SE, Pillay K, Maahs DM. ISPAD Clinical Practice Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes 2018; 19 Suppl 27:105-114. [PMID: 30058221 DOI: 10.1111/pedi.12737] [Citation(s) in RCA: 382] [Impact Index Per Article: 54.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Accepted: 07/27/2018] [Indexed: 12/23/2022] Open
Affiliation(s)
- Linda A DiMeglio
- Division of Pediatric Endocrinology and Diabetology and Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
| | - Carlo L Acerini
- Department of Paediatrics, University of Cambridge, Cambridge, UK
| | - Ethel Codner
- Institute of Maternal and Child Research (IDMI), School of Medicine, Universidad de Chile, Santiago, Chile
| | - Maria E Craig
- Institute of Endocrinology and Diabetes, Children's Hospital at Westmead, Sydney, Australia
| | - Sabine E Hofer
- Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria
| | | | - David M Maahs
- Division of Pediatric Endocrinology, Stanford University, Stanford, California
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33
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Aalders J, Hartman E, Nefs G, Nieuwesteeg A, Hendrieckx C, Aanstoot H, Winterdijk P, van Mil E, Speight J, Pouwer F. Mindfulness and fear of hypoglycaemia in parents of children with Type 1 diabetes: results from Diabetes MILES Youth - The Netherlands. Diabet Med 2018; 35:650-657. [PMID: 29385240 PMCID: PMC5947298 DOI: 10.1111/dme.13594] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/25/2018] [Indexed: 01/10/2023]
Abstract
AIMS To identify the sociodemographic and clinical correlates of fear of hypoglycaemia among parents of children (aged 4-18 years) with Type 1 diabetes and to examine the relationships between parental fear of hypoglycaemia, mindfulness and mindful parenting. METHODS Sociodemographic, self-reported clinical and psychological data were extracted from the cross-sectional Diabetes MILES Youth - The Netherlands dataset. Questionnaires included the Hypoglycaemia Fear Survey - Parent Worry (parental fear of hypoglycaemia), the Freiburg Mindfulness Inventory - Short version (mindfulness) and the Interpersonal Mindfulness in Parenting Scale (mindful parenting). RESULTS A total of 421 parents (359 mothers) participated. Hierarchical linear regression analyses showed that greater parental fear of hypoglycaemia was related to younger parental age, low educational level, non-Dutch nationality, more frequent blood glucose monitoring, and less general mindfulness. Adding mindful parenting to the model negated the previous contribution of general mindfulness. In this model, lower mindful parenting was related to greater parental fear of hypoglycaemia. In particular, parents with an increased ability to be less judgemental of themselves as parents and less reactive to emotions within parenting interactions reported less fear of hypoglycaemia. In total, 21% of the variance in parental fear of hypoglycaemia was explained. CONCLUSION Parental fear of hypoglycaemia was associated largely with parental characteristics, including non-modifiable sociodemographics (i.e. age, education, nationality) and modifiable psychological factors (i.e. mindful parenting). These findings suggest that it is important to further explore mindfulness-based interventions for parents to reduce fear of hypoglycaemia next to interventions to reduce hypoglycaemia.
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Affiliation(s)
- J. Aalders
- Department of Medical and Clinical PsychologyCenter of Research on Psychological and Somatic Dsorders (CoRPS)Tilburg UniversityTilburgThe Netherlands
| | - E. Hartman
- Department of Medical and Clinical PsychologyCenter of Research on Psychological and Somatic Dsorders (CoRPS)Tilburg UniversityTilburgThe Netherlands
| | - G. Nefs
- Department of Medical and Clinical PsychologyCenter of Research on Psychological and Somatic Dsorders (CoRPS)Tilburg UniversityTilburgThe Netherlands
- Diabeter Centre for Pediatric and Adolescent Diabetes Care and ResearchRotterdamThe Netherlands
- Department of Medical PsychologyRadboud University Medical CentreRadboud Institute for Health ScienceNijmegenThe Netherlands
| | - A. Nieuwesteeg
- Department of Medical and Clinical PsychologyCenter of Research on Psychological and Somatic Dsorders (CoRPS)Tilburg UniversityTilburgThe Netherlands
- Máxima Medical CentreVeldhovenThe Netherlands
| | - C. Hendrieckx
- School of PsychologyDeakin UniversityGeelong, MelbourneAustralia
- Australian Centre for Behavioural Research in DiabetesDiabetes VictoriaMelbourneAustralia
| | - H.‐J. Aanstoot
- Diabeter Centre for Pediatric and Adolescent Diabetes Care and ResearchRotterdamThe Netherlands
| | - P. Winterdijk
- Diabeter Centre for Pediatric and Adolescent Diabetes Care and ResearchRotterdamThe Netherlands
| | - E. van Mil
- Kidz&Ko, Jeroen Bosch Hospital‘s‐HertogenboschThe Netherlands
| | - J. Speight
- School of PsychologyDeakin UniversityGeelong, MelbourneAustralia
- Australian Centre for Behavioural Research in DiabetesDiabetes VictoriaMelbourneAustralia
- AHP ResearchHornchurchUK
- Department of PsychologyUniversity of Southern DenmarkOdenseDenmark
| | - F. Pouwer
- School of PsychologyDeakin UniversityGeelong, MelbourneAustralia
- Department of PsychologyUniversity of Southern DenmarkOdenseDenmark
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34
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Autoimmune comorbidities in multiple sclerosis: what is the influence on brain volumes? A case-control MRI study. J Neurol 2018; 265:1096-1101. [PMID: 29508133 DOI: 10.1007/s00415-018-8811-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 02/22/2018] [Accepted: 02/24/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Several studies indicated that multiple sclerosis (MS) is frequently associated with other autoimmune diseases. However, it is little known if the coexistence of these conditions may influence the radiologic features of MS, and in particular the brain volumes. OBJECTIVES To evaluate the effect of autoimmune comorbidities on brain atrophy in a large case-control MS population. METHODS A group of MS patients affected by a second autoimmune disorder, and a control MS group without any comorbidity, were recruited. Patients underwent a brain MRI and volumes of whole brain (WB), white matter (WM), and gray matter (GM) with cortical GM were estimated by SIENAX. RESULTS The sample included 286 MS patients, of which 30 (10.5%) subjects with type 1 diabetes (T1D), 53 (18.5%) with autoimmune thyroiditis (AT) and 4 (0.1%) with celiac disease. Multiple regression analysis found an association between T1D and lower GM (p = 0.038) and cortical GM (p = 0.036) volumes, independent from MS clinical features and related to T1D duration (p < 0.01), while no association was observed with AT and celiac disease. CONCLUSIONS Our data support the importance of considering T1D as possible factors influencing the brain atrophy in MS. Further studies are needed to confirm our data and to clarify the underlying mechanisms.
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35
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Hoekel J, Narayanan A, Rutlin J, Lugar H, Al-Lozi A, Hershey T, Tychsen L. Visual pathway function and structure in Wolfram syndrome: patient age, variation and progression. BMJ Open Ophthalmol 2018; 3:e000081. [PMID: 29657975 PMCID: PMC5895968 DOI: 10.1136/bmjophth-2017-000081] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 10/30/2017] [Accepted: 11/09/2017] [Indexed: 01/24/2023] Open
Abstract
Background/aims To report alterations in visual acuity and visual pathway structure over an interval of 1–3 years in a cohort of children, adolescents and young adults who have Wolfram syndrome (WFS) and to describe the range of disease severity evident in patients with WFS whose ages differed by as much as 20 years at first examination. Methods Annual, prospective ophthalmological examinations were performed in conjunction with retinal nerve fibre layer (RNFL) analysis. Diffusion tensor MRI-derived fractional anisotropy was used to assess the microstructural integrity of the optic radiations (OR FA). Results Mean age of the 23 patients with WFS in the study was 13.8 years (range 5–25 years). Mean log minimum angle resolution visual acuity was 0.66 (20/91). RNFL thickness was subnormal in even the youngest patients with WFS. Average RNFL thickness in patients with WFS was 57±8 µ or ~40% thinner than that measured in normal (94±10 µ) children and adolescents (P<0.01). Lower OR FA correlated with worse visual acuity (P=0.006). Subsequent examinations showed declines (P<0.05) in visual acuity, RNFL thickness and OR FA at follow-up intervals of 12–36 months. However, a wide range of disease severity was evident across ages: some of the youngest patients at their first examination had deficits more severe than the oldest patients. Conclusion The genetic mutation of WFS causes damage to both pregeniculate and postgeniculate regions of the visual pathway. The damage is progressive. The decline in visual pathway structure is accompanied by declines of visual function. Disease severity differs widely in individual patients and cannot be predicted from their age.
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Affiliation(s)
- James Hoekel
- Department of Ophthalmology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri, USA
| | - Anagha Narayanan
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Jerrel Rutlin
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Heather Lugar
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Amal Al-Lozi
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Tamara Hershey
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.,Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.,Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Lawrence Tychsen
- Department of Ophthalmology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri, USA.,Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri, USA
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36
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Hosseini SMH, Mazaika P, Mauras N, Buckingham B, Weinzimer SA, Tsalikian E, White NH, Reiss AL. Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes. Hum Brain Mapp 2018; 37:4034-4046. [PMID: 27339089 DOI: 10.1002/hbm.23293] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Revised: 05/24/2016] [Accepted: 06/12/2016] [Indexed: 02/05/2023] Open
Abstract
Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization-an architecture that is simultaneously highly segregated and integrated-the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034-4046, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- S M Hadi Hosseini
- Department of Psychiatry and Behavioral Sciences, Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, California.
| | - Paul Mazaika
- Department of Psychiatry and Behavioral Sciences, Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, California
| | - Nelly Mauras
- Division of Endocrinology, Nemours Children's Health System, Jacksonville, Florida
| | - Bruce Buckingham
- Division of Pediatric Endocrinology, Stanford University, Stanford, California
| | - Stuart A Weinzimer
- Division of Pediatric Endocrinology, Yale University, New Haven, Connecticut
| | - Eva Tsalikian
- Division of Pediatric Endocrinology, University of Iowa, Iowa City, Iowa
| | - Neil H White
- Department of Pediatrics, Washington University, St. Louis, Missouri
| | - Allan L Reiss
- Department of Psychiatry and Behavioral Sciences, Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, California
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Lee A, Shen M, Qiu A. Psychiatric polygenic risk associates with cortical morphology and functional organization in aging. Transl Psychiatry 2017; 7:1276. [PMID: 29225336 PMCID: PMC5802582 DOI: 10.1038/s41398-017-0036-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 08/04/2017] [Accepted: 09/07/2017] [Indexed: 01/23/2023] Open
Abstract
Common brain abnormalities in cortical morphology and functional organization are observed in psychiatric disorders and aging, reflecting shared genetic influences. This preliminary study aimed to examine the contribution of a polygenetic risk for psychiatric disorders (PRScross) to aging brain and to identify molecular mechanisms through the use of multimodal brain images, genotypes, and transcriptome data. We showed age-related cortical thinning in bilateral inferior frontal cortex (IFC) and superior temporal gyrus and alterations in the functional connectivity between bilateral IFC and between right IFC and right inferior parietal lobe as a function of PRScross. Interestingly, the genes in PRScross, that contributed most to aging neurodegeneration, were expressed in the functioanlly connected cortical regions. Especially, genes identified through the genotype-functional connectivity association analysis were commonly expressed in both cortical regions and formed strong gene networks with biological processes related to neural plasticity and synaptogenesis, regulated by glutamatergic and GABAergic transmission, neurotrophin signaling, and metabolism. This study suggested integrating genotype and transcriptome with neuroimage data sheds new light on the mechanisms of aging brain.
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Affiliation(s)
- Annie Lee
- 0000 0001 2180 6431grid.4280.eDepartment of Biomedical Engineering, National University of Singapore, Singapore, 117576 Singapore
| | - Mojun Shen
- 0000 0004 0637 0221grid.185448.4Singapore Institute for Clinical Sciences, The Agency for Science, Technology and Research, Singapore, 117609 Singapore
| | - Anqi Qiu
- Department of Biomedical Engineering, National University of Singapore, Singapore, 117576, Singapore. .,Singapore Institute for Clinical Sciences, The Agency for Science, Technology and Research, Singapore, 117609, Singapore. .,Clinical Imaging Research Center, National University of Singapore, Singapore, 117456, Singapore.
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Siller AF, Lugar H, Rutlin J, Koller JM, Semenkovich K, White NH, Arbelaez AM, Shimony J, Hershey T. Severity of clinical presentation in youth with type 1 diabetes is associated with differences in brain structure. Pediatr Diabetes 2017; 18:686-695. [PMID: 27488913 PMCID: PMC5290262 DOI: 10.1111/pedi.12420] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 06/30/2016] [Accepted: 07/01/2016] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVE Differences in cognition and brain structure have been found in youth with type 1 diabetes compared with controls, even after relatively short disease duration. To determine whether severity of clinical presentation contributes to these differences, we obtained structural magnetic resonance imaging (MRI) scans in youth ages 7-17 who were either newly diagnosed with type 1 diabetes (<3.5 months from diagnosis, n = 46) or a sibling without diabetes (n = 28). RESEARCH DESIGN AND METHODS Severity of presentation was measured by the presence of diabetic ketoacidosis (DKA) and degree of hyperglycemia exposure [hemoglobin A1c (HbA1c)] at diagnosis. MRI were obtained using T1-weighted, T2-weighted, and diffusion-weighted sequences. RESULTS Within the group with type 1 diabetes, 12 subjects presented in DKA and 34 did not. After controlling for age, sex, and multiple comparisons, the type 1 diabetes group had lower volume in the left temporal-parietal-occipital cortex compared with controls. Within the type 1 diabetes group, DKA at presentation was associated with lower radial, axial, and mean diffusivity (MD) throughout major white matter tracts and higher HbA1c was associated with lower hippocampal, thalamic, and cerebellar white matter volumes, lower right posterior parietal cortical thickness, and greater right occipital cortical thickness. CONCLUSION These data suggest that severity of clinical presentation is an important factor in predicting brain structural differences in youth with type 1 diabetes approximately 3 months after diagnosis.
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Affiliation(s)
| | | | | | | | | | - Neil H. White
- Department of Pediatrics,Department of Medicine,St. Louis Children’s Hospital
| | | | | | - Tamara Hershey
- Department of Psychiatry,Department of Radiology,Department of Neurology
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39
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Continuous subcutaneous insulin infusion in children less than 6 years-old: Long-term progress. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2017. [DOI: 10.1016/j.anpede.2016.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Colino E, Martín Frías M, Roldán B, Álvarez MÁ, Yelmo R, Barrio R. Infusión subcutánea continua de insulina en menores de 6 años: evolución a largo plazo. An Pediatr (Barc) 2017; 87:276-283. [DOI: 10.1016/j.anpedi.2016.12.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 12/18/2016] [Accepted: 12/21/2016] [Indexed: 12/20/2022] Open
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Moran C, Beare R, Phan T, Starkstein S, Bruce D, Romina M, Srikanth V. Neuroimaging and its Relevance to Understanding Pathways Linking Diabetes and Cognitive Dysfunction. J Alzheimers Dis 2017; 59:405-419. [DOI: 10.3233/jad-161166] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Chris Moran
- Department of Medicine, Peninsula Health, Peninsula Clinical School, Monash University, Melbourne, VIC, Australia
- Aged Care Services, Caulfield Hospital, Alfred Health, Melbourne, VIC, Australia
- Stroke and Ageing Research Group, Vascular Brain Ageing Division, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
- Neurosciences, Monash Medical Centre, Monash Health, Melbourne, VIC, Australia
| | - Richard Beare
- Department of Medicine, Peninsula Health, Peninsula Clinical School, Monash University, Melbourne, VIC, Australia
- Stroke and Ageing Research Group, Vascular Brain Ageing Division, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
- Neurosciences, Monash Medical Centre, Monash Health, Melbourne, VIC, Australia
| | - Thanh Phan
- Stroke and Ageing Research Group, Vascular Brain Ageing Division, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
- Neurosciences, Monash Medical Centre, Monash Health, Melbourne, VIC, Australia
| | - Sergio Starkstein
- Fremantle Hospital, WA, Australia
- University of Western Australia, WA, Australia
| | - David Bruce
- Fremantle Hospital, WA, Australia
- University of Western Australia, WA, Australia
| | - Mizrahi Romina
- Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
| | - Velandai Srikanth
- Department of Medicine, Peninsula Health, Peninsula Clinical School, Monash University, Melbourne, VIC, Australia
- Stroke and Ageing Research Group, Vascular Brain Ageing Division, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
- Neurosciences, Monash Medical Centre, Monash Health, Melbourne, VIC, Australia
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Guàrdia-Olmos J, Gallardo-Moreno GB, Gudayol-Ferré E, Peró-Cebollero M, González-Garrido AA. Effect of verbal task complexity in a working memory paradigm in patients with type 1 diabetes. A fMRI study. PLoS One 2017; 12:e0178172. [PMID: 28582399 PMCID: PMC5459425 DOI: 10.1371/journal.pone.0178172] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 05/08/2017] [Indexed: 12/12/2022] Open
Abstract
Type 1 diabetes (T1D) is commonly diagnosed in childhood and adolescence, and the developing brain has to cope with its deleterious effects. Although brain adaptation to the disease may not result in evident cognitive dysfunction, the effects of T1D on neurodevelopment could alter the pattern of BOLD fMRI activation. The aim of this study was to explore the neural BOLD activation pattern in patients with T1D versus that of healthy matched controls while performing two visuospatial working memory tasks, which included a pair of assignments administered through a block design. In the first task (condition A), the subjects were shown a trial sequence of 3 or 4 white squares positioned pseudorandomly around a fixation point on a black background. After a fixed delay, a second corresponding sequence of 3 or 4 red squares was shown that either resembled (direct, 50%) or differed from (50%) the previous stimulation order. The subjects were required to press one button if the two spatial sequences were identical or a second button if they were not. In condition B, the participants had to determine whether the second sequence of red squares appeared in inverse order (inverse, 50%) or not (50%) and respond by pressing a button. If the latter sequence followed an order distinct from the inverse sequence, the subjects were instructed to press a different button. Sixteen patients with normal IQ and without diabetes complications and 16 healthy control subjects participated in the study. In the behavioral analysis, there were no significant differences between the groups in the pure visuo-spatial task, but the patients with diabetes exhibited poorer performance in the task with verbal stimuli (p < .001). However, fMRI analyses revealed that the patients with T1D showed significantly increased activation in the prefrontal inferior cortex, subcortical regions and the cerebellum (in general p < .001). These different activation patterns could be due to adaptive compensation mechanisms that are devoted to improving efficiency while solving more complex cognitive tasks.
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Affiliation(s)
- Joan Guàrdia-Olmos
- Facultat de Psicologia, Universitat de Barcelona, Institut de Neurociències. Institute of Complex Systems (UBICS), Passeig de la Vall d’Hebron 171, Barcelona, Spain
| | - Geisa B. Gallardo-Moreno
- Instituto de Neurociencias, Universidad de Guadalajara, Francisco de Quevedo 180, Colonia Arcos Vallarta, Guadalajara, Jalisco, Mexico
| | - Esteve Gudayol-Ferré
- Facultad de Psicología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico
| | - Maribel Peró-Cebollero
- Facultat de Psicologia, Universitat de Barcelona, Institut de Neurociències. Institute of Complex Systems (UBICS), Passeig de la Vall d’Hebron 171, Barcelona, Spain
| | - Andrés A. González-Garrido
- Instituto de Neurociencias, Universidad de Guadalajara, Francisco de Quevedo 180, Colonia Arcos Vallarta, Guadalajara, Jalisco, Mexico
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Meng Y, Wang W, Kang J, Wang X, Sun L. Role of the PI3K/AKT signalling pathway in apoptotic cell death in the cerebral cortex of streptozotocin-induced diabetic rats. Exp Ther Med 2017; 13:2417-2422. [PMID: 28565857 DOI: 10.3892/etm.2017.4259] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 01/26/2017] [Indexed: 12/18/2022] Open
Abstract
Diabetes mellitus is associated with cognitive dysfunction. Numerous previous studies have shown that type 1 diabetes-induced hyperglycaemia causes structural brain damage, such as a decrease in whole-brain grey matter. The impact of diabetes mellitus on the cerebral cortex is poorly understood and requires further clarification. In the present study, diabetes was induced via an intraperitoneal injection of streptozotocin (50 mg/kg). Hematoxylin and eosin (H&E) staining was performed to detect the morphological changes in the cerebral cortex, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining was used to detect neuronal apoptosis and western blotting was performed to determine protein expression levels. Nine weeks after the induction of diabetes, the body weight was significantly lower and the blood glucose levels were significantly higher in the diabetic rats than in the control rats (P<0.05). H&E staining revealed nuclear chromatin condensation and cytoplasmic shrinkage in the cerebral cortex of the diabetic rats and TUNEL staining further indicated apoptotic changes in the cerebral cortex of the diabetic rats. The ratio of B-cell lymphoma 2 (Bcl-2) -associated X protein/Bcl-2 and the expression of cytochrome c and activated caspase-3 (cleaved caspase-3) were significantly increased, whereas the ratio of phosphorylated AKT/AKT was significantly decreased in the diabetic rats compared with that in the control rats (P<0.05). Taken together, these results suggested that diabetes mellitus may induce neuronal apoptosis in the cerebral cortex by downregulating AKT phosphorylation.
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Affiliation(s)
- Yan Meng
- Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Weiwei Wang
- Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Jinsong Kang
- Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Xinxue Wang
- Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Liankun Sun
- Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
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Pourabbasi A, Tehrani-Doost M, Qavam SE, Arzaghi SM, Larijani B. Association of diabetes mellitus and structural changes in the central nervous system in children and adolescents: a systematic review. J Diabetes Metab Disord 2017; 16:10. [PMID: 28271054 PMCID: PMC5335845 DOI: 10.1186/s40200-017-0292-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2017] [Accepted: 02/10/2017] [Indexed: 12/15/2022]
Abstract
Background The relationship between diabetes and academic performance have been of great interest to researchers during the year to date. Many studies have been conducted to discover this relationship during three recent decades. But, evaluation of the structural changes of brain in the context of diabetes is of paramount importance especially in children and adolescents. Methods This study is a systematic review conducted to investigate the structural changes in the central nervous system in children and adolescents living with diabetes. Among about 500 papers published in this area in Pubmed and SCOPUS, 13 articles in the field of assessing structural changes in the central nervous system in children and adolescents with diabetes mellitus were entered into the evaluation process. Results As can be seen in these studies, a huge proportion of structures of the central nervous system have been affected by diabetes that include different areas of gray and white matters. In the majority of these studies, it has become clear that high glycemic changes, especially recurrent hyperglycemic attacks are very seriously associated with structural changes in the brain. Conclusion It seems the findings of this review can positively aid other researchers to develop medical guidelines to prevent or resolve the brain changes in central nervous structure and consequently cognitive impairments in children and adolescents.
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Affiliation(s)
- Ata Pourabbasi
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Tehrani-Doost
- Department of Psychiatry, Rouzbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Soqra Ebrahimi Qavam
- Faculty of psychology and education, Allameh Tabataba'ee university, Tehran, Iran
| | - Seyed Masoud Arzaghi
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Shari'ati Hospital, North Kargar St., Tehran, Iran
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Hamed SA. Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications. Expert Rev Clin Pharmacol 2017; 10:409-428. [PMID: 28276776 DOI: 10.1080/17512433.2017.1293521] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Sherifa A. Hamed
- Department of Neurology and Psychiatry, Assiut University Hospital , Assiut, Egypt
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Abstract
IN BRIEF In children and adolescents with type 1 diabetes, exposure to glycemic extremes (severe hypoglycemia, chronic hyperglycemia, and diabetic ketoacidosis) overlaps with the time period of most active brain and cognitive development, leading to concerns that these children are at risk for cognitive side effects. This article summarizes the existing literature examining the impact of glycemic extremes on cognitive function and brain structure in youth with type 1 diabetes and points out areas for future research.
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Affiliation(s)
- Allison Cato
- Nemours Children’s Health System, Jacksonville, FL
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Parkin CG, Homberg A, Hinzmann R. 9th Annual Symposium on Self-Monitoring of Blood Glucose, April 28-30, 2016, Madrid, Spain. Diabetes Technol Ther 2016; 18:727-747. [PMID: 27710038 DOI: 10.1089/dia.2016.0336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
International experts in the field of diabetes and diabetes technology met in Madrid, Spain, for the 9th Annual Symposium on Self-Monitoring of Blood Glucose. The goal of these meetings is to establish a global network of experts, thus facilitating new collaborations and research projects to improve the lives of people with diabetes. The 2016 meeting comprised a comprehensive scientific program, parallel interactive workshops, and two keynote lectures.
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McNeilly AD, Gallagher JR, Dinkova-Kostova AT, Hayes JD, Sharkey J, Ashford MLJ, McCrimmon RJ. Nrf2-Mediated Neuroprotection Against Recurrent Hypoglycemia Is Insufficient to Prevent Cognitive Impairment in a Rodent Model of Type 1 Diabetes. Diabetes 2016; 65:3151-60. [PMID: 27411381 DOI: 10.2337/db15-1653] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 07/07/2016] [Indexed: 11/13/2022]
Abstract
It remains uncertain whether recurrent nonsevere hypoglycemia (Hypo) results in long-term cognitive impairment in type 1 diabetes (T1D). This study tested the hypothesis that specifically in the T1D state, Hypo leads to cognitive impairment via a pathological response to oxidative stress. Wild-type (Control) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) null mice were studied. Eight groups of mice (Control and Nrf2(-/-) ± T1D and ± Hypo) were subject to recurrent, twice-weekly, insulin or saline injections over 4 weeks, after which cognitive function was assessed and brain tissue analyzed. Recurrent moderate hypoglycemia in T1D, but not Control, mice significantly impaired cognitive performance, and this was associated with hippocampal oxidative damage and inflammation despite an enhanced expression of Nrf2 and its target genes Hmox1 and Nqo1 In Nrf2(-/-) mice, both T1D and Hypo independently resulted in impaired cognitive performance, and this was associated with oxidative cell damage and marked inflammation. Together, these data suggest that Hypo induces an Nrf2-dependent antioxidant response in the hippocampus, which counteracts oxidative damage. However, in T1D, this neuroprotective mechanism is insufficient to prevent neuronal oxidative damage, resulting in chronic deficits in working and long-term memory.
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Affiliation(s)
- Alison D McNeilly
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K
| | - Jennifer R Gallagher
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K
| | - Albena T Dinkova-Kostova
- Division of Cancer Research, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K
| | - John D Hayes
- Division of Cancer Research, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K
| | - John Sharkey
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K. Division of Neuroscience, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K
| | - Michael L J Ashford
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K
| | - Rory J McCrimmon
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, Dundee, U.K.
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Moulton CD, Costafreda SG, Horton P, Ismail K, Fu CHY. Meta-analyses of structural regional cerebral effects in type 1 and type 2 diabetes. Brain Imaging Behav 2016; 9:651-62. [PMID: 25563229 DOI: 10.1007/s11682-014-9348-2] [Citation(s) in RCA: 108] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Diabetes is associated with macrovascular and microvascular complications and is a major risk factor for neurological and psychiatric disorders, such as dementia and depression. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) have distinct etiologies and pathophysiological effects while sharing a common endpoint of persistent hyperglycemia. Neuroimaging studies in T1DM have revealed reductions in numerous regions, including the parahippocampal and occipital regions, while in T2DM there have been numerous reports of hippocampal atrophy. This meta-analysis aimed to identify consistent regional abnormalities in cerebral structures in T1DM and T2DM respectively, and also to examine the impact of potential confounds, including age, depression and vascular risk factors. Neuroimaging studies of both voxel-based morphometry (VBM) data and volumetric data were included. Ten T1DM studies (n = 613 patients) and 23 T2DM studies (n = 1364 patients) fulfilled inclusion criteria. The T1DM meta-analysis revealed reduced bilateral thalamus grey matter density in adults. The T2DM meta-analysis revealed reduced global brain volume and regional atrophy in the hippocampi, basal ganglia, and orbitofrontal and occipital lobes. Moreover, hippocampal atrophy in T2DM was not modified by hypertension, although there were more marked reductions in younger patients relative to healthy controls. In conclusion, T1DM and T2DM demonstrated distinct cerebral effects with generalised and specific target areas of grey matter reduction. Thalamic atrophy in T1DM may be a substrate of associated cognitive deficits. In T2DM, global cerebral atrophy may reflect atherosclerotic factors, while hippocampal atrophy was an independent effect providing a potential common neuropathological etiology for the comorbidity of T2DM with dementia and depression.
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Affiliation(s)
- Calum D Moulton
- Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK.
| | - Sergi G Costafreda
- Division of Psychiatry, Faculty of Brain Sciences, University College London, London, UK
| | - Paul Horton
- Department of Old Age Psychiatry, Institute of Psychiatry, King's College London, London, UK
| | - Khalida Ismail
- Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
| | - Cynthia H Y Fu
- School of Psychology, University of East London, London, UK
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50
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Abstract
Hypoglycemia and fear of hypoglycemia limit appropriate glycemic control in many children and adolescents with type 1 diabetes. Traditional approaches to the prevention of hypoglycemia including patient education about modifiable risk factors for hypoglycemia (changes in insulin, diet, and exercise) and frequency of self glucose monitoring remain important for hypoglycemia prevention. Continuous glucose monitoring systems with or without a partial closed-loop control of insulin infusion have been very useful in the prevention of hypoglycemia. Oral carbohydrate and parenteral glucagon continue to be the mainstays of hypoglycemia treatment. In the future, we can look forward to regulatory approval of closed-loop insulin delivery and glucose monitoring systems to facilitate euglycemia, as well as glucagon administered by the intranasal route to treat hypoglycemia.
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Affiliation(s)
- Dayna E McGill
- MassGeneral Hospital for Children, Joslin Diabetes Center, Harvard Medical School, 5th Floor, Pediatrics, 175 Cambridge Street, Boston, MA, 02114, USA
| | - Lynne L Levitsky
- Division of Pediatric Endocrinology, MassGeneral Hospital for Children, Harvard Medical School, 5th Floor, Pediatrics, 175 Cambridge Street, Boston, MA, 02114, USA.
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