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Claesson TB, Mutter S, Putaala J, Salli E, Gordin D, Groop PH, Martola J, Thorn LM. Age at type 1 diabetes onset does not influence attained brain volume. BMC Endocr Disord 2025; 25:43. [PMID: 39966749 PMCID: PMC11834590 DOI: 10.1186/s12902-025-01868-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 02/05/2025] [Indexed: 02/20/2025] Open
Abstract
INTRODUCTION Type 1 diabetes is suspected to hamper brain growth, implying that people with earlier diabetes onset would, on average, achieve lower maximal brain volume. We set out to test this hypothesis. METHODS Examining brain MRI scans of middle-aged people with type 1 diabetes, we related age at diabetes onset to intracranial volume in 180 participants, as well as to cerebral gray and white matter volumes in a subset of 113 (63%) participants, using fractional polynomial regression models. Of the participants, 118 (67%) had been diagnosed with diabetes before 18 years of age. RESULTS Of our participants, 54% were women, the median age 40.0 (IQR 33.2-45.0) years and the range of age at diabetes onset was 1.2-39.0 years. We found no association between age at diabetes onset and intracranial volume (p = 0.85), cerebral white (p = 0.10), or gray matter volumes (p = 0.12). Further, correlations between age at diabetes onset and the measured brain volumes were poor in analyses stratified for sex (all correlation coefficients ρ ≤ 0.16). CONCLUSIONS We found no association between age at diabetes onset and attained intracranial volume or gray or white matter volumes, indicating that type 1 diabetes may not have a clinically significant influence on brain growth.
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Affiliation(s)
- Tor-Björn Claesson
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Folkhälsan Research Centre, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Stefan Mutter
- Folkhälsan Research Centre, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Jukka Putaala
- Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Eero Salli
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Daniel Gordin
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
- Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Per-Henrik Groop
- Folkhälsan Research Centre, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Juha Martola
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Lena M Thorn
- Folkhälsan Research Centre, Helsinki, Finland.
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, PoB 20, Helsinki, FIN-00014, Finland.
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Stanisławska-Kubiak M, Majewska KA, Krasińska A, Wais P, Majewski D, Mojs E, Kȩdzia A. Brain functional and structural changes in diabetic children. How can intellectual development be optimized in type 1 diabetes? Ther Adv Chronic Dis 2024; 15:20406223241229855. [PMID: 38560719 PMCID: PMC10981223 DOI: 10.1177/20406223241229855] [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: 06/20/2023] [Accepted: 01/11/2024] [Indexed: 04/04/2024] Open
Abstract
The neuropsychological functioning of people with type 1 diabetes (T1D) is of key importance to the effectiveness of the therapy, which, in its complexity, requires a great deal of knowledge, attention, and commitment. Intellectual limitations make it difficult to achieve the optimal metabolic balance, and a lack of this alignment can contribute to the further deterioration of cognitive functions. The aim of this study was to provide a narrative review of the current state of knowledge regarding the influence of diabetes on brain structure and functions during childhood and also to present possible actions to optimize intellectual development in children with T1D. Scopus, PubMed, and Web of Science databases were searched for relevant literature using selected keywords. The results were summarized using a narrative synthesis. Disturbances in glucose metabolism during childhood may have a lasting negative effect on the development of the brain and related cognitive functions. To optimize intellectual development in children with diabetes, it is essential to prevent disorders of the central nervous system by maintaining peri-normal glycemic levels. Based on the performed literature review, it seems necessary to take additional actions, including repeated neuropsychological evaluation with early detection of any cognitive dysfunctions, followed by the development of individual management strategies and the training of appropriate skills, together with complex, multidirectional environmental support.
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Affiliation(s)
- Maia Stanisławska-Kubiak
- Department of Clinical Psychology, Poznan University of Medical Sciences, ul. Bukowska 70, Poznan 60-812, Poland
| | - Katarzyna Anna Majewska
- Department of Pediatric Diabetes, Auxology and Obesity, Poznan University of Medical Sciences, Poznan, Poland
| | - Agata Krasińska
- Department of Pediatric Diabetes, Auxology and Obesity, Poznan University of Medical Sciences, Poznan, Poland
| | - Paulina Wais
- Department of Pediatric Diabetes, Auxology and Obesity, Poznan University of Medical Sciences, Poznan, Poland
| | - Dominik Majewski
- Department of Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Ewa Mojs
- Department of Clinical Psychology, Poznan University of Medical Sciences, Poznan, Poland
| | - Andrzej Kȩdzia
- Department of Pediatric Diabetes, Auxology and Obesity, Poznan University of Medical Sciences, Poznan, Poland
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Yonamine CY, Michalani MLE, Moreira RJ, Machado UF. Glucose Transport and Utilization in the Hippocampus: From Neurophysiology to Diabetes-Related Development of Dementia. Int J Mol Sci 2023; 24:16480. [PMID: 38003671 PMCID: PMC10671460 DOI: 10.3390/ijms242216480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 11/12/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023] Open
Abstract
The association of diabetes with cognitive dysfunction has at least 60 years of history, which started with the observation that children with type 1 diabetes mellitus (T1D), who had recurrent episodes of hypoglycemia and consequently low glucose supply to the brain, showed a deficit of cognitive capacity. Later, the growing incidence of type 2 diabetes mellitus (T2D) and dementia in aged populations revealed their high association, in which a reduced neuronal glucose supply has also been considered as a key mechanism, despite hyperglycemia. Here, we discuss the role of glucose in neuronal functioning/preservation, and how peripheral blood glucose accesses the neuronal intracellular compartment, including the exquisite glucose flux across the blood-brain barrier (BBB) and the complex network of glucose transporters, in dementia-related areas such as the hippocampus. In addition, insulin resistance-induced abnormalities in the hippocampus of obese/T2D patients, such as inflammatory stress, oxidative stress, and mitochondrial stress, increased generation of advanced glycated end products and BBB dysfunction, as well as their association with dementia/Alzheimer's disease, are addressed. Finally, we discuss how these abnormalities are accompained by the reduction in the expression and translocation of the high capacity insulin-sensitive glucose transporter GLUT4 in hippocampal neurons, which leads to neurocytoglycopenia and eventually to cognitive dysfunction. This knowledge should further encourage investigations into the beneficial effects of promising therapeutic approaches which could improve central insulin sensitivity and GLUT4 expression, to fight diabetes-related cognitive dysfunctions.
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Affiliation(s)
- Caio Yogi Yonamine
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark;
| | - Maria Luiza Estimo Michalani
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil; (M.L.E.M.); (R.J.M.)
| | - Rafael Junges Moreira
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil; (M.L.E.M.); (R.J.M.)
| | - Ubiratan Fabres Machado
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil; (M.L.E.M.); (R.J.M.)
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Dolatshahi M, Sanjari Moghaddam H, Saberi P, Mohammadi S, Aarabi MH. Central nervous system microstructural alterations in Type 1 diabetes mellitus: A systematic review of diffusion Tensor imaging studies. Diabetes Res Clin Pract 2023; 205:110645. [PMID: 37004976 DOI: 10.1016/j.diabres.2023.110645] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 02/18/2023] [Accepted: 03/24/2023] [Indexed: 04/03/2023]
Abstract
AIMS Type 1 diabetes mellitus (T1DM) is a chronic childhood disease with potentially persistent CNS disruptions. In this study, we aimed to systematically review diffusion tensor imaging studies in patients with T1DM to understand the microstructural effects of this entity on individuals' brains METHODS: We performed a systematic search and reviewed the studies to include the DTI studies in individuals with T1DM. The data for the relevant studies were extracted and a qualitative synthesis was performed. RESULTS A total of 19 studies were included, most of which showed reduced FA widespread in optic radiation, corona radiate, and corpus callosum, as well as other frontal, parietal, and temporal regions in the adult population, while most of the studies in the juvenile patients showed non-significant differences or a non-persistent pattern of changes. Also, reduced AD and MD in individuals with T1DM compared to controls and non-significant differences in RD were noted in the majority of studies. Microstructural alterations were associated with clinical profile, including age, hyperglycemia, diabetic ketoacidosis and cognitive performance. CONCLUSION T1DM is associated with microstructural brain alterations including reduced FA, MD, and AD in widespread brain regions, especially in association with glycemic fluctuations and in adult age.
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Affiliation(s)
- Mahsa Dolatshahi
- NeuroImaging Laboratories, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, United States; NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | | | - Parastoo Saberi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Soheil Mohammadi
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohammad Hadi Aarabi
- Department of Neuroscience and Padova Neuroscience Center (PNC), University of Padova, Padova, Italy.
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5
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Jacobson AM, Braffett BH, Erus G, Ryan CM, Biessels GJ, Luchsinger JA, Bebu I, Gubitosi-Klug RA, Desiderio L, Lorenzi GM, Trapani VR, Lachin JM, Bryan RN, Habes M, Nasrallah IM. Brain Structure Among Middle-aged and Older Adults With Long-standing Type 1 Diabetes in the DCCT/EDIC Study. Diabetes Care 2022; 45:1779-1787. [PMID: 35699949 PMCID: PMC9346989 DOI: 10.2337/dc21-2438] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 04/17/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Individuals with type 1 diabetes mellitus (T1DM) are living to ages when neuropathological changes are increasingly evident. We hypothesized that middle-aged and older adults with long-standing T1DM will show abnormal brain structure in comparison with control subjects without diabetes. RESEARCH DESIGN AND METHODS MRI was used to compare brain structure among 416 T1DM participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study with that of 99 demographically similar control subjects without diabetes at 26 U.S. and Canadian sites. Assessments included total brain (TBV) (primary outcome), gray matter (GMV), white matter (WMV), ventricle, and white matter hyperintensity (WMH) volumes and total white matter mean fractional anisotropy (FA). Biomedical assessments included HbA1c and lipid levels, blood pressure, and cognitive assessments of memory and psychomotor and mental efficiency (PME). Among EDIC participants, HbA1c, severe hypoglycemia history, and vascular complications were measured longitudinally. RESULTS Mean age of EDIC participants and control subjects was 60 years. T1DM participants showed significantly smaller TBV (least squares mean ± SE 1,206 ± 1.7 vs. 1,229 ± 3.5 cm3, P < 0.0001), GMV, and WMV and greater ventricle and WMH volumes but no differences in total white matter mean FA versus control subjects. Structural MRI measures in T1DM were equivalent to those of control subjects who were 4-9 years older. Lower PME scores were associated with altered brain structure on all MRI measures in T1DM participants. CONCLUSIONS Middle-aged and older adults with T1DM showed brain volume loss and increased vascular injury in comparison with control subjects without diabetes, equivalent to 4-9 years of brain aging.
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Affiliation(s)
- Alan M. Jacobson
- NYU Long Island School of Medicine, NYU Langone Hospital–Long Island, Mineola
| | | | - Guray Erus
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
| | | | - Geert J. Biessels
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Netherlands
| | | | - Ionut Bebu
- The Biostatistics Center, The George Washington University, Rockville, MD
| | - Rose A. Gubitosi-Klug
- Case Western Reserve University School of Medicine, Rainbow Babies & Children’s Hospital, Cleveland, OH
| | - Lisa Desiderio
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
| | | | | | - John M. Lachin
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
| | | | - Mohamad Habes
- Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Ilya M. Nasrallah
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
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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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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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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: 57] [Impact Index Per Article: 14.3] [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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Abstract
PURPOSE OF REVIEW To synthesize findings from studies of neurocognitive complications in children with type 1 diabetes (T1D) and highlight potential risk and protective factors. RECENT FINDINGS Emerging evidence suggests that hyperglycemia and time in range may be more important for brain development than episodes of hypoglycemia. Further, diabetic ketoacidosis (DKA) at the time of T1D diagnosis appears to be a particular risk factor for neurocognitive complications, particularly deficits in executive function skills and memory, with differences in cerebral white matter microstructure seen via advanced magnetic resonance imaging methods, and lower scores on measures of attention and memory observed among children who were diagnosed in DKA. Other factors that may influence neurocognitive development include child sleep, caregiver distress, and diabetes device use, presumably due to improved glycemic control. We highlight neurocognitive risk and protective factors for children with T1D and priorities for future research in this high-risk population.
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Affiliation(s)
- Sarah S Jaser
- Department of Pediatrics, Vanderbilt University Medical Center, 2525 West End Ave., Suite 1200, Nashville, TN, 37203, USA.
| | - Lori C Jordan
- Department of Pediatrics, Vanderbilt University Medical Center, 2525 West End Ave., Suite 1200, Nashville, TN, 37203, USA
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Radiology and Radiological Science, Vanderbilt University Medical Center, Nashville, TN, USA
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Kamrath C, Tittel SR, Kapellen TM, von dem Berge T, Heidtmann B, Nagl K, Menzel U, Pötzsch S, Konrad K, Holl RW. Early versus delayed insulin pump therapy in children with newly diagnosed type 1 diabetes: results from the multicentre, prospective diabetes follow-up DPV registry. THE LANCET CHILD & ADOLESCENT HEALTH 2020; 5:17-25. [PMID: 33253630 DOI: 10.1016/s2352-4642(20)30339-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 10/01/2020] [Accepted: 10/07/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Although continuous subcutaneous insulin infusion therapy (ie, insulin pump therapy) is associated with improved metabolic control compared with multiple daily insulin injections in children with type 1 diabetes, it is unclear when it is best to start it after diagnosis. In this study, we aimed to compare the outcomes between early and delayed start of insulin pump therapy in young patients with type 1 diabetes. METHODS We based the current study on data from the multicentre, prospective diabetes follow-up registry (ie, Diabetes-Patienten-Verlaufsdokumentation [DPV]). The DPV registry comprises 501 diabetes centres from Germany, Austria, Switzerland, and Luxembourg. We included patients diagnosed with type 1 diabetes between 2004 and 2014, who were aged between 6 months and 15 years at the time of diagnosis, who had started insulin pump therapy either within the first 6 months (ie, the early treatment group) or in the second to third year (ie, the delayed treatment group) after diabetes diagnosis, and who were treated with insulin pump therapy for at least 1 year. The outcome parameters included the glycated haemoglobin (HbA1c) values, the cardiovascular risk profile, and rates of acute complications and diabetes-associated hospital admissions (ie, hospitalisation) during the most recent documented treatment year with insulin pump therapy. Statistical models were adjusted for age at diabetes diagnosis, year of diagnosis, sex, immigrant background, use of continuous glucose monitoring, centre size, and the German Index of Socioeconomic Deprivation 2012 terciles. FINDINGS Our study sample comprised 8332 patients from 311 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The early treatment group consisted of 4004 (48·1%) of 8332 patients, and the delayed treatment group consisted of 4328 (51·9%). The median diabetes duration during follow-up was 6·7 years (IQR 5·1-8·7 in the early group; 5·0-8·7 in the delayed group) in both groups. Patients with early initiation of insulin pump therapy compared with those with delayed initiation of insulin pump therapy had significantly lower estimated mean HbA1c values (7·9% [95% CI 7·8-7·9] and 62·6 mmol/mol [95% CI 62·1-63·2] vs 8·0% [8·0-8·1] and 64·1 mmol/mol [63·6-64·6]; p=0·0006), and lower rates of hypoglycaemic coma (incidence risk ratio 0·44 [95% CI 0·24-0·79]; p=0·0064) and hospitalisation (0·86 [95% CI 0·78-0·94]; p=0·0016). A better cardiovascular risk profile was observed in patients with early initiation of insulin pump therapy than in those with delayed initiation: an estimated mean systolic blood pressure of 117·6 mm Hg (95% CI 117·2-117·9) versus 118·5 mm Hg (118·2-118·9), p=0·0007; and HDL cholesterol of 62·8 mg/dL (95% CI 62·2-63·5) versus 60·6 mg/dL (60·0-61·2), p<0·0001; however, diastolic blood pressure; concentrations of LDL cholesterol, non-HDL cholesterol, and triglycerides; and estimated body-mass index standard deviation scores during follow-up did not differ significantly between both groups. INTERPRETATION Our findings provide evidence for improved clinical outcomes associated with the early initiation of insulin pump therapy in children with type 1 diabetes. FUNDING The German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung), German Robert Koch Institute, German Diabetes Association, and Diabetes Agenda 2010.
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Affiliation(s)
- Clemens Kamrath
- Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
| | - Sascha R Tittel
- ZIBMT, Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany; German Center for Diabetes Research, Munich, Germany
| | - Thomas M Kapellen
- Department of Women and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
| | - Thekla von dem Berge
- Diabetes Center for Children and Adolescents, Children's Hospital Auf der Bult, Hannover, Germany
| | - Bettina Heidtmann
- Department of Pediatric Endocrinology and Diabetology, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany
| | - Katrin Nagl
- Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria
| | - Ulrike Menzel
- Department of Paediatric Endocrinology, AKK Altonaer Kinderkrankenhaus, Hamburg, Germany
| | - Simone Pötzsch
- Department for Children and Adolescent Medicine, Helios Vogtland Clinic Plauen, Plauen, Germany
| | - Katja Konrad
- Department of Pediatric and Adolescent Medicine, Elisabeth-Hospital Essen, Essen, Germany
| | - Reinhard W Holl
- ZIBMT, Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany; German Center for Diabetes Research, Munich, Germany
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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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12
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Gaweł WB, Deja G, Kamińska H, Tabor A, Skała-Zamorowska E, Jarosz-Chobot P. How does a predictive low glucose suspend (PLGS) system tackle pediatric lifespan challenges in diabetes treatment? Real world data analysis. Pediatr Diabetes 2020; 21:280-287. [PMID: 31715059 DOI: 10.1111/pedi.12944] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 09/17/2019] [Accepted: 10/28/2019] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVES The aim of the study was to assess the benefits of a predictive low glucose suspend (PLGS) system in real-life in children and adolescents with type 1 diabetes of different age and age-related clinical challenges. METHODS Real life retrospective and descriptive analysis included 44 children (26 girls) with type 1 diabetes who were introduced to PLGS system. We divided them in three age groups: I (3-6 years old, n = 12), II (7-10 y/o, n = 16), III (11-19 y/o, n = 16). All children and their caregivers received unified training in self-management during PLGS therapy. Patients' data included: age, HbA1C levels, sex. While from the CGM metric, we obtained: time of sensor use (SENSuse), time in range (TiR): in, below and over target range and average blood glycemia (AVG), insulin suspension time (INSsusp). RESULTS SENSuse was 93% in total, with 92%, 94%, and 87% in age groups I, II, III, respectively. In total the reduction of mean HbA1C from 7.61% to 6.88% (P < .05), while for the I, II, and III it was 7.46% to 6.72%, 6.91% to 6.41%, and 8.46 to 7.44%, respectively (P < .05). Although we observed a significant reduction of HbA1C, the time below target range was minimal. Specific findings included: group I-longest INSsusp (17%), group II-lowest glycemic variability (CV) (36%), and group III-highest AVG (169 mg/dL). There was a reverse correlation between suspend before low and age (-0.32, P < .05). In group I CV reduced TiR in target range (TiRin) (-0.82, P < .05), in group II use of complex boluses increased TiRin (0.52, P < .05). In group III higher CV increased HbA1C (0.64, P < .05) while reducing TiRin (-0.72, P < .05). CONCLUSIONS PLGS is a suitable and safe therapeutic option for children with diabetes of all age and it is effective in addressing age-specific challenges. PLGS improves glycemic control in children of all age, positively affecting its different parameters.
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Affiliation(s)
- Władysław B Gaweł
- Students' Scientific Association at the Department of Children's Diabetology, Medical University of Silesia, Katowice, Poland
| | - Grażyna Deja
- Department of Children's Diabetology, Medical University of Silesia, Katowice, Poland
| | - Halla Kamińska
- Department of Children's Diabetology, Medical University of Silesia, Katowice, Poland
| | - Aleksandra Tabor
- Students' Scientific Association at the Department of Children's Diabetology, Medical University of Silesia, Katowice, Poland
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13
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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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14
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Salehi P, Roberts AJ, Kim GJ. Efficacy and Safety of Real-Life Usage of MiniMed 670G Automode in Children with Type 1 Diabetes Less than 7 Years Old. Diabetes Technol Ther 2019; 21:448-451. [PMID: 31166801 DOI: 10.1089/dia.2019.0123] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The Medtronic MiniMed 670G system with SmartGuard™ (Medtronic, Northridge, CA) is a commercial hybrid closed-loop (HCL) system approved for use in 2018 for children >7 years. Studies of this HCL system in subjects >7 years old show improvement in glycemic control, but no study has described its use in younger children. This is a retrospective analysis of patients with type 1 diabetes (T1D) <7 years of age who used the 670G HCL system at Seattle Children's Hospital for 3 months. We compared 2-week data from Carelink™ while in manual mode (MM) with suspend before low active with those in auto mode (AM). We used two tailed t-test to compare variables related to glycemic control. Sixteen children were reviewed [age of AM start: average 4.3 years (range 2-6); 10 male]. The average time in AM was 6.3 ± 2.9 months (range 3-12). There was a statistically significant change for A1c [MM 7.9% (62.8 mmol/mol), AM 7.4% (57.4 mmol/mol); P-value <0.001], percentage time in range (MM 42.8%, AM 56.2%; P-value <0.001), percentage hypoglycemia (MM 1.3%, AM 2.4%; P-value 0.04), and average sensor glucose [MM 200 mg/dL (11.1 mmol/L), AM 176 mg/dL (9.8 mmol/L); P-value <0.001]. No serious adverse reports noted. This case series showed improvement in glycemic control in very young children using the 670G HCL. We did note more hypoglycemia although no serious adverse events, such as hypoglycemic seizure, were reported. A HCL system can be used in young children with T1D safely and effectively and should be an option for children <7 years.
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Affiliation(s)
- Parisa Salehi
- Division of Endocrinology, Seattle Children's Hospital, Seattle, Washington
| | - Alissa J Roberts
- Division of Endocrinology, Seattle Children's Hospital, Seattle, Washington
| | - Grace J Kim
- Division of Endocrinology, Seattle Children's Hospital, Seattle, Washington
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15
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Dong Y, Wang Q, Yao H, Xiao Y, Wei J, Xie P, Hu J, Chen W, Tang Y, Zhou H, Liu J. A promising structural magnetic resonance imaging assessment in patients with preclinical cognitive decline and diabetes mellitus. J Cell Physiol 2019; 234:16838-16846. [PMID: 30786010 DOI: 10.1002/jcp.28359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/30/2019] [Accepted: 02/01/2019] [Indexed: 01/18/2023]
Abstract
Subjective cognitive decline (SCD) is frequently reported in diabetic patients. Diabetes mellitus (DM) is associated with changes in the microstructure of the brain arise in diabetic patients, including changes in gray matter volume (GMV). However, the underlying mechanisms of changes in GMV in DM patients with cognitive impairment remain uncertain. Here, we present an overview of amyloid-β-dependent cognitive impairment in DM patients with SCD. Moreover, we review the evolving insights from studies on the GMV changes in GMV and cognitive dysfunction to which provide the mechanisms of cognitive impairment in T2DM. Ultimately, the novel structural magnetic resonance imaging (MRI) protocol was used for detecting neuroimaging biomarkers that can predict the clinical outcomes in diabetic patients with SCD. A reliable MRI protocol would be helpful to detect neurobiomarkers, and to understand the pathological mechanisms of preclinical cognitive impairment in diabetic patients.
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Affiliation(s)
- Yulan Dong
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China
| | - Qi Wang
- Department of Radiology, the Hunan Province Hospital, Changsha, China
| | - Hailun Yao
- Institute of Pharmacy and Medical Technology, Hunan Polytechnic of Environment and Biology, Hengyang, Hunan, China
| | - Yawen Xiao
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China
| | - Jiaohong Wei
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China
| | - Peihan Xie
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China
| | - Jun Hu
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China
| | - Wen Chen
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China
| | - Yan Tang
- Department of Ultrasound, the First Affiliated Hospital of University of South China, Hengyang, China
| | - Hong Zhou
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China.,Hengyang Medical College, University of South China, Hengyang, China
| | - Jincai Liu
- Department of Radiology, the First Affiliated Hospital of University of South China, Hengyang, China
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16
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Lin LW, Tsai FS, Yang WT, Lai SC, Shih CC, Lee SC, Wu CR. Differential change in cortical and hippocampal monoamines, and behavioral patterns in streptozotocin-induced type 1 diabetic rats. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2018; 21:1026-1034. [PMID: 30524676 PMCID: PMC6281071 DOI: 10.22038/ijbms.2018.29810.7197] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Objectives Diabetes mellitus (DM) is a widespread metabolic disorder worldwide. Clinical physicians have found diabetic patients have mild to middle cognitive dysfunction and an alteration of brain monoaminergic function. This study explored the change in various patterns of behavioral models and brain monoamine function under streptozotocin (STZ)-induced type 1 diabetes. Materials and Methods We established a type 1 DM model via intravenous injection with STZ (65 mg/kg) in rats. Three weeks after the STZ injection, various behavioral measurements including the inhibitory avoidance test, active avoidance test and Morris water maze were conducted. Finally, all rats were dissected and the concentrations of monoamines and their metabolites in cortex and hippocampus were measured by high performance liquid chromatography with electrochemical detection. Results We found that STZ induced type 1 diabetes (hyperglycemia and lack of insulin) in rats. STZ-induced diabetic rats had cognitive impairment in acquisition sessions and long-term retention of the active avoidance test. STZ-induced diabetic rats also had cognitive impairment in spatial learning, reference and working memory of the Morris water maze. STZ significantly reduced concentrations of norepinephrine (NE) in the cortex and dopamine (DA) in the hippocampus, but increased concentrations of DA and serotonin (5-HT) in the cortex 35 days after injection. The concentration of 5-HT in the hippocampus was also significantly increased. Conclusion The data suggested that this cognitive impairment after a short-term period of STZ injection might be related to cortical NE dysfunction, differential alteration of cortical and hippocampal DA function, and brain 5-HT hyperfunction.
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Affiliation(s)
- Li-Wei Lin
- School of Chinese Medicines for Post-Baccal aureate, I-Shou University, Kaohsiung 82445, Taiwan
| | - Fan-Shiu Tsai
- School of Chinese Medicines for Post-Baccal aureate, I-Shou University, Kaohsiung 82445, Taiwan
| | - Wen-Ta Yang
- Taichung Hospital, Ministry of Health and Welfare, Taichung 402, Taiwan
| | - Shang-Chih Lai
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97071, Taiwan
| | - Chun-Chuan Shih
- School of Chinese Medicines for Post-Baccal aureate, I-Shou University, Kaohsiung 82445, Taiwan
| | - Sheng-Chi Lee
- Pintung Branch, Kaohsiung Veterans General Hospital, Pintung 91245, Taiwan
| | - Chi-Rei Wu
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 402, Taiwan
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17
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Fox LA, Hershey T, Mauras N, Arbeláez AM, Tamborlane WV, Buckingham B, Tsalikian E, Englert K, Raman M, Jo B, Shen H, Reiss A, Mazaika P. Persistence of abnormalities in white matter in children with type 1 diabetes. Diabetologia 2018; 61:1538-1547. [PMID: 29654376 PMCID: PMC5991628 DOI: 10.1007/s00125-018-4610-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 03/12/2018] [Indexed: 01/18/2023]
Abstract
AIMS/HYPOTHESIS Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes. METHODS One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA1c levels were obtained every 3 months. RESULTS Axial diffusivity was lower in children with diabetes at baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (p = 0.037). Fractional anisotropy was positively correlated with performance (p < 0.002) and full-scale IQ (p < 0.02). CONCLUSIONS/INTERPRETATION These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.
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Affiliation(s)
- Larry A Fox
- Pediatric Endocrinology, Nemours Children's Health System, 807 Children's Way, Jacksonville, FL, 32207, USA.
| | - Tamara Hershey
- Department of Psychiatry and Radiology, Washington University in St Louis and the St Louis Children's Hospital, St Louis, MO, USA
| | - Nelly Mauras
- Pediatric Endocrinology, Nemours Children's Health System, 807 Children's Way, Jacksonville, FL, 32207, USA
| | - Ana Maria Arbeláez
- Department of Psychiatry and Radiology, Washington University in St Louis and the St Louis Children's Hospital, St Louis, MO, USA
| | | | - Bruce Buckingham
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
| | - Eva Tsalikian
- Department of Pediatric Endocrinology, The University of Iowa, Iowa City, IA, USA
| | - Kim Englert
- Pediatric Endocrinology, Nemours Children's Health System, 807 Children's Way, Jacksonville, FL, 32207, USA
| | - Mira Raman
- Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Booil Jo
- Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Hanyang Shen
- Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Allan Reiss
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
- Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
- Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
| | - Paul Mazaika
- Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
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Gupta OT, MacKenzie M, Burris A, Jenkins BB, Collins N, Shade M, Santa-Sosa E, Stewart SM, White PC. Camp-based multi-component intervention for families of young children with type 1 diabetes: A pilot and feasibility study. Pediatr Diabetes 2018; 19:761-768. [PMID: 29243325 DOI: 10.1111/pedi.12624] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 09/15/2017] [Accepted: 11/21/2017] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Managing type 1 diabetes mellitus (T1DM) in preschool-aged children has unique challenges that can negatively impact glycemic control and parental coping. OBJECTIVE To evaluate the impact of a camp-based multi-component intervention on glycated hemoglobin A1c (HbA1c) in young children with T1DM and psychosocial measures for their parents. SUBJECTS AND METHODS Two separate cohorts of 18 children (ages 3-5 years) and their families participated in a camp-based intervention that included didactic and interactive parent education, child-centered education and family-based recreational activities. In Camp 1.0, measures of HbA1c, parental fear of hypoglycemia, mealtime behaviors and quality of life (QOL) were compared before and after an initial session (I) and follow-up booster session (II) 6 months later. Based on these results, the intervention was consolidated into 1 session (Camp 2.0) and repeated with additional measures of parental stress and parental self-efficacy with diabetes management tasks. RESULTS Participants in Camp 2.0 exhibited a significant decrease in mean HbA1c level (-0.5%, P = .002) before and after camp. Mothers exhibited a significant improvement in diabetes-specific QOL (Camp 1.0/Session I and Camp 2.0) and reduction in stress as measured on the Pediatric Inventory for Parent (PIP) assessment (Camp 2.0). The booster session in Camp 1.0 showed no added benefit. CONCLUSIONS A family centered, camp-based multi-component intervention in young children with T1DM improved HbA1c and perceived QOL and stress in their mothers.
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Affiliation(s)
- Olga T Gupta
- Division of Endocrinology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
| | | | - Angie Burris
- Children's Health Children's Medical Center, Dallas, Texas
| | | | - Nikki Collins
- Children's Health Children's Medical Center, Dallas, Texas
| | - Molly Shade
- Department of Anthropology, University of North Texas, Denton, Texas
| | - Eileen Santa-Sosa
- Children's Health Children's Medical Center, Dallas, Texas.,Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Sunita M Stewart
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Perrin C White
- Division of Endocrinology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
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19
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Goethals ER, de Wit M, Van Broeck N, Lemiere J, Van Liefferinge D, Böhler S, De Wulf M, Dello E, Laridaen J, Van Hecke L, Van Impe S, Casteels K, Luyckx K. Child and parental executive functioning in type 1 diabetes: Their unique and interactive role toward treatment adherence and glycemic control. Pediatr Diabetes 2018; 19:520-526. [PMID: 28758314 DOI: 10.1111/pedi.12552] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 05/30/2017] [Accepted: 05/31/2017] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE Managing type 1 diabetes (T1D) requires the ability to make complex and critical decisions regarding treatment, to execute complex tasks accurately, and to make adjustments when problems arise. This requires effective neuropsychological competences of patients and their families, especially in the domain of executive functioning (EF): the ability to self-monitor, plan, solve problems, and set priorities. Previous research focused mainly on child EF, neglecting the impact of parental EF. This study included both mothers and fathers and examined associations between child and parental EF and treatment adherence to T1D in a broad age range of patients. METHODS Parents of 270 patients (6-18 years) with T1D (mean age 12.7 years; 52.6% female) were included. Mothers (N = 232) and fathers (N = 168) completed questionnaires on child and parental EF and on treatment adherence. Analyses examined the associations linking child and parental EF to treatment adherence and glycemic control (and potential moderation effects in these associations) using hierarchical linear regression. RESULTS Child EF problems were negatively associated with treatment adherence. As an indication of moderation, this effect was stronger in older children. Better treatment adherence and glycemic control were reported when both child and parent showed less EF problems. Effects were more pronounced in mothers than in fathers. CONCLUSIONS This study demonstrated a significant interplay between child and parental EF in the association with treatment adherence and glycemic control. Researchers and clinicians should remain attentive toward the role of neuropsychological concepts such as EF. Implementation in clinical practice seems meaningful.
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Affiliation(s)
- Eveline R Goethals
- Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium
- Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium
| | - Maartje de Wit
- Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands
| | - Nady Van Broeck
- Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium
| | - Jurgen Lemiere
- Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium
- Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium
| | | | - Susanne Böhler
- Department of Pediatrics, University Hospital Brussels, Brussels, Belgium
| | - Marian De Wulf
- Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium
| | - Elke Dello
- Department of Pediatrics, Hospital Maas & Kempen, Bree, Belgium
| | - Jolien Laridaen
- Department of Pediatrics, University Hospital Ghent, Ghent, Belgium
| | - Lynn Van Hecke
- Department of Pediatrics, Delta Hospital Roeselare, Roeselare, Belgium
| | - Shana Van Impe
- Department of Pediatrics, Queen Paola Children's Hospital ZNA, Antwerp, Belgium
| | - Kristina Casteels
- Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium
- Department of Development and Regeneration, University of Leuven, Leuven, Belgium
| | - Koen Luyckx
- Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium
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20
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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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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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22
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Haynes A, Hermann JM, Miller KM, Hofer SE, Jones TW, Beck RW, Maahs DM, Davis EA, Holl RW. Severe hypoglycemia rates are not associated with HbA1c: a cross-sectional analysis of 3 contemporary pediatric diabetes registry databases. Pediatr Diabetes 2017; 18:643-650. [PMID: 27878914 PMCID: PMC7162500 DOI: 10.1111/pedi.12477] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 09/07/2016] [Accepted: 10/15/2016] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVE To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries. METHODS Data for patients with type 1 diabetes, aged <18 years with a minimum duration of diabetes of 2 years, were extracted from each registry for a 12-month observation period between 2011 and 2012 (7,102 T1DX, 18,887 DPV, and 865 WACDD). Rates of severe hypoglycemia (self-reported loss of consciousness/convulsion) were estimated per 100 patient-years and analyzed by HbA1c, source registry, treatment regimen, and age group. RESULTS Overall, the severe hypoglycemia rate per 100 patient years was 7.1, 3.3, and 6.7 in T1DX, DPV, and WACDD patients, respectively. Lower HbA1c was not associated with an increased rate of severe hypoglycemia when examined by source registry, treatment regimen, or age group. CONCLUSION An inverse relationship between mean HbA1c and risk of severe hypoglycemia was not observed in this study of 3, independent cohorts of children and adolescents with type 1 diabetes. Investigation in other large, longitudinal cohorts is recommended to further characterize the contemporary relationship between glycemic control and risk of severe hypoglycemia rates in pediatric patients with type 1 diabetes.
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Affiliation(s)
- Aveni Haynes
- Telethon Kids Institute, The University of Western Australia, Perth, Australia
| | - Julia M. Hermann
- University of Ulm, ZIBMT, Institute of Epidemiology and Medical Biometry, Ulm, Germany,German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | | | - Sabine E. Hofer
- Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria
| | - Timothy W. Jones
- Telethon Kids Institute, The University of Western Australia, Perth, Australia,Department of Diabetes & Endocrinology, Princess Margaret Hospital, Perth, Australia
| | - Roy W. Beck
- Jaeb Center for Health Research, Tampa, Florida
| | - David M. Maahs
- Department of Pediatrics, Stanford University, Stanford, California
| | - Elizabeth A. Davis
- Telethon Kids Institute, The University of Western Australia, Perth, Australia,Department of Diabetes & Endocrinology, Princess Margaret Hospital, Perth, Australia
| | - Reinhard W. Holl
- University of Ulm, ZIBMT, Institute of Epidemiology and Medical Biometry, Ulm, Germany,German Center for Diabetes Research (DZD), München-Neuherberg, Germany
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23
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Sundberg F, Barnard K, Cato A, de Beaufort C, DiMeglio LA, Dooley G, Hershey T, Hitchcock J, Jain V, Weissberg-Benchell J, Rami-Merhar B, Smart CE, Hanas R. ISPAD Guidelines. Managing diabetes in preschool children. Pediatr Diabetes 2017; 18:499-517. [PMID: 28726299 DOI: 10.1111/pedi.12554] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Revised: 05/14/2017] [Accepted: 05/31/2017] [Indexed: 01/09/2023] Open
Affiliation(s)
- Frida Sundberg
- The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.,Institute of Clinical Sciences, Department of Pediatrics, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Katharine Barnard
- Faculty of Health and Social Sciences, Bournemouth University, Bournemouth, UK
| | - Allison Cato
- Neurology Division, Nemours Children's Health System, Jacksonville, Florida
| | - Carine de Beaufort
- Clinique Pediatrique, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg.,Department of Pediatrics, UZ Brussels, Jette, Belgium
| | - Linda A DiMeglio
- Department of Pediatrics, Section of Pediatric Endocrinology/Diabetology, Indiana University School of Medicine, Indianapolis, Indiana
| | | | - Tamara Hershey
- Psychiatry Department, Washington University School of Medicine, St. Louis, Missouri.,Radiology Department, Washington University School of Medicine, St. Louis, Missouri
| | | | - Vandana Jain
- Pediatric Endocrinology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
| | - Jill Weissberg-Benchell
- Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
| | - Birgit Rami-Merhar
- Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
| | - Carmel E Smart
- Department of Endocrinology, John Hunter Children's Hospital and University of Newcastle, Newcastle, Australia
| | - Ragnar Hanas
- Institute of Clinical Sciences, Department of Pediatrics, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.,Department of Pediatrics, NU Hospital Group, Uddevalla, Sweden
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24
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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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25
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Greene DJ, Williams III AC, Koller JM, Schlaggar BL, Black KJ. Brain structure in pediatric Tourette syndrome. Mol Psychiatry 2017; 22:972-980. [PMID: 27777415 PMCID: PMC5405013 DOI: 10.1038/mp.2016.194] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Revised: 08/05/2016] [Accepted: 09/06/2016] [Indexed: 01/21/2023]
Abstract
Previous studies of brain structure in Tourette syndrome (TS) have produced mixed results, and most had modest sample sizes. In the present multicenter study, we used structural magnetic resonance imaging (MRI) to compare 103 children and adolescents with TS to a well-matched group of 103 children without tics. We applied voxel-based morphometry methods to test gray matter (GM) and white matter (WM) volume differences between diagnostic groups, accounting for MRI scanner and sequence, age, sex and total GM+WM volume. The TS group demonstrated lower WM volume bilaterally in orbital and medial prefrontal cortex, and greater GM volume in posterior thalamus, hypothalamus and midbrain. These results demonstrate evidence for abnormal brain structure in children and youth with TS, consistent with and extending previous findings, and they point to new target regions and avenues of study in TS. For example, as orbital cortex is reciprocally connected with hypothalamus, structural abnormalities in these regions may relate to abnormal decision making, reinforcement learning or somatic processing in TS.
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Affiliation(s)
- D J Greene
- Department of Psychiatry, Washington University School of Medicine, St Louis, MO USA
- Department of Radiology, Washington University School of Medicine, St Louis, MO USA
| | | | - J M Koller
- Department of Psychiatry, Washington University School of Medicine, St Louis, MO USA
| | - B L Schlaggar
- Department of Psychiatry, Washington University School of Medicine, St Louis, MO USA
- Department of Radiology, Washington University School of Medicine, St Louis, MO USA
- Department of Neurology, Washington University School of Medicine, St Louis, MO USA
- Department of Neuroscience, Washington University School of Medicine, St Louis, MO USA
- Department of Pediatrics, Washington University School of Medicine, St Louis, MO USA
| | - K J Black
- Department of Psychiatry, Washington University School of Medicine, St Louis, MO USA
- Department of Radiology, Washington University School of Medicine, St Louis, MO USA
- Department of Neurology, Washington University School of Medicine, St Louis, MO USA
- Department of Neuroscience, Washington University School of Medicine, St Louis, MO USA
| | - and The Tourette Association of America Neuroimaging Consortium
- Department of Psychiatry, Washington University School of Medicine, St Louis, MO USA
- Department of Radiology, Washington University School of Medicine, St Louis, MO USA
- Washington University School of Medicine, St Louis, MO USA
- Department of Neurology, Washington University School of Medicine, St Louis, MO USA
- Department of Neuroscience, Washington University School of Medicine, St Louis, MO USA
- Department of Pediatrics, Washington University School of Medicine, St Louis, MO USA
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26
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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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27
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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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28
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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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29
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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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30
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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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31
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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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32
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Semenkovich K, Patel PP, Pollock AB, Beach KA, Nelson S, Masterson JJ, Hershey T, Arbeláez AM. Academic abilities and glycaemic control in children and young people with Type 1 diabetes mellitus. Diabet Med 2016; 33:668-73. [PMID: 26173465 PMCID: PMC4713372 DOI: 10.1111/dme.12854] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/07/2015] [Indexed: 12/11/2022]
Abstract
AIMS To determine if children and young people aged < 23 years with Type 1 diabetes differ in academic ability from age-matched control subjects without Type 1 diabetes and whether academic scores are related to glycaemic control. METHODS Using a cross-sectional study design, we administered cognitive and academic tests (Woodcock-Johnson III Spatial Relations, General Information, Letter-Word Recognition, Calculation and Spelling tests) to young people with Type 1 diabetes (n=61) and control subjects (n=26) aged 9-22 years. The groups did not differ in age or gender. Participants with Type 1 diabetes had a disease duration of 5-17.7 years. History of glycaemic control (HbA1c , diabetic ketoacidosis and severe hypoglycaemic episodes) was obtained via medical records and interviews. RESULTS The participants with Type 1 diabetes had a lower mean estimated verbal intelligence (IQ) level compared with those in the control group (P=0.04). Greater exposure to hyperglycaemia over time was associated with lower spelling abilities within the group with Type 1 diabetes (P=0.048), even after controlling for age, gender, socio-economic status, blood glucose level at time of testing and verbal IQ (P=0.01). History of severe hypoglycaemia or ketoacidosis was not associated with differences in academic abilities. CONCLUSIONS In children and young people, Type 1 diabetes was associated with a lower verbal IQ. Moreover, increased exposure to hyperglycaemia was associated with lower spelling performance. These results imply that hyperglycaemia can affect cognitive function and/or learning processes that may affect academic achievement.
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Affiliation(s)
- K Semenkovich
- Departments of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - P P Patel
- Departments of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - A B Pollock
- Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, USA
| | - K A Beach
- Departments of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - S Nelson
- Department of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
| | - J J Masterson
- Department of Communication Sciences and Disorders, Missouri State University, Springfield, MO, USA
| | - T Hershey
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
- Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
| | - A M Arbeláez
- Departments of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
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Cato MA, Mauras N, Mazaika P, Kollman C, Cheng P, Aye T, Ambrosino J, Beck RW, Ruedy KJ, Reiss AL, Tansey M, White NH, Hershey T. Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes over 18 Months. J Int Neuropsychol Soc 2016; 22:293-302. [PMID: 26786245 PMCID: PMC4856439 DOI: 10.1017/s1355617715001289] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. METHODS A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. RESULTS Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. CONCLUSIONS The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.
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Affiliation(s)
- M. Allison Cato
- Division of Neurology, Nemours Children’s Health System, Jacksonville, Florida, 32207
| | - Nelly Mauras
- Division of Endocrinology, Nemours Children’s Health System, Jacksonville, Florida, 32207
| | - Paul Mazaika
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, 94305
| | - Craig Kollman
- Jaeb Center for Health Research, Tampa, Florida, 33647
| | - Peiyao Cheng
- Jaeb Center for Health Research, Tampa, Florida, 33647
| | - Tandy Aye
- Department of Pediatric Endocrinology, Stanford University, Stanford, California, 94305
| | - Jodie Ambrosino
- Yale Children’s Diabetes Program, Yale University, New Haven, Connecticut, 06520
| | - Roy W. Beck
- Jaeb Center for Health Research, Tampa, Florida, 33647
| | | | - Allan L. Reiss
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, 94305
- Department of Radiology, Stanford University, Stanford, California, 94305
- Department of Pediatrics, Stanford University, Stanford, California, 94305
| | - Michael Tansey
- Division of Pediatric Psychology, University of Iowa Children’s Hospital, Iowa City, Iowa, 52242
| | - Neil H. White
- Departments of Pediatrics, Washington University, St. Louis, Missouri, 63110
| | - Tamara Hershey
- Department of Psychiatry, Washington University, St. Louis, Missouri, 63110
- Department of Neurology, Washington University, St. Louis, Missouri, 63110
- Department of Radiology, Washington University, St. Louis, Missouri, 63110
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Lo W, O'Donnell M, Tancredi D, Orgain M, Glaser N. Diabetic ketoacidosis in juvenile rats is associated with reactive gliosis and activation of microglia in the hippocampus. Pediatr Diabetes 2016; 17:127-39. [PMID: 25594864 DOI: 10.1111/pedi.12251] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 12/10/2014] [Accepted: 12/12/2014] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Type 1 diabetes may be associated with structural and functional alterations in the brain. The role of diabetic ketoacidosis (DKA) in causing these alterations has not been well explored. METHODS We used immunohistochemical staining to investigate cellular alterations in brain specimens from juvenile rats with DKA before, during, and after treatment with insulin and saline, and compared these to samples from diabetic rats and normal controls. RESULTS Glial fibrillary acidic protein (GFAP) staining intensity was increased in the hippocampus during DKA and increased further during insulin/saline treatment. Twenty-four and 72 h after treatment, hippocampal GFAP intensity declined but remained above control levels. There were no significant changes in GFAP intensity in the cortex or striatum. OX42 staining intensity was increased during untreated DKA and increased further during insulin/saline treatment in the hippocampus and cortex. NeuN staining intensity was decreased after DKA treatment in the striatum but not in other regions. CONCLUSIONS DKA causes inflammatory changes in the brain including reactive gliosis and activation of microglia. These findings are present during untreated DKA, but intensify during insulin/saline treatment. The hippocampus was disproportionately affected, consistent with previous studies showing deficits in hippocampal functions in rats after DKA recovery and decreased memory capacity in children with a history of DKA.
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Affiliation(s)
- Weei Lo
- Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA
| | - Martha O'Donnell
- Departments of Physiology and Membrane Biology, University of California Davis, School of Medicine, Sacramento, CA, USA
| | - Daniel Tancredi
- Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA
| | - Myra Orgain
- Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA
| | - Nicole Glaser
- Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA
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Mazaika PK, Weinzimer SA, Mauras N, Buckingham B, White NH, Tsalikian E, Hershey T, Cato A, Aye T, Fox L, Wilson DM, Tansey MJ, Tamborlane W, Peng D, Raman M, Marzelli M, Reiss AL. Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes 2016; 65:476-85. [PMID: 26512024 PMCID: PMC4747456 DOI: 10.2337/db15-1242] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 10/17/2015] [Indexed: 12/11/2022]
Abstract
Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4-10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes.
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Affiliation(s)
- Paul K Mazaika
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
| | - Stuart A Weinzimer
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT
| | - Nelly Mauras
- Department of Pediatrics, Division of Endocrinology, Diabetes and Metabolism, Nemours Children's Health System, Jacksonville, FL
| | - Bruce Buckingham
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
| | - Neil H White
- Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Eva Tsalikian
- Department of Pediatric Endocrinology, The University of Iowa, Iowa City, IA
| | - Tamara Hershey
- Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Allison Cato
- Division of Neurology, Nemours Children's Health System, Jacksonville, FL
| | - Tandy Aye
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
| | - Larry Fox
- Department of Pediatrics, Division of Endocrinology, Diabetes and Metabolism, Nemours Children's Health System, Jacksonville, FL
| | - Darrell M Wilson
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
| | - Michael J Tansey
- Department of Pediatric Endocrinology, The University of Iowa, Iowa City, IA
| | - William Tamborlane
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT
| | - Daniel Peng
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
| | - Mira Raman
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
| | - Matthew Marzelli
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA Department of Bioengineering, Stanford University School of Medicine, Stanford, CA Department of Radiology, Stanford University School of Medicine, Stanford, CA
| | - Allan L Reiss
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA Department of Pediatrics, Stanford University School of Medicine, Stanford, CA Department of Radiology, Stanford University School of Medicine, Stanford, CA
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Abstract
The review considers the current views on the central nervous system (CNS) in diabetes mellitus (DM). It discusses an attitude towards the term 'diabetic encephalopathy'. The data of investigations of cognitive functions in types 1 and 2 DM and the brain structural imaging results obtained using up-to-date technologies are considered. The results of studies of the factors that induce cerebral changes in DM and their associated cognitive impairments are given. There is evidence that hyperglycemia has a more considerable impact on the above processes than hypoglycemia; other possible factors, apart from blood glucose control, are set out. The current views on the function of insulin in the CNS and the relationship of central insulin resistance to Alzheimer's disease are outlined. There are current data on intranasal insulin application that is still exploratory, but, as might be judged from the findings, may by a promising method for the treatment and prevention of cognitive decline in both patients with DM and those without this condition.
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Affiliation(s)
- E V Surkova
- Endocrinology Research Center, Ministry of Health of Russia, Moscow, Russia
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37
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Abstract
A constant supply of glucose to the brain is critical for normal cerebral metabolism. The dysglycemia of type 1 diabetes (T1D) can affect activity, survival, and function of neural cells. Clinical studies in T1D have shown impairments in brain morphology and function. The most neurotoxic milieu seems to be young age and/or diabetic ketoacidosis at onset, severe hypoglycemia under the age of 6 years followed by chronic hyperglycemia. Adverse cognitive outcomes seem to be associated with poorer mental health outcomes. It is imperative to improve outcomes by investigating the mechanisms of injury so that neuroprotective strategies independent of glycemia can be identified.
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Affiliation(s)
- Fergus J Cameron
- Department of Endocrinology and Diabetes, Royal Children's Hospital, Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Melbourne 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne 3010, Australia.
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Abstract
In this article, the author reviews the long-term outcomes and their precursors of type 1 diabetes starting in youth. The author also contrasts the changing incidence of these long-term complications as we have moved from the pre-Diabetes Control and Complications Trial (DCCT) to the post-DCCT standard of care and reviews the emerging data related to complications in youths with type 2 diabetes. Finally, the author reviews the recent understanding related to the effects of diabetes on the brain and cognition.
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Affiliation(s)
- Neil H White
- Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Box 8116, St Louis, MO 63110, USA.
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Ryan JP, Aizenstein HJ, Orchard TJ, Ryan CM, Saxton JA, Fine DF, Nunley KA, Rosano C. Age of Childhood Onset in Type 1 Diabetes and Functional Brain Connectivity in Midlife. Psychosom Med 2015; 77:622-30. [PMID: 26163816 PMCID: PMC4503367 DOI: 10.1097/psy.0000000000000206] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The development of Type 1 diabetes mellitus (T1DM) within the first 7 years of life has been linked to poorer cognitive performance. Adults with T1DM have altered functional brain connectivity, but no studies have examined whether earlier age of T1DM onset is associated with functional connectivity later in life. Accordingly, we tested the relationship between age of onset and resting state functional connectivity in a cohort of middle-aged adults with childhood-onset T1DM. METHODS Participants were from a subsample of the Pittsburgh Epidemiology of Diabetes Complications cohort and included 66 adults (mean age = 47.54 years, 32 men). Resting state blood oxygen level-dependent activity was used to calculate mean connectivity for eight functional brain networks. A multivariate analysis of variance examined associations between age of onset and network connectivity. Diffusion tensor and fluid-attenuated inversion recovery images were analyzed to identify microstructural alterations and white-matter hyperintensity volumes. RESULTS Later childhood onset of T1DM was associated with lower connectivity (F(8,57) = 2.40, p = .026). A significant interaction was present for current age such that an inverse association with age of onset for functional connectivity was present in older individuals (F(8,55) = 2.88, p = .035). Lower connectivity was associated with older age, increased white-matter hyperintensity volume, and lower microstructural integrity. CONCLUSIONS Diagnosis of T1DM later in childhood may be associated with lower brain functional connectivity, particularly in those surviving into older ages. These alterations may be an early marker for subsequent cognitive decrements. Future studies are warranted to understand the pathways underlying these associations.
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Affiliation(s)
- John P Ryan
- From the Departments of Psychiatry (J.P. Ryan, Aizenstein, C.M. Ryan, Fine) and Neurology (Saxton), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and Departments of Epidemiology (Orchard) and Epidemiology (Nunley, Rosano), University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania
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White M, O'Connell MA, Cameron FJ. Transition to adult endocrine services: What is achievable? The diabetes perspective. Best Pract Res Clin Endocrinol Metab 2015; 29:497-504. [PMID: 26051305 DOI: 10.1016/j.beem.2015.03.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Transition is defined as the 'purposeful, planned movement of adolescents and young adults with chronic physical and medical conditions from child-centred to adult-oriented health care systems' by Blum RW, (2002). The primary goal of transition is to ensure an uninterrupted process in healthcare delivery between the paediatric and adult settings; however, losses to follow up and decreased engagement with specialist services are common during this time. The current transition literature specifically pertaining to type 1 diabetes mellitus (T1DM) is often limited by incomplete data, the absence of control data and lack of follow up data spanning both the paediatric and adult years. This paper serves to review the current transition literature base, highlighting areas which warrant further study.
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Affiliation(s)
- Mary White
- Department of Endocrinology & Diabetes, The Royal Children's Hospital, 50 Flemington Road, Parkville, VIC 3052, Australia.
| | - Michele A O'Connell
- Department of Endocrinology & Diabetes, The Royal Children's Hospital, 50 Flemington Road, Parkville, VIC 3052, Australia.
| | - Fergus J Cameron
- Department of Endocrinology & Diabetes, The Royal Children's Hospital, 50 Flemington Road, Parkville, VIC 3052, Australia.
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41
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McNeilly AD, McCrimmon RJ. The Scylla and Charybdis of glucose control in childhood type 1 diabetes? Pediatr Diabetes 2015; 16:235-41. [PMID: 25727089 DOI: 10.1111/pedi.12270] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 02/05/2015] [Accepted: 02/05/2015] [Indexed: 11/27/2022] Open
Abstract
Glucose control in childhood type 1 diabetes is difficult and often characterized by significant glucose variability, including periods of prolonged hyperglycemia and intermittent episodes of hypoglycemia that can be severe. The brain of the developing child is thought to be more susceptible to metabolic insults because of its relatively high demand for glucose to fuel neuronal growth and differentiation. In this review we consider the impact of glucose variability, especially when associated with recurrent hypoglycemia, on long-term cognitive function in childhood type 1 diabetes. At present, this indicates a subtle effect of type 1 diabetes per se on a number of cognitive modalities. Within the population of children with type 1 diabetes, a history of severe hypoglycemia also appears to have an additional negative effect on cognitive function. However, interpretation of the literature is difficult in that the human studies draw largely from cross-sectional observational epidemiology while more basic work has used models that do not translate well into human disease. Moreover, it is likely to be many years before we will be able to clearly document the effects of recurrent hypoglycemia or chronic hyperglycemia on cognitive function. In the meantime, it seems appropriate to advocate that minimizing glucose variability when achieving glycemic targets should be the therapeutic goal of clinicians involved in the management of childhood type 1 diabetes.
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Affiliation(s)
- Alison D McNeilly
- Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, UK
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42
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Mauras N, Mazaika P, Buckingham B, Weinzimer S, White NH, Tsalikian E, Hershey T, Cato A, Cheng P, Kollman C, Beck RW, Ruedy K, Aye T, Fox L, Arbelaez AM, Wilson D, Tansey M, Tamborlane W, Peng D, Marzelli M, Winer KK, Reiss AL. Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes 2015; 64:1770-9. [PMID: 25488901 PMCID: PMC4407847 DOI: 10.2337/db14-1445] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 12/05/2014] [Indexed: 12/11/2022]
Abstract
Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain.
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Affiliation(s)
- Nelly Mauras
- Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic, Jacksonville, FL
| | - Paul Mazaika
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
| | - Bruce Buckingham
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
| | - Stuart Weinzimer
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT
| | - Neil H White
- Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO
| | - Eva Tsalikian
- Pediatric Endocrinology, University of Iowa, Iowa City, IA
| | - Tamara Hershey
- Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO
| | - Allison Cato
- Division of Neurology, Nemours Children's Clinic, Jacksonville, FL
| | | | | | - Roy W Beck
- Jaeb Center for Health Research, Tampa, FL
| | | | - Tandy Aye
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
| | - Larry Fox
- Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic, Jacksonville, FL
| | - Ana Maria Arbelaez
- Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO
| | - Darrell Wilson
- Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
| | - Michael Tansey
- Pediatric Endocrinology, University of Iowa, Iowa City, IA
| | - William Tamborlane
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT
| | - Daniel Peng
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
| | - Matthew Marzelli
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA Department of Bioengineering, Stanford University School of Medicine, Stanford, CA
| | - Karen K Winer
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
| | - Allan L Reiss
- Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA Department of Pediatrics, Stanford University School of Medicine, Stanford, CA Department of Radiology, Stanford University School of Medicine, Stanford, CA
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Litmanovitch E, Geva R, Rachmiel M. Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population. World J Diabetes 2015; 6:259-270. [PMID: 25789107 PMCID: PMC4360419 DOI: 10.4239/wjd.v6.i2.259] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/03/2014] [Accepted: 12/17/2014] [Indexed: 02/05/2023] Open
Abstract
Type 1 diabetes mellitus (T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction.
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Lin A, Northam EA, Werther GA, Cameron FJ. Risk factors for decline in IQ in youth with type 1 diabetes over the 12 years from diagnosis/illness onset. Diabetes Care 2015; 38:236-42. [PMID: 25488913 DOI: 10.2337/dc14-1385] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This study examined illness-related change in intelligence quotient (IQ) in a cohort of youth with type 1 diabetes studied prospectively from disease onset in childhood to follow-up 12 years later in late adolescence/early adulthood. RESEARCH DESIGN AND METHODS Participants included type 1 diabetes patients (n = 95; mean age at follow-up 21.3 years) and healthy control participants (HCs; n = 67; mean age at follow-up 21.0 years) from a cohort followed prospectively. Measures included Wechsler Preschool and Primary Scale of Intelligence-Revised, Wechsler Intelligence Scale for Children-Revised, and Wechsler Abbreviated Scale of Intelligence and prospective collection of data on metabolic control history. RESULTS Young people with type 1 diabetes showed greater decline in verbal IQ (VIQ) and full-scale IQ (FSIQ), but not performance IQ (PIQ), than HCs. Within the diabetes group, a younger age at diabetes onset was associated with a decline in PIQ and FSIQ (P ≤ 0.001). A history of hypoglycemic seizures was associated with a decline in VIQ (P = 0.002). Long-term metabolic control was not associated with changes in IQ. Interaction terms were not significant, suggesting no moderating effect of one diabetes-related variable over another. CONCLUSIONS The presence of diabetes may negatively influence some aspects of IQ over time. Specific illness risk factors, such as an earlier age of disease onset and a history of hypoglycemic seizures, appear to put the young person at greater risk. Academic progress of children identified as at risk should be monitored and educational supports provided if necessary.
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Affiliation(s)
- Ashleigh Lin
- Telethon Kids Institute, University of Western Australia, Perth, Australia
| | - Elisabeth A Northam
- Department of Psychology, Royal Children's Hospital, Melbourne, Australia Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Australia Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia
| | - George A Werther
- Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Australia Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia
| | - Fergus J Cameron
- Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Australia Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia
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45
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Cerebral perfusion in pediatric type 1 diabetes: relation to vascular complications, psychological and neurophysiological functions. Int J Diabetes Dev Ctries 2015. [DOI: 10.1007/s13410-014-0226-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Gallardo-Moreno GB, González-Garrido AA, Gudayol-Ferré E, Guàrdia-Olmos J. Type 1 Diabetes Modifies Brain Activation in Young Patients While Performing Visuospatial Working Memory Tasks. J Diabetes Res 2015; 2015:703512. [PMID: 26266268 PMCID: PMC4525461 DOI: 10.1155/2015/703512] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 06/30/2015] [Accepted: 07/01/2015] [Indexed: 12/23/2022] Open
Abstract
In recent years, increasing attention has been paid to the effects of Type 1 Diabetes (T1D) on cognitive functions. T1D onset usually occurs during childhood, so it is possible that the brain could be affected during neurodevelopment. We selected young patients of normal intelligence with T1D onset during neurodevelopment, no complications from diabetes, and adequate glycemic control. The purpose of this study was to compare the neural BOLD activation pattern in a group of patients with T1D versus healthy control subjects while performing a visuospatial working memory task. Sixteen patients and 16 matched healthy control subjects participated. There was no significant statistical difference in behavioral performance between the groups, but, in accordance with our hypothesis, results showed distinct brain activation patterns. Control subjects presented the expected activations related to the task, whereas the patients had greater activation in the prefrontal inferior cortex, basal ganglia, posterior cerebellum, and substantia nigra. These different patterns could be due to compensation mechanisms that allow them to maintain a behavioral performance similar to that of control subjects.
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Affiliation(s)
- Geisa B. Gallardo-Moreno
- Instituto de Neurociencias, Universidad de Guadalajara, Francisco de Quevedo 180, Colonia Arcos Vallarta, 44130 Guadalajara, JAL, Mexico
- *Geisa B. Gallardo-Moreno:
| | - Andrés A. González-Garrido
- Instituto de Neurociencias, Universidad de Guadalajara, Francisco de Quevedo 180, Colonia Arcos Vallarta, 44130 Guadalajara, JAL, Mexico
| | - Esteban Gudayol-Ferré
- Facultad de Psicología, Universidad Michoacana de San Nicolás de Hidalgo, Francisco Villa 450, 58120 Morelia, MICH, Mexico
| | - Joan Guàrdia-Olmos
- Facultat de Psicologia, Universitat de Barcelona, Institut de Recerca en Cervell, Cognició i Conducta (IR3C), Passeig de la Vall d'Hebron 171, 08035 Barcelona, Spain
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Pertierra-Cortada A, Ramon-Krauel M, Iriondo-Sanz M, Iglesias-Platas I. Instability of glucose values in very preterm babies at term postmenstrual age. J Pediatr 2014; 165:1146-1153.e2. [PMID: 25260622 DOI: 10.1016/j.jpeds.2014.08.029] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 07/07/2014] [Accepted: 08/14/2014] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To determine if very preterm (VPT) babies are capable of maintaining glucose levels within normal ranges at or near term postmenstrual age. STUDY DESIGN Glucose levels were intermittently or continuously monitored during 48 hours in a cohort of 60 VPT infants near hospital discharge. Hypoglycemic (≤45 mg/dL, 2.5 mmol/L) and hyperglycemic (≥140 mg/dL or 7.8 mmol/L, severe if ≥180 mg/dL or 10 mmol/L) episodes were considered relevant if they lasted longer than 30 minutes. Feeding regimes followed current practice. RESULTS With intermittent capillary, 2 hypoglycemic values and another 3 that were abnormally high were detected. With continuous monitoring, 6 babies (10.0%) had isolated hypoglycemia ≤45 mg/dL (2.5 mmol/L) (3 of them reaching 40 mg/dL, 2.2 mmol/L), 14 (23.3%) had isolated hyperglycemia, and 8 (13.3%) had episodes of both. The mean duration of hypoglycemia per patient was 2.8 ± 2.9 hours and 4.68 ± 4.35 hours in the case of hyperglycemia, with 12 infants becoming severely hyperglycemic. Of the 12 severely hyperglycemic patients, 5 also developed severe hypoglycemia. No specific characteristics identified the hypoglycemic babies. A history of intrauterine growth restriction (P = .037) and female sex (P = .063) seemed to increase the risk of severe hyperglycemia. CONCLUSIONS VPT infants continue to have abnormal glucose values, especially hyperglycemia, by the time of hospital discharge. No specific factors identify babies at higher risk for hypoglycemia, and intrauterine growth restriction and female sex seemed to predispose to hyperglycemia.
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Ullrich RL, Chase HP. Changing the hemoglobin A1c goals for children with type 1 diabetes. Diabetes Technol Ther 2014; 16:611-2. [PMID: 25271369 DOI: 10.1089/dia.2014.0219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Rachel L Ullrich
- Department of Pediatrics, University of Colorado , Aurora, Colorado
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Abstract
The impact of diabetes on the developing brain is well-accepted. Effects on neurocognitive functioning are moderate but have larger functional implications, especially when considered through a developmental lens. Pathophysiological factors such as severe hypoglycemia and chronic hyperglycemia can alter developmental trajectories in early childhood and perhaps at later periods. In this paper, we selectively review neurocognitive outcomes in pediatric diabetes (largely type 1), integrating recent research from developmental neuroscience and neuroimaging. We examine the effects of diabetes at different stages and place findings within a neurodevelopmental diathesis/stress framework. Early-onset diabetes is associated with specific effects on memory and more global cognitive late-effects, but less is known about cognitive outcomes of diabetes in later childhood and in adolescence, a time of increased neurobehavioral vulnerability that has received relatively limited empirical attention. Studies are also needed to better elucidate risk and protective factors that may moderate neurodevelopmental outcomes in youth with diabetes.
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Affiliation(s)
- David D Schwartz
- Section of Psychology, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA,
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