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Rama Chandran S, Jacob P, Choudhary P. A systematic review of the effect of prior hypoglycaemia on cognitive function in type 1 diabetes. Ther Adv Endocrinol Metab 2020; 11:2042018820906017. [PMID: 32110374 PMCID: PMC7025428 DOI: 10.1177/2042018820906017] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 01/17/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The effect of prior hypoglycaemia on cognitive function in type 1 diabetes is an important unresolved clinical question. In this systematic review, we aimed to summarize the studies exploring the impact of prior hypoglycaemia on any aspect of cognitive function in type 1 diabetes. METHODS We used a multidatabase search platform Healthcare Database Advanced Search to search Medline, PubMed, EMBASE, EMCARE, CINAHL, PsycINFO, BNI, HMIC, and AMED from inception until 1 May 2019. We included studies on type 1 diabetes of any age. The outcome measure was any aspect of cognitive function. RESULTS The 62 studies identified were grouped as severe hypoglycaemia (SH) in childhood (⩽18 years) and adult-onset (>18 years) diabetes, nonsevere hypoglycaemia (NSH) and nocturnal hypoglycaemia (NH). SH in early childhood-onset diabetes, especially seizures and coma, was associated with poorer memory (verbal and visuospatial), as well as verbal intelligence. Among adult-onset diabetes, SH was associated with poorer cognitive performance in the older age (>55 years) group only. Early versus late exposure to SH had a significant association with cognitive dysfunction (CD). NSH and NH did not have any significant association with CD, while impaired awareness of hypoglycaemia was associated with poorer memory and cognitive-processing speeds. CONCLUSION The effect of SH on cognitive function is age dependent. Exposure to SH in early childhood (<10 years) and older age groups (>55 years) was associated with a moderate effect on the decrease in cognitive function in type 1 diabetes [PROSPERO ID: CRD42019141321].
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Affiliation(s)
| | - Peter Jacob
- King’s College London, Weston Education Centre, London, UK
| | - Pratik Choudhary
- Department of Diabetes, King’s College Hospital, London, UK
- King’s College London, Weston Education Centre, London, UK
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Al-Abdulrazzaq D, Al-Taiar A, Shaltout A, Davidsson L, Al-Kandari H. Audit of glycemic control in patients with type 1 diabetes referred to a pediatric clinic in a specialized center in Kuwait. Diabetes Res Clin Pract 2019; 156:107827. [PMID: 31449872 DOI: 10.1016/j.diabres.2019.107827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 06/12/2019] [Accepted: 08/22/2019] [Indexed: 10/26/2022]
Abstract
INTRODUCTION Intensive glycemic control reduces the risk of microvascular and macrovascular complications. Furthermore, optimal glycemic control is essential for normal growth and development. Thus, there is a need to monitor and evaluate glycemic control in patients with type 1 diabetes (T1D). Our aim was to audit glycemic control in patients with T1D in a specialized center as per the Society of Pediatric and Adolescent Diabetes (ISPAD) Hemoglobin A1C (HbA1C) target recommendations published in 2014. METHODS This is a retrospective cross-sectional study reporting on glycemic control (HbA1C) of patients younger than 21 years of age and with T1D treated at Dasman Diabetes Institute (DDI) between January 2013 and December 2015. RESULTS A total of 470 patients with T1D (250 males and 220 females) were included. Only 53 (11.3%) patients met the ISPAD target for optimal glycemic control with HbA1C < 7.5% (58 mmol/mol). Older age was positively associated with poor glycemic control (p = 0.001) while Continuous Subcutaneous Insulin Infusion (CSII) therapy was negatively associated with poor glycemic control, adjusted Odds Ratio (OR) 0.33 (95% confidence interval (CI): 0.16-0.66) for CSII and adjusted OR 0.42 (95% CI: 0.27-0.64) for shifting to CSII (p < 0.001). CONCLUSION Achieving optimal glycemic control is a significant challenge for young patients with T1D. Glycemic control goals should be individualized to achieve such goals safely, realistically and with a better quality of life for patients with T1D.
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Affiliation(s)
- Dalia Al-Abdulrazzaq
- Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait; Department of Maternal and Child Research, Dasman Diabetes Institute, Kuwait.
| | - Abdulla Al-Taiar
- School of community and Environmental health, College of Health Sciences, Old dominion University, USA.
| | - Azza Shaltout
- Department of Maternal and Child Research, Dasman Diabetes Institute, Kuwait
| | - Lena Davidsson
- Department of Maternal and Child Research, Dasman Diabetes Institute, Kuwait.
| | - Hessa Al-Kandari
- Department of Maternal and Child Research, Dasman Diabetes Institute, Kuwait.
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Yu L, Chen Y, Xu Y, He T, Wei Y, He R. D-ribose is elevated in T1DM patients and can be involved in the onset of encephalopathy. Aging (Albany NY) 2019; 11:4943-4969. [PMID: 31307014 PMCID: PMC6682534 DOI: 10.18632/aging.102089] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 07/04/2019] [Indexed: 12/25/2022]
Abstract
Although many mechanisms have been proposed for diabetic encephalopathy in type 2 diabetes mellitus (T2DM), the risk factors for cognitive impairment in type 1 diabetes mellitus (T1DM) are less clear. Here, we show that streptozotocin (STZ)-induced T1DM rats showed cognitive impairment in both Y maze and Morris water maze assays, accompanied with D-ribose was significantly increased in blood and urine, in addition to D-glucose. Furthermore, advanced glycation end products (AGE), Tau hyperphosphorylation and neuronal death in the hippocampal CA4/DG region were detected in T1DM rats. The expression and activity of transketolase (TKT), an important enzyme in the pentose shunt, were decreased in the brain, indicating that TKT may be involved in D-ribose metabolism in T1DM. Support for these change was demonstrated by the activation of TKT with benfotiamine (BTMP) treatment. Decreased D-ribose levels but not D-glucose levels; markedly reduced AGE accumulation, Tau hyperphosphorylation, and neuronal death; and improved cognitive ability in T1DM rats were shown after BTMP administration. In clinical investigation, T1DM patients had high D-ribose levels in both urine and serum. Our work suggests that D-ribose is involved in the cognitive impairment in T1DM and may provide a potentially novel target for treating diabetic encephalopathy.
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Affiliation(s)
- Lexiang Yu
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing 100101, China
| | - Yao Chen
- School of Basic Medical Sciences of Southwest Medical University, Luzhou 646000, China
| | - Yong Xu
- Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Tao He
- School of Basic Medical Sciences of Southwest Medical University, Luzhou 646000, China
| | - Yan Wei
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing 100101, China
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
| | - Rongqiao He
- School of Basic Medical Sciences of Southwest Medical University, Luzhou 646000, China
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing 100101, China
- Alzheimer’s Disease Center, Beijing Institute for Brain Disorders, Center for Brain Disorders Research, Capital Medical University, Beijing 100069, China
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Giganti F, Gavazzi G, Righi S, Rossi A, Caprilli S, Giovannelli F, Toni S, Rebai M, Viggiano MP. Priming effect in children with Type 1 Diabetes Mellitus. Child Neuropsychol 2019; 26:100-112. [PMID: 31111792 DOI: 10.1080/09297049.2019.1617260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Previous studies have evidenced cognitive difficulties across various domains in Type 1 Diabetes Mellitus (T1DM) children, but the implicit memory system has not yet been systematically explored.Taking into account that the interplay between memory and perception may be modulated by the semantic category of the stimuli and their salience, we explored explicit and implicit memory using both object and food stimuli to verify whether for T1DM children there is a feebleness in performing the function of memory as a function of the stimuli used.Eighteen T1DM children and 47 healthy children performed an explicit recognition task in which they were requested to judge whether the presented image had already been shown ("old") or not ("new") and an identification priming task in which they were asked to name new and old pictures presented at nine ascending levels of spatial filtering.Results did not reveal any differences between controls and T1DM children in the explicit memory recognition task, whereas some differences between the two groups were found in the identification priming task. In T1DM children, the priming effect was observed only for food images.The dissociation between implicit and explicit memory observed in children with diabetes seems to be modulated by the category of the stimuli, and these results underscore the relevance of taking into account this variable when exploring cognitive functions.
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Affiliation(s)
- F Giganti
- Department of Neuroscience, Psychology, Drug Research, Child Health, University of Florence, Florence, Italy
| | - G Gavazzi
- Diagnostic and Nuclear Research Institute, IRCCS SDN, Napoli, Italy
| | - S Righi
- Department of Neuroscience, Psychology, Drug Research, Child Health, University of Florence, Florence, Italy
| | - A Rossi
- Department of Neuroscience, Psychology, Drug Research, Child Health, University of Florence, Florence, Italy
| | - S Caprilli
- Istituto di Psicoanalisi - ISIPSE, Rome, Italy
| | - F Giovannelli
- Department of Neuroscience, Psychology, Drug Research, Child Health, University of Florence, Florence, Italy
| | - S Toni
- Pediatric Diabetologic Unit, AOU Meyer, Florence, Italy
| | - M Rebai
- CRFDP, Normandie Université, Rouen, France
| | - M P Viggiano
- Department of Neuroscience, Psychology, Drug Research, Child Health, University of Florence, Florence, Italy
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Cameron FJ, Northam EA, Ryan CM. The effect of type 1 diabetes on the developing brain. THE LANCET CHILD & ADOLESCENT HEALTH 2019; 3:427-436. [PMID: 30987935 DOI: 10.1016/s2352-4642(19)30055-0] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 02/17/2019] [Accepted: 02/18/2019] [Indexed: 12/25/2022]
Abstract
The effect of type 1 diabetes on the developing brain is a topic of primary research interest. A variety of potential dysglycaemic insults to the brain can cause cellular and structural injury and lead to altered neuropsychological outcomes. These outcomes might be subtle in terms of cognition but appear to persist into adult life. Age and circumstance at diagnosis appear to play a substantial role in potential CNS injury. A history of diabetic ketoacidosis and chronic hyperglycaemia appear to be more injurious than previously suspected, whereas a history of severe hypoglycaemia is perhaps less injurious. Neurocognitive deficits manifest across multiple cognitive domains, including executive function and speed of information processing. Some evidence suggests that subtle brain injury might directly contribute to psychological and mental health outcomes. Impaired executive function and mental health, in turn, could affect patients' adherence and the ability to make adaptive lifestyle choices. Impaired executive functioning creates a potential feedback loop of diabetic dysglycaemia leading to brain injury, further impaired executive function and mental health, which results in suboptimal adherence, and further dysglycaemia. Clinicians dealing with patients with suboptimal glycaemic outcomes should be aware of these potential issues.
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Affiliation(s)
- Fergus J Cameron
- The Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, VIC, Australia; The Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia.
| | - Elisabeth A Northam
- The School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia
| | - Christopher M Ryan
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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He J, Ryder AG, Li S, Liu W, Zhu X. Glycemic extremes are related to cognitive dysfunction in children with type 1 diabetes: A meta-analysis. J Diabetes Investig 2018; 9:1342-1353. [PMID: 29573221 PMCID: PMC6215942 DOI: 10.1111/jdi.12840] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 02/22/2018] [Accepted: 03/13/2018] [Indexed: 12/18/2022] Open
Abstract
Aims/Introduction To examine the magnitude and pattern of cognitive dysfunction in children with type 1 diabetes, and the possible effects associated with other disease variables, such as early onset diabetes, severe hypoglycemia and hyperglycemia. Materials and Methods We carried out a meta‐analysis using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. We searched MedLine, Embase and PsycINFO to identify studies on cognitive function in children with type 1 diabetes that were published up until 30 September 2016. Effect sizes understood as the standardized mean differences between groups with diabetes and control groups (i.e., Hedges’ g) were calculated to quantify the extent of cognitive dysfunction in those groups consisting of children with diabetes. Results A total of 19 studies met our inclusion criteria, comprising 1,355 participants with type 1 diabetes and 696 controls. Compared with non‐diabetic controls, children with type 1 diabetes showed a significantly poorer cognitive performance overall (g = −0.46), as well as specific deficits in full‐scale intelligence (g = −1.06), attention (g = −0.60) and psychomotor speed (g = −0.46). Glycemic extremes were associated with poorer overall cognition (g = −0.18), as well as slightly lower performance in memory (g = −0.27). Conclusions We found that type 1 diabetes was associated with cognitive dysfunction characterized by a lowered intelligence, diminished attention and a slowing of psychomotor speed. Glycemic extremes, which are described as a period of high glucose levels and severe hypoglycemia, were related to cognitive dysfunction in children with type 1 diabetes.
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Affiliation(s)
- Jing He
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.,Medical Psychological Institute of Central South University, Changsha, China
| | - Andrew G Ryder
- Center for Clinical Research in Health & Department of Psychology, Concordia University, Montreal, Quebec, Canada.,Culture and Mental Health Research Unit & Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Shichen Li
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.,Medical Psychological Institute of Central South University, Changsha, China
| | - Wanting Liu
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.,Medical Psychological Institute of Central South University, Changsha, China
| | - Xiongzhao Zhu
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.,Medical Psychological Institute of Central South University, Changsha, China
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Li W, Huang E, Gao S. Type 1 Diabetes Mellitus and Cognitive Impairments: A Systematic Review. J Alzheimers Dis 2018; 57:29-36. [PMID: 28222533 DOI: 10.3233/jad-161250] [Citation(s) in RCA: 114] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Type 1 diabetes mellitus (T1DM) is a major subtype of diabetes and is usually diagnosed at a young age with insulin deficiency. The life expectancy of T1DM patients has increased substantially in comparison with that three decades ago due to the availability of exogenous insulin, though it is still shorter than that of healthy people. However, the relation remains unclear between T1DM and dementia as an aging-related disease. We conducted a systematic review of existing literature on T1DM and cognition impairments by carrying out searches in electronic databases Medline, EMBASE, and Google Scholar. We restricted our review to studies involving only human subjects and excluded studies on type 2 diabetes mellitus or non-classified diabetes. A meta-analysis was first performed on the relationship between T1DM and cognitive changes in youths and adults respectively. Then the review focused on the cognitive complications of T1DM and their relation with the characteristics of T1DM, glycemic control, diabetic complications, comorbidities, and others. First, age at onset, disease duration, and glycemic dysregulation were delineated for their association with cognitive changes. Then diabetic ketoacidosis, angiopathy, and neuropathy were examined as diabetic complications for their involvement in cognitive impairments. Lastly, body mass index and blood pressure were discussed for their relations with the cognitive changes. Future studies are needed to elucidate the pathogenesis of T1DM-related cognitive impairments or dementia.
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Affiliation(s)
- Wei Li
- Master of Physician Assistant Studies, School of Health and Rehabilitation Sciences, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA
| | - Edgar Huang
- School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA
| | - Sujuan Gao
- Department of Biostatistics, School of Medicine, Indiana University, Indianapolis, IN, USA
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Van Name MA, Hilliard ME, Boyle CT, Miller KM, DeSalvo DJ, Anderson BJ, Laffel LM, Woerner SE, DiMeglio LA, Tamborlane WV. Nighttime is the worst time: Parental fear of hypoglycemia in young children with type 1 diabetes. Pediatr Diabetes 2018; 19:114-120. [PMID: 28429581 PMCID: PMC5650950 DOI: 10.1111/pedi.12525] [Citation(s) in RCA: 102] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 03/03/2017] [Accepted: 03/06/2017] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Fear of hypoglycemia is common in parents of young children with type 1 diabetes (T1D), but little is known about the specific fears that parents most often experience. Hypoglycemia fear has been associated with poorer glycemic control in older children, though not yet studied in a large cohort of very young children. MATERIALS AND METHODS Parents of 549 children <7 years (mean 5.2 ± 1.2 years [19% <3 years]) with a mean diabetes duration of 2.4 ± 1.0 years (range 1-6 years) and mean HbA1c 8.2% ± 1.1% (66 ± 12 mmol/mol) registered in the T1D Exchange completed the worry scale of the Hypoglycemia Fear Survey modified for parents (HFS-P). RESULTS Mean parental fear of hypoglycemia worry score was 36.1 ± 23.1 (possible range 0-100), with most frequent worries related to the child having a low while asleep and the child not recognizing a low. The mean worry score was not associated with the child's age, glycemic control, or recent severe hypoglycemic event. Parental worries about lows while sleeping were significantly higher in pump users than non-users (61% vs. 45%; P < .001), and tended to be higher in CGM users than non-users (62% vs 51%; P = .02). CONCLUSIONS The greatest worries of parents of young children with T1D were related to hypoglycemia during sleep and other times/circumstances during which it would be difficult to detect hypoglycemia. Using advanced diabetes technologies may be an effort to temper fears about hypoglycemia during sleep, though the directionality of this relationship is undetermined. Additional studies can clarify this association and leverage use of diabetes technologies to improve glycemic control.
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Affiliation(s)
| | - Marisa E. Hilliard
- Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Ave., Houston, TX 77030
| | - Claire T. Boyle
- Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647
| | - Kellee M. Miller
- Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647
| | - Daniel J. DeSalvo
- Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Ave., Houston, TX 77030
| | - Barbara J. Anderson
- Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Ave., Houston, TX 77030
| | - Lori M. Laffel
- Joslin Diabetes Center, One Joslin Place, Boston, MA 02215
| | - Stephanie E. Woerner
- Indiana University School of Medicine, Rm 5960, 705 Riley Hospital Drive, Indianapolis, IN 46202
| | - Linda A. DiMeglio
- Indiana University School of Medicine, Rm 5960, 705 Riley Hospital Drive, Indianapolis, IN 46202
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Abo-el-Asrar M, Andrawes NG, Rabie MA, El-Gabry DA, Khalifa AG, El-Sherif M, Abdel Aziz K. Cognitive functions in children and adolescents with early-onset diabetes mellitus in Egypt. APPLIED NEUROPSYCHOLOGY-CHILD 2016; 7:21-30. [DOI: 10.1080/21622965.2016.1224186] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
| | - Nevine G. Andrawes
- Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Menan A. Rabie
- Psychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Dina Aly El-Gabry
- Psychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Abdel-Gawad Khalifa
- Psychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mariam El-Sherif
- Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Karim Abdel Aziz
- Psychiatry Department, College of Medicine, United Arab Emirates University, Al-Ain, United Arab Emirates
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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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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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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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Tonoli C, Heyman E, Roelands B, Pattyn N, Buyse L, Piacentini MF, Berthoin S, Meeusen R. Type 1 diabetes-associated cognitive decline: a meta-analysis and update of the current literature. J Diabetes 2014; 6:499-513. [PMID: 25042689 DOI: 10.1111/1753-0407.12193] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Revised: 05/07/2014] [Accepted: 06/29/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) can have a significant impact on brain structure and function, which is referred to as T1D-associated cognitive decline (T1DACD). Diabetes duration, early onset disease, and diabetes-associated complications are all proposed as factors contributing to T1DACD. However, there have been no comparisons in T1DACD between children and adults with T1D. To obtain a better insight into the occurrence and effects of T1DACD in T1D, the aim of the present meta-analysis was to investigate differences between children and adults and to analyse factors contributing T1DACD. METHODS Two electronic databases were consulted: PubMed and ISI Web of Knowledge. Literature published up until the end of 2013 was included in the analysis. Effect sizes (Cohen's d), which are standardized differences between experimental and control groups, were calculated. RESULTS There was a small to modest decrease in cognitive performance in T1D patients compared with non-diabetic controls. Children with T1D performed worse while testing for executive function, full intelligence quotient (IQ), and motor speed, whereas adults with T1D performed worse while testing the full, verbal and performance IQ, part of the executive function, memory, spatial memory, and motor speed. Episodes of severe hypoglycemia, chronic hyperglycemia, and age of onset can be significant factors influencing cognitive function in T1D. CONCLUSIONS The findings in the literature suggest that T1DACD is more severe in adults than children, indicating that age and diabetes duration contribute to this T1DACD.
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Affiliation(s)
- Cajsa Tonoli
- Department of Human Physiology and Sports Medicine, Faculty of Physical Education and Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium; Department EA4488, Physical Activity, Muscle, Health, University Lille Nord de France, Lille, France
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Danne T, Bangstad HJ, Deeb L, Jarosz-Chobot P, Mungaie L, Saboo B, Urakami T, Battelino T, Hanas R. ISPAD Clinical Practice Consensus Guidelines 2014. Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes 2014; 15 Suppl 20:115-34. [PMID: 25182312 DOI: 10.1111/pedi.12184] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 06/16/2014] [Indexed: 02/03/2023] Open
Affiliation(s)
- Thomas Danne
- Kinder- und Jugendkrankenhaus auf der Bult, Diabetes-Zentrum für Kinder und Judendliche, Hannover, Germany
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Rewers MJ, Pillay K, de Beaufort C, Craig ME, Hanas R, Acerini CL, Maahs DM. ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatr Diabetes 2014; 15 Suppl 20:102-14. [PMID: 25182311 DOI: 10.1111/pedi.12190] [Citation(s) in RCA: 226] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 06/16/2014] [Indexed: 12/24/2022] Open
Affiliation(s)
- Marian J Rewers
- Barbara Davis Center, University of Colorado Denver, Aurora, CO, USA
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Hypoglycemia induced by insulin as a triggering factor of cognitive deficit in diabetic children. ScientificWorldJournal 2014; 2014:616534. [PMID: 24790575 PMCID: PMC3982249 DOI: 10.1155/2014/616534] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Accepted: 02/18/2014] [Indexed: 12/12/2022] Open
Abstract
This paper provides an overview of insulin-induced hypoglycemia as a triggering factor of cognitive deficit in children with type 1 diabetes mellitus. For this purpose, databases from 1961 to 2013 were used with the objective of detecting the primary publications that address the impact of hypoglycemia on cognitive performance of diabetic children. The results obtained from experimental animals were excluded. The majority of studies demonstrated that the cognitive deficit in diabetic children involves multiple factors including duration, intensity, severity, and frequency of hypoglycemia episodes. Additionally, age at the onset of type 1 diabetes also influences the cognitive performance, considering that early inception of the disease is a predisposing factor for severe hypoglycemia. Furthermore, the results suggest that there is a strong correlation between brain damage caused by hypoglycemia and cognitive deterioration. Therefore, a more cautious follow-up and education are needed to impede and treat hypoglycemia in children with diabetes mellitus.
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Fullerton B, Jeitler K, Seitz M, Horvath K, Berghold A, Siebenhofer A, Cochrane Metabolic and Endocrine Disorders Group. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev 2014; 2014:CD009122. [PMID: 24526393 PMCID: PMC6486147 DOI: 10.1002/14651858.cd009122.pub2] [Citation(s) in RCA: 141] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Clinical guidelines differ regarding their recommended blood glucose targets for patients with type 1 diabetes and recent studies on patients with type 2 diabetes suggest that aiming at very low targets can increase the risk of mortality. OBJECTIVES To assess the effects of intensive versus conventional glycaemic targets in patients with type 1 diabetes in terms of long-term complications and determine whether very low, near normoglycaemic values are of additional benefit. SEARCH METHODS A systematic literature search was performed in the databases The Cochrane Library, MEDLINE and EMBASE. The date of the last search was December 2012 for all databases. SELECTION CRITERIA We included all randomised controlled trials (RCTs) that had defined different glycaemic targets in the treatment arms, studied patients with type 1 diabetes, and had a follow-up duration of at least one year. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data, assessed studies for risk of bias, with differences resolved by consensus. Overall study quality was evaluated by the 'Grading of Recommendations Assessment, Development, and Evaluation' (GRADE) system. Random-effects models were used for the main analyses and the results are presented as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. MAIN RESULTS We identified 12 trials that fulfilled the inclusion criteria, including a total of 2230 patients. The patient populations varied widely across studies with one study only including children, one study only including patients after a kidney transplant, one study with newly diagnosed adult patients, and several studies where patients had retinopathy or microalbuminuria at baseline. The mean follow-up duration across studies varied between one and 6.5 years. The majority of the studies were carried out in the 1980s and all trials took place in Europe or North America. Due to the nature of the intervention, none of the studies could be carried out in a blinded fashion so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the studies. Fifty per cent of the studies were judged to have a high risk of bias in at least one other category.Under intensive glucose control, the risk of developing microvascular complications was reduced compared to conventional treatment for a) retinopathy: 23/371 (6.2%) versus 92/397 (23.2%); RR 0.27 (95% CI 0.18 to 0.42); P < 0.00001; 768 participants; 2 trials; high quality evidence; b) nephropathy: 119/732 (16.3%) versus 211/743 (28.4%); RR 0.56 (95% CI 0.46 to 0.68); P < 0.00001; 1475 participants; 3 trials; moderate quality evidence; c) neuropathy: 29/586 (4.9%) versus 86/617 (13.9%); RR 0.35 (95% CI 0.23 to 0.53); P < 0.00001; 1203 participants; 3 trials; high quality evidence. Regarding the progression of these complications after manifestation, the effect was weaker (retinopathy) or possibly not existent (nephropathy: RR 0.79 (95% CI 0.37 to 1.70); P = 0.55; 179 participants with microalbuminuria; 3 trials; very low quality evidence); no adequate data were available regarding the progression of neuropathy. For retinopathy, intensive glucose control reduced the risk of progression in studies with a follow-up duration of at least two years (85/366 (23.2%) versus 154/398 (38.7%); RR 0.61 (95% CI 0.49 to 0.76); P < 0.0001; 764 participants; 2 trials; moderate quality evidence), while we found evidence for an initial worsening of retinopathy after only one year of intensive glucose control (17/49 (34.7%) versus 7/47 (14.9%); RR 2.32 (95% CI 1.16 to 4.63); P = 0.02; 96 participants; 2 trials; low quality evidence).Major macrovascular outcomes (stroke and myocardial infarction) occurred very rarely, and no firm evidence could be established regarding these outcome measures (low quality evidence).We found that intensive glucose control increased the risk for severe hypoglycaemia, however the results were heterogeneous and only the 'Diabetes Complications Clinical Trial' (DCCT) showed a clear increase in severe hypoglycaemic episodes under intensive treatment. A subgroup analysis according to the baseline haemoglobin A1c (HbA1c) of participants in the trials (low quality evidence) suggests that the risk of hypoglycaemia is possibly only increased for patients who started with relatively low HbA1c values (< 9.0%). Several of the included studies also showed a greater weight gain under intensive glucose control, and the risk of ketoacidosis was only increased in studies using insulin pumps in the intensive treatment group (very low quality evidence).Overall, all-cause mortality was very low in all studies (moderate quality evidence) except in one study investigating renal allograft as treatment for end-stage diabetic nephropathy. Health-related quality of life was only reported in the DCCT trial, showing no statistically significant differences between the intervention and comparator groups (moderate quality evidence). In addition, only the DCCT published data on costs, indicating that intensive glucose therapy control was highly cost-effective considering the reduction of potential diabetes complications (moderate quality evidence). AUTHORS' CONCLUSIONS Tight blood sugar control reduces the risk of developing microvascular diabetes complications. The evidence of benefit is mainly from studies in younger patients at early stages of the disease. Benefits need to be weighed against risks including severe hypoglycaemia, and patient training is an important aspect in practice. The effects of tight blood sugar control seem to become weaker once complications have been manifested. However, further research is needed on this issue. Furthermore, there is a lack of evidence from RCTs on the effects of tight blood sugar control in older patient populations or patients with macrovascular disease. There is no firm evidence for specific blood glucose targets and treatment goals need to be individualised taking into account age, disease progression, macrovascular risk, as well as the patient's lifestyle and disease management capabilities.
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Affiliation(s)
- Birgit Fullerton
- Goethe UniversityInstitute of General PracticeTheodor‐Stern‐Kai 7Frankfurt am MainHesseGermany60590
| | - Klaus Jeitler
- Medical University of GrazInstitute of General Practice and Evidence‐Based Health Services Research / Institute of Medical Informatics, Statistics and DocumentationAuenbruggerplatz 2/9GrazAustria8036
| | | | - Karl Horvath
- Medical University of GrazInstitute of General Practice and Evidence‐Based Health Services Research / Department of Internal Medicine, Division of Endocrinology and MetabolismAuenbruggerplatz 2/9GrazAustria8036
| | - Andrea Berghold
- Medical University of GrazInstitute of General Practice and Evidence‐Based Health Services Research / Institute of Medical Informatics, Statistics and DocumentationAuenbruggerplatz 2/9GrazAustria8036
| | - Andrea Siebenhofer
- Graz, Austria / Institute of General Practice, Goethe UniversityInstitute of General Practice and Evidence‐Based Health Services Research, Medical University of GrazFrankfurt am MainGermany
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Cognitive and motor perturbations in elderly with longstanding diabetes mellitus. Nutrition 2013; 30:628-35. [PMID: 24800665 DOI: 10.1016/j.nut.2013.11.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2013] [Revised: 10/11/2013] [Accepted: 11/06/2013] [Indexed: 01/21/2023]
Abstract
Type 2 diabetes mellitus is a chronic disease characterized by insulin resistance; inflammation; oxidative stress; vascular damage; and dysfunction of glucose, protein, and lipid metabolisms. However, comparatively less attention has been paid to neurologic alterations seen in elderly individuals with type 2 diabetes. We review clinical, metabolic, and biochemical aspects of diabetic encephalopathy (DE) and propose that quality of dietary lipids is closely linked to DE. This implies that preventive nutritional interventions may be designed to improve DE.
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de Beaufort CE, Lange K, Swift PGF, Aman J, Cameron F, Castano L, Dorchy H, Fisher LK, Hoey H, Kaprio E, Kocova M, Neu A, Njolstad PR, Phillip M, Schoenle E, Robert JJ, Urukami T, Vanelli M, Danne T, Barrett T, Chiarelli F, Aanstoot HJ, Mortensen HB. Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009. Pediatr Diabetes 2013; 14:422-8. [PMID: 22957743 DOI: 10.1111/j.1399-5448.2012.00922.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2012] [Revised: 07/15/2012] [Accepted: 08/02/2012] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE To investigate whether center differences in glycemic control are present in prepubertal children <11 yr with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS This cross-sectional study involved 18 pediatric centers worldwide. All children, <11 y with a diabetes duration ≥12 months were invited to participate. Case Record Forms included information on clinical characteristics, insulin regimens, diabetic ketoacidosis (DKA), severe hypoglycemia, language difficulties, and comorbidities. Hemoglobin A1c (HbA1c) was measured centrally by liquid chromatography (DCCT aligned, range: 4.4-6.3%; IFFC: 25-45 mmol/mol). RESULTS A total of 1133 children participated (mean age: 8.0 ± 2.1 y; females: 47.5%, mean diabetes duration: 3.8 ± 2.1 y). HbA1c (overall mean: 8.0 ± 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p < 0.001 resp. p = 0.179). Language difficulties showed a negative relationship with HbA1c (8.3 ± 1.2% vs. 8.0 ± 1.0%; p = 0.036). Frequency of blood glucose monitoring demonstrated a significant but weak association with HbA1c (r = -0.17; p < 0.0001). Although significant different HbA1c levels were obtained with diverse insulin regimens (range: 7.3-8.5%; p < 0.001), center differences remained after adjusting for insulin regimen (p < 0.001). Differences between insulin regimens were no longer significant after adjusting for center effect (p = 0.199). CONCLUSIONS Center differences in metabolic outcomes are present in children <11 yr, irrespective of diabetes duration, age, or gender. The incidence of severe hypoglycemia is lower than in adolescents despite achieving better glycemic control. Insulin regimens show a significant relationship with HbA1c but do not explain center differences. Each center's effectiveness in using specific treatment strategies remains the key factor for outcome.
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Affiliation(s)
- Carine E de Beaufort
- Pediatric Clinic, Centre Hospitalier de Luxembourg, Luxembourg, GD de Luxembourg.
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Osipoff JN, Dixon D, Wilson TA, Preston T. Prospective memory and glycemic control in children with type 1 diabetes mellitus: a cross-sectional study. INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY 2012. [PMID: 23198726 PMCID: PMC3541107 DOI: 10.1186/1687-9856-2012-29] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background Prospective memory is that memory which is required to carry out intended actions and is therefore essential in carrying out the daily activities required in the self-management of type 1 diabetes mellitus (T1DM). This study aimed to identify the relationships between prospective memory and diabetic control in children with T1DM. Method 94 children aged 6–18 years with T1DM completed an innovative prospective memory screen, PROMS, and a series of cognitive tests. Parents answered questionnaires about their children's diabetic histories and cognitive skills. Results No association between total PROMS score and glycemic control was found. Lower HbA1C was associated with higher (better) scores on the 20 minute event-based task on the PROMS. Parental concerns about working memory and metacognition in their children were mirrored by higher HbA1C. Conclusions This study suggests that there may be an association between glycemic control and prospective memory for event based tasks. Additional studies need to be done to determine reproducibility, causality, and if prospective memory based interventions can improve diabetic control.
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Affiliation(s)
- Jennifer N Osipoff
- Division of Pediatric Endocrinology, Department of Pediatrics, Stony Brook Children's Hospital, HSC Level 11 Room 080, Stony Brook, NY, 11794-8111, USA.
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Lehecka KE, Renukuntla VS, Heptulla RA. Insight into hypoglycemia in pediatric type 1 diabetes mellitus. INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY 2012; 2012:19. [PMID: 22716962 PMCID: PMC3441359 DOI: 10.1186/1687-9856-2012-19] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/25/2012] [Accepted: 04/15/2012] [Indexed: 02/06/2023]
Abstract
Hypoglycemia is a common complication of insulin treatment in type 1 diabetes mellitus and can occur in any patient with diabetes when glucose consumption exceeds supply. Many studies have been done to elucidate those factors that predict severe hypoglycemia: younger age, longer duration of diabetes, lower HgbA1c, higher insulin dose, lower Body Mass Index, male gender, Caucasian race, underinsurance or low socioeconomic status, and the presence of psychiatric disorders. Hypoglycemia can affect patients' relationships, occupation, and daily activities such as driving. However, one of the greatest impacts is patients' fear of severe hypoglycemic events, which is a limiting factor in the optimization of glycemic control. Therefore, the importance of clinicians' ability to identify those patients at greatest risk for hypoglycemic events is two-fold: 1) Patients at greatest risk may be counseled as such and offered newer therapies and monitoring technologies to prevent hypoglycemic events. 2) Patients at lower risk may be reassured and encouraged to improve their glycemic control. Since the risk of long-term complications with poor blood glucose control outweighs the risks of hypoglycemia with good blood glucose control, patients should be encouraged to aim for glucose concentrations in the physiologic range pre- and post-prandially. Advancements in care, including multiple daily injection therapy with analog insulin, continuous subcutaneous insulin infusion, and continuous glucose monitoring, have each subsequently improved glycemic control and decreased the risk of severe hypoglycemia.
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Affiliation(s)
- Kimberly E Lehecka
- Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA
| | - Venkat S Renukuntla
- Department of Pediatrics, Division of Pediatric Endocrinology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA
| | - Rubina A Heptulla
- Department of Pediatrics, Division of Pediatric Endocrinology, Albert Einstein College of Medicine/ The Children’s Hospital at Montefiore, 3415 Bainbridge Ave, Bronx, NY, 10467, USA
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Affiliation(s)
- Marit Rokne Bjørgaas
- Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Prinsesse Kristinas gate 1, N-7006 Trondheim, Norway.
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Blasetti A, Chiuri RM, Tocco AM, Di Giulio C, Mattei PA, Ballone E, Chiarelli F, Verrotti A. The effect of recurrent severe hypoglycemia on cognitive performance in children with type 1 diabetes: a meta-analysis. J Child Neurol 2011; 26:1383-91. [PMID: 21572053 DOI: 10.1177/0883073811406730] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The purpose of this study was to investigate the existence and extent of cognitive impairment in type 1 diabetic children with episodes of recurrent severe hypoglycemia, using meta-analysis to synthesize data across studies. The meta-analysis sample included: 441 children with diabetes and recurrent severe hypoglycemia, 560 children with diabetes and without recurrent severe hypoglycemia. Overall, children with type 1 diabetes and recurrent severe hypoglycemia had slightly lower performance than diabetic children without severe hypoglycemia, only in some cognitive domains: intelligence, memory, learning, and verbal fluency/language. Greater impairment was found in memory and learning. No impairment was found for motor speed. Our results seem to confirm the hypothesis that recurrent severe hypoglycemia has a selective negative effect on the children's cognitive functions. However, these results must be considered with caution taking into account factors such as small sample sizes, the different definitions of severe hypoglycemia, and the variety of neuropsychological tests used.
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Gonder-Frederick L, Nyer M, Shepard JA, Vajda K, Clarke W. Assessing fear of hypoglycemia in children with Type 1 diabetes and their parents. ACTA ACUST UNITED AC 2011; 1:627-639. [PMID: 22180760 DOI: 10.2217/dmt.11.60] [Citation(s) in RCA: 121] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This article summarizes the literature on fear of hypoglycemia in pediatric Type 1 diabetes and the assessment of this fear in both children with Type 1 diabetes and their parents. The most common instrument for assessing fear of hypoglycemia in this population is the children's and parent's versions of the Hypoglycemia Fear Survey (HFS), although studies using other assessment measures are also reviewed. Studies using this survey have identified variables contributing to fear of hypoglycemia in children with Type 1 diabetes and their parents, such as history of frequent or traumatic hypoglycemia, as well as trait anxiety. In addition to this summary of the literature, new data are presented supporting the reliability of hypoglycemic fear assessment in younger children and comparing fear of hypoglycemia in children in different age groups (6-18 years old) and their parents. Also reviewed are studies investigating the relationship between fear of hypoglycemia and diabetes control, which have yielded inconsistent results. Given the potential importance of fear of hypoglycemia in pediatric diabetes, there has been limited research in this area.
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Ly TT, Anderson M, McNamara KA, Davis EA, Jones TW. Neurocognitive outcomes in young adults with early-onset type 1 diabetes: a prospective follow-up study. Diabetes Care 2011; 34:2192-7. [PMID: 21844288 PMCID: PMC3177715 DOI: 10.2337/dc11-0697] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The aim of this study was to reexamine the neurocognitive function of a cohort of young adults with early-onset type 1 diabetes and compare their cognitive function to a matched control group. We also examined whether cognitive function was related to prospectively obtained severe hypoglycemia history, long-term glycemic control, or severe diabetic ketoacidosis. RESEARCH DESIGN AND METHODS Testing included Wechsler Intelligence Scale for Children and Adults, Wechsler Memory Scale, Cattell Culture Fair Intelligence Test (CCFIT), Wisconsin Card Sorting Test (WCST), youth and adult self-report, and Beck Depression Inventory. We tested 34 control subjects (mean ± SE, age 19.5 ± 0.5 years) and 33 type 1 diabetic subjects (age 19.3 ± 0.5 years, age at type 1 diabetes onset 3.3 ± 0.3 years, A1C from diagnosis 8.7 ± 0.1%, and diabetes duration 16.0 ± 0.5 years). RESULTS There was no difference in full-scale IQ scores in type 1 diabetic and control subjects (100.7 ± 2.0 vs. 102.5 ± 1.4). There was no difference between groups in memory subtests or in reporting of emotional and behavioral difficulties. The type 1 diabetes group scored lower on the CCFIT for fluid intelligence compared with control subjects (P = 0.028) and also scored lower on WCST with more perseverative errors (P = 0.002) and fewer categories completed (P = 0.022). CONCLUSIONS These data suggest no difference in general intellectual ability, memory, and emotional difficulties in our cohort of young adults with early-onset type 1 diabetes compared with control subjects and no deterioration over time. There were, however, findings to suggest subtle changes leading to poorer performance on complex tasks of executive function.
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Affiliation(s)
- Trang T Ly
- Department of Endocrinology & Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.
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Barat P, Tastet S, Vautier V. Impact neuropsychologique à long terme du diabète de type 1 chez l’enfant. Arch Pediatr 2011; 18:432-40. [DOI: 10.1016/j.arcped.2011.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2010] [Revised: 10/28/2010] [Accepted: 01/24/2011] [Indexed: 10/18/2022]
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Blasetti A, Di Giulio C, Tocco AM, Verrotti A, Tumini S, Chiarelli F, Altobelli E. Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population-based study. Pediatr Diabetes 2011; 12:4-10. [PMID: 20723102 DOI: 10.1111/j.1399-5448.2010.00655.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE Hypoglycemia remains a central problem in the management of type 1 diabetes mellitus (T1DM) and limits the achievement of good or normal glycemic control. The Diabetes Control and Complication Trial showed that intensive treatment of T1DM increased the risk of severe hypoglycemia (SH) when compared to conventional therapy. The aim of our study was to determine the incidence of SH and associated variables in a population of children and adolescents with T1DM. RESEARCH DESIGN AND METHODS We performed a 7.5-yr prospective study enrolling 195 patients aged 13.9 ± 6.6 yr. The study was carried out by referring to the T1DM population-based register in the Abruzzo region of Italy. The incidence of SH, defined as blood glucose levels <50 mg/dL (<2.77 mmol/L) associated with altered states of consciousness (including confusional state, seizures, and coma) was recorded. Glycated hemoglobin (HbA1c) percentage, insulin dose, insulin regimen, time since diagnosis, and age at onset were also recorded. RESULTS One hundred and thirty-three severe hypoglycemic events occurred during the study period; the overall incidence was 9.4 episodes per 100 patient-years. Significant predictors of hypoglycemia were diabetes duration >10 yr (p = 0.01), basal/bolus insulin ratio (ratio of daily basal insulin units to daily bolus insulin units) >0.8 (p = 0.01). No relationship was found between hypoglycemic episodes and HbA1c levels, daily insulin requirements, or insulin regimen. CONCLUSIONS In these patients, a relatively low incidence of SH was recorded, without pronounced association with lower HbA1c or multiple daily injection insulin therapy. SH seems to be mainly related to management of diabetes. We believe that the main path to SH prevention is through patient and family education in the management of T1DM.
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Affiliation(s)
- Annalisa Blasetti
- Department of Pediatrics, University of Chieti, Via dei Vestini 5, Chieti, Italy.
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Silverstein JM, Musikantow D, Puente EC, Daphna-Iken D, Bree AJ, Fisher SJ. Pharmacologic amelioration of severe hypoglycemia-induced neuronal damage. Neurosci Lett 2011; 492:23-8. [PMID: 21272612 DOI: 10.1016/j.neulet.2011.01.045] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Accepted: 01/19/2011] [Indexed: 10/18/2022]
Abstract
Hypoglycemia is a common complication for insulin treated people with diabetes. Severe hypoglycemia, which occurs in the setting of excess or ill-timed insulin administration, has been shown to cause brain damage. Previous pre-clinical studies have shown that memantine (an N-methyl-d-aspartate receptor antagonist) and erythropoietin can be neuroprotective in other models of brain injury. We hypothesized that these agents might also be neuroprotective in response to severe hypoglycemia-induced brain damage. To test this hypothesis, 9-week old, awake, male Sprague-Dawley rats underwent hyperinsulinemic (0.2 U kg(-1)min(-1)) hypoglycemic clamps to induce severe hypoglycemia (blood glucose 10-15 mg/dl for 90 min). Animals were randomized into control (vehicle) or pharmacological treatments (memantine or erythropoietin). One week after severe hypoglycemia, neuronal damage was assessed by Fluoro-Jade B and hematoxylin and eosin staining of brain sections. Treatment with both memantine and erythropoietin significantly decreased severe hypoglycemia-induced neuronal damage in the cortex by 35% and 39%, respectively (both p<0.05 vs. controls). These findings demonstrate that memantine and erythropoietin provide a protective effect against severe hypoglycemia-induced neuronal damage.
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Affiliation(s)
- Julie M Silverstein
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine,Washington University, St. Louis, MO 63110, USA
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Pacaud D, Dewey D. Neurocognitive outcome of children exposed to severe hypoglycemiain utero. ACTA ACUST UNITED AC 2011. [DOI: 10.2217/dmt.10.10] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Vanhorebeek I, Gielen M, Boussemaere M, Wouters PJ, Grandas FG, Mesotten D, Van den Berghe G. Glucose dysregulation and neurological injury biomarkers in critically ill children. J Clin Endocrinol Metab 2010; 95:4669-79. [PMID: 20668035 DOI: 10.1210/jc.2010-0805] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
Abstract
CONTEXT Targeting normoglycemia with intensive insulin therapy (IIT) improved short-term outcome of pediatric intensive care unit (PICU) patients but increased the incidence of hypoglycemia. Both hyperglycemia and hypoglycemia may adversely affect the developing brain. OBJECTIVE We studied the impact of targeting normoglycemia with IIT on brain injury markers. DESIGN This is a preplanned analysis of PICU patients included in a randomized controlled study. SETTING The study was conducted at a university hospital PICU. PATIENTS Seven hundred PICU patients participated. INTERVENTIONS Patients were assigned to IIT targeting normal-for-age fasting blood glucose levels or insulin infusion only to prevent excessive hyperglycemia. MAIN OUTCOME MEASURES Serum S100B and neuron-specific enolase (NSE), biomarkers of astrocytic and neuronal damage, respectively, were measured on fixed days (n = 700) and in a nested case-control design before and after hypoglycemia (n = 126). RESULTS Admission levels of S100B and NSE differed according to diagnosis and illness severity (P < 0.0001). IIT did not affect the time course of these markers. Patients experiencing hypoglycemia in PICU had higher S100B and NSE from admission onward than those without hypoglycemia. In the nested case-control study, both markers decreased after hypoglycemia (P = 0.001 and P = 0.009), unlike in the controls on matched days. CONCLUSIONS IIT in PICU did not evoke neurological damage detectable by circulating S100B and NSE, despite increased incidence of hypoglycemia. Elevated markers in patients with hypoglycemia were not caused by hypoglycemia itself but rather reflect an increased incidence of hypoglycemia in the most severely ill. This hypoglycemia risk appears difficult to capture by classical illness severity scores.
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Affiliation(s)
- Ilse Vanhorebeek
- Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
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Asvold BO, Sand T, Hestad K, Bjørgaas MR. Cognitive function in type 1 diabetic adults with early exposure to severe hypoglycemia: a 16-year follow-up study. Diabetes Care 2010; 33:1945-7. [PMID: 20805272 PMCID: PMC2928338 DOI: 10.2337/dc10-0621] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE We assessed adulthood cognition in relation to early exposure to severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS Sixteen years subsequent to a study of cognitive function in 28 diabetic children and 28 matched control subjects, we reexamined the same subjects with a 96% participation rate. Diabetic subjects were classified as with (n = 9) or without (n = 18) early (<or=10 years of age) SH, which was defined as convulsions or loss of consciousness. RESULTS Overall, cognitive scores were 0.9 SDs lower in subjects with early SH compared with subjects without early SH (P = 0.003). The two diabetic groups particularly differed with respect to problem solving, verbal function, and psychomotor efficiency. Earlier age at first incident of SH was associated with poorer cognition (P for trend = 0.001). CONCLUSIONS The findings suggest that early exposure to SH may have lasting and clinically relevant effects on cognition.
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Affiliation(s)
- Bjørn O Asvold
- Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
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Patiño-Fernández AM, Delamater AM, Applegate EB, Brady E, Eidson M, Nemery R, Gonzalez-Mendoza L, Richton S. Neurocognitive functioning in preschool-age children with type 1 diabetes mellitus. Pediatr Diabetes 2010; 11:424-30. [PMID: 20456084 PMCID: PMC2921563 DOI: 10.1111/j.1399-5448.2009.00618.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Neurocognitive functioning may be compromised in children with type 1 diabetes mellitus (T1DM). The factor most consistently implicated in the long-term neurocognitive functioning of children with T1DM is age of onset. The pediatric literature suggests that glycemic extremes may have an effect on the neurocognitive functioning of children, but findings are mixed. The purpose of this study was to compare the neurocognitive functioning of young children with T1DM diagnosed before 6 yr of age and healthy children (i.e., without chronic illness). Additionally, in the children with T1DM, we examined the relationship between their neurocognitive functioning and glycemic control. Sixty-eight (36 with T1DM and 32 without chronic illness) preschool-age children (M age = 4.4 yr ) were recruited and administered a battery of instruments to measure cognitive, language, and fine motor skills. Children with T1DM performed similar to the healthy controls and both groups' skills fell in the average range. Among children with diabetes, poor glycemic control [higher hemoglobin A1c (HbA1c)] was related to lower general cognitive abilities (r = -0.44,p < 0.04), slower fine motor speed (r = -0.64,p < 0.02), and lower receptive language scores (r = -0.39,p < 0.04). Such findings indicate that young children with T1DM already demonstrate some negative neurocognitive effects in association with chronic hyperglycemia.
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Affiliation(s)
- Anna Maria Patiño-Fernández
- University of Miami Miller School of Medicine, Department of Pediatrics/Division of Clinical Psychology, Miami, FL 33136, USA
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Wysokiński A, Zboralski K, Orzechowska A, Gałecki P, Florkowski A, Talarowska M. Normalization of the Verbal Fluency Test on the basis of results for healthy subjects, patients with schizophrenia, patients with organic lesions of the chronic nervous system and patients with type 1 and 2 diabetes. Arch Med Sci 2010; 6:438-46. [PMID: 22371783 PMCID: PMC3282524 DOI: 10.5114/aoms.2010.14268] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2009] [Revised: 02/27/2009] [Accepted: 05/01/2009] [Indexed: 11/24/2022] Open
Abstract
INTRODUCTION Verbal fluency is the ability to form and express words compatible with required criteria. Verbal fluency is necessary for optimal communication and for normal social and occupational functioning. The Verbal Fluency Test is a good indicator of frontal lobe dysfunction, particularly of the left frontal cortex. MATERIAL AND METHODS The aim of the study was to compare verbal fluency in healthy subjects (n = 50), patients with paranoid schizophrenia (n = 36), patients with organic lesions of the central nervous system (CNS) (n = 33), and patients with diabetes (n = 62) - type 1 diabetes (n = 31) and type 2 diabetes (n = 31). RESULTS Healthy subjects and patients with diabetes achieved the highest results in all categories of the Verbal Fluency Test. Patients with paranoid schizophrenia achieved significantly lower results. Sten norms of the Verbal Fluency Test were developed for the general population. Using these norms it was found that subjects with schizophrenia or with organic lesions of the CNS had very poor results more often and very high results less frequently compared to healthy subjects and also to patients with diabetes. CONCLUSIONS This observation is consistent with the neurodevelopmental hypothesis of schizophrenia, in which cognitive functions of the frontal lobe (e.g. verbal fluency) play a major role in the psychopathological picture. We have also demonstrated that in patients with type 1 and 2 diabetes verbal fluency is comparable with healthy subjects.
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Affiliation(s)
- Adam Wysokiński
- Corresponding author: Adam Wysokiński, MD, Clinic Of Adult Psychiatry, Medical University of Lodz, Unit XIB, J. Babiński Hospital Aleksandrowska, 159 91-229, Lodz, Poland, Phone: +48 42 652-12-89, Fax: +48 42 640-50-52. E-mail:
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Lin A, Northam EA, Rankins D, Werther GA, Cameron FJ. Neuropsychological profiles of young people with type 1 diabetes 12 yr after disease onset. Pediatr Diabetes 2010; 11:235-43. [PMID: 20070555 DOI: 10.1111/j.1399-5448.2009.00588.x] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Lowered neuropsychological performance is evident in youth with type 1 diabetes, although evidence for associations with specific illness variables is inconsistent. This study examined the neuropsychological profiles of a cohort of youth with type 1 diabetes studied prospectively from diagnosis 12 yr previously. METHODS A total of 106 youth with type 1 diabetes and 75 healthy controls participated. There were no significant group differences on Full-scale IQ assessed on study entry 12 yr previously, current socioeconomic status, gender distribution, or age. Neuropsychological tests assessed eight cognitive domains: verbal abilities, perceptual reasoning, new learning, working memory, non-verbal processing speed, mental efficiency, divided attention, and sustained attention. Episodes of serious hypoglycemia and HbA(1c) levels were recorded from diagnosis. RESULTS Youth with type 1 diabetes performed more poorly than controls on working memory (p < .05). Early onset diabetes was related to poorer sustained (p < .001) and divided attention (p = .001), new learning, and mental efficiency (both p < .05). Hypoglycemia was found to adversely effect verbal abilities, working memory, and non-verbal processing speed (all p < .05). Poorer working memory was associated with hyperglycemia (p < .05). Youth with any combination of two or three illness risk factors (i.e., early onset diabetes, hypo-, hyperglycemia), performed more poorly than controls and youth with no or one risk on verbal abilities, working memory, and mental efficiency. CONCLUSIONS This study documents poorer neuropsychological performance and its association with illness risk factors in youth with type 1 diabetes. Findings suggest that early disease onset and hypoglycemia impact on the developing central nervous system, with hyperglycemia playing a lesser role.
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Affiliation(s)
- Ashleigh Lin
- Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia.
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Puente EC, Silverstein J, Bree AJ, Musikantow DR, Wozniak DF, Maloney S, Daphna-Iken D, Fisher SJ. Recurrent moderate hypoglycemia ameliorates brain damage and cognitive dysfunction induced by severe hypoglycemia. Diabetes 2010; 59:1055-62. [PMID: 20086229 PMCID: PMC2844814 DOI: 10.2337/db09-1495] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Although intensive glycemic control achieved with insulin therapy increases the incidence of both moderate and severe hypoglycemia, clinical reports of cognitive impairment due to severe hypoglycemia have been highly variable. It was hypothesized that recurrent moderate hypoglycemia preconditions the brain and protects against damage caused by severe hypoglycemia. RESEARCH DESIGN AND METHODS Nine-week-old male Sprague-Dawley rats were subjected to either 3 consecutive days of recurrent moderate (25-40 mg/dl) hypoglycemia (RH) or saline injections. On the fourth day, rats were subjected to a hyperinsulinemic (0.2 units x kg(-1) x min(-1)) severe hypoglycemic ( approximately 11 mg/dl) clamp for 60 or 90 min. Neuronal damage was subsequently assessed by hematoxylin-eosin and Fluoro-Jade B staining. The functional significance of severe hypoglycemia-induced brain damage was evaluated by motor and cognitive testing. RESULTS Severe hypoglycemia induced brain damage and striking deficits in spatial learning and memory. Rats subjected to recurrent moderate hypoglycemia had 62-74% less brain cell death and were protected from most of these cognitive disturbances. CONCLUSIONS Antecedent recurrent moderate hypoglycemia preconditioned the brain and markedly limited both the extent of severe hypoglycemia-induced neuronal damage and associated cognitive impairment. In conclusion, changes brought about by recurrent moderate hypoglycemia can be viewed, paradoxically, as providing a beneficial adaptive response in that there is mitigation against severe hypoglycemia-induced brain damage and cognitive dysfunction.
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Affiliation(s)
- Erwin C. Puente
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, Missouri
| | - Julie Silverstein
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, Missouri
| | - Adam J. Bree
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, Missouri
| | - Daniel R. Musikantow
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, Missouri
| | - David F. Wozniak
- Department of Psychiatry, Washington University, St. Louis, Missouri
| | - Susan Maloney
- Department of Psychiatry, Washington University, St. Louis, Missouri
| | - Dorit Daphna-Iken
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, Missouri
| | - Simon J. Fisher
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, Missouri
- Department of Cell Biology and Physiology, Washington University, St. Louis, Missouri
- Corresponding author: Simon Fisher,
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Shehata G, Eltayeb A. Cognitive function and event-related potentials in children with type 1 diabetes mellitus. J Child Neurol 2010; 25:469-74. [PMID: 19762507 DOI: 10.1177/0883073809341667] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Type 1 diabetes mellitus is associated with cognitive changes, but the extent of cognition decline depends on age at onset, duration of diabetes, and occurrence of attacks of hypoglycemia or ketoacidosis. This study was designed to assess cognitive function in a group of children with type 1 diabetes mellitus. A total of 40 diabetic children were recruited from the pediatric department of Assiut University Hospital, Egypt. Forty healthy children matched for age, sex, and socioeconomic status were chosen as controls for comparison. Cognition was assessed using Stanford-Binet and event-related potentials tests. Compared to the control group, patients reported a significant reduction in intelligent quotient, comprehension, abstract visual reasoning, quantitative reasoning, bead memory, and total short memory testing for cognitive functions. Prolonged N1, P200, N2, and P300 latencies and reduced P300-N2 amplitude were reported. Significant negative correlations were identified in most studied cognitive functions and ketoacidosis or family history of diabetes mellitus.
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Affiliation(s)
- Ghaydaa Shehata
- Department of Neurology and Psychiatry, Assiut University, Assiut, Egypt.
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Northam EA, Lin A. Hypoglycaemia in childhood onset type 1 diabetes--part villain, but not the only one. Pediatr Diabetes 2010; 11:134-41. [PMID: 19538515 DOI: 10.1111/j.1399-5448.2009.00545.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Affiliation(s)
- Elisabeth A Northam
- Department of Psychology, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
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Ohmann S, Popow C, Rami B, König M, Blaas S, Fliri C, Schober E. Cognitive functions and glycemic control in children and adolescents with type 1 diabetes. Psychol Med 2010; 40:95-103. [PMID: 19400976 DOI: 10.1017/s0033291709005777] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND The relationship between metabolic control and cognitive function in adolescents with type 1 diabetes (DM type 1) is not clear. We compared the quality of glycemic control (GC) and cognitive measures in adolescents with DM type 1 to find out if the quality of diabetes management is related to cognitive impairment. METHOD We assessed executive functions (EFs) and other neuropsychological and psychosocial variables in 70 adolescent patients with DM type 1 and 20 age-matched controls. Patients were divided into two groups according to their last hemoglobin A1c (HbA1c): acceptable (HbA1c 5.9-8.0%, mean 6.9%, 36 patients, mean age 14 years) and non-optimal (HbA1c 8.2-11.6%, mean 9.3%, 34 patients, mean age 15.6 years). RESULTS We found impaired EFs, mainly problems of concept formation (p=0.038), cognitive flexibility (p=0.011) and anticipation (p=0.000), in the patients with DM type 1. Both groups did not differ in intelligence, most assessed EFs and adjustment to chronic illness (Youth Self-Report; YSR). Younger patients (<15 years) were cognitively less flexible. GC was worse in older patients and in patients with longer duration of the disease. We also found significant differences between patients with diabetes and controls concerning somatic complaints, internalizing problems (Child Behavior Checklist; CBCL) and social activity (CBCL and YSR). CONCLUSIONS DM type 1 is associated with cognitive deficits in adolescents independent of the quality of metabolic control and the duration of the disease. These deficits are probably related to the disease, especially in patients with early-onset diabetes.
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Affiliation(s)
- S Ohmann
- Department of Child and Adolescent Psychiatry, Medical University of Vienna, Austria
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Abstract
AbstractDiabetes is a chronic metabolic disease which can lead to numerous complications. One of these disturbances is cognitive function impairment. A group of 62 patients with type 1 and type 2 diabetes. There is a correlation between certain clinical features among diabetic patients and cognitive functions. Negative influence on cognitive functions have a higher level of total cholesterol, a higher level of LDL cholesterol, a lower level of HDL cholesterol concentration in the blood, a higher level of glucose after meals, a higher level of basic insulin dose and insulin dose taken just before the examination, longer duration of the diabetes and a lot of hypoglycemic episodes. There is no influence on cognitive functions from glucose levels before meals, the type of the insulin therapy, or the number of hyperglycemic episodes and value rate of hemoglobin HbA1C.
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Clarke W, Jones T, Rewers A, Dunger D, Klingensmith GJ. Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatr Diabetes 2009; 10 Suppl 12:134-45. [PMID: 19754624 DOI: 10.1111/j.1399-5448.2009.00583.x] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Affiliation(s)
- William Clarke
- Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, USA.
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Rewers M, Pihoker C, Donaghue K, Hanas R, Swift P, Klingensmith GJ. Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatr Diabetes 2009; 10 Suppl 12:71-81. [PMID: 19754620 DOI: 10.1111/j.1399-5448.2009.00582.x] [Citation(s) in RCA: 129] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Affiliation(s)
- Marian Rewers
- Barbara Davis Center, University of Colorado Denver, Aurora, CO 80045-6511, USA
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Bangstad HJ, Danne T, Deeb L, Jarosz-Chobot P, Urakami T, Hanas R. Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes 2009; 10 Suppl 12:82-99. [PMID: 19754621 DOI: 10.1111/j.1399-5448.2009.00578.x] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
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Bree AJ, Puente EC, Daphna-Iken D, Fisher SJ. Diabetes increases brain damage caused by severe hypoglycemia. Am J Physiol Endocrinol Metab 2009; 297:E194-201. [PMID: 19435850 PMCID: PMC2711670 DOI: 10.1152/ajpendo.91041.2008] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Insulin-induced severe hypoglycemia causes brain damage. The hypothesis to be tested was that diabetes portends to more extensive brain tissue damage following an episode of severe hypoglycemia. Nine-week-old male streptozotocin-diabetic (DIAB; n = 10) or vehicle-injected control (CONT; n = 7) Sprague-Dawley rats were subjected to hyperinsulinemic (0.2 U.kg(-1).min(-1)) severe hypoglycemic (10-15 mg/dl) clamps while awake and unrestrained. Groups were precisely matched for depth and duration (1 h) of severe hypoglycemia (CONT 11 +/- 0.5 and DIAB 12 +/- 0.2 mg/dl, P = not significant). During severe hypoglycemia, an equal number of episodes of seizure-like activity were noted in both groups. One week later, histological analysis demonstrated extensive neuronal damage in regions of the hippocampus, especially in the dentate gyrus and CA1 regions and less so in the CA3 region (P < 0.05), although total hippocampal damage was not different between groups. However, in the cortex, DIAB rats had significantly (2.3-fold) more dead neurons than CONT rats (P < 0.05). There was a strong correlation between neuronal damage and the occurrence of seizure-like activity (r(2) > 0.9). Separate studies conducted in groups of diabetic (n = 5) and nondiabetic (n = 5) rats not exposed to severe hypoglycemia showed no brain damage. In summary, under the conditions studied, severe hypoglycemia causes brain damage in the cortex and regions within the hippocampus, and the extent of damage is closely correlated to the presence of seizure-like activity in nonanesthetized rats. It is concluded that, in response to insulin-induced severe hypoglycemia, diabetes uniquely increases the vulnerability of specific brain areas to neuronal damage.
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Affiliation(s)
- Adam J Bree
- Division of Endocrinology, Metabolism, & Lipid Research, Washington University in St. Louis, Campus Box 8127, 660 South Euclid Ave., St. Louis, MO 63110, USA
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McCrea SM. A review and empirical study of the composite scales of the Das-Naglieri cognitive assessment system. Psychol Res Behav Manag 2009; 2:59-79. [PMID: 22110322 PMCID: PMC3218775 DOI: 10.2147/prbm.s5074] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Alexander Luria’s model of the working brain consisting of three functional units was formulated through the examination of hundreds of focal brain-injury patients. Several psychometric instruments based on Luria’s syndrome analysis and accompanying qualitative tasks have been developed since the 1970s. In the mid-1970s, JP Das and colleagues defined a specific cognitive processes model based directly on Luria’s two coding units termed simultaneous and successive by studying diverse cross-cultural, ability, and socioeconomic strata. The cognitive assessment system is based on the PASS model of cognitive processes and consists of four composite scales of Planning–Attention–Simultaneous–Successive (PASS) devised by Naglieri and Das in 1997. Das and colleagues developed the two new scales of planning and attention to more closely model Luria’s theory of higher cortical functions. In this paper a theoretical review of Luria’s theory, Das and colleagues elaboration of Luria’s model, and the neural correlates of PASS composite scales based on extant studies is summarized. A brief empirical study of the neuropsychological specificity of the PASS composite scales in a sample of 33 focal cortical stroke patients using cluster analysis is then discussed. Planning and simultaneous were sensitive to right hemisphere lesions. These findings were integrated with recent functional neuroimaging studies of PASS scales. In sum it was found that simultaneous is strongly dependent on dual bilateral occipitoparietal interhemispheric coordination whereas successive demonstrated left frontotemporal specificity with some evidence of interhemispheric coordination across the prefrontal cortex. Hence, support for the validity of the PASS composite scales was found as well as for the axiom of the independence of code content from code type originally specified in 1994 by Das, Naglieri, and Kirby.
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Affiliation(s)
- Simon M McCrea
- JP Das Developmental Disabilities Center, Department of Educational Psychology, Faculty of Education, University of Alberta, Edmonton, Alberta, Canada
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Datz N, Rachmiel M. Highlights of the 34th annual ISPAD meeting, 13-16 August 2008, Durban, South Africa. Pediatr Diabetes 2009; 10:82-7. [PMID: 19140900 DOI: 10.1111/j.1399-5448.2008.00493.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Nicolin Datz
- Centre of Pediatric Endocrinology and Diabetes, Kinderkrankenhaus auf der Bult, Hannover, Germany.
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