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Chua C, Tan CSH, Lim SC, Vasanwala RF. A Unique Phenotype of Maturity-Onset Diabetes of the Young With a Novel Disease-Causing Insulin Gene Variant. JCEM CASE REPORTS 2025; 3:luae230. [PMID: 39717432 PMCID: PMC11663494 DOI: 10.1210/jcemcr/luae230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Indexed: 12/25/2024]
Abstract
Maturity-onset diabetes of the young (MODY) represents 1% to 5% of patients with diabetes mellitus (DM), and numerous genes associated with MODY have been identified. While mutations of the insulin gene (INS) are known to cause permanent neonatal DM, rare disease-causing variants have also been found in MODY. These patients demonstrate variable clinical phenotypes-from milder forms requiring lifestyle or oral agent interventions to severe forms requiring lifelong insulin. We present a case of MODY arising from a novel disease-causing INS variant, in an adolescent with atypical features. He was obese with clinical evidence of insulin resistance, diagnosed with DM through opportunistic oral glucose tolerance testing. He developed symptomatic hyperglycemia with worsening glycemic trend, requiring treatment with high-dose insulin and metformin. After 2.5 years, his glycemic profile normalized following weight loss, and pharmacotherapy was discontinued. Targeted gene testing revealed a de novo novel missense variant in exon 2 of the INS gene (p.His29Tyr), confirmed using bidirectional Sanger sequencing. Insulin resistance in patients with MODY can worsen their clinical course and increase risks of long-term complications. Management of these patients should be individualized. This case highlights the utility of genetic testing in diagnosing uncommon and variable forms of MODY, particularly those with atypical features.
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Affiliation(s)
- Cherie Chua
- Department of Paediatric Endocrinology, Kandang Kerbau Women's and Children's Hospital, 229899 Singapore
| | - Clara Si Hua Tan
- Clinical Research Unit, Khoo Teck Puat Hospital, 768828 Singapore
| | - Su Chi Lim
- Diabetes Centre, Khoo Teck Puat Hospital, 768828 Singapore
- Department of Medicine, Khoo Teck Puat Hospital, 768828 Singapore
| | - Rashida Farhad Vasanwala
- Department of Paediatric Endocrinology, Kandang Kerbau Women's and Children's Hospital, 229899 Singapore
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Zhou ZY, Wang JY, Li ZX, Zheng HL, Zhou YN, Huang LN, Wang LJ, Ding XW, Sun X, Cai K, Zhao R, Shi Y, Chen AF, Pan ZQ, Cao J, Lin FQ, Zhao JY. Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2402086. [PMID: 38946582 PMCID: PMC11434239 DOI: 10.1002/advs.202402086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 06/18/2024] [Indexed: 07/02/2024]
Abstract
Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.
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Affiliation(s)
- Ze-Yu Zhou
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Ji-Ying Wang
- Department of Pain Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Zhi-Xiao Li
- Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Hong-Li Zheng
- Department of Pain Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Ya-Nan Zhou
- Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Li-Na Huang
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20080, China
| | - Li-Juan Wang
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20080, China
| | - Xiao-Wei Ding
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Xin Sun
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Ke Cai
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Rui Zhao
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yan Shi
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Alex F Chen
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Zhi-Qiang Pan
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, 221004, China
| | - Jing Cao
- Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Fu-Qing Lin
- Department of Pain Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Jian-Yuan Zhao
- Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
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Zrubka Z, Kertész G, Gulácsi L, Czere J, Hölgyesi Á, Nezhad HM, Mosavi A, Kovács L, Butte AJ, Péntek M. The Reporting Quality of Machine Learning Studies on Pediatric Diabetes Mellitus: Systematic Review. J Med Internet Res 2024; 26:e47430. [PMID: 38241075 PMCID: PMC10837761 DOI: 10.2196/47430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/29/2023] [Accepted: 11/17/2023] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Diabetes mellitus (DM) is a major health concern among children with the widespread adoption of advanced technologies. However, concerns are growing about the transparency, replicability, biasedness, and overall validity of artificial intelligence studies in medicine. OBJECTIVE We aimed to systematically review the reporting quality of machine learning (ML) studies of pediatric DM using the Minimum Information About Clinical Artificial Intelligence Modelling (MI-CLAIM) checklist, a general reporting guideline for medical artificial intelligence studies. METHODS We searched the PubMed and Web of Science databases from 2016 to 2020. Studies were included if the use of ML was reported in children with DM aged 2 to 18 years, including studies on complications, screening studies, and in silico samples. In studies following the ML workflow of training, validation, and testing of results, reporting quality was assessed via MI-CLAIM by consensus judgments of independent reviewer pairs. Positive answers to the 17 binary items regarding sufficient reporting were qualitatively summarized and counted as a proxy measure of reporting quality. The synthesis of results included testing the association of reporting quality with publication and data type, participants (human or in silico), research goals, level of code sharing, and the scientific field of publication (medical or engineering), as well as with expert judgments of clinical impact and reproducibility. RESULTS After screening 1043 records, 28 studies were included. The sample size of the training cohort ranged from 5 to 561. Six studies featured only in silico patients. The reporting quality was low, with great variation among the 21 studies assessed using MI-CLAIM. The number of items with sufficient reporting ranged from 4 to 12 (mean 7.43, SD 2.62). The items on research questions and data characterization were reported adequately most often, whereas items on patient characteristics and model examination were reported adequately least often. The representativeness of the training and test cohorts to real-world settings and the adequacy of model performance evaluation were the most difficult to judge. Reporting quality improved over time (r=0.50; P=.02); it was higher than average in prognostic biomarker and risk factor studies (P=.04) and lower in noninvasive hypoglycemia detection studies (P=.006), higher in studies published in medical versus engineering journals (P=.004), and higher in studies sharing any code of the ML pipeline versus not sharing (P=.003). The association between expert judgments and MI-CLAIM ratings was not significant. CONCLUSIONS The reporting quality of ML studies in the pediatric population with DM was generally low. Important details for clinicians, such as patient characteristics; comparison with the state-of-the-art solution; and model examination for valid, unbiased, and robust results, were often the weak points of reporting. To assess their clinical utility, the reporting standards of ML studies must evolve, and algorithms for this challenging population must become more transparent and replicable.
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Affiliation(s)
- Zsombor Zrubka
- HECON Health Economics Research Center, University Research and Innovation Center, Óbuda University, Budapest, Hungary
| | - Gábor Kertész
- John von Neumann Faculty of Informatics, Óbuda University, Budapest, Hungary
| | - László Gulácsi
- HECON Health Economics Research Center, University Research and Innovation Center, Óbuda University, Budapest, Hungary
| | - János Czere
- Doctoral School of Innovation Management, Óbuda University, Budapest, Hungary
| | - Áron Hölgyesi
- HECON Health Economics Research Center, University Research and Innovation Center, Óbuda University, Budapest, Hungary
- Doctoral School of Molecular Medicine, Semmelweis University, Budapest, Hungary
| | - Hossein Motahari Nezhad
- HECON Health Economics Research Center, University Research and Innovation Center, Óbuda University, Budapest, Hungary
- Doctoral School of Business and Management, Corvinus University of Budapest, Budapest, Hungary
| | - Amir Mosavi
- John von Neumann Faculty of Informatics, Óbuda University, Budapest, Hungary
| | - Levente Kovács
- Physiological Controls Research Center, University Research and Innovation Center, Óbuda University, Budapest, Hungary
| | - Atul J Butte
- Bakar Computational Health Sciences Institute, University of California, San Francisco, CA, United States
| | - Márta Péntek
- HECON Health Economics Research Center, University Research and Innovation Center, Óbuda University, Budapest, Hungary
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Leslie RD, Ma RCW, Franks PW, Nadeau KJ, Pearson ER, Redondo MJ. Understanding diabetes heterogeneity: key steps towards precision medicine in diabetes. Lancet Diabetes Endocrinol 2023; 11:848-860. [PMID: 37804855 DOI: 10.1016/s2213-8587(23)00159-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/30/2023] [Accepted: 05/27/2023] [Indexed: 10/09/2023]
Abstract
Diabetes is a highly heterogeneous condition; yet, it is diagnosed by measuring a single blood-borne metabolite, glucose, irrespective of aetiology. Although pragmatically helpful, disease classification can become complex and limit advances in research and medical care. Here, we describe diabetes heterogeneity, highlighting recent approaches that could facilitate management by integrating three disease models across all forms of diabetes, namely, the palette model, the threshold model and the gradient model. Once diabetes has developed, further worsening of established diabetes and the subsequent emergence of diabetes complications are kept in check by multiple processes designed to prevent or circumvent metabolic dysfunction. The impact of any given disease risk factor will vary from person-to-person depending on their background, diabetes-related propensity, and environmental exposures. Defining the consequent heterogeneity within diabetes through precision medicine, both in terms of diabetes risk and risk of complications, could improve health outcomes today and shine a light on avenues for novel therapy in the future.
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Affiliation(s)
| | - Ronald Ching Wan Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, China; Laboratory for Molecular Epidemiology in Diabetes, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Paul W Franks
- Novo Nordisk Foundation, Hellerup, Denmark; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmo, Sweden; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Harvard T H Chan School of Public Health, Boston, MA, USA
| | - Kristen J Nadeau
- Anschutz Medical Campus, University of Colorado, Aurora, CO, USA
| | - Ewan R Pearson
- Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK
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Wilson V. Managing type 2 diabetes in children and young people: challenges and solutions. Nurs Child Young People 2023; 35:35-42. [PMID: 37005859 DOI: 10.7748/ncyp.2023.e1460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2022] [Indexed: 04/04/2023]
Abstract
Growing numbers of children and young people are diagnosed with type 2 diabetes, partly due to the obesogenic environment they grow up in. The increasing prevalence of type 2 diabetes is seen particularly in adolescent girls and in children and young people of non-white ethnic backgrounds. There are numerous challenges relating to the diagnosis, treatment and management of type 2 diabetes in children and young people, notably the fact that the condition can lead to serious complications and often triggers high levels of anxiety and stress in patients and families. This article outlines the challenges faced by children and young people with type 2 diabetes, their families and carers, and suggests ways in which nurses can support them with the aim of achieving optimal management and self-management.
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Wilson V. Managing type 1 diabetes in children and young people: challenges and solutions. Nurs Child Young People 2023; 35:e1465. [PMID: 37272192 DOI: 10.7748/ncyp.2023.e1465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2022] [Indexed: 06/06/2023]
Abstract
Type 1 diabetes is the most common form of diabetes in school-age children. Effective management and self-management at home and during school hours are essential to improve the quality of life of children and young people and reduce their risk of developing complications such as cardiovascular disease and kidney disease. There are, however, multiple barriers to effective management and self-management, notably in adolescence. Interventions, education and support based on clear psychoeducational principles improve the outcomes of children and young people. This article explores type 1 diabetes including its causes and risk factors, presentation and diagnosis, complications and comorbidities, and treatment and management. It focuses in particular on the role of nurses in supporting self-management and on the challenges of type 1 diabetes care in school.
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Vidmar AP, Durazo-Arvizu R, Weigensberg MJ, Alderete TL, Goran MI. Rapid Decline in β-Cell Function and Increasing Adiposity Are Associated With Conversion to Type 2 Diabetes in At-Risk Latino Youth. Diabetes 2023; 72:735-745. [PMID: 36972018 PMCID: PMC10202769 DOI: 10.2337/db22-1034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 03/22/2023] [Indexed: 04/16/2023]
Abstract
Youth-onset type 2 diabetes (T2D) is becoming increasingly prevalent, especially among Latino youth, and there is limited information on its pathophysiology and causative factors. Here, we describe findings from a longitudinal cohort study in 262 Latino children with overweight/obesity at risk of developing T2D with annual measures of oral and intravenous glucose tolerance (IVGTT), body composition, and fat distribution. Logistic binomial regression was used to identify significant predictors in those who developed T2D compared with matched control participants, and mixed-effects growth models were used to compare rates of change in metabolic versus adiposity measures between groups. Overall conversion rate to T2D at year 5 was 2% (n = 6). Rate of decline in disposition index (DI), measured with an IVGTT, over 5 years was three times higher in case patients (-341.7 units per year) compared with the extended cohort (-106.7 units per year) and 20 times higher compared with control participants (-15.2 units per year). Case patients had significantly higher annual increases in fasting glucose, hemoglobin A1c (HbA1c), waist circumference, and trunk fat, and there was an inverse correlation between rate of decline in DI and rates of increase in adiposity measures. T2D development in at-risk Latino youth is associated with a substantial and rapid decrease in DI that is directly correlated with increases in fasting glucose, HbA1c, and adiposity. ARTICLE HIGHLIGHTS Youth-onset type 2 diabetes is becoming increasingly prevalent, especially among Latino youth, and there is limited information on its pathophysiology and causative factors. Overall conversion rate to type 2 diabetes over 5 years was 2%. In youth who converted to type 2 diabetes, disposition index decreased rapidly by 85% compared with that in patients who did not convert during the study period. There was an inverse correlation between rate of decline in disposition index and rates of increase in various adiposity measures.
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Affiliation(s)
- Alaina P. Vidmar
- Division of Endocrinology, Department of Pediatrics, Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA
- Department of Pediatrics, Keck School of Medicine, Los Angeles, CA
| | - Ramon Durazo-Arvizu
- Southern California Clinical and Translational Science Institute Biostatistics Core, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Marc J. Weigensberg
- Department of Pediatrics, University of Southern California, Los Angeles, CA
| | - Tanya L. Alderete
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO
| | - Michael I. Goran
- Division of Endocrinology, Department of Pediatrics, Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA
- Department of Pediatrics, Keck School of Medicine, Los Angeles, CA
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Berman C, Vidmar AP, Chao LC. Glucagon-like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes in Youth. TOUCHREVIEWS IN ENDOCRINOLOGY 2023; 19:38-45. [PMID: 37313232 PMCID: PMC10258616 DOI: 10.17925/ee.2023.19.1.38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 04/20/2023] [Indexed: 06/15/2023]
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained traction for the management of type 2 diabetes and obesity. Unlike several classes of antidiabetic medications that contribute to weight gain, GLP-1RAs not only reduce haemoglobin A1c, but also promote weight loss. While there is a large body of evidence supporting its safety and efficacy in adults, paediatric clinical trial data have only emerged in recent years. This review will discuss the limited treatment options for paediatric type 2 diabetes and the mechanism of action of GLP-1RAs as it pertains to physiological pathways relevant for type 2 diabetes, obesity and their related comorbidities. The outcomes of paediatric trials evaluating liraglutide, exenatide, semaglutide and dulaglutide in paediatric type 2 diabetes and obesity will be closely examined, including differences compared with adult studies. Finally, potential barriers and strategies to expanding GLP-1RA access in adolescents will be discussed. Future studies are needed to determine if the cardio-and renal-protective benefits of GLP-1RAs apply to youth-onset type 2 diabetes.
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Affiliation(s)
- Casey Berman
- Division of Endocrinology, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA
| | - Alaina P Vidmar
- Division of Endocrinology, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA
- Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
| | - Lily C Chao
- Division of Endocrinology, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA
- Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
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Libman I, Haynes A, Lyons S, Pradeep P, Rwagasor E, Tung JYL, Jefferies CA, Oram RA, Dabelea D, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2022: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2022; 23:1160-1174. [PMID: 36537527 DOI: 10.1111/pedi.13454] [Citation(s) in RCA: 75] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/09/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Ingrid Libman
- Division of Pediatric Endocrinology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Aveni Haynes
- Children's Diabetes Centre, Telethon Kids Institute, Perth, Western Australia, Australia
| | - Sarah Lyons
- Pediatric Diabetes and Endocrinology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Praveen Pradeep
- Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India
| | - Edson Rwagasor
- Rwanda Biomedical Center, Rwanda Ministry of Health, Kigali, Rwanda
| | - Joanna Yuet-Ling Tung
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong, Hong Kong
| | - Craig A Jefferies
- Starship Children's Health, Te Whatu Ora Health New Zealand, Auckland, New Zealand
| | - Richard A Oram
- Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
| | - Dana Dabelea
- Department of Epidemiology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Maria E Craig
- The Children's Hospital at Westmead, Sydney, New South Wales (NSW), Australia.,University of Sydney Children's Hospital Westmead Clinical School, Sydney, NEW, Australia.,Discipline of Paediatrics & Child Health, School of Clinical Medicine, University of NSW Medicine & Health, Sydney, NSW, Australia
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Meseret F, Belachew A, Tesfa G, Mengesha T, Embiale T, Alemu A, Dagne M. Time to first optimal glycemic control and its predictors among type 1 diabetic children in Bahir Dar city public referral hospitals, North West Ethiopia: a retrospective follow up study. BMC Pediatr 2022; 22:563. [PMID: 36153485 PMCID: PMC9508760 DOI: 10.1186/s12887-022-03604-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 09/05/2022] [Indexed: 11/21/2022] Open
Abstract
Background Recognizing the level of glycemic control of a client is an important measure/tool to prevent acquiring complications and risk of death from diabetes. However, the other most important variable, which is the time that the patient stayed in that poor glycemic level before reaching optimal glycemic control, has not been studied so far. Therefore, this study aim to estimate time to first optimal glycemic control and identify predictors among type 1 diabetic children in Bahir Dar city public referral hospitals, Northwest, Ethiopia, 2021. Methods A Retrospective cohort study was conducted at Bahir Dar city public referral hospitals among a randomly selected sample of 385 patients with type 1 diabetes who were on follow up from January 1, 2016 to February30, 2021.Data were collected by using a data abstraction tool and then entered into Epi-data version 4.6 and exported into STATA 14.0 statistical software. Descriptive statistics, Kaplan Meier plots and median survival times, Log-rank test and Cox-proportional hazard regression were used for reporting the findings of this study. After performing Cox-proportional hazard regression, model goodness-of-fit and assumptions were checked. Finally, the association between independent variables and time to first optimal glycemic control in months was assessed using the multivariable Cox Proportional Hazard model and variables with a p-value < 0.05 were considered as statistically significant. Results Median survival time to first optimal glycemic control among type 1 diabetic clients was 8 months (95%CI: 6.9–8.9). The first optimal glycemic achievement rate was 8.2 (95%CI: 7.2–9.2) per 100 person/month observation. Factors that affect time to first optimal glycemic control were age > 10–14 years (AHR = 0.32;95%CI = 0.19–0.55), increased weight (AHR = 0.96;95%CI = 0.94–0.99), having primary care giver (AHR = 2.09;95%CI = 1.39–3.13), insulin dose (AHR = 1.05;95%CI = 1.03–1.08), duration of diabetes ≥4 years (AHR = 0.64;95%CI = 0.44–0.94), adherence to diabetic care (AHR = 9.72;95%CI = 6.09–15.51), carbohydrate counting (AHR = 2.43;95%CI = 1.12–5.26), and comorbidity (AHR = 0.72;95%CI = 0.53–0.98). Conclusion The median survival time to first optimal glycemic control in this study was long. Age, weight, primary care giver, insulin dose, duration of diabetes, adherence, and carbohydrate counting, including history of comorbidity were determinant factors. Giving attention for overweight and comorbid illness prevention, increasing either the dose or frequency of insulin during initial treatment; counseling parent (for both the mother and father) about adherence to diabetic care focusing on insulin drugs and how to audit their children’s diet as prescription helps to reduce the length of glycemic control.
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Costello E, Goodrich J, Patterson WB, Rock S, Li Y, Baumert B, Gilliland F, Goran MI, Chen Z, Alderete TL, Conti DV, Chatzi L. Diet Quality Is Associated with Glucose Regulation in a Cohort of Young Adults. Nutrients 2022; 14:nu14183734. [PMID: 36145110 PMCID: PMC9501084 DOI: 10.3390/nu14183734] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/07/2022] [Accepted: 09/08/2022] [Indexed: 12/23/2022] Open
Abstract
Young-onset type 2 diabetes and prediabetes is a growing epidemic. Poor diet is a known risk factor for T2D in older adults, but the contribution of diet to risk factors for T2D is not well-described in youth. Our objective was to examine the relationship of diet quality with prediabetes, glucose regulation, and adiposity in young adults. A cohort of young adults (n = 155, age 17-22) was examined between 2014-2018, and 89 underwent a follow-up visit from 2020-2022. At each visit, participants completed diet and body composition assessments and an oral glucose tolerance test. Adherence to four dietary patterns was assessed: Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI), Mediterranean diet, and Diet Inflammatory Index (DII). Regression analyses were used to determine adjusted associations of diet with risk for prediabetes and adiposity. Each one-point increase in DASH or HEI scores between visits reduced the risk for prediabetes at follow-up by 64% (OR, 95% CI: 0.36, 0.17-0.68) and 9% (OR, 95% CI: 0.91, 0.85-0.96), respectively. The DASH diet was inversely associated with adiposity, while DII was positively associated with adiposity. In summary, positive changes in HEI and DASH scores were associated with reduced risk for prediabetes in young adults.
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Affiliation(s)
- Elizabeth Costello
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
- Correspondence:
| | - Jesse Goodrich
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
| | - William B. Patterson
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Sarah Rock
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
| | - Yiping Li
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
| | - Brittney Baumert
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
| | - Frank Gilliland
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
| | - Michael I. Goran
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
- Department of Pediatrics, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA
| | - Zhanghua Chen
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
| | - Tanya L. Alderete
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA
| | - David V. Conti
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
| | - Leda Chatzi
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90032, USA
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12
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Shah AS, Nadeau KJ, Dabelea D, Redondo MJ. Spectrum of Phenotypes and Causes of Type 2 Diabetes in Children. Annu Rev Med 2022; 73:501-515. [PMID: 35084995 PMCID: PMC9022328 DOI: 10.1146/annurev-med-042120-012033] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Several factors, including genetics, family history, diet, physical activity, obesity, and insulin resistance in puberty, appear to increase the risk of type 2 diabetes in youth. Youth-onset type 2 diabetes is often thought of as a single entity but rather exists as a spectrum of disease with differences in presentation, metabolic characteristics, clinical progression, and complication rates. We review what is currently known regarding the risks associated with developing type 2 diabetes in youth. Additionally, we focus on the spectrum of phenotypes of pediatric type 2 diabetes, discuss the pathogenic underpinnings and potential therapeutic relevance of this heterogeneity, and compare youth-onset type 2 diabetes with type 1 diabetes and adult-onset type 2 diabetes. Finally, we highlight knowledge gaps in prediction and prevention of youth-onset type 2 diabetes.
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Affiliation(s)
- Amy S. Shah
- Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio 45229, USA
| | - Kristen J. Nadeau
- Children’s Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Department of Epidemiology, and Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA
| | - Maria J. Redondo
- Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas 77030, USA
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13
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Kahkoska AR, Pokaprakarn T, Alexander GR, Crume TL, Dabelea D, Divers J, Dolan LM, Jensen ET, Lawrence JM, Marcovina S, Mottl AK, Pihoker C, Saydah SH, Kosorok MR, Mayer-Davis EJ. The Impact of Racial and Ethnic Health Disparities in Diabetes Management on Clinical Outcomes: A Reinforcement Learning Analysis of Health Inequity Among Youth and Young Adults in the SEARCH for Diabetes in Youth Study. Diabetes Care 2022; 45:108-118. [PMID: 34728528 PMCID: PMC8753766 DOI: 10.2337/dc21-0496] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 09/30/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To estimate difference in population-level glycemic control and the emergence of diabetes complications given a theoretical scenario in which non-White youth and young adults (YYA) with type 1 diabetes (T1D) receive and follow an equivalent distribution of diabetes treatment regimens as non-Hispanic White YYA. RESEARCH DESIGN AND METHODS Longitudinal data from YYA diagnosed 2002-2005 in the SEARCH for Diabetes in Youth Study were analyzed. Based on self-reported race/ethnicity, YYA were classified as non-White race or Hispanic ethnicity (non-White subgroup) versus non-Hispanic White race (White subgroup). In the White versus non-White subgroups, the propensity score models estimated treatment regimens, including patterns of insulin modality, self-monitored glucose frequency, and continuous glucose monitoring use. An analysis based on policy evaluation techniques in reinforcement learning estimated the effect of each treatment regimen on mean hemoglobin A1c (HbA1c) and the prevalence of diabetes complications for non-White YYA. RESULTS The study included 978 YYA. The sample was 47.5% female and 77.5% non-Hispanic White, with a mean age of 12.8 ± 2.4 years at diagnosis. The estimated population mean of longitudinal average HbA1c over visits was 9.2% and 8.2% for the non-White and White subgroup, respectively (difference of 0.9%). Within the non-White subgroup, mean HbA1c across visits was estimated to decrease by 0.33% (95% CI -0.45, -0.21) if these YYA received the distribution of diabetes treatment regimens of the White subgroup, explaining ∼35% of the estimated difference between the two subgroups. The non-White subgroup was also estimated to have a lower risk of developing diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy with the White youth treatment regimen distribution (P < 0.05), although the low proportion of YYA who developed complications limited statistical power for risk estimations. CONCLUSIONS Mathematically modeling an equalized distribution of T1D self-management tools and technology accounted for part of but not all disparities in glycemic control between non-White and White YYA, underscoring the complexity of race and ethnicity-based health inequity.
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Affiliation(s)
- Anna R. Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Teeranan Pokaprakarn
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - G. Rumay Alexander
- School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Tessa L. Crume
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO
- Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO
| | - Jasmin Divers
- Division of Health Services Research, Department of Foundations of Medicine, NYU Long Island School of Medicine, Mineola, NY
| | - Lawrence M. Dolan
- Division of Endocrinology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Elizabeth T. Jensen
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC
| | - Jean M. Lawrence
- Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Santica Marcovina
- Department of Medicine, Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle, WA
| | - Amy K. Mottl
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | | | - Sharon H. Saydah
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA
| | - Michael R. Kosorok
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Elizabeth J. Mayer-Davis
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
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14
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Haynes A, Sanderson E, Smith GJ, Curran JC, Maple-Brown L, Davis EA. Demographic and clinical characteristics of a population-based pediatric cohort of type 1 and type 2 diabetes in Western Australia (1999-2019). Pediatr Diabetes 2021; 22:1102-1107. [PMID: 34536247 DOI: 10.1111/pedi.13264] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/09/2021] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES To determine demographic and clinical characteristics of youth diagnosed with type 1 (T1D) or type 2 (T2D) diabetes aged ≤15 years from 1999 to 2019 in Western Australia, and examine time to first diagnosis of diabetes complications. METHODS A retrospective cohort study was conducted of patients identified from the population-based, prospective Western Australian Children's Diabetes Database and longitudinal data extracted for available demographic and clinical variables. Patients were followed from diagnosis to transition to adult services, death, or December 31, 2019. Cox proportional hazards regression models were used to analyse time to first diagnosis of hypertension, high cholesterol or microalbuminuria, after adjusting for sex, age at diagnosis, time period of diagnosis, hemoglobin A1c , and body max index Z-score. RESULTS 2438 eligible patients were identified (2209 [91%] T1D: 229 [9%] T2D). The mean age at diagnosis was lower in patients with T1D (8.5 [±4.0] vs. 12.7 [±2.0] years). A higher proportion of patients with T2D were female (58% vs. 47%) and of Aboriginal ethnicity (59% vs. 2%). The median HbA1c (interquartile range) at diagnosis was lower 8.9% [6.7, 11.5] (74 mmol/mol [50, 102]) versus 11.6% [10.1, 13.3] (103 mmol/mol [87, 122]) and mean body max index Z-score higher (2.05 [±0.66] vs. 0.37 [±0.95]), in patients with T2D compared to T1D. Patients with T2D had a higher risk of hypertension, high cholesterol, and microalbuminuria (aHR 3.39 [95%CI:2.04, 5.63], 2.69 [95%CI:1.21, 5.98], and 19.79 [95%CI:10.99, 35.64] respectively).
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Affiliation(s)
- Aveni Haynes
- Children's Diabetes Centre, Telethon Kids Institute, The University of Western Australia, Perth, Australia
| | - Elaine Sanderson
- Department of Endocrinology & Diabetes, Perth Children's Hospital, Perth, Australia
| | - Grant J Smith
- Children's Diabetes Centre, Telethon Kids Institute, The University of Western Australia, Perth, Australia
| | - Jacqueline C Curran
- Department of Endocrinology & Diabetes, Perth Children's Hospital, Perth, Australia
| | - Louise Maple-Brown
- Department of Endocrinology, Royal Darwin Hospital, Tiwi, Australia.,Menzies School of Health Research, Charles Darwin University, Casuarina, Australia
| | - Elizabeth A Davis
- Children's Diabetes Centre, Telethon Kids Institute, The University of Western Australia, Perth, Australia.,Department of Endocrinology & Diabetes, Perth Children's Hospital, Perth, Australia
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15
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Haris B, Saraswathi S, Al‐Khawaga S, Hasnah R, Saeed A, Mundekkadan S, Hamed N, Afyouni H, Abdel‐Karim T, Mohammed S, Khalifa A, Al‐Maadheed M, Al‐Zyoud M, Shamekh A, Elawwa A, Al‐Khalaf F, Boughorbel S, Petrovski G, Hussain K. Epidemiology, genetic landscape and classification of childhood diabetes mellitus in the State of Qatar. J Diabetes Investig 2021; 12:2141-2148. [PMID: 34101350 PMCID: PMC8668069 DOI: 10.1111/jdi.13610] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/24/2021] [Accepted: 05/27/2021] [Indexed: 12/29/2022] Open
Abstract
AIMS/INTRODUCTION To study the epidemiology, genetic landscape and causes of childhood diabetes mellitus in the State of Qatar. MATERIALS AND METHODS All patients (aged 0-18 years) with diabetes mellitus underwent biochemical, immunological and genetic testing. American Diabetes Association guidelines were used to classify types of diabetes mellitus. The incidence and prevalence of all the different types of diabetes mellitus were calculated. RESULTS Total number of children with diabetes mellitus was 1,325 (type 1 n = 1,096, ≥1 antibody; type 2 n = 104, type 1B n = 53; maturity onset diabetes of the young n = 20; monogenic autoimmune n = 4; neonatal diabetes mellitus n = 10;, syndromic diabetes mellitus n = 23; and double diabetes mellitus n = 15). The incidence and prevalence of type 1 diabetes were 38.05 and 249.73 per 100,000, respectively, and for type 2 were 2.51 and 23.7 per 100,000, respectively. The incidence of neonatal diabetes mellitus was 34.4 per 1,000,000 live births, and in indigenous Qataris the incidence was 43.6 per 1,000,000 live births. The prevalence of type 1 diabetes and type 2 diabetes in Qatari children was double compared with other nationalities. The prevalence of maturity onset diabetes of the young in Qatar was 4.56 per 100,000. CONCLUSIONS This is the first prospective and comprehensive study to document the epidemiology and genetic landscape of childhood diabetes mellitus in this region. Qatar has the fourth highest incidence of type 1 diabetes mellitus, with the incidence and prevalence being higher in Qatari compared with non-Qatari. The prevalence of type 2 diabetes mellitus is also higher in Qatar than in Western countries. The incidence of neonatal diabetes mellitus is the second highest in the world. GCK is the most common form of maturity onset diabetes of the young, and a large number of patients have type 1B diabetes mellitus.
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Affiliation(s)
- Basma Haris
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Saras Saraswathi
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Sara Al‐Khawaga
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Reem Hasnah
- Translational ResearchSidra MedicineDohaQatar
| | - Amira Saeed
- Translational ResearchSidra MedicineDohaQatar
| | - Shihab Mundekkadan
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Noor Hamed
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Houda Afyouni
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | | | - Shayma Mohammed
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Amel Khalifa
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Maryam Al‐Maadheed
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Mahmoud Al‐Zyoud
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Ahmed Shamekh
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Ahmed Elawwa
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Fawziya Al‐Khalaf
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | | | - Goran Petrovski
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
| | - Khalid Hussain
- Division of EndocrinologyDepartment of PediatricsSidra MedicineDohaQatar
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16
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Kahkoska AR, Dabelea D. Diabetes in Youth: A Global Perspective. Endocrinol Metab Clin North Am 2021; 50:491-512. [PMID: 34399958 PMCID: PMC8374087 DOI: 10.1016/j.ecl.2021.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Diabetes is a common disease among pediatric populations in the United States and worldwide. The incidence of type 1 and type 2 diabetes is increasing, with disproportional increases in racial/ethnic subpopulations. As the prevalence of obesity continue to increase, type 2 diabetes now represents a major form of pediatric diabetes. The management of diabetes in youth centers on maintaining glycemic control to prevent acute and chronic complications. This article summarizes the epidemiology, etiology, management, and complications of type 1 and type 2 diabetes in youth, as well as future directions and opportunities.
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Affiliation(s)
- Anna R Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, McGavran-Greenberg Hall 2205A, Chapel Hill, NC 27599, USA.
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Colorado School of Public Health, University of Colorado School of Medicine, Anschutz Medical Campus, 13001 East 17th Avenue, Box B119, Room W3110, Aurora, CO 80045, USA
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17
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Grøndahl MFG, Johannesen J, Kristensen K, Knop FK. Treatment of type 2 diabetes in children: what are the specific considerations? Expert Opin Pharmacother 2021; 22:2127-2141. [PMID: 34420454 DOI: 10.1080/14656566.2021.1954160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: The number of individuals under 18 years of age with type 2 diabetes is increasing at an alarming rate worldwide. These patients are often characterized by obesity and they often experience a more rapid disease progression than adults with type 2 diabetes. Thus, focus on prevention and management of complications and comorbidities is imperative. With emphasis on weight loss and optimal glycemic control, treatment includes lifestyle changes and pharmacotherapy, which in this patient group is limited to metformin, liraglutide and insulin. In selected cases, bariatric surgery is indicated.Areas covered: This perspective article provides an overview of the literature covering pathophysiology, diagnosis, characteristics and treatment of pediatric type 2 diabetes, and outlines the gaps in our knowledge where further research is needed. The paper draws on both mechanistic studies, large scale intervention trials, epidemiological studies and international consensus statements.Expert opinion: Type 2 diabetes in pediatric patients is an increasing health care problem, and the current treatment strategies do not successfully meet the many challenges and obstacles in this patient group. Treatments must be early, intensive, multifaceted and durable. Also, prevention of obesity and type 2 diabetes in at-risk children should be addressed and prioritized on all levels.
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Affiliation(s)
- Magnus F G Grøndahl
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jesper Johannesen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Pediatrics, Copenhagen University Hospital, Herlev and Gentofte, Denmark
| | - Kurt Kristensen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Steno Diabetes Center Aarhus - Children and Adolescence, Aarhus University, Aarhus, Denmark
| | - Filip K Knop
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Steno Diabetes Center Copenhagen, Gentofte, Denmark.,Novo Nordisk Foundation for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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18
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Pyle L, Kelsey MM. Youth-onset type 2 diabetes: translating epidemiology into clinical trials. Diabetologia 2021; 64:1709-1716. [PMID: 34075436 DOI: 10.1007/s00125-021-05480-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 03/10/2021] [Indexed: 12/17/2022]
Abstract
Globally, the proportion of new diagnoses of youth-onset diabetes represented by type 2 diabetes is increasing, and youth with type 2 diabetes commonly have complications and comorbidities, as well as a higher rate of mortality. In this review, we summarise what is known about the natural progression of youth-onset type 2 diabetes from published clinical trials and large-scale prospective epidemiological studies. It is important to note that the robust pathophysiological and treatment data specifically related to individuals with a diabetes onset at ≤20 years of age largely hails from the USA. Youth-onset type 2 diabetes is characterised by pathophysiological heterogeneity and inadequate glycaemic control, highlighting the need for new treatment approaches and innovative study designs in populations of varied genetic and cultural backgrounds.
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Affiliation(s)
- Laura Pyle
- Section of Paediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA
| | - Megan M Kelsey
- Section of Paediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
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19
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Serbis A, Giapros V, Kotanidou EP, Galli-Tsinopoulou A, Siomou E. Diagnosis, treatment and prevention of type 2 diabetes mellitus in children and adolescents. World J Diabetes 2021; 12:344-365. [PMID: 33889284 PMCID: PMC8040084 DOI: 10.4239/wjd.v12.i4.344] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/31/2021] [Accepted: 03/25/2021] [Indexed: 02/06/2023] Open
Abstract
During the last two decades, there have been several reports of an increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents, especially among those belonging to minority ethnic groups. This trend, which parallels the increases in prevalence and degree of pediatric obesity, has caused great concern, even though T2DM remains a relatively rare disease in children. Youth T2DM differs not only from type 1 diabetes in children, from which it is sometimes difficult to differentiate, but also from T2DM in adults, since it appears to be an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Despite the recent research, many aspects of youth T2DM still remain unknown, regarding both its pathophysiology and risk factor contribution, and its optimal management and prevention. Current management approaches include lifestyle changes, such as improved diet and increased physical activity, together with pharmacological interventions, including metformin, insulin, and the recently approved glucagon-like peptide-1 analog liraglutide. What is more important for everyone to realize though, from patients, families and physicians to schools, health services and policy-makers alike, is that T2DM is a largely preventable disease that will be addressed effectively only if its major contributor (i.e., pediatric obesity) is confronted and prevented at every possible stage of life, from conception until adulthood. Therefore, relevant comprehensive, coordinated, and innovative strategies are urgently needed.
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Affiliation(s)
- Anastasios Serbis
- Department of Pediatrics, University Hospital of Ioannina, Ioannina 45500, Greece
| | - Vasileios Giapros
- Department of Child Health, University of Ioannina, Ioannina 45500, Greece
| | - Eleni P Kotanidou
- Department of Pediatrics, Medical School, Aristotle University Thessaloniki, Thessaloniki 54636, Greece
| | | | - Ekaterini Siomou
- Department of Pediatrics, University Hospital of Ioannina, Ioannina 45500, Greece
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20
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Chen A, Wang H, Su Y, Zhang C, Qiu Y, Zhou Y, Wan Y, Hu B, Li Y. Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications. Front Endocrinol (Lausanne) 2021; 12:720466. [PMID: 34456875 PMCID: PMC8387814 DOI: 10.3389/fendo.2021.720466] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/22/2021] [Indexed: 12/17/2022] Open
Abstract
Diabetic vascular complications (DVC) including macrovascular and microvascular lesions, have a significant impact on public health, and lead to increased patient mortality. Disordered intercellular cascades play a vital role in diabetic systemic vasculopathy. Exosomes participate in the abnormal signal transduction of local vascular cells and mediate the transmission of metabolic disorder signal molecules in distant organs and cells through the blood circulation. They can store different signaling molecules in the membrane structure and release them into the blood, urine, and tears. In recent years, the carrier value and therapeutic effect of exosomes derived from stem cells have garnered attention. Exosomes are not only a promising biomarker but also a potential target and tool for the treatment of DVC. This review explored changes in the production process of exosomes in the diabetic microenvironment and exosomes' early warning role in DVC from different systems and their pathological processes. On the basis of these findings, we discussed the future direction of exosomes in the treatment of DVC, and the current limitations of exosomes in DVC research.
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Affiliation(s)
| | | | | | | | | | | | | | - Bo Hu
- *Correspondence: Yanan Li, ; Bo Hu,
| | - Yanan Li
- *Correspondence: Yanan Li, ; Bo Hu,
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21
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Katsiki N, Ferrannini E, Mantzoros C. New American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) guidelines for the pharmacotherapy of type 2 diabetes: Placing them into a practicing physician's perspective. Metabolism 2020; 107:154218. [PMID: 32222374 DOI: 10.1016/j.metabol.2020.154218] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Niki Katsiki
- First Department of Internal Medicine, Diabetes Center, Division of Endocrinology and Metabolism, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | | | - Christos Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
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