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Artlett CM, Abdelwahab SH, Hoffman WH, Calikoglu AS. Early expression of neuroinflammation in an untreated fatal case of diabetic ketoacidosis. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2024; 68:e240074. [PMID: 39529986 PMCID: PMC11554359 DOI: 10.20945/2359-4292-2024-0074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 05/26/2024] [Indexed: 11/16/2024]
Abstract
We present the case of a young adult who had lethargy and significant weight loss for the three weeks before his death. The history of the present illness suggested a prodrome of several weeks, with progressive weakness indicating an advancing metabolic decompensation. To our knowledge, this is the first study performed on human brain tissue with type 1 diabetes (T1D) and likely diabetic ketoacidosis (DKA) before treatment. We studied neuroinflammatory markers in an insulin-deficient state without treatment compared with those found in a treated patient with T1D/DKA of similar age and race who died shortly after treatment. The frontal cortex and hippocampus were stained for tight junction proteins, RAGE, NLRP3, and HMGB1. Other markers that can disrupt the blood-brain barrier, such as IL-17, IL-6, IL-1β, GFAP, and IL-10 were also tested. This case study reveals that neuroinflammatory markers are expressed in the DKA brain at a lower level before treatment than those found to be expressed in the brain after treatment. These findings suggest that in DKA, dehydration minimizes inflammation which could be exacerbated with fluids promoting neuroinflammation and cognitive deficits. These findings require further studies and could identify therapeutic targets to reduce the progression of neuroinflammation and brain edema.
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Affiliation(s)
- Carol M. Artlett
- Drexel UniversityDrexel University College of MedicineDepartment of Microbiology and ImmunologyPhiladelphiaPAUnited StatesDepartment of Microbiology and Immunology, Drexel University College of Medicine, Drexel University, Philadelphia PA
| | - Sabri H. Abdelwahab
- University of North CarolinaDepartment of GeneticsChapel HillNCUnited StatesDepartment of Genetics, University of North Carolina, Chapel Hill NC
| | - William H. Hoffman
- Augusta UniversityMedical College of GeorgiaSection of Pediatric EndocrinologyAugustaGAUnited StatesSection of Pediatric Endocrinology, Medical College of Georgia, Augusta University, Augusta, GA
| | - Ali S. Calikoglu
- University of North CarolinaDivision of Pediatric EndocrinologyChapel HillNCUnited StatesDivision of Pediatric Endocrinology, University of North Carolina, Chapel Hill NC
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Atakul G, Korkmaz HA, Gönüllü A, Sandal ÖS, Köprülü Ö, Uyar N, Karaaslan U, Apa H, Ağın H, Özkan B. Does an episode of diabetic ketoacidosis affect thyroid function tests in pediatric patients? J Pediatr Endocrinol Metab 2024; 37:400-404. [PMID: 38568210 DOI: 10.1515/jpem-2024-0022] [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: 01/10/2024] [Accepted: 03/13/2024] [Indexed: 05/05/2024]
Abstract
OBJECTIVES The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA). METHODS Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group. RESULTS A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak. CONCLUSIONS Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests.
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Affiliation(s)
- Gülhan Atakul
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Huseyin Anıl Korkmaz
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
- Pediatric Endocrinology, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Ahmet Gönüllü
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Özlem Saraç Sandal
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Özge Köprülü
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
- Pediatric Endocrinology, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Nilüfer Uyar
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
- Pediatric Endocrinology, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Utku Karaaslan
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Hurşit Apa
- Pediatric Emergency Care, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Hasan Ağın
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
| | - Behzat Özkan
- Pediatric Intensive Care Unit, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
- Pediatric Endocrinology, Health Sciences University, Dr. Behçet Uz Children's Diseases and Surgery Training and Research Hospital, İzmir, Türkiye
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Hamtzany O, Weiser G, Heiman E, Avnon-Ziv C, Auerbauch A, Levy-Khademi F. Leukocytosis and C-Reactive Protein Levels as Indicators of Infection in Children With Diabetic Ketoacidosis. Pediatr Emerg Care 2023; 39:828-831. [PMID: 36988575 DOI: 10.1097/pec.0000000000002934] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is one of the serious complications of type 1 diabetes mellitus and may be aggravated by infection. Diagnosing an infection in a patient with DKA is often complicated because of the overlap of symptoms and the presence of leukocytosis in both conditions. Reliable indicators for the diagnosis of bacterial infection in DKA may reduce unnecessary use of antibiotics and enable closer monitoring of patients at risk. METHODS This is a retrospective study. The study cohort included 180 children and adolescents with type 1 diabetes mellitus who were admitted to the Pediatric Emergency Department at Shaare Zedek Medical Center and had blood test results. We compared white blood cell count, C-reactive protein (CRP) levels, blood glucose levels, pH, the degree of acidosis, and the incidence of infection in patients with and without DKA. RESULTS The incidence of probable bacterial infection in the entire cohort was 13.9%: 15.7% in the DKA group and 7.5% in the non-DKA group ( P = 0.65). The incidence of leukocytosis was significantly higher in patients with DKA ( P = 0.0003), although this was not related to bacterial infection. The CRP levels were higher in the DKA group with infection than without infection, and this was statistically significant ( P = 0.008). CONCLUSIONS Our findings suggest that leukocytosis in DKA is not a reliable indicator of concomitant bacterial infection. In contrast, CRP levels were not related to the DKA or degree of acidosis and were significantly higher in patients with infection within the DKA group, and are therefore a more reliable indicator of concomitant infection in these patients.
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Dai L, Wang A, Gu H, Zhang Y, Zuo Y, Meng X, Chen P, Tian X, Li H, Wang Y. Urinary ketone bodies and stroke recurrence in patient with acute ischemic stroke or TIA. J Clin Neurosci 2023; 117:79-83. [PMID: 37778303 DOI: 10.1016/j.jocn.2023.09.019] [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: 07/16/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Urine ketone bodies may appear in different states in the acute stage of stroke. We aimed to examine the association between urine ketone bodies and recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in this study. METHODS In Third China National Stroke Registry (CNSR-III), 14,015 patients with AIS or TIA were screened for urine ketone bodies. The outcomes were any stroke, ischemic stroke and combined vascular events within 1 year. The association of urine ketone bodies with recurrent stroke were analyzed by Cox proportional hazards. RESULTS During 1 year of follow-up, 1,335 (9.53%) participants experienced recurrent stroke. After adjustment for conventional confounding factors, patients with urine ketone bodies test positive had a higher risk of recurrent stroke (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.13-1.82), compared to those were negative. The correlation between positive urine ketone bodies and recurrent stroke were consistent in patient with (HR, 1.45; 95% CI, 1.00-2.12) and without (HR, 1.40; 95% CI, 1.02-1.94) diabetes. No significant interaction between urine ketone bodies and diabetes were observed. CONCLUSIONS Positive ketone bodies in urine was independently associated with recurrent stroke in patients with AIS or TIA.
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Affiliation(s)
- Liye Dai
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Anxin Wang
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Hongqiu Gu
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yijun Zhang
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yingting Zuo
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China; Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Xia Meng
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Pan Chen
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xue Tian
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China; Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Hao Li
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yongjun Wang
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
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Chai J, Sun Z, Zhou Q, Xu J. Evaluation of Trace Elements Levels and Construction of Auxiliary Prediction Model in Patients with Diabetes Ketoacidosis in Type 1 Diabetes. Diabetes Metab Syndr Obes 2023; 16:3403-3415. [PMID: 37929055 PMCID: PMC10624197 DOI: 10.2147/dmso.s425156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 10/22/2023] [Indexed: 11/07/2023] Open
Abstract
Background Trace elements play an important role in reflecting physical metabolic status, but have been rarely evaluated in diabetes ketoacidosis (DKA). Since clinical biochemical parameters are the first-line diagnostic data mastered by clinical doctors and DKA has a rapid progression, it is crucial to fully utilize clinical data and combine innovative parameters to assist in assessing disease progression. The aim of this study was to evaluate the levels of trace elements in DKA patients, followed by construction of predictive models combined with the laboratory parameters. Methods A total of 96 T1D individuals (48 DKA patients) were collected from the First Hospital of Jilin University. Serum calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), iron (Fe) and selenium (Se) were measured by Inductively Coupled Plasma Mass Spectrometry, and the data of biochemical parameters were collected from the laboratory information system. Training and validation sets were used to construct the model and examine the efficiency of the model. The lambda-mu-sigma method was used to evaluate the changes in the model prediction efficiency as the severity of the patient's condition increases. Results Lower levels of serum Mg, Ca and Zn, but higher levels of serum Fe, Cu and Se were found in DKA patients. Low levels of total protein (TP), Zn and high levels of lipase would be an efficient combination for the prediction of DKA (Area under curves for training set and validation set were 0.867 and 0.961, respectively). The examination test confirmed the clinical applicability of the constructed models. The increasing predictive efficiency of the model was found with NACP. Conclusion More severe oxidative stress in DKA led to further imbalance of trace elements. The combination of TP, lipase and Zn could predict DKA efficiently, which would benefit the early identification and prevention of DKA to improve prognosis.
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Affiliation(s)
- Jiatong Chai
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Zeyu Sun
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Qi Zhou
- Department of Pediatrics, First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Jiancheng Xu
- Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, People’s Republic of China
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Ahmad R, Narwaria M, Singh A, Kumar S, Haque M. Detecting Diabetic Ketoacidosis with Infection: Combating a Life-Threatening Emergency with Practical Diagnostic Tools. Diagnostics (Basel) 2023; 13:2441. [PMID: 37510185 PMCID: PMC10378387 DOI: 10.3390/diagnostics13142441] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and can lead to patient demise if not immediately treated. From the recent literature, the diabetic ketoacidosis mortality rate, depending on age, is 2-5%. Insulin discontinuation and infection remain the two most common triggers for diabetic ketoacidosis. About 50% of cases of ketoacidosis result from bacterial infections like urinary tract infections and pneumonia. It is also important to diagnose the presence of infection in diabetic ketoacidosis patients to prevent the excessive use of antibiotics, which may lead to antibiotic resistance. Although performing bacterial culture is confirmatory for the presence or absence of bacterial infection, the time required to obtain the result is long. At the same time, emergency treatment needs to be started as early as possible. METHODS This narrative review examines various septic markers to identify the appropriate tools for diagnosis and to distinguish between diabetic ketoacidosis with and without infection. Electronic databases were searched using the Google engine with the keywords "Diabetes Mellitus", "Diabetic Ketoacidosis", "Infection with Diabetic Ketoacidosis", "biomarkers for infection in Diabetic Ketoacidosis", "Procalcitonin", "Inflammatory cytokines in DKA", "Lactic acidosis in DKA", and "White blood cell in infection in DKA". RESULTS This narrative review article presents the options for diagnosis and also aims to create awareness regarding the gravity of diabetic ketoacidosis with infection and emphasizes the importance of early diagnosis for appropriate management. Diabetes mellitus is a clinical condition that may lead to several acute and chronic complications. Acute diabetic ketoacidosis is a life-threatening condition in which an excess production of ketone bodies results in acidosis and hypovolemia. Infection is one of the most common triggers of diabetic ketoacidosis. When bacterial infection is present along with diabetic ketoacidosis, the mortality rate is even higher than for patients with diabetic ketoacidosis without infection. The symptoms and biomarkers of diabetic ketoacidosis are similar to that of infection, like fever, C reactive protein, and white blood cell count, since both create an environment of systemic inflammation. It is also essential to distinguish between the presence and absence of bacterial infection to ensure the appropriate use of antibiotics and prevent antimicrobial resistance. A bacterial culture report is confirmatory for the existence of bacterial infection, but this may take up to 24 h. Diagnosis needs to be performed approximately in the emergency room upon admission since there is a need for immediate management. Therefore, researching the possible diagnostic tools for the presence of infection in diabetic ketoacidosis patients is of great importance. Several of such biomarkers have been discussed in this research work.
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Affiliation(s)
- Rahnuma Ahmad
- Department of Physiology, Medical College for Women and Hospital, Dhaka 1230, Bangladesh
| | - Mahendra Narwaria
- Asian Bariatrics Plus Hospital, V Wing-Mondeal Business Park, S G Highways, Ahmedabad 380054, India
| | - Arya Singh
- Asian Bariatrics Plus Hospital, V Wing-Mondeal Business Park, S G Highways, Ahmedabad 380054, India
| | - Santosh Kumar
- Department of Periodontology, Karnavati School of Dentistry, Karnavati University, Gandhinagar 382422, India
| | - Mainul Haque
- Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur 57000, Malaysia
- Department of Scientific Research Center (KSRC), Karnavati School of Dentistry, Karnavati University, Gandhinagar 382422, India
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Hassan EM, Mushtaq H, Mahmoud EE, Chhibber S, Saleem S, Issa A, Nitesh J, Jama AB, Khedr A, Boike S, Mir M, Attallah N, Surani S, Khan SA. Overlap of diabetic ketoacidosis and hyperosmolar hyperglycemic state. World J Clin Cases 2022; 10:11702-11711. [PMID: 36405291 PMCID: PMC9669841 DOI: 10.12998/wjcc.v10.i32.11702] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/14/2022] [Accepted: 09/27/2022] [Indexed: 11/08/2022] Open
Abstract
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia state (HHS) are two life-threatening metabolic complications of diabetes that significantly increase mortality and morbidity. Despite major advances, reaching a uniform consensus regarding the diagnostic criteria and treatment of both conditions has been challenging. A significant overlap between these two extremes of the hyperglycemic crisis spectrum poses an additional hurdle. It has well been noted that a complete biochemical and clinical patient evaluation with timely diagnosis and treatment is vital for symptom resolution. Worldwide, there is a lack of large-scale studies that help define how hyperglycemic crises should be managed. This article will provide a comprehensive review of the pathophysiology, diagnosis, and management of DKA-HHS overlap.
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Affiliation(s)
- Esraa Mamdouh Hassan
- Critical Care Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
| | - Hisham Mushtaq
- Medicine, St. Vincent's Medical Center, Bridgeport, CT 06606, United States
| | - Esraa Elaraby Mahmoud
- Medicine, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Sherley Chhibber
- Medicine, Mercy Catholic Medical Center, Darby, PA 19025, United States
| | - Shoaib Saleem
- Medicine, Mayo Hospital, Lahore 54000, Punjab, Pakistan
| | - Ahmed Issa
- Medicine, Medical University of the Americas, Nevis, West Indies
| | - Jain Nitesh
- Critical Care Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
| | - Abbas B Jama
- Critical Care Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
| | - Anwar Khedr
- Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Sydney Boike
- Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, United States
| | - Mikael Mir
- Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, United States
| | - Noura Attallah
- Critical Care Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
| | - Salim Surani
- Medicine & Pharmacology, Texas A&M University Health Science Center, College Station, TX 77843, United States
- Anesthesiolgy, Mayo Clinic, Rochester, MN 55905, United States
| | - Syed A Khan
- Critical Care Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
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Glaser N, Fritsch M, Priyambada L, Rewers A, Cherubini V, Estrada S, Wolfsdorf JI, Codner E. ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes 2022; 23:835-856. [PMID: 36250645 DOI: 10.1111/pedi.13406] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 01/01/2023] Open
Affiliation(s)
- Nicole Glaser
- Department of Pediatrics, Section of Endocrinology, University of California, Davis School of Medicine, Sacramento, California, USA
| | - Maria Fritsch
- Department of Pediatric and Adolescent Medicine, Division of General Pediatrics, Medical University of Graz, Austria Medical University of Graz, Graz, Austria
| | - Leena Priyambada
- Division of Pediatric Endocrinology, Rainbow Children's Hospital, Hyderabad, India
| | - Arleta Rewers
- Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado, USA
| | - Valentino Cherubini
- Department of Women's and Children's Health, G. Salesi Hospital, Ancona, Italy
| | - Sylvia Estrada
- Department of Pediatrics, Division of Endocrinology and Metabolism, University of the Philippines, College of Medicine, Manila, Philippines
| | - Joseph I Wolfsdorf
- Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Ethel Codner
- Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile
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Glaser NS, Quayle KS, McManemy JK, Nigrovic LE, Tzimenatos L, Stoner MJ, Bennett JE, Trainor JL, Rewers A, Schunk JE, Myers SR, Kwok MY, Brown KM, Ghetti S, Casper TC, Olsen CS, Kuppermann N. Clinical Characteristics of Children with Cerebral Injury preceding Treatment of Diabetic Ketoacidosis. J Pediatr 2022; 250:100-104. [PMID: 35944716 DOI: 10.1016/j.jpeds.2022.07.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 07/12/2022] [Accepted: 07/28/2022] [Indexed: 11/15/2022]
Abstract
Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.
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Affiliation(s)
- Nicole S Glaser
- Department of Pediatrics, University of California Davis Health, University of California Davis School of Medicine, CA.
| | - Kimberly S Quayle
- Division of Emergency Medicine, Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine in St. Louis, St Louis, MO
| | - Julie K McManemy
- Division of Emergency Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX
| | - Lise E Nigrovic
- Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA
| | - Leah Tzimenatos
- Department of Emergency Medicine, University of California Davis Health, University of California Davis School of Medicine, Sacramento, CA
| | - Michael J Stoner
- Division of Emergency Medicine, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University School of Medicine, Columbus, OH
| | - Jonathan E Bennett
- Division of Emergency Medicine, Nemours/AI DuPont Hospital for Children, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA
| | - Jennifer L Trainor
- Division of Emergency Medicine, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Arleta Rewers
- Division of Emergency Medicine, Department of Pediatrics, The Colorado Children's Hospital, University of Colorado-Denver School of Medicine, Aurora, CO
| | - Jeff E Schunk
- Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT
| | - Sage R Myers
- Division of Emergency Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | - Maria Y Kwok
- Division of Emergency Medicine, Department of Pediatrics, New York Presbyterian Morgan Stanley Children's Hospital, Columbia University College of Physicians and Surgeons, New York, NY
| | - Kathleen M Brown
- Division of Emergency Medicine, Department of Pediatrics, Children's National Medical Center, The George Washington School of Medicine and Health Sciences, Washington, DC
| | - Simona Ghetti
- Department of Psychology, University of California Davis, Sacramento, CA
| | - T Charles Casper
- Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT
| | - Cody S Olsen
- Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT
| | - Nathan Kuppermann
- Department of Pediatrics, University of California Davis Health, University of California Davis School of Medicine, CA; Department of Emergency Medicine, University of California Davis Health, University of California Davis School of Medicine, Sacramento, CA
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Acute kidney injury and diabetic kidney disease in children with acute complications of diabetes. Pediatr Nephrol 2022; 38:1643-1652. [PMID: 36227434 PMCID: PMC10060302 DOI: 10.1007/s00467-022-05735-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 08/12/2022] [Accepted: 09/02/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied. METHODS The study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed. RESULTS AKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 × 103/µL, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control. CONCLUSIONS Diabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Boddhula S, Boddhula SK, Reddy Garlapati P, Patel MJ, Ekanem S, Adapa S, Fong V, Balaji S, Murthi S, Gayam V. Diabetic Ketoacidosis and COVID-19: A Case Series From an Inner-City Community Teaching Hospital in New York. Cureus 2022; 14:e26580. [PMID: 35936183 PMCID: PMC9351819 DOI: 10.7759/cureus.26580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/04/2022] [Indexed: 12/15/2022] Open
Abstract
Introduction: Throughout the coronavirus disease 2019 (COVID-19) pandemic, studies have repeatedly shown that COVID-19 outcomes are more severe in the elderly and those with comorbidities, with diabetes being a significant risk factor associated with more severe infection. Here, we present the clinical characteristics of 25 patients with pre-existing type 2 diabetes mellitus who presented with diabetic ketoacidosis (DKA) and COVID-19 in a community hospital in Brooklyn, New York, and identify possible predictors of mortality. Methods: This retrospective case series recruited patients from March 1st to April 9th, 2020, with lab-confirmed COVID-19 and met DKA criteria on admission (based on American Diabetes Association diagnostic criteria for DKA). Results: Of the 25 patients who met the inclusion criteria, 22 were African American and three were Hispanic. Common comorbidities in addition to diabetes were hypertension, obesity, coronary artery disease, and dyslipidemia. Fever, cough, myalgias, and shortness of breath were common presenting symptoms. Most patients had elevated inflammatory markers erythrocyte sedimentation rate, C-reactive protein, D-dimer, and ferritin, but higher values increased the odds of mortality. The overall survival was 64%, with those recovering having more extended hospital stays but requiring less time in the intensive care unit. At the same time, those who died were more likely to require mechanical ventilation, have an acute cardiac injury, and/or be obese. Despite numerous studies on COVID and diabetes, only a few studies described DKA. Conclusion: This observational retrospective study illustrated that patients with diabetes are at risk of developing DKA with COVID-19 and identified some predictors of mortality. However, further studies with larger sample sizes and a control group are necessary to understand better the effects of COVID-19 on DKA and their clinical outcomes.
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12
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Horiya M, Anno T, Shigemoto R, Koyama K, Kawasaki F, Tomoda K, Kaku K, Kaneto H. Acute respiratory distress syndrome triggered by marked cytokine storm in a subject with diabetic ketoacidosis: A case report. Medicine (Baltimore) 2022; 101:e29119. [PMID: 35357353 PMCID: PMC11319312 DOI: 10.1097/md.0000000000029119] [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: 01/29/2022] [Accepted: 03/03/2022] [Indexed: 01/08/2023] Open
Abstract
RATIONALE Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury. Many causes of acute direct and indirect lung injury have been described as possible initiators of ARDS. According to the literature data, ARDS could be a rare complication associated with the acute onset of diabetic ketoacidosis (DKA). Moreover, it has been suggested that cytokine release during DKA is involved in the above-mentioned acute clinical complications of DKA. PATIENTCONCERNS A 48-year-old Japanese woman with a 4-year history of type 1 diabetes mellitus was brought to an emergency room with symptoms of deteriorated consciousness. Three days before, she was diagnosed with influenza A infection. DIAGNOSIS Inflammation markers were markedly elevated and she was under DKA condition. Since her respiratory conditions were suddenly and markedly aggravated 2 days later, we diagnosed her as ARDS and continued systemic management with the ventilator.Interleukin-6 (IL-6) level was markedly elevated at the onset of ARDS, although IL-6 level was high at the onset of DKA. ARDS was suggested to be caused by marked cytokine storm and DKA. INTERVENTIONS We continued to treat her hyperglycemic crises. Moreover, we continued systemic management with the ventilator. OUTCOMES Approximately three weeks later, her general conditions were stabilized and ventilator management was stopped. We successfully treated her ARDS and hyperglycemic crises. LESSONS This case is very important because it shows that DKA can induce cytokine storm, which leads to the onset of ARDS. Therefore, monitoring various cytokines such as IL-6, which are associated with ARDS during the period of treatment of DKA is beneficial.
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Affiliation(s)
- Megumi Horiya
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan,
| | - Takatoshi Anno
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan,
| | - Ryo Shigemoto
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan,
| | - Katsumasa Koyama
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan,
| | - Fumiko Kawasaki
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan,
| | - Koichi Tomoda
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan,
| | - Kohei Kaku
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan,
| | - Hideaki Kaneto
- Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
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13
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Aldhaeefi M, Aldardeer NF, Alkhani N, Alqarni SM, Alhammad AM, Alshaya AI. Updates in the Management of Hyperglycemic Crisis. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2022; 2:820728. [PMID: 36994324 PMCID: PMC10012093 DOI: 10.3389/fcdhc.2021.820728] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 12/24/2021] [Indexed: 12/14/2022]
Abstract
Diabetes mellitus (DM) affects the metabolism of primary macronutrients such as proteins, fats, and carbohydrates. Due to the high prevalence of DM, emergency admissions for hyperglycemic crisis, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are fairly common and represent very challenging clinical management in practice. DKA and HHS are associated with high mortality rates if left not treated. The mortality rate for patients with DKA is < 1% and ~ 15% for HHS. DKA and HHS have similar pathophysiology with some few differences. HHS pathophysiology is not fully understood. However, an absolute or relative effective insulin concentration reduction and increased in catecholamines, cortisol, glucagon, and growth hormones represent the mainstay behind DKA pathophysiology. Reviewing the patient’s history to identify and modify any modifiable precipitating factors is crucial to prevent future events. The aim of this review article is to provide a review of the DKA, and HHS management based on the most recently published evidence and to provide suggested management pathway of DKA of HHS management in practice.
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Affiliation(s)
- Mohammed Aldhaeefi
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- *Correspondence: Mohammed Aldhaeefi,
| | - Namareq F. Aldardeer
- Department of Pharmacy Services, King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia
| | - Nada Alkhani
- Department of Pharmacy Services, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Shatha Mohammed Alqarni
- Doctor of Pharmacy Program, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abdullah M. Alhammad
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
- Department of Pharmacy Services, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Abdulrahman I. Alshaya
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Riyadh, Saudi Arabia
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14
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Sakou II, Soldatou A, Seretis A, Karanasios E, Paltoglou G, Karavanaki K. Markedly elevated troponin and NT-proBNP and myocardial dysfunction in an adolescent with severe diabetic ketoacidosis: a case report. Clin Pediatr Endocrinol 2022; 31:192-198. [PMID: 35928382 PMCID: PMC9297169 DOI: 10.1297/cpe.2022-0017] [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: 02/21/2022] [Accepted: 04/16/2022] [Indexed: 12/04/2022] Open
Abstract
Severe diabetic ketoacidosis (DKA), rarely, may be associated with elevated troponin and
proBNP levels in adults with a history of diabetes. However, few cases have reported this
association in children with severe and complicated DKA. We describe a case of severe DKA
(pH: 6.89, HCO3: 6.5) in a 14-yr-old female adolescent in which the symptoms of DKA were
presented days before the diagnosis. The patient was under the effect of acidosis
(Kussmaul respiration) for 12 h before admission to our hospital, where she was admitted
in a critical clinical condition. After successful treatment with DKA with intensive
intravenous fluid and regular insulin, the patient presented with abnormal cardiac rhythm,
disturbance of interventricular septum motility, a mild decrease in left ventricular
systolic function, negative T waves in leads III and aVF, and a marked increase in
troponin and brain natriuretic peptide (NT-proBNP) levels. All abnormal findings
completely resolved within 8 days after the initiation of DKA treatment. The phenomenon in
our case was transient, and the patient had a good long-term outcome. However, it
represents a challenge for clinicians; therefore, emphasis should be given to cardiac
monitoring during the course of severe and prolonged DKA in children and adolescents.
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Affiliation(s)
- Irine-Ikbale Sakou
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Children’s Hospital, Athens, Greece
| | - Alexandra Soldatou
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Children’s Hospital, Athens, Greece
| | - Aristeidis Seretis
- Cardiology Deparment, “P&A Kyriakou” Children’s Hospital, Athens, Greece
| | | | - George Paltoglou
- University Research Institute of Maternal and Child Health and Precision Medicine, Athens, Greece
| | - Kyriaki Karavanaki
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Children’s Hospital, Athens, Greece
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15
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Huang B, Yang S, Ye S. Systemic Infection Predictive Value of Procalcitonin to Lactic Acid Ratio in Diabetes Ketoacidosis Patients. Diabetes Metab Syndr Obes 2022; 15:2127-2133. [PMID: 35911501 PMCID: PMC9325875 DOI: 10.2147/dmso.s371437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 07/19/2022] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Early detection of bacterial infections associated with adequate antibiotic treatment is key to improving diabetic ketoacidosis (DKA) outcomes. Our study aimed to investigate the different sepsis markers (including procalcitonin to lactic acid ratio, PLR) to diagnose bacterial infection in patients with DKA within one hour after admission. METHODS A total of 165 patients diagnosed with DKA were enrolled between July 2014 and July 2018 and divided into an infection group (N =62) and a non-infection group (N=103) based on the positive aetiological tests such as blood culture, sputum culture, urine culture, or definite focus of pulmonary, soft tissue, kidney, etc. RESULTS Our findings suggest the following: 1) leucocytes (threshold above 10×109 /L) and PLR (threshold above 0.438) within one hour after admission can help to identify patients with infection in the context of DKA. 2) A subgroup analysis demonstrated that PLR also has a high diagnostic efficacy for infection in patients with DKA, regardless of the type of diabetes. CONCLUSION This study concludes that leucocyte count (threshold > 10×109/L) and PLR (threshold above 0.438) show a diagnostic value to help distinguish DKA patients with infection. By combining these two markers, the reduction of antibiotic misuse may be possible.
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Affiliation(s)
- Bin Huang
- Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China
- Research Institution of Diabetes, University of Science and Technology of China, Hefei, People’s Republic of China
| | - Shengju Yang
- Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China
| | - Shandong Ye
- Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China
- Correspondence: Shandong Ye, Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China, Email
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16
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Iftikhar S, Rehman AU, Ameer MZ, Nawaz A, Aemaz Ur Rehman M, Farooq H, Asmar A, Ebaad Ur Rehman M. The association of posterior reversible encephalopathy syndrome with COVID-19: A systematic review. Ann Med Surg (Lond) 2021; 72:103080. [PMID: 34840779 PMCID: PMC8605817 DOI: 10.1016/j.amsu.2021.103080] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/15/2021] [Accepted: 11/16/2021] [Indexed: 01/08/2023] Open
Abstract
The rise in Coronavirus disease 2019 (COVID-19) cases is revealing its unique neurological manifestations. In light of the emerging evidence, a possible association with Posterior Reversible Encephalopathy Syndrome (PRES) is being consistently reported. We conducted a systematic literature search on four databases namely Pubmed/MEDLINE, Cochrane, Google Scholar, and Science Direct. After rigorous screening as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a total of 34 articles describing 56 cases were selected as a part of this review. The mean age of the patients was 56.6 ± 15.3 years. The most common clinical presentation of PRES was altered mental status (58.9%) followed by seizures (46.4%) and visual disturbances (23.2%) while hypertension and diabetes mellitus were the most commonly reported comorbidities. 91.1% of the cases reported Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) findings suggestive of PRES in the brain. Symptomatic management was employed in most of the cases to control seizures and blood pressure, and 44 patients (78.5%) fully or partially recovered. The most likely underlying mechanism involves COVID-19 mediated cytokine storm syndrome that leads to endothelial damage and increased permeability of the cerebral vessels, thus causing the characteristic edema of PRES. High neuronal and glial cell expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors also suggests the possibility of direct viral damage. Since timely diagnosis and treatment reports a good prognosis, it is vital for physicians and neurologists to be well-versed with this association.
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Affiliation(s)
- Sadaf Iftikhar
- Mayo Hospital, King Edward Medical University, Lahore, 54000, Pakistan
| | | | | | - Ahmad Nawaz
- King Edward Medical University, Lahore, 54000, Pakistan
| | | | - Hareem Farooq
- Mayo Hospital, King Edward Medical University, Lahore, 54000, Pakistan
| | - Abyaz Asmar
- Mayo Hospital, King Edward Medical University, Lahore, 54000, Pakistan
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17
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Hoffman WH, Whelan SA, Lee N. Tryptophan, kynurenine pathway, and diabetic ketoacidosis in type 1 diabetes. PLoS One 2021; 16:e0254116. [PMID: 34280211 PMCID: PMC8289002 DOI: 10.1371/journal.pone.0254116] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 06/20/2021] [Indexed: 12/22/2022] Open
Abstract
Diabetic ketoacidosis (DKA) is a serious complication of complete insulin deficiency and insulin resistance in Type 1 diabetes (T1D). This results in the body producing high levels of serum ketones in an attempt to compensate for the insulin deficiency and decreased glucose utilization. DKA's metabolic and immunologic dysregulation results in gradual increase of systemic and cerebral oxidative stress, along with low grade systemic and cerebral inflammation and the development of pretreatment subclinical BE. During treatment the early progression of oxidative stress and inflammation is hypothesized to advance the possibility of occurrence of crisis of clinical brain edema (BE), which is the most important cause of morbidity and mortality in pediatric DKA. Longitudinal neurocognitive studies after DKA treatment show progressive and latent deficits of cognition and emphasize the need for more effective DKA treatment of this long-standing conundrum of clinical BE, in the presence of systemic osmotic dehydration, metabolic acidosis and immune dysregulation. Candidate biomarkers of several systemic and neuroinflammatory pathways prior to treatment also progress during treatment, such as the neurotoxic and neuroprotective molecules in the well-recognized tryptophan (TRP)/kynurenine pathway (KP) that have not been investigated in DKA. We used LC-MS/MS targeted mass spectrometry analysis to determine the presence and initiation of the TRP/KP at three time points: A) 6-12 hours after initiation of treatment; B) 2 weeks; and C) 3 months following DKA treatment to determine if they might be involved in the pathogenesis of the acute vasogenic complication of DKA/BE. The Trp/KP metabolites TRP, KYN, quinolinic acid (QA), xanthurnenic acid (XA), and picolinic acid (PA) followed a similar pattern of lower levels in early treatment, with subsequent increases. Time point A compared to Time points B and C were similar to the pattern of sRAGE, lactate and pyruvic acid. The serotonin/melatonin metabolites also followed a similar pattern of lower quantities at the early stages of treatment compared to 3 months after treatment. In addition, glutamate, n-acetylglutamate, glutamine, and taurine were all lower at early treatment compared to 3 months, while the ketones 3-hydroxybutaric acid and acetoacetate were significantly higher in the early treatment compared to 3 months. The two major fat metabolites, L-carnitine and acetyl-L-carnitine (ALC) changed inversely, with ALC significantly decreasing at 2 weeks and 3 months compared to the early stages of treatment. Both anthranilic acid (AA) and 3-OH-anthranilic acid (3OH-AA) had overall higher levels in the early stages of treatment (A) compared to Time points (B and C). Interestingly, the levels of AA and 3OH-AA early in treatment were higher in Caucasian females compared to African American females. There were also differences in the metabolite levels of QA and kynurenic acid (KA) between genders and between races that may be important for further development of custom targeted treatments. We hypothesize that the TRP/KP, along with the other inflammatory pathways, is an active participant in the metabolic and immunologic pathogenesis of DKA's acute and chronic insults.
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Affiliation(s)
- William H. Hoffman
- Department of Pediatrics, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America
- * E-mail: (WHH); (SAW)
| | - Stephen A. Whelan
- Department of Chemistry, Chemical Instrumentation Center (CIC), Boston University, Boston Massachusetts, United States of America
- * E-mail: (WHH); (SAW)
| | - Norman Lee
- Department of Chemistry, Chemical Instrumentation Center (CIC), Boston University, Boston Massachusetts, United States of America
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18
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Darrat M, Gilmartin B, Kennedy C, Smith D. Acute respiratory distress syndrome in a case of diabetic ketoacidosis requiring ECMO support. Endocrinol Diabetes Metab Case Rep 2021; 2021:EDM200192. [PMID: 34236038 PMCID: PMC8284957 DOI: 10.1530/edm-20-0192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 06/15/2021] [Indexed: 11/08/2022] Open
Abstract
SUMMARY Acute respiratory distress syndrome (ARDS) is a rare but life-threatening complication of diabetic ketoacidosis (DKA). We present the case of a young female, with no previous diagnosis of diabetes, presenting in DKA complicated by ARDS requiring extra corporeal membrane oxygenation (ECMO) ventilator support. This case report highlights the importance of early recognition of respiratory complications of severe DKA and their appropriate management. LEARNING POINTS ARDS is a very rare but life-threatening complication in DKA. The incidence of ARDS remains unknown but less frequent than cerebral oedema in DKA. The mechanism of ARDS in DKA has multifactorial aetiology, including genetic predisposition. Early recognition and consideration of rare pulmonary complication of DKA can increase survival rate and provide very satisfactory outcomes. DKA patients who present with refractory ARDS can be successfully rescued by ECMO support.
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Affiliation(s)
- Milad Darrat
- Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland
| | - Brian Gilmartin
- Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland
| | - Carmel Kennedy
- Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland
| | - Diarmuid Smith
- Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland
- School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
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19
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Prabhu YD, Borthakur A, A G S, Vellingiri B, Valsala Gopalakrishnan A. Increased pro-inflammatory cytokines in ovary and effect of γ-linolenic acid on adipose tissue inflammation in a polycystic ovary syndrome model. J Reprod Immunol 2021; 146:103345. [PMID: 34116484 DOI: 10.1016/j.jri.2021.103345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/29/2021] [Accepted: 06/03/2021] [Indexed: 11/25/2022]
Abstract
Polycystic Ovary Syndrome (PCOS), a major endocrine disorder, affects the reproductive function of a woman, along with an association with metabolic conditions like insulin resistance and inflammation. The inflammatory nature of PCOS is much debated over, owing to numerous cases of elevation in cytokine levels. Studies have shown the beneficiary effect of Gamma-Linolenic acid (GLA) in reducing inflammation related to many conditions such as atopic dermatitis, rheumatoid arthritis, arterial disease, obesity, and even PCOS. The study aims at assessing the expression of inflammatory cytokines in the ovary and Peri-ovarian adipose tissue (POAT) of the Dehydroepiandrosterone (DHEA) induced PCOS rat model. Further, this study also evaluates the effect of γ-linolenic Acid (GLA) on these cytokines in POAT. Female Wistar rats were subcutaneously injected with 60 mg/kg DHEA daily for 28 days. These PCOS-induced rats were then orally administered with 50 mg/kg GLA for 14 days. The gene expression of cytokines was assessed by Real Time-PCR. The study showed an increase in the expression of cytokines in the ovary and POAT of the DHEA group. This suggests the role of ovarian adipose in adding to the pro-inflammatory state of PCOS. Moreover, the administration of GLA to the PCOS-induced rats resulted in a reduction of cytokine expression from the POAT, indicating that the compound was successful in reducing the associated inflammation. The study throws light on the possibility of using GLA as a supplementary or naturalistic alternative in ameliorating ovarian adipose-associated inflammation that accompanies PCOS.
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Affiliation(s)
- Yogamaya D Prabhu
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Atreyee Borthakur
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Subeka A G
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Balachandar Vellingiri
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
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20
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Chen YC, Tsai SJ. Bilateral cerebral infarction in diabetic ketoacidosis and bilateral internal carotid artery occlusion: A case report and review of literature. World J Clin Cases 2021; 9:3787-3795. [PMID: 34046484 PMCID: PMC8130090 DOI: 10.12998/wjcc.v9.i15.3787] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/02/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus (T1DM). Very rarely does DKA lead to cerebral edema, and it is even rarer for it to result in cerebral infarction. Bilateral internal carotid artery occlusion (BICAO) is also rare and can cause fatal stroke. Moreover, case reports about acute cerebral infarction throughout both internal carotid arteries with simultaneous BICAO are very scarce. In this study, we present a patient with BICAO, T1DM, hypertension, and hyperlipidemia, who had a catastrophic bilateral cerebral infarction after a DKA episode. We briefly introduce BICAO and the mechanisms by which DKA results in cerebral infarction. CASE SUMMARY A 41-year-old woman presented with ischemic stroke that took place 3 mo prior over the left corona radiata, bilateral frontal lobe, and parietal lobe with right hemiplegia and Broca's aphasia. She had a history of hypertension for 5 years, hyperlipidemia for 4 years, hyperthyroidism for 3 years, and T1DM for 31 years. The first brain magnetic resonance imaging not only revealed the aforementioned ischemic lesions but also bilateral internal carotid artery occlusion. She was admitted to our ward for rehabilitation due to prior stroke sequalae. DKA took place on hospital day 2. On hospital day 6, she had a new massive infarction over the bilateral anterior cerebral artery and middle cerebral artery territory. After weeks of aggressive treatment, she remained in a coma and on mechanical ventilation due to respiratory failure. After discussion with her family, compassionate extubation was performed on hospital day 29 and she died. CONCLUSION DKA can lead to cerebral infarction due to several mechanisms. In people with existing BICAO and several stroke risk factors such as hypertension, T1DM, hyperlipidemia, DKA has the potential to cause more serious ischemic strokes.
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Affiliation(s)
- Yi-Chung Chen
- Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Su-Ju Tsai
- Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
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21
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Mondal S, DasGupta R, Lodh M, Gorai R, Choudhury B, Hazra AK, Ganguly A. Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients. Diabetes Metab Syndr 2021; 15:795-801. [PMID: 33839639 PMCID: PMC8004476 DOI: 10.1016/j.dsx.2021.03.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/08/2021] [Accepted: 03/22/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM COVID-19 infection predisposes to diabetic ketoacidosis(DKA); whether glucocorticoids enhances this risk is unknown.We aimed to study the occurrence of DKA after initiating glucocorticoids in patients with type 2 diabetes mellitus(T2DM) and moderate-to-severe COVID-19, and identify predictors for it. METHODS Patients with T2DM and moderate or severe COVID-19 infection were prospectively observed for development of new-onset DKA for one week following initiation of parenteral dexamethasone. Clinical and biochemical parameters were compared between those who developed DKA (Group A) and those who didnot (Group B). Logistic regression was done to identify independent risk-factors predicting DKA; ROC-curve analysis to determine cut-offs for the parameters in predicting DKA. RESULTS Amongst 302 patients screened, n = 196 were finally included, of whom 13.2% (n = 26,Group A) developed DKA. Patients in Group A were younger, had lower BMI, increased severity of COVID-19 infection, higher HbA1c%, CRP, IL-6, D-dimer and procalcitonin at admission (pall < 0.02). Further, admission BMI (OR: 0.43, CI: 0.27-0.69), HbA1c % (OR: 1.68, CI: 1.16-2.43) and serum IL-6 (OR: 1.02, CI: 1.01-1.03) emerged as independent predictors for DKA. Out of these, IL-6 levels had the highest AUROC (0.93, CI: 0.89-0.98) with a cut-off of 50.95 pg/ml yielding a sensitivity of 88% and specificity of 85.2% in predicting DKA. CONCLUSION There is significant incidence of new-onset DKA following parenteral glucocorticoids in T2DM patients with COVID-19, especially in those with BMI <25.56 kg/m2, HbA1c% >8.35% and IL-6 levels >50.95 pg/ml at admission.
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Affiliation(s)
- Sunetra Mondal
- Department of Endocrinology and Metabolism, HealthWorld Hospitals, Durgapur, India.
| | - Riddhi DasGupta
- Department of Endocrinology and Metabolism, HealthWorld Hospitals, Durgapur, India.
| | | | - Ramprasad Gorai
- Department of Critical Care Medicine, HealthWorld Hospitals, Durgapur, India.
| | - Brojen Choudhury
- Department of Critical Care Medicine, HealthWorld Hospitals, Durgapur, India.
| | - Arindam Kumar Hazra
- Department of Critical Care Medicine, HealthWorld Hospitals, Durgapur, India.
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22
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Fukunaga S, Hoshino Y, Sonoda H, Kawanishi M, Yamauchi A, Kato S, Yoshikane K, Shiina H, Tanabe K, Ito T. A Remarkable Elevation in the Procalcitonin Levels Due to Diabetic Ketoacidosis in a Hemodialysis Patient. Intern Med 2021; 60:1231-1235. [PMID: 33229806 PMCID: PMC8112968 DOI: 10.2169/internalmedicine.5841-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Procalcitonin (PCT), a marker of the inflammatory response during infections, can be elevated by diabetic ketoacidosis (DKA). A male patient in his 50s with diabetic nephropathy on hemodialysis presented with vomiting and a reduced level of consciousness and was diagnosed with DKA. His PCT level was markedly elevated, but bacterial cultures (blood, urine, and stool) were negative. The PCT level decreased after DKA improvement. In this patient, DKA probably enhanced the PCT levels. As DKA can increase the PCT levels, an elevation of the PCT levels in DKA patients may not be indicative of infectious diseases, and non-infectious causes of DKA should therefore be considered.
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Affiliation(s)
- Shohei Fukunaga
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Yuki Hoshino
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Hirotaka Sonoda
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Miharu Kawanishi
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Asuka Yamauchi
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Shiho Kato
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Kaori Yoshikane
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Hiroaki Shiina
- Department of Urology, Shimane University Faculty of Medicine, Japan
| | - Kazuaki Tanabe
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
| | - Takafumi Ito
- Department of Internal Medicine IV, Shimane University Faculty of Medicine, Japan
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23
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Azova S, Rapaport R, Wolfsdorf J. Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema. Pediatr Diabetes 2021; 22:148-160. [PMID: 33197066 PMCID: PMC10127934 DOI: 10.1111/pedi.13152] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 10/06/2020] [Accepted: 10/29/2020] [Indexed: 01/24/2023] Open
Abstract
Cerebral edema (CE) is a potentially devastating complication of diabetic ketoacidosis (DKA) that almost exclusively occurs in children. Since its first description in 1936, numerous risk factors have been identified; however, there continues to be uncertainty concerning the mechanisms that lead to its development. Currently, the most widely accepted hypothesis posits that CE occurs as a result of ischemia-reperfusion injury, with inflammation and impaired cerebrovascular autoregulation contributing to its pathogenesis. The role of specific aspects of DKA treatment in the development of CE continues to be controversial. This review critically examines the literature on the pathophysiology of CE and attempts to categorize the findings by types of brain injury that contribute to its development: cytotoxic, vasogenic, and osmotic. Utilizing this scheme, we propose a multifactorial pathway for the development of CE in patients with DKA.
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Affiliation(s)
- Svetlana Azova
- Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Robert Rapaport
- Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Joseph Wolfsdorf
- Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
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24
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Uysal E, Acar YA, Celik R, Nasuhbeyoglu N. PLASMA INTERLEUKIN-6 LEVELS MAY BE ASSOCIATED WITH THE LENGTH OF STAY TIME OF ADULT HYPERGLYCEMIC PATIENTS IN AN INTENSIVE CARE UNIT. ACTA ENDOCRINOLOGICA-BUCHAREST 2020; 16:311-315. [PMID: 33363652 DOI: 10.4183/aeb.2020.311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Context Estimation of intensive care unit (ICU) length of stay time (LOS) may be challenging, and pro-inflammatory cytokines can be used as a marker for this purpose. Objective The current study aimed to investigate the association between pro-inflammatory cytokine levels and LOS in hyperglycemic patients admitted to adult ICU. Design This is a prospective observational study. Subjects and Methods All adult ICU patients with a blood glucose level higher than 250 mg/dL, during the study period were included. Hospitalization day demographics were recorded, and plasma IL-6, IL1-ß, and TNF-α concentrations were measured. Results A total of 74 patients were enrolled in the study. Diabetic ketoacidosis (DKA) was positive in 31 patients, and the remaining 43 were in the non-DKA (NDKA) group. There was no difference between the two groups in terms of age, gender, LOS, hemoglobin, hematocrit, lactate levels, and platelets count. IL-6, IL-1ß, and TNF-α levels did not show any difference between DKA and NDKA groups (p=0.784, 0.413, and 0.288, respectively). There was a positive correlation between IL-6 levels and LOS (n=74, Pearson correlation=0.330; p=0.004). Conclusions Among pro-inflammatory cytokines, IL-6 showed a better performance for the prediction of LOS than IL-1ß, TNF-α, and CRP.
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Affiliation(s)
- E Uysal
- Bagcilar Training and Research Hospital - Department of Emergency Medicine, Istanbul, Turkey
| | - Y A Acar
- University of Health Sciences, Gulhane School of Medicine - Emergency Medicine, Ankara Turkey
| | - R Celik
- Bagcilar Training and Research Hospital - Department of Internal Medicine, Istanbul, Turkey
| | - N Nasuhbeyoglu
- Bagcilar Training and Research Hospital - Department of Microbiology and Clinical Microbiology, Istanbul, Turkey
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25
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Valk T, McMorrow C. Managing hyperglycemia during the COVID-19 pandemic: Improving outcomes using new technologies in intensive care. SAGE Open Med 2020; 8:2050312120974174. [PMID: 33282306 PMCID: PMC7686601 DOI: 10.1177/2050312120974174] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
Hyperglycemia is a significant risk for mortality in COVID-19 infections and is most dramatically noted in critically ill patients. Hyperglycemia and/or diabetes are noted in approximately 30%-40% of patients admitted with COVID-19 infections. Previous studies have shown a marked increase in mortality related to increased glucose concentrations and reduction with improved glucose control. In vivo and in vitro studies reveal the mechanisms by which hyperglycemia increases virulence and how glucose control and insulin reduce it. Optimal glucose control in intensive care is limited by manual sampling of glucose and intravenous insulin adjustment, as well as increased nursing workload and the need of protective equipment. Tools for safe and effective automation of glucose control in intensive care are discussed. A suitable closed loop device could save the lives of thousands of hospitalized hyperglycemic individuals infected with COVID-19 while protecting medical professionals from infection risk.
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Affiliation(s)
- Timothy Valk
- Admetsys Corporation, Boston MA,
USA
- Admetsys Research Unit, Winter
Park, FL, USA
| | - Carol McMorrow
- Admetsys Corporation, Boston MA,
USA
- Admetsys Research Unit, Winter
Park, FL, USA
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26
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Castellanos L, Tuffaha M, Koren D, Levitsky LL. Management of Diabetic Ketoacidosis in Children and Adolescents with Type 1 Diabetes Mellitus. Paediatr Drugs 2020; 22:357-367. [PMID: 32449138 DOI: 10.1007/s40272-020-00397-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Diabetic ketoacidosis (DKA) is the end result of insulin deficiency in type 1 diabetes mellitus (T1D). Loss of insulin production leads to profound catabolism with increased gluconeogenesis, glycogenolysis, lipolysis, and muscle proteolysis causing hyperglycemia and osmotic diuresis. High levels of counter-regulatory hormones lead to enhanced ketogenesis and the release of 'ketone bodies' into the circulation, which dissociate to release hydrogen ions and cause an overwhelming acidosis. Dehydration, hyperglycemia, and ketoacidosis are the hallmarks of this condition. Treatment is effective repletion of insulin, fluids and electrolytes. Newer approaches to early diagnosis, treatment, and prevention may diminish the risk of DKA and its childhood complications including cerebral edema. However, the potential for some technical and pharmacologic advances in the management of T1D to increase DKA events must be recognized.
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Affiliation(s)
- Luz Castellanos
- Division of Pediatric Endocrinology and Pediatric Diabetes Center, Massachusetts General Hospital, 175 Cambridge Street, 5th Floor, Boston, MA, 02114, USA
| | - Marwa Tuffaha
- Division of Pediatric Endocrinology and Pediatric Diabetes Center, Massachusetts General Hospital, 175 Cambridge Street, 5th Floor, Boston, MA, 02114, USA
| | - Dorit Koren
- Division of Pediatric Endocrinology and Pediatric Diabetes Center, Massachusetts General Hospital, 175 Cambridge Street, 5th Floor, Boston, MA, 02114, USA
| | - Lynne L Levitsky
- Division of Pediatric Endocrinology and Pediatric Diabetes Center, Massachusetts General Hospital, 175 Cambridge Street, 5th Floor, Boston, MA, 02114, USA.
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27
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Hoffman WH, Ishikawa T, Blum J, Tani N, Ikeda T, Artlett CM. Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis. J Clin Res Pediatr Endocrinol 2020; 12:160-167. [PMID: 31514489 PMCID: PMC7291407 DOI: 10.4274/jcrpe.galenos.2019.2019.0076] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE To determine the time relationships of soluble receptor for glycation end-products (sRAGE), [a decoy of the advanced glycation end-products (AGE)-RAGE axis] and D-lactate, (a metabolite of methylglyoxal) in the inflammatory response to diabetic ketoacidosis (DKA). METHODS Sixteen children and adolescents with type 1 diabetes (T1D) had blood samples obtained, 6-12 hours into treatment, at three weeks and three months post start of treatment. sRAGE and D-lactate concentrations at three months were considered baseline. Expression of RAGE was investigated in the myocardium of a newly diagnosed and untreated young person with fatal T1D/DKA. RESULTS sRAGE 6-12 hours after the start of treatment was 39% lower than the values at two weeks (p=0.0036) and at three months (p=0.0023) post treatment. D-lactate was higher during treatment than at three weeks (p=0.04) and at three months (p=0.035). CONCLUSION sRAGE concentration was decreased during treatment, compared to concentrations at two weeks and three months after treatment. The increased D-lactate during treatment was in keeping with the known increase in dicarbonyls at this time. The finding of RAGE expression in a young myocardium prior to DKA treatment suggested cardiovascular inflammation pre-treatment and at a young age.
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Affiliation(s)
- William H. Hoffman
- Augusta University, Medical College of Georgia, Department of Pediatrics, Georgia, USA,* Address for Correspondence: Augusta University, Medical College of Georgia, Department of Pediatrics, Georgia, USA Phone: +919-830-3900 E-mail:
| | - Takaki Ishikawa
- Osaka City University Faculty of Medicine, Department of Legal Medicine, Abeno Osaka, Japan
| | - James Blum
- University of North Carolina-Wilmington, Department of Mathematics and Statistics, North Carolina, USA
| | - Naoto Tani
- Osaka City University Faculty of Medicine, Department of Legal Medicine, Abeno Osaka, Japan
| | - Tomoya Ikeda
- Osaka City University Faculty of Medicine, Department of Legal Medicine, Abeno Osaka, Japan
| | - Carol M. Artlett
- Drexel University College of Medicine, Department of Microbiology and Immunology, Pennsylvania, USA
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28
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Hoffman WH, Cudrici CD, Boodhoo D, Tatomir A, Rus V, Rus H. Intracerebral matrix metalloproteinase 9 in fatal diabetic ketoacidosis. Exp Mol Pathol 2019; 108:97-104. [PMID: 30986397 PMCID: PMC6563901 DOI: 10.1016/j.yexmp.2019.04.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 02/22/2019] [Accepted: 04/11/2019] [Indexed: 02/08/2023]
Abstract
There is increasing awareness that in addition to the metabolic crisis of diabetic ketoacidosis (DKA) caused by severe insulin deficiency, the immune inflammatory response is likely an active multicomponent participant in both the acute and chronic insults of this medical crisis, with strong evidence of activation for both the cytokine and complement system. Recent studies report that the matrix metalloproteinase enzymes and their inhibitors are systemically activated in young Type 1 diabetes mellitus (T1D) patients during DKA and speculate on their involvement in blood-brain barrier (BBB) disruption. Based on our previous studies, we address the question if matrix metalloproteinase 9 (MMP9) is expressed in the brain in the fatal brain edema (BE) of DKA. Our data show significant expression of MMP9 on the cells present in brain intravascular areas. The presence of MMP9 in intravascular cells and that of MMP+ cells seen passing the BBB indicates a possible role in tight junction protein disruption of the BBB, possibly leading to neurological complications including BE. We have also shown that MMP9 is expressed on neurons in the hippocampal areas of both BE/DKA cases investigated, while expression of tissue inhibitor of metalloproteinases 1 (TIMP1) was reduced in the same areas. We can speculate that intraneuronal MMP9 can be a sign of neurodegeneration. Further studies are necessary to determine the role of MMP9 in the pathogenesis of the neurologic catastrophe of the brain edema of DKA. Inhibition of MMP9 expression might be helpful in preserving neuronal function and BBB integrity during DKA.
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Affiliation(s)
- William H Hoffman
- Department of Pediatrics, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Cornelia D Cudrici
- Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA
| | - Dallas Boodhoo
- Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - Alexandru Tatomir
- Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - Violeta Rus
- Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - Horea Rus
- Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA.
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29
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Popovic D, Lalic K, Jotic A, Milicic T, Bogdanovic J, Đorđevic M, Stankovic S, Jeremic V, Lalic NM. The Inflammatory and Hemostatic Cardiovascular Risk Markers During Acute Hyperglycemic Crisis in Type 1 and Type 2 Diabetes. J Med Biochem 2019; 38:126-133. [PMID: 30867640 PMCID: PMC6410996 DOI: 10.2478/jomb-2018-0024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 06/05/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND We analyzed cardiovascular inflammatory (C-reactive protein (CRP), interleukin 6 (IL-6)), haemostatic (homocysteine) risk markers in lean and obese patients at admission and acute hyperglicemic crisis (AHC) resolving, involving diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). METHODS In that context, we included group A: N = 20 obese, B: N=20 lean patients with DKA; C: N = l0 obese, D: N=10 lean patients with HHS; E: N = 15 obese, F: N=15 lean controls. CRP IL-6, homocysteine were determined by ELISA. RESULTS Our results showed that CRP IL-6, and homocysteine levels decreased in all groups: (A: p<0.001; B: p<0.001, C: p<0.05; D: p<0.001 mg/L), (A: p<0.001 B: p<0.001, C: p<0.001, D: p<0.01 pg/mL), (A: p<0.001, B: p <0.001; C: p<0.05, D: p=0.001 μmol/L), respectively, at resolving AHC. However, CRP persisted higher (p<0.001, p<0.01), IL-6 lower (p<0.05, p<0.001), while homocysteine levels turned out to be similar to controls. CONCLUSIONS AHC is associated with increased inflammatory and hemostatic cardiovascular risk markers. Also, insulin therapy in AHC has had more pronounced favorable effect on IL-6 and homocystein than on CRP.
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Affiliation(s)
- Dragana Popovic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Katarina Lalic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Jotic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Tanja Milicic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Bogdanovic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Maja Đorđevic
- Emergency Center, Clinical Centar of Serbia, Clinical Center of Serbia, Belgrade, Serbia
| | - Sanja Stankovic
- Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia
| | - Veljko Jeremic
- Department for Operations Research and Statistics, Faculty of Organizational Sciences, University of Belgrade, Belgrade, Serbia
| | - Nebojsa M. Lalic
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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31
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Gallo de Moraes A, Surani S. Effects of diabetic ketoacidosis in the respiratory system. World J Diabetes 2019; 10:16-22. [PMID: 30697367 PMCID: PMC6347653 DOI: 10.4239/wjd.v10.i1.16] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 11/08/2018] [Accepted: 12/13/2018] [Indexed: 02/05/2023] Open
Abstract
Diabetes affects approximately 30 million persons in the United States. Diabetes ketoacidosis is one of the most serious and acute complications of diabetes. At the time of presentation and during treatment of diabetic ketoacidosis (DKA), several metabolic and electrolyte derangements can ultimately result in respiratory compromise. Most commonly, hypokalemia, hypomagnesemia and hypophosphatemia can eventually lead to respiratory muscles failure. Furthermore, tachypnea, hyperpnea and more severely, Kussmaul breathing pattern can develop. Also, hydrostatic and non-hydrostatic pulmonary edema can occur secondary to volume shifts into the extracellular space and secondary to increased permeability of the pulmonary capillaries. The presence of respiratory failure in patients with DKA is associated with higher morbidity and mortality. Being familiar with the causes of respiratory compromise in DKA, and how to treat them, may represent better outcomes for patients with DKA.
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Affiliation(s)
- Alice Gallo de Moraes
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Salim Surani
- Division of Pulmonary, Critical Care and Sleep Medicine, Texas A and M University, Corpus Christy, TX 78412, United States
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32
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Pavić I, Tješić Drinković D, Galić S, Tješić Drinković D, Rojnić Putarek N. ACUTE RESPIRATORY DISTRESS SYNDROME IN A FOUR-YEAR-OLD BOY WITH DIABETIC KETOACIDOSIS - CASE REPORT. Acta Clin Croat 2018; 57:588-592. [PMID: 31168194 PMCID: PMC6536282 DOI: 10.20471/acc.2018.57.03.24] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
SUMMARY – Among many disease states as known initiators of acute respiratory distress syndrome (ARDS), diabetic ketoacidosis (DKA) is the rarest one. We present a 4-year-old boy with DKA as the first manifestation of insulin-dependent diabetes mellitus who developed ARDS, required tracheal intubation and mechanical ventilation, and survived without significant sequels. To improve survival of patients with ARDS as a complication of DKA, physicians should be aware of this rare pulmonary complication and its appropriate management.
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Affiliation(s)
| | - Dorian Tješić Drinković
- 1Zagreb Children's Hospital, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 2Zagreb University Hospital Centre, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 3Zagreb University Hospital Centre, Pediatric Intensive Care Unit, Zagreb, Croatia; 4Zagreb University Hospital Centre, Department of Pediatric Gastroenterology and Nutrition, Zagreb, Croatia; 5Zagreb University Hospital Centre, Department of Pediatric Endocrinology and Diabetes, Zagreb, Croatia
| | - Slobodan Galić
- 1Zagreb Children's Hospital, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 2Zagreb University Hospital Centre, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 3Zagreb University Hospital Centre, Pediatric Intensive Care Unit, Zagreb, Croatia; 4Zagreb University Hospital Centre, Department of Pediatric Gastroenterology and Nutrition, Zagreb, Croatia; 5Zagreb University Hospital Centre, Department of Pediatric Endocrinology and Diabetes, Zagreb, Croatia
| | - Duška Tješić Drinković
- 1Zagreb Children's Hospital, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 2Zagreb University Hospital Centre, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 3Zagreb University Hospital Centre, Pediatric Intensive Care Unit, Zagreb, Croatia; 4Zagreb University Hospital Centre, Department of Pediatric Gastroenterology and Nutrition, Zagreb, Croatia; 5Zagreb University Hospital Centre, Department of Pediatric Endocrinology and Diabetes, Zagreb, Croatia
| | - Nataša Rojnić Putarek
- 1Zagreb Children's Hospital, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 2Zagreb University Hospital Centre, Department of Pulmonology, Allergology, Rheumatology and Clinical Immunology, Zagreb, Croatia; 3Zagreb University Hospital Centre, Pediatric Intensive Care Unit, Zagreb, Croatia; 4Zagreb University Hospital Centre, Department of Pediatric Gastroenterology and Nutrition, Zagreb, Croatia; 5Zagreb University Hospital Centre, Department of Pediatric Endocrinology and Diabetes, Zagreb, Croatia
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Posterior reversible encephalopathy syndrome with spinal cord involvement (PRES-SCI) as a rare complication of severe diabetic ketoacidosis: a case report and review of the literature. Childs Nerv Syst 2018; 34:701-705. [PMID: 29330587 DOI: 10.1007/s00381-018-3724-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 01/05/2018] [Indexed: 10/18/2022]
Abstract
INTRODUCTION In addition to diffuse brain oedema, diabetic ketoacidosis (DKA) can lead to ischaemic or haemorrhagic stroke, extrapontine myelinolysis, and sinovenous thrombosis. However, posterior reversible encephalopathy syndrome (PRES) and spinal cord oedema are rarely reported in patients with DKA. METHODS We present a case of a 17-year-old-girl who developed headache, blurred vision, and paraplegia after her DKA was controlled. Sequential magnetic resonance (MR) scans of the brain and spinal cord were performed. RESULTS Brain MR showed large patchy lesions in the bilateral white matter of the parieto-occipital lobes, which had high T2 signal intensity and low T1 signal intensity. MR scanning of the spinal cord showed longitudinal confluent central spinal cord T2 hyperintensity spanning seven thoracic spinal segments. With symptomatic treatment, the patient's headache and vision disturbance subsided within 1 week. Subsequent MR scans demonstrated that the lesion in the spinal cord had decreased significantly in 10 days, and the large patchy lesions in the brain disappeared completely in 2 months. Her paraplegia improved gradually without obvious sequela 3 months later. The evolution of the disease and radiological findings supported the diagnosis of PRES with spinal cord involvement. CONCLUSION To the best of our knowledge, this is the first case report describing PRES with spinal cord involvement as a complication of DKA. PRES is a rare complication that should be considered along with other neurological complications of DKA when focal deficits appear.
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34
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Mostofizadeh N, Arefnia S, Hashemipour M, Dehkordi EH. Thrombotic Thrombocytopenic Purpura in a Child with Diabetic Ketoacidosis. Adv Biomed Res 2018. [PMID: 29531931 PMCID: PMC5840966 DOI: 10.4103/2277-9175.225928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Thrombotic thrombocytopenic purpura (TTP) secondary to diabetic ketoacidosis has been rarely reported and is considered as a rare complication. If left untreated, this condition could be life threatening with considerable morbidity and mortality. Herein, we report a 6-year-old girl with reduced consciousness and respiratory distress with a history of polydipsia and polyuria in the 2 weeks before hospitalization. The patient was initially diagnosed as diabetic ketoacidosis based on clinical and laboratory findings and treated accordingly. After treatment and during hospitalization although she had gained relative consciousness, she experienced seizure and reduced consciousness again. Considering laboratory and clinical findings and the patient's underlying conditions (thrombocytopenia, renal failure, and high lactate dehydrogenase), TTP was suspected although ADAMTS13 test could not be done. Treatment with plasmapheresis was initiated, and after 48 h, the patient was conscious, and laboratory indices became normal within a few days. The patient was discharged after full recovery. TTP should be considered as a rare complication of diabetic ketoacidosis in patients with thrombocytopenia, renal failure, and reduced consciousness and should be immediately treated.
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Affiliation(s)
- Neda Mostofizadeh
- Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Serajaddin Arefnia
- Department of Pediatrics, School of Medicine and Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahin Hashemipour
- Endocrine and Metabolism Research Center, Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elham Hashemi Dehkordi
- Metabolism Research Center, Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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35
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Glaser N, Little C, Lo W, Cohen M, Tancredi D, Wulff H, O'Donnell M. Treatment with the KCa3.1 inhibitor TRAM-34 during diabetic ketoacidosis reduces inflammatory changes in the brain. Pediatr Diabetes 2017; 18:356-366. [PMID: 27174668 DOI: 10.1111/pedi.12396] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 03/30/2016] [Accepted: 04/06/2016] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) causes brain injuries in children ranging from subtle to life-threatening. Previous studies suggest that DKA-related brain injury may involve both stimulation of Na-K-Cl cotransport and microglial activation. Other studies implicate the Na-K-Cl cotransporter and the Ca-activated K channel KCa3.1 in activation of microglia and ischemia-induced brain edema. In this study, we determined whether inhibiting cerebral Na-K-Cl cotransport or KCa3.1 could reduce microglial activation and decrease DKA-related inflammatory changes in the brain. METHODS Using immunohistochemistry, we investigated cellular alterations in brain specimens from juvenile rats with DKA before, during and after insulin and saline treatment. We compared findings in rats treated with and without bumetanide (an inhibitor of Na-K-Cl cotransport) or the KCa3.1 inhibitor TRAM-34. RESULTS Glial fibrillary acidic protein (GFAP) staining intensity was increased in the hippocampus during DKA, suggesting reactive astrogliosis. OX42 staining intensity was increased during DKA in the hippocampus, cortex and striatum, indicating microglial activation. Treatment with TRAM-34 decreased both OX42 and GFAP intensity suggesting a decreased inflammatory response to DKA. Treatment with bumetanide did not significantly alter OX42 or GFAP intensity. CONCLUSIONS Inhibiting KCa3.1 activity with TRAM-34 during DKA treatment decreases microglial activation and reduces reactive astrogliosis, suggesting a decreased inflammatory response.
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Affiliation(s)
- Nicole Glaser
- Department of Pediatrics, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Christopher Little
- Department of Pediatrics, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Weei Lo
- Department of Pediatrics, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Michael Cohen
- Department of Physiology and Membrane Biology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Daniel Tancredi
- Department of Pediatrics, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Heike Wulff
- Department of Pharmacology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Martha O'Donnell
- Department of Physiology and Membrane Biology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
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Hoffman WH, Artlett CM, Boodhoo D, Gilliland MGF, Ortiz L, Mulder D, Tjan DHT, Martin A, Tatomir A, Rus H. Markers of immune-mediated inflammation in the brains of young adults and adolescents with type 1 diabetes and fatal diabetic ketoacidosis. Is there a difference? Exp Mol Pathol 2017; 102:505-514. [PMID: 28533125 DOI: 10.1016/j.yexmp.2017.05.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Accepted: 05/18/2017] [Indexed: 12/17/2022]
Abstract
Due to the limited data on diabetic ketoacidosis and brain edema (DKA/BE) in children/adolescents and the lack of recent data on adults with type 1 diabetes (T1D), we addressed the question of whether neuroinflammation was present in the fatal DKA of adults. We performed immunohistochemistry (IHC) studies on the brains of two young adults with T1D and fatal DKA and compared them with two teenagers with poorly controlled diabetes and fatal DKA. C5b-9, the membrane attack complex (MAC) had significantly greater deposits in the grey and white matter of the teenagers than the young adults (p=0.03). CD59, a MAC assembly inhibitory protein was absent, possibly suppressed by the hyperglycemia in the teenagers but was expressed in the young adults despite comparable average levels of hyperglycemia. The receptor for advanced glycation end products (RAGE) had an average expression in the young adults significantly greater than in the teenagers (p=0.02). The autophagy marker Light Chain 3 (LC3) A/B was the predominant form of programmed cell death (PCD) in the teenage brains. The young adults had high expressions of both LC3A/B and TUNEL, an apoptotic cell marker for DNA fragmentation. BE was present in the newly diagnosed young adult with hyperglycemic hyperosmolar DKA and also in the two teenagers. Our data indicate that significant differences in neuroinflammatory components, initiated by the dysregulation of DKA and interrelated metabolic and immunologic milieu, are likely present in the brains of fatal DKA of teenagers when compared with young adults.
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Affiliation(s)
- William H Hoffman
- Department of Pediatrics, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
| | - Carol M Artlett
- Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, United States
| | - Dallas Boodhoo
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Mary G F Gilliland
- Department of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27858, United States
| | - Luis Ortiz
- Department of Pediatrics, Nephrology, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States
| | - Dries Mulder
- Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands
| | - David H T Tjan
- Department of Intensive Care, Gelderse Vallei Hospital, Ede, The Netherlands
| | - Alvaro Martin
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Alexandru Tatomir
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Horea Rus
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Research Service, Veterans Administration Maryland Health Care System, MD 21201, United States.
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Histological and cognitive alterations in adult diabetic rats following an episode of juvenile diabetic ketoacidosis: Evidence of permanent cerebral injury. Neurosci Lett 2017; 650:161-167. [DOI: 10.1016/j.neulet.2017.04.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 04/03/2017] [Accepted: 04/18/2017] [Indexed: 01/26/2023]
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Hamed S, Metwalley KA, Farghaly HS, Sherief T. Serum Levels of Neuron-Specific Enolase in Children With Diabetic Ketoacidosis. J Child Neurol 2017; 32:475-481. [PMID: 28056586 DOI: 10.1177/0883073816686718] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Neuron-specific enolase is a sensitive marker of neuronal damage in various neurologic disorders. This study aimed to measure serum neuron-specific enolase levels at different time points and severities of diabetic ketoacidosis. This study included 90 children (age 9.2 ± 3.4 years) with diabetic ketoacidosis. Neuron-specific enolase was measured at 3 time points (baseline and after 12 and 24 hours of starting treatment). Among patients, 74.4% had diagnosis of new diabetes, 60% had Glasgow Coma Scale score <15, and 75.6% had moderate/severe diabetic ketoacidosis. Compared with controls (n = 30), children with diabetic ketoacidosis had higher neuron-specific enolase levels at the 3 time points ( P = .0001). In multiple regression analysis, the factors associated with higher neuron-specific enolase levels were younger age, higher glucose, lower pH, and bicarbonate values. This study indicates that serum neuron-specific enolase is elevated in diabetic ketoacidosis and correlated with the severity of hyperglycemia, ketosis, and acidosis. This study indicates that diabetic ketoacidosis may cause neuronal injury from which the patients recovered partially but not completely.
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Affiliation(s)
- Sherifa Hamed
- 1 Department of Neurology and Psychiatry, Assiut University Hospital, Assiut, Egypt
| | | | - Hekma Saad Farghaly
- 2 Department of Pediatrics, Assiut University Children's Hospital, Assiut, Egypt
| | - Tahra Sherief
- 3 Department of Clinical Pathology, Assiut University Hospital, Assiut, Egypt
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Garro A, Chodobski A, Szmydynger-Chodobska J, Shan R, Bialo SR, Bennett J, Quayle K, Rewers A, Schunk JE, Casper TC, Kuppermann N, Glaser N. Circulating matrix metalloproteinases in children with diabetic ketoacidosis. Pediatr Diabetes 2017; 18:95-102. [PMID: 26843101 PMCID: PMC4974171 DOI: 10.1111/pedi.12359] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 12/16/2015] [Accepted: 12/17/2015] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Matrix metalloproteinases (MMPs) mediate blood-brain barrier dysfunction in inflammatory disease states. Our objective was to compare circulating MMPs in children with diabetic ketoacidosis (DKA) to children with type 1 diabetes mellitus without DKA. RESEARCH DESIGN AND METHODS This was a prospective study performed at five tertiary-care pediatric hospitals. We measured plasma MMP-2, MMP-3, and MMP-9 early during DKA (time 1; within 2 h of beginning intravenous fluids) and during therapy (time 2; median 8 h; range: 4-16 h). The primary outcome was MMP levels in 34 children with DKA vs. 23 children with type 1 diabetes without DKA. Secondary outcomes included correlations between MMPs and measures of DKA severity. RESULTS In children with DKA compared with diabetes controls, circulating MMP-2 levels were lower (mean 77 vs. 244 ng/mL, p < 0.001), MMP-3 levels were similar (mean 5 vs. 4 ng/mL, p = 0.57), and MMP-9 levels were higher (mean 67 vs. 25 ng/mL, p = 0.002) early in DKA treatment. MMP-2 levels were correlated with pH at time 1 (r = 0.45, p = 0.018) and time 2 (r = 0.47, p = 0.015) and with initial serum bicarbonate at time 2 (r = 0.5, p = 0.008). MMP-9 levels correlated with hemoglobin A1c in DKA and diabetes controls, but remained significantly elevated in DKA after controlling for hemoglobin A1c (β = -31.3, p = 0.04). CONCLUSIONS Circulating MMP-2 levels are lower and MMP-9 levels are higher in children during DKA compared with levels in children with diabetes without DKA. Alterations in MMP expression could mediate BBB dysfunction occurring during DKA.
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Affiliation(s)
- Aris Garro
- Departments of Pediatrics and Emergency Medicine, Rhode Island Hospital, Providence, RI, USA,Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Adam Chodobski
- Warren Alpert Medical School, Brown University, Providence, RI, USA
| | | | - Rongzi Shan
- Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Shara R Bialo
- Departments of Pediatrics and Emergency Medicine, Rhode Island Hospital, Providence, RI, USA,Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Jonathan Bennett
- Department of Pediatrics, Sidney Kimmel Medical College at Thomas Jefferson University, Wilmington, DE, USA
| | - Kimberly Quayle
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Arleta Rewers
- Department of Pediatrics, University of Colorado, School of Medicine, Denver, CO, USA
| | - Jeffrey E Schunk
- Department of Pediatrics, University of Utah, School of Medicine, Salt Lake City, UT, USA
| | - T Charles Casper
- Department of Pediatrics, University of Utah, School of Medicine, Salt Lake City, UT, USA
| | - Nathan Kuppermann
- Department of Emergency Medicine, University of California Davis, Davis, CA, USA
| | - Nicole Glaser
- Department of Pediatrics, University of California Davis, Davis, CA, USA
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Jones R, Redler K, Witherick J, Fuller G, Mahajan T, Wakerley BR. Posterior reversible encephalopathy syndrome complicating diabetic ketoacidosis; an important treatable complication. Pediatr Diabetes 2017; 18:159-162. [PMID: 26764016 DOI: 10.1111/pedi.12362] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Revised: 11/17/2015] [Accepted: 12/22/2015] [Indexed: 11/29/2022] Open
Abstract
Development of acute neurological symptoms secondary to cerebral oedema is well described in diabetic ketoacidosis (DKA) and often has a poor prognosis. We present the clinical and radiological data of a 17-yr-old girl who developed cortical blindness, progressive encephalopathy, and seizures caused by posterior reversible encephalopathy syndrome (PRES) that developed after her DKA had resolved. Vasogenic oedema in PRES resolves if the underlying trigger is identified and eliminated. In this case, hypertension was identified as the likely precipitating factor and following treatment her vision and neurological symptoms rapidly improved. We suggest how recent DKA may have contributed to the development of PRES in this patient.
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Affiliation(s)
- Rachel Jones
- Department of Neurology, Gloucestershire Royal Hospital, Gloucester, UK
| | - Kasey Redler
- Department of Neurology, Gloucestershire Royal Hospital, Gloucester, UK
| | | | - Geraint Fuller
- Department of Neurology, Gloucestershire Royal Hospital, Gloucester, UK
| | - Tripti Mahajan
- Department of Diabetes, Gloucestershire Royal Hospital, Gloucester, UK
| | - Benjamin R Wakerley
- Department of Neurology, Gloucestershire Royal Hospital, Gloucester, UK.,Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
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Immune modulation of some autoimmune diseases: the critical role of macrophages and neutrophils in the innate and adaptive immunity. J Transl Med 2017; 15:36. [PMID: 28202039 PMCID: PMC5312441 DOI: 10.1186/s12967-017-1141-8] [Citation(s) in RCA: 229] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 02/03/2017] [Indexed: 12/16/2022] Open
Abstract
Macrophages and neutrophils are key components involved in the regulation of numerous chronic inflammatory diseases, infectious disorders, and especially certain autoimmune disease. However, little is known regarding the contribution of these cells to the pathogenesis of autoimmune disorders. Recent studies have aimed to clarify certain important factors affecting the immunogenicity of these cells, including the type and dose of antigen, the microenvironment of the cell-antigen encounter, and the number, subset, and phenotype of these cells, which can prevent or induce autoimmune responses. This review highlights the role of macrophage subsets and neutrophils in injured tissues, supporting their cooperation during the pathogenesis of certain autoimmune diseases.
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Reyes-Umpierrez D, Davis G, Cardona S, Pasquel FJ, Peng L, Jacobs S, Vellanki P, Fayfman M, Haw S, Halkos M, Guyton RA, Thourani VH, Umpierrez GE. Inflammation and Oxidative Stress in Cardiac Surgery Patients Treated to Intensive Versus Conservative Glucose Targets. J Clin Endocrinol Metab 2017; 102:309-315. [PMID: 27841946 PMCID: PMC5413099 DOI: 10.1210/jc.2016-3197] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 11/07/2016] [Indexed: 12/18/2022]
Abstract
OBJECTIVE We aimed to determine (a) longitudinal changes of inflammatory and oxidative stress markers and (b) the association between markers of inflammation and perioperative complications in coronary artery bypass surgery (CABG) patients treated with intensive vs conservative blood glucose (BG) control. METHODS Patients with diabetes (n = 152) and without diabetes with hyperglycemia (n = 150) were randomized to intensive (n = 151; BG: 100-140 mg/dL) or to conservative (n = 151; BG: 141-180 mg/dL) glycemic targets. Plasma cortisol, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α, interleukin-6 (IL-6), thiobarbituric acid-reactive substances, and 2'-7'-dichlorofluorescein were measured prior to and at days 3, 5, and 30 after surgery. RESULTS Intensive glycemic control resulted in lower mean BG (132 ± 14 mg/dL vs 154 ± 17 mg/dL, P < 0.001) in the intensive care unit. Plasma cortisol and inflammatory markers increased significantly from baseline after the third and fifth day of surgery (P < 0.001), and returned to baseline levels at 1 month of follow-up. Patients with perioperative complications had higher levels of cortisol, hsCRP, IL-6, and oxidative stress markers compared with those without complications. There were no significant differences in inflammatory and oxidative stress markers between patients, with or without diabetes or complications, treated with intensive or conventional glucose targets. CONCLUSION We report no significant differences in circulating markers of acute inflammatory and oxidative stress response in cardiac surgery patients, with or without diabetes, treated with intensive (100-140 mg/dL) or conservative (141-180 mg/dL) insulin regimens.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Michael Halkos
- Joseph B. Whitehead Department of Surgery, Emory University, Atlanta, Georgia 30303
| | - Robert A. Guyton
- Joseph B. Whitehead Department of Surgery, Emory University, Atlanta, Georgia 30303
| | - Vinod H. Thourani
- Joseph B. Whitehead Department of Surgery, Emory University, Atlanta, Georgia 30303
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Fatal Pulmonary Embolism Due to Inherited Thrombophilia Factors in a Child With Wolfram Syndrome. J Pediatr Hematol Oncol 2016; 38:e254-6. [PMID: 27379531 DOI: 10.1097/mph.0000000000000634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Wolfram syndrome-1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus (DM), optic atrophy, diabetes insipidus, and deafness. Poorly controlled type 1 DM increases the risk for thrombosis. However, coexistence of DM and hereditary thrombosis factors is rarely observed. Here we present the case of a 13.5-year-old, nonfollowed girl newly diagnosed with poorly controlled Wolfram syndrome on the basis of the results of clinical and laboratory examinations. On the eighth day after diabetic ketoacidosis treatment, pulmonary embolism developed in the subject. Thrombus identified in the right atrium using echocardiography was treated by emergency thrombectomy. Homozygous mutation in the methylenetetrahydrofolate reductase gene C677T, heterozygous factor-V Leiden mutation, and active protein C resistance were identified in the patient. The patient was lost because of a recurring episode of pulmonary embolism on the 86th day of hospitalization. We present this case to highlight the need for investigating hereditary thrombosis risk factors in diabetic patients in whom thromboembolism develops.
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Srettabunjong S, Limgitisupasin W. Severe acute hemorrhagic pancreatitis secondary to cholelithiasis as a rare cause of sudden unexpected death in medico-legal case: A case report. Medicine (Baltimore) 2016; 95:e4680. [PMID: 27559973 PMCID: PMC5400340 DOI: 10.1097/md.0000000000004680] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Acute pancreatitis (AP) is an uncommon disease with a wide clinical course varying from mild and self-limiting to severe with eventual death. However, death caused by AP is rare. Most cases of AP reported in the English-language literature are based on clinical data; few are medico-legal studies. CASE PRESENTATION The author recently experienced a case of sudden unexpected death in a young man caused by extensive severe hemorrhagic AP secondary to cholelithiasis, not chronic alcoholism, which is a much more prominent etiology of AP in medico-legal perspectives. The deceased had complained of dizziness, nausea, and fatigue without significant abdominal pain for about 1 week and received some home medications for symptomatic treatment including an antibiotic drug from a clinic just 2 days prior to his death. He had complained of lower extremity weakness, intense thirst, and subsequently collapsed and was brought to a nearby hospital where he was pronounced dead shortly after his admission following unsuccessful advanced cardiopulmonary resuscitation attempts. CONCLUSION This case is herein reported with an extensive review of the pertinent literature to highlight the findings of the case and raise awareness within the medico-legal profession and also the medical profession.
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Affiliation(s)
- Supawon Srettabunjong
- Department of Forensic Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Correspondence: Supawon Srettabunjong, Department of Forensic Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (e-mail: )
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Kanikarla-Marie P, Jain SK. Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes. Free Radic Biol Med 2016; 95:268-77. [PMID: 27036365 PMCID: PMC4867238 DOI: 10.1016/j.freeradbiomed.2016.03.020] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 03/16/2016] [Accepted: 03/21/2016] [Indexed: 12/19/2022]
Abstract
Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients.
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Affiliation(s)
- Preeti Kanikarla-Marie
- Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA
| | - Sushil K Jain
- Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
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Hu TX, Tan QY, Ruan Y, Ruan Y, Wang XJ, Yao JQ, Wang HL, Wang J. Study on the relationship of acute ketosis intoxication and type 2 diabetes mellitus. JOURNAL OF ACUTE DISEASE 2016. [DOI: 10.1016/j.joad.2016.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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Hoffman WH, Sharma M, Cihakova D, Talor MV, Rose NR, Mohanakumar T, Passmore GG. Cardiac antibody production to self-antigens in children and adolescents during and following the correction of severe diabetic ketoacidosis. Autoimmunity 2016; 49:188-96. [PMID: 26911924 DOI: 10.3109/08916934.2015.1134509] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Diabetic cardiomyopathy (DC) is an independent phenotype of diabetic cardiovascular disease. The understanding of the pathogenesis of DC in young patients with type 1 diabetes (T1D) is limited. The cardiac insults of diabetic ketoacidosis (DKA) and progression of DC could include development of antibodies (Abs) to cardiac self-antigens (SAgs) such as: myosin (M), vimentin (V) and k-alpha 1 tubulin (Kα1T). The goal of this study is to determine if the insults of severe DKA and its inflammatory cascade are associated with immune responses to SAgs. Development of Abs to the SAgs were determined by an ELISA using sera collected at three time points in relation to severe DKA (pH < 7.2). Results demonstrate significant differences between the development of Abs to VIM and a previously reported diastolic abnormality (DA) during DKA and its treatment and a NDA group at 2-3 months post DKA (p = 0.0452). A significant association is present between T1D duration (<3 years) and Abs to Kα1T (p = 0.0134). Further, Abs to MYO and VIM are associated with inflammatory cytokines. We propose that severe DKA initiates the synthesis of Abs to cardiac SAgs that are involved in the early immunopathogenesis of DC in young patients with T1D.
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Affiliation(s)
- William H Hoffman
- a Department of Pediatrics , Georgia Regents University (Medical College of Georgia) , Augusta , GA , USA
| | - Monal Sharma
- b Department of Surgery , Washington University School of Medicine , St. Louis, MO , USA
| | - Daniela Cihakova
- c Department of Pathology , The Johns Hopkins University School of Medicine, The William H. Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health , Baltimore , MD , USA
| | - Monica V Talor
- d Department of Pathology , The Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Noel R Rose
- c Department of Pathology , The Johns Hopkins University School of Medicine, The William H. Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health , Baltimore , MD , USA
| | - T Mohanakumar
- e Departments of Surgery , Pathology and Immunology, Washington University School of Medicine , St. Louis, MO , USA , and
| | - Gregory G Passmore
- f Medical Laboratory, Imaging and Radiologic Sciences, Georgia Regents University , Augusta , GA , USA
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Singh D, Cantu M, Marx MHM, Akingbola O. Diabetic Ketoacidosis and Fluid Refractory Hypotension. Clin Pediatr (Phila) 2016; 55:182-4. [PMID: 25948040 DOI: 10.1177/0009922815584549] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Dinesh Singh
- Tulane University School of Medicine, New Orleans, LA, USA
| | - Marissa Cantu
- Tulane University School of Medicine, New Orleans, LA, USA
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Jessup AB, Grimley MB, Meyer E, Passmore GP, Belger A, Hoffman WH, Çalıkoğlu AS. Effects of Diabetic Ketoacidosis on Visual and Verbal Neurocognitive Function in Young Patients Presenting with New-Onset Type 1 Diabetes. J Clin Res Pediatr Endocrinol 2015; 7:203-10. [PMID: 26831554 PMCID: PMC4677555 DOI: 10.4274/jcrpe.2158] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE To evaluate the effects of diabetic ketoacidosis (DKA) on neurocognitive functions in children and adolescents presenting with new-onset type 1 diabetes. METHODS Newly diagnosed patients were divided into two groups: those with DKA and those without DKA (non-DKA). Following metabolic stabilization, the patients took a mini-mental status exam prior to undergoing a baseline battery of cognitive tests that evaluated visual and verbal cognitive tasks. Follow-up testing was performed 8-12 weeks after diagnosis. Patients completed an IQ test at follow-up. RESULTS There was no statistical difference between the DKA and non-DKA groups neither in alertness at baseline testing nor in an IQ test at follow-up. The DKA group had significantly lower baseline scores than the non-DKA group for the visual cognitive tasks of design recognition, design memory and the composite visual memory index (VMI). At follow-up, Design Recognition remained statistically lower in the DKA group, but the design memory and the VMI tasks returned to statistical parity between the two groups. No significant differences were found in verbal cognitive tasks at baseline or follow-up between the two groups. Direct correlations were present for the admission CO2 and the visual cognitive tasks of VMI, design memory and design recognition. Direct correlations were also present for admission pH and VMI, design memory and picture memory. CONCLUSION Pediatric patients presenting with newly diagnosed type 1 diabetes and severe but uncomplicated DKA showed a definite trend for lower cognitive functioning when compared to the age-matched patients without DKA.
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Affiliation(s)
- Ashley B. Jessup
- University of North Carolina at Chapel Hill Faculty of Medicine, Division of Pediatric Endocrinology, North Carolina, United States of America
| | - Mary Beth Grimley
- University of North Carolina at Chapel Hill Faculty of Medicine, Department of Psychiatry, North Carolina, United States of America
| | - Echo Meyer
- University of North Carolina at Chapel Hill Faculty of Medicine, Department of Psychiatry, North Carolina, United States of America
| | - Gregory P. Passmore
- Georgia Regents University (Formerly Georgia Health Sciences University), Medical Laboratory, Imaging and Radiological Sciences, Georgia, United States of America
| | - Ayşenil Belger
- University of North Carolina at Chapel Hill Faculty of Medicine, Department of Psychiatry, North Carolina, United States of America
| | - William H. Hoffman
- Georgia Regents University, Department of Pediatric Endocrinology and Diabetes, Georgia, United States of America
| | - Ali S. Çalıkoğlu
- University of North Carolina at Chapel Hill Faculty of Medicine, Division of Pediatric Endocrinology, North Carolina, United States of America
,* Address for Correspondence: University of North Carolina at Chapel Hill Faculty of Medicine, Division of Pediatric Endocrinology, North Carolina, United States of America Phone: +1 919 962 27 96 E-mail:
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Nett ST, Noble JA, Levin DL, Cvijanovich NZ, Vavilala MS, Jarvis JD, Flori HR. Biomarkers and genetics of brain injury risk in diabetic ketoacidosis: A pilot study. J Pediatr Intensive Care 2015; 3. [PMID: 26097769 DOI: 10.3233/pic-14091] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Diabetic ketoacidosis (DKA) is the primary cause of death for children with diabetes, especially when complicated by cerebral edema. Central nervous system (CNS) involvement is common, however the mechanism of, and predictors of CNS dysfunction/injury are largely unknown. In this observational pilot study, blood was collected from pediatric DKA patients at three time points (consent, 12 hr and 24 hr after beginning treatment), to test genetic markers, ribonucleic acid expression and plasma biomarkers reflecting inflammation (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and cerebral dysfunction and/or possible injury (S100β, glial fibrillary acidic protein [GFAP]). Thirty patients were enrolled in the study. The average age was 11.3 yr, 73% were new onset diabetes and 53% were female. Forty percent exhibited abnormal mentation (Glasgow Coma Scale <15), consistent with CNS dysfunction. IL-6 and TNF-α were elevated in plasma, suggesting systemic inflammation. GFAP was measurable in 45% of patients and correlated positively with GCS. Only two patients had detectable levels of S100β. In conclusion, children with DKA often present with evidence of acute neurologic dysfunction or injury. We have demonstrated the feasibility of exploring genetic and biochemical markers of potential importance in the pathophysiology of CNS dysfunction and/or possible injury in DKA. We have identified IL-6, TNF-α and GFAP as potentially important markers for further exploration. A larger, follow-up study will help to better understand the extent and type of CNS injury in DKA as well as the mechanism underlying this dysfunction/injury.
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Affiliation(s)
- Sholeen T Nett
- Department of Pediatric Critical Care Medicine, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA
| | - Janelle A Noble
- Children's Hospital Oakland Research Institute, Oakland, CA, USA
| | - Daniel L Levin
- Department of Pediatric Critical Care Medicine, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA
| | - Natalie Z Cvijanovich
- Department of Pediatric Critical Care Medicine, Children's Hospital and Research Center Oakland, Oakland, CA, USA
| | - Monica S Vavilala
- Department of Pediatric Critical Care Medicine, University of Washington Children's Hospital, Seattle, WA, USA
| | - J Dean Jarvis
- Department of Pediatric Critical Care Medicine, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA
| | - Heidi R Flori
- Department of Pediatric Critical Care Medicine, Children's Hospital and Research Center Oakland, Oakland, CA, USA
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