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 uni...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.展开更多
AIM:To investigate the mechanism of the tight junction(TJ) disruption and the association between tumor necrosis factor(TNF)-α and matrix metalloproteinase(MMPs) under hyperosmotic condition in primary human corneal ...AIM:To investigate the mechanism of the tight junction(TJ) disruption and the association between tumor necrosis factor(TNF)-α and matrix metalloproteinase(MMPs) under hyperosmotic condition in primary human corneal epithelial cells(HCECs).METHODS:The cultured HCECs were exposed to media which adding sodium chloride(Na Cl) for hyperosmolar stress or adding rh-TNF-α(10 ng/m L). NF-κB inhibitor(5 μmol/L) or GM-6001(potent and broad spectrum MMP inhibitor, 20 μmol/L)was added 1 h before that treatment. The integrity of TJ proteins was determined by immunofluorescent(IF) staining. The m RNA levels of TNF-α and MMPs were evaluated by quantitative reverse transcription polymerase chain reaction(RT-q PCR) and the protein expression by enzyme-linked immunosorbent assay(ELISA).RESULTS:TJ proteins ZO-1 and Occludin were disrupted in primary HCECs exposed to hyperosmotic medium. The m RNA expression and protein production of TNF-α increased significantly in hyperosmotic media at 500 m Os M. TNF-α mediated the expression and production of MMP-1, MMP-13, MMP-9, and MMP-3 stimulated by hyperosmotic stress. The production of MMPs in hyperosmolar media were increased through the increase of TNF-α. GM-6001 prevent the destruction of ZO-1 and Occludin in hyperosmolar stress and rh-TNF-α treated medium. TNF-α induced activation of MMPs was involved in the TJ disruption by hyperosmolarity.CONCLUSION:TJ proteins ZO-1 and Occludin are disrupted by hyperosmolar stress and TNF-α, but protected by MMP inhibitor(GM-6001). It suggests that TNF-α/MMP pathway mediates the TJ disruption in primary HCECs exposed to hyperosmotic stress.展开更多
To protect from COVID-19 pandemic, several vaccines were developed infection with expected immunity against a SARS-CoV-2 infection. Short time side effects are reported. New onset diabetes was reported after SARS-CoV-...To protect from COVID-19 pandemic, several vaccines were developed infection with expected immunity against a SARS-CoV-2 infection. Short time side effects are reported. New onset diabetes was reported after SARS-CoV-2 infection. Here we report a case of new onset diabetes presenting with hyperosmolar hyperglycemic state, whose symptoms followed right after the second dose of Pfizer-BioNTech COVID-19 Vaccine. He is a 56-year old, obese Afro-American Veteran with no family history of diabetes and with HbA1C of 5.6 forty-five days prior to the hospitalization. He noted polyurea and excessive thirst following the second dose Pfizer-BioNTech COVID-19 vaccine. Hospitalized with hyperosmolar state and HbA1C of more than 14, he was treated initially with insulin drip and changed to basal, bolus regimen. In addition, he had new onset of oral thrush, requiring antifungal therapy. He needed higher doses of insulin during hospitalization and at discharge. He rapidly recovered and could be tapered off insulin in 4 months and recovered to normal glycemic state. We conclude that this is the second state to present with hyperosmolar state, and first case with rapid recovery of glycemic state.展开更多
Diabetic ketoacidosis(DKA)and hyperglycemic hyperosmolar state(HHS)are acute,life-threatening complications of diabetes.The overlap of these conditions,termed hyperosmolar diabetic ketoacidosis(H-DKA),is associated wi...Diabetic ketoacidosis(DKA)and hyperglycemic hyperosmolar state(HHS)are acute,life-threatening complications of diabetes.The overlap of these conditions,termed hyperosmolar diabetic ketoacidosis(H-DKA),is associated with substantial morbidity due to its complex pathophysiology and high complication rates.Notably,cases of H-DKA with glucose levels exceeding 50 mmol/L are rarely reported in the literature.This study details the clinical course of two H-DKA patients who exhibited extreme hyperglycemia at presentation,despite having no prior diagnosis of diabetes.Both patients underwent aggressive fluid resuscitation and insulin therapy,alongside careful management of acute complications.Vital signs and laboratory parameters demonstrated substantial normalization within 3 days of treatment initiation,and no acute or long-term complications related to the therapeutic interventions were observed.These cases underscore the efficacy of timely and intensive therapeutic interventions in mitigating the risks associated with extreme hyperglycemia in H-DKA and highlight critical strategies for optimal patient outcomes.展开更多
文摘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.
文摘AIM:To investigate the mechanism of the tight junction(TJ) disruption and the association between tumor necrosis factor(TNF)-α and matrix metalloproteinase(MMPs) under hyperosmotic condition in primary human corneal epithelial cells(HCECs).METHODS:The cultured HCECs were exposed to media which adding sodium chloride(Na Cl) for hyperosmolar stress or adding rh-TNF-α(10 ng/m L). NF-κB inhibitor(5 μmol/L) or GM-6001(potent and broad spectrum MMP inhibitor, 20 μmol/L)was added 1 h before that treatment. The integrity of TJ proteins was determined by immunofluorescent(IF) staining. The m RNA levels of TNF-α and MMPs were evaluated by quantitative reverse transcription polymerase chain reaction(RT-q PCR) and the protein expression by enzyme-linked immunosorbent assay(ELISA).RESULTS:TJ proteins ZO-1 and Occludin were disrupted in primary HCECs exposed to hyperosmotic medium. The m RNA expression and protein production of TNF-α increased significantly in hyperosmotic media at 500 m Os M. TNF-α mediated the expression and production of MMP-1, MMP-13, MMP-9, and MMP-3 stimulated by hyperosmotic stress. The production of MMPs in hyperosmolar media were increased through the increase of TNF-α. GM-6001 prevent the destruction of ZO-1 and Occludin in hyperosmolar stress and rh-TNF-α treated medium. TNF-α induced activation of MMPs was involved in the TJ disruption by hyperosmolarity.CONCLUSION:TJ proteins ZO-1 and Occludin are disrupted by hyperosmolar stress and TNF-α, but protected by MMP inhibitor(GM-6001). It suggests that TNF-α/MMP pathway mediates the TJ disruption in primary HCECs exposed to hyperosmotic stress.
文摘To protect from COVID-19 pandemic, several vaccines were developed infection with expected immunity against a SARS-CoV-2 infection. Short time side effects are reported. New onset diabetes was reported after SARS-CoV-2 infection. Here we report a case of new onset diabetes presenting with hyperosmolar hyperglycemic state, whose symptoms followed right after the second dose of Pfizer-BioNTech COVID-19 Vaccine. He is a 56-year old, obese Afro-American Veteran with no family history of diabetes and with HbA1C of 5.6 forty-five days prior to the hospitalization. He noted polyurea and excessive thirst following the second dose Pfizer-BioNTech COVID-19 vaccine. Hospitalized with hyperosmolar state and HbA1C of more than 14, he was treated initially with insulin drip and changed to basal, bolus regimen. In addition, he had new onset of oral thrush, requiring antifungal therapy. He needed higher doses of insulin during hospitalization and at discharge. He rapidly recovered and could be tapered off insulin in 4 months and recovered to normal glycemic state. We conclude that this is the second state to present with hyperosmolar state, and first case with rapid recovery of glycemic state.
基金supported by the Special Funds for Economic and Scientific Development of Medical and Health Science and Technology Program Projects in Longgang District,Shenzhen(LGKCYLWS2022-004).
文摘Diabetic ketoacidosis(DKA)and hyperglycemic hyperosmolar state(HHS)are acute,life-threatening complications of diabetes.The overlap of these conditions,termed hyperosmolar diabetic ketoacidosis(H-DKA),is associated with substantial morbidity due to its complex pathophysiology and high complication rates.Notably,cases of H-DKA with glucose levels exceeding 50 mmol/L are rarely reported in the literature.This study details the clinical course of two H-DKA patients who exhibited extreme hyperglycemia at presentation,despite having no prior diagnosis of diabetes.Both patients underwent aggressive fluid resuscitation and insulin therapy,alongside careful management of acute complications.Vital signs and laboratory parameters demonstrated substantial normalization within 3 days of treatment initiation,and no acute or long-term complications related to the therapeutic interventions were observed.These cases underscore the efficacy of timely and intensive therapeutic interventions in mitigating the risks associated with extreme hyperglycemia in H-DKA and highlight critical strategies for optimal patient outcomes.
