The Impact of Hyperosmolarity on Long-Term Outcome in Patients Presenting with Severe Hyperglycemic Crisis: A Population Based Study

Kruljac, Ivan; Čačić, Marko; Ćaćić, Petra; Biloš, Lora Stanka Kirigin; Kust, Davor; Perić, Božidar; Filipović-Grčić, Maja; Mirošević, Gorana; Ostojić, Vedran; Štefanović, Mario; Vrkljan, Milan

doi:10.1055/s-0043-117416

Cited by 9 publications

(9 citation statements)

References 23 publications

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“…Our study also found HHS occurs more commonly in elderly female patients, with the majority of patients having infections as the leading precipitating factor. As reported in previous studies, advanced age, male gender, high glucose, high leukocyte count, low bicarbonates, and altered mental status were associated with increased mortality of HHS [ 8 , 34 ]. In our study, we revealed a novel prognostic factor and a new protective factor for HHS patients.…”

Section: Discussionmentioning

confidence: 58%

Clinical profiles, outcomes and risk factors among type 2 diabetic inpatients with diabetic ketoacidosis and hyperglycemic hyperosmolar state: a hospital-based analysis over a 6-year period

She

Wang

et al. 2020

BMC Endocr Disord

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Objective Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most common hyperglycemic emergencies (HEs) associated with diabetes mellitus. Individuals with HEs can present with combined features of DKA and HHS. The objective of this study is to assess the clinical characteristics, therapeutic outcomes, and associated predisposing factors of type 2 diabetic patients with isolated or combined HEs in China. Methods We performed a retrospective analysis of 158 patients with type 2 diabetes (T2DM), complicated with DKA, HHS, or DKA combined with HHS (DKA-HHS) in Shanghai Tongji Hospital, China from 2010 to 2015. Admission clinical features, therapeutic approaches and treatment outcomes of those patients were extracted and analyzed. Results Of the 158 patients with T2DM, 65 (41.1%) patients were DKA, 74 (46.8%) were HHS, and 19 (12.0%) were DKA-HHS. The most common precipitants were infections (111, 70.3%), newly diagnosed diabetes (28,17.7%) and non-compliance to medications (9, 5.7%). DKA patients were divided into mild, moderate and severe group, based on arterial blood gas. Spearman correlation analysis revealed that C-reaction protein (CRP) was positively correlated with severity of DKA, whereas age and fasting C peptide were inversely correlated with severity of DKA (P < 0.05). The mortality was 10.8% (17/158) in total and 21.6% (16/74) in the HHS group, 5.9% (1/17) in DKA-HHS. Spearman correlation analysis indicated that death in patients with HHS was positively correlated to effective plasma osmolality (EPO), renal function indicators and hepatic enzymes, while inversely associated with the continuous subcutaneous insulin infusion (CSII) therapy. Logistic regression analysis suggested that elevated blood urea nitrogen (BUN) on admission was an independent predisposing factor of mortality in HHS, while CSII might be a protective factor for patients with HHS. Furthermore, the receiver-operating characteristic (ROC) curve analysis indicated that BUN had the largest area under the ROC curves for predicting death in patients with HHS. Conclusions Our findings showed elevated CRP and decreased fasting C-peptide might serve as indicator for severe DKA. Elevated BUN might be an independent predictor of mortality in patients with HHS, whereas CSII might be a protective factor against death in HHS.

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Section: Discussionmentioning

confidence: 58%

Clinical profiles, outcomes and risk factors among type 2 diabetic inpatients with diabetic ketoacidosis and hyperglycemic hyperosmolar state: a hospital-based analysis over a 6-year period

She

Wang

et al. 2020

BMC Endocr Disord

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“…Among adult T2D patients, HHS at diagnosis was associated with older age compared with control [29]. Older patients may not recognize diabetes symptoms, similar to younger children.…”

Section: Discussionmentioning

confidence: 88%

Multicentre analysis of hyperglycaemic hyperosmolar state and diabetic ketoacidosis in type 1 and type 2 diabetes

et al. 2020

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Aims To compare diabetes patients with hyperglycaemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), and patients without decompensation (ND). Methods In total, 500,973 patients with type 1 or type 2 diabetes of all ages registered in the diabetes patient follow-up (DPV) were included. Analysis was stratified by age (≤ / > 20 years) and by manifestation/follow-up. Patients were categorized into three groups: HHS or DKA—during follow-up according to the most recent episode—or ND. Results At onset of diabetes, HHS criteria were met by 345 (68.4% T1D) and DKA by 9824 (97.6% T1D) patients. DKA patients had a lower BMI(-SDS) in both diabetes types compared to ND. HbA1c was higher in HHS/DKA. During follow-up, HHS occurred in 1451 (42.2% T1D) and DKA in 8389 patients (76.7% T1D). In paediatric T1D, HHS/DKA was associated with younger age, depression, and dyslipidemia. Pump usage was less frequent in DKA patients. In adult T1D/T2D subjects, metabolic control was worse in patients with HHS/DKA. HHS and DKA were also associated with excessive alcohol intake, dementia, stroke, chronic kidney disease, and depression. Conclusions HHS/DKA occurred mostly in T1D and younger patients. However, both also occurred in T2D, which is of great importance in the treatment of diabetes. Better education programmes are necessary to prevent decompensation and comorbidities.

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“…Local and systemic osmotic alterations have been associated with a number of disorders, such as brain injury (Kawamata et al, 2007), hyper-/hyponatremia state (Reynolds et al, 2006), inflammatory and infectious processes (Brocker et al, 2012), renal failure (Kuwabara et al, 2017), and diabetes (Umpierrez and Korytkowski, 2016). The hyperglycemic hyperosmolar state (HHS) is a serious acute complication of diabetes decompensation, especially in type 2 diabetes mellitus (T2DM), with critical prognosis and a repercussion for renal failure (Johnson et al, 2014;Pasquel and Umpierrez, 2014;Umpierrez and Korytkowski, 2016;Kruljac et al, 2018). Given the well-known interrelationship between osmolality, glycemia, and kidney transport function, it is plausible to hypothesize that part of the biological effect of glucose at high concentrations can be attributed to its osmotic action, which has not been directly investigated in the context of the paracellular barrier function (Aluksanasuwan et al, 2017;Kruljac et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…The hyperglycemic hyperosmolar state (HHS) is a serious acute complication of diabetes decompensation, especially in type 2 diabetes mellitus (T2DM), with critical prognosis and a repercussion for renal failure (Johnson et al, 2014;Pasquel and Umpierrez, 2014;Umpierrez and Korytkowski, 2016;Kruljac et al, 2018). Given the well-known interrelationship between osmolality, glycemia, and kidney transport function, it is plausible to hypothesize that part of the biological effect of glucose at high concentrations can be attributed to its osmotic action, which has not been directly investigated in the context of the paracellular barrier function (Aluksanasuwan et al, 2017;Kruljac et al, 2018). Interestingly, we have shown in a previous work that acute (24 h) and chronic (72 h) exposure to high glucose, at concentrations that simulate hyperglycemia in prediabetic (180 mg/dL) and diabetic (360 mg/dL) patients, induces changes in tubular epithelial barrier function mediated by TJ in a concentration and time-dependent manner in the renal Madin-Darby Canine Kidney (MDCK) cell line (Mongelli-Sabino et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Increased osmolality enhances the tight junction‐mediated barrier function in a cultured renal epithelial cell line

Canuto

Collares-Buzato

2018

Cell Biology International

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Osmotic alterations are associated with several human diseases, including diabetic nephropathy. We have previously shown that high glucose, which is a well-known osmotic agent, induces significant disruption of the tight junction (TJ)-mediated tubular barrier of the Madin-Darby canine kidney (MDCK) cell line. In this study, we investigated the effect of acute (24 h) and chronic (72 h) exposure to increased osmolality (with a 14.5 mM mannitol solution) on TJ-mediated barrier function in MDCK cells. The treatment with mannitol significantly increased the transepithelial electrical resistance (TEER) and accelerated the TEER recovery after Ca 2þ switch assay in comparison with control monolayers. Immunofluorescence and Western blot analyses showed that mannitol treatment induced a significant increase in the tight junctional and cellular content of claudin-1 (a barrier-forming claudin) as well as a significant decrease in claudin-2 (a pore-forming claudin) junctional and cellular contents. These data suggest that an increased osmolality induces enhancement of the TJ-mediated barrier of MDCK cells, and that, therefore, the negative effect of high glucose on the epithelial paracellular barrier cannot be attributed to its osmotic actions. In addition, a subtle increase in osmolality may have an impact on kidney function and renalrelated diseases.

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The Impact of Hyperosmolarity on Long-Term Outcome in Patients Presenting with Severe Hyperglycemic Crisis: A Population Based Study

Abstract: Infection, use of furosemide and benzodiazepines may be important precipitating factors of HHS. Prospective clinical trials are mandatory to analyze the safety of ACE-inhibitors and benzodiazepines in elderly patients with diabetes.

Cited by 9 publications

References 23 publications

Clinical profiles, outcomes and risk factors among type 2 diabetic inpatients with diabetic ketoacidosis and hyperglycemic hyperosmolar state: a hospital-based analysis over a 6-year period

Clinical profiles, outcomes and risk factors among type 2 diabetic inpatients with diabetic ketoacidosis and hyperglycemic hyperosmolar state: a hospital-based analysis over a 6-year period

Multicentre analysis of hyperglycaemic hyperosmolar state and diabetic ketoacidosis in type 1 and type 2 diabetes

Increased osmolality enhances the tight junction‐mediated barrier function in a cultured renal epithelial cell line

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