Acute Diabetic Ketoacidosis Research Articles

Fulminant Type 1 Diabetes in an 81-Year-Old Male with Rhabdomyolysis-Induced Acute Kidney Injury Successfully Withdrawn from Hemodialysis: A Case Report

ABSTRACT Objective: Fulminant type 1 diabetes mellitus (FT1DM), a distinct subtype of type 1 diabetes, is characterized by a rapid onset of severe hyperglycemia and diabetic ketoacidosis (DKA). DKA sometimes induces severe rhabdomyolysis, which causes renal failure, and it requires permanent hemodialysis (HD), especially in elderly patients. Some cases of FT1DM progress to rhabdomyolysis-induced acute kidney injury (AKI). Methods: We report the case of an 81-year-old male with rhabdomyolysis-induced AKI, the oldest patient reported to date, associated with acute FT1DM onset. Results: Although the patient required HD, he was successfully withdrawn from HD within 2 months. Conclusion: Even in such advanced age patients, prompt renal replacement therapy gives the prospect for recovering kidney function and circumvents the need for permanent renal replacement therapy. Abbreviations: AKI acute kidney injury CHDF continuous hemodiafiltration CK creatinine kinase DKA diabetic ketoacidosis FT1DM fulminant type 1 diabetes mellitus HD hemodialysis HLA human leukocyte antigen RRT renal replacement therapy

Comparison of interference in 4 Jaffe creatinine assays using acute diabetic ketoacidosis samples

Background and aim Creatinine assays are now standardised, however the effect of elevated glucose and ketoacids during acute diabetic ketoacidosis (DKA) on different Jaffe creatinine assays is unknown. We aim to assess this interference on different platforms using the Vitros enzymatic creatinine method as the gold standard. Methods Samples were collected from patients presenting to Emergency Department with DKA and analysed using 4 Jaffe assays (Architect, Roche, Beckman Coulter and Siemens) and 1 enzymatic assay (Vitros). Results Of the eighteen patients (12 M, 6F, age 32.1 ± 12.4 years), admission pH was 7.12 ± 0.16, HCO3 was 8.2 ± 4 mmol/L, glucose was 36.2 ± 13.8 mmol/L and capillary ketone was 5.7 ± 1.2 mmol/L. The average enzymatic creatinine value was 115.3 ± 64.2 μmol/L. All Jaffe creatinine results were significantly higher (p Discussion Falsely elevated plasma creatinine results might delay the administration of intravenous potassium in DKA patients and clinicians need to be aware of this potential interference which appeared most marked on the Abbott platform.

CXCL1/CXCL8 (GROα/IL-8) in human diabetic ketoacidosis plasma facilitates leukocyte recruitment to cerebrovascular endothelium in vitro

Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications, possibly due to leukocyte-endothelial interactions. Our aim was to determine whether DKA-induced inflammation promoted leukocyte adhesion to activated human cerebrovascular endothelium. Plasma was obtained from children with type 1 diabetes either in acute DKA or in an insulin-controlled state (CON). Plasma concentrations of 21 inflammatory analytes were compared between groups. DKA was associated with altered circulating levels of ↑CXCL1 (GROα), ↑CXCL8 (IL-8), ↑IL-6, ↑IFNα2, and ↓CXCL10 (IP-10) compared with CON. These plasma analyte measurements were then used to create physiologically relevant cytokine mixtures (CM). Human cerebral microvascular endothelial cells (hCMEC/D3) were stimulated with either plasma (DKA-P or CON-P) or CM (DKA-CM or CON-CM) and assessed for polymorphonuclear leukocyte (PMN) adhesion. Stimulation of hCMEC/D3 with DKA-P or DKA-CM increased PMN adhesion to hCMEC/D3 under "flow" conditions. PMN adhesion to hCMEC/D3 was suppressed with neutralizing antibodies to CXCL1/CXCL8 or their hCMEC/D3 receptors CXCR1/CXCR2. DKA-P, but not DKA-CM, initiated oxidative stress in hCMEC/D3. Expression of ICAM-1, VCAM-1, and E-selectin were unaltered on hCMEC/D3 by either DKA-P or DKA-CM. In summary, DKA elicits inflammation in children associated with changes in circulating cytokines/chemokines. Increased CXCL1/CXCL8 instigated PMN adhesion to hCMEC/D3, possibly contributing to DKA-associated intracranial vascular complications.

Surgical management of acute esophageal necrosis

I read with great interest the article by Drs. M.H. Wu and H.Y. Wu [1] on acute esophageal necrosis (AEN). The authors described two patients with AEN and emphasized the role of esophagectomy in the treatment of this rare syndrome. While I welcome reports of new cases of ‘‘black esophagus’’ that stir scientific discussion about the condition, I disagree with the proposed, rather aggressive, surgical approach to manage AEN. In my original paper, I introduced a staging system that describes the progression of AEN based on the endoscopic and pathologic findings [2]. It should be noted that black esophagus is a striking medical condition that may present with acute gastrointestinal hemorrhage in patients with hemodynamic compromise, debilitated health, sepsis, multiorgan failure, acute gastric outlet obstruction and diabetic ketoacidosis. The mainstay of treatment of AEN is supportive medical therapy with acid suppression, nil-per-os restriction, red blood cell transfusion, and importantly, correction of the underlying medical condition that has led to the development of the AEN. The overall mortality rate in patients with black esophagus is high at 31 %, but the mortality specific to the esophageal disease is only 6 %. To date, surgical resection has been reserved only for cases of esophageal perforation, an event typically caused by external compression by a ruptured thoracic aorta, gastric volvulus or severe thromboembolic disease [3]. It may also be considered in situations with rapid clinical decompensation in the absence of any other explanation. I absolutely disagree with the authors that esophagectomy is indicated for a wide group of stage 1 AEN cases. I further disagree that surgical intervention is necessary for stages 2 and 3 of AEN to prevent the development of esophageal strictures. A subgroup of patients with diabetes mellitus has a low chance of developing stricture or stenotic complications, and all patients generally do well with endoscopic balloon dilatation [2]. In conclusion, the surgical management of AEN should be performed only in select cases of perforation/mediastinitis. The passage of a nasogastric tube, and especially a Sengstaken–Blakemore tube, in AEN patients should be prohibited, as the friability of the esophagus will lead to tragic perforation and death, as was seen in the second patient. In their description of their two cases of AEN, the authors failed to explain the need for rapid surgical treatment of patients with black esophagus, without first attempting conventional medical management.

Analiza zaburzeń równowagi kwasowo-zasadowej w cukrzycowej śpiączce ketonowej na podstawie metody Stewarta — opis przypadku

This case report presents a 49 year-old female with type 1 diabetes admitted to the intensive care unit with acute respiratory failure and severe diabetic ketoacidosis with an initial measurement of blood glucose level of 1,200 mg L⁻¹, pH 6.78, serum HCO₃ ⁻ 3.2 mmoL L⁻¹ and BE -31.2 mmoL L⁻¹. Analysis of the blood gasometric parameters with the Stewart approach and the traditional Henderson-Hasselbalch concept enabled the discovery of metabolic acidosis caused by unidentified anions (mainly ketons). A treatment protocol with intensive fluid management with 0.9% NaCl, intensive intravenous insulin therapy, and potassium supplementation was administered. Analysis of the gasometric parameters after 12 hours of treatment according to the Stewart approach compared to the Henderson-Hasselbalch concept disclosed that metabolic acidosis caused by the unidentified anions has resolved almost completely and been replaced by metabolic hyperchloremic acidosis. The hyperchloremic acidosis was caused by the intensive fluid resuscitation with 0.9% NaCl, which contains a high chloride load, exceeding the chloride levels observed in human serum. Fluid management with balanced fluids other than saline was continued, together with intravenous insulin infusion, potassium supplementation, and 5% glucose administration. Analysis of this case study revealed the advantages of the Stewart approach to acid base abnormalities compared to the traditional Henderson-Hasselbalch concept. The Stewart approach allows the diagnosis of the exact causes of severe life-threatening metabolic acidosis and the appropriate modification of the therapeutic mangement of patients with diabetic ketoacidosis.

Clinical features of diabetes mellitus cases complicated by Burkholderia pseudomallei septicemia.

The aim of this study was to analyze the clinical characteristics of diabetes mellitus patients with Burkholderia pseudomallei septicemia and evaluate strategies of diagnosis and treatment. The clinical characteristics, diagnosis, treatment, and prognosis of 39 diabetes mellitus patients with B. pseudomallei septicemia were retrospectively analyzed. Farmers, fishermen and workers were found to be high-risk groups. The clinical manifestations of patients were diverse without specific features, but mainly presented manifestations of acute fulminant septicemia, diabetic ketoacidosis, and abscesses in tissues or/and organs. Patients showed high mortality and misdiagnosis rates and were prone to relapses and long treatment duration as there are currently few effective and sensitive antibiotics for the disease. Consequently, the cost of treatment for the disease was high. Early diagnosis, a prolonged course of heavy doses of sensitive intravenous antibiotics, drainage of abscesses, intensive insulin therapy, and supportive treatment are the keys for successful management of the disease. Regular follow-ups combined with long-term blood glucose control can help reduce the disease recurrence.

Acute Pancreatitis and Diabetic Ketoacidosis following L-Asparaginase/Prednisone Therapy in Acute Lymphoblastic Leukemia

Acute pancreatitis and diabetic ketoacidosis are unusual adverse events following chemotherapy based on L-asparaginase and prednisone as support treatment for acute lymphoblastic leukemia. We present the case of a 16-year-old Hispanic male patient, in remission induction therapy for acute lymphoblastic leukemia on treatment with mitoxantrone, vincristine, prednisone, and L-asparaginase. He was hospitalized complaining of abdominal pain, nausea, and vomiting. Hyperglycemia, acidosis, ketonuria, low bicarbonate levels, hyperamylasemia, and hyperlipasemia were documented, and the diagnosis of diabetic ketoacidosis was made. Because of uncertainty of the additional diagnosis of acute pancreatitis as the cause of abdominal pain, a contrast-enhanced computed tomography was performed resulting in a Balthazar C pancreatitis classification.

Diabetic ketoacidosis as a presenting symptom of complicated pancreatic cancer

Diabetic ketoacidosis as a presenting symptom of complicated pancreatic cancer

Increased systemic Th17 cytokines are associated with diastolic dysfunction in children and adolescents with diabetic ketoacidosis.

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA.

C-peptide in diabetes diagnosis and therapy

C-peptide is known for several decades. It is released in equimolar amounts together with insulin from the pancreatic beta cells. Still there has been quite remarkable lack of interest in C-peptide. C-peptide is rarely used to classify type of diabetes although it seems self-evident that it is important to estimate the function of those cells which do not function good enough and therefore causes a syndrome which requires life-long treatment and leads to serious complications. Not until recent years C-peptide is accepted as a relevant outcome in trials aiming at preservation of beta cell function, although it is known for decades that some C-peptide is associated with less complications in type 1 diabetes (T1D). Preservation of beta cell function is important to make diabetes milder, and when beta cell function can be preserved before clinical manifestation of T1D, we are on our way to prevent that disease. Residual C-peptide/insulin secretion can be of value in classification of diabetes in different types. C-peptide may give valuable clinical information on why patients are more or less stable/labile in their blood glucose and more or less easy to treat. It explains why patients with T1D have different tendency to develop severe acute complications, both severe hypoglycaemia and diabetic keto-acidosis (DKA). Longstanding C-peptide may decrease risk of developing severe late complications. Finally, although still under debate, C-peptide seems to have several effects on different organs suggesting that it is an important hormone, interesting per se, and not only as a reflection of insulin secretion.

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Introduction: Hospitals vary in their use of intensive care units (ICUs) for patients with diabetic ketoacidosis (DKA). At Beth Israel Medical Center, insulin infusions for DKA are only permitted in the emergency department (ED) or in an ICU. DKA patients must, therefore, remain in the ED until anion gap normalization (followed by admission to a regular medical ward) or go to an ICU. We sought to assess the impact on length of stay (LOS) - of triaging DKA patients with anion gaps to the ICU versus triaging of patients with anion gap normalization in the ED to medical floors. Hypothesis: Patients admitted to the medical ICU for DKA have longer hospital LOS without appreciable changes in mortality. Methods: We conducted a retrospective analysis of all adults presenting to the ED with a primary diagnosis of DKA from November 1st 2006-October 31st 2007, and November 1st 2010-October 31st 2011. Demographics, co-morbidities, concomitant acute diagnoses, laboratory values and DKA severity were compared between patients triaged to the ICU and those sent to the floor after anion gap closure in the ED using t-test and chi square analyses as appropriate. DKA severity (0/1 (least)-IV (most) severe) was determined using initial HCO3, calculated osmolarity and anion gap. Hospital LOS (primary outcome) and ED LOS were compared for each grade of DKA severity using Spearman rank correlation and after adjustment for DKA severity using linear regression. Results: Our cohort included 112 patients; 61 (54.5%) admitted to the ICU and 51 to the floor. There were no statistically significant differences in gender, age and co-morbidities between groups. Patients who went to the ICU had higher finger sticks, potassium, leukocytes and anion gaps, with lower HCO3 (P<0.05). ICU use increased with DKA severity (grade 0/I 10.7% up to grade IV 84.6%, (p<0.05). Patients who went to the ICU had shorter ED LOS but longer hospital LOS (P<0.05). When stratified by DKA severity, ED LOS was shorter for patients who went to the ICU with DKA grades II, III and IV (P<0.05), but not for grade 0/I. Hospital LOS was longer for patients who went to the ICU with grades 0/I and IV DKA (P<0.05), but not for grades II and III. After adjustment for DKA severity, all patients who went to the ICU had longer hospital LOS (median (IQR): 5.5 (3.2,4.6) vs. 4.6 (2.8,3.2) days, p<0.001) and shorter ED LOS (8.5 (6.8,7.2) vs. 10.0 (7.2,8.5) hours, p<0.001). Hospital survival was 100% in both groups. Conclusions: Patients with DKA who go to the ICU in our institution have shorter ED LOS, but longer hospital LOS even after adjustment for DKA severity.

New Role for Grb10 Signaling in the Pancreas

After surgically removing the canine pancreas, Joseph von Mering and Oskar Minkowski linked the pancreas with diabetes for the first time (1). Their observation led to the use of purified pancreatic extracts to successfully treat diabetic patients some 30 years later, then to the identification and application of subcutaneous insulin delivery, as well as more recent islet transplantation therapies (2). Despite these life-saving advances, diabetes is still a global health care problem. However, there remains much to learn about the mechanisms involved in glucose homeostasis. Insulin receptor signaling is the central molecular pathway and remains the subject of intense research activity. Mouse knockout models have played a pivotal role in bridging the gap between our understanding of the relevant molecular mechanisms and glucose homeostasis in the whole animal (3–5). In this issue, Zhang et al. (6) report on the pancreas-specific disruption of the Grb10 signaling adaptor protein gene. This builds on a long tradition of mouse knockout experiments targeting components of the insulin-signaling pathway. Seminally, germline or “global” disruption of the insulin receptor ( Insr ) gene revealed a subtle effect of Insr signaling on fetal growth (7) as well as perinatal lethality due to acute diabetic ketoacidosis (8,9). The physiological effects of gene disruption can be difficult to interpret when they involve such a severe phenotype and/or when signaling is altered within multiple insulin-sensitive tissues. To circumvent these problems “conditional” or tissue-specific mouse knockouts can be generated using Cre-lox technology, an approach used to great effect within the glucose homeostasis field. In a series …

Endocrine emergencies in critically ill patients: Challenges in diagnosis and management

Endocrine emergencies pose unique challenges for the attending intensivist while managing critically ill patients. Besides taking care of primary disease state, one has to divert an equal attention to the possible associated endocrinopathies also. One of the common reasons for inability to timely diagnose an endocrinal failure in critically ill patients being the dominance of other severe systemic diseases and their clinical presentation. The timely diagnosis and administration of therapeutic interventions for these endocrine disorders can improve the outcome in critically ill patients. The timely diagnosis and administration of timely therapeutics in common endocrine disorders like severe thyroid disease, acute adrenal insufficiency and diabetic ketoacidosis significantly influence the outcome and prognosis. Careful evaluation of clinical history and a high degree of suspicion are the corner stone to diagnose such problems. Aggressive management of the patient is equally important as the complications are devastating and can prove highly fatal. The present article is an attempt to review some of the common endocrine emergencies in intensive care unit and the challenges associated with their diagnosis and management.

Cytokine response to diabetic ketoacidosis (DKA) in children with type 1 diabetes (T1DM)

It has been suggested that cytokine release during DKA may result in capillary perturbation and thus may contribute to the development of its acute clinical complications (i.e.cerebral or pulmonary edema). We studied in 38 newly diagnosed T1DM children with DKA, aged 7.68±3.07 years, plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumour necrosis factor-α) and also WBC (white blood cell count), hs-CRP (high sensitivity C-reactive protein), GH (growth hormone) and cortisol, prior to, during and 120h after DKA management, with the aim to monitor their levels at different time-points and in different degrees of DKA severity. Prior to DKA management the levels of IL-6, IL-8, IL-10, WBC and cortisol were elevated, but were all reduced within 120 h after DKA management. Then the patients were divided into two groups: a. moderate/severe: pH≤7.2, b. mild DKA: pH>7.2. In the group with moderate/severe DKA (ph≤7.2), IL-10 levels were the highest of all cytokines, but were significantly decreased after 6h (91.76 vs 18.04 pg/mL, p=0.008), with no further change, while IL-6 levels were decreased at 120 h (28.32 vs 11.9 pg/mL, p=0.003). The above were not observed in the group with mild DKA. In conclusion, in the children with DKA of our study, in the group with moderate/severe DKA the IL-10 levels were prematurely reduced at 6 hours, while the IL-6 levels remained high and were reduced at 120 hours after the DKA management. These changes may be responsible for increased capillary perturbation, which could lead to the subsequent development of acute DKA complications.

Acute pancreatitis and diabetic ketoacidosis in pregnancy: a case report

The Galle Medical Journal is published by the Galle Medical Association. The journal is published quarterly in March, June, September and December each year. The submissions are accepted throughout the year. The aims of the Journal are to foster co-operation among the medical fraternity and to be a forum to make literary contributions, share experiences encountered in medical practice, update their knowledge and have debates on topics related to all aspects of medicine.

Life-saving decompressive craniectomy for diffuse cerebral edema during an episode of new-onset diabetic ketoacidosis

Diabetic ketoacidosis (DKA), a well-known complication of diabetes mellitus, is associated with severe diffuse cerebral edema leading to brain herniation and death. Survival from an episode of symptomatic cerebral edema has been associated with debilitating neurological sequelae, including motor deficits, visual impairment, memory loss, seizures, and persistent vegetative states. A review of the literature reveals scant information regarding the potential surgical options for these cases. The authors present their case in which they used a craniectomy to treat this life-threatening condition. After reportedly suffering nausea and vomiting, a 12-year-old male presented to the emergency room with lethargy and was diagnosed with acute DKA. After appropriate treatment, the patient became comatose. A CT scan revealed diffuse cerebral edema. To decrease intracranial pressure and prevent further progression of brain herniation, a bifrontal decompressive craniectomy with duraplasty was performed. The patient's neurological function gradually improved, and he returned to school and his regular activities with only minimal cognitive deficits. Given the high mortality and morbidity associated with DKA-related edema, we believe decompressive craniectomy should be considered for malignant cerebral edema and herniation syndrome.

Causes of mortality in diabetes mellitus: data from a tertiary teaching hospital in India

Background:Mortality studies can show the relative contribution of diabetes to mortality in the total population, and they can provide important descriptions of the changes in causes and frequency of diabetes...

Pitfalls in Outpatient Diabetes Management

T he challenges of treating patients with diabetes are many. Patients usually require oral medications and/or insulin to control glucose levels. Such medications require careful titration as well as monitoring for side effects or adverse reactions. Additionally, patients must be educated and motivated by their caregivers to monitor glucose levels, control carbohydrate consumption, and aggressively participate in self-care to control their disease. Such treatment allows patients to minimize the likelihood that they will develop chronic complications of diabetes such as microvascular or macrovascular disease. In addition to the usual challenges regarding diabetes control, diabetes can also be exacerbated by factors such as medication changes, surgery, and illnesses. Such conditions can lead to acute decompensation of glucose control even in the setting of previously well-controlled disease. Acute complications of diabetes such as diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) may develop, which can be life-threatening and must be treated aggressively.1 Although it is important for physicians to understand the treatment of acute complications of diabetes, it is perhaps even more important to be versed in techniques of averting acute hyperglycemia. Three common causes of diabetes exacerbation include intercurrent illness, surgery or trauma, and use of corticosteroids. Intercurrent illnesses can be challenging to any patient with a chronic disease, but they are especially problematic in patients with diabetes. Such conditions exacerbate hyperglycemia, and even patients with well-controlled diabetes may develop considerable hyperglycemia. Infections have long been recognized as a major cause of acute hyperglycemia, DKA, and HHS.1,2 Hyperglycemia in response to infection likely takes place as a result of several pathogenic mechanisms. Gram-negative lipopolysaccharide has been shown to increase insulin resistance significantly, possibly mediated through increase in stress hormones such as cortisol and growth hormone.3 Because patients with diabetes are unable to increase insulin production and …

Causes of admission to intensive care units in the Hajj period of the Islamic Year 1424 (2004)

BACKGROUNDApproximately 2 to 3 million pilgrims perform Hajj every year. We describe the pattern of diseases, complications, and outcome of pilgrims who required admission to intensive care units (ICUs) during the Hajj period of the Islamic year 1424 (2004).METHODSThis was a cross-sectional study of all patients admitted to 104 ICU beds in four hospitals in Mena and three hospitals in Arafat during the Hajj.RESULTSOf 140 patients admitted to ICUs, 75 (54%) patients were older than 60 years. The risk of complications and death increased with age, with the highest risk noticed among pilgrims older than 80 years. Ninety-four (67.6%) patients were men. Eighty-nine (63.6%) patients were admitted with cardiovascular diseases and 37 (26.4%) patients with infections. Myocardial infarction (25%) and pneumonia (22%) were the most common admitting diagnoses. Trauma accounted for only 6.4% (9 patients) of admissions. Sixty-three (45.0%) patients recovered and were discharged or transferred to hospital wards in stable condition, 40 (28.6%) were transferred to tertiary care centers for specialized services, 21 (15.0%) were transferred to tertiary care centers after closure of the temporary hospitals in Mena and Arafat, 15 (10.7%) patients died, and one (0.7%) patient was discharged against medical advice.CONCLUSIONThis study revealed information on the pattern of diseases and the most common causes of admission of pilgrims to ICUs and the required medical services during Hajj. It is hoped that this information will be of help to health care planners and officials to provide optimal and cost effective health care services to pilgrims in Hajj.

Infective Endocarditis and Acute Purulent Pericarditis in a Patient with Hyperglycemia

A diabetic patient was admitted to our hospital for infective endocarditis with acute purulent pericarditis and diabetic ketoacidosis. Echocardiography revealed attachment of vegetation to the chordae tendineae in the left ventricle and pericaridial effusion. The vegetation was enlarged and pendulated for a few days despite maximal antimicrobial therapy. Surgical resection was desirable to decrease the risk of embolic complications and cardiovascular collapse. We could not open the heart because of accumulation of purulent pericardial fluid, and right renal infarction was complicated. We believe that the immunocompromised and hypercoagulable state due to diabetes caused these conditions.