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Background: Many studies indicated that mean platelet volume (MPV) and platelet distribution width (PDW) may be valuable in the diagnosis and management of clinical disorders; also, serum butyrylcholinesterase activity (BChE) was suggested to be linked to systemic inflammation and oxidative stress. Limited studies measured these readily available markers in children with diabetic ketoacidosis (DKA). Our objectives were to measure MPV, PDW and BChE in children with DKA; and to assess if any of these markers reflects the severity of DKA., Methods: Our study included: 30 children with DKA (DKA group), 30 diabetic children (Non-DKA group) and 30 apparently healthy children (control group). MPV, PDW and BChE were measured in all children. Additional blood samples were withdrawn from the DKA group to assess these markers at discharge from hospital., Results: MPV, PDW and BChE were significantly altered in the DKA group than the other two groups; and their levels improved significantly at discharge of the DKA group (p < 0.05). The three markers were found to equally to predict the presence of DKA, but MPV was the most suitable risk marker for DKA diagnosis (OR = 4.251, CI 95% =1.463-12.351, p = 0.003). Regarding their relation with DKA severity, they did not correlate significantly with arterial PH or serum HCO3 - (p > 0.05)., Conclusion: DKA in children is associated with changes in MPV, PDW and BChE activity, which improve after resolution of the condition. Elevated MPV can be a suitable risk marker for DKA. None of the studied markers correlated with the severity of DKA.

A rapid gas chromatographic mass spectrometric method for measuring anions associated with acute anion gap metabolic acidosis is described. The method is an extension of a previous method. The method quantifies glycolic acid, beta-hydroxybutyric acid with good linearity and pyroglutamic acid with a reproducible curvature relation between 1 and 20 mmol/L and can help the clinician distinguish effectively between ethylene glycol poisoning, alcoholic and diabetic ketoacidosis and cysteine deficiency so early that it will have clinical consequences.

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.

Objectives: To assess the benefit of using the flash glucose monitoring system (FGMS) in children and adolescents with type 1 diabetes mellitus (T1DM) during Ramadan fasting. Methods: A prospective pilot study of 51 participants visited the pediatric diabetes clinic at King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia from between June until and July 2016. The FreeStyle® Libre™ FGMS (Abbott Diabetes Care, Alameda, CA, USA) was used. Hypoglycemia was defined as glucose values of less than 70 mg/dL, while hyperglycemia as glucose values of more than 150 mg/dL for all participants based on our institute's protocol. Results: Participants were able to fast for 67.0% of the total days eligible for fasting, whereas they did not fast on 33% of the days due to either hypoglycemia (15.4%) or non-diabetes-related reasons (17.6 %). None of the participants developed severe hypoglycemia. The mean number of hyperglycemic episodes during fasting hours was 1.29, per day, which was higher than that of hypoglycemic episodes (0.7). None of the participants developed diabetic ketoacidosis (DKA). Glycemic control with mean of estimated hemoglobin A1C reading during Ramadan (8.16 ± 1.64% [pre study]) to 8.2 ± 1.63% [post study] p=0.932. Conclusions: Children and adolescents with T1DM who use the FGMS could fast without the risk of life-threatening episodes of severe hypoglycemia (namely seizure, coma), or DKA during Ramadan. Adequate education and good glycemic control prior to Ramadan are important strategies in combination with the use of an FGMS to achieve better outcome.

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., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new antidiabetic drugs that regulate blood glucose levels by increasing urinary glucose excretion. In May 2015, the U.S. Food and Drug Administration (FDA) issued a warning that SGLT2 inhibitors may lead to ketoacidosis. In this report, we describe a case of life-threatening euglycemic ketoacidosis associated with SGLT2 inhibition and evaluate possible mechanisms and triggers.

There is little data documenting cortisol levels in children with diabetic ketoacidosis (DKA), despite the fact that untreated adrenal insufficiency (AI) could worsen the outcome of DKA. In this cross-sectional study, we assessed serum cortisol levels in 28 children with DKA and new onset type 1 diabetes mellitus evaluated at our center over a 5-year period. Average duration of diabetes-related symptoms was positively associated with age ( P = .002), and significantly lower hemoglobin A1c levels were observed in the youngest children. The mean cortisol level was 40.9 µg/dL, with a range of 7.8 to 119 µg/dL. Cortisol levels were found to be inversely associated with serum pH ( P = .007). There was no difference in the clinical outcome of the 4 patients who had cortisol levels less than 18 µg/dL. Overall, we did not find clinical or laboratory evidence of diminished cortisol reserve; however, the possibility of AI must be kept in mind when treating children with DKA.

A 46-year-old woman with a history of Graves' disease presented with the chief complaints of appetite loss, weight loss, fatigue, nausea, and sweating. She was diagnosed with diabetic ketoacidosis (DKA), thyroid storm, and influenza A. She was treated with an intravenous insulin drip, intravenous fluid therapy, intravenous hydrocortisone, oral potassium iodine, and oral methimazole. As methimazole-induced neutropenia was suspected, the patient underwent thyroidectomy. It is important to maintain awareness that thyroid storm and DKA can coexist. Furthermore, even patients who have relatively preserved insulin secretion can develop DKA if thyroid storm and infection develop simultaneously.

Although most women with type 1 diabetes experience the normal transition to menopause, there is little information about the impact of hormone replacement therapy on their glycemic profiles. A 54-year-old postmenopausal woman with fulminant type 1 diabetes was admitted to our hospital due to diabetic ketoacidosis. She was treated with fluid replacement and a continuous insulin infusion. Thereafter, her glycemic profile was well maintained by daily multiple insulin injections. However, her glycemic profiles immediately deteriorated following the administration of progesterone in hormone replacement therapy. This transient deterioration implies that external progesterone can lead to the deterioration of glycemic profiles in postmenopausal women with type 1 diabetes.

Severe hypertriglyceridemia is a known, but uncommon complication of diabetic ketoacidosis. We discuss the case of a 23-year-old, previously healthy, woman who initially presented to the emergency department with abdominal pain. Grossly lipemic serum due to extremely high triglyceride (38.6 mmol/L) and cholesterol (23.2 mmol/L) levels were observed with a high blood glucose (23 mmol/L) and a low pH of 7.06 on a venous blood gas. She was treated successfully with fluids and insulin and had no sequale of pancreatitis or cerebral edema. Her triglycerides and cholesterol was normalized in three days and she was discharged home on insulin therapy after five days. Further history revealed a recent change in diet with no meat, fish or poultry consumption in the last 12 months and concomitantly an increase in carbohydrate intake which might have contributed to her extremely high serum lipid levels. This case demonstrates that clinicians should be mindful of the different presentations of diabetic ketoacidosis. Key words: diabetic ketoacidosis, hypertriglyceridemia, hyperlipidemia, vegan diet, carbohydrate diet. Correspondence: Hrafnkell Stefansson, hrafnkell.stefans@gmail.com.

Diabetic ketoacidosis is characterized by hyperglycemia, anion-gap acidosis, and increased plasma ketones. After the resolution of hyperglycemia, persistent diuresis is rare. We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia. Physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with SGLT2 inhibitors.

Introduction: Diabetic ketoacidosis (DKA) is one of the most serious complications of diabetes. It is characterised by the triad of hyperglycemia (blood sugar >250 mg/dl), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L) and ketosis. Rarely these patients can present with blood glucose (BG) levels of less than 200 mg/dl, which is defined as euglycemic DKA. The possible etiology of euglycemic DKA includes the recent use of insulin, decreased caloric intake, heavy alcohol consumption, chronic liver disease and glycogen storage disorders. DKA in pregnancy has also been reported to present with euglycemia. The recent use of sodium glucose cotransporter 2 (SGLT2) inhibitors has shed light on another possible mechanism of euglycemic DKA. Clinicians may also be misled by the presence of pseudonormoglycemia., Conclusion: Euglycemic DKA thus poses a challenge to physicians, as patients presenting with normal BG levels in ketoacidosis may be overlooked, leading to a delay in appropriate management strategies. In this article, we review all the possible etiologies and the associated pathophysiology of patients presenting with euglycemic DKA. We also discuss the approach to diagnosis and management of such patients. Despite euglycemia, ketoacidosis in diabetic patients remains a medical emergency and must be treated in a quick and appropriate manner., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Vitamin D deficiency (VDD) adversely affects bone health. US data on prevalence of VDD or vitamin D insufficiency (VDI) at diagnosis of type 1 diabetes (T1D) is lacking. Low serum 25-hydroxyvitamin D (25OHD) is speculated to increase the risk of developing T1D., Objectives: Assess the prevalence of pediatric VDD and VDI at diagnosis of T1D, and investigate correlations with demographic and clinical parameters., Methods: We performed a retrospective Institutional Review Board (IRB)-approved chart review of all T1D cases diagnosed from January 2011 to August 2012, all having the same 25OHD assay performed at Quest Diagnostics. Definitions for VDD, VDI, and vitamin D sufficiency (VDS) were 25OHD levels (ng/mL) ≤ 20, 21-29, and ≥ 30, respectively. We termed 25OHD <30 ng/mL as Low-D., Results: We identified 185 autoantibody positive T1D subjects (51% female) with 25OHD measured, 51% Caucasian, 25% Hispanic, 4% mixed-Hispanic, 4% African American, and 16% other/mixed race. Mean age 9.8 yr (0.9-18.6). Most had Low-D (58%), 40% VDI, 18% VDD, and 42% VDS. No gender or age differences among the 25OHD groups. Low-D was more common (p < 0.0001) in Hispanics (81%) vs Caucasians (44%), but VDD rates were similar. Low-D subjects were heavier than VDS (p = 0.018). All four with elevated celiac titers were VDS. Diabetic ketoacidosis was present in 33%, but more common (44%) in Low-D vs. VDS (18%) (p < 0.0001), and trended higher in VDD (61%) vs. VDI (36%). Seventy-seven percentage with DKA had Low-D., Conclusion: VDD and insufficiency are common, even in Caucasians, at onset of T1D in pediatrics, worse in those with DKA., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

Aims/hypothesis: The aim of this study was to assess the risk of death during hospital admission for diabetic ketoacidosis (DKA) and, subsequently, following discharge. In addition, we aimed to characterise the risk factors for multiple presentations with DKA., Methods: We conducted a retrospective cohort study of all DKA admissions between 2007 and 2012 at a university teaching hospital. All patients with type 1 diabetes who were admitted with DKA (628 admissions of 298 individuals) were identified by discharge coding. Clinical, biochemical and mortality data were obtained from electronic patient records and national databases. Follow-up continued until the end of 2014., Results: Compared with patients with a single DKA admission, those with recurrent DKA (more than five episodes) were diagnosed with diabetes at an earlier age (median 14 [interquartile range 9-23] vs 24 [16-34] years, p < 0.001), had higher levels of social deprivation (p = 0.005) and higher HbA1c values (103 [89-108] vs 79 [66-96] mmol/mol; 11.6% [10.3-12.0%] vs 9.4% [8.2-10.9%], p < 0.001), and tended to be younger (25 [22-36] vs 31 [23-42] years, p = 0.079). Antidepressant use was greater in those with recurrent DKA compared with those with a single episode (47.5% vs 12.6%, p = 0.001). The inpatient DKA mortality rate was no greater than 0.16%. A single episode of DKA was associated with a 5.2% risk of death (4.1 [2.8-6.0] years of follow-up) compared with 23.4% in those with recurrent DKA admissions (2.4 [2.0-3.8] years of follow-up) (HR 6.18, p = 0.001)., Conclusions/interpretation: Recurrent DKA is associated with substantial mortality, particularly among young, socially disadvantaged adults with very high HbA1c levels., Competing Interests: Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Duality of interest statement The authors declare that there is no duality of interest associated with this manuscript. Contribution statement FWG and KAL conceived this study with subsequent input from WLT and JG in developing study design and contributing to data collection and analysis. FWG wrote the initial draft of the manuscript with revisions provided from all authors. The final manuscript was approved by all authors. FWG is the guarantor of this work.

Ethnopharmacological Relevance: Life-long insulin is the standard treatment for type 1 diabetes mellitus (T1DM). The role of traditional Chinese medicine (TCM) in T1DM is still not clear. The aim of this study is to explore the prescription pattern of TCM and its impact on the risk of diabetic ketoacidosis (DKA) in patients with T1DM., Materials and Methods: We retrieved samples from the registry for catastrophic illness patients from the National Health Insurance Research Database (NHIRD). Based on a frequency (1:4) matched case-control design, patients with T1DM in 2000-2011 were designated as cases (TCM users) and controls (non-TCM users). TCM treatment for patients with T1DM was analyzed. The incidence of DKA and the annual costs of emergency visits and hospitalizations were evaluated for all causes., Results: Overall, 416 subjects were TCM users, whereas a total of 1608 matched subjects were classified as non-TCM users. The most common Chinese herbal formula and single herb is Liu-wei-di-huang-wan (Six-ingredient pill of Rehmannia) and Huang-qi (Radix Astragali; Astragalus membranaceus (Fisch.) Bunge, Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao), respectively. Compared with non-TCM users, we found a 33% reduction in DKA incidence for all TCM users (aHR 0.67, 95% CI 0.56-0.81, p <0.000) and a 40% reduction for users receiving TCM treatment for more than 180 days (aHR 0.58, 95% CI 0.41-0.82, p <0.01). There were no significant differences between TCM users and non-users in the frequency and medical costs of emergency visits and hospitalizations., Conclusions: Integrative TCM use may reduce the risk of DKA in patients with T1DM. Our results suggest that TCM may have a substantial positive impact on the management of TIDM., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Diabetic ketoacidosis (DKA) is a relatively common endocrine disorder in dogs and is routinely associated with concurrent pancreatic injury., Objectives: The aims of this study were to determine the prevalence of pancreatic injury in dogs with DKA based on measurement of pancreatic lipase immunoreactivity in serum (PLI); compare demographic, clinicopathologic, and ultrasonographic findings in dogs with and without evidence of concurrent pancreatic injury; determine the impact of pancreatic injury on duration of hospitalization and short-term outcome., Animals: One hundred and nineteen dogs with DKA with or without concurrent pancreatic injury., Methods: Retrospective study. Dogs with DKA were divided into three groups on the basis of PLI results: positive for pancreatic injury (PLIpos ), negative for pancreatic injury (PLIneg ), and not tested (PLIna ). Demographics, clinicopathologic test results, findings on abdominal ultrasonography (AUS), duration of hospitalization, and short-term outcome were compared between the three groups., Results: Based on serum PLI activity, 45 dogs (73%) with DKA had evidence of concurrent pancreatic injury. Median total carbon dioxide was significantly lower in the PLIpos dogs compared to the PLIneg dogs. There was fair agreement (κ = 0.26) between serum PLI activity and AUS. Evidence of pancreatic injury was not associated with significantly longer periods of hospitalization (PLIpos median 6 days, range 4-7 days, PLIneg median 4 days, range 3-6 days) and did not influence short-term outcome (PLIpos failure to survive to discharge 11/45, 24%, PLIneg failure to survive to discharge 2/17, 12%)., Clinical Importance: Concurrent pancreatic injury is common in dogs with DKA, but did not affect prognosis in this population of dogs., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Context and Objective: Diabetic ketoacidosis (DKA) is associated with a metabolic alkalosis, which is thought to be due to vomiting. However, alkalosis can occur in DKA without vomiting. We retrospectively reviewed the acid-base disturbances in DKA admissions without vomiting., Participants and Methods: We included admissions of the patients with blood glucose and beta-hydroxybutyrate (βOHB) levels > 250 mg/dL and > 1.0 mmol/L, respectively. Admissions without vomiting were classified into a group with a βOHB > 3.0 mmol/L (DKA group) and a group with βOHB of 1.0-3.0 mmol/L (pre-DKA group). The acid-base status was analyzed by the modified base excess (BE) method. BE effects were calculated by changes in sodium (BE free water, [BEFW]), and chloride (BECl). Positive and negative values for each parameter suggested alkalosis and acidosis, respectively., Results: Forty-five included admissions were divided into DKA (n = 34) and pre-DKA (n =11) groups. Sodium-corrected chloride level and the chloride/sodium ratio were significantly lower in the DKA group than in the pre-DKA group. In both groups, BEFW values were modestly negative. The mean BECl values were positive in both groups, but significantly higher in the DKA group. The alkalinizing effects by hypochloremia diminished the base deficit in the DKA group by approximately 25%. The BECl value significantly correlated with serum total ketone levels (r = 0.66; P < .0001)., Conclusion: The modified BE method successfully proved the presence of hypochloremic alkalosis in DKA without vomiting. This suggests the direct participation of serum ketoacids in the pathogenesis of hypochloremic alkalosis.

Objectives: The pyruvate dehydrogenase complex (PDH) is an essential enzyme in aerobic metabolism. Ketones are known to inhibit PDH activity, but the extent of this inhibition is unknown in patients with diabetic ketoacidosis (DKA)., Methods: We enrolled adult patients presenting to the emergency department in hyperglycemic crisis. Patients were classified as DKA or hyperglycemia without ketoacidosis based on laboratory criteria. Healthy controls were also enrolled. PDH activity and quantity were measured in isolated peripheral blood mononuclear cells. We compared PDH values between groups and measured the relationship of PDH values to measures of acid-base status., Results: Twenty-seven patients (17 with DKA) and 31 controls were enrolled. Patients with DKA had lower PDH activity and quantity compared to the two other groups. PDH activity was significantly correlated with serum bicarbonate and pH and inversely correlated with the anion gap., Conclusions: DKA is associated with greater suppression of PDH activity than hyperglycemia without ketoacidosis, and this is correlated with measures of acid-base status. Future studies may determine whether PDH depression plays a role in the pathophysiology of DKA and whether modification of PDH could decrease time to DKA resolution., (© 2016 by the Society for Academic Emergency Medicine.)

Aim: Procalcitonin (PCT) and C-reactive protein (CRP) are biomarkers of bacterial infection with distinct clinical qualities. This study aimed to determine the occurrence and significance of discrepancies in plasma PCT and CRP levels in hospitalised children., Methods: This was a single centre, retrospective analysis of simultaneous PCT and CRP measurements. Clinical characteristics, microbiological findings and diagnoses were compared between cases in which only PCT or CRP levels were elevated., Results: We studied 635 pairs of PCT and CRP measurements and found discrepancies in 29% of these. In the group with increased PCT and low CRP, there were more children with hypoxia or haemodynamic stress (14 versus 0, p < 0.001) and more bacteraemic patients (eight versus zero, p = 0.001) than in the group with low PCT and increased CRP. The latter group was associated with focal bacterial infections (three versus 18, p = 0.009), inflammatory conditions (one versus 12, p = 0.016) and postoperative setting (one versus 19, p = 0.001). Diabetic ketoacidosis was associated with a marked elevation of PCT., Conclusion: Discrepancies in plasma PCT and CRP levels occurred in 29% of acutely ill children. Both biomarkers can increase in the absence of bacterial infection, but PCT may offer an advantage over CRP in the diagnosis of bacteraemia., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus., Materials and Methods: BR profiles of 3118 female and 2427 male patients from the "Diabetes-Patienten-Verlaufsdokumentation" registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The "variability index" was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate., Results: The variability Index correlated positively with severe hypoglycemia (r = .06; p<0.001), hypoglycemic coma (r = .05; p = 0.002), and microalbuminuria (r = 0.05; p = 0.006). In addition, a higher variability index was associated with higher frequency of diabetic ketoacidosis (r = .04; p = 0.029) in male adult patients. Logistic regression analysis adjusted for age, gender, duration of disease and total basal insulin confirmed significant correlations of the variability index with severe hypoglycemia (β = 0.013; p<0.001) and diabetic ketoacidosis (β = 0.012; p = 0.017)., Conclusions: Basal rate profiles with higher variability are associated with an increased frequency of acute complications in adults with type 1 diabetes.

Objectives: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D., Methods: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes., Results: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function., Conclusions: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.

Background: Diabetic ketoacidosis (DKA) in children is associated with cerebrovascular-related complications. We recently reported that DKA facilitates leukocyte adherence to the brain microvascular endothelium. Adhered leukocytes can release enzymes that instigate vascular dysfunction. Our aims were to measure plasma levels of leukocyte-derived matrix metalloproteinases (MMPs) from DKA patients and to correlate plasma MMP concentrations with DKA severity., Methods: Plasma was obtained from children with type 1 diabetes, either in DKA (n = 16) or insulin controlled (CON; n = 16). Antibody microarray and gelatin zymography were used to quantify plasma MMPs and their endogenous tissue inhibitors (TIMPs). MMP concentrations were correlated with DKA severity (blood pH). Quantitative PCR of leukocyte mRNA was used to help determine the origin of plasma MMPs., Results: DKA was associated with altered plasma levels of ↓MMP-2 (P < 0.001), ↑MMP-8 (P < 0.001), ↑MMP-9 (P < 0.05), and ↑TIMP-4 (P < 0.001), as compared with CON. Elevated MMP-8 and MMP-9 were both positively correlated with DKA severity (P < 0.05). DKA was associated with increased leukocyte mRNA for MMP-8, MMP-9, and TIMP-4 (P < 0.005)., Conclusion: MMPs are dynamically regulated during DKA. Plasma MMP-8 and MMP-9 concentrations correlate with DKA severity and are known to degrade brain microvascular endothelial cell tight junctions. Thus, leukocyte-derived MMPs might contribute to DKA-associated cerebrovascular complications.

Hypokalemia is common during the treatment of diabetic ketoacidosis (DKA); however, severe hypokalemia at presentation prior to insulin treatment is exceedingly uncommon. A previously healthy 8-yr-old female presented with new onset type 1 diabetes mellitus, severe DKA (pH = 6.98), and profound hypokalemia (serum K = 1.3 mmol/L) accompanied by cardiac dysrhythmia. Insulin therapy was delayed for 9 h to allow replenishment of potassium to safe serum levels. Meticulous intensive care management resulted in complete recovery. This case highlights the importance of measuring serum potassium levels prior to initiating insulin therapy in DKA, judicious fluid and electrolyte management, as well as delaying and/or reducing insulin infusion rates in the setting of severe hypokalemia., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have been suggested to predispose to ketoacidosis. Here, we present a case of diabetic ketoacidosis (DKA) developed in an obese, poorly controlled male patient with T2D treated with the SGLT2i dapagliflozin. He was admitted with DKA 5 days after the initiation of treatment with the SGLT2i dapagliflozin. On admission, the primary symptoms were nausea and dizziness, and he was hypertensive (170/103) and tachycardic (119 bpm) and had mild hyperglycaemia (15.3 mmol/l), severe ketonuria and severe metabolic acidosis (pH 7.08). He responded well to infusions of insulin, glucose and saline and was discharged after 72 hr with insulin as the only glucose-lowering therapy. After 1 month, dapagliflozin was reintroduced as add-on to insulin with no recurrent signs of ketoacidosis. During acute illness or other conditions with increased insulin demands in diabetes, SGLT2i may predispose to the formation of ketone bodies and ensuing acidosis., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Initial serum potassium (K+) in diabetic ketoacidosis (DKA) often does not reflect the true amount of total body K+ storage, and it is not a good predictor of subsequent hypokalemia. In this study, we tested the hypothesis that a deficiency of the total body K+ storage can be detected initially on surface electrocardiography (ECG)., Method: Medical records of 350 patients with a diagnosis of DKA were reviewed. Data regarding serial basic metabolic panels, arterial blood gases, serum ketones, and total K+ replacement that patient received during admission were collected. We compared biochemical findings for patients with and without QTU corrected (QTUc) prolongation by using the t test. Patients who were taking medications known to affect QTUc or cause ST-T changes were excluded., Results: After exclusion criteria, 61 patients were enrolled in this study. In 38 patients (62.9%), QTUc was more than or equal to 450 milliseconds. Patients with prolonged QTc received statistically more K+ supplementation during admission (P = .014). They also had lower serum K+ level during their hospital course (P = .002) compared to patients with normal QTUc intervals. No significant difference was found between initial serum K+, calcium, glucose, anion gap, acidosis, age, or heart rate between these 2 groups., Conclusion: The significant relationship between K+ depletion and the ECG changes observed in this study deserves further consideration. Our findings confirm the concept that the ECG is an easy and reliable tool for early diagnosis of hypokalemia in patients with DKA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

Diabetic ketoacidosis (DKA) during pregnancy is a rare but very serious complication that requires early recognition and treatment to prevent severe complications. Here we present three cases in which DKA occurred during normoglycaemia, demonstrating the importance of early recognition. In pregnancy, DKA can occur at lower blood glucose levels than usual due to several pregnancy-related factors, such as altered metabolism, increased insulin resistance, lower buffering capacity related to chronic hyperventilation and hunger. Symptoms that are common during pregnancy, such as vomiting, may be missed as a first sign of DKA. In patients with type 1 diabetes mellitus (especially those on continuous subcutaneous insulin infusion) insulin administration must never be discontinued, as this prevents lipolysis and ketone formation. Physicians and patients need to be aware of the risks and management of DKA in pregnancy.

A recent increase in euglycemic diabetic ketoacidosis (euDKA)-a metabolic state with plasma bicarbonate exceeding 10 mEq/L and blood glucose levels lower than 300 mg/dL-has caught regulators and providers by surprise. It's been more than 40 years since the British Medical Journal expanded the "panorama of diabetic metabolic upsets" with an article on euDKA. Although still rare, the occurrence of euDKA is becoming slightly more common. Unlike the more widely known diabetic ketoacidosis, this condition is devoid of blood glucose elevation. Over two years, the Food and Drug Administration (FDA) Adverse Event Reporting System database linked 73 episodes of euDKA to the use of one of the newest drug classes used in diabetes, the SGLT-2 inhibitors. Subsequently, FDA issued a warning in May 2015 regarding this class of medications. FDA's continued investigation led to a labeling change for this class in December 2015, describing increased risk of euDKA. Health care providers, patients, and caregivers need to increase vigilance, as this seemingly silent complication can be fatal.

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and the novel systemic inflammation marker platelet-to-lymphocyte ratio (PLR) may be associated with clinical outcome in patients with DKA. This study aimed to investigate the utility of PLR in predicting 90-day clinical outcomes in patients with DKA. Patient data exacted from the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was analyzed. A cutoff value for PLR of 267.67 was determined using Youden index (P < 0.05) and used to categorize subjects into a high PLR group and a low PLR group. The hazard ratios (HRs) and 95% confidence intervals (CIs) for DKA were calculated across PLR. Clinical outcomes in our study were defined as intensive care unit (ICU) 90-day readmission and all-cause mortality. A total of 278 ICU admissions were enrolled and stratified by cutoff value of PLR. The incidence of readmission and mortality was 17.8% in the high PLR group, significantly higher than 7.4% in the low PLR group. In the multivariable model, after adjusting for known confounding variables including clinical parameters, comorbidities, laboratory parameters, the HRs for DKA were 2.573 (95% CI 1.239-5.345; P = 0.011), 2.648 (95% CI 1.269-5.527; P = 0.009), and 2.650 (95% CI 1.114-6.306; P = 0.028), respectively. The Kaplan-Meier survival curve showed that a high PLR level was associated with a higher risk for 90-day outcomes in patients with DKA. The authors report that higher PLR presents a higher risk for 90-day incidence of readmission and mortality in patients with DKA. It appears to be a novel independent predictor of 90-day outcomes in critically ill DKA patients in ICU units., Competing Interests: The authors have no conflicts of interest to disclose.

Aim: The aim of this study was to evaluate the incidence of diabetic ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes in 2006-2007 and 2013-2014., Method: The study group consisted of 426 children aged 0-18 years with type 1 diabetes onset admitted to our hospital in 2006-2007 (group A) and 2013-2014 (group B). The study comprised the analysis of medical and laboratory records from patients' medical charts and the electronic database., Results: There was no difference between groups A and B in the percentage of children admitted with diabetic ketoacidosis (25% versus 28%, resp., P = 0.499). Among children with diabetic ketoacidosis, severe metabolic decompensation (pH < 7.1) appeared in similar frequency in groups A and B (28% versus 30%, resp., P = 0.110). In group B, children with diabetic ketoacidosis were statistically younger compared to patients without ketoacidosis (P = 0.015) and had higher HbA1c levels (P = 0.006). In both groups, a 2-fold increase in diabetic ketoacidosis was noted in children under the age of 3, compared to overall frequency., Conclusion: No decrease in diabetic ketoacidosis has been noted in the recent years. Although the prevalence and severity of diabetic ketoacidosis remain stable, they are unacceptably high. The youngest children are especially prone to ketoacidosis.

Objective: To determine if treatment of DKA in a sample of adult medical intensive care unit (MICU) patients was consistent with the 2006 ADA Hyperglycemic Crises in Adult Patients with Diabetes Clinical Guidelines., Methods: Medical records were reviewed for all adult patients admitted to a MICU with a diagnosis of DKA between July 1, 2007 and June 30, 2010. The primary composite endpoint assessed fluid resuscitation (total mL/kg) at 24 hours, insulin bolus dose, and continuous insulin infusion (units/kg or units/kg/hour) to determine whether the 2006 ADA clinical guidelines for Hyperglycemic Crises in Adult Patients with Diabetes were followed. Secondary outcome measures were DKA resolution, ICU length of stay, frequency of rebound DKA within 48 hours, frequency of hypoglycemia, and time to transition to subcutaneous insulin., Results: A total of 60 patients met inclusion criteria. For patients treated in compliance with the clinical guidelines compared to those that were not, total volume IV fluid infused during the first 24 hours (4.88 ± 0.77 mL/kg/hour and 2.74 ± 1.08 mL/kg/hour), mean dose of the insulin bolus (0.13 ± 0.04 units/kg and 0.06 ± 0.06 units/kg) and initial rate of the insulin infusions (0.11 ± 0.02 units/kg/hour and 0.08 ± 0.03 units/kg/hour) were significantly different (p <0.001). Treatment of 12 patients (20%) followed the 2006 ADA clinical guidelines, and mean time to resolution of DKA and MICU length of stay trended toward a shorter duration in these patients., Conclusion: Compliance with the 2006 ADA Hyperglycemic Crises in Adult Patients with Diabetes clinical guidelines was low for treatment of DKA in a sample of adult patients admitted to a MICU. Institutional guidelines for the management of diabetic ketoacidosis should be investigated as a strategy to improve compliance with national guidelines., (Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Type 1 diabetes is an insulin-dependent metabolic disorder always associated with ketoacidosis and a high morbidity rate in teenagers. The in situ single molecule detection of insulin receptors on healthy and diseased erythrocytes is helpful to understand the pathomechanism of type 1 diabetes ketoacidosis (T1-DKA), which would also benefit the diagnosis and treatment of T1-DKA. Here, we demonstrated, for the first time, the single molecule interaction between insulin and insulin receptor on erythrocytes from a healthy volunteer and a T1-DKA patient using high sensitivity atomic force microscopy (AFM) in PBS solution. The single molecule force results demonstrated the decreased binding force and binding probability between insulin and insulin receptor on T1-DKA erythrocytes, implying the deficit of insulin receptor functions in T1-DKA. The binding kinetic parameters calculated from dynamic force spectroscopy indicated that the insulin-insulin receptor complexes on T1-DKA erythrocytes were less stable than those from healthy volunteer. Using high resolution AFM imaging, a decreased roughness was found both in intact T1-DKA erythrocytes and in the purified membrane of T1-DKA erythrocytes, and an increased stiffness was also found in T1-DKA erythrocytes. Moreover, AFM, which was used to investigate the single molecule interactions between insulin-insulin receptor, cell surface ultrastructure and stiffness in healthy and diseased erythrocytes, was expected to develop into a potential nanotool for pathomechanism studies of clinical samples at the nanoscale.

Diabetic ketoacidosis (DKA) frequently causes subtle brain injuries in children. Rarely, these injuries can be severe and life threatening. The physiological processes leading to brain injury during DKA are poorly understood. S100B is a calcium-binding protein secreted by astrocytes. Elevated serum S100B levels are documented in several types of brain injuries. S100B may have either neuroprotective or neurotoxic effects, depending upon the concentration. We undertook the current studies to measure alterations in S100B production and secretion during DKA. We measured serum S100B concentrations in juvenile rats during and after DKA, and used immunohistochemistry to measure S100B expression in the hippocampus, cortex and striatum. Compared to levels in both normal and hyperglycemic control rats, serum S100B levels during DKA were significantly reduced. Serum S100B gradually rose after DKA, returning to levels of hyperglycemic controls by 72 h. S100B expression in the hippocampus was also significantly reduced 24h after DKA. There were no significant changes in S100B expression in other brain regions. Our findings contrast with those for other types of brain injuries in which both serum S100B levels and astrocyte S100B expression are typically elevated. These data suggest that serum S100B measurement cannot be used as an indicator of brain injury during DKA. Whether reduced S100B production or secretion is involved in the pathogenesis of DKA-related brain injury should be investigated., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Sodium glucose Cotransporter-2 (SGLT2) inhibitors are a new class of drug approved for the treatment of type-2 diabetes; however they are also increasingly used off label in type-1 diabetic patients. SGLT2 Inhibitors work by increasing glucose excretion in urine. Euglycemic diabetic ketoacidosis (DKA) is potentially life threatening side effect as patients have normal glucose and minimal symptoms thus delaying diagnosis and treatment. Our case report highlights the risk of using SGLT2 inhibitors in type-1 diabetes and also supports the need for long term studies to define clear efficacy and complications of SGLT 2 inhibitors in both type-1 and type 2 diabetes mellitis.

Unlabelled: The prevalence of type 1 diabetes (T1D) varies greatly between countries. However, over the past several decades, a global rise in the incidence of T1D in the pediatric population has been noted. The aim of our study was to investigate the incidence of T1D in children living in the Lesser Poland during the period of time from January 1, 1987, to December 31, 2012, and to analyze the demographic characteristics and occurrence of diabetic ketoacidosis (DKA) in patients with newly diagnosed T1D in the second part of the study (2006-2012). During 26 years, 636 children (331 boys, 305 girls) aged 0-14 years were newly diagnosed with T1D (0-4 years old, n = 131; 5-9 years old, n = 253, 10-14 years old, n = 252). The standardized incidence ratio (SIR) ranged significantly (p < 0.001) from 5.2/100,000/year in 1987 to 21.9/100,000/year in 2012. The highest SIR was observed in age group 5-9 years old (21.2) and the lowest in 0-4 years old (8.8). There was no association with sex or living in urban or rural area. On admission, DKA was diagnosed in 22.4 % of patients. There were no significant differences relating to the presence of DKA (p = 0.912) in subsequent years., Conclusions: The incidence of T1D among children is increasing rapidly with the highest SIR in the 5-9 years old age group. DKA is still an important problem in the pediatric population., What Is Known: • The incidence of pediatric type 1 diabetes mellitus in Europe is increasing. The initial manifestation of the type 1 diabetes mellitus is diabetic ketoacidosis. What is New: • This is the longest (26 years) continuous analysis of the incidence of type 1 diabetes in Poland and the first analysis focused on the incidence rate and also on presence of diabetic ketoacidosis.

Background: The use of capillary blood 3-β-hydroxybutyrate (3HB) is a more precise method than urine ketones measurement for the diagnosis of diabetic ketoacidosis. Fasting ketonuria is common during normal pregnancy, while there is evidence that it is increased among pregnant women with Gestational Diabetes Mellitus (GDM) who are on a diet. 3HB levels have been related to impaired offspring psychomotor development. Reports with concomitant measurement of blood and urine ketones in women with GDM who followed a balanced diet are lacking., Objective: To compare the prevalence of fasting ketonemia and ketonuria in women with GDM following the Institute of Medicine diet instructions and assess their possible relation with metabolic parameters and therapeutic interventions., Research Design and Methods: 180 women with GDM were studied. In each patient, in successive visits, capillary blood and urine ketones were simultaneously measured. The total measurements were 378, while the average number of measurements per patient was 2.1., Results: The prevalence of ketonuria was significantly higher than that of ketonemia (x(2)=21.33, p &#60;0.001). Significantly higher mean 3HB levels were observed with respect to ketonuria severity (p=0.001). Bedtime carbohydrate intake was associated with significantly lower 3HB levels (p=0.035). Insulin treatment was associated with significant 3HB levels reduction (p=0.032). Body weight reduction per week between two serial visits was associated with increased 3HB levels (p=0.005). Multiple linear regression analysis showed that weight loss remained the only independent predictor of 3HB levels., Conclusions: The presence of ketonemia was significantly lower than the presence of ketonuria. Weight loss per week was the only independent factor found to be associated with increased levels of 3HB. The clinical significance of this small increase requires further investigation.

Aim: Previously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA1c levels., Methods: In the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40 min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables., Results: The maximum plasma glucose level after 200 min of glucose perfusion was 20.9±3.7 mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA1c levels (r=-0.085, P=0.38)., Conclusion: Neither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

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.

Objective: To study the impact of maternal country of birth on type-1-diabetes (T1D) therapy and outcome., Study Design and Methods: 27,643 T1D patients aged ≤20 years with documented maternal country of birth from the multicenter German/Austrian diabetes patient registry (DPV) were analyzed. Patients were categorized based on their mother's origin: Germany/Austria (reference), Turkey, Southern Europe, and Eastern Europe. To compare BMI standard deviation score (BMI-SDS), diabetes therapy and outcome between groups, multivariable regression was applied with adjustments for age, sex and duration of diabetes. Based on observed marginal frequencies, adjusted estimates were calculated. Linear regression was used for continuous data, logistic regression for binary data and Poisson regression for count data. All statistical analyses were performed using SAS 9.4. Significance was set at a two-tailed p<0.05., Results: 83.3% of patients were offspring of native mothers. A Turkish, Southern or Eastern European background was documented in 2.4%, 1.7% and 4.3% of individuals. After demographic adjustment, patients with migration background had a higher mean BMI-SDS (Turkey, Southern Europe or Eastern Europe vs. Germany/Austria: 0.58±0.03, 0.40±0.04, or 0.37±0.02 vs. 0.31±0.01; ±SE) and a lower use of insulin pumps (26.8%, 27.9%, or 32.6% vs. 37.9%) compared to offspring of native mothers. Mean HbA1c was worst in individuals of Turkish mothers (Turkey vs. Germany/Austria: 69.7±0.7 vs. 66.6±0.1 mmol/mol; ±SE). Patients of Eastern European descent had an increased rate of severe hypoglycemia (22.09±0.13 vs. 16.13±0.02 events per 100 patient-years) and ketoacidosis was more prevalent in offspring of Turkish or Southern European mothers (7.50±0.10, or 7.13±0.11 vs. 6.54±0.02 events per 100 patient-years). Patients of Turkish descent were more often hospitalized (57.2±2.7 vs. 48.5±0.4 per 100 patient-years). All differences were significant., Conclusion: The differences in diabetes therapy and outcome among patients with distinct migration background suggest that specific challenges have to be considered in clinical care.

Background: The recommended place for treatment of diabetic ketoacidosis in children is a paediatric High Dependency Unit. This facility is not available in all areas where children with type 1 diabetes mellitus are cared for., Aims: This study investigates the safety and efficacy of diabetic ketoacidosis management in a community general hospital without a paediatric high dependency unit., Methods: Data from children with diabetic ketoacidosis were collected from all diabetes related admissions in Dr Gray's Hospital, Elgin from 2001 to 2010. Observations were compared with safety indicators (pH, bicarbonate, glucose, electrolytes and cerebral oedema) and were reviewed for the recovery to normal values (pH, bicarbonate), without abnormal fluctuation (electrolytes, glucose) and without neurological complications (cerebral oedema)., Results: The 114 patients generated 251 diabetes-related admissions, 118 for diabetic ketoacidosis treatment of whom 99 patients were treated with intravenous fluids and insulin. The mean time to recover to a pH of at least 7.30 was 655 minutes (120-1410 min). There were 79 (4.37% of 1808) glucose readings dropping more than 5.0 mmol/l per hour. There were six hypoglycaemic events (2.3-2.9 mmol/l) and in one case potassium dropped to 2.2 mmol/l. There was no case which developed into cerebral oedema., Conclusion: Treatment of diabetic ketoacidosis in a community general hospital managed with a protocol for fluids, insulin and strict monitoring has shown to be effective in achieving recovery and to safely avoid complications., (© The Author(s) 2015.)

A mathematical model of whole-body acid-base and fluid-electrolyte balance was used to provide information leading to the diagnosis and fluid-therapy treatment in patients with complex acid-base disorders. Given a set of measured laboratory-chemistry values for a patient, a model of their unique, whole-body chemistry was created. This model predicted deficits or excesses in the masses of Na(+), K(+), Cl(-) and H2O as well as the plasma concentration of unknown or unmeasured species, such as ketoacids, in diabetes mellitus. The model further characterized the acid-base disorder by determining the patient's whole-body base excess and quantitatively partitioning it into ten components, each contributing to the overall disorder. The results of this study showed the importance of a complete set of laboratory measurements to obtain sufficient accuracy of the quantitative diagnosis; having only a minimal set, just pH and PCO2, led to a large scatter in the predicted results. A computer module was created that would allow a clinician to achieve this diagnosis at the bedside. This new diagnostic approach should prove to be valuable in the treatment of the critically ill.

Objective: Physical activity (PA) can improve cardiovascular risk in the general population and in patients with type 2 diabetes. Studies also indicate an HbA(1c)-lowering effect in patients with type 2 diabetes. Since reports in patients with type 1 diabetes are scarce, this analysis aimed to investigate whether there is an association between PA and glycemic control or cardiovascular risk in subjects with type 1 diabetes., Research Design and Methods: A total of 18,028 adults (≥18 to <80 years of age) from Germany and Austria with type 1 diabetes from the Diabetes-Patienten-Verlaufsdokumentation (DPV) database were included. Patients were stratified according to their self-reported frequency of PA (PA0, inactive; PA1, one to two times per week; PA2, more than two times per week). Multivariable regression models were applied for glycemic control, diabetes-related comorbidities, and cardiovascular risk factors. Data were adjusted for sex, age, and diabetes duration. P values for trend were given. SAS 9.4 was used for statistical analysis., Results: An inverse association between PA and HbA(1c), diabetic ketoacidosis, BMI, dyslipidemia (all P < 0.0001), and hypertension (P = 0.0150), as well as between PA and retinopathy or microalbuminuria (both P < 0.0001), was present. Severe hypoglycemia (assistance required) did not differ in PA groups (P = 0.8989), whereas severe hypoglycemia with coma was inversely associated with PA (P < 0.0001)., Conclusions: PA seemed to be beneficial with respect to glycemic control, diabetes-related comorbidities, and cardiovascular risk factors without an increase of adverse events. Hence, our data underscore the recommendation for subjects with type 1 diabetes to perform regular PA., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To investigate whether serum bicarbonate (HCO3) levels can be used to accurately diagnose diabetic ketoacidosis (DKA) and classify its severity in children with new-onset diabetes mellitus (NODM)., Methods: Retrospective study of all patients with NODM presenting to Boston Children's Hospital from October 1, 2007, to July 1, 2013. DKA was defined as blood glucose ≥200 mg/dL, venous pH (vpH) <7.3, and urine ketones ≥2+, and severe DKA as vpH <7.1. Linear regression was used to assess serum HCO3 as a predictor of vpH, and logistic regression to evaluate serum HCO3 as a predictor of DKA and severe DKA., Results: Of 690 study cohort subjects (47% girls, age 10.8 ± 4.3 years, 76.7% white), 19.4% presented with DKA. The relationship between serum HCO3 and vpH was log-linear (r = 0.87, 95% CI 0.85-0.89, P < .001). HCO3 predicted vpH (R(2) 0.75, P < .001) using the formula vpH = 6.81301 + (0.17823*ln[HCO3]) and DKA and severe DKA (c-statistic 0.97 [95% CI 0.96-0.99, P < .001] and 0.99 [95% CI 0.991-0.999, P < .001], respectively). HCO3 cutoffs of <18 and <8 mmol/L had sensitivities of 91.8% and 95.2%, and specificities of 91.7% and 96.7%, respectively, to diagnose DKA and severe DKA. Findings were similar in a validation cohort of 197 subjects., Conclusions: Serum HCO3 concentration alone can substitute for vpH to diagnose DKA and classify severity in children with NODM. It is suggested as an alternative to reliance on vpH, especially in settings in which access to vpH measurement is limited., (Copyright © 2015 by the American Academy of Pediatrics.)

Purpose: This practice improvement project was formulated to determine accuracy rate in differentiating between two hyperglycemic crises (diabetes ketoacidosis [DKA] and hyperosmolar hyperglycemic nonketotic syndrome [HHNKS]) in a clinical population of individuals who manifested hyperglycemia and diabetes mellitus (DM). We hypothesized that HHNKS was commonly misdiagnosed as DKA. Our primary aim was to determine frequency of correct HHNKS diagnoses. A second aim was to review the literature and present an evidence-based protocol to assist providers with the differential diagnosis of HHNKS from DKA., Data Sources: Electronic health records (N = 911) were selected by ICD-9 codes for hyperglycemia, DKA, and HHNKS. A retrospective record review indicated n = 436 met the blood glucose level depicting HHNKS. Additional laboratory findings were compared with diagnostic criteria from the literature., Conclusions: HHNKS was commonly misdiagnosed and mismanaged as DKA. Only n = 9 (5%) patients with type 2 DM were correctly diagnosed and managed as having HHNKS. Of the records misdiagnosed with DKA, 74 (39%) actually manifested HHNKS clinical features. Of these, n = 24 (36%) were readmitted within 2 weeks., Implications for Practice: Early recognition of HHNKS is essential for appropriate condition management. HHNKS-specific algorithms are essential for expediting accurate diagnosis, managing appropriately, minimizing mortality, reducing stay length, and avoiding readmissions., (© 2015 American Association of Nurse Practitioners.)