Severe DKA Research Articles

197-OR: Six Months Experience on Hybrid Closed-Loop System in Children and Adolescents Previously Treated with Multiple Daily Injections

Aim: Evaluation of six months experience on MiniMed 670G Hybrid Closed Loop (HCL) system in patients with type 1 diabetes (T1D), previously treated with Multiple Daily Injections (MDI). Methods: This is a 6-months prospective observational study of patients (7 to 18 years) with T1D on MDI, starting the MiniMed 670G system, using a 10-day initiation protocol: 2-days, HCL system assessment; 5-days, HCL system training (2-hours sessions in 5 consecutive days); 3-days, Manual Mode use of HCL system and 6 months, Auto Mode use of the HCL system. Results: MiniMed 670G was initiated in 47 patients (age 12.2±3.2 years). All patients used the system for six months period. Auto Mode usage was 87.2% at the first month and 89.6% at the 6-months of Auto Mode initiation. The mean HbA1c decreased from 8.4±1.5% (68±16.4 mmol/mol) at baseline, 6.7±0.8% (50±8.7 mmol/mol) at 3-months (p=0.021), to 6.9±0.7% (52±7.7 mmol/mol) at 6-months of MiniMed 670G initiation (p=0.024). Time in Range (70-180mg/dL) significantly increased over the time (Figure 1). No severe hypoglycemia nor DKA were found. Conclusion: Children and adolescents with T1D can successfully initiate the HCL system, achieve and maintain better glycemic control than previous MDI regimen. Low attrition rate and the sustainability of the results are likely due to patients’ selection, structured educational program and HCL system by itself. Disclosure G. Petrovski: None. J. Campbell: None. F. AlKhalaf: None. F. Umer: None. K. Hussain: None.

Abstract #810933: Concurrent Venous Thrombosis and Cerebral Edema in an Adolescent With New Onset Diabetes and Severe DKA

Abstract #810933: Concurrent Venous Thrombosis and Cerebral Edema in an Adolescent With New Onset Diabetes and Severe DKA

A case of ischaemic stroke associated with severe DKA

A case of ischaemic stroke associated with severe DKA

Successful management of severe diabetic ketoacidosis in a patient with type 2 diabetes with insulin allergy: a case report

BackgroundDiabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes that requires immediate treatment. Allergic reaction to insulin is rare, especially when using recombinant human insulin. The clinical presentation of insulin allergy can range from minor local symptoms to a severe generalized allergic reaction such as anaphylaxis. A limited number of cases have been reported on the treatment of severe DKA in patients with type 2 diabetes with insulin allergy. Here, we describe a patient with type 2 diabetes with insulin allergy in which severe DKA resolved after the initiation of continuous intravenous (IV) recombinant human insulin infusion.Case presentationA 58-year-old man with type 2 diabetes initiated subcutaneous insulin administration (SIA) after failure of oral antidiabetic treatment. Symptoms of an allergic reaction developed, including pruritic wheals appearing within 10 min of injection and lasting over 24 h. Both skin prick and intradermal tests were positive with different types of insulin. Two days before admission, he stopped SIA because of allergic symptoms and then experienced weakness and upper abdominal pain. On admission, he was in severe metabolic acidosis with a pH of 6.984 and bicarbonate of 2.5 mmol/litre. The blood glucose level was 20.79 mmol/litre, BUN 4.01 mmol/litre, creatinine 128 μmol/litre, and urinary ketone 11.44 mmol/litre. Over 24 h, metabolic acidosis was refractory to IV fluids, bicarbonate and potassium replacement, as well as haemodialysis. Ultimately, he received continuous IV recombinant human insulin infusion at a rate of 0.1 units/kg/hour, in combination with haemodiafiltration, and no further allergic reactions were observed. On day 5, ketonaemia and metabolic acidosis completely resolved. He had transitioned from IV insulin infusion to SIA on day 14. He was discharged on day 21 with SIA treatment. Three months later, he had good glycaemic control but still had allergic symptoms at the insulin injection sites.ConclusionsIn this patient, SIA caused an allergic reaction, in contrast to continuous IV insulin infusion for which allergic symptoms did not appear. Continuous IV recombinant human insulin infusion in combination with haemodiafiltration could be an option for the treatment of severe DKA in patients with diabetes with insulin allergy.

2406-PUB: Characterization of Hypoglycemia following New-Onset Diabetes Mellitus Education

Background: Beginning in January 2017, our institution transitioned new-onset diabetes mellitus education to the ambulatory setting for all children 5 years of age and older. During this transition, our education and practice standards were reviewed and updated. Education historically had been provided during a two-day inpatient hospitalization. With the shift to ambulatory education, teaching was spread out to three separate classes in the first month after diagnosis given that the patients were not under direct supervision. Our primary aim was to prevent hypoglycemia at home, so we introduced new standard insulin doses during the education transition. Glargine doses were reduced to 0.2 units/kg (< 5 years), 0.25 units/kg (5-10 years), and 0.3 units/kg (> 10 years) to minimize hypoglycemia risk while preventing DKA. Due to the lower basal insulin, we lowered insulin sensitivity factors (ISF) to 150 for children under 5 years, 75 for 5-10 years, and 50 for children 11 and older. Corrections were given at meal time to prevent stacking of insulin. Initial carbohydrate ratios remained the same. Methods: We monitored incidence of high-risk events between classes by characterizing the frequency of hypoglycemia less than 70 mg/dL, hypoglycemia less than 50 mg/dL, use of glucagon, and development of ketones/DKA. Results: From 1/3/2017 to 12/31/2018 there were 451 patients diagnosed with diabetes at our center. Hypoglycemia questionnaires were completed by 320/451 (71%) of patients/families 1 week after diagnosis. Hypoglycemic episodes with BG < 70 mg/dL occurred in 41% of patients and BG < 50 mg/dL occurred in 8% of patients. Only 1 patient required glucagon for a severe hypoglycemic episode. While 22% of patients had ketones, no patients developed DKA after initial diagnosis. Conclusions: Conservative dosing with glargine, along with more aggressive carbohydrate and correction dosing at meals is safe and effective in preventing severe hypoglycemia and DKA for patients educated in the ambulatory setting. Disclosure T.S. Musick: None. R. McDonough: None.

1059-P: Glycemic Outcomes from the MiniMed™ 670G System Pivotal Trials in Patients 2-75 Years of Age

Background: The MiniMed™ 670G system is FDA-approved and CE-marked for patients with T1D aged ≥7 years. Glycemic outcomes of patients aged 2-75 years with T1D using the system at home for 3 months were evaluated and compared. Methods: Data from 151 children (n=46, 2-6 years and n=105, 7-13 years) enrolled at 9 sites; and 124 adolescents and adults (n=30, 14-21 years and n=94, 22-75 years) enrolled at 10 sites, during 2-week Manual Mode use (run-in phase) followed by 3-month Auto Mode use (study phase) were analyzed. Glycemic outcomes (HbA1c, time spent at sensor glucose [SG] ranges, SG, and SG variability, etc.) were compared across age groups. Results: Data from run-in and study phases are shown (Table). Across age groups there was a 0.4% to 0.5% decrease in HbA1c and a 5.5% to 8.8% increase in time in range. During the study phases of the pediatric (2-13 years) and older cohort (14-75 years) trials, there were no episodes of severe hypoglycemia or DKA, and no serious device-related adverse events. Conclusions: These findings indicate that 3-month MiniMed™ 670G Auto Mode use in patients as young as two years of age with T1D, similar to older cohorts using the system, can safely improve glycemic outcomes compared to 2-week open-loop Manual Mode. Disclosure T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker's Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc. Consultant; Self; Medtronic MiniMed, Inc., Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. O. Pinhas-Hamiel: None. K.K. Kaiserman: Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Medtronic MiniMed, Inc. Speaker's Bureau; Self; Medtronic MiniMed, Inc. D.R. Liljenquist: None. D.I. Shulman: None. M.A. Wood: None. X. Chen: None. J. Shin: Employee; Self; Medtronic. T.L. Cordero: Employee; Self; Medtronic. S.W. Lee: Employee; Self; Medtronic. F.R. Kaufman: Employee; Self; Medtronic.

MON-128 Pneumomediastinum in Diabetic Ketoacidosis

Background: Pneumomediastinum (PM) is a well recognized but uncommon complication in DKA. Recognizing PM as a mostly benign and self resolving complication of DKA will prevent unnecessary investigations. Clinical case: A 27 year male with history of type 2 diabetes and DKA in the past presented to the emergency with decreased appetite, cramping abdominal pain, vomiting, central chest pain and shortness of breath for three days. He had been non-compliant with his insulin and had not used any for the past week. He was obese with BMI of 31 kg/m2, afebrile, tachycardic HR 121/min, tachypnic RR 23/min, blood pressure was 173/91, spO2 98%, oral mucosa was dry and abdomen was mildly tender.He was found to be in DKA with pH of 6.9, anion gap 23(6-12), bicarbonate 7 mEq/L(22-28), beta-hydroxy-butyrate 100 mmol/L(0.3-0.5), sodium 137 mEq/L(136-145), potassium 6 mEq/L(3.5-5.0), chloride 107 mEq/L (98-106), BUN 17 mmol/L(8-20), creatinine 1.79 mg/dL(0.7-1.3), lipase 153 U/L(<160). DKA was treated with IV fluids, bicarbonate and insulin. Chest xray showed pneumomediastinum which was confirmed with the CT chest. Gastrograffin esophagogram was also done which ruled out esophageal perforation. Serial chest xrays were done which showed resolution of PM in three days.PM complicating DKA is rare, and has been reported mostly in young males taking insulin. Pneumothorax, pneumopericardium, and epidural pneumatosis are other pneumo-complications reported in DKA patients. Vomiting and Kussmaul’s breathing associated with severe DKA can cause alveolar overdistension and barotrauma with subsequent air leakage into the mediastinum. Hamman’s sign is a frequent physical exam finding. A standard chest radiograph (2-view xrays to find small PM) or CT can establish the diagnosis of PM. PM in DKA has a relatively benign course, and treatment is mainly supportive. In situations with high suspicion of esophageal rupture, contrast esophagogram needs to be done, however such incidence is very rare. Conclusion: PM complicating DKA is a rare finding with benign course and excellant prognosis. Patient presents with chest pain or breathlessness, Kussmaul's respirations and profound acidosis. Chest radiography should be ordered to confirm the diagnosis. Resolution follows treatment of DKA. Esophageal perforation is very rare, which can be ruled out with contrast esophagogram in high clinical suspision. Recognizing severe DKA can cause PM will prevent unnecessary investigations. Reference: Makdsi F, Kolade VO. Diabetic ketoacidosis with pneumomediastinum: a case report. Cases J. 2009;2:8095. Steenkamp D, Patel V, Minkin R. A Case of Pneumomediastinum: A Rare Complication of Diabetic Ketoacidosis. Clinical Diabetes Apr 2011, 29 (2) 76-77.

OR14-1 Pharmacodynamics, Safety, Tolerability, and Efficacy of Oral Insulin Formulation (Oshadi Icp) among Young Adults with Type 1 Diabetes: A Summary of Clinical Studies Phases I, Ib, and Ii

Background Replacement of subcutaneous (SC) insulin by oral insulin for Type I diabetes (T1D) could promote patient compliance and minimize hyperinsulinemia. Oshadi Drug Administration Ltd. has developed an oral carrier for proteins delivery, composed of known ingredients, including polysaccharides and nano-silica , and based on quantum theory of biochemical reactions. Objectives To assess the pharmacodynamics of Oshadi oral insulin formulation (Oshadi-I) and the safety, tolerability and glucose-lowering effect of Oshadi oral insulin, proinsulin and c-peptide formulation (Oshadi-Icp) in young patients with T1D. Methods Phase I: a single blinded crossover between Oshadi-I and placebo. Glucose concentration was followed over 13 hours post a single dose. Phase Ib: a crossover open label comparison between 2 sessions of 3 days of Oshadi-Icp or placebo. During both sessions patients stayed at the research unit, provided with identical low carbs diet and minimal doses of SC insulin. Phase II:a prospective 4 weeks open-label follow-up of patients using an insulin pump combined with Oshadi-Icp at home. During Phases Ib and II iinterstitial glucose (IG) was monitored by CGMS, and capillary glucose by finger pricks (CG). Mean IG, mean CG, their area under the curve (AUC), weight adjusted total daily dose (TDD) of SC insulin, BMI, HbA1c, fructosamine, and safety parameters were compared. Results Eight patients, mean age 27.7±4.8 years, 5 males, were included in Phase I study, 10 patients mean age 26.2±4.7 years, 7 males, were included in Phase Ib study, and 16 patients mean age 23.5± 4.6 years, 12 males, were included in Phase II study. Oshadi-Icp was well tolerated, with no adverse events nor clinically relevant changes in vital signs, electrocardiograms, and standard safety laboratory parameters during all study phases. Phase I demonstrated a significantly lower plasma glucose AUC within 7 hours post Oshadi-I compared with placebo: 1116.1mg/dl±107.0 vs. 1345.7mg/dl ±82.0, p <0.01. Phase Ib study demonstrated significantly lower mean post meals GC, AUC-GC and mean insulin TDD at the third day during Oshadi-Icp session compared to placebo: 207.5mg/dl± 6.0 vs. 265.4mg/dl±3.9, p<0.001, 3107.57mg/dl±20.5 vs. 4031.58mg/dl±26.76, p<0.001, 0.14 ±0.04 IU/kg/day vs. 0.18 ±0.06 IU/kg/day, p≤0.01. Four episodes of GC ≤70mg/dL were detected during the Oshadi Icp session and 1 episode of mild DKA was detected during the placebo session. Phase II study demonstrated the ratio of SC insulin dose to carbohydrate intake was significantly lower during Oshasi-Icp month 78-80% for each week compared to baseline 100%. Fructosamine was stable throughout the study, with no episodes of severe hypoglycemia and DKA. Conclusions A substantial safety and glucose lowering effect of Oshadi-Icp formulation were demonstrated. Its clinical potential and beneficial effect for patients with T1D should be further studied.

DKA cases over the last three years: has anything changed?

BackgroundDiabetic ketoacidosis (DKA) has been related mainly to type 1 diabetes mellitus (T1DM). However, it is not solely related to T1DM. The purpose of this study was to assess the prevalence of DKA among type 1 and type 2 patients with diabetes mellitus, who were hospitalized in our Clinic due to DKA, as well as to determine the etiology beyond DKA. Patients and methodsA cohort of 109 patients with DKA, 17–86 years of age, who were hospitalized in the Department of Endocrinology, Diabetes and Metabolism of our hospital between 2015 and 2017, were included in the study. ResultsAmong the 109 patients, 50 (45.9%) had mild DKA, 48 (44.1%) had moderate DKA, whereas 11 patients (10%) had severe DKA. Sixty-five patients (60%) developed DKA as the first manifestation of T1DM, 30 patients (27%) developed DKA in the context of type 2 diabetes (T2DM), mainly due to the co-existence of serious infections, 11 patients (10%) had T1DM, but had omitted their insulin dosages, and 3 patients (3%) developed DKA due to unknown reasons. ConclusionsMost patients with DKA presented with mild and moderate DKA and only a minority presented with the severe form of the disease. The etiology of DKA was mainly T1DM and less frequent uncontrolled T2DM, usually due to the co-existence of severe infections, while only in a tiny minority, the causes remained unidentifiable.

Patient and disease characteristics of adult patients with type 1 diabetes in Germany: an analysis of the DPV and DIVE databases.

Background:An understanding of the current status of patients with type 1 diabetes mellitus (T1DM) can help to provide appropriate treatment.Methods:This was a retrospective analysis of the DIabetes Versorgungs-Evaluation (DIVE) and the Diabetes-Patienten-Verlaufsdokumentation (DPV) databases for Germany.Results:The analysis included 56,250 people with T1DM (54.2% male), a median age of 36.8 years, and a median diabetes duration of 12.4 years. 15.3% were obese (body mass index ≥ 30kg/m2). Long-acting insulin analogs were used by 53.3%, short-acting analogs by 72.1%, and oral antidiabetic drugs by 4.7%. Patients had a median glycosylated hemoglobin (HbA1c) of 7.8%. There was a drop in HbA1c and an increase in the rate of hypertension, oral antidiabetic drug use, and in the rate of severe hypoglycemia (all p < 0.01) with age. Flash glucose monitoring (FGM) showed the best glucose values with fewer complications compared to other monitoring systems. HbA1c and FBG were lower in patients using a pump versus multiple daily injections (MDIs; 7.7 versus 7.9% and 7.8 versus 8.7 mmol/l; all adjusted p < 0.01). Patients had a lower risk of at least one severe hypoglycemic or DKA episode during the most recent treatment year with pump treatment compared to MDI (9.4% versus 10.5% and 4.7% versus 6.1%, both adjusted p < 0.01).Conclusion:The data demonstrated less-than-optimal glycemic control in the young, an increasing metabolic pattern in T1DM with increasing age, a benefit of FGM to improve HbA1c control and adverse effects, as well as benefits of pump treatment over MDIs.

CSII Use in Hospitalized Patients—Adherence to Policy and Safety of Use

Continuous subcutaneous insulin infusion (CSII) therapy is routinely used in diabetes management for patients expecting to use their insulin pumps during hospitalizations. For hospital personnel, this is unfamiliar and complex technology, which necessitates implementing policies and guidelines for standardizing CSII use in the inpatient setting. This study aims to examine adherence to an institutional CSII policy and safety glucometrics for hospitalized patients using CSII. We performed an IRB-exempt retrospective review of CSII user records from January to June 2017. Policy adherence was evaluated for appropriate provider and nurse order set use and documentation in the electronic medical record. 81 patients with 111 admissions on CSII were evaluated. Mean age was 42±16.9 years, 62% were female and 82.7% had type 1 diabetes. Median LOS was 5 days for 788 total patient days, HgbA1c 8.3 ± 1.78, and baseline admission blood glucose (BG) was 175 mg/dL. CSII was continued in 62% of admissions with 12.6% discontinuing use due to medical and surgical contraindications. Overall adherence to the policy was high with documented endocrinology consultations in 100%, provider specified basal rates in 96%, specified bolus doses in 92%, specified correction doses in 83%, specified target BG in 90%, and nurse documented verified doses on the MAR in 93%. Nurse documentation of CSII in the Lines/Drains/Airways flowsheets was 16%. Hypoglycemia (BG&amp;lt;70mg/dL), severe hypoglycemia (BG&amp;lt;40 mg/dL), and uncontrolled hyperglycemia (BG&amp;gt;299mg/dL) were present in 10%, 0.8%, and 10.5% of patient days, respectively. Rates of DKA in CSII users was 0.9%. Policy adherence was effectively achieved for CSII use in hospitals. Rates of hypoglycemia and uncontrolled hyperglycemia were high with very low incidence of severe hypoglycemia or DKA episodes. These results suggest that CSII is possible to safely continue in hospitalized patients, but future studies are necessary to determine how to modify pump rates and optimize glycemic control. Disclosure K. Yang: None. M.B. Ateya: Stock/Shareholder; Self; AbbVie Inc.. R. Gianchandani: None.

Diabetes-Specific Risk Taking—Psychometric Properties of a Measure for Adolescents with Type 1 Diabetes (T1D)

Among people with T1D, adolescents have the poorest adherence and worst glycemic control of any other age group, despite recent advances in treatment and technology. Clinically, adolescents are known to take risks with their diabetes care (e.g., driving without first checking blood glucose), but these risky diabetes behaviors have not been empirically studied. We report psychometric properties of the new 31-item Diabetes-Specific Risk-Taking Inventory (DSRI) for youth 15-18 years old. On the DSRI, youth report the frequency they engaged in 31 diabetes-specific risk-taking behaviors over the past year. We surveyed a national sample of 224 adolescents (participants in the T1Dx registry) (M age=16.4±1.1, 47% female, M A1c=8.3±1.3, 76.8% on insulin pumps) in a cross-sectional design. Participants completed the DSRI as well as measures of adherence, general risk-taking, executive functioning, depressive symptoms, and incidence of severe hypoglycemia and DKA over the past year, using a secure web portal, RedCap. The DSRI demonstrated excellent internal reliability (internal consistency: α=.90; item-total correlations: r range=.21-.64). Construct validity was demonstrated through significant associations (all p&amp;lt;.01) with validated measures: more frequent diabetes-specific risk-taking was related to poorer adherence (r=-.75), greater general risk-taking (r=.57), greater executive dysfunction (r=.34), more depressive symptoms (r=-26), and report of severe hypoglycemia over the past year (r=.22). The DSRI was not associated with DKA. Overall, initial psychometrics suggest the DSRI reliably and validly captures risks that adolescents take with their diabetes care. This self-report measure has the potential to be an innovative and actionable clinical tool that can be used to screen for high risk behaviors that are not routinely assessed in clinical care and inform transition readiness from pediatric to adult care. Disclosure R.M. Wasserman: None. S.R. Patton: None. M.A. Clements: Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Glooko, Inc.. J.H. Finch: None. K. Boschert: None. D.D. Schwartz: None. B. Anderson: Advisory Panel; Self; Sanofi-Aventis.

Reduced Rate of Acute Complications with Tubeless Insulin Pump Use—Data from 2,640 Patients in the German/Austrian DPV Registry

Little is known about the rates of acute complications when switching from MDI or traditional insulin pumps to tubeless insulin pump therapy. The German/Austrian Diabetes patients follow-up-registry (DPV) includes 2691 patients with type 1 (n=2640), type 2 (n=17) and LADA/other (n=34) diabetes types treated for 1.3±1.3 years with a tubeless insulin pump (Omnipod® Insulin Management System, Insulet Corp, Billerica, MA) since 2013. Patients with type 1 diabetes had a mean age of 12.3 year [IQR 9.6-15.0], diabetes duration 2.5 year [0.7-5.9], HbA1c 7.7% [6.8-8.3]. The prior treatment modality was 59.3% MDI, 37.5% other pump and 2.4% tubeless pump as initial therapy (0.3% unknown). Discontinuation of tubeless pump treatment in patients with type 1 diabetes was 7.3% and occurred after 0.7±0.9 mo. Despite the typical age-dependent increase in HbA1c in this primarily adolescent population, the rate of severe hypoglycemia (Level 3), hypoglycemic coma and DKA decreased between 29% to 76% with Omnipod System use compared to the year prior to treatment switch in the total cohort and type 1 patients with 3 year follow-up (n=835) (Table). In conclusion, analysis of the DPV registry shows that use of the Omnipod System has high treatment retention rates in type 1 diabetes and is associated with low rates of severe hypoglycemia and DKA in this age-group prone to acute complications.Three Year Outcomes with Omnipod System UseVariable (mean)Total CohortPatients with 3 yr Follow-upPost-OmnipodPost-OmnipodPre-Omnipod (prior year)1 yr (n=2167)2 yr (n=1351)3 yr (n=848)Pre-Omnipod (prior year)1 yr (n=835)2 yr (n=835)3 yr (n=835)Age, yr13.914.714.414.611.512.413.514.4BMI-SDS0.440.540.560.600.430.500.550.61Insulin dose, U/kg/d0.820.760.790.820.790.770.790.83HbA1c, %7.697.597.857.947.557.497.817.97Severe hypoglycemia (Level 3) patients affected per year, %5.25.54.33.75.77.24.73.6Severe hypoglycemia (coma) patients affected per year, %1.51.41.00.51.71.81.40.4DKA patients affected per year, %5.83.33.02.16.63.63.02.2 Disclosure T. Biester: Speaker's Bureau; Self; Medtronic, Ypsomed AG. T. Danne: Speaker's Bureau; Self; A. Menarini Diagnostics. Advisory Panel; Self; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Dexcom, Inc.. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; DreaMed Diabetes, Ltd.. Research Support; Self; Insulet Corporation. Speaker's Bureau; Self; Menarini Group. E. Bollow: None. A. Schwandt: None. B. Heidtmann: None. B. Rami-Merhar: Speaker's Bureau; Self; A. Menarini Diagnostics, Eli Lilly and Company, Medtronic MiniMed, Inc., Roche Diabetes Care Health and Digital Solutions. T. Haak: Speaker's Bureau; Self; Abbott. Advisory Panel; Self; Roche Diabetes Care Health and Digital Solutions, Sanofi, Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, AstraZeneca. R.W. Holl: None.

Overnight to Early-Morning Glycemic Outcomes in Children Using the MiniMed™ 670G Hybrid Closed-Loop (HCL) System

In-home use of the MiniMed™ 670G system with SmartGuard™ technology for 3 months improved A1C, 24-hour, and overnight (10PM-7AM) glycemia in T1D patients ≥14 years.1 Recently, the system was shown to improve A1C and time in target range (TIR) (&amp;gt;70-180mg/dL, 3.9-10mmol/L) during 24-h and overnight periods in T1D children aged 7-13 years. Effect of the system on insulin delivery and early morning glycemia was also examined. During a 2 week run-in phase in Manual Mode and a 3-month study phase using HCL Auto Mode; 24-hour, 10PM-7AM, and 3AM-7AM insulin delivery (programmed hourly basal rates during Manual Mode, variable basal from 0 units to an individualized daily maximum every 5min during Auto Mode); time in sensor glucose (SG) ranges; and SG SD were examined in 1T1D children (mean±SD age 10.8±1.8 years). The table shows Auto Mode use across periods. Total insulin delivered increased from baseline run-in (1990 patient-days) through study phase (10,602 patient-days); SG, TIR, and SG SD improved. During the study phase, there was no severe hypoglycemia, DKA, or serious device-related AEs. The ability of the MiniMed™ 670G system to automate basal insulin delivery and safely improve 24-hour and overnight glycemic control in children was comparable to that observed in patients 14-75 years, over 3 months. Improved early morning glycemia further indicates that patients ≥7 years can benefit from this HCL therapy. Disclosure G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc.. Research Support; Self; Medtronic, Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Novo Nordisk Inc., Bigfoot Biomedical. D.I. Shulman: Other Relationship; Self; Novo Nordisk Inc.. Research Support; Self; Medtronic MiniMed, Inc.. Board Member; Self; Pediatric Endocrine Society. Research Support; Self; Versartis, Inc. M.A. Wood: Research Support; Self; Medtronic MiniMed, Inc. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. S. Huang: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic. S.W. Lee: Employee; Self; Medtronic. T.L. Cordero: Employee; Self; Medtronic. F.R. Kaufman: Employee; Self; Medtronic.

SGLT2 inhibitor-induced euglycaemic diabetic ketoacidosis may be due to abrupt, severe and transient impaired glucose sensing in susceptible individuals with a hitherto unrecognised beta cell SGLT variant

Euglycaemic diabetic ketoacidosis (EDKA) is a rare complication of treatment with SGLT2 inhibitors in patients with type 2 diabetes. Uncertainty remains about its precise mechanistic basis, but the physiological derangement is acute and profound, yet reversible with cessation of the drug. It is reminiscent of other “non type 1” presentations with DKA such as ketosis prone diabetes, except that glucose levels are usually normal. Impaired beta cell glucose sensing that mimicked a state of hypoglycaemia could theoretically lead to abrupt and transient cessation of insulin secretion. GLUT2 mediates glucose sensing in beta cells. In other tissues such as enterocytes, GLUT2 mediated glucose transport is controlled by SGLT1. Although the affinity of SGLT1 for SGLT2 inhibitors is low, hypothetically a rare variant within the SGLT family with a hitherto unrecognised role in GLUT2 mediated glucose sensing might have an affinity for the SGLT2 inhibitor ligand and thus give rise to acute, severe but reversible euglycaemic DKA in susceptible patients.

Use of telemedicine improves glycemic control and quality of life in type 1 diabetes children on insulin pump therapy

Rationale: Healthcare access plays a significant role in the improvement and maintaining of glycemic control and quality of life in type 1 diabetes mellitus (T1DM) patients on continuous subcutaneous insulin infusion (CSII).&#x0D; Aims: The aim of the study was to evaluate the feasibility of remote support in children and adolescents with type 1 diabetes mellitus (T1DM) and its effect on glycemic control and quality of life.&#x0D; Materials and methods: In 40 children and adolescents (132,7 years, 18/22 m/f) on CSII with inadequately controlled T1DM (HbA1c7,5%) we evaluated the effectiveness of telemedical support (TS), as compared with conventional support (CS). Parameters of glycemic control (HbA1c, average glycemia, SD, etc.) and quality of a life were obtained on follow-up visits. Patients and their parents in ТМ group twice a month sent their insulin pump data using to CSII center and diabetologists sent back their advice via e-mail, phone or Skype. The primary end point was the change from the baseline HbA1c level and the proportion of patients achieving HbA1c of less than 7.5%.&#x0D; Results: At 24 weeks, the baseline mean HbA1c (8.7% in the two study groups) had decreased to 7.7% in the TS group, as compared with 8.4% in the CS group (P0,05). The proportion of patients who reached the HbA1c target (7,5%) was greater in the TS group (50%) than in the CS group (20%, p0,05). A number of quality of life indicators for both parents and children with T1DM at the end of the study compared to baseline significantly increased in the TS group compared with the TC group (p0.05). During the study period rate of severe hypoglycemia and DKA in TS group (0 and 10 cases per 100 person-years) did not differ significantly from that in CS group (0 and 20 cases per 100 person-years, P0,05).&#x0D; Conclusion: In children with inadequately controlled T1DM, telemedical support proved to be feasible and resulted in significant improvement in glucose control (HbA1c, glucose variability) and quality of life without the increase in the incidence of DKA and severe glycemia.

Initial Fluid Therapy in Pediatric Diabetic Ketoacidosis: A comparison of Hypertonic Saline Solution and Normal Saline Solution.

The optimal fluid therapy in children with DKA is a matter of debate, especially if we take into account its association with cerebral edema, the most important complication. Hypertonic Saline Solution is used in the treatment of cerebral edema, and also has been used for volume resuscitation in children with shock. To compare the effects of 3% saline and 0.9% saline solutions on changes in vital parameters, sodium and chloride levels, lactate and pH; time needed for the correction of hyperglycemia; time needed for the control of ketoacidosis and incidence of cerebral edema. Open-label prospective RCT in which 40 children with moderate to severe DKA were randomized to receive either 3% saline or 0.9% saline as initial fluid therapy. There was no significant difference between the two groups in the clinical vital parameters, time for the correction of hyperglycemia and the resolution of acidosis. Patients in the 3% saline group had a higher increase in sodium and chloride from baseline compared to the 0.9% saline group. The acidemia was noted to worsen in both groups after the initiation of fluid therapy, which was not associated with clinical deterioration. The frequency of cerebral edema was similar in both groups. Both 0.9% saline and 3% saline were equally effective as initial fluid in children with DKA with respect to hemodynamic improvement, the resolution of acidosis and the correction of hyperglycemia, but the use of 3% saline solution did not preclude the development of cerebral edema and has the potential to cause hypernatremia, hyperchloremia and hyperchloremic metabolic acidosis.

Clinical Presentation and Biochemical Abnormalities in Patients Presented with Diabetic Ketoacidosis in BIRDEM Hospital

Objective: To see the clinical presentation and biochemical abnormalities in hospitalized patients of Diabetic ketoacidosis.Methodology: This cross sectional observational study was carried enrolling 55 subjects with Diabetic ketoacidosis, in the Department of Medicine, BIRDEM General Hospital, Dhaka, over a period of six months starting from April 2013 to September 2013.Results: The mean age was 48.35±16.76 with age range from 30 to 68 years. Infection (pneumonia, urinary tract infection, cellulitis) 22(40%), omission of insulin or drugs 14 (25.4%), myocardial infarction 5(9.0%), and reduction of insulin dose 3(5.4%) worked as precipitating cause.Most patients had drowsiness 16(29.0%), moderate dehydration 30(55.5%), signs of infection 22(40%). About 13(23.56%) had Kussmaul’s type of respiratory pattern. Other signs were less obvious. Majority of the subjects 40(72.7%) had 3+ ketonuria at the time of admission in hospital. About 32(58.1%) of the known diabetic patients were on insulin from the beginning of their diagnosis.19 (34.4%) were initially on OHA followed by insulin and 14 (25.4%) patients took OHA alone.7 patients were on dietary modification and exercise without any drugs. Majority 52 (96.46%) patients had blood sugar level between 21-34 mmol/l and mean HbA1c was 12.31(SD±2.50).About 4(7.2%) patients had severe hyponatraemia and 22(40%) patients had hypokalaemia. Eight (14.5%) patients had severe acidosis while 18(32.7%) patients had only mild acidosis. Most of the subjects 29(52.7%) had moderate acidosis. Complete cure from DKA was observed in 53(96.3%) subjects. Only 2(3.6%) subjects developed cerebral oedema. It took 4 to 5 days in mild group, 6 to 8 days in moderate DKA and more than 9 days in severe DKA for recovery.Conclusion: From the study result it could be concluded that infection control and regular administration of insulin or control of diabetes and proper Diabetes Self Management Education (DSME) can prevent diabetic ketoacidosis.Bangladesh Crit Care J March 2017; 5(1): 7-10

Striving for control: lessons learned from a successful international Type 1 Diabetes Youth Challenge.

To demonstrate whether young people with T1D using modern insulin treatment and CGM could successfully participate in extreme sport activity while maintaining good glycemic control. The challenge took place in Crete/Greece over 4days combining a long-distance trek of different levels of severity with final destination the summit of the White Mountains at 2080m. Eleven participants (5/6 female/male, age 18.2±1.3years, T1D duration 7.9±3.5years, HbA1c 7.3±.7% (56±16mmol/mol); mean±SD) from 11 SWEET centers in Belgium, Brazil, Canada, Germany, Greece, France, India, Italy, Portugal, Slovenia and Sweden participated to the challenge. Five participants were on CSII, six on MDI; all were wearing a continuous glucose monitoring system. The glycemic targets during trekking were defined as 80-180mg/dl (4.4-10mmol/l). All participants completed the challenge. In total, the group walked 54.5km under varying climate conditions (temperature 14-35°C). During the challenge, insulin requirements decreased significantly compared to baseline: total daily insulin by 31.1±16.7% (p<.001), basal by 30.8±14.9% (p<.001), and prandial by 32.5±28.0% (p=.023), with no differences between participants with CSII or MDI.No episode of severe hypoglycemia or DKA occurred. Mean glucose levels were 170.7±60.1mg/dl with 61.5±18.7% of CGM values in the target range, 5.4±5.4% under 80mg/dl and 32.8±16.6% above 180mg/dl. The results of this SWEET Initiative activity demonstrated that well-educated adolescents and young adults with T1D using modern insulin treatments are able to perform successfully even extraordinary physical challenges while maintaining good glycemic control without diabetes-related acute complications.

Spontaneous Dissemination in Neighboring Provinces of DKA Prevention Campaign Successfully Launched in Nineties in Parma's Province.

Aim: to investigate how much effectiveness of the historical campaign of DKA prevention at T1D diagnosis has survived in Parma’s province where this was launched in Nineties, and how much it has spontaneously spread in the neighboring provinces. Method: children aged 6-14 years with newly diagnosed TID coming from province of Parma (Group 1) and from two other nearby provinces (Group 2) were investigated. Clinical and laboratory data were retrospectively collected from medical files of each patient and included age, gender, capillary pH, serum bicarbonate, 3-beta-hydroxybutyrate (3HB), glycated hemoglobin (HbAlc) at the time of admittance from 1st January 2012 and 31 December 2016. Results: no DKA condition was globally found in 25/36 patients (69.4%): 16/17 and 9/19 patients belonged to Group 1 and 2 respectively (p=0.002). Mild or moderate DKA was reported in 5.9% patients of Group 1 and in 47.31% (p=0.005) patients from Group 2. Severe DKA was observed in only 1 child from Group 2. Normal 3-beta-hydroxybutyrate (3HB) serum levels was reported in the 25 patients without DKA at diabetes diagnosis. Duration of hyperglycemia-related symptoms before overt T1D diagnosis was shorter (4.6±2.5 days) in patients with 3HB levels <1 mmol/dl than in those with 3HB levels exceeding 1 mmol/dl (9.6±4.2 days, p<0.0001). HbA1c values were on overage lower in patients without DKA (9.9±1.2%) than in patients with DKA at diabetes diagnosis (13.60±1.3%; p<0,001). Conclusion: 1) the campaign for DKA prevention, launched in Nineties and renewed at beginning of Twenties in Parma’s province, continues to be effective in the same province after several years; 2) in the two control provinces despite no information campaign being officially promoted in loco, an unexpected decrease in severe DKA incidence as well a shorter latency before overt T1D diagnosis were observed in the same period. (www.actabiomedica.it)