Insulin Infusion Rate Research Articles

Hyperglycemia as an Independent Predictor for Covid-19 Morbidity and Mortality

Background/Aim: A wealth of immunological evidence points out that hyperglycemic status (regardless of diabetes) makes individuals more susceptible to infection as well as higher in-hospital complications. In this study, we primarily aimed to identify the clinical and biochemical negative impacts of hyperglycemia risk factor across the two comparative cohorts. Secondly, we also explored the prognosticating utilities of three proposed BG related prognosticators in moderate-severe admitted SARS-CoV-2 infected patients. Methods: This study was retrospectively between Mar 2020 and Sep 2021. All retrievable and calculated variables were thereafter divided into two studied cohorts, Survivors Cohort (Cohort I) and Non-Survivors Cohort (Cohort II). Independent and One-Sample T-Tests and Chi-Square Test were used for comparative analysis and relative risk estimation. The Receiver operating characteristic analysis was used to explore the area under the curve and the sensitivity analysis was also performed to investigate the optimal cutoff values for the BG related prognosticators. Results: The mean age of the whole study cohort was 59.40±10.60 years, and the Non-Survivors Cohort were insignificantly younger than the Survivors Cohort. Survivors Cohort had insignificantly higher average blood glucose level than Non-Survivors Cohort. Oppositely, Survivors Cohort had significantly lower average total daily insulin dosing compared to Non-Survivors Cohort. The overall hospital length of stay (LOS) which it was significantly lower in Non-Survivors Cohort compared to Survivors Cohort. Conclusion: As there were many cconcerns for the effect of hyperglycemia on immune cells and subsequently the overall clinical impacts, there is an urgent necessity to track the daily blood glucose levels, the changes in blood glucose from baseline, or alternatively the insulin infusion rate to keep their averages around 149.9 mg/dl, -38%, and 1.35 IU/hr.

The management of diabetic ketoacidosis in adults-An updated guideline from the Joint British Diabetes Society for Inpatient Care.

This article summarises the Joint British Diabetes Societies for Inpatient Care guidelines on the management of ketoacidosis; available at https://abcd.care/resource/management-diabetic-ketoacidosis-dka-adults. The document explicitly states that when a person aged 16-18 is under the care of the paediatric team, then the paediatric guideline should be used, and if they are cared for by an adult team, then this guideline should be used. The guideline takes into account new evidence on the use of the previous version of this document, particularly the high prevalence of hypoglycaemia and hypokalaemia, and recommends that when the glucose concentration drops below 14mmol/L, that de-escalating the insulin infusion rate from 0.1 to 0.05units/kg/h should be considered. Furthermore, a section has been added to address the recognition that use of sodium glucose co-transporter 2 inhibitors is associated with an increased risk of euglycaemic ketoacidosis. The management of ketoacidosis in people with end-stage renal failure or on dialysis is also mentioned. Finally, the algorithms to illustrate the guideline have been updated.

Safety and Efficacy of Various Intravenous Insulin Infusion Rates in Patients With and Without Diabetes Presenting With Hypertriglyceridemia.

The use of IV insulin infusions in the acute management of hypertriglyceridemia has only been evaluated in small observational studies and case reports. To evaluate the safety and efficacy of IV insulin infusions in the acute management of hypertriglyceridemia. This was a retrospective chart review of adult patients who received an IV insulin infusion for the acute management of hypertriglyceridemia. The primary efficacy and safety outcomes were the number of patients who achieved a triglyceride level <500 mg/dL and experienced hypoglycemia (<70 mg/dL), respectively. A subgroup analysis was performed to compare outcomes between patients with and without diabetes, in addition to the IV insulin infusion rate received. In the total population (n = 51), there were no statistically significant differences between the insulin intensity groups in the number of patients who achieved TG levels <500 mg/dL. Compared to patients with a past medical history of diabetes, more patients without a past medical history of diabetes achieved triglyceride levels <500 mg/dL (14% vs 53%, respectively, P < 0.001). The number of hypoglycemic events observed in patients with and without a past medical history of diabetes were 5 (14%) and 4 (27%), respectively (P = 0.023). Our findings suggest that patients who present with lower initial TG levels are more likely to achieve TG levels <500 mg/dL. To minimize the risk of hypoglycemia providers should consider prescribing a concomitant dextrose infusion and limiting IV insulin infusion rates ≤ 0.075 units/kg/h.

Evaluation of Insulin Infusion Rates for the Treatment of Diabetic Ketoacidosis in the Emergency Department.

Introduction:There is minimal literature to support the appropriate dosing for the initiation of IV regular insulin therapy in DKA patients. A 0.1 unit/kg bolus followed by 0.1 units/kg/hour or 0.14 units/kg/hour is commonly utilized and recommended in guidelines.Objective:We sought to assess clinical and safety outcomes associated with various insulin infusion starting doses in patients diagnosed with DKA in the emergency department in an effort to help guide prescribing.Methods:A retrospective cohort study was conducted within an academic emergency department and included patients who received continuous infusion regular insulin with an ICD-10 code for DKA between January 2016 and January 2019. A predictive regression model was applied to test if predefined lab values influenced the starting insulin infusion rates. Clinical and safety outcomes were evaluated by starting insulin infusion rate. Data was analyzed based on starting insulin infusion rates.Results:347 patients met inclusion criteria with 92 (26.5%) patients receiving <0.07 units/kg/hr, 123 (35.4%) patients receiving 0.07 to 0.099 units/kg/hr, 123 (35.4%) patients receiving 0.10 to 0.139 units/kg/hr, and 9 (2.6%) patients receiving ≥0.14 units/kg/hr. After adjusting for baseline labs, glucose was the only significant predictor of the initial infusion rate (p < 0.001). For every 100 mg/dL increase in the baseline glucose value, the initial infusion rate increased by 0.005 units/kg/hr. There was no difference between insulin starting infusion rates and length of stay, rates of hypoglycemia, hypokalemia, or dysrhythmias.Conclusion:Glucose levels significantly influenced the insulin starting infusion rate, with no identified differences in adverse effects or clinical outcomes.

Managing hyperglycaemia during antenatal steroid administration, labour and birth in pregnant women with diabetes - an updated guideline from the Joint British Diabetes Society for Inpatient Care.

This article summarises the Joint British Diabetes Societies for Inpatient Care guidelines on the management of glycaemia in pregnant women with diabetes on obstetric wards and delivery units, Joint British Diabetes Societies (JBDS) for Inpatient Care Group, ABCD (Diabetes Care) Ltd. The updated guideline offers two approaches - the traditional approach with tight glycaemic targets (4.0-7.0mmol/L) and an updated pragmatic approach (5.0-8.0mmol/L) to reduce the risk of maternal hypoglycaemia whilst maintaining safe glycaemia. This is particularly relevant for women with type 1 diabetes who are increasingly using Continuous Glucose Monitoring (CGM) and Continuous Subcutaneous Insulin Infusion (CSII) during pregnancy. All women with diabetes should have a documented delivery plan agreed during antenatal clinic appointments. Hyperglycaemia following steroid administration can be managed either by increasing basal and prandial insulin doses, typically by 50% to 80%, or by adding a variable rate of intravenous insulin infusion (VRIII). Glucose levels, either capillary blood glucose or CGM glucose levels, should be measured at least hourly from the onset of established labour, artificial rupture of membranes or admission for elective caesarean section. If intrapartum glucose levels are higher than 7.0 or 8.0mmol/L on two consecutive occasions, VRIII is recommended. Hourly capillary blood glucose rather than CGM glucose measurements should be used to adjust VRIII. The recommended substrate fluid to be administered alongside a VRIII is 0.9% sodium chloride solution with 5% glucose and 0.15% potassium chloride (KCl) (20mmol/L) or 0.3% KCl (40mmol/L) at 50ml/hr. Both the VRIII and CSII rates should be reduced by at least 50% after delivery.

The choice of the insulin basal rate regimen at initiation of insulin pump therapy in routine clinical practice

Background: Numbers of patients with diabetes mellitus using insulin pumps have been increasing every year. Successful achievement of glycemic targets with continuous subcutaneous insulin infusion (CSII) is based on an adequate basal rate of infusion, carbohydrate coefficient and insulin sensitivity index. There are two approaches to basal insulin infusion rate, namely the flat one and the circadian; however, at present there is no convincing data on which one should be chosen at the start of insulin pump therapy.Aim: To compare two regimens of basal insulin infusion rate at initiation of insulin pump therapy in routine clinical practice.Materials and methods: We analyzed data from 120 patients with Type 1 diabetes mellitus, who were switched on insulin pump therapy in the Department of Endocrinology from 2017 to 2018. At initiation of CSII, 60 patients used the flat basal rate profile and the other 60 patients used the circadian basal rate, calculated with the Renner's scale. Safety of the two basal rate regimens was assessed based on glucose variability measured with continuous glucose monitoring during the first two days after the start of insulin pump therapy.Results: Mean (± SD) coefficients of variation in the groups with circadian and flat basal rate at Day 1 were 31.06±12.13 and 32.74±10.7, respectively (p=0.423); at Day 2, 26.78±11.27 and 28.83±10.7 (p=0.309). Median [Q1; Q3] areas under glucose curve (AUC) values above the glucose targets in the groups with circadian and flat basal rate at Day 1 were 0.37 [0.03; 0.89] and 0.48 [0.08; 1.75], respectively, at Day 2 0.44 [0.03; 1.57] and 0.31 [0.1; 1.5], respectively (p&gt;0.05). Median glucose AUC values below the goal in groups with circadian basal rate and flat basal rate on the first day were 0.01 [0; 0.06] and 0.02 [0; 0.1], respectively (p=0.855), on the second day – 0.00 [0; 0.01] and 0.00 [0; 0.02], respectively (р=0.085). We also haven’t found any between-group differences in the prevalence of glucose deviations below and above the target, as well as in the time spent in normoglycaemia.Conclusion: The comparative analysis of two basal insulin rate regimens in Type 1 diabetic patients switched to insulin pump therapy has shown no significant differences between them. The use of Renner’s scale has no clinical advantages over the fixed basal insulin regimen at initiation of insulin pump therapy in adults.

Comparison of Adult Diabetic Ketoacidosis Treatment Protocols From Canadian Emergency Departments

BackgroundDiabetic ketoacidosis (DKA) is a common acute life-threatening complication of poorly controlled diabetes mellitus contributing to considerable mortality and morbidity. Use of standardized treatment protocols improves patient outcomes in the emergency department (ED) for many conditions, but variability in adult DKA treatment protocols has not been assessed across EDs. In this study, we compared DKA treatment protocols from adult EDs across Canada to highlight inconsistencies in recommended DKA management. MethodsED staff in Canada were solicited for their treatment protocols used to guide acute ED DKA management. Information regarding initial fluid resuscitation and maintenance fluid, potassium replacement, insulin therapy and bicarbonate administration was abstracted from each protocol, collated in a table and compared. ResultsThirty-six unique protocols were obtained representing 85 institutions (40 urban and 45 rural, with a 65.1% response rate) across Canada, with no protocol use for 4 urban centres. Similarities in protocols included the intravenous insulin infusion rate and instructions for switching to subcutaneous insulin. Variability was noted in the rate, amount and type of fluid bolus given (0.5 to 2 L of normal saline or Ringer’s lactate over 15 minutes to 2 hours), the criteria determining the amount, potassium supplementation at normo/hypokalemic ranges, when to add dextrose to maintenance fluid, insulin bolus inclusion and bicarbonate administration. ConclusionsThis is the first comparison of adult DKA treatment protocols in Canada. Although several common approaches were identified, variability was found in initial fluid boluses, initial insulin bolus and role of bicarbonate, necessitating further study to ensure local DKA protocols reflect current evidence-based best practices for optimal patient clinical outcomes.

EP.TU.200Improving variable rate insulin infusion compliance in general surgery

Abstract Aims 1. Audit the current variable rate insulin infusion (VRII) practice per local guidelines. 2. Understand barriers to good VRII practice to create an intervention. 3. Re-Audit the VRII practice following intervention. Methods Junior doctors were surveyed using Likert scales (1 to 5: not at all confident to very confident) as well as closed and open questions. Chain action reaction (CAR) theory was used. Six domains were identified against a local proforma. Initial audit and questionnaire were collected from November 2019 to January 2020 and analysed using Microsoft Excel. Intervention consisted of a condensed one-page algorithm with group teaching. Re-audit data was collected between June 2020 to August 2020 for comparison. Results Questionnaire – 53.6% (15/28) of juniors responded. Challenges included conversion oral hypoglycaemics and complexity of the guidance. Group teaching and a condensed portable format were the most popular modalities for delivery of further education. Initial Audit – 12 VRII charts were audited. 33.3% (4/12) were completed correctly. Areas of significant need for improvement were as follows: ensuring long-acting insulin is prescribed, transferring from a VRII back to oral medications and appropriate fluid prescribing. Re-Audit – 18 charts were audited following intervention. Of these, 66.7% (12/18) were completed correctly. There was a significant improvement in appropriate fluid prescribing and long-acting insulin prescriptions. Conclusions Understanding the factors involved throughout the chain of how VRIIs are prescribed has helped to implement a positive intervention in our department. The improvement has been significant (100% better) however there is still further work required to improve compliance.

An independent central point OPTICS clustering algorithm for semi-supervised outlier detection of continuous glucose measurements

Continuous glucose monitoring (CGM) collects a host of time-series sensor data and is committed to fully automated systems for glucose control as an essential part. Outlier data in CGM measurements caused by faults may seriously affect the computation of insulin infusion rates and endanger the safety of patients. In this paper, a semi-supervised outlier detection method is proposed for anomaly detection of glucose concentration measurements based on a density-based clustering algorithm, named independent central point OPTICS (ICP-OPTICS). An optimization function is designed to improve the clustering performance and solve the problem of outlier detection with the distance measurement and information entropy of weighted time series. The proposed method in the application can be configured automatically with no prior knowledge except only some clean samples. The UVa/Padova simulator and real dataset are used to evaluate the performance of the method. Compared with the present work, the statistical results show that the method is much better in effectiveness and superiority. Furthermore, the proposed method also provides a possible reference significance for outlier detection in other practice applications.

A CASE OF RECURRENT PANCREATITIS DUE TO HYPERTRIGLYCERIDEMIA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypertriglyceridemia (HTG) accounts for 10% of all cases of acute pancreatitis (AP). It can present as acute or recurrent episodes of AP typically in the presence of coexistent conditions, such as inadequately controlled diabetes (DM), excess alcohol consumption or medication use. We present a case of recurrent pancreatitis in a patient with history of HTG and non-compliance with medication. CASE PRESENTATION: A 39-years-old female with history of HTG, DM and alcohol dependance disorder presented to the ED with 1-day history of severe epigastric pain radiating to her back, associated with nausea and non-bilious vomiting. On examination she was hemodynamically stable. There was marked tenderness to palpation in the epigastric region. Her initial laboratory findings were significant for fasting serum glucose (FSG) of 323 mg/dL, severe hyponatremia 118mEq/L, Calc Osmolality 249mOsm/L, total cholesterol 794 mg/dL and triglycerides 6088 mg /dl. Computed tomogram of the abdomen showed moderate fluid and diffuse peripancreatic inflammatory stranding. The patient was managed for AP with intravenous fluids (IV D5-NS), fixed rate insulin infusion and narcotics for pain control. She was also commenced on Atorvastatin 40mg and Gemfibrozil 600mg, twice daily. Once the patient's condition stabilized, she was discharged with subcutaneous insulin, Metformin and lipid lowering agents. DISCUSSION: Hypertriglyceridemia is a rare but well-known cause of acute pancreatitis. Although the precise mechanism is not known, it is proposed that HTG causes an excess of free fatty acids (FFAs) and elevated chylomicrons leading to rise in plasma viscosity, which may induce ischemia in pancreatic tissue and trigger organ inflammation.[1] The clinical presentation includes epigastric pain, increased serum levels of pancreatic enzymes and typical AP findings on imaging.[2] Serum triglyceride levels rapidly decrease within the first 48 hours of onset of acute AP, therefore earliest possible determination of serum triglyceride levels is crucial [3].Multiple treatment modalities including Insulin and/or heparin, plasmapheresis and oral lipid lowering agents have been evaluated. Fibrates have been proven effective in lowering triglyceride levels and raising HDL levels, and are generally considered to be first-choice drugs for the treatment of HTG [4,5]. Our patient showed good response to treatment with Insulin infusion and fibrates. She refused plasmapheresis trial. CONCLUSIONS: We suggest routine testing of triglyceride levels in patients presenting with signs and symptoms suggestive of acute pancreatitis especially in those with pre-existing medical co-morbidities. REFERENCE #1: 1.Nicolò de Pretis, Antonio Amodio, Luca Frulloni Hypertriglyceridemic pancreatitis: Epidemiology, pathophysiology and clinical managementUnited European Gastroenterol J. 2018 Jun; 6(5): 649–655. REFERENCE #2: 2. Scherer J, Singh VP, Pitchumoni CS, Yadav D Issues in hypertriglyceridemic pancreatitis: an update.J Clin Gastroenterol. 2014 Mar; 48(3):195-203. REFERENCE #3: 3. Maki KC, Bays HE, Dicklin MR. Treatment options for the management of hypertriglyceridemia: strategies based on the best-available evidence. J. Clin. Lipidol. 6(5), 413–426 (2012) DISCLOSURES: no disclosure on file for Moses Bachan; no disclosure on file for Zinobia Khan; No relevant relationships by Dileep Kumar, source=Web Response No relevant relationships by Ambreen Shahzadi, source=Web Response

An efficient nonlinear explicit model predictive control to regulate blood glucose in type-1 diabetic patient under parametric uncertainties

With the aim of regulating plasma glucose level in a type-1 diabetic patient, a nonlinear explicit model predictive control (NEMPC) is developed. The computational complexity in analytical method due to iterative process can be avoided by NEMPC. The amplitude of control signal defines the exogenous insulin infusion rate. Therefore, it should be taken a special care such that physiological needs can be satisfied. The control signal is also minimized to avoid physical hazard due to oscillation. The cost of actuator is also minimized as small size actuator can care the control signal generated by the proposed method. Thus, a cost effective control scheme is suggested by using nonlinear EMPC to regulate blood glucose level in type-1 diabetic patient. Different types of cases with nominal parameters, uncertainties in parameter and disturbances, uncertainties in states of initial condition are examined using the proposed method. The robustness of the proposed control logic is also checked with control variability analysis. Different risk factor of hyperglycemia and hypoglycemia is also verified. The simulation results shows the effectiveness of proposed control scheme for regulating glucose concentration in type-1 diabetic patients. An improvement of settling the glucose level from hyperglycemia to basal level within 120 min avoiding chance of hypoglycemia shows the effectiveness of proposed method than existing one.

Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes.

Background: Decreased insulin clearance could be a relatively upstream abnormality in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Previous studies have shown that sodium-glucose cotransporter 2 inhibitor (SGLT2i) increases insulin–C-peptide ratio, a marker of insulin clearance, and improves metabolic parameters. We evaluated the effects of the SGLT2i tofogliflozin on metabolic clearance rate of insulin (MCRI) with a hyperinsulinemic euglycemic clamp study, the gold standard for measuring systemic insulin clearance. Methods: Study participants were 12 Japanese men with type 2 diabetes. We evaluated MCRI and tissue-specific insulin sensitivity with a hyperinsulinemic euglycemic clamp (insulin infusion rate, 40 mU/m2·min) before and immediately after a single dose (n = 12) and 8 weeks (n = 9) of tofogliflozin. We also measured ectopic fat in muscle and liver and the abdominal fat area using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively, before and after 8 weeks of tofogliflozin. Results: MCRI did not change after a single dose of tofogliflozin (594.7 ± 67.7 mL/min·m2 and 608.3 ± 90.9 mL/min·m2, p = 0.61) or after 8 weeks (582.5 ± 67.3 mL/min·m2 and 602.3 ± 67.0 mL/min·m2, p = 0.41). The 8-week treatment significantly improved glycated hemoglobin and decreased body weight (1.7%) and the subcutaneous fat area (6.4%), whereas insulin sensitivity and ectopic fat in muscle and liver did not change significantly. Conclusions: MCRI did not change after a single dose or 8 weeks of tofogliflozin. Increased MCRI does not precede a decrease in body fat or improved glycemic control.

Study of blood glucose and insulin infusion rate in real-time in diabetic rats using an artificial pancreas system.

Artificial pancreas system (APS) is an emerging new treatment for type 1 diabetes mellitus. The aim of this study was to develop a rat APS as a research tool and demonstrate its application. We established a rat APS using Medtronic Minimed Pump 722, Medtronic Enlite sensor, and the open artificial pancreas system as a controller. We tested different dilutions of Humalog (100 units/ml) in saline ranged from 1:3 to 1:20 and determined that 1:7 dilution works well for rats with ~500g bodyweight. Blood glucose levels (BGL) of diabetic rats fed with chow diet (58% carbohydrate) whose BGL was managed by the closed-loop APS for the total duration of 207h were in euglycemic range (70-180 mg/dl) for 94.5% of the time with 2.1% and 3.4% for hyperglycemia (>180mg/dl) and hypoglycemia (<70 mg/dl), respectively. Diabetic rats fed with Sucrose pellets (94.8% carbohydrate) for the experimental duration of 175h were in euglycemic range for 61% of the time with 35% and 4% for hyperglycemia and hypoglycemia, respectively. Heathy rats fed with chow diet showed almost a straight line of BGL ~ 95 mg/dl (average 94.8 mg/dl) during the entire experimental period (281h), which was minimally altered by food intake. In the healthy rats, feeding sucrose pellets caused greater range of BGL in high and low levels but still within euglycemic range (99.9%). Next, to study how healthy and diabetic rats handle supra-physiological concentrations of glucose, we intraperitoneally injected various amounts of 50% dextrose (2, 3, 4g/kg) and monitored BGL. Duration of hyperglycemia after injection of 50% dextrose at all three different concentrations was significantly greater for healthy rats than diabetic rats, suggesting that insulin infusion by APS was superior in reducing BGL as compared to natural insulin released from pancreatic β-cells. Ex vivo studies showed that islets isolated from diabetic rats were almost completely devoid of pancreatic β-cells but with intact α-cells as expected. Lipid droplet deposition in the liver of diabetic rats was significantly lower with higher levels of triacylglyceride in the blood as compared to those of healthy rats, suggesting lipid metabolism was altered in diabetic rats. However, glycogen storage in the liver determined by Periodic acid-Schiff staining was not altered in diabetic rats as compared to healthy rats. A rat APS may be used as a powerful tool not only to study alterations of glucose and insulin homeostasis in real-time caused by diet, exercise, hormones, or antidiabetic agents, but also to test mathematical and engineering models of blood glucose prediction or new algorithms for closed-loop APS.

Extreme High Insulin Requirements in Two Non-Diabetic Patients Following Cardiac Transplantation

Introduction: Blood glucose (BG) management is challenging following cardiac transplantation (CT) due to insulin resistance (IR) induced by post-operative stress and inflammation, intravenous pressors, and high-dose steroids. Severe IR manifested by extreme insulin requirements is rare. We report 2 such patients without prior history of diabetes (DM) requiring massive doses of IV insulin in the immediate post-op period. Patient 1: A 59 y/o male with hypertrophic cardiomyopathy (CM) presented with symptoms of acute decompensated heart failure and ultimately underwent orthotopic CT. At baseline, HbA1c was 5.8% and BMI 23 kg/m2. Exam was significant for acanthosis nigricans. He received 1g IV methylprednisolone (MP) during surgery and 125 mg IV Q 8 hours subsequently. His blood glucose (BG) immediately post-op was 312 mg/dL and was started on IV insulin. Despite doses up to 93 U/hr, BG remained >300mg/dl. With steroid taper, insulin requirements declined rapidly. He was transitioned to small dose of insulin glargine and was discharged on metformin monotherapy with near-normal BGs. Patient 2: 49 y/o male with a genetic CM was admitted for elective orthotopic CT. At baseline, HbA1c was 5.8% and BMI 32 kg/m2. Exam was significant for central obesity. He received similar doses of IV MP as patient 1 but also required inotropes (dobutamine, epinephrine, milrinone mixed in 5% dextrose containing fluids.) His BG immediately post-op was 284 mg/dL and was started on IV insulin. Despite doses up to 85 U/hr, BG remained >250 mg/dl. With steroid taper, insulin requirements resolved rapidly and he was discharged with normal BGs off all DM agents. Pseudo insulin resistance (i.e. line occlusion or erroneous IV insulin solution concentration) was excluded in both cases. Conclusion: Although many patients require high insulin doses after CT, rarely are infusion rates as high as in our patients achieved, particularly in non-diabetic individuals. We propose that it was the combination of underlying IR/prediabetes, counter-regulatory hormones, proinflammatory cytokines, increased lipolysis, with exogenous steroids and catecholamine-based inotropic agents that resulted in extreme inhibition of insulin action. However, because this combination of factors is not necessarily rare in post-CT patients, other factors must have been at play and will remain to be elucidated. From a pragmatic standpoint, because of rapid decrease in BG levels as steroids were tapered, we recommend very close follow-up of such patients with rapid decreases in insulin infusion rates as necessitated by trends in prevailing glycemia to prevent hypoglycemia. It would also be helpful to target a slightly higher glucose goal in such patients to prevent subsequent hypoglycemia.

Intravenous Insulin Resistance in a Critically Ill Patient Secondary to Decreased Peripheral Perfusion

Introduction: Intravenous (IV) insulin infusion is the preferred treatment modality for hyperglycemia in the intensive care unit (ICU) due to its short duration of action and easy titratability. However, administration of IV insulin has challenges. These include frequent monitoring, site infiltration, and high insulin dose requirements with other ICU medications such as epinephrine. There are, however, limited reports demonstrating an elevated insulin requirement due to poor peripheral perfusion. Below illustrates such a case, necessitating a change from peripheral to central IV insulin administration. Case Presentation: A 50 year old male with well controlled type 2 diabetes and previous aortic valve replacement presented to our facility for prosthetic valve endocarditis complicated by aortic root abscess. He was admitted to the ICU, treated with IV antibiotics, abscess washout and aortic valve replacement. Preoperatively, he was started on IV regular insulin via continuous infusion through a central line. During the pre and intraoperative periods, his hourly IV insulin requirement ranged from 2.4 to 5 units/ hour (hr). His blood glucose (BG) ranged from 107-251mg/dL (n 70-99mg/dL). The patient became hypotensive intraoperatively requiring vasopressor support. Dobutamine and norepinephrine infusions were started via central access and were continued postoperatively at steady rates. Vasopressin was added through central access as the patient failed to meet hemodynamic targets. Postoperatively, the propofol infusion was discontinued and the IV regular insulin infusion was moved to the peripheral line where the propofol had previously been administered. BG increased steadily to a maximum of 402 mg/dL despite an increase in the peripheral IV insulin rate to 152.4 units/hr. The site of the IV insulin drip was changed to another solitary peripheral access without success in decreasing the IV insulin infusion rate. The elevated requirements were deemed secondary to the patient’s lack of peripheral perfusion and should decrease with transition to a central line. A preemptive decrease in insulin drip rate to 10% of the peripheral dose was used to avoid hypoglycemia. The insulin drip was changed to a central access with a rate of 15units/ hr. BG values declined to a range of 140 -180 mg/dL. The patient remained on the multiple vasopressors for hemodynamic support, however, the insulin drip was able to be decreased and ultimately, discontinued. Conclusion: This case illustrates a unique challenge in the treatment of hyperglycemia with multifactorial shock and our approach to management. Elevated IV insulin requirements persisted despite stability in vasopressor dose, change to a solitary peripheral IV site, and lack of interfering medications in the treatment regimen. This is the first case to demonstrate a relationship between high IV insulin requirements and poor peripheral perfusion.

Paraneoplastic Hypoglycemia Leading to Insulin Independence in a Patient With Type 1 Diabetes

Introduction: Hypoglycemia is a rare paraneoplastic manifestation of several non-islet cell tumors (NICT) that is rarely reported in individuals with diabetes. We report the first case of a patient with type 1 diabetes (T1D) and a recurrent gastrointestinal stromal tumor (GIST) who required discontinuation of all insulin therapy with continuous parenteral glucose infusions to avoid hypoglycemia. Case: The patient is an underweight (BMI 14.9 kg/m2) 59-year-old female with a 24-year history of T1D treated with insulin pump therapy who was diagnosed with GIST in 2003. Following surgical resection with postoperative adjuvant therapy, she remained tumor free until 2012 when she had disease recurrence unresponsive to several tyrosine kinase inhibitors. In 2014, she reported frequent episodes of documented hypoglycemia despite continued reductions in basal insulin infusion rates. Laboratory testing following several hours of insulin discontinuation revealed undetectable insulin and C-peptide levels, low IGF-1, normal IGF-2, and an IGF-2: IGF-1 ratio of 7.86. Thyroid, kidney and adrenal tests were normal. Initiation of prednisone alone then in combination with octreotide did not abate the hypoglycemia. During a hospitalization for hypoglycemia, exogenous insulin therapy was discontinued and 10% dextrose infusions started. Attempts at weaning the dextrose infusions resulted in hypoglycemia, prompting insertion of a PICC line prior to discharge home with continuous 25% dextrose infusions at 40-60 mg per hour. Discussion: NICT hypoglycemia (NICTH) is characterized by excessive tumor production of IGF-2 or pro-IGF-2. The structure of IGF-2 is similar to insulin, allowing cross reactivity at the insulin receptor. IGF binding proteins (IGFBPs) are responsible for transporting IGF-2 in plasma. Abnormal processing of the gene for IGF-2 results in increased production of the more biologically active pro-IGF-2 that does not form a complex with IGFBP3 and is available to interact with insulin receptors. In patients with normal IGF-2 (chronic kidney disease, poor nutritional status), an IGF-2: IGF-1 ratio >3 can be used to confirm NICTH. IGFBP-3 was not measured in this patient but it is likely this was low due to her poor nutritional status. The most definitive treatment for NICTH is resection of the tumor. Pharmacological management can be considered in patients who are not surgical candidates, but is not always successful as was observed in this patient. Conclusion:This is an unusual case of malignancy associated hypoglycemia in a woman with type 1 diabetes who required discontinuation of all insulin therapy as well as continuous dextrose infusions to achieve euglycemia and briefly maintain an acceptable quality of life over a period of several months.

Flash Glucose Monitoring Compared to Capillary Glucose Levels in Patients With Diabetic Ketoacidosis: Potential Clinical Applications

ObjectiveFrequent, finger-prick capillary blood glucose measurement is standard care, used to drive insulin infusion rates for inpatients being resuscitated from diabetic ketoacidosis (DKA). Over recent years there has been a shift toward continuous interstitial glucose monitoring, allowing monitoring of glucose without repeated invasive testing. While continuous interstitial glucose monitoring has been safely and reliably utilized in the outpatient setting, it has yet to be studied in acutely unwell patients with DKA. The aim of this study, allowing for physiologically lower interstitial compared to capillary glucose, was to determine if interstitial flash glucose monitoring (FGM) would lead to insulin infusion rates that were similar to capillary blood glucose (CapBG) in DKA. MethodsIn this study, 10 patients with diabetes mellitus, assessed to be in DKA, were enrolled. At the same time as standard DKA management commencement, simultaneous FGM measurements were obtained. Duplicate paired glucose readings were then analyzed for agreement. ResultsActual (CapBG-driven) and predicted (FGM determined) insulin infusion rates were similar. Minor differences in predicted insulin infusion rates were noted in 2/10 patients at higher glucose concentrations, which may relate to the lag in change in glucose in the interstitial space. ConclusionBased on our results, a trial of clinical outcomes in patients with DKA treated with insulin infusion rates driven by CapBG versus subcutaneous FGM appears justified. The FGM method of testing may improve patient comfort, obviate fatigue, improve staff time and direct patient contact, and potentially facilitate rapid discharge.

Управление и поддержка принятия решений в системе персонализированной инсулинотерапии

Insulin therapy automation is an actual research line in the glycemic control of diabetes mellitus type 1 patients. Development of closed-loop systems and methods will allow blood glucose maintaining in the physiological range. The work proposes the personalized insulin therapy system considered as a closed-loop control system based on feedback and external disturbances compensation principles. Automatic feedback-based glycemic control includes proportional reg-ulation of basal insulin infusion rate in relation to optimized thresholds inside the target range. To achieve bidirectional glycemic regulation the author proposes model predictive control for calculation of not only optimal profile of bolus infusion but also recommended corrective dose of carbohydrates. Besides, the comparative analysis of trends in measured and predicted profiles of blood glucose allows detecting and compensation of its unpredicted deviations. In silico testing of developed algorithms on nine virtual adults for 72 hours shows an ability for glucose maintaining in the target range for whole system operation time.

Glucose Response to Fast- and Long-Acting Insulin in People with Type 2 Diabetes

In type 2 diabetes (T2D), injections with long-acting insulin can become necessary to regulate blood glucose and avoid long-term complications. However, finding a safe and effective insulin dose, a process known as titration, is both challenging and time demanding. In this paper, we propose a new method for safe and rapid identification of a personalized insulin dose with long-acting insulin through short-term use of fast-acting insulin in an artificial pancreas (AP). To illustrate this novel concept, we simulate our method by modelling the glucose response to fast-and long-acting insulin in people with T2D. We apply a simple control-algorithm for the AP to adjust the insulin infusion rate during fasting periods. In this case-study, we simulate an insulin naïve T2D patient on AP treatment for one week, gradually adjusting the insulin infusion rate. After one week, we convert the insulin infusion rate, unit-to-unit, to a daily injection of long-acting insulin. We compare our method to titration with the standard of care 2-0-2 algorithm. Our simulations indicate that we can reduce the titration period from five weeks to a single week, whilst easing the burden on the patient.

Initial titration for people with type 1 diabetes using an artificial pancreas

For people with type 1 diabetes and some with type 2 diabetes, the problem of insulin titration, i.e. finding an adequate basal rate of insulin, is a complex and time-consuming task. This paper proposes a simple model-free algorithm and a procedure for fast initial titration in people with type 1 diabetes (T1D). A modified proportional-integral-derivative (PID) controller (i) updates the estimated insulin basal rate, and (ii) administers micro-boli of insulin every 5 minutes using glucose measurements from a continuous glucose monitor (CGM). A bolus calculator mitigates the effect of meals and reduces postprandial peaks. We evaluate the performance of our system qualitatively and numerically using a virtual clinic of 1,000 T1D patients with a broad inter-patient variability representative of a real population of people with T1D. We let the titration phase run for three consecutive days, followed by a three-day test phase using the newly computed basal insulin infusion rate. The proposed algorithm is able to provide a safe titration and individualized treatment for people with T1D.