Insulin Infusion Rate Research Articles

Twenty-Four Hour Fasting (Basal Rate) Tests to Achieve Custom-Tailored, Hour-by-Hour Basal Insulin Infusion Rates in Patients With Type 1 Diabetes Using Insulin Pumps (CSII).

Twenty-four hour fasting periods are being used to scrutinize basal insulin infusion rates for pump-treated patients with type 1 diabetes. Data from 339 consecutive in-patients with adult type 1 diabetes on insulin pump therapy undergoing a 24-hour fast as a basal rate test were retrospectively analyzed. Hourly programmed basal insulin infusion rates and plasma glucose concentrations within, below, or above arbitrarily defined target ranges were assessed for periods of the day of special interest (eg, 01:00-07:00 am, "dawn" period, 04:00-07:00 pm, and "dusk" period). Statistics: χ2-tests, paired t-tests were used. Basal rates (mean: 0.90 ± 0.02 IU/h) showed circadian variations with peaks corresponding to "dawn" (1.07 ± 0.02 IU/h from 01:00 to 07:00 am) and, less prominently, "dusk" (0.95 ± 0.02 IU/h from 03:00 to 07:00 pm). Individual mean plasma glucose concentrations averaged 6.6 ± 0.1 mmol/L, with 53.1% in the predefined "strict" (4.4-7.2 mmol/L) target range. Interestingly, during the "dawn" period, plasma glucose was significantly higher (by 0.5 ± 0.1 mmol/L [95% confidence interval: 0.3-0.8 mmol/L; P < .0001]) and the odds ratio for hypoglycemia was significantly lower compared to the reference period. Twenty-four hour fasting periods as basal rate tests frequently unravel periods with inappropriate basal insulin infusion rates potentially responsible for fasting hyper- or hypoglycemia. Notably, the higher basal insulin infusion rate found during the "dawn" period seems to be justified and may need to be accentuated.

Abstract P2025: Primary Aldosteronism Decreases Insulin Secretion and Increases Insulin Clearance in Humans

Primary aldosteronism is associated with an increased risk of diabetes, but the mechanism is uncertain. We enrolled 9 patients with primary aldosteronism and assessed insulin secretion and insulin sensitivity beforte and after 3-12 months after either adrenalectomy (n-6) or medical treatment (n=3). Plasma 8AM Aldosterone ( p =0.02) and 11-deoxycorticosterone ( p =0.02) decreased after treatment, whereas cortisol was unchanged ( p =0.57). Systolic blood pressure (131.1±3.6 vs 124.3±7.7; p =0.43), serum potassium (3.7±0.1 vs 4.1±0.1 mEq/L; p =0.063), and creatinine (1.1±0.1 vs 1.2±0.1 mg/dL; p =0.35) were similar after treatment. During hyperglycemic clamps, we infused glucose to increase plasma glucose to a target of 200mg/dL ( a ). The insulin response ( b , 218.6±39.8 vs 403.1±42.0 pM insulin mean at 90-120 min, p =0.004) and L-arginine stimulated insulin response ( c) increased compared to Pre-Treatment assessment. C-peptide results were similar to insulin alterations. Comparison to control subjects matched for age, race, sex, and BMI ( Figure , gray line and area indicating mean±95%CI) indicated that insulin secretion after treatment was comparable to healthy individuals. During hyperinsulinemic-euglycemic clamps, insulin clearance (steady state insulin divided by insulin infusion rate) increased after treatment (855±68 vs 615±57 mL/min, p =0.031). Insulin sensitivity decreased after treatment (30.7±2.1 vs 18.5±1.6 M/I; p =0.016), but disposition index was unchanged (acute insulin response x M/I; p =0.81).

Understanding safety differently: developing a model of resilience in the use of intravenous insulin infusions in hospital in-patients—a feasibility study protocol

BackgroundIntravenous insulin infusions are considered the treatment of choice for critically ill patients and non-critically ill patients with persistent raised blood glucose who are unable to eat, to achieve optimal...

Influences of the Grifola Gargal extracts on insulin resistance induced by high-fructose diet in rats

，It has been well known that the high fructose diet causes the insulin resistance. And it has been reported that certain components of mushrooms effects on insulin resistance. The purpose of this study was to evaluate the effects of Grifola Gargal (mushroom) extracts on insulin resistance induced by highfructose diet. Male rats of strain aged 7 weeks were divided into 3 groups, such as high-fructose diet (Fru), high-fructose diet ＋ Grifola Gargal extracts (1.5％ in diet; Fru ＋ G), and standard chow-diet (Control) groups. For these rats, after one overnight fasts, a sequential euglycemic clamp experiment with two different insulin infusion rates of 3.0 (L-clamp) and 30.0 mU/kg BW/min (H-clamp) was performed. Glucose infusion rates (GIRs), calculated respectively from 60 to 90 min in L-clamp, and 150 to 180 min in H-clamp, were recognized an sign of whole body insulin action. High-fructose feeding markedly reduced GIRs in both L- and H-clamp experiments compared with Control. In L-clamp experiment, the effects of Grifola Gargal extracts were not shown. However, in H-clamp, GIR were increased by Grifola Gargal extracts compared with Fru, and reached the same levels as in Control. Therefore, we demonstrated that the administration of Grifola Gargal extracts did not affect insulin sensitivity, but produced a significant rise in insulin responsiveness.

62-LB: Quantifying Insulin-Mediated and Noninsulin Mediated Glucose Disposal during Exercise in Patients with Type 1 Diabetes

Introduction: Glycemic control during exercise is challenging for people with type 1 diabetes. Better quantification of insulin dynamics at different exercise intensities and across insulin loading conditions is necessary for accurate insulin dosing during exercise. Methods: Twenty seven participants with type 1 diabetes were evaluated during 3 separate 10-hour fasting aerobic exercise studies with low, medium, and high levels of insulin infusion (100%, 150%, and 300% of basal rate) across two exercise arms: moderate (40-45% of VO2 max), and intense (60-65% of VO2 max) exercise. Glucose levels were clamped during a 3-hour run-in period, followed by 45 minutes of exercise on a treadmill. 6,6-2H2-dideuterated glucose was infused to match endogenous glucose production during the entire trial. Glucose tracer data were fitted to a two-compartment ODE model, solved via Bayesian inference. We intend to quantify insulin and non-insulin mediated disposal of glucose by observing the rate of disposal (Rd) across different rates of insulin infusion in each exercise arm. Results: Area under the curve (AUC) of Rd during 45 minutes of moderate exercise increased by 0.084 mmol/L for every percent increase in baseline insulin infusion rate (95% CI=0.064-0.104, p&amp;lt;0.001). AUC during intense exercise increased by 0.109 mmol/L (95% CI= 0.079-0.139, p&amp;lt;0.001). Mixed-effects model analysis showed no difference between exercise arms. Conclusion: Results indicate Rd is substantial during exercise but that the difference in glucose uptake during aerobic exercise at 40-45% VO2 max may be comparable with 60-65% VO2 max. Disclosure T.P. Nguyen: None. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc., Zealand Pharma A/S. Consultant; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc. L.M. Wilson: None. D. Branigan: None. V. Gabo: None. B. Senf: None. F.H. Guillot: None. J. El Youssef: None. Funding National Institutes of Health

1073-P: A Study of Flat and Circadian Insulin infusion Rates in Continuous Subcutaneous Insulin Infusion (CSII) in Adults with Type 1 Diabetes (FIRST1D)

Background and Aims: Initiation of continuous subcutaneous insulin therapy (CSII) in people with type 1 diabetes (T1D) requires conversion of a basal insulin dose to a continuous infusion regimen. There are limited data to guide the optimal insulin profile to rapidly achieve target glucose and minimize healthcare professional input. The aim of this study was to compare circadian and flat insulin infusion rates in CSII naïve adults with T1D. Materials and Methods: Adults with T1D who met the NICE criteria for CSII were recruited. Participants were randomized to either a circadian profile or a flat basal rate, each calculated from the total daily dose. Basal rate testing was undertaken on days 7, 14 and 28 of CSII and basal rates were adjusted according to protocol. The primary outcome was the between group difference in absolute change in insulin basal rate over 24 hours following 3 rounds of basal testing. Secondary outcomes included the number of basal rate changes and the time blocks. Data from blinded continuous glucose monitoring were also collected. Results: Seventeen participants (mean age 33.3 (SD 8.6)) were recruited. There was no significant difference in absolute change in insulin basal rates between the two groups (p=0.85) from baseline to the end of the study. In the circadian basal group, there was significant variation in the number of changes made across the 24 one-hour blocks with the most changes early in the morning (p=0.005). In the flat basal group, there were no significant variation in the number of changes made across the time points (p=0.09). Conclusion: Commencing CSII with a flat or circadian profile does not impact on the magnitude of basal rate insulin changes during optimization in the first 28 days. The circadian profile requires changes at specific time points, while the flat basal rate requires even optimization throughout the 24-hour period. Further development of the circadian profile early in the morning may address this. Disclosure S.K. Rilstone: None. M. Reddy: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi. Funding Roche

724-P: Timing of Basal Insulin Reduction to Prevent Hypoglycemia during Exercise in Adults and Adolescents with Type 1 Diabetes Using Insulin Pump Therapy: Preliminary Results

Background We have shown that the reduction of basal insulin (-80%) 40-min before exercise is insufficient to reduce the time spent on hypoglycemia (Roy-Fleming et al., 2018. Diabetes and Metabolism). These results suggest that earlier basal insulin reductions need to be tested. We compared the efficacy of two timings to decrease basal insulin infusion rate to reduce exercise-induced hypoglycemia in patients with T1D using insulin pump therapy. Furthermore, we explored if decreased muscle vasoreactivity (secondary to decreased insulin levels) is associated with a reduced time spent in hypoglycemia. Methods: 13 adults and adolescents (10 adults; 5 adolescents; mean A1C: 8,2±1,0%) practiced 60-min exercise sessions (ergocyle) at 60% VO2peak, 240 minutes after a standardized lunch. In randomized order, we compared an 80% reduction of basal insulin applied 40-min (T-40) and 90-min (T-90) before exercise onset. Near-infrared spectroscopy (NIRS) was used to investigate muscle hemodynamic at vastus lateralis. Venous blood samples for glycemia measurement were drawn every 10 min during exercise. Results: T-90 strategy could reduce hypoglycemia risk during exercise: glycemic drop during exercise tend to be more important during T-40 vs. T-90 strategy (-41.44 ± 57.65 mg/dl vs. -14.05 ± 34.23 mg/dl respectively; p=0.09). This trend is confirmed by the repeated measures ANOVA test, which shows a significant interaction effects (blood glucose level during exercise × strategy “T90 vs. T-40”) (p = 0.01). However, contrary to our hypothesis, the estimation of local muscle perfusion measured by NIRS shows comparable results between 2-strategies. Conclusion: Our preliminary results in 15 DT1 patients (planned 20) show that decreasing basal insulin infusion rate by 80% up to 90 minutes before exercise onset tend to reduce exercise-induced hypoglycemia. This drop does not seem to be related to a decrease in local muscle perfusion. Disclosure S. Tagougui: None. N. Taleb: None. E. Heyman: None. V. Messier: Other Relationship; Self; Eli Lilly and Company. C. Suppere: None. S. Berthoin: None. R. Rabasa-Lhoret: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S.

Robust multi-objective blood glucose control in Type-1 diabetic patient.

In this study, an automatic robust multi‐objective controller has been proposed for blood glucose (BG) regulation in Type‐1 Diabetic Mellitus (T1DM) patient through subcutaneous route. The main objective of this work is to control the BG level in T1DM patient in the presence of unannounced meal disturbances and other external noises with a minimum amount of insulin infusion rate. The multi‐objective output‐feedback controller with H∞, H2 and pole‐placement constraints has been designed using linear matrix inequality technique. The designed controller for subcutaneous insulin delivery was tested on in silico adult and adolescent subjects of UVa/Padova T1DM metabolic simulator. The experimental results show that the closed‐loop system tracks the reference BG level very well and does not show any hypoglycaemia effect even during the long gap of a meal at night both for in silico adults and adolescent. In the presence of 50 gm meal disturbance, average adult experience normoglycaemia 92% of the total simulation time and hypoglycaemia 0% of total simulation time. The robustness of the controller has been tested in the presence of irregular meals and insulin pump noise and error. The controller yielded robust performance with a lesser amount of insulin infusion rate than the other designed controllers reported earlier.

1046-P: Day-to-Day Variability of Insulin Requirements in Inpatients on General Wards

Aim: To characterize variability of exogenous insulin requirements during fully closed-loop insulin delivery in hospitalized patients with hyperglycaemia requiring subcutaneous insulin. Methods: We retrospectively analyzed data from randomized trials investigating fully closed-loop insulin delivery for up to 15 days in inpatients with hyperglycaemia on general wards (type 1 diabetes excluded). We calculated insulin amounts delivered by closed-loop overnight (2300-0449), during breakfast (0500-1059), lunch (1100-1659), and evening meal (1700-2249). The coefficient of variation (CV) quantified between day and between night variability of insulin requirements in inpatients using closed-loop for at least 5 days. Results: Data from 487 days in 55 participants were analyzed [age 69(8)years, weight 100(32)kg, baseline HbA1c 8.0(2.1)%, duration of diabetes 18(13)years, duration of insulin 9(10)years, mean(SD)]; 14.5% of participants received dialysis, 29.1% enteral/parenteral nutrition and 21.8% steroids. Closed-loop directed insulin infusion rate was 1.6(0.8), 2.9(1.2), 3.1(1.4), 2.1(1.0)units/kg/h during overnight, breakfast, lunch, and evening meal periods, respectively. The CV of insulin delivery was higher between nights than between any of the daytime periods [overnight 54(21)% compared with 42(21)% at breakfast, 41(16)% lunchtime and 48(17)% dinner; p=0.001]. Conclusions: Overnight exogenous insulin requirements are more variable than daytime requirements. Particular attention needs to be paid to glucose management overnight to prevent dysglycaemia in inpatients receiving insulin therapy on general wards. Disclosure C.K. Boughton: None. L. Bally: None. H. Thabit: Research Support; Self; Dexcom, Inc. S. Hartnell: Advisory Panel; Self; Dexcom, Inc., JDRF. Speaker's Bureau; Self; Sanofi. D. Herzig: None. A. Vogt: None. E. Andereggen: None. Y. Ruan: None. M.E. Wilinska: None. M. Evans: Advisory Panel; Self; Dexcom, Inc., Medtronic, Roche Diabetes Care, Zucara Therapeutics Inc. Research Support; Self; MedImmune, Sanofi. Speaker's Bureau; Self; AstraZeneca. Other Relationship; Self; Abbott, Eli Lilly and Company, Novo Nordisk Inc. M.M. Wertli: None. A.P. Coll: None. C. Stettler: None. R. Hovorka: Advisory Panel; Self; Novo Nordisk A/S. Research Support; Self; Abbott, Dexcom, Inc., Medtronic. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; B. Braun Medical Inc., Medtronic.

Improving fixed rate insulin infusion prescriptions in ­patients admitted with diabetic ketoacidosis in Basildon Hospital – a local quality improvement project

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes and some cases of type 2 diabetes. Intravenous fluids and fixed rate insulin infusion (FRII) remain the mainstay of treatment for this condition.[1][1] However, given the complex nature of the treatment regime of this

Improving fixed rate insulin infusion prescriptions in ­patients admitted with diabetic ketoacidosis in Basildon Hospital – a local quality improvement project

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes and some cases of type 2 diabetes. Intravenous fluids and fixed rate insulin infusion (FRII) remain the mainstay of treatment for this condition.[1][1] However, given the complex nature of the treatment regime of this

Severe hypokalaemia in diabetic ketoacidosis: a contributor to central pontine myelinolysis?

SummaryHypokalaemia at presentation of diabetic ketoacidosis is uncommon as insulin deficiency and metabolic acidosis shifts potassium extracellularly. However, hypokalaemia is a recognised complication of the management of diabetic ketoacidosis as insulin administration and correction of metabolic acidosis shifts potassium intracellularly. We describe the case of a 9-year-old girl with newly diagnosed type 1 diabetes mellitus presenting in diabetic ketoacidosis, with severe hypokalaemia at presentation due to severe and prolonged emesis. After commencing management for her diabetic ketoacidosis, her serum sodium and osmolality increased rapidly. However, despite maximal potassium concentrations running through peripheral access, and multiple intravenous potassium ‘corrections’, her hypokalaemia persisted. Seventy two hours after presentation, she became drowsy and confused, with imaging demonstrating central pontine myelinolysis – a rare entity seldom seen in diabetic ketoacidosis management in children despite rapid shifts in serum sodium and osmolality. We review the literature associating central pontine myelinolysis with hypokalaemia and hypothesise as to how the hypokalaemia may have contributed to the development of central pontine myelinolysis. We also recommend an approach to the management of a child in diabetic ketoacidosis with hypokalaemia at presentation.Learning points:Hypokalaemia is a recognised complication of treatment of paediatric diabetic ketoacidosis that should be aggressively managed to prevent acute complications.Central pontine myelinolysis is rare in children, and usually observed in the presence of rapid correction of hyponatraemia. However, there is observational evidence of an association between hypokalaemia and central pontine myelinolysis, potentially by priming the endothelial cell membrane to injury by lesser fluctuations in osmotic pressure.Consider central pontine myelinolysis as a complication of the management of paediatric diabetic ketoacidosis in the presence of relevant symptoms with profound hypokalaemia and/or fluctuations in serum sodium levels.We have suggested an approach to the management strategies of hypokalaemia in paediatric diabetic ketoacidosis which includes oral potassium supplements if tolerated, minimising the duration and the rate of insulin infusion and increasing the concentration of potassium intravenously (via central line if necessary).

Effect of Injection Site Cooling and Warming on Insulin Glargine Pharmacokinetics and Pharmacodynamics.

In type 1 diabetes (T1D), closed-loop systems provide excellent overnight fasting blood glucose control by adjusting the insulin infusion rate based on corresponding changes in sensor glucose levels. In patients on multiple daily insulin (MDI) injections, such control in overnight glucose levels has not been possible due to the inability to alter the absorption rate of long-acting insulin after injection. In this study, we tested the hypothesis that increases/decreases of fasting glucose levels could be achieved by cooling/warming the skin around the injection site, which would result in lower/higher Glargine absorption rates from its subcutaneous depot. Fourteen subjects with T1D (4 females; age 39.6 ± 16.7 years, HbA1c 7.8 ± 1.1%, BMI 25.4 ± 2.8 kg/m2) on MDI therapy underwent fasting pharmacokinetic and pharmacodynamic studies that started at ~8 am and lasted 240 min on 3 separate days in random order: a control day without warming or cooling of the injection site and two experimental days, one day with injection site warming and the other with cooling. Cooling the skin around the glargine injection site reduced insulin concentrations by >40% (P < .01 versus the warming study, P = .21 versus the control study), accompanied by a 55 mg/dL increase in serum glucose (P < .01 versus the control study). Conversely, skin warming prevented the fall in serum insulin (P = .2 versus the control study; P < .01 versus the cooling study), resulting in a 40 mg/dL reduction in serum glucose (P < .001 versus the cooling study, P = .11 versus the control study). This proof of concept study has shown that cooling and warming the skin around the injection site provides a means to decrease and increase the rate of absorption and action of insulin glargine from its subcutaneous depot.

A mathematical model of the intravenous glucose tolerance test illustrating an n-order decay rate of plasma insulin in healthy and type 2 diabetic subjects

The most accurate considered method to determine the insulin sensitivity (SI) and glucose effectiveness (SG), that is the intravenous glucose tolerance test (IVGTT). In this study, the modified minimal model with additions of an n-order decay rate of plasma insulin function and an insulin infusion rate function is introduced. This modified model enables estimation of two main feature of type 2 diabetes (T2D) diagnostic, that is the index of SI and SG. In this paper, the modified model has been was used to study four cases published IVGTT data, including normal glucose tolerance (NGT) or healthy subjects and T2D subjects with different types of insulin infusion rates. This modified model study has been shown that in NGT subjects had higher SI and SG index than T2D subjects. The R2 value, the coefficient of determination of between measured and calculated plasma concentrations of these four cases, is above 0.95, which indicates good agreement.

SUN-171 Glargine Use in a Neonatal Diabetic

BACKGROUND Neonatal Diabetes (ND) is rare with incidence estimated at 1 / 100,000-500,000 live births. Duration of ND and insulin requirements vary with average therapy lasting 3 months. Genetic mutations are reported in 90% of transient forms with mutations in the region of 6q24 accounting for 70% of mutations. Sulfonylurea is the preferred initial treatment, but when patients fail to respond, insulin is required, raising difficulties in treatment and blood glucose (BG) monitoring. CLINICAL CASE A 2040 gram male was delivered at 37 weeks gestation to a 40 year old mother. Prenatal history included IUGR and the infant developed persistent hypoglycemia on day of life (DOL) two characterized by pallor, apnea and hypothermia. He was acidotic with multiple BG values ≥ 250mg/dl. He was placed NPO without dextrose in his TPN. On DOL four he resumed enteral feeds but BG rose to 297mg/dl with concurrent insulin level of 0.07 mIU/L and undetectable C-Peptide. He was started on continuous IV insulin infusion ranging from 0.05u/k/hr-0.2units/k/hr. He received one dose of Regular insulin (0.2 units (U) resulting in dramatic BG drop < 50 mg/dl requiring IV dextrose bolus. Enteral feeds resumed on DOL 10 along with Glyburide at 0.1mg/kg BID. BG rose to ≥250 mg/dl despite increasing Glyburide to 2mg/kg/day and C-Peptide remained undetectable. Continuous IV insulin infusion was resumed ranging from 0.01- 0.05u/k/hr. Glyburide was discontinued after 2 weeks due to ineffectiveness. Genetic testing confirmed a 6q24 mutation consistent with transient ND, overexpression of 6q genes, and a suspected methylation disorder. Because overexpression down-regulates insulin secretion potentially leading to a poor response to Sulfonylurea, a second Sulfonylurea trial was attempted, but also failed. The infant was started on continuous subcutaneous insulin infusion (insulin pump) but multiple site failures prevented effective glycemic control and continuous IV insulin infusion was resumed. After 3 months, continuous IV insulin infusion rate had increased to 1.5 units/day. With increasing body weight and insulin requirements, he was transitioned to 1 unit insulin Glargine daily and then BID. BG remained in the 100 - 300 mg/dl range on a program of Glargine 1 unit SQ BID plus 1 unit of Regular insulin if BG ≥500 mg/dl. He is now 5 months old with an increasing need for insulin and A1c = 9.0%. Because his pre-prandial BG ranged from 300-400mg/dl without hypoglycemia, the Glargine dose was increased to 1.5 units SQ in the AM and 1.0 units SQ in the PM. CONCLUSION This is the rare case of a patient with ND having increasing insulin requirements at 5 months of age who did not respond to Sulfonylurea treatment. Predicting how long insulin requirements will last is currently unknown. The 6q24 mutation is involved in the mutation of a protein that induces apoptosis of cells involved in insulin secretion from beta cells.

Optimal regulation of blood glucose level in Type I diabetes using insulin and glucagon.

The Glucose-Insulin-Glucagon nonlinear model accurately describes how the body responds to exogenously supplied insulin and glucagon in patients affected by Type I diabetes. Based on this model, we design infusion rates of either insulin (monotherapy) or insulin and glucagon (dual therapy) that can optimally maintain the blood glucose level within desired limits after consumption of a meal and prevent the onset of both hypoglycemia and hyperglycemia. This problem is formulated as a nonlinear optimal control problem, which we solve using the numerical optimal control package . Interestingly, in the case of monotherapy, we find the optimal solution is close to the standard method of insulin based glucose regulation, which is to assume a variable amount of insulin half an hour before each meal. We also find that the optimal dual therapy (that uses both insulin and glucagon) is better able to regulate glucose as compared to using insulin alone. We also propose an ad-hoc rule for both the dosage and the time of delivery of insulin and glucagon.

The Official Journal of ATTD Advanced Technologies &amp; Treatments for Diabetes Conference Berlin, Germany—February 20–23, 2019

The Official Journal of ATTD Advanced Technologies &amp; Treatments for Diabetes Conference <i>Berlin, Germany—February 20–23, 2019</i>

Prospective evaluation of a dynamic insulin infusion algorithm for non critically-ill diabetic patients: A before-after study.

IntroductionInsulin infusion is recommended during management of diabetic patients in critical care units to rapidly achieve glycaemic stability and reduce the mortality. The application of an easy-to-use standardized protocol, compatible with the workload is preferred. Glycaemic target must quickly be reached, therefore static algorithms should be replaced by dynamic ones. The dynamic algorithm seems closer to the physiological situation and appreciates insulin sensitivity. However, the protocol must meet both safety and efficiency requirements. Indeed, apprehension from hypoglycaemia is the main deadlock with the dynamic algorithms, thus their application remains limited. In contrary to the critical care units, to date, no prospective study evaluated a dynamic algorithm of insulin infusion in non-critically ill patients.AimThis study primarily aimed to evaluate the efficacy of a dynamic algorithm of intravenous insulin therapy in non-critically-ill patients, and addressed its safety and feasibility in different departments of our university hospital.MethodsA "before-after" study was conducted in five hospital departments (endocrinology and four “non-expert” units) comparing a dynamic algorithm (during the "after" period-P2) to the static protocol (the “before” period-P1). Static protocol is based on determining insulin infusion according to an instant blood glycaemia (BG) level at a given time. In the dynamic algorithm, insulin infusion rate is determined according to the rate of change of the BG (the previous and actual BG under a specific insulin infusion rate). Additionally, two distinct glycaemic targets were defined according to the patients’ profile: 100–180 mg/dl (5.5–10 mmol/l) for vigorous patients and 140–220 mg/dl (7.8–12.2 mmol/l) for frail ones. Different BG measurements for each patient were collected and recorded in a specific database (e-CRF) in order to analyse the rates of hypo- and hyperglycaemia. A satisfaction survey was also performed. A study approval was obtained from the institutional revision board before starting the study.ResultsOver 8 months, 72 and 66 patients during P1 and P2 were respectively included. The dynamic algorithm was more efficient, with reduced time to control hyperglycaemia (P1 vs P2:8.3 vs 5.3 hours; HR: 2.02 [1.27; 3.21]; p<0.01), increased the number of in-target BG measurements (P1 vs P2: 37.0% vs 41.8%; p<0.05), and reduced the glycaemic variability related to each patient (P1 vs P2, %CV: 40.9 vs 38.2;p<0.05, Index Correlation Class:0.30 vs 0.14; p<0.05). In patients after the first event of hypoglycemia after having started the infusion, new events were lower (P1 vs P2: 19.4 vs 11.4; p<0.001) thanks to an earlier reaction to hypoglycaemia (8.3% during P1 vs 44.3% during P2; p = 0.004). With the dynamic algorithm, the percentage of recurrence of mild hypoglycaemia was significantly lower in frail patients (20.5% vs 10.2%; p<0.001), and in patients managed in the non-expert units (18 vs 7.1%, p<0.001). The %CV was significantly improved in frail patients (36.9%). Mean BG measurements for each patient/day were 5.5±1.1 during P1 and 6.0±1.6 during P2 (p = 0.6). The threat from hypoglycaemia and the difficulty in using dynamic algorithm are barriers for nurses’ adherence.ConclusionsThis dynamic algorithm for non-critically-ill patients is more efficient and safe than the static protocol, and adapted for frail patients and non-expert units.

Glycemic control in intensive care unit: Experience of a tertiary care center

Background: Hyperglycemia complicates the course of illness of many critically ill patients and contributes to the increased morbidity and mortality in adult intensive care units (ICUs). Objective: The objective of this study is to compare the effectiveness of a modified nurse-implemented insulin infusion protocol (NIIP) against the original protocol used in the adult ICUs, in terms of controlling hyperglycemia while averting significant hypoglycemia. Methodology: Blood glucose (BG) readings that were collected over 3 months in medical and surgical ICUs (SICUs) while on the original insulin infusion protocol were retrospectively reviewed. A modified insulin infusion protocol was prepared by a dedicated adult ICU quality focus group composed of physicians, nurses, clinical pharmacists, and quality representative. The rate of insulin infusion was increased by 10%–20% for the BG ranges above 13.1 mmol/L, allowing early transition from a mild-to-moderate scale. The new protocol was implemented for 2 months, and BG readings were compared to the results of the original insulin infusion protocol. Results: A total of 3490 BG readings in the medical ICU and 3006 in SICU were analyzed. Hyperglycemia was found in 1743 readings (26.83%) while on the original insulin protocol. When the modified insulin infusion protocol was applied, hyperglycemia was significantly less (19.83%, P

Sensor-based detection and estimation of meal carbohydrates for people with diabetes

Abstract People with type 1 diabetes (T1D) must estimate the carbohydrate (CHO) content in meals to compute the bolus insulin correctly. To release T1D patients from the cumbersome task of counting CHO, we develop a method for detecting meals that can be used in blood glucose (BG) control. The algorithm detects a meal and estimates the meal onset and the amount of CHO. The inputs of the meal detector are the continuous glucose monitoring (CGM) data and the insulin infusion rate. We use second-order linear input-output models for insulin to subcutaneous glucose dynamics and for CHO to subcutaneous glucose dynamics. The models are converted to a linear discrete-time state-space model. A white noise double integrator models the unknown meal disturbances. The state-space model is augmented with the unknown meal disturbance (CHO ingestion rate) and a Kalman filter (KF) estimates the CHO rate (g/min). The algorithm uses two tests to announce a meal. The first test is a cumulative sum algorithm that detects changes in the KF innovation and estimates the onset of change. The second test is comparison of the estimated CHO rate with a threshold to detect a change in the rate. If both tests simultaneously detect a change, an optimal smoother estimates the meal-size. If the estimated meal-size reaches a certain amount, the algorithm announces a meal. Furthermore, we integrate a bolus calculator (BC) with the meal detector. We test the algorithm for nine virtual T1D patients. In total, the patients eat 45 meals in 13.5 days. The detection sensitivity is 93% and the detection delay has a median of 40 min. The median of the meal onset estimation bias is 5 min. Out of 42 detected meals, the algorithm underestimates 26 meals with a median bias of −19 g, and it overestimates 16 meals with a median bias of 21 g. The meal detector with the BC reduces the BG postprandial peak from 274 mg/dL (unbolused meals) to 207 mg/dL, and it increases the mean time in euglycemia from 50% to 79%. The meal detector combined with the BC improves glycemia for the virtual patients in this study.