Metaheuristic Optimization of Insulin Infusion Protocols Using Historical Data with Validation Using a Patient Simulator

Metaheuristic search algorithms are used to develop new protocols for optimal intravenous insulin infusion rate recommendations in scenarios involving hospital in-patients with Type 1 Diabetes. Two metaheuristic search algorithms are used, namely, Particle Swarm Optimization and Covariance Matrix Adaption Evolution Strategy. The Glucose Regulation for Intensive Care Patients (GRIP) serves as the starting point of the optimization process. We base our experiments on a methodology in the literature to evaluate the favorability of insulin protocols, with a dataset of blood glucose level/insulin infusion rate time series records from 16 patients obtained from the Waikato District Health Board. New and significantly better insulin infusion strategies than GRIP are discovered from the data through metaheuristic search. The newly discovered strategies are further validated and show good performance against various competitive benchmarks using a virtual patient simulator.

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Insulin resistance in spontaneously hypertensive rats. Difference in interpretation based on insulin infusion rate or on plasma insulin in glucose clamp studies

Diabetes ◽

10.2337/diabetes.42.9.1364 ◽

1993 ◽

Vol 42 (9) ◽

pp. 1364-1371 ◽

Cited By ~ 5

Author(s):

R. H. Rao

Keyword(s):

Insulin Resistance ◽

Infusion Rate ◽

Spontaneously Hypertensive Rats ◽

Plasma Insulin ◽

Insulin Infusion ◽

Glucose Clamp ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Insulin Infusion Rate

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Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.1.240 ◽

1996 ◽

Vol 80 (1) ◽

pp. 240-244 ◽

Cited By ~ 61

Author(s):

M. D. Vukovich ◽

P. J. Arciero ◽

W. M. Kohrt ◽

S. B. Racette ◽

P. A. Hansen ◽

...

Keyword(s):

Infusion Rate ◽

Insulin Action ◽

Insulin Infusion ◽

Glucose Disposal ◽

Inactive State ◽

Transporter Protein ◽

Glut 4 ◽

Insulin Infusion Rate ◽

Endurance Runners ◽

Trained Runners

The purpose of this investigation was to determine whether decreased insulin action after 6 days of inactivity in endurance-trained runners was associated with a decrease in skeletal muscle glucose transporter protein levels (GLUT-4) in the gastrocnemius muscle. Seven endurance runners (5 men and 2 women) volunteered to participate in this investigation. All subjects had normal glucose tolerance as determined by the National Diabetes Data Group guidelines. Each individual completed two hyperinsulinemic euglycemic clamps at insulin infusion rates of 15 (LO) and 40 (HI) mU.m-2.min-1, one approximately 18 h after a training bout and the second after 6 days of inactivity (IA). Muscle biopsies for the measurement of GLUT-4 were obtained from the gastrocnemius before each clamp. Glucose disposal rates during the last 30 min of each insulin infusion were significantly reduced after 6 days of IA, averaging 6.45 +/- 1.04 mg.kg fat-free mass (FFM)-1.min-1 before and 4.55 +/- 0.56 mg.kg FFM-1.min-1 after detraining for the LO insulin infusion rate and 13.77 +/- 0.88 mg.kg FFM-1.min-1 before and 11.81 +/- 0.60 mg.kg FFM-1.min-1 after detraining for the HI insulin infusion rate (both P < 0.05), despite the fact that plasma insulin was higher in the inactive state (LO, 19.2 +/- 0.9 microU/ml before and 23.4 +/- 1.5 microU/ml after detraining; HI, 56.0 +/- 2.0 microU/ml before and 61.6 +/- 1.6 microU/ml after detraining; P < 0.05)). Calculated insulin clearance was greater in the trained than in the inactive state (P < 0.03). Muscle GLUT-4 transporter protein after 6 days of IA was reduced by 17.5 +/- 5.4% (P < 0.02). These results demonstrate that 6 days of IA reduces insulin action in endurance-trained runners and suggest that a reduction in muscle GLUT-4 transporter level plays a role in the decrease in glucose disposal rates.

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P1796FACTORS PREDICTING SUBCUTANEOUS INSULIN REQUIREMENT AFTER KIDNEY TRANSPLANT

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1796 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Beena Bansal ◽

Shyam Bansal

Keyword(s):

Kidney Transplant ◽

Insulin Infusion ◽

Insulin Dose ◽

Insulin Requirement ◽

P Value ◽

Subcutaneous Insulin ◽

Duration Of Diabetes ◽

Transplant Patients ◽

Intravenous Insulin ◽

Insulin Infusion Rate

Abstract Background and Aims Diabetes is the most common cause for end stage renal disease leading to kidney transplant. Post transplant glycemic management has significant impact on long term outcomes, but is challenging, especially while transitioning patients from intravenous to subcutaneous insulin dose. This study was therefore planned to assess factors which influence subcutaneous insulin dose after kidney transplant. Method Data was prospectively collected from 98 consecutive kidney transplant patients with type 2 diabetes at a tertiary care hospital in India, with regards to age, gender, height, weight, duration of diabetes, pre transplant insulin dose, pre transplant use of oral antidiabetics. First two days after transplant patients are nil by mouth and are on insulin infusion (column based method). On third day, patients are transitioned to multiple subcutaneous insulin. We assessed and recorded the subcutaneous insulin dose requirement by 4th and 5th day. Results Mean (SD) for patients’ age was 52.28 (6.32) years, height 167.83 (5.64) cm, weight 70.55 (14.32) kg, body mass index 25.39 (4.72) kg/m2 and duration of diabetes 13.3 (7.02) years. All 98 transplant recipients were male. Mean insulin requirement before transplant was 15.37 (20.24) units/day. Mean post transplant intravenous insulin infusion rate for 4 hours before transitioning to subcutaneous insulin was 2.07 (0.987) units/hour. Mean subcutaneous insulin requirement after transplant was 73.18 (25.45) units/day or 1.12 (0.61) units/kgbw. Mean basal insulin dose was 25.32 (10.91) units. Mean bolus dose before breakfast was 10.75 (4.37) units, before lunch was 20.12 (7.4)) units, before evening snack was 6.65 (3.43) units and before dinner was 10.75 (4.11) units. In terms of proportion of total daily dose (TDD), mean basal insulin was 0.34 (0.08) of TDD, bolus dose before breakfast was 0.15 (0.03) of TDD, before lunch was 0.28 (0.05) of TDD, before evening snack was 0.09 (0.04) of TDD and before dinner was 0.15 (0.04) of TDD. Subcutaneous insulin dose after transplant correlated with insulin dose of the recipient before transplant (Pearson’s coefficient 0.43; p value 0.003) and weight of the patient (Pearson’s coefficient 0.32; p value 0.001). It did not correlate with age of the recipient, duration of diabetes, intravenous insulin infusion rate or tac level. On multivariate linear regression analysis to assess the factors predicting subcutaneous insulin dose after transplant, only pre-transplant insulin dose was significant (p value 0.046). Age of the recipient, duration of diabetes, weight of the patient, intravenous insulin infusion rate or preoperative use of oral anti diabetic were not significant Conclusion In kidney transplant patients with type 2 diabetes, only pre transplant insulin dose predicted the subcutaneous insulin dose post transplant.

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Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.3.e338 ◽

1991 ◽

Vol 260 (3) ◽

pp. E338-E344 ◽

Cited By ~ 5

Author(s):

M. J. Muller ◽

A. Fenk ◽

H. U. Lautz ◽

O. Selberg ◽

H. Canzler ◽

...

Keyword(s):

Liver Cirrhosis ◽

Energy Expenditure ◽

Metabolic Rate ◽

Oxidation Rate ◽

Infusion Rate ◽

Glucose Oxidation ◽

Insulin Infusion ◽

Resting Metabolic Rate ◽

Insulin Infusion Rate ◽

Glucose Storage

Energy expenditure and substrate metabolism were investigated in 10 patients with alcoholic liver cirrhosis (EtOH-Ci) and 10 healthy controls (C). Resting metabolic rate (RMR) varied from 1,269 to 2,467 kcal/day in C and from 1,228 to 2,098 kcal/day in EtOH-Ci. RMR was significantly related to fat-free mass (FFM) in both groups, but EtOH-Ci decreased FFM and increased RMR when expressed per kilogram FFM (+33%). Glucose intolerance, hyperinsulinemia, and a decreased C-peptide-to-insulin ratio were observed in EtOH-Ci after a test meal. Concomitantly, nonoxidative glucose metabolism was reduced in association with normal increases in glucose oxidation. EtOH-Ci reduced insulin sensitivity (-59%) and maximal insulin-dependent glucose disposal (-40%) during a sequential two-step glucose clamp protocol (phase 1: 1 mU.kg body wt-1.min-1 insulin infusion rate + euglycemia; phase 2: 4 mU.kg body wt-1.min-1 insulin infusion rate + 165 mg/dl plasma glucose concentration). This was explained by reduced glucose storage (-99%, -51%) in association with normal responses in glucose oxidation rate, plasma lactate concentration, lipid oxidation rate, and rate of lipogenesis. Defective glucose storage was independent of reduced FFM. EtOH-Ci increased glucose-induced thermogenesis by 57%. We conclude that increased resting metabolic rate, enhanced thermogenesis, defective glucose storage, and normal glucose oxidation together result in increased energy needs and favor negative energy balance in patients with alcoholic cirrhosis.

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Higher insulin infusion rate but not 24-h insulin consumption is associated with hypoglycemia in critically ill patients

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2015.09.018 ◽

2015 ◽

Vol 110 (3) ◽

pp. 322-327

Author(s):

John J. Radosevich ◽

Asad E. Patanwala ◽

Paul D. Frey ◽

Yong G. Lee ◽

Holly Paddock ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Infusion Rate ◽

Insulin Infusion ◽

Insulin Infusion Rate

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Short-term topiramate treatment does not improve insulin sensitivity or secretion in obese insulin-resistant women

Acta Endocrinologica ◽

10.1530/eje-12-0500 ◽

2012 ◽

Vol 167 (6) ◽

pp. 839-845 ◽

Cited By ~ 4

Author(s):

Maria A Sleddering ◽

Marieke Snel ◽

Trea C M Streefland ◽

Hanno Pijl ◽

Ingrid M Jazet

Keyword(s):

Insulin Sensitivity ◽

Infusion Rate ◽

Insulin Infusion ◽

Cell Function ◽

Controlled Study ◽

Β Cell ◽

Insulin Resistant ◽

Insulin Infusion Rate ◽

Long Term Treatment ◽

Β Cell Function

ObjectiveLong-term treatment with topiramate reduces body weight and improves insulin sensitivity in obese humans. Our aim was to evaluate the effect of topiramate treatment for 4 weeks on insulin sensitivity and secretion, independent of weight loss.DesignRandomized, double-blind, crossover, placebo-controlled study.MethodsThirteen obese (BMI 36.6±1.3 kg/m2 (mean±s.e.m.)), insulin-resistant (homeostasis model of assessment-insulin resistance 2.0±0.2) women received topiramate (T, maximum dose of 75 mg) and placebo (P) for 4 weeks, separated by a 4-week washout period. Insulin sensitivity and β-cell function were assessed using a two-step hyperinsulinemic euglycemic clamp with stable isotopes and a hyperglycemic clamp.ResultsHepatic and peripheral insulin sensitivities were not affected by topiramate treatment (glucose disposal rate (step 1 (insulin infusion rate 10 mU/m2 per min) T: 17.5±0.8 vs P: 18.5±1.0 μmol/kgLBM per min, t=1.016, P=0.33; step 2 (insulin infusion rate 40 mU/m2 per min) T: 27.9±3.2 vs P: 28.8±1.9 μmol/kgLBM per min, t=0.418, P=0.68)). Subjects lost a small amount of weight during the topiramate period (T: −1.0±0.2 vs P: −0.1±0.2 kg, t=2842, P=0.15). There were no changes in body fat mass, blood pressure, and fasting glucose. β-Cell function was not affected by topiramate as evidenced by an unaltered area under the curve of early (0–10 min; T: 1929.6±265.7 vs P: 2024.7±333.6 pmol/l, t=−0.357, P=0.73) and late (80–120 min; T: 28 017.7±5029.9 vs P: 31 567.7±5376.2 pmol/l, t=−1.481, P=0.16) phase insulin levels during hyperglycemia. The use of topiramate was associated with significant side effects such as paresthesia, nausea, dizziness, and concentration problems.ConclusionsLow-dose topiramate treatment for 4 weeks, relative to placebo, had no significant effect on insulin sensitivity in overweight/obese adult females without established diabetes.

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