Variability In Blood Glucose Concentrations Research Articles

Closed-loop artificial endocrine pancreas from Japan.

The development of a closed-loop artificial pancreas (AP) in the Western countries and Japan is different. In Western countries, wearable AP with a closed-loop glycemic control system has been developed as a treatment for patients with type 1 and type 2 diabetes. On the contrary, in Japan, bedside closed-loop AP explored by a Japanese company (Nikkiso, Tokyo, Japan) has developed as perioperative glycemic control device in surgical patients and acute care patients with emergency. In this article, we reviewed the scientific evidence in the past and present and future prospects of perioperative glycemic control using bedside AP with a closed-loop system in Japan. Conventional perioperative strict glycemic controls have three major problems: hyperglycemia, hypoglycemia, and variability in blood glucose concentrations. In Japan, perioperative strict glycemic control using the current bedside AP STG-55 (Nikkiso, Tokyo, Japan) has been developed since 2010. This novel glycemic control method achieved not only stable glycemic control without hyperglycemia, hypoglycemia, and less variability of blood glucose concentrations but also reduced postoperative infectious complications in patients undergoing major surgeries. Among the rapidly increasing number of surgical or emergency patients with diabetes, frailty, and sarcopenia of intrinsic glucose intolerance, more sophisticated and smaller AP available easily in operating rooms and intensive care units will be warranted to promote improved therapeutic outcomes in such critically ill patients.

Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury.

The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n=19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n=19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100-150mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48h were 0.72, 0.78, and 0.79mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.

Current topics in glycemic control by wearable artificial pancreas or bedside artificial pancreas with closed-loop system.

The incidence of diabetes is increasing at an unprecedented pace and has become a serious health concern worldwide during the last two decades. Despite this, adequate glycemic control using an artificial pancreas has not been established, although the 21st century has seen rapid developments in this area. Herein, we review current topics in glycemic control for both the wearable artificial pancreas for type 1 and type 2 diabetic patients and the bedside artificial pancreas for surgical diabetic patients. In type 1 diabetic patients, nocturnal hypoglycemia associated with insulin therapy remains a serious problem that could be addressed by the recent development of a wearable artificial pancreas. This smart phone-like device, comprising a real-time, continuous glucose monitoring system and insulin pump system, could potentially significantly reduce nocturnal hypoglycemia compared with conventional glycemic control. Of particular interest in this space are the recent inventions of a low-glucose suspend feature in the portable systems that automatically stops insulin delivery 2h following a glucose sensor value<70mg/dL and a bio-hormonal pump system consisting of insulin and glucagon pumps. Perioperative tight glycemic control using a bedside artificial pancreas with the closed-loop system has also proved safe and effective for not only avoiding hypoglycemia, but also for reducing blood glucose level variability resulting in good surgical outcomes. We hope that a more sophisticated artificial pancreas with closed-loop system will now be taken up for routine use worldwide, providing enormous relief for patients suffering from uncontrolled hyperglycemia, hypoglycemia, and/or variability in blood glucose concentrations.

Perioperative intensive insulin therapy using an artificial endocrine pancreas with closed-loop glycemic control system: the effects of no hypoglycemia

BackgroundWe examined whether perioperative intensive insulin therapy (IIT) using an artificial pancreas (AP) with a closed-loop glycemic control system can be used to prevent hypoglycemia in surgical patients. MethodsBetween 2006 and 2012, perioperative glycemic control using an AP was performed in 427 patients undergoing general surgery. A total of 305 patients undergoing IIT using an AP in the target blood glucose range of 80 to 110 mg/dL were enrolled in the study. Data were collected prospectively and were reviewed or analyzed retrospectively. ResultsNo patients had hypoglycemia. Perioperative mean blood glucose level and achievement rates in target blood glucose range of 80 to 110 mg/dL were 100.5 ± 11.9 mg/dL and 88.1% ± 16.0%, respectively. For the 3 primary operative methods, including hepatic, pancreatic, and esophageal resections, there were no significant differences in glycemic control stability between the types of surgery. ConclusionPerioperative IIT using an AP with a closed-loop glycemic control system can be used to prevent hypoglycemia and maintain stable glycemic control with less variability of blood glucose concentration.

Closed-loop control strategy for type I diabetic patients

Administering ‘optimal’ amount of insulin to maintain the blood glucose (BG) concentration in the normoglycaemic range is vital in type I diabetics. Insulin injection therapy is widely practiced for the maintenance of blood glucose levels within the normoglycemic range (70–100 mg/dL) for type I diabetics. Current insulin therapy for patients with type I diabetes often results in high variability in blood glucose concentrations and may cause hyperglycemic/hypoglycemic episodes. Closing the glucose control loop with a fully automated electro-mechanical pancreas will improve the quality of life for insulin-dependent patients. The performances of the nominal continuous H∞ controller and robust controllers are compared with the proportional-integral-derivative (PID) and internal model control (IMC) controllers. The resulting PID and IMC controllers are designed by considering first order plus delay time (FOPDT) model of the system to be controlled.

The evaluation of the ability of closed-loop glycemic control device to maintain the blood glucose concentration in intensive care unit patients*

Reduction in the variability of blood glucose concentration might be an important aspect of blood glucose management. A closed-loop glycemic control device (STG-22; NIKKISO, Tokyo, Japan) has been developed to maintain blood glucose levels within the target range through automatic infusion of insulin and glucose. We hypothesized that the STG-22 system could provide optimal blood glucose management without causing hypoglycemic events in patients admitted to intensive care units. In this study, we investigated the feasibility of glycemic control with the STG-22 system. Furthermore, we evaluated the variability in blood glucose concentration associated with the use of the STG-22 system. Retrospective analysis. A five-bed medical/surgical intensive care unit in a university hospital. Two hundred eight patients admitted to the intensive care unit between August 2006 and July 2009. None. We calculated the mean and sd of blood glucose concentrations in each patient during intensive insulin therapy (target range, 90-110 mg/dL) administered using STG-22. In addition, to evaluate the blood glucose control achieved using STG-22, the durations for which the blood glucose level was maintained at 70-110 mg/dL, 110-150 mg/dL, 150-180 mg/dL, and>180 mg/dL were calculated. The average operation time of STG-22 was 33.9±42.4 hrs. The blood glucose level was maintained at 70-110 mg/dL for 49.5% of the study period; the corresponding values for 110-150 mg/dL, 150-180 mg/dL, and>180 mg/dL were 31.4%, 7.0%, and 6.9%, respectively. No hypoglycemic events occurred. The sd of blood glucose levels was 19.9±10.9 mg/dL. After a level of 150 mg/dL was achieved, the sd of blood glucose was 12.6±3.1 mg/dL. STG-22 can help maintain optimal blood glucose levels without causing hypoglycemia in patients admitted to the intensive care unit. In addition, the use of this device might help decrease the variability in blood glucose concentration. Further randomized clinical trials are required to elucidate whether the low glucose variability maintained using STG-22 can contribute to improving the outcomes of patients admitted to the intensive care unit.

The evaluation of the ability of the STG-22 to decrease the variability of blood glucose concentration in ICU patients

The evaluation of the ability of the STG-22 to decrease the variability of blood glucose concentration in ICU patients

Adaptive control strategy for regulation of blood glucose levels in patients with type 1 diabetes

Current insulin therapy for patients with type 1 diabetes often results in high variability in blood glucose concentrations and may cause hyperglycemic/hypoglycemic episodes. Closing the glucose control loop with a fully automated electro-mechanical pancreas will improve the quality of life for insulin-dependent patients. An adaptive control algorithm is proposed to keep glucose concentrations within normoglycemic range and dynamically respond to glycemic challenges. A model-based control strategy is used to calculate the required insulin infusion rate, while the model parameters are recursively tuned. The algorithm handles delays associated with insulin absorption, time-lag between subcutaneous and blood glucose concentrations, and variations in inter/intra-subject glucose–insulin dynamics. Simulation results for simultaneous meal and physiological disturbances are demonstrated for subcutaneous insulin infusion.

What Is a NICE-SUGAR for Patients in the Intensive Care Unit?

What Is a NICE-SUGAR for Patients in the Intensive Care Unit?

Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients

Survey of Anesthesiology: April 2007 - Volume 51 - Issue 2 - p 67-68 doi: 10.1097/01.sa.0000248499.73757.21

Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients

Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients

Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients

Intensive insulin therapy may reduce mortality and morbidity in selected surgical patients. Intensive insulin therapy also reduced the SD of blood glucose concentration, an accepted measure of variability. There is no information on the possible significance of variability in glucose concentration. The methods included extraction of blood glucose values from electronically stored biochemical databases and of data on patient's characteristics, clinical features, and outcome from electronically stored prospectively collected patient databases; calculation of SD of glucose as a marker of variability and of several indices of glucose control in each patient; and statistical assessment of the relation between these variables and intensive care unit mortality. There were 168,337 blood glucose measurements in the study cohort of 7,049 critically ill patients (4.2 hourly measurements on average). The mean +/- SD of blood glucose concentration was 1.7 +/- 1.3 mM in survivors and 2.3 +/- 1.6 mM in nonsurvivors (P < 0.001). Using multiple variable logistic regression analysis, both mean and SD of blood glucose were significantly associated with intensive care unit mortality (P < 0.001; odds ratios [per 1 mM] 1.23 and 1.27, respectively) and hospital mortality (P < 0.001 and P = 0.013; odds ratios [per 1 mM] 1.21 and 1.18, respectively). The SD of glucose concentration is a significant independent predictor of intensive care unit and hospital mortality. Decreasing the variability of blood glucose concentration might be an important aspect of glucose management.

Myocardial infarction and type II diabetes--preferential treatment for high risk patients?

To compare variability of blood glucose concentration in patients with type II diabetes with (cases) and without (controls) myocardial infarction. A secondary objective was identification of predictive factors for higher blood glucose on discharge from hospital. A retrospective matched case-control study. Medical notes of 101 type II diabetic patients admitted with a myocardial infarction (MI) and 101 type II diabetic patients (controls) matched on gender and age with no MI were reviewed. Blood glucose concentrations over two consecutive 48-h periods were collected. Demographic data and therapy on admission/discharge were also collected. Patient characteristics were comparable on recruitment excluding family history of cardiovascular disease (P=0.003), dyslipidaemia (P=0.004) and previous history of MI (P=0.007). Variability of blood glucose in cases was greater over the first 48 h compared with the second 48 h (P=0.03), and greater when compared with controls over the first 48 h (P=0.01). Cases with blood glucose on discharge >8.2 mmol / L (n=45) were less likely to have a history of previous MI (P=0.04), ischaemic heart disease (P=0.03) or hypertension (P=0.02). Type II diabetics with an MI have higher and more variable blood glucose concentrations during the first 48 h of admission. Only cardiovascular 'high risk' patients had target blood glucose set on discharge. The desirability of all MI patients with diabetes, having standardized-glucose infusions to reduce variability of blood glucose, should be evaluated in a randomized controlled trial.

Periodic high extracellular glucose enhances production of collagens III and IV by mesangial cells

We examined the effects of periodic changes in extracellular glucose concentration on matrix production and proliferation using three groups of cultured rat mesangial cells (MCs): 1) MCs in medium with continuous 5 mM glucose (CL), 2) MCs in medium alternating daily between 5 and 25 mM glucose (PH), and 3) MCs in medium with continuous 25 mM glucose (CH). MCs cultured in PH for 10 days produced 329 and 110% more type III collagen protein than MCs cultured in CL and CH, respectively. MCs cultured in PH induced 31 and 14% more type IV collagen than MCs cultured in CL and CH, respectively. Extracellular glucose concentration had no effect on the amount of type I collagen produced. MCs cultured in PH or CH for 5 days also expressed increased levels of type I, III, and IV collagen mRNA compared with MCs cultured in CL. MCs cultured in PH for 8-10 days also produced significantly more DNA than MCs in CL or CH. These data suggest that the temporal pattern of exposure to high extracellular glucose plays a role in regulating matrix formation and cellular proliferation by MCs. Furthermore, periodic elevations of extracellular glucose had a greater stimulatory effect on collagen production than a sustained elevation. These results suggest that decreasing the variability of blood glucose concentration may decrease the adverse effect of elevated glucose levels on MC matrix production and the progression of diabetic glomerulopathy.