Continuous Insulin Infusion Research Articles

AP@home: The Artificial Pancreas Is Now at Home.

In the past years the development of an artificial pancreas (AP) has made great progress and many activities are ongoing in this area of research. The major step forward made in the last years was moving the evaluation of AP systems from highly controlled experimental conditions to daily life conditions at the home of patients with diabetes; this was also the aim of the European Union-funded AP@home project. Over a time period of 5 years a series of clinical studies were performed that culminated in 2 "final studies" during which an AP system was used by patients in their home environment for 2 or 3 months without supervision by a physician, living their normal lives. Two different versions of the AP system developed within this project were evaluated. A significant improvement in glycated hemoglobin was observed during closed-loop conditions despite the fact that during the control period the patients used the best currently available therapeutic option. In addition, a "single-port AP system" was developed within the project that combines continuous glucose monitoring and insulin infusion at a single tissue site. By using such a combined device the patients not only have to carry one less device around, the number of access points through the skin is also reduced from 2 to 1. In summary, close cooperation of 12 European partners, both academic centers and industry, enabled the development and evaluation of AP systems under daily life conditions. The next step is to develop these into products in cooperation with commercial partners.

Development of a cross-disciplinary continuous insulin infusion protocol for non-critically ill patients in a French university hospital.

In non-critically ill patients, the use of an insulin syringe pump allows the management of temporary situations during which other therapies cannot be used (failure of subcutaneous injections, awaiting advice from the diabetes team, emergency situations, prolonged corticosteroid therapy, initiation of an artificial nutrition, need for a fasting status, etc.). To manage the risks related to this «never event», the use of a standard validated protocol for insulin administration and monitoring is an essential prerequisite. To this end, a multidisciplinary approach is recommended. With the support of our subcommission «Endocrinology-Diabetology», we proceeded with a «step-by-step process» to create such a standardized protocol: (1) review of all existing protocols in our hospital; (2) overview of the literature data concerning insulin infusion protocols developed by multidisciplinary teams in France and abroad; (3) development of a standardized protocol for non-intensive care unit patients, respecting the current recommendations and adapting it to the working habits of health teams; and (4) validation of the protocol Two protocols based on the same structure but adapted to the health status of the patient have been developed. The protocols are divided in to three parts: (1) golden rules to make the use of the protocol appropriate and safe; (2) the algorithm (a double entry table) corresponding to a dynamic adaptation of insulin doses, clearly defining the target and the 'at risk situations'; and (3) practical aspects of the protocol: preparation of the syringe, treatment initiation and traceability. The protocols have been validated by the institution. Our standardized insulin infusion protocol is simple, easy to implement, safe and is likely to be applicable in diverse care units. However, the efficiency, safety and the workability of our protocols have to be clinically evaluated.

Case Study: Remission of Type 2 Diabetes After Outpatient Basal Insulin Therapy.

Diabetes is a chronic, progressive disease with potentially serious sequelae. Treatment for type 2 diabetes often begins with oral agents and eventually requires insulin therapy. As the disease progresses, drug therapies are often intensified and rarely reduced to control glycemia. Conversely, in type 1 diabetes, some patients experience a “honeymoon period” shortly after diagnosis, wherein insulin needs decrease significantly before intensification is needed (1). No comparable honeymoon period has been widely described for type 2 diabetes. However, a few studies have demonstrated that drug-free glycemic control can be achieved in type 2 diabetes for 12 months on average after a 2-week continuous insulin infusion (2–4). Here, we describe an unusual case of a 26-month drug holiday induced with outpatient basal insulin in a patient newly diagnosed with type 2 diabetes. A 69-year-old white woman (weight 72.7 kg, height 59 inches, BMI 32.3 kg/m2) was diagnosed with type 2 diabetes in June 2011. She presented with an A1C of 17.6% (target <7%) and a fasting blood glucose (FBG) of 452 mg/dL (target 70–130 mg/dL). Before diagnosis, the patient had not used any oral or parenteral steroids nor had she experienced any traumatic physical or emotional event or illness that could have abruptly increased her blood glucose. Metformin 500 mg twice daily was initiated at diagnosis, but was discontinued 9 days later to avoid risk of lactic acidosis, as her serum creatinine was 1.5 mg/dL. At that time, her fasting self-monitoring of blood glucose (SMBG) values ranged from 185 to 337 mg/dL. Treatment with 25 units of insulin detemir daily (0.34 units/kg/day) was initiated in place of metformin. The patient was counseled on diet modifications and encouraged to exercise. One month later (July 2011), the patient’s fasting SMBG values had improved to a range of 71–212 mg/dL with a …

Intensive versus conventional glycaemic control for treating diabetic foot ulcers.

The estimated likelihood of lower limb amputation is 10 to 30 times higher amongst people with diabetes compared to those without diabetes. Of all non-traumatic amputations in people with diabetes, 85% are preceded by a foot ulcer. Foot ulceration associated with diabetes (diabetic foot ulcers) is caused by the interplay of several factors, most notably diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD) and changes in foot structure. These factors have been linked to chronic hyperglycaemia (high levels of glucose in the blood) and the altered metabolic state of diabetes. Control of hyperglycaemia may be important in the healing of ulcers. To assess the effects of intensive glycaemic control compared to conventional control on the outcome of foot ulcers in people with type 1 and type 2 diabetes. In December 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; Elsevier SCOPUS; ISI Web of Knowledge Web of Science; BioMed Central and LILACS. We also searched clinical trial databases, pharmaceutical trial databases and current international and national clinical guidelines on diabetes foot management for relevant published, non-published, ongoing and terminated clinical trials. There were no restrictions based on language or date of publication or study setting. Published, unpublished and ongoing randomised controlled trials (RCTs) were considered for inclusion where they investigated the effects of intensive glycaemic control on the outcome of active foot ulcers in people with diabetes. Non randomised and quasi-randomised trials were excluded. In order to be included the trial had to have: 1) attempted to maintain or control blood glucose levels and measured changes in markers of glycaemic control (HbA1c or fasting, random, mean, home capillary or urine glucose), and 2) documented the effect of these interventions on active foot ulcer outcomes. Glycaemic interventions included subcutaneous insulin administration, continuous insulin infusion, oral anti-diabetes agents, lifestyle interventions or a combination of these interventions. The definition of the interventional (intensive) group was that it should have a lower glycaemic target than the comparison (conventional) group. All review authors independently evaluated the papers identified by the search strategy against the inclusion criteria. Two review authors then independently reviewed all potential full-text articles and trials registry results for inclusion. We only identified one trial that met the inclusion criteria but this trial did not have any results so we could not perform the planned subgroup and sensitivity analyses in the absence of data. Two ongoing trials were identified which may provide data for analyses in a later version of this review. The completion date of these trials is currently unknown. The current review failed to find any completed randomised clinical trials with results. Therefore we are unable to conclude whether intensive glycaemic control when compared to conventional glycaemic control has a positive or detrimental effect on the treatment of foot ulcers in people with diabetes. Previous evidence has however highlighted a reduction in risk of limb amputation (from various causes) in people with type 2 diabetes with intensive glycaemic control. Whether this applies to people with foot ulcers in particular is unknown. The exact role that intensive glycaemic control has in treating foot ulcers in multidisciplinary care (alongside other interventions targeted at treating foot ulcers) requires further investigation.

Insulinoterapia contínua versus múltiplas injeções de insulina no tratamento da diabetes tipo 1: um estudo longitudinal

ObjectiveTo compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. Methods40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). ResultsAlthough mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15–40 patients have severe hypoglycemic events versus 5–40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. ConclusionsThis is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy.

Hyperhidrosis–Hypertension–Hypotension in Scorpion Envenoming Syndrome: Insulin–Glucose Infusion Reverses All the Clinical Manifestations Caused by Massive Release of Counter-Regulatory Hormones due to Killer Scorpion (Buthidae family) Stings

Death due to poisonous scorpion (Buthidae family) stings is common in many of the developing countries all over the world. Severe uncontrollable pain at the site of sting (without local oedema) results in autonomic storm, release massive quantities of catecholamines, angiotensin II, ACTH, glucocorticoids, glucagon, ADH, aldosterone, either suppressed insulin secretion/or hyperinsulinemia – insulin resistance causing hyperglycemia and a sudden increase in Free Fatty Acid levels (FFA). The increase in catecholamine and angiotensin II hormonal levels cause hyperhidrosis, initial transient hypertension, hyper salivation, hypotension, mydriasis, miosis, DIC, acute pancreatitis, and many other clinical manifestations. Suddenly increased FFA levels are toxic, produce inactivation of Na+–K+ATPase activities, arrhythmias, conduction defects, myocardial infarction, cardiogenic pulmonary oedema, Acute Respiratory Distress Syndrome (ARDS), multisystem organ failure and death. Hyperhidrosis is harmful and wasteful loss of fluid and electrolytes resulting in peripheral circulatory failure, hypotension and death. Based on our animal experimental studies and treating the scorpion sting victims with insulin glucose infusion, we consider that insulin has a primary metabolic role in preventing and reversing hyperhidrosis, hypertension, hypotension, cardiovascular changes, cardiogenic and non-cardiogenic pulmonary (ARDS) oedema. Treatment: Continuous infusion of regular crystalline insulin at the rate of 0.3 U/g glucose and glucose at the rate of 0.1 g/kg body weight/hour, for 48–72 hour, supplementation of potassium (if required), and maintenance of acid–base fluid and electrolyte balance.

Time-dependent changes in insulin requirement for maternal glycemic control during antenatal corticosteroid therapy in women with gestational diabetes: a retrospective study.

Though recommended for pregnant women at risk of preterm birth to improve perinatal outcomes, antenatal corticosteroid (ACS) treatment can cause maternal hyperglycemia, especially in cases of glucose intolerance. A standardized protocol for preventing hyperglycemia during ACS treatment remains to be established. We herein retrospectively investigated the time-dependent changes in insulin dose required for maternal glycemic control during ACS treatment in gestational diabetes (GDM). Twelve singleton pregnant women with GDM who received 12 mg of betamethasone intramuscularly twice 24 hours apart were included in this analysis. Of those, eight also received ritodrine hydrochloride for preterm labor. The blood glucose levels were maintained at 70-120 mg/dL with continuous intravenous infusion of insulin and nothing by mouth for 48 hours after the first betamethasone administration. After the first dose of betamethasone, the insulin dosage needed for glycemic control gradually increased and reached a maximum (6.6 ± 5.8 units/hr) at 10 hours, then, decreased to 4.1 ± 1.5 units/hr at 24 hours. Similar changes in the insulin requirement were found after the second betamethasone dose (the maximum insulin dosage: 5.5 ± 1.6 units/hr at 9 hours following the second administration). Women treated with ritodrine hydrochloride needed more insulin, than those without ritodrine hydrochloride treatment (130.8 ± 15.0 vs. 76.8 ± 15.2 units/day, respectively, p < 0.05). Our data indicated that the requirement for insulin is highest 9-10 hours after each dose of betamethasone. When GDM is treated with ACS, levels of blood glucose should be carefully monitored, especially in patients treated with ritodrine hydrochloride.

Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study

ObjectiveTo compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes mellitus. Methods40 patients with type 1 diabetes mellitus (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). ResultsAlthough mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15–40 patients have severe hypoglycemic events versus 5–40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. ConclusionsThis is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy.

Hypoglycemia and hyperglycemia in extremely low-birth-weight infants

Materials and methods All inborn ELBW neonates admitted to our NICU during a 5-year period were eligible for this retrospective analysis. Exclusion criteria were: birth weight (BW) 240 mg/dL in a single determination or >180 mg/dL in two determinations at 2-hour intervals. Continuous intravenous insulin infusion was started after an ineffective glucose restriction.

Use of intravenous insulin aspart for treatment of naturally occurring diabetic ketoacidosis in dogs.

To characterize the utility and safety of IV insulin aspart in the treatment of diabetes ketoacidosis (DKA) in dogs and to determine the times to resolution of hyperglycemia, ketonemia, and acidemia in dogs treated with IV insulin aspart. Prospective noncontrolled single arm study of dogs with DKA between February 2010 and March 2011. University teaching hospital. Six dogs with spontaneous DKA and blood glucose (BG) concentration >13.8 mmol/L (250 mg/dL), pH between 7.0 and 7.35, and blood beta-hydroxybutyrate >2.0 mmol/L were treated with an IV continuous rate infusion (CRI) of aspart insulin. The time to biochemical resolution of DKA was defined as the time interval from when the IV CRI of aspart insulin began until marked hyperglycemia (BG concentration >13.8 mmol/L [250 mg/dL]), acidemia (venous pH <7.35), and ketonemia (beta-hydroxybutyrate concentration >2.0 mmol/L) resolved. Aspart insulin was administered as an IV CRI at an initial dose of 0.09 U/kg/h. The dose was adjusted according to a previously published protocol. The median time to biochemical resolution of DKA in dogs treated with insulin aspart was 28 hours (range, 20-116 h). Mean BG concentration decreased significantly from the time IV fluid resuscitation began (32.0 mmol/L [576 mg/dL]; range, 14.9-38.9 mmol/L [268-700 mg/dL]) until 6 hours later when IV aspart insulin CRI began (20.1 mmol/L [363 mg/dL]; range, 9.4-26.1 mmol/L [169-470 mg/dL], P = 0.03). No adverse effects were observed in association with IV insulin aspart administration. Median cost of hospitalization was US$3,477 (range, US$1,483-10,469). Median total units per kilogram of administered IV insulin aspart was 2.97 U/kg (range, 2.04-10.52 U/kg). Intravenous CRI of insulin aspart is a safe and effective treatment for DKA in dogs. IV fluid resuscitation is recommended prior to insulin administration.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case.

Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18,984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials.

Intermittent insulin treatment mimics ischemic postconditioning via MitoKATP channels, ROS, and RISK

Objectives. It has previously been demonstrated that 15-min continuous insulin infusion at immediate reperfusion affords cardioprotection. This study sought to reduce the treatment time of insulin and test if intermittent insulin infusions can mimic ischemic postconditioning. Design. In a Langendorff perfused rat heart model of regional ischemia, hearts were at the onset of reperfusion subjected to either 5- or 1-min continuous insulin infusion or 3 × 30 s intermittent insulin infusions (InsPost); with or without inhibitors of Akt (SH-6), p70s6-kinase (rapamycin), mitochondrial ATP-sensitive potassium channels (5-hydroxydecanoic acid [5-HD]), or a scavenger of reactive oxygen species (ROS; 2-mercaptopropionyl glycine [MPG]). Infarct size is expressed as percent of area at risk and presented as mean ± standard error of the mean or s.e.m. Results. Only InsPost was able to reduce infarct size compared with controls (InsPost 33 ± 6% vs. Ctr 52 ± 4%, p < 0.05.). This cardioprotection was abrogated by co-administering SH-6, rapamycin, 5-HD, or MPG. (InsPost + SH-6 56 ± 9%, InsPost + Rapa 55 ± 8%, InsPost + 5-HD 56 ± 7%, InsPost + MPG 60 ± 3% vs. InsPost 33 ± 6% p < 0.05). These results were corroborated by a significant increase in phosphorylated Akt and p70s6k in the InsPost group compared with controls. Conclusion. Short intermittent insulin infusions can mimic ischemic postconditioning and reduce myocardial infarct size via Akt/p70s6k and mKATP channels/ROS-dependent signaling.

Intensive Versus Conventional Glycemic Control in Patients with Diabetes During Enteral Nutrition After Gastrectomy

BackgroundThis study compared intensive and conventional glycemic management strategies in diabetic patients receiving enteral nutrition after gastrectomy. MethodsDiabetic patients (n = 212) who underwent gastrectomy between September 2006 and March 2014 were randomized to intensive glycemic (IG) management with continuous insulin infusion (target glucose 4.4–6.1 mmol/l (80–110 mg/dl)) or conventional glycemic (CG) management with intermittent bolus insulin (target glucose <11.1 mmol/l (<200 mg/dl)). Outcomes included blood glucose concentrations, insulin administration, and postoperative morbidity and mortality. ResultsBlood glucose levels were lower (5.4±1.2 vs. 9.5±1.8 mmol/l, P < 0.001) and mean insulin dose was higher (55 ± 15 vs.32 ± 16 units/day, P < 0.001) in the IG than in the CG group. Rates of severe hypoglycemia (7.5 vs. 0.9 %, P = 0.035) and achievement of target blood glucose (86.3 vs. 72.6 %, P = 0.023) were higher, while severe hyperglycemia rate was lower (1.9 vs. 11.3 %, P = 0.010), in the IG group. Surgical site infection rate was lower in the IG group (4.7 vs. 13.2 %, P < 0.030). Rates of other infective complications, bleeding, delayed gastric emptying, obstruction, hepatic dysfunction, renal dysfunction, and circulatory insufficiency were similar in the two groups. ConclusionsIntensive glycemic control in diabetic patients receiving enteral nutrition after gastrectomy was associated with a lower surgical site infection rate but a higher hypoglycemia rate.

The effect of insulin therapy algorithms on blood glucose levels in patients following cardiac surgery: A systematic review.

A number of insulin infusion algorithms, with varying methods and effects, have been developed to guide the management of postoperative hyperglycemia in critically ill patients. The objective of this study was to investigate the effect of insulin therapy algorithms on blood glucose levels in patients in critical care environments following cardiac surgery. Types of participants: Adult patients aged 18 or older who were admitted to a critical care environment after cardiac surgery and who received insulin therapy for glycemic control during the acute postoperative phase of their admission. Types of intervention: The intervention of interest was continuous intravenous insulin therapy. Types of studies: Experimental study designs including randomized controlled trials, non-randomized controlled trials and controlled before and after studies published in the English language were included in this review. Types of outcomes: Primary outcomes of interest included objective measures of glycemic control and secondary outcomes of interest included the incidence of adverse events. The search aimed to find both published and unpublished studies through electronic databases, reference lists, key reports and the World Wide Web. An extensive search was undertaken for the following databases: Medline, CINAHL, PubMed, Embase, Scopus, the Cochrane Library, Dare, Social Science Index, ProQuest, and MedNar. Databases were searched up to March 2014. All studies selected were assessed by two reviewers independently for methodological quality prior to inclusion in the review using the standardized Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument critical appraisal tool. Any disagreements that arose between the reviewers were resolved through discussion. Quantitative data was extracted from papers included in the review using the standardized data extraction tool from Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. All results were subject to double data entry. Statistical pooling of the data in meta-analysis was carried out using Review Manager meta-analysis software where possible. Odds Ratios, Relative Risks, Weighted Means Differences and their 95% Confidence Interval were calculated where appropriate. Where statistical pooling was not possible due to the heterogeneity of the studies the findings are presented in narrative form including tables and figures. Thirteen studies were included in the final review. Pooled data demonstrated significantly improved mean blood glucose levels (Weighted Means Differences -27.24, 95% Confidence Interval: -27.77 - -26.72), p < 0.00001 and achievement of target blood glucose levels range (Relative Risks 1.43, 95% Confidence Interval: 1.18 - 1.72), p = 0.0002, among participants who received the paper nomogram continuous intravenous insulin method of glucose control compared to the bolus regime group. Studies that investigated paper nomogram directed continuous intravenous insulin compared to computer calculator directed continuous intravenous insulin demonstrated a statistically significant improved mean blood glucose levels (Weighted Means Differences -23.74, 95% Confidence Interval: -24.45 - -23.02), p <0.00001 and higher percentage of time in which glucose levels were within the target range in the computer calculator group. A significantly lower incidence (p < 0.05) of hyperglycemia was observed in the computerized calculator directed CII group (1.3 ± 1.2%) compared to the paper nomogram CII (6.5 ± 2%). There is evidence of a benefit of continuous insulin infusions for patients following cardiac surgery with the computer calculator CII method achieving optimal glycemic control. The implementation of a computer calculator CII algorithm allows for individualized patient treatment. However, given the limited availability of the computer based algorithm, the implementation of a paper based algorithm would be justified. Future studies to compare the methods of computer calculator directed CII to paper nomogram directed CII should be undertaken using more rigorous research designs such as randomized controlled trials with sufficiently powered sample sizes. Definitions for both hypoglycemia and hyperglycemia should be standardized.

Continuous postoperative insulin infusion reduces deep sternal wound infection in patients with diabetes undergoing coronary artery bypass grafting using bilateral internal mammary artery grafts: a propensity-matched analysis.

Deep sternal wound infection (DSWI), especially in patients with diabetes mellitus (DM), is a major concern after coronary artery bypass grafting (CABG) with bilateral internal mammary artery (BIMA) grafts. We evaluated the risk of DSWI and other clinical outcomes between continuous insulin infusion therapy (CIT) and insulin sliding scale therapy (IST) in a cohort of DM patients who underwent CABG with BIMA. The clinical records of DM patients who underwent isolated CABG with BIMA were retrospectively reviewed. The study population consisted of 95 patients who received CIT and 126 patients who received IST. Furthermore, a one-to-one matched analysis based on estimated propensity scores for patients who received CIT or IST yielded two groups comprising 58 patients each. The proportion of patients with DSWI, overall survival rates and major adverse cardiac events were compared between the two groups in the overall and the propensity-matching cohort. The prevalence of DSWI requiring debridement and closure was significantly reduced in the CIT group compared with that in the IST group [1/95 (1.1%) vs 9/126 (7.1%), P = 0.031]; these results were not attenuated even after propensity-matching analysis [0/58 (0%) vs 6/58 (10.3%), P = 0.031]. The mean preoperative glucose levels were similar between the two groups (157.5 ± 54.6 vs 176.1 ± ±70 mg/dl, P = 0.063), whereas the mean glucose values were significantly lower on the first and second operative days in the CIT group than in the IST group (132.9 ± 44.1 vs 197.8 ± 78.6 mg/dl, P < 0.0001; 153.5 ± 58.8 vs 199.6 ± 89.1 mg/dl, P < 0.0001, respectively). The glucose variability levels within 24 h postoperatively were significantly higher in the IST group (46.1 ± 19.4 vs 66.4 ± 26.8 mg/dl, P < 0.0001). The 30-day and 1-year survival rates were similar between the two groups (100 vs 99.2%, P = 0.384; 96.6 vs 94.4%, P = 0.454). No results were changed in the propensity-matching models. The CIT approach reduced the variability in glucose concentration and resulted in fewer instances of DSWI after CABG with BIMA grafts.

Efficacy of oral glucocorticoid and cyclosporine in a case of rituximab-refractory type B insulin resistance syndrome.

We describe a case of type B insulin resistance syndrome associated with systemic lupus erythematosus (SLE) that was refractory to rituximab and successfully treated with a combination of oral glucocorticoids and cyclosporine. Prior to treatment, insulin resistance was severe, and application of a hyperinsulinemic euglycemic clamp was not possible despite the continuous intravenous infusion of insulin at a maximum rate of 9.0 mU/kg/min. The addition of cyclosporine to oral glucocorticoid therapy resulted in remission of insulin resistance. The combination of oral prednisolone and cyclosporine might be effective in treating type B insulin resistance syndrome, particularly in rituximab-resistant cases. However, nephrotoxicity is a particular concern for patients receiving long-term cyclosporine therapy.

Hyperglycemia in Critically Ill Patients: Management and Prognosis.

Introduction:Hyperglycemia is a common complication of critical illness. Patients in intensive care unit with stress hyperglycemia have significantly higher mortality (31%) compared to patients with previously confirmed diabetes (10%) or normoglycemia (11.3%). Stress hyperglycemia is associated with increased risk of critical illness polyneuropathy (CIP) and prolonged mechanical ventilation. Intensive monitoring and insulin therapy according to the protocol are an important part of the treatment of critically ill patients.Objective:To evaluate the incidence of stress hyperglycemia, complications and outcome in critically ill patients in our Medical intensive care unit.Materials and methods:This study included 100 patients hospitalized in Medical intensive care unit during the period January 2014–March 2015 which were divided into three groups: Diabetes mellitus, stress-hyperglycemia and normoglycemia. During the retrospective-prospective observational clinical investigation the following data was obtained: age, gender, SAPS, admission diagnosis, average daily blood glucose, highest blood glucose level, glycemic variability, vasopressor and corticosteroid therapy, days on mechanical ventilation, total days of hospitalization in Medical intensive care unit, and outcome.Results:Patients with DM treated with a continuous insulin infusion did not have significantly more complications than patients with normoglycemia, unlike patients with stress hyperglycemia, which had more severe prognosis. There was a significant difference between the maximum level of blood glucose in recovered and patients with adverse outcome (p = 0.0277). Glycemic variability (difference between max. and min. blood glucose) was the strongest predictor of adverse outcome. The difference in glycemic variability between the stress-hyperglycemia and normoglycemic group was statistically significant (p = 0.0066). There was no statistically significant difference in duration of mechanical ventilation and total days of hospitalization in the intensive care unit between the groups.Conclusion:Understanding of the objectives of glucose regulation and effective glycemic control is essential for the proper optimization of patient outcomes.

Suppressed Insulin Secretion, Elevated Mediators of Inflammation, Hyper-Insulinemia-Insulin Resistance: Insulin Administration Reverses Cardiovascular, Metabolic Changes, Pulmonary Edema and All Other Clinical Manifestations in Scorpion Envenoming Syndrome

Death due to poisonous scorpion stings is common in many tropical and sub-tropical countries. Scorpion envenoming syndrome causes stimulation of neuro-endocrine axis resulting in autonomic storm, intense stimulation of sympathetic nervous system, massive release of catecholamines, angiotensin II, suppressed insulin secretion, glucagon, glucocorticoids, increased free fatty acid levels, hyperglycemia, hyper-insulinemia, insulin resistance, acute myocarditis, initial hypertension, hypotension, arrhythmias, conduction defects, ischemia, infarction, acute pancreatitis, CNS damage, motor aphasia, hemiplegia, mydriasis, hyperhidrosis, acute respiratory distress syndrome, disseminated intravascular coagulation, multi system organ failure, shock and death. The scorpion envenoming syndrome also causes stimulation of immuno-pathological axis, systemic and local inflammation, increase in production of proinflammatory cytokines IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12, TNF-α, IFN-γ and NO and contribute to immunological imbalance, hyperglycemia, hyper-insulinemia, insulin resistance, multi-system organ failure, shock and death. Elevated levels of TNF-α cause impaired glucose tolerance and induce insulin resistance for endogenously secreted insulin. Insulin administration reversed metabolic, respiratory changes, cardiogenic and non-cardiogenic pulmonary edema, electrocardiographic, cardiovascular changes and many other manifestations in our experimental animals and in our scorpion sting victims with scorpion envenoming syndrome. Treatment: Continuous infusion of regular crystalline insulin at the rate of 0.3 U/g glucose and glucose at the rate of 0.1g/kg body weight/h, for 48–72 h, with supplementation of potassium as needed, maintenance of fluid, electrolytes, acidbase balance.

A pilot study comparing a protocol using intermittent administration of glargine and regular insulin to a continuous rate infusion of regular insulin in cats with naturally occurring diabetic ketoacidosis

The goal of this pilot study was to compare regular insulin administered by continuous rate infusion (CRI) to an approach using insulin glargine and regular insulin administered intermittently. Prospective randomized clinical trial. University teaching hospital. Sixteen cats with diabetic ketoacidosis (DKA). Cats with DKA were randomized to either low-dose regular insulin CRI (CRI group; n = 8) or intermittent short- and long-acting insulin injections (subcutaneous [SC] glargine plus intramuscular [IM] regular insulin; SC/IM group; n = 8). Time of normalization of pH, bicarbonate, hyperglycemia, ketonemia, and appetite, as well as duration of hospitalization were recorded. Eleven of 16 cats (59%) survived to discharge, with no difference in survival between groups (P = 0.99). Times of resolution of hyperglycemia (P = 0.02) and ketonemia (P = 0.04), and normalization of pH (P = 0.04), and bicarbonate (P = 0.03) were significantly shorter in the SC/IM group. Cats in the SC/IM group also had a significantly shorter duration of hospitalization (SC/IM: median = 54 hr [range, 19-118 hr]; CRI: median = 111 hr [range, 58-271 hr]; P = 0.04). Time of first meal was not significantly different between groups. Although further research is required, an approach using intermittent short- and long-acting insulin injections appeared to be an effective option for treatment of DKA in cats.

Report of a 7 year case–control study of continuous intraperitoneal insulin infusion and subcutaneous insulin therapy among patients with poorly controlled type 1 diabetes mellitus: Favourable effects on hypoglycaemic episodes

AimsContinuous intraperitoneal insulin infusion (CIPII) is a last-resort treatment option for patients with type 1 diabetes mellitus (T1DM) who fail to reach adequate glycaemic control with subcutaneous (SC) insulin therapy. Aim was to compare the long-term effects of CIPII and SC insulin therapy among patients with T1DM in poor glycaemic control. MethodsPatients in which CIPII was initiated in 2006 were compared with a control group of T1DM patients who continued SC therapy. Linear mixed models were used to calculate differences between the baseline (2006) and final (2013) measurements within and between groups. ResultsA total of 95 patients of which 21 were using CIPII and 74 using SC insulin were included. Within the CIPII group, the number of hypoglycaemic episodes decreased with −5 (95% CI −8 to −3) per 2 weeks while it remained stable among SC patients. Over time, only the number of hypoglycaemic episodes decreased more with CIPII as compared to SC insulin treatment (difference: −6 (95% CI −9 to −4)). There were no differences between treatment groups regarding clinical parameters and quality of life scores over time. Pump or catheter dysfunction led to ketoacidosis in 6 patients: 2 using CIPII and 4 SC insulin. ConclusionsAfter 7 years of follow-up, there is a persistent decline of hypoglycaemic events among CIPII treated T1DM patients. Besides less hypoglycaemic episodes with CIPII therapy, there are no differences between long-term CIPII and SC insulin therapy.