Continuous Insulin Therapy Research Articles

La Suppléance Insulinique : nouvelles insulines, nouveaux procédés d'administration

The demonstrated role of the tight control of hyperglycaemia for the prevention of long-term diabetic complications has reoriented the goals of insulin supply toward the search for restoration of the effects of physiological insulin secretion rather than the simple survival of insulin deficient patients and the reduction in the number of daily insulin injections to be performed. Normal blood glucose control requires the availability of a fast-acting insulin therapy at meal time in order to reduce hyperglycaemic excursions and a basal insulin therapy able to stabilize blood glucose between meals. Reduction of induced hypoglycaemic risk represents the secondary objective beside the main goal of avoiding hyperglycaemia. Fast-acting analogues, by a faster dissociation of their hexameric conformation after their injection or infusion in subcutaneous tissue, reduce post-meal hyperglycaemia, while their shortened duration of action versus regular insulin minimizes late post-absorptive risk of hypoglycaemia. Long-acting analogues, by their precipitation in subcutaneous tissue or their slowly reversible binding to albumin, provide a benefit on blood glucose stability versus NPH or zinc insulins. Continuous insulin therapy using pumps offers both a better blood glucose stability than multiple daily injections and a broader flexibility in life mode. Using the peritoneal route by implantable pumps is a mean to improve blood glucose stability in poorly controlled patients in spite of optimized subcutaneous insulin therapy. The development of glucose sensors provides reinforced information on blood glucose, versus self-monitoring by capillary blood measurements, that contributes to a better adaptation of insulin therapy. First trials of connections between blood glucose data and insulin delivery open a perspective toward glucose-modulated insulin therapy, at least in periods outside meals, leading to first models of semi-automated artificial endocrine pancreas. The alternative of a cellular insulin supply by pancreas or islet transplantation looked promising during recent years, but lack of transplants and adverse events related to immune suppression limit their use to very specific cases where benefit/risk ratio is positive.

Weight gain is associated with improved glycaemic control but with adverse changes in plasma lipids and blood pressure isn Type 1 diabetes

To assess the effects of weight gain on metabolic control, plasma lipids and blood pressure in patients with Type 1 diabetes. Patients in the EURODIAB Prospective Complications Study (n = 3250) were examined at baseline and 1800 (55%) were re-examined a mean of 7.3 years later. Patients had Type 1 diabetes, defined as a diagnosis made before age 36 years and with a need for continuous insulin therapy within a year of diagnosis. Patients were aged 15-60 years at baseline and were stratified for age, sex and duration of diabetes. The change in HbA(1c) from baseline to follow-up examination was significantly more favourable in those who gained 5 kg or more during follow-up ('marked weight gain') than in patients who gained less or no weight or lost weight ('less or no weight gain'). In those with marked weight gain, there was a significantly greater rise in plasma triglycerides and total cholesterol and significantly less favourable changes in low-density lipoprotein and high-density lipoprotein cholesterol compared with those with less or no weight gain, with or without adjustment for HbA(1c). Systolic and diastolic blood pressure also rose significantly more in the group with marked weight gain. Weight gain in patients with Type 1 diabetes has adverse effects on plasma lipids and blood pressure, despite a small improvement in glycaemic control.

A one-year retrospective audit of the DIGAMI protocol

Aim To assess the impact of post-MI diabetes-care upon changes in diabetes therapy and on cardiovascular risk factors. Patients and methods Retrospective audit of case notes of patients with diabetes who were treated according to the DIGAMI protocol following an acute MI and who had completed at least one year of follow-up (n=86). Results A majority of patients continued insulin therapy beyond the standard recommendation of three months (7%, 84%, 75% at 0, 3 and 12 months respectively) resulting in an increase in the number of patients attending hospital diabetes clinics (17%, 94% and 61%). A majority of patients belonged to DIGAMI low-risk group 1 (85%) which was the category of patients shown to have a significant survival benefit in the original DIGAMI cohort. At the end of one year an increased number of patients achieved targets for control of systolic BP (49, 59 and 77 at 0, 3 and 12 months), diastolic BP (44, 74 and 77%), TC (34, 73 and 80%) and HbA1C (24, 45 and 60%) (p<0.05 for all). Weight increased progressively (82 kg, 87 kg A and 88 kg, p<0.05). Percentage of smokers was reduced (31, 9 and 11, p<0.05). Conclusion There was a significant rise in the number of patients receiving long-term insulin therapy, and attending secondary care follow-up. A significant and sustained increase was observed in achieving targets for HbA1C, BP and cholesterol.

Scintigraphic monitoring of catheter-port systems in type I diabetics with continuous insulin therapy.

We developed a non-invasive scintigraphic procedure to control the function of percutaneous catheter-port systems for continuous insulin therapy. The aim of the study was to evaluate the scintigraphic results and to compare the absorption kinetics of intraperitoneal and umbilical catheter-ports. Seven patients with intraperitoneal and nine patients with umbilical catheter-port systems implanted into the partially redilated umbilical vein were investigated. All these patients had normal functioning catheter-ports. Additionally, three patients with intraperitoneal and three patients with umbilical catheter-port dysfunction confirmed either by radiography or laparoscopy were studied. After the injection of (99 m)TcO (4)(-) into the port a region-of-interest was drawn around the activity at the tip of the catheter and the half-life of tracer absorption (T(1/2)) calculated. The normal intraperitoneal catheter-port group showed a T(1/2) value of 6.7 +/- 3.2 min and the normal umbilical catheter-port group a T(1/2) of 6.6 +/- 2.0 min. There was no significant difference in T(1/2) between intraperitoneal and umbilicial systems. The dysfunctional catheter-port group (T(1/2) 19.3 +/- 6.7 min) differed ( p = 0.0005) from the normal catheter-port group (T(1/2) 6.7 +/- 3.2 min). On the basis of the normal group an upper threshold value of T(1/2) was calculated to be 11.8 min. Imaging with (99 m)TcO (4)(-) is an accurate, non-invasive, and quick method to assess the function of insulin catheter-ports. A T(1/2) value > 11.8 min is indicative of a catheter dysfunction. Umbilical and intraperitoneal catheter-ports show similar absorption rates of (99 m)TcO (4)(-).

Effect of Hyperglycemia and Continuous Intravenous Insulin Infusions on Outcomes of Cardiac Surgical Procedures: The Portland Diabetic Project

ObjectiveTo describe the main findings of the Portland Diabetic Project, which elucidates the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineates the protective effects of intravenous insulin therapy in reducing those adverse outcomes. ResultsIn this ongoing 17-year prospective, nonrandomized, interventional study of 4,864 patients with diabetes who underwent an open-heart surgical procedure, we investigated the effects of hyperglycemia, and its subsequent reduction by continuous intravenous insulin (CII) therapy, on in-hospital outcomes. Increasing blood glucose levels were found to be directly associated with increasing rates of death, deep sternal wound infections (DSWI), length of hospital stay (LOS), and hospital cost. In separate multivariate analyses, increasing hyper-glycemia was found to be independently predictive of increasing mortality (P<0.0001), DSWI (P = 0.017), and LOS (P<0.002). Conversely, CII therapy, designed to achieve predetermined target blood glucose levels, independently reduced the risks of death and DSWI by 57% and 66%, respectively (P<0.0001 for both). Target blood glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the effect of the CII therapy on improved outcomes. Coronary artery bypass grafting-related mortality (2.5%) and DSWI rates (0.8%) in patients with diabetes were normalized to those of the nondiabetic population by the use of the Portland CII Protocol. ConclusionPerioperative hyperglycemia in patients undergoing a cardiac surgical procedure affects biochemical and physiologic functions, which, in turn, adversely alter mortality, LOS, and infection rates. The Portland CII Protocol is a cost-efficient method that effectively eliminates hyperglycemia and reduces postoperative morbidity and mortality in patients with diabetes undergoing an open-heart operation. CII protocols should be the standard care for glycometabolic control in all patients undergoing cardiac surgical procedures. (Endocr Pract. 2004; 10[Suppl 2]:21-33)

A 2-Year Pilot Trial of Continuous Subcutaneous Insulin Infusion Versus Intensive Insulin Therapy in Patients with Newly Diagnosed Type 1 Diabetes (IMDIAB 8)

In a pilot study, the metabolic effects of continuous subcutaneous insulin infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at diagnosis in patients with Type 1 diabetes and continued for a 2-year period were evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs. ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight. CSII was started immediately after admission to the hospital. Parameters of metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were evaluated for a 2-year follow-up period. Data are presented for a total of 19 patients who remained in the study for its duration. Two years after diagnosis, mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups, respectively (p=not significant). Compared with baseline values, an increase of baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was observed; however, the difference between the groups was not significant. The insulin requirement for the entire duration of the study, but not at entry and 3 months, was significantly higher in CSII compared with ISIT patients (0.62 +/- 0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial completion patients on CSII continued with this mode of therapy. Implementation of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2 years thereafter achieved similar and optimal metabolic control, but more insulin was required with the CSII group. Both types of intensive insulin therapy combined with NA are able to preserve C-peptide secretion or even increase baseline levels for up to 2 years after diagnosis.

Pancreas after kidney transplantation.

After three decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for patients with insulin-dependent diabetes mellitus (IDDM) and advanced diabetic nephropathy with end-stage renal disease (ESRD) and for

Selecting Children and Adolescents for Insulin Pump Therapy: Medical and Behavioral Considerations

The use of continuous insulin therapy via a subcutaneously implanted catheter connected to an external pump is being used increasingly in the management of childhood type 1 diabetes. This form of intensive diabetes management places multiple demands on young patients to achieve near-normal blood glucose levels. Therefore, appropriate selection of pediatric candidates for pump therapy is critical to achieving successful outcomes. Although few empirical data are available on readiness evaluations conducted with pump candidates, clinical data suggest several factors important in the consideration of these individuals, including age, medical history, and psychosocial functioning. The focus of this case presentation is to describe key factors for health care professionals to consider in transitioning children and adolescents to the insulin pump, based on our pediatric pump program at Children’s National Medical Center in Washington, D.C. S.P., is a 10-year-old boy with a 3-year history of type 1 diabetes. In May 2000, while on three insulin injections per day, he requested insulin pump therapy in order to increase lifestyle flexibility. His height was at the 90–95th percentile, and his weight was at greater than the 75th percentile. His hemoglobin A1c (A1C) concentration was 6.9%. His anticipated pump start was set to coincide with his tenth birthday. As a requirement of our program, S.P. was asked to learn carbohydrate counting and to obtain psychological consultation per our center’s protocol. After psychological and nutritional evaluations, there were concerns related to untreated anxiety with obsessive-compulsive tendencies as well as the need for additional carbohydrate-counting practice. We therefore delayed his pump start for 5 months and asked S.P. and his family to seek additional psychological counseling and nutritional support to increase the likelihood of pump success. ### Medical and Behavioral Considerations Insulin pump therapy provides a more physiologically precise manner of delivering insulin compared to self-injections with less variable insulin absorption …

Factors associated with discontinuing insulin therapy after diabetic ketoacidosis in adult diabetic patients.

To assess the factors associated with successful discontinuation of insulin therapy after diabetic ketoacidosis (DKA) in adult patients. Patients (>or= 18 years) attending the Endocrine and Metabolism Clinic at a major hospital in southern Taiwan were recruited. After recovery from the acute stage, those with no contraindications to oral antidiabetic agents, with adequate beta cell reserve, and with no antiglutamic acid decarboxylase (GAD) antibody were treated with oral agents. Sixty-six patients (38 males, 28 females, aged 18-76 years) were included, and 21 qualified for treatment with oral agents. These 21 patients were older at diagnosis of diabetes (45.5 +/- 14.0 vs. 40.0 +/- 13.8 years, P = 0.047), had shorter diabetes duration (median 0 vs. 5.5 months, P = 0.040), higher BMI (median 23.4 vs. 19.5 kg/m2, P < 0.001), higher serum osmolality during DKA (352.1 +/- 40.7 vs. 318.0 +/- 16.4 mmol/kg, P = 0.005), and lower insulin dose following recovery (median 0.49 vs. 0.83 unit/kg/d, P < 0.001) than those patients that had to continue insulin therapy. Thirteen patients (8 males, 5 females; 62%) successfully discontinued insulin for at least one year without recurrence of DKA. Multiple logistic regression analyses showed that BMI >or= 25 kg/m2 (adjusted relative risk (ARR) 8.85, 95% CI 1.05, 8.39), diabetes onset age >or= 40 years (ARR 8.08, 95% CI 1.16, 6.95), and undiagnosed diabetes before DKA (ARR 8.90, 95% CI 1.19, 7.51) were significant factors associated with successful discontinuation of insulin therapy. We identified three independent clinical factors associated with successful discontinuation of insulin therapy after DKA.

Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USA

Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USA

Insulin Infusion Improves Neutrophil Function in Diabetic Cardiac Surgery Patients

Diabetic patients are at increased risk of wound infection after major surgery, but the effect of perioperative glucose control on postoperative wound infection rates after surgery is uncertain.We tested the effect of an insulin infusion on perioperative neutrophil function in diabetic patients scheduled for coronary artery bypass surgery. Participants (n = 26) were randomly allocated to receive either aggressive insulin therapy (AIT) or standard insulin therapy (SIT) during surgery. Blood was drawn for neutrophil testing before surgery, 1 h after the completion of cardiopulmonary bypass, and on the first postoperative day. Neutrophil phagocytic activity decreased to 75% of baseline activity in the AIT group and to 47% of baseline activity in the SIT group (P < 0.05 between groups). No important differences in neutrophil antibody-dependent cell cytotoxicity were found. This study documents a potentially beneficial effect of continuous insulin therapy in diabetic patients who require major surgery. Implications: A continuous insulin infusion and glucose control during surgery improves white cell function in diabetic patients and may increase resistance to infection after surgery. (Anesth Analg 1999;88:1011-6)

Diabetes Mellitus

Diabetes Mellitus

The Effects of Diet and Insulin Therapy on Coagulation Factor VII, Blood Viscosity, and Platelet Release Proteins in Diabetic Patients with Secondary Sulphonylurea Failure

The effect of intensified dietary measures and subsequently insulin therapy upon haemorheological measures were studied in Type 2 diabetic patients with secondary sulphonylurea failure. Coagulation factors VIIc and VIIIc, fibrinogen, plasma viscosity, whole blood viscosity, beta-thromboglobulin, platelet factor 4, von Willebrand factor, and euglobulin clot lysis time were measured at baseline, after 3 months intensified dietary therapy and after 4 months insulin therapy. During intensified dietary therapy there was a significant fall in serum cholesterol (p less than 0.05) and a small decrease in weight, but no significant change in blood glucose control. Factor VIIc levels fell significantly (1.22 (SE 0.07) vs 1.42 (0.08) u ml-1, p less than 0.01), and plasma viscosity and whole blood viscosity (23 s-1) also improved (both p less than 0.05). Insulin therapy was instituted with either continuous subcutaneous insulin therapy or twice daily injections of soluble and isophane (NPH) insulin. During this period glycosylated haemoglobin improved (mean (SE) 49.5 (1.4) vs 65.0 (2.1) mmol-HMF mol-Hb-1, p less than 0.001; normal range 29-39 mmol-HMF mol-Hb-1) as did serum triglyceride (p less than 0.01), but weight increased (p less than 0.001). The only haemorheological changes with insulin were increased levels of the platelet release proteins beta-thromboglobulin (37 (3) vs 28 (2) micrograms l-1, p less than 0.01) and platelet factor 4 (median 7.5 (range 3.0-18.0) vs 4.5 (2.0-10.5) micrograms l-1, p less than 0.01).

PRE AND POSTOPERATIVE CARE OF DIABETIC PATIENTS-COMPARISON OF PREPARED OPERATION AND EMERGENCY OPERATION

To elucidate pre and postoperative care of diabetic patients a comparative study of prepared operation and emergency operation has been made. Diabetic patients of undergone emergency operation were more likely to have infection due to uncontrolled diabetic state and easely progress to sepsis.Preopertive management with insulin with which daily blood sugar level is adjusted to under 200 mg/dl is necessary for patients group untreted or treated with oral antidiabetics before admission. In postoperative period the blood sugar should be controlled between 100 and 200 mg/dl. Usually we administer insulin either by drip infusion or continuous intravenous infusion.In postoperative period of the emergency operation or major operation the diabetic patients under poor control should be treated by continuous intravenous insulin therapy, when frequent blood sugar monitering should be mandatory. Amount of glucose for each unit of insulin was 3.1g in emergency operation and 9.3 g in prepared operation. The prognosis of emergency operation turned out to be poor.

Resistance and allergy to recombinant human insulin

Insulin allergy and antibody-mediated resistance may complicate therapy with animal insulins. We describe a 53-year-old man manifesting both resistance and persistent systemic allergy despite treatment with recombinant human insulin. Insulin resistance and symptoms of allergy appeared in this patient several months after initiating therapy with mixed beef-pork insulin, as is often the case. Symptoms initially improved, but persisted, and then worsened again, despite continuous human insulin therapy. Total insulin-binding capacity by Scatchard analysis, high plasma insulin-binding capacity, and specific anti-insulin antibody levels were consistent with an immunologic form of insulin resistance. Glucocorticoid therapy was required both to reduce allergic findings and to restore glycemic control. Although recently available human insulins may be less immunogenic than animal forms, immune responses to exogenous human insulin still may pose significant clinical problems.

Peripheral Diabetic Neuropathy

Diabetic neuropathy is a common complication of diabetes mellitus with significant morbidity and mortality. Hyperglycemia with its secondary metabolic, vascular, and enzymatic consequences is most likely to be the predominant cause. The clinical manifestations includes a wide range of somatic and autonomic syndromes. Painful diabetic neuropathy may require symptomatic treatment. The precise role of therapies such as continuous subcutaneous insulin therapy and aldose reductase inhibitors remains to be clarified.

Effect of insulin therapy on established diabetic nephropathy in rats.

The effectiveness of insulin therapy on early diabetic nephropathy has not been established. In this study we examined the influence of continuous subcutaneous insulin on the progression of established nephropathy in streptozocin-induced diabetic rats. Normal controls and diabetic rats were studied for 11 mo. During the first 6 mo, all the diabetic rats received 2 U protamine zinc insulin s.c. twice weekly. During the last 5 mo of study, diabetic rats either continued on the occasional subcutaneous insulin regimen or received regular insulin by continuous subcutaneous infusion. Six months after the initiation of the study, the diabetic rats were severely hyperglycemic, and their relative mesangial areas had increased. Continued poor glycemic control in the rats receiving occasional insulin was associated with relative increased mesangial area (25.2 +/- 1.0% of glomerular area) and significant proteinuria (148 +/- 17 mg/24 h) compared with normal controls. In contrast, the use of continuous subcutaneous insulin therapy with improved glycemic control arrested mesangial changes (19.5 +/- 1.4% of glomerular area) and prevented the excessive proteinuria (71 +/- 13 mg/24 h). Indeed, these parameters did not differ from age-matched controls. We conclude that in the rat, continuous subcutaneous insulin therapy instituted after the development of early glomerular pathology is effective in arresting the disease process.

Conversion from low-dose insulin therapy to glipizide in patients with non-insulin-dependent diabetes mellitus

This study examines the effect of glipizide therapy in patients with non-insulin-dependent diabetes mellitus (NIDDM) previously treated with a low-dose insulin regimen. To determine the comparative safety and efficacy of these two treatment regimens, 135 patients with NIDDM who received low-dose insulin (40 units per day or less) were enrolled in a prospective, multicenter trial. After a four-week period of continued insulin therapy, therapy was converted to the second-generation oral sulfonylurea, glipizide. This report includes efficacy data on 79 patients with NIDDM who completed an eight- to 10-week course of glipizide therapy. A majority of these patients were obese (more than 120 percent of ideal body weight), with a mean age of 61.4 years, and a mean duration of diabetes of 10.0 years. Conversion from low-dose insulin resulted in no deterioration in overall glycemic control as reflected by an unchanged glycosylated hemoglobin at 16 weeks. Seventy patients (89 percent) attained fair glucose control and continued an additional 12 weeks of glipizide maintenance therapy. Subgroup analysis by fasting plasma glucose criteria demonstrated that 44 percent of these patients had statistically significant improvements in glucose control with glipizide as compared with insulin therapy. As this study showed, many patients with NIDDM currently receiving treatment with low-dose insulin can have maintained and some even improved glucose and lipid parameters when therapy is converted to glipizide. The rate of hypoglycemic adverse reactions corrected for duration of treatment in all 135 patients was 0.32 event per patient-month of therapy with insulin as compared with 0.12 event per patient-month of therapy with glipizide. When issues of efficacy, safety, and convenience are considered, it might be more appropriate to administer an oral sulfonylurea to patients with NIDDM rather than proceeding to therapy with insulin.

Continuous subcutaneous insulin therapy during early pregnancy

Intensive metabolic control of diabetes is probably important during formation of the embryo early in pregnancy. The purpose of this study was to determine the efficacy and complications of continuous subcutaneous insulin infusion therapy during the fifth to the tenth week of gestation. Twenty-four insulin-dependent subjects were trained to use blood glucose self-monitoring and the Auto Syringe portable insulin infusion pump (AS6C). Regular insulin was administered as a basal infusion of 18 +/- 8 U/24 hours (+/- SD) (12.2 +/- 3.9 mU . kg-1 . h-1) and as bolus injections of 6 +/- 3 U before meals and 1.2 +/- 1 U before snacks. Reasonable control of fasting (119 +/- 30 mg/dL) and postprandial (133 +/- 34 mg/dL) hyperglycemia was achieved, accompanied by an average of 2.2 +/- 1.5 symptomatic hypoglycemic episodes per week. The frequency of complications with this new therapy declined as the authors gained experience in teaching the system. The persistence of good diabetic control in many of the subjects after they returned to conventional insulin therapy points to the need for a controlled trial of continuous subcutaneous insulin infusion therapy versus intensive conventional therapy in pregnancy.

Continuous subcutaneous insulin therapy during early pregnancy : Kitzmiller JL; Younger MD; Hare JW; et al. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

International Journal of Gynecology & ObstetricsVolume 24, Issue 5 p. 392-392 Citations from the literature diseases in pregnancy Continuous subcutaneous insulin therapy during early pregnancy Kitzmiller JL; Younger MD; Hare JW; et al. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA First published: October 1986 https://doi.org/10.1016/0020-7292(86)90181-5Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume24, Issue5October 1986Pages 392-392 RelatedInformation