Glycerol-insulin raises circulating insulin antibodies in type I diabetic patients treated with permanently implanted devices

The instability of insulin in the reservoirs of implantable insulin delivery devices has been a major obstacle in implementing this form of therapy. To overcome the problem of precipitation, a glycerol-insulin preparation has been used in large-scale long-term clinical trials. The aim of this study was to evaluate the stability of the glycerol-insulin solution and its effects on circulating insulin antibodies in eight type I diabetic patients who were implanted with an Infusaid pump (Infusaid Corporation, Norwood, MA) and followed for 1 year or more. Total insulin requirement did not change throughout the observation period. Plasma free insulin was higher during treatment with glycerol-insulin than with the standard insulin treatment (P less than .02). Insulin antibodies increased in all patients (P less than .05). High-performance liquid HPLC analysis of insulin samples from the pump reservoirs showed the generation of insulin modification products at a daily rate of 1.84%, reaching 40% to 50% of the total reservoir content 3 weeks after refilling; among these products, high molecular weight species accounted for about 15%. It is concluded that glycerol-insulin is not an adequate insulin preparation for use in implanted devices. Insulin deteriorated in the pump reservoirs, and insulin antibody concentration increased in the treated patients. It is believed that this antibody production is favored by circulating insulin fragments and polymers of insulin generated inside the pump reservoirs.     

Will long acting insulin analogs influence the use of insulin pump therapy in type 1 diabetes?

Insulin pump therapy enjoys a steadily growing number of users and is associated with an approximately 0.5% lower A1c as compared to flexible insulin injection therapy in type 1 diabetes patients. An important question is whether superiority of insulin pump therapy persists in the era of rapid acting analogs and will persist in the era of long acting analogs. Pooled data of three randomized clinical trials using rapid acting analogs in both arms shows a 0.35% lower A1c when on the pump. Treatment effect was shown to be larger in those with higher baseline A1c's. Results of three trials comparing insulin pump therapy with regimens consisting of both rapid acting and long acting analogs are inconsistent, probably indicating the advantage of pump therapy at group level is likely to have become relatively small. Therefore, the challenge for the treatment team is to identify those patients who benefit most from insulin pump treatment. Poor glycemic control merits a trial of insulin pump therapy in the motivated patient. Other indications for insulin pump therapy include the need for several basal rates, a life style characterized by unpredictable physical activity and patient preference.     

Continuous subcutaneous insulin infusion therapy decreases insulin resistance in type 1 diabetes

The influence of continuous sc insulin infusion therapy for 6 weeks on sensitivity to insulin (euglycemic clamp technique) and hepatic glucose production (3-[3H]glucose technique) was measured in 10 type 1 diabetic patients whose mean duration of diabetes was 8 yr. Mean diurnal blood glucose fell from 8.5 +/- 0.8 (SEM) mmol/liter to 6.0 +/- 0.6 mmol/liter (P less than 0.05) and glycosylated hemoglobin from 10.5 +/- 0.4% to 8.7 +/- 0.3%. Insulin requirements declined by 23% from 47 +/- 4 U/day prepump to 36 +/- 2 U/day after 6 weeks of pump therapy (P less than 0.01). During the insulin clamp, plasma insulin was maintained at approximately 90 mU/liter and plasma glucose at approximately 5.0 mmol/liter in all studies. The rate of glucose metabolism in diabetic patients during conventional therapy (4.65 +/- 0.41 mg/kg X min) was 35% lower than in normal subjects (7.20 +/- 0.42 mg/kg X min, n = 14, P less than 0.001). After 6 weeks of pump therapy, total glucose uptake increased by 27% to 5.90 +/- 0.60 mg/kg X min, P less than 0.05 vs. prepump). This was still 18% lower than in the normal subjects (P less than 0.05). Basal hepatic glucose production in the diabetic patients during conventional therapy (3.07 +/- 0.14 mg/kg X min) was 70% higher than in the normal subjects (1.79 +/- 0.07 mg/kg X min, n = 7, P less than 0.001). After 6 weeks of pump therapy, hepatic glucose production fell to 2.48 +/- 0.19 mg/kg X min (P less than 0.05), which was still 40% higher than in the normal subjects (P less than 0.01). Basal hepatic glucose production was directly related to the fasting plasma glucose level (r = 0.67, P less than 0.001) and inversely proportional to fasting insulin concentration (r = -0.48, P less than 0.05) in the diabetic patients. Specific tracer insulin binding to erythrocytes in the diabetic patients (19.4 +/- 1.5%) was comparable to that in the normal subjects (19.6 +/- 1.2%) and remained unchanged during pump therapy. Thus the improved metabolic control resulting from pump therapy is associated with enhancement in sensitivity to insulin, and reduction in basal hepatic glucose production.     

Ramadan fasting in diabetes patients on insulin pump therapy augmented by continuous glucose monitoring: an observational real-life study

Abstract Background and Aims: Hypoglycemia during the daytime of Ramadan fasting is the most feared complication of diabetes. Insulin pump therapy has been proposed as the ideal "theoretical" method for insulin delivery. We report a prospective observational, single-center study of insulin-treated patients using insulin pump therapy during Ramadan 2011. Patients and Methods: Twenty-one patients (10 males and 11 females) were selected; median age was 26 years. They adjusted their insulin as per their usual practices. Outcome measures obtained before and during Ramadan included body weight, glycosylated hemoglobin, blood glucose, total insulin dose differences, overriding tendency, suspension time during fasting, and number of hypoglycemic episodes. Results: The patients fasted for a median of 29 days. The observed changes during Ramadan were overall not significant quantitatively, but some trends were noted. The total insulin administered during Ramadan was not different from that in the pre-Ramadan period, but there was a redistribution of insulin over a 24-h period in relation to the changes in the daily lifestyle and eating patterns. Basal insulin was decreased during the daytime by 5-20% from before Ramadan and increased during the nighttime. The mean change in the overall amount of basal insulin was not significant. A larger than usual amount of insulin bolus was given at the meals Iftar, Fowala, and Suhur; the change in the total amount of bolus insulin as a percentage change from total insulin was also not significant. No major hypoglycemic episodes were reported. Minor hypoglcemic episodes were equally distributed between daytime and nighttime and were managed by either basal insulin adjustment or suspension from the pump. Conclusions: This study confirms the advantages provided by insulin pump use in patients with diabetes were enhanced by the use of continuous glucose monitoring. We provided more evidence-based advice on how best to adjust the insulin pump during fasting.     

Insulin pump therapy in type 1 pediatric patients: now and into the year 2000

There are a number of medical conditions such as growth failure in children, pregnancy, lipid abnormalities, and early complications that are improved by the meticulous glycemic control that can be achieved with insulin pump therapy (CSII). By using an insulin pump, many patients with severe hypoglycemia, the dawn phenomenon, extremes of glycemic excursion, recurrent diabetic ketoacidosis (DKA) and hypoglycemia unawareness have amelioration of these problems. However, pump therapy involves problems such as weight gain, recurrent ketosis due to pump failure, infections, and risk of hypoglycemia. Owing to many developmental issues, young children may not be able to wear the pump without parental supervision. We have used the pump at night time only in these patients. This has allowed children of 7-10 years of age to benefit from improved nocturnal glycemia without the risk of pump therapy when they are without an adult to help. We have also used the pump in subjects with recurrent DKA and in our general patient population (mean age 13.6+/-3.9 years). In our pump cohort, CSII led to improvement in quality of life, knowledge, adherence, and responsibility. A reduction in hypoglycemia, DKA rate and mean HbA(1c) was associated with pump usage. For this to occur, however, pump education must be geared to the pediatric subject and his/her family. Education materials and tools help in learning how to use the pump and how to deal with the intricacies of basal and bolus dosing, and the effect of exercise, food and illness on diabetes management. The pump has improved since it was first introduced and these modifications have made it easier, more painless and less hazardous. With the development of continuous glucose sensors and implantable pumps, the next century will see pump therapy lead to the artificial pancreas.     

Outpatient-to-Inpatient Transition of Insulin Pump Therapy: Successes and Continuing Challenges

Background

Insulin pump therapy is a complex technology prone to errors when employed in the hospital setting. When patients on insulin pump therapy require hospitalization, practitioners caring for them must decide whether to allow continued pump use. We provide the largest review regarding transitioning insulin pump therapy from the outpatient to inpatient setting.

Method

Records of inpatient insulin pump users were retrospectively analyzed at a metropolitan Phoenix hospital between January 2006 and December 2009. Adherence to institutional procedures on insulin pump use was assessed, glycemic control was determined, and adverse events were examined.

Results

We examined records on 65 patients with insulin pumps, totaling 125 hospitalizations. Mean (standard deviation) patient age was 55 (17) years, diabetes duration was 27 (14) years, pump duration was 6 (5) years, length of hospital stay was 4.7 (6.3) days, hemoglobin A1c was 7.3 (1.3)%, 85% had type 1 diabetes mellitus, 57% were women, and 97% were white. Admissions involving insulin pumps increased (23 in 2006, 17 in 2007, 40 in 2008, and 45 in 2009). Insulin pump therapy was continued in 83 (66%) hospitalizations. Among these hospitalizations, endocrinology consultations were obtained in 89%, consent agreements were found in 83%, insulin pump order sets were completed in 89%, admission glucose was checked in 100%, and nursing assessments of pump insertion sites were documented in 89%, but bedside insulin pump flow sheets were found in only 55%. Mean glucose of 175 (57) mg/dl was not significantly different than that in hospitalizations where insulin pumps were discontinued [175 (42) mg/dl] or used intermittently [177 (7) mg/dl]. There was one instance of a pump catheter kinking; however, no other adverse events (pump site infections, mechanical pump failure, diabetic ketoacidosis) were observed, and there were no use-related fatalities.

Conclusions

Most patients using insulin pumps can safely have their therapy transitioned when hospitalized. A policy on inpatient continuous subcutaneous insulin infusion use can be successfully implemented. Compliance with required procedures can be achieved, although there was room to improve adherence with some process measures. Further study is needed to determine how to optimize glycemic control when pumps are allowed during hospitalization.     

Insulinpumpentherapie in der Pädiatrie

In Germany, continuous subcutaneous insulin infusion (CSII) has been firmly established as an intensive insulin regimen for paediatric and adolescent patients with diabetes mellitus. The individually programmable basal rate and the option of triggering a meal bolus without a painful injection permit an almost physiologic insulin substitution. This allows for near-normal metabolic control with no increased risk of adverse effects. Compared with other age groups, young children aged newborn to less than 5 years constitute the highest percentage of pump users. Because of their low insulin dose requirements and their high insulin sensitivity, the CSII options are particularly advantageous for them; for example, their rate of severe hypoglycaemia is significantly reduced. To initiate CSII treatment, a clear indication must be defined, the patient must accept the pump treatment, and the patient and his or her family need specific pump education.     

Treatment of type 1 diabetes in children and adolescents using modern insulin pumps

In the last decades, we are experiencing an increasing use of insulin pumps for the treatment of type 1 diabetes in children and adolescents. The most frequent reasons for switching from insulin injection schemes to pump therapy are frequent and/or severe hypoglycaemia, dawn phenomenon, poor glycaemic control, wish for more flexibility in daily life, and needle phobia. In toddlers and preschoolers, pumps are frequently introduced from the onset of type 1 diabetes. Pumps offer the possibility of adjusting basal insulin rates individually on an age-depended manner as well as of optimizing meal-related insulin requirements according to the meal composition by using three different kinds of boluses. Structured and intensive education of patients and their families on basics and specific requirements of insulin pump therapy is essential in order to get them familiar with the devices and their features. There is increasing evidence both from multicentre cross-sectional studies as well as from meta-analyses of randomized clinical trials in paediatric populations showing that patients with pump therapy can achieve a more favourable metabolic control accompanied with less hypoglycaemic events than those with multiple daily injections.     

A review of the security of insulin pump infusion systems

Insulin therapy has enabled patients with diabetes to maintain blood glucose control to lead healthier lives. Today, rather than injecting insulin manually using syringes, a patient can use a device such as an insulin pump to deliver insulin programmatically. This allows for more granular insulin delivery while attaining blood glucose control. Insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result, security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this article, we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components, which include the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues.     

Insulintherapie in der Schwangerschaft

The paper focuses on the special requirements of insulin therapy in pregnant women with diabetes because glucose goals, frequency and timing of glucose monitoring, and the dynamics of insulin adjustment differ substantially from when a woman is not pregnant. Planning of pregnancy with preconceptional optimizing of glucose control is essential; there is good evidence that the level of HbA_1c seems to determine the whole course of pregnancy. Studies have shown that there is no significant difference in achievement of good perinatal outcome comparing insulin application by insulin pump or by intensified conventional insulin therapy (ICT); the same is valid for human insulin versus analogs. Meanwhile, long-term analogs are also considered safe in pregnancy. Glucose goals are substantially lower than outside pregnancy but individual maternal risk of hypoglycemia must be taken into account. Personal consultation with a diabetologist at least every 2 weeks is highly recommended to adjust the rapidly changing insulin demand during the course of pregnancy. Fetal growth as a parameter of potential over- or undernutrition must also be considered. Standards at the delivery hospital for glucose and insulin management of the fetus during and after delivery are required. The same principles of insulin therapy are valid for women with type 2 diabetes. Insulin demand can be very high in the third trimester, and sometimes glucose goals can be reached only by additional off-label use of metformin. In women taking oral agents before pregnancy it is recommended to switch to insulin before conception. During breast feeding, women should stay on insulin for better glucose control.     

Use of continuous subcutaneous insulin infusion (insulin pump) therapy in the hospital setting: proposed guidelines and outcome measures

PURPOSE: Individuals whose diabetes is being treated in the outpatient setting via an insulin pump often wish to maintain this therapy during hospitalization. The authors propose guidelines for management of patients on insulin pumps who require a hospital admission. METHODS: A collaborative interinstitutional task force reviewed current available information regarding the use of insulin pumps in the hospital. RESULTS: There was little information in the medical literature on how to manage individuals on established insulin pump therapy during a hospital stay. The task force believed that a policy that promotes patient independence through continuation of insulin pump therapy while ensuring patient safety was possible. A set of contraindications for continued use of pump therapy in the hospital are proposed. A sample patient consent form and order set are presented. Finally, measures that can be used to assess effectiveness of an inpatient insulin pump policy are outlined. CONCLUSIONS: Patients on established insulin pump therapy do not necessarily have to discontinue treatment while hospitalized. However, clear policies and procedures should be established at the institutional level to guide continued use of the technology in the acute care setting.     

External insulin pump treatment in the day-to-day management of diabetes: benefits and future prospectives

The aim of diabetes treatment is to achieve tight glucose control to avoid the development of chronic diabetes complications while reducing the frequency of hypoglycaemic episodes. The main clinical indications of pump therapy in type 1 diabetes are persistently elevated HbA(1c) in spite of the best attempts of intensified insulin therapy with multiple daily injections (MDI) and/or frequent, disabling or severe hypoglycaemia. Several trials have demonstrated the superiority of continuous subcutaneous insulin infusion (CSII) over MDI, and highlighted the benefits of using short-acting insulin analogues. However, new MDI regimens with long-acting insulin analogues challenge insulin pump therapy in some indications, thus indicating the need for precise selection of those patients who will benefit the most from CSII. In type 2 diabetes, pump therapy may be an invaluable tool in selected patients characterized by chronic elevation of HbA(1c), obesity and high insulin requirements. In addition, in any case, specific education, training and ongoing evaluation of the benefit/risk ratio of the treatment are mandatory. Furthermore, there is continuing progress in the development of pump and catheter features, and insulin kinetics can still be improved. These technical advances are part of the work in progress towards developing closed-loop systems.     

Insulin Therapy and Colorectal Adenoma Risk Among Patients with Type 2 Diabetes Mellitus: A Case-Control Study in Korea

Purpose Patients with Type 2 diabetes mellitus may be at increased colorectal adenoma and cancer risk. Moreover, chronic insulin therapy may increase the risk of colorectal cancer among patients with Type 2 diabetes mellitus. We investigated to determine whether insulin therapy might increase the risk of colorectal adenoma among clinically confirmed patients with Type 2 diabetes mellitus. Methods We conducted a retrospective study among patients with Type 2 diabetes mellitus who underwent total colonoscopy between January 2003 and July 2006 at Hallym University Sacred Heart Hospital. Among them (n = 325), patients with histologically confirmed colorectal adenomas (n = 100) and the same number of controls matched by age and sex were selected and analyzed. Results Adenoma cases showed significantly higher rate of chronic insulin therapy (more than 1 year) than controls (P = 0.018). In multivariate regression analysis, patients who received chronic insulin therapy had three times the risk of colorectal adenoma compared with patients who received no insulin (odds ratio, 3; 95 percent confidence interval, 1.1–8.9; P = 0.04). Conclusions Chronic insulin therapy was associated with increased colorectal adenoma risk among Type 2 diabetes mellitus patients. This result may provide a need for more intensive colorectal cancer screening program in patients with Type 2 diabetes mellitus, especially those who receive chronic insulin therapy.     

Insulin pump therapy for type 2 diabetes

Insulin pump therapy, or continuous subcutaneous insulin infusion, has become an increasingly popular mode of therapy for patients with type 1 diabetes mellitus. Although the benefits of insulin pump therapy, such as less glycemic variability and a more flexible lifestyle, should be similar for patients with type 1 and type 2 diabetes mellitus, data on the use of insulin pump therapy in patients with type 2 diabetes are limited. This article reviews the basic principles of insulin pump therapy, the advantages and disadvantages encountered with its use, and the clinical situations where it may be considered for patients with type 2 diabetes.     

Guidelines for application of continuous subcutaneous insulin infusion (insulin pump) therapy in the perioperative period

Case reports indicate that diabetes patients receiving outpatient insulin pump therapy have been allowed to continue treatment during surgical procedures. Although allowed during surgery, there is actually little information in the medical literature on how to manage patients receiving insulin pump therapy during a planned surgical procedure. A multidisciplinary work group reviewed current information regarding the use of insulin pumps in the perioperative period. Although the work group identified safety issues specific to surgical scenarios, it believed that with the use of standardized guidelines and a checklist, continuation of insulin pump therapy during the perioperative period is feasible. A sample set of protocols have been developed and are summarized. A policy outlining clear procedures should be established at the institutional level to guide physicians and other staff if the devices are to be employed during the perioperative period. Additional clinical experience with the technology in surgical scenarios is needed, and consensus should be developed for insulin pump use in the perioperative phases of care.     

Addition of insulin to oral therapy in patients with type 2 diabetes

BACKGROUND: A majority of individuals with type 2 diabetes will eventually require exogenous insulin therapy to achieve or maintain glycemic control. This review provides practical recommendations for adding insulin therapy for patients with type 2 diabetes whose glucose levels are inadequately controlled with oral medications. METHODS: We used a systematic review of MEDLINE to retrieve relevant articles from 1990 to 2004 using the search terms insulin therapy, combination oral therapy, glycemic control, insulin analogs, insulin glargine, and basal insulin, which we supplemented with a review of clinical practice guidelines from the American Diabetes Association and the American Association of Clinical Endocrinologists. RESULTS: Type 2 diabetes mellitus is becoming more common in the United States and is likely to increase in prevalence as obesity, a risk factor for type 2 diabetes, likewise increases. Treatment often begins with oral monotherapy, but after 3 years of treatment, more than half of patients will require more than one pharmacological agent, and eventually most patients will require insulin. Adding insulin to oral therapy at an earlier stage in treatment provides improved glycemic control without promoting increased hypoglycemia or weight gain, lowers the risk of microvascular complications by 25%, and reduces the amount of insulin patients require. Various insulin preparations, including the newer analog insulins, with different onsets and durations of action are available to help meet individual patients' dosing needs. CONCLUSIONS: The addition of insulin to oral antidiabetic therapy can improve glycemic control. Newer insulin analogs can emulate normal physiologic insulin secretion and potentially limit diabetes-related comorbidity.     

Insulin pump therapy in patients with Type 1 diabetes mellitus: results of the Nationwide Quality Circle in Germany (ASD) 1999-2000.

BACKGROUND AND AIMS: Only a few specialised centres in Germany initiated insulin pump therapy before 1990. Initiation of pump therapy involves the participation in a structured treatment and teaching programme (TTP). During the last decade insulin pump therapy has been widely used. The impact of this decentralisation on the quality of care is still unknown. The aim of this trial was both to evaluate the outcome of insulin pump therapy outside specialised centres and to identify features that might be associated with persistently increased HbA1 c levels. PATIENTS AND METHODS: 250 patients with type 1 diabetes mellitus (age 36.0 +/- 13.1 years; diabetes duration 16.1 +/- 9.9 years), who were on continuous subcutaneous insulin infusion (CSII) therapy during 1999 - 2000, were individually included in the study. Second examination was performed one year after participation in the in-patient TTP for insulin pump therapy. Patients were recruited from 21 member institutions of the Working Group for Structured Diabetes Therapy of the German Diabetes Association. Further details were sought by questionnaire on those patients with persistently increased HbA1c (> 1.7 fold of mean normal range.) RESULTS: One year after participation in the TTP for CSII relative HbA1c (original value/mean normal of the local method [Müller et al., 1999]) decreased from 1.51 (0.9 - 3.2) to 1.44 (0.9 - 3.6) (p < 0.0001), severe hypoglycaemia from 0.46 to 0.12/patient/year (p < 0.001), severe ketoacidosis from 0.08 to 0.05/patients/year (p = 0.003) and hospitalisation from 5.2 to 3.1 days/patient/year (p = 0.002). In 43/207 (17%) the incidence of severe hypoglycaemia was unchanged (before 0.12 and after TTP 0.14/patients/year), there was slight increase in severe ketoacidosis (before 0.15; after TTP 0.23/patients/year) and hospitalisation days were unchanged (before 4.5; after TTP 4.4 days/patients/year). The following factors were associated with adverse outcomes: psychological problems including eating disorders and alcohol abuse (28%), lack of interest in self-management (28%) and social problems (11%). In 28% there was no follow-up treatment by diabetologists specialised in pump therapy. CONCLUSION: The benefits of insulin pump therapy are improvement of HbA1c, reduction of hypoglycaemia, ketoacidosis and hospitalisation days as well as improved flexibility. It is possible to draw up a list of clinical criteria and service requirements, which are likely to reduce failures.     

Optimizing Insulin Therapy in Pregnant Women with Type 1 Diabetes Mellitus

Pregnancy complicated by type 1 diabetes mellitus is associated with an increased risk of complications in the mother and infant. Normal or near normal glycemic control prior to and during pregnancy reduces many of these risks to levels observed in the general population. This degree of glycemic control is generally achievable only with intensive insulin therapy: multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) via an insulin pump. These therapeutic regimens have been found to result in comparable glycemic control, although CSII provides increased flexibility in terms of patient lifestyle, and may reduce the incidence of hypoglycemia. Frequent home blood glucose monitoring is imperative during pregnancy in order to optimize glycemic control and reduce the risk of hypoglycemia. Furthermore, insulin requirements change significantly over the course of pregnancy. The new short-acting insulin analogs, insulin lispro and insulin aspart, have pharmacodynamic properties which make them ideal for use during pregnancy. Although the number of published studies evaluating the use of insulin lispro during pregnancy is limited, the majority support its safety. No studies of insulin aspart in pregnancy have been published in full. In addition to optimization of glycemic control, frequent assessment for development and/or progression of microvascular complications is necessary during pregnancy.     

The renaissance of insulin pump treatment in childhood type 1 diabetes

Current goals for the treatment of children and adolescents with type 1 diabetes mellitus include achieving near-normal blood sugar levels, minimizing the risk of hypoglycemia, optimizing quality of life, and preventing or delaying long-term microvascular and macrovascular complications. Continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, provides a treatment option that can assist in the attainment of all of these goals in all ages of children. In pediatric patients, CSII has been demonstrated to reduce both glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children are reviewed, as well as criteria for patient selection and practical considerations using pump therapy in youth with T1DM. Supported by grants from the National Institute of Health (K12 DK063709, T32 DK063703 and RR 00125), the Juvenile Diabetes Research Foundation, and the Stephen I. Morse Pediatric Diabetes Research Fund.     

Use of pramlintide: the patient's perspective

Pramlintide is the first new antihyperglycemic agent approved for both type 2 and type 1 diabetes since insulin was developed in the 1920s. It is a synthetic analogue of human amylin, a naturally occurring neuroendocrine hormone synthesized by pancreatic beta cells. Pramlintide helps regulate the rate of glucose appearance and improves glucose control postprandially. This action is accomplished through suppressing inappropriate postprandial glucagon secretion and regulating gastric emptying, and is associated with a feeling of satiety. It is given at mealtimes and is indicated for use in type 2 and type 1 diabetes as an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. Pramlintide therapy should only be considered for patients who are receiving ongoing care under the guidance of a health care professional skilled in the use of insulin and supported by services of diabetes educators. Pramlintide is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in type 1 diabetes. Appropriate patient selection, careful patient instruction, and insulin dose adjustments help reduce this risk. In type 2 diabetes, pramlintide is initiated at 60 microg and may be increased to 120 microg two to three times daily with meals. In type 1 diabetes, pramlintide is initiated at 15 microg and may be increased to 30 or 60 microg with meals. Mealtime insulin should be reduced by 50% at pramlintide initiation and adjusted as the pramlintide dose is increased. It should be given subcutaneously with an insulin syringe and should not be mixed with insulin. The most commonly reported side effect is mild to moderate nausea with initiation, which is usually transient and short term in nature. Frequent self-monitoring of blood glucose is important during initiation to assist in insulin adjustments. Insulin type, dose, and timing as well as basal/bolus balance may require adjustment during pramlintide initiation. Despite requiring additional injections, patients report satisfaction with pramlintide therapy.