Insulin Pump Treatment Research Articles

Use of Continuous Subcutaneous Insulin Infusion in Young Adolescents With Diabetes Mellitus: A Case Study

Continuous subcutaneous insulin infusion (CSII) was initiated in a young female adolescent with severe insulin resistance, decreased growth velocity, and poor metabolic control. The patient's insulin dose had been 3 u/kg/day, and it was hypothesized that her insulin requirements would be much less when only regular insulin was used. Because of the potential risk of severe hypoglycemia from giving regular insulin in amounts equivalent to her injection total daily dose as a constant subcutaneous infusion, the patient was hospitalized to begin pump therapy. Hourly glucose levels were collected for 24 hours to determine insulin requirements with this therapy. The patient subsequently required a significantly reduced dose of insulin (1.2 u/kg/day) with CSII, and her growth velocity improved. Metabolic control based on glycosylated hemoglobin levels also improved. Insulin pump treatment proved to be a viable solution for this young adolescent who required large doses of insulin to maintain reasonable control. Challenges of using this type of therapy in young patients are discussed.

Glucose counterregulation in type 1 diabetic patients with decreased symptoms of hypoglycemia after insulin pump treatment

We were interested in studying whether impaired hypoglycemic awareness after intensified insulin treatment with insulin pumps is associated with impaired glucose counterregulation. Glucose counterregulatory hormones were measured in 7 type I diabetic patients with altered symptoms after 6 months of continuous subcutaneous insulin infusion (CSII) (group 1) and in 9 patients with unchanged symptoms of hypoglycemia under CSII (group 2). The groups did not differ in diabetic control, duration of diabetes, or prevalence of neuropathy. Counterregulatory hormone response to an insulin-induced episode of hypoglycemia was measured before (first test) and after 6 months (second test) of CSII. Glucose nadirs and glucose recovery were similar in both groups and both tests. The mean plasma glucagon values demonstrate a lack of glucagon response in both groups and both tests. Growth hormone and cortisol increased in both groups and both tests without any difference between the groups or first and second tests. Epinephrine response was similar in both tests of group 2 (first test: 50 +/- 5 to 416 +/- 73; second test; 45 +/- 5 to 456 pg/ml), while in group 1 the response was not increased significantly in the second test [first test: 32 +/- 6 to 346 +/- 63; second test: 44 +/- 7 to 575 +/- 91 pg/ml; areas under curve (AUC) 11,977 and 16,345 pg x ml-1 x 90 min-1 (p = 0.36)].(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin Pump Therapy: Indication, Method, Technology

The last decade, with the introduction and increasing technical sophistication of portable insulin-infusion pump systems, has seen insulin-infusion therapy introduced, gain limited popularity as a treatment option, and, in many countries, fall from favor with the move to multiple injection regimens and pen injection devices. The time is right for an appraisal of the true role of insulin-pump treatment, synthesizing the many anecdotal reports and few controlled studies into useful guidelines for the safe and effective use of this demanding form of insulin delivery. Unfortunately, this book fails to meet the requirement for a critical and analytical review, and its usefulness is thus severely limited.

A consultation system for insulin therapy

This paper describes a computer system to advice on insulin therapy for diabetic in-patients. A mathematical model was developed to describe the effect of insulin on blood glucose (BG) level. The system uses an adaptive approach to analyse the response to an applied insulin dosage. It learns the patient's individual parameters. All conventional injection and insulin pump regimens are supported. The individualised model is used to predict BG level of the proposed insulin dosage. The system uses a generate-reject strategy to output optimum insulin therapy in terms of optimum BG. The predictive capability of the system was tested and it is able to predict BG with a precision of 2.5 mmol/l after 3 days and 6 days of insulin pump treatment and conventional injection therapy, respectively.

Antithrombin III activity, von Willebrand factor antigen and platelet function in young diabetic patients treated with multiple insulin injections versus insulin pump treatment

Abstract. In a prospective study with cross‐over design 20 patients with insulin‐dependent diabetes mellitus of more than 2 years duration were treated for 6 months with continuous subcutaneous insulin infusion (CSII) and multiple insulin injections (MII).Metabolic control, platelet aggregability, thromboxane B2 levels in serum and plasma as well as antithrombin III (ATIII) activity and von Willebrand factor antigen were evaluated. A good metabolic control was obtained by both intensified regimens. No difference could be demonstrated between either platelet function tests or serum level of von Willebrand factor antigen during treatment with CSII and MII. However, the plasma level of ATIII activity was significantly higher (P < 0.01) during MII treatment as compared to CSII treatment. There was no correlation between ATIII activity and daily insulin requirement or serum fructosamine.In conclusion, long‐term metabolic control with MII has a favourable effect on ATIII activity in plasma. This may be important for a delay in onset and progression of diabetic vascular complications.

Antithrombin III activity, von Willebrand factor antigen and platelet function in young diabetic patients treated with multiple insulin injections versus insulin pump treatment

In a prospective study with cross-over design 20 patients with insulin-dependent diabetes mellitus of more than 2 years duration were treated for 6 months with continuous subcutaneous insulin infusion (CSII) and multiple insulin injections (MII). Metabolic control, platelet aggregability, thromboxane B2 levels in serum and plasma as well as antithrombin III (ATIII) activity and von Willebrand factor antigen were evaluated. A good metabolic control was obtained by both intensified regimens. No difference could be demonstrated between either platelet function tests or serum level of von Willebrand factor antigen during treatment with CSII and MII. However, the plasma level of ATIII activity was significantly higher (P less than 0.01) during MII treatment as compared to CSII treatment. There was no correlation between ATIII activity and daily insulin requirement or serum fructosamine. In conclusion, long-term metabolic control with MII has a favourable effect on ATIII activity in plasma. This may be important for a delay in onset and progression of diabetic vascular complications.

Glucagon responses to intravenous arginine and oral glucose in insulin-dependent diabetic patients during six months conventional or continuous subcutaneous insulin infusion

To elucidate the impact of subcutaneous insulin infusion (CSII) treatment on the glucagon response to intravenous (IV) arginine and to oral glucose a 6-month prospective randomized study in insulin-dependent diabetics was carried out. The effects were investigated of CSII (7 patients) and conventional insulin treatment (UCT) (9 patients) on the changes in glucagon, growth hormone, glucose, lactate, glycerol, 3-hydroxybutyrate, and alanine to IV arginine and to oral glucose in insulin-dependent diabetics who were made euglycemic and isoinsulinemic using the artifical pancreas (Biostator, Miles, Elkhart, IN). HbA 1c was significantly lower in the group treated by CSII. Despite the improved glycemic control no significant change in the responses of A-cell secretion to arginine or glucose challenges was found. In addition, there were no significant differences in hormone or metabolite values between the two groups at entry to the study or after 6 months of either therapy. Thus, normalization of the A-cell sensitivity to glucose in insulin-dependent diabetic subjects requires further amelioration of the intermediary metabolism than can be achieved with insulin pump treatment.

Cutaneous complications induced by continuous subcutaneous infusion. Experimental studies with portable mini-pumps.

In healthy volunteers, possible complications at the needle site were studied during short-term as well as continuous subcutaneous infusion of aqueous fluid with portable mini-pumps. Local complications, such as leakage of fluid, erythema, and bacterial contamination of the hypodermic needle were associated with the duration of the indwelling time, but not with the total volume delivered during every experiment. The hypodermic steel needle caused pain when the subcutaneous fat tissue layer was thin. These findings may have clinical relevance for the performance of continuous subcutaneous hormone infusion therapy (e.g. insulin-pump treatment of type-I diabetes mellitus).

Sustained Normoglycemia and Remission Phase in Newly Diagnosed Type I Diabetic Subjects.Comparison Between Continuous Subcutaneous Insulin Infusion and Conventional Therapy During a One Year Follow-Up

After onset of type I diabetes 7 diabetics were randomized to subcutaneous insulin pump treatment (CSII) (age 12 to 29 years, mean: 21 years) and 7 diabetics to conventional insulin treatment (CI) (age 14 to 28 years, mean: 21 years). HbA1, glycosylated serum proteins and mean blood glucose (MBG) as parameters of metabolic control were determined monthly. After 2 months both groups showed HbA1 values in the normal range. Mean MBG values were (mean +/- SD) 116 +/- 7 mg/dl for CSII and 118 +/- 14 mg/dl for CI. Residual insulin secretion was determined monthly by fasting C-peptide. After 14 days, 5, 7, 8 months fasting C-peptide values were significantly (P less than 0.05) higher in CI. After one year fasting C-peptide was comparable in both groups (CSII and CI mean: 0.06 nmol/l). The administered insulin dose was comparable in both groups with a 55% reduction of insulin dose after 5 months in CSII (0.35 +/- 0.15 U/kg/24 h) and in CI after 7 months (0.31 +/- 0.28 U/kg/24 h). After 12 months of insulin therapy about 60% of the initial insulin dose was injected in both groups. 1 patient on CSII (12 years) and 2 patients on CI (15, 28 years) showed a complete remission (for 3-9 months) with no exogenous insulin and normal HbA1 values. 50% of the patients had episodes where they did need less than 0.2 U/kg/24 h insulin to maintain optimal diabetic control (3 CSII, 4 CI). During the first year of insulin treatment in type I diabetes with CSII as well as with CI a comparable near normalisation of diabetic control could be achieved.

Evaluation of insulin pump treatment under routine conditions

Sixty-six patients with insulin-dependent diabetes mellitus (IDDM) initiated insulin pump treatment under routine conditions. Four patients (6%) discontinued treatment. One patient died. 61 patients were followed for a total period of 130 patient years. A sustained decrease in HbA1c was obtained during insulin pump treatment. The frequency of the following acute side effects was: ketoacidosis 0.06 episodes per patient per year, severe hypoglycaemia 0.09 episodes per patient per year and infection at the injection site 0.06 episodes per patient per year. Insulin pump treatment was well accepted by the patients; all but one wanted to continue insulin pump treatment. The major advantages were greater quality of life, greater flexibility as to meal times and better blood glucose regulation. The major disadvantages were technical problems: blockage of the infusion system, greater treatment expenses and the large pump size. We conclude that insulin pump treatment is well accepted as long-term treatment in selected IDDM patients. The improvement in metabolic control can be sustained through several years, and the frequency of severe hypoglycaemia during pump treatment is comparable to that of conventional insulin treatment. The risk of ketoacidosis requires more attention from the physician.

Metabolic control in newly kidney transplanted insulin-dependent diabetics: Improvement by insulin pump treatment (CSII)

Management of glucose homeostasis in newly kidney transplanted insulin-dependent diabetic patients is difficult. To examine whether continuous subcutaneous insulin infusion (CSII) could reverse this problem, six consecutive kidney-transplanted Type I diabetic patients either proceeded with conventional insulin therapy (CIT) or were changed to CSII beginning on the third postoperative day. After a mean of 13 days, the insulin administration mode was changed from CIT to CSII (n=3) or from CSII to CIT (n=3), and continued for a further 15 days. Mean blood glucose calculated on the basis of four daily measurements (8.00, 12.00, 17.00, 22.00 h) during the study periods was significantly lower during CSII (8.0±0.4 mmol/l, mean±SEM) than on CIT (11.0±0.6 mmol/l; p<0.005). Moreover, the variability of blood glucose expressed as the M-value was lower during the pump treatment compared to CIT ( p<0.001), while the number of blood glucose values below 3.0 mmol/l was similar (3.8 vs. 4.4%). Diurnal metabolic and hormonal profiles were twice determined on each regimen with 2 hourly sampling. Glycemic control was again found to be improved during CSII therapy as compared to CIT ( p<0.01 or 0.05< p<0.10). Moreover, insulin pump treatment resulted in a significant reduction of two major intermediary metabolites, lactate and glycerol ( p<0.05 and p<0.01, respectively). The improved metabolic state during CSII was probably due 1) to a more physiologic serum-free insulin pattern, which exhibited postprandial plasma peaks mimicking that of non-diabetic subjects; and 2) to an increased ability to combat varying insulin resistance post-transplantation. In conclusion, in newly kidney transplanted insulin-dependent diabetics, insulin pump therapy results in improved (almost normal) metabolic control compared to that achieved with CIT.

Acute cutaneous complications and catheter needle colonization during insulin-pump treatment.

Forty unselected type I (insulin-dependent) diabetic patients with insulin pumps were examined three times for cutaneous complications and bacterial colonization of their subcutaneous catheter needles. Fifty-eight of the 120 needles were contaminated, 42 of them with Staphylococcus epidermis. Cutaneous complications, i.e, erythema of greater than or equal to 1-mm diam at the needle-insertion site, were seen with similar frequency. Significantly fewer (P less than .001) cutaneous complications and contaminated needles were found when a disinfectant was sprayed on the skin before insertion of the needle. The results indicate that infection along the indwelling subcutaneous needle contributes substantially to cutaneous complications during continuous subcutaneous insulin infusion and that these complications can successfully be prevented by appropriate antiseptic measures.

Interaction between plastic catheter tubings and regular insulin preparations used for continuous subcutaneous insulin-infusion therapy.

In search of possible interactions between plastic tubings used for insulin-pump treatment and commercial regular insulin preparations, various catheter sets made from polyvinyl chloride (PVC), polyethylene (PE), and nylon plastics were perfused at 30 degrees C in a laboratory setting for up to 72 h. The perfused insulin solutions were analyzed by high-performance liquid chromatography and atomic absorption spectroscopy. Although no plasticizer, e.g., dioctyl phthalate, or nickel or chromium ions were found in the perfusates, substantial interactions between the plastics and the insulin solutions were detected, extraction of bacteriostatic additives from the insulin solutions in particular. The PVC retained up to 88% of the bacteriostatics from the insulin preparations, whereas PE tubings retained only 10-15%. Whether the loss of preservatives during perfusion through PVC catheters predisposes to cutaneous infections during insulin-pump therapy remains to be shown.

Diurnal plasma profiles of metabolite and hormone concentration in insulin-dependent diabetic patients during conventional insulin treatment and continuous subcutaneous insulin infusion

In addition to hyperglycaemia, derangement of metabolic and hormonal control may play an important role in the development of microvascular complications in diabetes. Little, however, is known about the impact of insulin pump treatment on metabolic and hormonal parameters. In a 6-month prospective randomized study in insulin-dependent diabetics we therefore investigated the effects of continuous subcutaneous insulin infusion by pump (10 patients) and conventional insulin treatment (10 patients) on the 24-h profiles of blood glucose, glycerol, lactate, 3-hydroxybutyrate, insulin, glucagon and growth hormone by measuring the respective concentrations every 2 h. We found that average blood glucose levels and HbA1c were significantly lower in the group treated by continuous subcutaneous insulin infusion as compared with the group on conventional insulin treatment. Furthermore, we observed an improvement in diurnal levels of lactate and 3-hydroxybutyrate in the pump-treated group which was not seen in the conventionally treated group. A slight increment in alanine was seen in the group treated with insulin pump. Serum growth hormone, glycerol, plasma free insulin as well as the daily insulin supply were unchanged and identical in the two groups. It is noteworthy that in the pump group, the decrease in blood glucose and 3-hydroxybutyrate takes place concomitantly with a significant suppression of glucagon.

Insulin pump treatment in insulin-dependent diabetes mellitus. Children, adolescents, and young adults

Twenty-four children, teenagers, and young adults (8 to 26 years old) with insulin-dependent diabetes mellitus were treated with continuous subcutaneous insulin infusion (CSII). Criteria for using CSII included persistent high glycohemoglobin (GHb) values and/or wide swings in blood glucose values despite arduous efforts to improve glycemia. Thirty percent discontinued CSII. Improvement was significant by three months for GHb and blood glucose values, but plateaued thereafter. Only three patients attained a normal GHb value. No predictors for degree of control were identified. Diabetic ketoacidosis did not occur more frequently with CSII. Electromechanical problems with the devices, patient errors, or local skin problems occurred in 50% of patients, although none produced ketoacidosis or severe hypoglycemia. Dietary noncompliance and decreased intensive home monitoring were contributory factors. Better ways to predict success or failure are needed if normalization or even near-normalization is a goal of CSII in younger patients with insulin-dependent diabetes mellitus followed up in a nonresearch setting. (<i>JAMA</i>1986;255:617-621)

Effect of Insulin Pump Treatment for One Year on Renal Function and Retinal Morphology in Patients with IDDM

The effect of strict metabolic control for 1 yr on renal function and retinal morphology was estimated in 24 insulin-dependent diabetic individuals (age 29 +/- 8 yr, diabetes duration 10 +/- 6 yr) with Albustix negative urine and minimal or no background retinopathy before the study. They were randomized to conventional insulin treatment (CIT) or continuous subcutaneous insulin infusion (CSII) with a portable pump. During CSII treatment the metabolic status was significantly improved and glomerular filtration rates (GFR) were found to decline (from 130 +/- 18 to 116 +/- 15 ml/min/1.73 m2, P less than 0.01). The mean value of urinary albumin excretion (UAE) was not statistically significantly reduced (from 15.3 +/- 24.1 to 6.8 +/- 1.5 mg/24 h, P greater than 0.1). In the CIT group both GFR and UAE values were unchanged. In all subjects before treatment we found a positive correlation between the metabolic status, estimated by the HbA1c values, and GFR as well as UAE values, respectively (r = 0.64, P less than 0.01 and r = 0.42, P less than 0.05). We conclude that elevated GFR values can be reduced toward normal level by insulin pump treatment for 1 yr. Retinal morphology was found to deteriorate in four of 12 CIT subjects and in three of 12 CSII subjects. However, the progression was mild and in most individuals only due to a slight increase in the number of microaneurysms. Pump treatment did not induce proliferation and "cotton-wool" exudates were not detectable in any pump subject after 1 yr of treatment. We conclude that CSII treatment for 1 yr was unable to stop the progression of retinopathy in individuals with minimal or no retinopathy on entering the study. On the other hand, pump treatment did not induce cotton-wool exudates or proliferation in these subjects as previously reported in subjects with more severe retinopathy before CSII treatment.

Intensive insulin therapy reduces counterregulatory hormone responses to hypoglycemia in patients with type I diabetes.

Counterregulatory hormone responses to hypoglycemia were examined in six healthy controls and in six patients with type I diabetes before and after 4 to 8 months of insulin pump treatment. The insulin clamp technique was used to provide an identical hypoglycemic stimulus (about 50 mg/dL) in each study group. Before pump treatment, the release of counterregulatory hormones (except glucagon) during the hypoglycemic period was not significantly different in diabetics from that in normal controls. However, when values before and after pump treatment in diabetics were compared, there were significant reductions in epinephrine (304 +/- 70 and 127 +/- 43 pg/mL; p less than 0.01), growth hormone (45 +/- 12 and 18 +/- 5 ng/mL; p less than 0.05), and cortisol (20 +/- 3 and 10 +/- 2 micrograms/dL; p less than 0.01) levels during hypoglycemia. Defective glucagon release during hypoglycemia in the diabetics was not corrected by pump treatment. Intensive insulin treatment of patients with type I diabetes causes a generalized reduction in counterregulatory hormone release after a moderate fall in blood glucose levels. This reduction may impair glucose counterregulation and diminish perception of hypoglycemia, thereby increasing the risk of hypoglycemic episodes.

Pituitary response to growth hormone-releasing factor in diabetes. Failure of glucose-mediated suppression.

To evaluate the mechanism underlying raised growth hormone levels in diabetes, we compared the response to growth hormone-releasing factor (GRF) in type I diabetic and healthy control subjects. In 12 poorly controlled diabetic subjects (fasting plasma glucose 276 +/- 27 mg/dl) basal serum growth hormone levels were elevated by 200-300% (P less than 0.02), yet the incremental increase in growth hormone after GRF injection was no greater than in control subjects. Furthermore, five additional diabetic subjects with normal growth hormone levels after long-term insulin pump treatment also showed an identical response to GRF. Thus, raised basal growth hormone levels in diabetes and the fall that follows intensive insulin treatment may reflect changes in hypothalamic regulation of, rather than in pituitary responsiveness to, GRF. However, when five normal subjects were restudied during glucose infusion, even quite modest hyperglycemia (plasma glucose approximately 150 mg/dl) caused marked suppression of the response to GRF (P less than 0.005). Thus, the "normal" response to GRF in poorly controlled diabetes is actually inappropriate. Failure of the pituitary to suppress in response to hyperglycemia in diabetes implies a second abnormality that may further aggravate disordered growth hormone secretion.

Insulin pump treatment of diabetes. Decision-making without definitive data

Insulin pump treatment of diabetes. Decision-making without definitive data

Insulin pump treatment for diabetes: unanswered questions.

Insulin pump treatment for diabetes: unanswered questions.