Continuous Sc Insulin Infusion Research Articles

Insulin glulisine for continuous subcutaneous insulin infusion in pediatric type 1 diabetes.

We evaluated the efficacy and safety of insulin glulisine (GLU) used for continuous s.c. insulin infusion (CSII) in 20 children with type 1 diabetes after 1year of GLU treatment. There were no significant differences in mean plasma glucose before breakfast and before dinner between before and after using GLU, but the levels after breakfast and after dinner significantly improved, from 192.5±31.7 to 162.0±27.3mg/dL for breakfast, and from 191.1±33.3 to 161.1±24.5mg/dL for dinner (P<0.01). Mean hemoglobin A1c significantly decreased (from 8.0±0.8 to 7.7±0.8%, P<0.05), and the mean frequency of hypoglycemia significantly reduced after using GLU (from 8.3±4.9 to 6.0±3.4/month, P<0.05). In conclusion, the use of GLU rather than other rapid-acting analogues for CSII might be an effective treatment option in children with type 1 diabetes.

Suspension of basal insulin to avoid hypoglycemia in type 1 diabetes treated with insulin pump.

SummaryTreatment with continuous s.c. insulin infusion (CSII) provides better glycemic control and lower risk of hypoglycemia than conventional therapy with multiple daily insulin injections. These benefits have been related to a more reliable absorption and an improved pharmacokinetic profile of insulin delivered through CSII therapy. However, even for patients treated with CSII, exaggerated postmeal hyperglycemic excursions and late postabsorptive hypoglycemia can still constitute a therapeutic challenge. Two female patients with type 1 diabetes who began treatment with CSII required to increase their previous breakfast insulin-to-carbohydrate ratio in order to achieve postprandial glycemic goals. However, they simultaneously presented recurrent episodes of late hypoglycemia several hours after breakfast bolus. Advancing the timing of the bolus was ineffective and bothersome for patients. In both cases, the best therapeutic option was to set a basal insulin rate of zero units per hour during 6 h after breakfast. Even so, they need to routinely take a midmorning snack with 10–20 g of carbohydrates to avoid late postabsorptive hypoglycemia. They have been using this insulin schedule for about 3 years without complications. The action of prandial insulin delivered through insulin pumps can be inappropriately delayed for the requirements of some patients. Although suspension of basal rate can be an acceptable therapeutic alternative for them, these cases demonstrate that new strategies to improve the bioavailability of prandial insulin infused through CSII are still needed.Learning points CSII remains the most physiologically suitable system of insulin delivery available today.Additionally, the duration of action of prandial insulin delivered through insulin pumps can be excessively prolonged in some patients with type 1 diabetes.These patients can present recurrent late episodes of hypoglycemia several hours after the administration of insulin boluses.The routine suspension of basal insulin for several hours, leaving meal bolus to cover both prandial and basal insulin requirements, can be a therapeutic option for these subjects.

Ovarian hyperandrogenism in adolescents and young women with type I diabetes is primarily related to birth weight and body mass index

To clarify the effects of insulin therapy on ovarian androgen production, hyperandrogenism and polycystic ovary syndrome (PCOS) in adolescents and young women with type 1 diabetes (T1D). Case-control study. Children's research hospital. Fifty-four consecutive T1D subjects (age, 15-25 years), without residual endogenous insulin secretion, treated by intensive insulin therapy (multiple injection therapy [MI] or continuous SC insulin infusion [CSII]); and one-hundred fifty age-matched healthy women. Analysis of the prevalence and risk factors of ovarian hyperandrogenism and PCOS in T1D adolescents and young women. Biometric, glycemic, and metabolic parameters. Evaluation of androgen levels and ovary ultrasound during the early follicular phase of the menstrual cycle. Androgen levels were significantly higher in T1D subjects than in the control group (T, 68.8 ± 23.4 vs. 46.1 ± 20.8 ng/dL). Four subjects (7.4%) were affected by PCOS according to the Rotterdam criteria. No correlation was evident between HbA1c% and androgen levels. No significant differences were evident between subjects on MI or CSII therapy. Multivariable linear regression analysis showed a direct and independent effect of age and body mass index on T levels. T levels were also negatively affected by birth weight. Androgen levels are significantly increased in T1D adolescents and young women treated by intensive insulin therapy. The presence and severity of ovarian hyperandrogenism seem to be primarily related to common risk factors such as age, low birth weight, overweight, and obesity.

Lipoatrophy Induced by Subcutaneous Insulin Infusion: Ultrastructural Analysis and Gene Expression Profiling

Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication of insulin therapy. We aimed to analyze the ultrastructural and molecular aspects of LA lesions. Macroscopic and microscopic morphology of SAT beneath the LA areas from patients with type 1 diabetes treated with Lispro insulin by continuous sc insulin infusion was studied using magnetic resonance imaging, immunohistochemistry, electron microscopy, and quantitative PCR for adipose tissue-specific genes. SAT was present in LA lesions characterized by: 1) smaller, unilocular perilipin-positive adipocytes, with lipofuscin granules; 2) some "slimmed cells" losing lipid droplets as those we observed during starvation; and 3) numerous perivascular preadipocytes. We did not identify inflammatory cells. SAT in LA areas displayed a strong leptin down-regulation and an increase of AEBP1, a preadipocyte marker. Our results clearly indicate that the remarkable reduction in fat cell lipid droplets and adipocyte size justifies the decrease of SAT without a reduction in adipocyte number because of necrosis or apoptosis. Thus, immune cells and any other toxic damaging fat cells were not involved in the generation of LA. We speculate that adipocytes chronically exposed to high local insulin concentrations could become severely insulin resistant, dramatically increasing lipolysis and giving rise to "slimmed cells." Clinical LA regression could be explained by the active recruitment of preadipocytes, even if they were unable to differentiate and regenerate adipose tissue unless the insulin injection was removed.

Effects of moderate-severe exercise on blood glucose in Type 1 diabetic adolescents treated with insulin pump or glargine insulin

Few papers focus on exercise-related blood glucose (BG) in patients on continuous sc insulin infusion (CSII) or multiple daily injections (MDI) with glargine. The main objective was to evaluate the degree of glycemic control in Type 1 diabetes mellitus adolescents on CSII doing physical activity with pump switched on or off. These findings were also compared with a small group of patients on MDI with glargine. Eight patients on CSII (basal rate continued or turned off in alternating sessions) and 5 on MDI joined 4 sessions of moderate-severe exercise. Post-exercise BG significantly increased with the pump off and was unchanged/decreased with the pump on and MDI groups vs baseline. The hypoglycemia rate was not different among the 3 groups at any time. Pump on: hypoglycemias more frequent both at bedtime (p=0.031) and at awakening (p<0.001) than before dinner and at awakening than at bed-time (p=0.044). Pump off: hypoglycemias more frequent both at bed-time (p=0.010) and at awakening (p=0.031) than before dinner. MDI: no differences. Glargine is safe and reducing the pre-lunch insulin is unnecessary. Subjects on insulin pump should not stop the basal rate. If they stop the pump, some actions are advisable: pre-exercise insulin bolus, pre-sleeping snack rich in carbohydrates, slight reduction of the overnight basal rate. On the other hand, if the basal rate is unmodified, the ingestion of sugary drinks during the exercise, the reduction of the overnight basal rate, a reduction of the pre-dinner insulin bolus and/or a pre-sleeping snack should be considered.

Twenty-Four-Hour Simultaneous Subcutaneous Basal-Bolus Administration of Insulin and Amylin in Adolescents with Type 1 Diabetes Decreases Postprandial Hyperglycemia

The purpose of this study was to examine the effect of continuous sc replacement of amylin and insulin for a 24-h period on glucose homeostasis in adolescents with type 1diabetes. Thirteen adolescents with type 1 diabetes on insulin pump therapy participated in a randomized, controlled, crossover design study comparing continuous sc insulin monotherapy (part A) vs. continuous sc insulin and pramlintide infusion (part B). In part A, basal and bolus insulin infusion was per prescribed home regimen. In part B, the basal insulin infusion was the same as part A, but prandial insulin boluses were reduced by 20%. Basal and prandial bolus pramlintide were administered simultaneously via another pump. All boluses were given as a dual wave. The study regimen resulted in a 26% reduction in postprandial hyperglycemia as compared to insulin monotherapy (area under the curve, 600 min, 2610 +/- 539 vs. 692 +/- 861 mg/liter . min) (P < 0.008). Glucagon concentrations were suppressed postprandially (P < 0.003) but not in the postabsorptive state, whereas plasma insulin concentrations were unchanged. Simultaneous continuous sc pramlintide and insulin infusion has the potential of improving glucose concentrations by way of physiological replacement.

Continuous SC insulin infusion (CSII) results in a greater decrease in HbA1c levels

Continuous SC insulin infusion (CSII) results in a greater decrease in HbA1c levels

Daily insulin requirement of children and adolescents with type 1 diabetes: effect of age, gender, body mass index and mode of therapy.

The purpose of this study was to generate insulin dose (ID) percentiles for children and adolescents with type 1 diabetes mellitus (DM1) having the opportunity to assess this important parameter in relation to age and sex. Daily IDs per weight (ID/kg) were recorded in 22,177 patients with DM1 (3-25 years of age, DM1 duration of more than 2 years, 48% female) and ID percentiles (ID-Perc) were created statistically. The ID-Perc were compared between male and female, and between multiple insulin injection therapy (MIT) and continuous s.c. insulin infusion (CSII). A multivariate regression analysis was performed for ID in the third year of DM1 with ID/kg, body weight, age, gender, and insulin delivery regimen as variables. The 50th ID-Perc (P50) varied among 0.67 IU/kg (age 3 years), 0.93 IU/kg (13 years), and 0.70 IU/kg (23 years) increasing from early childhood to adolescence and decreasing toward adulthood. Highest P50 ID was found at 12 years in females (0.94 IU/kg) and at 14 years in males (0.92 IU/kg). Using ICT, the ID was significantly higher compared with CSII (P50: 0.94 IU/kg versus 0.79 IU/kg at 13 years). In multivariate regression analysis, ID was significantly (P>0.001) associated with age, gender, and insulin delivery regime. The ID-Perc were significantly different during various periods of childhood and were influenced by gender, body weight, and insulin injection regimes. Therefore, the presented data 1) provide evidence to interpret individual ID in children and adolescents with DM1 and 2) more specifically identify children with unusually high (insulin resistance and non-compliance) or low (MODY and persistent remission) insulin requirement.

Intensive insulin therapy in preschool-aged diabetic children: From multiple daily injections to continuous subcutaneous insulin infusion through indwelling catheters

In this study, glycemic control, diabetes care indices and quality of life (QoL) were assessed in 2 groups of newly diagnosed Type 1 diabetic subjects <6 yr old who were randomized to multiple daily injections with (Group A) or without (Group B) an indwelling catheter. Group A [12 males (M)/8 females (F), mean age 3.2+/-1.4 yr] and Group B (9M/11F, mean age 3.9+/-1.8 yr) were evaluated at baseline and after 6 and 12 months of treatment. No significant difference was observed in metabolic control (glycosylated hemoglobin) or in the number of hypoglycemic events between the groups. Patients in Group A had a greater number of daily insulin injections, monitored blood glucose more frequently and had a lower total daily insulin dose per kg (p<0.05). QoL was better in group A. At the end of the study 30% of group A patients progressed to continuous sc insulin infusion (CSII), while no child in Group B switched to a different insulin regimen. Based on these findings, indwelling catheter therapy may be helpful for selected CSII candidates.

Intensive Insulin Therapy in Type 2 Diabetes

Exogenous insulin is eventually required in many patients with type 2 diabetes due to a progressive decline in pan- creatic γ-cell function. Insulin is usually initiated when other therapeutic modalities have failed to achieve glycemic control. Candidates for intensive management should be motivated, compliant, educable, and without other medical conditions and physical limitations that would preclude accurate and reliable monitoring and insulin administration. When combination therapy with a basal insulin plus oral antidiabetic drugs is not successful, therapy may be intensi- fied with a premixed or split-mixed regimen of intermediate- and fast-acting insulin equally divided between the pre- breakfast and predinner periods. For patients who do not achieve glucose control on combination basal or split-mixed regimens, an intensive basal-bolus multiple-injection regimen is indicated. Continuous SC insulin infusion pumps may be particularly useful in patients who do not respond satisfactorily to more conventional treatment strategies. Fast- acting insulin analogues should be used in the majority of patients requiring insulin because of their more physiologic pharmacokinetic profile. Inhaled insulin is a new alternative to SC insulin for patients with type 2 diabetes requiring insulin. (Insulin. 2007;2(Suppl B):$34-$40.

Basal insulin supplementation in Type 1 diabetic children: A long-term comparative observational study between continuous subcutaneous insulin infusion and glargine insulin

No long-term data are available on the efficacy of glargine insulin in comparison with continuous sc insulin infusion (CSII) in children and adolescents affected by Type 1 diabetes (T1D). Our aim was to compare the 2-yr efficacy of the 2 insulin approaches, in order to know how to best supply basal insulin in these patients. Thirty-six 9 to 18-yr-old consecutive children with at least 3 yr previous T1D diagnosis were enrolled. As part of routine clinical care, the patients consecutively changed their previous insulin scheme (isophane insulin at bedtime and human regular insulin at meals) and were randomly selected in order to receive either multiple daily injections (MDI) treatment with once-daily glargine and human regular insulin at meals, or CSII with aspart or lispro insulin. Both groups showed a significant decrease in glycosylated hemoglobin (HbA1c) values during the 1st year of therapy, though only in the CSII treated children was the decrease also observed during the 2nd year. The overall insulin requirement significantly decreased only in the CSII group and exclusively during the 1st year, while no significant differences were observed concerning body mass index SD score, severe hypoglycemic episodes and basal insulin supplementation. The work illustrates the first long-term study comparing the efficacy of CSII to MDI using glargine as basal insulin in children. Only with CSII were better HbA1c values obtained for prolonged periods of time, so that CSII might be considered the gold standard of intensive insulin therapy also for long-term follow-ups.

Age-related differences in metabolic response to continuous subcutaneous insulin infusion in pre-pubertal and pubertal children with Type 1 diabetes mellitus

The aim of this study was to evaluate clinical and metabolic data in a cohort of Type 1 diabetes (T1DM) children before and after 2 yr of continuous s.c. insulin infusion (CSII). Forty seven T1DM patients were subdivided into two groups: Group A (20 pre-pubertal children, mean age 7.43+/-3.19 yr); Group B (27 pubertal adolescents, mean age 14.47+/-1.91 yr). No statistically significant differences in body mass index (BMI) occurred in either groups after starting CSII or during follow-up. The frequency of mild-hypoglycemias significantly declined during pump therapy only in Group A (p<0.05). Both pre-pubertal and pubertal patients required a significant reduction in their total insulin requirement after 12 and 24 months of CSII. The total percentage of daily insulin doses delivered as basal rates was similar in both groups and was negatively associated (beta=-2.956, p=0.05) with glycosylated hemoglobin (HbA1c) values. No significant correlation was found between the percentage of the basal insulin rate and the number of daily boluses. Differences in timing of the highest insulin requirement were observed between the two groups. Group A had a higher insulin basal rate late in the evening (20:00-24:00 h), while Group B had a higher insulin requirement early in the morning (03:00-07:00 h). The HbA1c levels significantly improved in Group A after 6-12 and 24 months of CSII. In Group B a reduction of HbA1c values was observed only after 6 months of pump therapy (p=0.05). CSII is an effective therapy for all ages but different metabolic requirements should also be taken into account.

Continuous SC insulin infusion worth it for diabetes in the UK

Continuous SC insulin infusion worth it for diabetes in the UK

Continuous SC insulin infusion "worthwhile investment" in diabetes

Continuous SC insulin infusion "worthwhile investment" in diabetes

Continuous SC insulin infusion “worthwhile investment” in diabetes

Continuous SC insulin infusion “worthwhile investment” in diabetes

Efficacy and safety of insulin aspart compared to buffered human insulin by continuous SC insulin infusion

Efficacy and safety of insulin aspart compared to buffered human insulin by continuous SC insulin infusion

Continuous SC insulin infusion improves metabolic control

Continuous SC insulin infusion improves metabolic control

Benefits of nocturnal continuous SC insulin infusion

Benefits of nocturnal continuous SC insulin infusion

The degree/rapidity of the metabolic deterioration following interruption of a continuous subcutaneous insulin infusion is influenced by the prevailing blood glucose Level.

This study aims at investigating the influence of the prevailing blood glucose level on the metabolic deterioration that follows a nocturnal interruption of a continuous sc insulin infusion (CSII). Fifteen CSII-treated, C-peptide negative, diabetic patients have been studied CSII was interrupted from 2300 h to 0500 h. Blood was collected hourly from 2200 h to 0600 h. According to blood glucose (BG) levels at 2300 h, patients were classified as hypoglycemic (BG between 1.5 and 2.5 mmol/L, n = 5), normoglycemic (BG between 4.0 and 8.0 mmol/L, n = 5), or hyperglycemic (BG between 9.0 and 15.0 mmol/L, n = 5). At 2300 h, BG (mean +/- SEM) was 1.9 +/- 0.1, 6.2 +/- 0.7 and 11.2 +/- 1.0 mmol/L, respectively. After 6 h of CSII interruption, BG increased to 13.5 +/- 1.3, 14.1 +/- 1.2, and 19.4 +/- 1.2 mmol/L, respectively. At 2300 h, plasma 3-OH-butyrate levels were similar in the three groups (around 150 micromol/L). At 0500 h, significantly higher values were obtained for hyperglycemic (1460 +/- 127 micromol/L) than for normoglycemic (868 +/- 150 micromol/L) or hypoglycemic (837 +/- 80 micromol/L) patients. Enhanced lipolysis in initially hyperglycemic patients may contribute to accelerated ketogenesis and metabolic degradation. In conclusion, the metabolic deterioration that follows CSII interruption is influenced by the initial metabolic situation. Hypoglycemic patients deteriorate more rapidly, and hyperglycemic patients suffer a more important degradation. The latter are prone to rapid ketoacidosis if accidental CSII interruption occurs.

Insulin Regulates the Serum Levels of Low Molecular Weight Insulin-Like Growth Factor-Binding Protein*

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.