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Insulin Dose (insulin + dose)

Distribution by Scientific Domains

Medical Sciences	97%

Distribution within Medical Sciences

Diabetes	82%
Pediatrics	5%
3 Other Subdomains	13%

Kinds of Insulin Dose

daily insulin dose

total daily insulin dose

Selected Abstracts

Addition of insulin lispro protamine suspension or insulin glargine to oral type 2 diabetes regimens: a randomized trial

DIABETES OBESITY & METABOLISM, Issue 10 2010
K. Strojek
Aims: The addition of basal insulin to existing oral therapy can help patients with type 2 diabetes (T2D) achieve glycaemic targets. This study compares the efficacy and safety of insulin lispro protamine suspension (ILPS) and insulin glargine in insulin-naive patients with T2D and inadequate control on oral antihyperglycaemic medication (OAM). Materials and Methods: An open-label, randomized, multicentre, multinational 24-week study of 471 patients receiving ,2 OAMs for ,3 months with a body mass index between 25 and 45 kg/m2 and HbA1c 7.5,10.0% was conducted. ILPS was injected once or twice daily vs. glargine injected once daily plus prestudy OAMs. Primary objective compared the HbA1c change from baseline. Results: HbA1c change from baseline to endpoint was similar in both groups [,1.46% (ILPS) and ,1.41% (glargine)]. Least-squares mean difference (95% CI) for HbA1c (,0.05 [,0.21, 0.11]%), glycaemic variability (0.06 [,0.06, 0.19] mmol/l) and weight change (,0.01 [,0.61, 0.59] kg) showed non-inferiority (margins of 0.4%, 0.8 mmol/l and 1.5 kg, respectively). Percentages of patients achieving HbA1c <7.0% were 43.8% ILPS and 41.2% glargine. Mean daily insulin dose was 0.39 vs. 0.35 U/kg (p = 0.02) and weight gain was 1.04 vs. 1.07 kg for ILPS vs. glargine (p = 0.98). Overall hypoglycaemia (episodes/patient/year) was similar for ILPS and glargine (24.2 ± 28.8 vs. 23.0 ± 30.9); nocturnal (6.1 ± 10.6 vs. 4.1 ± 9.4, p < 0.001) rates were higher for ILPS. Severe hypoglycaemia was higher for ILPS vs. glargine (n = 9 vs. n = 2; p = 0.04). Conclusions: At endpoint, ILPS was non-inferior to glargine in HbA1c change from baseline, but associated with increased risk of hypoglycaemia. [source]

Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes

DIABETES OBESITY & METABOLISM, Issue 2 2010
T. Vilsbøll
Objective: To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes. Methods: After a 2 week placebo run-in period, eligible patients inadequately controlled on long-acting, intermediate-acting or premixed insulin (HbA1c , 7.5% and , 11%), were randomised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period. The study capped the proportion of randomised patients on insulin plus metformin at 75%. Further, the study capped the proportion of randomised patients on premixed insulin at 25%. The metformin dose and the insulin dose were to remain stable throughout the study. The primary endpoint was HbA1c change from baseline at week 24. Results: Mean baseline characteristics were similar between the sitagliptin (n = 322) and placebo (n = 319) groups, including HbA1c (8.7 vs. 8.6%), diabetes duration (13 vs. 12 years), body mass index (31.4 vs. 31.4 kg/m2), and total daily insulin dose (51 vs. 52 IU), respectively. At 24 weeks, the addition of sitagliptin significantly (p < 0.001) reduced HbA1c by 0.6% compared with placebo (0.0%). A greater proportion of patients achieved an HbA1c level < 7% while randomised to sitagliptin as compared with placebo (13 vs. 5% respectively; p < 0.001). Similar HbA1c reductions were observed in the patient strata defined by insulin type (long-acting and intermediate-acting insulins or premixed insulins) and by baseline metformin treatment. The addition of sitagliptin significantly (p < 0.001) reduced fasting plasma glucose by 15.0 mg/dl (0.8 mmol/l) and 2-h postmeal glucose by 36.1 mg/dl (2.0 mmol/l) relative to placebo. A higher incidence of adverse experiences was reported with sitagliptin (52%) compared with placebo (43%), due mainly to the increased incidence of hypoglycaemia (sitagliptin, 16% vs. placebo, 8%). The number of hypoglycaemic events meeting the protocol-specified criteria for severity was low with sitagliptin (n = 2) and placebo (n = 1). No significant change from baseline in body weight was observed in either group. Conclusion: In this 24-week study, the addition of sitagliptin to ongoing, stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes. [source]

Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitus

DIABETES OBESITY & METABOLISM, Issue 6 2005
Suzanne M. Strowig
The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation. [source]

Comparison of insulin lispro protamine suspension and insulin detemir in basal-bolus therapy in patients with Type 1 diabetes

DIABETIC MEDICINE, Issue 5 2010
A. R. Chacra
Diabet. Med. 27, 563,569 (2010) Abstract Aims, The efficacy of two basal insulins, insulin lispro protamine suspension (ILPS) and insulin detemir, was compared in basal-bolus regimens in Type 1 diabetes. Methods, In this 32-week, multinational, parallel-group, randomized, controlled trial, adult patients with Type 1 diabetes received ILPS or insulin detemir, injected twice daily (before breakfast and bedtime) and prandial insulin lispro three times daily. The primary outcome was change in glycated haemoglobin (HbA1c) from baseline to endpoint. Results, Least squares mean (±se) changes in HbA1c were similar between groups, meeting non-inferiority (margin, 0.4%): ,0.69 ± 0.07% for ILPS and ,0.59 ± 0.07% for insulin detemir [between-treatment difference ,0.10%; 95% confidence interval (CI) ,0.29, 0.10]. Standard deviation of fasting blood glucose was similar (non-inferiority margin 0.8 mmol/l): 2.74 ± 0.14 mmol/l for ILPS and 2.38 ± 0.14 mmol/l for insulin detemir (CI ,0.03, 0.75). Patients on ILPS gained more weight (1.59 ± 0.23 kg vs. 0.62 ± 0.24 kg; CI 0.34, 1.60; margin 1.5 kg). Weight-adjusted daily total and prandial insulin doses were lower for ILPS (prandial insulin, 0.38 ± 0.01 U/kg/day for ILPS, 0.44 ± 0.01 U/kg/day for insulin detemir; P = 0.004); daily basal insulin dose was similar. All hypoglycaemia incidence and rate and nocturnal hypoglycaemia incidence were similar between groups; nocturnal hypoglycaemia rate was lower for insulin detemir (mean ± sd 0.79 ± 1.23 for ILPS, 0.49 ± 0.85 for insulin detemir; P = 0.001). Severe hypoglycaemia rate was 0.03 ± 0.11 for ILPS and 0.02 ± 0.10 for insulin detemir (P = 0.37). Conclusions, ILPS-treated patients with Type 1 diabetes achieved similar glycaemic control as insulin detemir-treated patients after 32 weeks. Glucose variability was similar. While weight gain and nocturnal hypoglycaemia rate were statistically higher with ILPS, the clinical relevance is unclear. [source]

The effect of biopsy-positive silent coeliac disease and treatment with a gluten-free diet on growth and glycaemic control in children with Type 1 diabetes

DIABETIC MEDICINE, Issue 12 2009
S. Sun
Abstract Objective, To determine the effect of coeliac disease and treatment with a gluten-free diet on growth and glycaemic control in asymptomatic children with Type 1 diabetes. Methods, Data were compared in children with coeliac disease diagnosed by annual antibody screening and jejunal biopsy and treated with a gluten-free diet (n = 49) against individuals who were antibody negative (n = 49) matched for age, sex and duration of diabetes. Results, No differences in growth were observed. In the years prior to diagnosis of coeliac disease, mean glycated haemoglobin (HbA1c) was lower in cases compared with control subjects [8.3 ± 1.1% vs. 8.7 ± 0.9%, P = 0.02 (mean ± sd)]. In cases, HbA1c deteriorated 12 months from the start of a gluten-free diet to levels similar to control subjects (8.9 ± 1.5% vs. 8.8 ± 1.5%, P -value for analysis of variance = 0.9). In regression analysis, the diagnosis of coeliac disease and start of a gluten-free diet was associated with a rise in HbA1c in the first year of treatment [odds ratio 1.56 (95% confidence intervals 1.16,2.10), P = 0.003] after adjusting for insulin dose and regimen and other variables. Conclusions, In children with Type 1 diabetes, lower HbA1c prior to diagnosis of silent coeliac disease rises following treatment with a gluten-free diet to levels similar to those without coeliac disease. Although unproven, these observations may relate to abnormalities at the small bowel mucosa before the appearance of circulating coeliac antibodies. [source]

Lower levels of circulating IGF-I in Type 1 diabetic women with frequent severe hypoglycaemia during pregnancy

DIABETIC MEDICINE, Issue 7 2008
L. Ringholm Nielsen
Abstract Aims Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin-like growth factor I (IGF-I) levels. Methods A prospective, observational study of 107 consecutive pregnant women with Type 1 diabetes. Blood samples were drawn for IGF-I and placental GH analyses at 8, 14, 21, 27 and 33 weeks. Severe hypoglycaemic events were reported within 24 h. Results Eleven women (10%) experienced frequent severe hypoglycaemia (, 5 events), accounting for 60% of all events. Throughout pregnancy, IGF-I levels were 25% lower in these women (P < 0.005) compared with the remaining women, despite similar placental GH levels. Eighty per cent of the severe hypoglycaemic events occurred before 20 weeks when IGF-I levels were at their lowest. This finding was not explained by differences in insulin dose, median plasma glucose levels or glycated haemoglobin. History of severe hypoglycaemia the year preceding pregnancy and impaired hypoglycaemia awareness,being the only predictors of frequent severe hypoglycaemia in a logistic regression analysis,were not associated with IGF-I or placental GH levels at 8 weeks. Conclusions In women with Type 1 diabetes experiencing frequent severe hypoglycaemia during pregnancy, IGF-I levels are significantly lower compared with the remaining women despite similar placental GH levels. IGF-I levels are lowest in early pregnancy where the incidence of severe hypoglycaemia is highest. IGF-I may be a novel factor of interest in the investigation of severe hypoglycaemia in patients with Type 1 diabetes. [source]

Comparison of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) in paediatric Type 1 diabetes: a multicentre matched-pair cohort analysis over 3 years

DIABETIC MEDICINE, Issue 1 2008
B. I. Jakisch
Abstract Aims To conduct a multicentre, matched-pair cohort analysis comparing glycaemic control and adverse events of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) in paediatric patients. Methods Using standardized computer-based prospective documentation, HbA1c, insulin dose, body mass index,standard deviation score (BMI,SDS), rate of hypoglycaemia, rate of diabetic ketoacidosis (DKA) and intensity of care were analysed in 434 matched pairs during a follow-up period of 3 years after initiation of MDI or CSII. Results HbA1c was significantly lower in the CSII group during the first year of new regimen (CSII 7.5 ± 0.05 vs. MDI 7.7 ± 0.06; P < 0.05), but rose to the same level as in the MDI group during year 3. Insulin requirement remained significantly lower in the CSII group. The BMI,SDS increased in both study groups, with no significant difference. The rate of severe hypoglycaemia decreased significantly after the change of regimen (CSII 17.87 ± 2.85 vs. MDI 25.14 ± 3.79; P < 0.05) and during year 3 of the regimen, particularly when compared with baseline (,21% vs. ,16%). The rate of DKA was lower at baseline in the CSII group and remained significantly lower over all 3 years. Intensity of care was the same in both subsets. Conclusions Employing a large cohort, this matched-pair analysis has demonstrated over a 3-year study period that CSII is a safe form of intensive insulin therapy with similar glycaemic effects, but with significantly reduced rates of hypoglycaemia and DKA and a lower insulin requirement when compared with MDI. [source]

Nocturnal hypoglycaemia in Type 1 diabetic patients, assessed with continuous glucose monitoring: frequency, duration and associations

DIABETIC MEDICINE, Issue 5 2007
I. M. E. Wentholt
Abstract Aims, We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple-injection therapy (MIT) using a continuous subcutaneous glucose sensor. Methods, A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA1c 7.8 ± 0.9%) and 33 patients on MIT (HbA1c 8.7 ± 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA1c, diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated. Results, Nocturnal hypoglycaemia , 3.9 mmol/l occurred in 33.3% of both the CSII- (8/24) and MIT-treated patients (11/33). Mean (± sd; median, interquartile range) duration of hypoglycaemia , 3.9 mmol/l was 78 (± 76; 57, 23,120) min per night for the CSII- and 98 (± 80; 81, 32,158) min per night for the MIT-treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia. Conclusions, Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value. [source]

A longitudinal observational study of insulin therapy and glycaemic control in Scottish children with Type 1 diabetes: DIABAUD 3

DIABETIC MEDICINE, Issue 11 2006
Scottish Study Group for the Care of the Young with Diabetes
Abstract Objective/background, Our objective was to investigate glycaemic control in children with Type 1 diabetes in Scotland and to analyse the effect of changing ,conventional' insulin regimen strategies on outcome. DIABAUD 2 (1997,1998) (D2) demonstrated that average glycaemic control in young people with Type 1 diabetes in Scotland was poor, with mean HbA1c of 9.0%. Over 90% were then treated with a twice-daily insulin regimen. The aim of DIABAUD 3 (2002,2004) (D3) was to determine if control had improved, and to examine changes in insulin regimen and effects on glycaemic control. Methods, In DIABAUD 3, data were collected prospectively on children aged < 15 years. in nine out of 15 centres throughout Scotland. HbA1c on 986 subjects was measured in a single Diabetes Control and Complications Trial-aligned laboratory. The results were compared with those from DIABAUD 2, for the same nine centres. Multiple regression comparison was performed to adjust for imbalance in relevant confounders (e.g. age, duration, height and weight, insulin dose and centre). Results, For D3, the age range was 1.1,14.9 years (62% aged 10,14 years), mean (± sd) HbA1c 9.2% ± 1.5 (compared with D2, 9.0% ± 1.5). Only 9.7% achieved the target of HbA1c < 7.5%. The number of subjects in D3 on twice-daily injections was 51% (compared with 94% in D2), 43% on three-times-daily injections (2% in D2) and 2.3% on four or more (1.9% in D2): HbA1c did not differ in these groups. In both the D2 and D3 cohorts, HbA1c rose with age. After adjustment for other variables in the combined datasets, insulin regimen was not a significant predictor of HbA1c (F = 0.19, d.f. = 3, 1774; P = 0.90). Conclusion, The glycaemic control in young people in Scotland remains poor and above the national target. Over 4 years, moderate intensification of insulin therapy (i.e. from two to three injections each day, usually reflecting splitting of the evening dose) across the population failed to improve the average HbA1c and reduce the increase seen with age. A national programme away from ,conventional' to an ,intensive' regimen of insulin therapy is required. [source]

Circulating adipocytokines in non-diabetic and Type 1 diabetic children: relationship to insulin therapy, glycaemic control and pubertal development

DIABETIC MEDICINE, Issue 6 2006
F. Celi
Abstract Aim To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. Methods The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-, were measured in 91 children, aged 11.1 ± 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. Results Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA1c. Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-, concentrations were similar in non-diabetic and diabetic children. Conclusions Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations. [source]

Insulin pump therapy vs. multiple daily injections in obese Type 2 diabetic patients

DIABETIC MEDICINE, Issue 8 2005
J. Wainstein
Abstract Aims To compare the efficacy of insulin pump treatment with multiple daily injections in the treatment of poorly controlled obese Type 2 diabetic patients already receiving two or more daily injections of insulin plus metformin. Methods Forty obese Type 2 diabetic subjects (using insulin) were randomized to treatment with continuous subcutaneous infusion pump (CSII) (Minimed®) or multiple daily insulin injections (MDI). At the end of the first 18-week treatment period, patients underwent a 12-week washout period during which they were treated with MDI plus metformin. They were then crossed-over to the other treatment for an 18-week follow-up period. Patients performed 4-point daily self blood-glucose monitoring (SBGM) on a regular basis and 7-point monitoring prior to visits 2, 8, 10 and 16. A subset of patients underwent continuous glucose monitoring using the Minimed® continuous glucose monitoring system (CGMS) at visits 2, 8, 10 and 16. A standard meal test was performed in which serum glucose was tested at fasting and once each hour for 6 h following a test meal. Glucose levels were plotted against time and the area under the curve (AUC) was calculated. HbA1c, weight, daily insulin dose and hypoglycaemic episodes were recorded. Results In obese Type 2 diabetic patients already treated with insulin, treatment with CSII significantly reduced HbA1c levels compared with treatment with MDI. An additional CSII treatment benefit was demonstrated by reduced meal-test glucose AUC. Initial reduction of daily insulin requirement observed in CSII-treated subjects during the first treatment period was attributable to a period effect and did not persist over time. Conclusions In the intent-to-treat analysis, CSII appeared to be superior to MDI in reducing HbA1c and glucose AUC values without significant change in weight or insulin dose in obese, uncontrolled, insulin-treated Type 2 diabetic subjects. [source]

Pregnancy outcome in Type 1 diabetes mellitus treated with insulin lispro (Humalog)

DIABETIC MEDICINE, Issue 1 2003
E. A. Masson
Abstract Aims The use of insulin lispro in pregnancy has not been systematically investigated despite its increasing use. Pooled data from seven centres with experience in the use of insulin lispro were accumulated to evaluate pregnancy outcome in women with Type 1 diabetes. Methods Seven units with specialist obstetric diabetes services were recruited to describe their total experience with insulin lispro in pregnancy. Outcomes with respect to the rate of miscarriage, congenital abnormality, perinatal mortality and maternal parameters were recorded in a standardized format. Results Outcomes on 71 babies from 76 pregnancies were documented. There were six (7.8%) early miscarriages. All 71 babies were liveborn with a mean gestational age of 37.2 weeks, and median birthweight of 3230 g. Seven babies weighed > 4 kg. There were four congenital abnormalities (5.6%). There was a 72% increase in the mean insulin dose (0.75,1.29 IU/kg per day). Maternal glycaemic control improved throughout pregnancy. No women developed retinopathy de novo during pregnancy and six with established retinopathy required laser therapy during pregnancy. Conclusions The use of insulin lispro in Type 1 diabetes during pregnancy results in outcomes comparable to other large studies of diabetic pregnancy. [source]

Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial

DIABETIC MEDICINE, Issue 11 2000
P. D. Home
SUMMARY Aims To compare the efficacy of insulin aspart, a rapid-acting insulin analogue, with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus. Methods Prospective, multi-centre, randomized, open-labelled, parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1070 adult subjects with Type 1 diabetes. Study patients were randomized 2:1 to insulin aspart or unmodified human insulin before main meals, with NPH-insulin as basal insulin. Main outcome measures were blood glucose control as assessed by HbA1c, eight-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia, and adverse events. Results After 6 months, insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 (95% confidence interval 0.03,0.22) %Hb, P < 0.02. Eight-point blood glucose profiles showed lower post-prandial glucose levels (mean baseline-adjusted ,0.6 to ,1.2 mmol/l, P < 0.01) after all main meals, but higher pre-prandial glucose levels before breakfast and dinner (0.7,0.8 mmol/l, P < 0.01) with insulin aspart. Satisfaction with treatment was significantly better in patients treated with insulin aspart (WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ) baseline-adjusted difference 2.3 (1.2,3.3) points, P < 0.001). The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 (0.59,1.18, NS). Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart (1.3 vs. 3.4% of patients, P < 0.05), as were late post-prandial (4,6 h) events (1.8 vs. 5.0% of patients, P < 0.005). Conclusions These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control, hypoglycaemia, and quality of life, in people with Type 1 diabetes mellitus. [source]

Switch to oral hypoglycemic agent therapy from insulin injection in patients with type 2 diabetes

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2008
Takashi Okamoto
Aim: We aimed to determine the feasibility of substituting thiazolidinedione-based therapy for insulin injection therapy in patients with type 2 diabetes. Methods: Thirty-six subjects (17 men and 19 women) aged 67.8 ± 11.3 years with an average insulin dose of 0.46 ± 0.17 U/kg bodyweight, a duration of insulin therapy of 6.1 ± 8.2 years and an average hemoglobin A1c (HbA1c) of 6.8 ± 1.3% were switched from insulin injection therapy to pioglitazone, glimepiride and voglibose combination therapy. Results: The number of subjects achieving HbA1c levels of less than 7% at 4 months was 30. The success rate of switch therapy was 83% (30/36). HbA1c was significantly reduced from 6.7 ± 1.3% to 5.9 ± 0.7% at 4 months after the switch (P < 0.01) in 32 patients who completed the planned 4-month study. No adverse effects including heart failure, liver dysfunction or severe hypoglycemia were observed. The insulin dose and the maximum blood glucose on the switch day were significantly lower and the age was significantly higher in the subjects who achieved HbA1c less than 7% at 4 months compared to those who did not (P < 0.05). Conclusion: Thiazolidinedione-based oral combination therapy may efficiently and safely substitute relatively high-dose insulin injection therapy in patients with type 2 diabetes. [source]

ORIGINAL ARTICLE: Many patients with Type 1 diabetes estimate their prandial insulin need inappropriately

JOURNAL OF DIABETES, Issue 3 2010
Aila J. AHOLA
Abstract Background:, Many factors contribute to the need for prandial insulin in Type 1 diabetes. However, patients' success in achieving normal postprandial glucose concentration is understudied. The aim of the present study was to determine how often patients with Type 1 diabetes achieve normal postprandial glucose concentrations and to evaluate factors associated with postprandial hypo- and hyperglycemia. Methods:, Data on food intake, physical activity, insulin administration, and blood glucose concentration were collected using a self-administered questionnaire from 331 patients with Type 1 diabetes (43% men; mean age 49 ± 12 years; mean diabetes duration 32 ± 13 years). Of these, 179 provided data on blood glucose concentrations measured 110,150 min postprandially. One such meal per patient was randomized for analyses. Results:, Hypoglycemia (<4.0 mmol/L), normoglycemia (4.0,7.9 mmol/L), and hyperglycemia (,8.0 mmol/L) were observed after 23%, 36%, and 41% of meals, respectively. The three postprandial glycemia groups did not differ with respect to the meal composition or the timing of the postprandial blood glucose measurement. In women, postprandial hyperglycemia was associated with shorter diabetes duration and higher preprandial blood glucose concentration, whereas postprandial hypoglycemia was associated with higher physical activity. No single factor explained the postprandial glycemic state in men. Conclusions:, A total of 64% of patients estimated their prandial insulin need inappropriately, suggesting that estimation of the optimal prandial insulin dose is not easy, even after a long duration of diabetes. [source]

Effect of input excitation on the quality of empirical dynamic models for type 1 diabetes

AICHE JOURNAL, Issue 5 2009
Daniel A. Finan
Abstract Accurate prediction of future blood glucose trends has the potential to significantly improve glycemic regulation in type 1 diabetes patients. A model-based controller for an artificial ,-cell, for example, would determine the most efficacious insulin dose for the current sampling interval given available input,output data and model predictions of the resultant glucose trajectory. The two inputs most influential to the glucose concentration are bolused insulin and meal carbohydrates, which in practice are often taken simultaneously and in a specified ratio. This linear dependence has adverse effects on the quality of linear dynamic models identified from such data. On the other hand, inputs with greater degrees of excitation may force the subject into extreme hypoglycemia or hyperglycemia, and thus may be clinically unacceptable. Inputs with good excitation that do not endanger the subject are shown to result in models that can predict glucose trends reasonably accurately, 1,2 h ahead. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source]

Development and in-vivo evaluation of insulin-loaded chitosan phthalate microspheres for oral delivery

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2007
Udhumansha Ubaidulla
Novel chitosan phthalate microspheres containing insulin were prepared by emulsion cross-linking technique. The feasibility of these microspheres as oral insulin delivery carriers was evaluated. The pH-responsive release behaviour of insulin from microspheres was analysed. The ability of chitosan phthalate-insulin microspheres to enhance intestinal absorption and improve the relative pharmacological availability of insulin was investigated by monitoring the plasma glucose and insulin level of streptozotocin-induced diabetic rats after oral administration of microspheres at insulin dose of 20 IU kg,1. In simulated gastric fluid (pH 2.0), insulin release from the microspheres was very slow. However, as the pH of the medium was changed to simulated intestinal fluid (pH 7.4), a rapid release of insulin occurred. The relative pharmacological efficacy for chitosan phthalate microspheres (18.66 ± 3.84%) was almost four-fold higher than the efficacy of the chitosan phthalate-insulin solution administration (4.08 ± 1.52%). Chitosan phthalate microspheres sustained the plasma glucose at pre-diabetic level for at least 16 h. These findings suggest that the microsphere is a promising carrier as oral insulin delivery system. [source]

Evidence for lymphatic transport of insulin by topically applied biphasic vesicles

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2003
Martin J. King
ABSTRACT The cutaneous delivery pathway through the lymphatics of a novel transdermal lipid-based delivery system (biphasic vesicles), which was previously shown to deliver sustained physiological levels of basal insulin in a pain-free manner across the skin, was evaluated in a diabetic rat model. Transdermal patches (one per rat) containing insulin in biphasic vesicles (1,10 mg recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 73 h. Blood glucose was monitored approximately every 2,10 h using a Lifescan glucose meter. Inguinal lymph node insulin levels were analysed by ELISA. Insulin in the lymph nodes increased in a dose- and time-dependent manner. Maximal transdermal insulin concentrations in the lymph nodes were observed with both 140 IU (5 mg: 43.0 + 18.0 ,IU mg,1 (mean + s.e.m., n = 4)) and 280 IU (10 mg: 48.0 + 19.6 ,IU mg,1 (mean + s.e.m., n = 4)) doses of recombinant insulin at t = 73 h. The level of insulin in the lymph nodes after subcutaneous injection of 1 mg insulin at the peak blood glucose response was 35.8 ,IU mg,1 (n = 2), before falling to 0.35 ,IU mg,1 by t = 48 h (n = 2). The lymphatics is involved in the transdermal insulin delivery by biphasic vesicles. This is the first report on the lymphatic transport of a protein after non-invasive topical application on the skin. [source]

Prolonged honeymoon phase in an adolescent with diabetes and thyrotoxicosis provides support for the accelerator hypothesis

PEDIATRIC DIABETES, Issue 4pt2 2008
Nadeem Abdullah
Abstract:, A 14-yr-old female presented with diabetes and Graves' disease. Eighteen months later, she was euthyroid on carbimazole, and her haemoglobin A1c (HbA1c) was normal (5.2%) on a small insulin dose (0.3,0.4 units/kg/day). An assessment of her pancreatic beta-cell reserve, determined by comparing HbA1c and insulin dose, suggested that this was greater than other patients with type 1 diabetes in our service 18 months postdiagnosis (n = 185). We suspect that excess thyroid hormone led to an insulin-resistant state and accelerated her presentation with hyperglycaemia. Insulin resistance fell once normal thyroid function was restored and helped to attenuate further beta-cell destruction when beta-cell mass was relatively well preserved. [source]

The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

PEDIATRIC DIABETES, Issue 4pt1 2008
Monique L Stone
Objective:, To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM) Research design and methods:, Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10,18 yr, puberty (,Tanner breast stage 2 or testicular volume >4 mL), insulin dose ,1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests. Results:, Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (,0.3 vs. ,0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone. Conclusion:, The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM. [source]

Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes

PEDIATRIC DIABETES, Issue 3pt2 2008
Minna Päivärinta
Background:, Insulin glargine is a long-acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes. Objective:, We evaluated the clinical course of diabetes in children and adolescents who were switched from NPH to insulin glargine. Methods:, Between August 2003 and November 2004, a total of 76 subjects were switched to glargine in our clinic, treating 340 children with type 1 diabetes. All the subjects had been receiving insulin NPH, and their serum C-peptide levels had been non-detectable for at least 1 yr. Data were collected retrospectively, and 12,18 months after the change, experiences with glargine were inquired using a questionnaire. Seven subjects (9.2%) discontinued glargine before 12 months, and seven refused to participate. Results:, Data for 62 subjects were analyzed. At the switch (0 months), their mean age was 12.7 yr (range 5.1,17.5), mean duration of diabetes was 6.7 yr (range 1.8,14.3), and mean hemoglobin A1c was (HbA1c) 9.2%. Twelve months later (+12 months), the mean HbA1c remained similar (9.2%), the proportion of long-acting insulin was smaller (47.7 vs. 58.1%; p < 0.001), and the daily insulin dose was lower (0.97 vs. 1.05 IU/kg; p < 0.001). The number of injections was lower at +12 months (17.7% with more than five injections vs. 64.5%; p < 0.001). No differences were seen in weight for height or the number of severe hypoglycemias. Most subjects who continued with glargine for ,12 months considered glargine better than NPH. Conclusions:, A switch to insulin glargine retains a similar glycemic control and does not change the number of severe hypoglycemias. [source]

The severity of clinical presentation of type 1 diabetes in children does not significantly influence the pattern of residual ,-cell function and long-term metabolic control

PEDIATRIC DIABETES, Issue 1 2003
Silvana Salardi
Abstract: Aim:, The purpose of the present study was to compare relationships between the clinical presentation of type 1 diabetes in children and residual ,-cell secretion and long-term metabolic control. Methods:, This retrospective study was conducted in 66 diabetic children with age at diagnosis ranging from 0.7 to 14.8 yr. The patients showed contrasting characteristics at diagnosis: either diabetic ketoacidosis (DKA) (group 1, n = 29) or absence of metabolic derangement (group 2, n = 37) associated with marked (group 2A, n = 12) or mild hyperglycemia (group 2B, n = 25). A regular follow-up was available for at least 10 yr (10,32 yr) in all cases and for 20 yr in 23 cases. C-peptide levels were measured from diagnosis and thereafter at intervals for the first years of disease until becoming permanently undetectable. Results:, C-peptide levels at diagnosis were undetectable in about 20% of the cases both with and without DKA. C-peptide levels at diagnosis, the duration of measurable C-peptide levels and the maximum value found during follow-up were not significantly different in the three groups and were not correlated with glycated hemoglobin (GHb) calculated throughout the whole period. No differences were found between the groups of patients concerning GHb values and insulin dose at 10, 15 and 20 yr of disease. The patients of group 2A, characterized by an extremely high glycemic level without ketoacidosis, had a significantly higher prevalence of HLA DR3/4 heterozygosity. Conclusions:, The severity of clinical presentation at diagnosis does not significantly influence residual ,-cell function, and long-term metabolic control. [source]

Characteristics of glycemic control in young children with type 1 diabetes

PEDIATRIC DIABETES, Issue 4 2002
Francine Ratner Kaufman
Abtract: Background: The Diabetes Control and Complications Trial (DCCT) demonstrated that the rate-limiting step to the intensification of diabetes management in adolescents and adults was hypoglycemia. Young children were presumed to be at even greater risk for hypoglycemia with severe consequences, particularly if they had HbA1c levels < 8%. Subjects: A retrospective chart review was performed on 148 patients with type 1 diabetes on insulin injection therapy who were < 8 yr of age (mean age 5.7 ± 1.5, mean diabetes duration 3.0 ± 1.4 yr) followed quarterly from July 1999 to June 2001. Methods:, The subjects were divided into two groups based on their mean HbA1c values (< 8 vs. , 8%) averaged over the 2-yr time period. The following variables were analyzed comparing the two groups: age, duration of diabetes, insulin dose, severe hypoglycemic episodes, episodes of diabetic ketoacidosis (DKA), percentage of glucose levels above, within, and below the target range, and number of diabetes home-management competencies obtained. Results:, Patients with HbA1c < 8% spent more time within target range (40.0 vs. 29.5%, p = 0.0001) and less time above their target range (36.9 vs. 51.2%, p = 0.0003). There was no difference in the percentage of glucose levels below target (23.2 vs. 19.4%, p = NS), percentage of severe hypoglycemic episodes (3 vs. 7 episodes per 100 patient-yr, p = NS), or episodes of DKA (1 vs. 3 episodes per 100 patient-yr, p = NS) between the two groups. Subjects with lower HbA1c levels had acquired more home-management competencies (4.0 vs. 3.5, p = 0.01). Conclusions:, If families are competent in fundamental diabetes management, young children can achieve HbA1c levels < 8.0% without increasing the risk of hypoglycemia. [source]

Usefulness of the addition of metformin to insulin in pediatric patients with type 1 diabetes mellitus

PEDIATRICS INTERNATIONAL, Issue 4 2005
Tatsuhiko Urakami
Abstract, Background:,The aim of this study was to evaluate the effect of metformin in addition to insulin therapy in adolescents and young adults with type 1 diabetes mellitus. Methods:,Nine patients, two males and seven females, aged 18.1 ± 3.0 years, with type 1 diabetes mellitus were studied. They were relatively overweight with a body mass index (BMI) of 24.2 ± 1.8 and had high levels of HbA1c at 9.5 ± 1.2% despite high doses of insulin of 74.0 ± 31.2 U/day. Metformin at the dose of 500,750 mg daily was administered to the patients in addition to insulin therapy for 1 year. Results:,HbA1c, BMI and insulin dose were compared before 1 year without metformin therapy, at baseline, and at 3, 6 and 12 months during the use of metformin in addition to insulin therapy. HbA1c lowered (8.6 ± 1.4**, 8.4 ± 1.3**, 8.4 ± 1.2*%), BMI was reduced (23.9 ± 1.7*, 23.8 ± 1.8, 23.5 ± 1.8*), and insulin requirement decreased (69.8 ± 29.7*, 68.7 ± 29.8**, 67.3 ± 29.1**U/d) significantly after the start of metformin therapy (*P < 0.05, **P < 0.01 vs at baseline). There were no adverse events, not even lactic acidosis, during the study period. Conclusion:,Metformin is safe and may represent a useful adjunct to the management of type 1 diabetes mellitus in adolescents and young adults who have poor glycemic control despite a large amount of insulin. [source]

The Effect of Metformin in Overweight Patients with Type 1 Diabetes and Poor Metabolic Control

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009
Iben Brock Jacobsen
Double-blinded intervention with 2000 mg metformin or placebo daily in 24 type 1 diabetic patients as adjunct to intensive insulin therapy. Primary endpoint was HbA1c, while secondary endpoints were body weight, frequency of hypoglycaemia, blood pressure, lipids, insulin dosage and self-monitored blood glucose profiles were measured. After 24 weeks, no difference in HbA1c was seen between the metformin and placebo groups (,0.5 ± 0.3 vs. ,0.2 ± 0.2%, P = 0.26. , mean ± S.E.M). Mean diurnal blood glucose profiles showed no statistical significant difference between the groups. The total daily insulin dose (IU) was significantly reduced in the metformin group compared to placebo after 24 weeks (,5.9 ± 2.2 vs. 2.9 ± 1.7, P = 0.004. , mean ± S.E.M). An increase in the frequency of hypoglycaemia was seen in the metformin group (0.7 ± 0.9 vs. 0.3 ± 0.5 events patient,1 week,1, P = 0.005), and a reduction in body weight was found using metformin compared to placebo (,3.0 ± 1.0 vs. 0.8 ± 1.1, P = 0.02. , mean ± S.E.M). Lipids and blood pressure did not differ significantly after intervention. Metformin, as adjunct to intensive insulin therapy, was associated with a reduction in the total daily insulin dose and a significant weight loss in patients with type 1 diabetes mellitus. [source]

Insulin requirement in preschoolers treated with insulin pumps at the onset of type 1 diabetes mellitus

ACTA PAEDIATRICA, Issue 3 2009
Agnieszka Szypowska
Abstract The aim: The aim of this study is to analyze changes in the basal insulin requirement in preschoolers treated with insulin pump at the onset of T1DM, using system to calculate meal time insulin. Methods: 58 children (31 girls) under 6 years (mean age 3.3 ± 1.5 years) initiated on insulin pump therapy within 2 months after recognition of T1DM and treated at least for 1 year were analyzed during a follow-up period of 165 patient-years. Data was collected every 6 months: HbA1c, BMI SDS, diabetic ketoacidosis, severe hypoglycaemia, total daily insulin dose (TDD) and basal insulin. Results: Basal insulin rose from 10% in the third month and did not exceed 30% of TDD after 12 months (p<0.0001). In the third month, 46% of children were without basal insulin; this group included significantly older children (3.7 ± 1.4 vs. 2.8 ± 1.4 years; p = 0.01), which had lower TDD (0.33 ± 0.18 vs. 0.54 ± 0.23u/kg/d; p = 0.0007) than children with basal insulin. HbA1c persisted ,7.3%. Conclusion: In preschool children initiated on CSII therapy at the time of T1DM diagnosis the first year of treatment is critical for altering the basal insulin dose. Preschoolers with TDD lower than 0.5U/kg/d may not require basal insulin. Moreover, basal insulin did not exceed 30% of TDD in the first years after T1DM onset. [source]

Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept study

DIABETES OBESITY & METABOLISM, Issue 5 2006
M. Hausmann
Aim:, This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. Methods:, Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 ± 6.6 years, body mass index 32.7 ± 4.2 kg/m2, glycosylated haemoglobin (HbA1c) 8.4 ± 0.8% (mean ± s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. Results:, INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (,2.7 vs. ,3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (,1.23 vs. ,1.05%), body weight (,1.9 vs. ,2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (,1.15 ,mol/l; p < 0.001) but not with GLA [,0.52 ,mol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. Conclusions:, In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies. [source]

Comparison of insulin lispro protamine suspension and insulin detemir in basal-bolus therapy in patients with Type 1 diabetes

Reversible cognitive deterioration after a single episode of severe hypoglycaemia: a case report

DIABETIC MEDICINE, Issue 12 2004
T. Kubiak
Abstract A case of a male 34-year-old Type 1 diabetic patient who experienced a prolonged severe hypoglycaemic episode is presented. After the hypoglycaemic event, the patient suffered from moderate to severe neuropsychological impairments. On the basis of neuropsychological assessment results, diabetes therapy was modified (less complex insulin regimen, fixed insulin doses and fixed carbohydrate distribution). At a follow-up examination (3 months), presumable complete recovery of cognitive function was observed. This case demonstrates the possible detrimental neuropsychological effects of severe hypoglycaemia, that, in this case, turned out to be reversible. It highlights the clinical implications of impaired cognitive function on self-care and self-management abilities and the usefulness of neuropsychological testing in clinical diabetes care. [source]

Recent advances in treatment of youth with Type 1 diabetes: better care through technology

DIABETIC MEDICINE, Issue 11 2001
W. V. Tamborlane
Abstract While treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid-acting insulin analogues provides a means to achieve better control of post-prandial hyperglycaemia with less late post-prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long-acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self-monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas. Diabet. Med. 18, 864,870 (2001) [source]