A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion

Aim: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety.
Methods: In this open, randomized, controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized to CIPII or CSII. The aim was to obtain the best possible blood glucose while avoiding hypoglycemia.
Results: The frequency of any hypoglycemia was similar (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910). The incidence of severe hypoglycemia with CSII was more than twice the one with CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean blood glucose, and glucose fluctuations were not statistically different. Treatment-related severe complications occurred mainly during CIPII: port infections (0.47 events / patient year), abdominal pain (0.21 events / patient year), insulin underdelivery (0.14 events / patient year). Weight gain was greater with CSII (+ 1.5 kg vs. − 0.1 kg, p = 0.013), quality of life better with CIPII.
Conclusions: In type 1 diabetes CIPII with DiaPort reduces the number of severe episodes of hypoglycemia and improves quality of life with no weight gain. Because of complications, indications for CIPII must be strictly controlled. CIPII with DiaPort is an alternative therapy when CSII is not fully successful and provides an easy method of intraperitoneal therapy.     

Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes

In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential.     

Variation of insulin absorption during subcutaneous and peritoneal infusion in insulin-dependent diabetic patients with unsatisfactory long-term glycaemic response to continuous subcutaneous insulin infusion.

The aim of present study was to analyse the reproducibility of plasma-free insulin profiles of subcutaneously (CSII) and intraperitoneally (CIPII) administered insulin in 6 C-peptide-negative, type 1, diabetic patients. The patients were selected for CIPII because of unsatisfactory, long-term, metabolic response to CSII. Plasma-free insulin was measured repeatedly, twice during subcutaneous infusion and twice during intraperitoneal infusion, for 4 hours, following a standard breakfast. In the CSII experiment, insulin was given as a meal-dose of 0.1 U per kg body weight, and in the CIPII experiment the meal-dose was 0.05 U per kg body weight. The dose-induced peak occurred earlier after the CIPII than with the CSII (60.0 +/- 8.0 vs 133.6 +/- 16.3 min). In conclusion, the intra-patient coefficient of variation (C.V.) of plasma-free-insulin profiles at 0-60 min and 0.240 min, as well as the peak time, were markedly lower for CIPII insulin than for CSII, indicating a more reproducible way of insulin administration with CIPII in this selected group of patients.     

Continuous intraperitoneal insulin infusion partly restores the glucagon response to hypoglycaemia in type 1 diabetic patients

The glycaemic and hormonal responses to a hypoglycaemic event induced by an i.v. bolus of insulin was studied in seven type 1 diabetic patients treated first with continuous subcutaneous insulin infusion (CSII) and subsequently with continuous intraperitoneal insulin infusion (CIPII). Arterialised blood glucose and venous hormonal responses were analyzed. HbA1c was improved by CIPII. Although a regimen of a higher basal insulin infusion rate was applied during CIPII the basal peripheral venous insulin levels were lower. The i.v. bolus of insulin resulted in hypoglycaemia in both tests but was more pronounced during the CSII test expressed as a smaller area under the curve (AUC) for the first hour (13.0 +/- 2.3 vs. 13.7 +/- 1.2 mmol l(-1) h(-1), p=0.016, CSII vs. CIPII). The hypoglycaemia resulted in a significant and similar increase in the plasma levels of adrenaline, cortisol and growth hormone in both experiments. A significant increase in the glucagon level was only observed during CIPII. The incremental glucagon response was also significantly more pronounced in the CIPII test expressed as maximal responses (7.5 +/- 3.0 vs. 17.0 +/- 3.1 pg ml(-1), p =0.048, CSII vs. CIPII) as well as incremental AUC (5.1 +/- 12.0 vs. 44.4 +/- 13.2 pg ml(-1) h(-1), p =0.027, CSII vs. CIPII). It seems that CIPII in type 1 diabetic patients could improve the glucagon release to hypoglycaemia. This observation may contribute in explaining why CIPII is associated with a lower incidence of hypoglycaemia in spite of an improvement in metabolic control.     

Report of a 7 year case–control study of continuous intraperitoneal insulin infusion and subcutaneous insulin therapy among patients with poorly controlled type 1 diabetes mellitus: Favourable effects on hypoglycaemic episodes

AimsContinuous intraperitoneal insulin infusion (CIPII) is a last-resort treatment option for patients with type 1 diabetes mellitus (T1DM) who fail to reach adequate glycaemic control with subcutaneous (SC) insulin therapy. Aim was to compare the long-term effects of CIPII and SC insulin therapy among patients with T1DM in poor glycaemic control.MethodsPatients in which CIPII was initiated in 2006 were compared with a control group of T1DM patients who continued SC therapy. Linear mixed models were used to calculate differences between the baseline (2006) and final (2013) measurements within and between groups.ResultsA total of 95 patients of which 21 were using CIPII and 74 using SC insulin were included. Within the CIPII group, the number of hypoglycaemic episodes decreased with −5 (95% CI −8 to −3) per 2 weeks while it remained stable among SC patients. Over time, only the number of hypoglycaemic episodes decreased more with CIPII as compared to SC insulin treatment (difference: −6 (95% CI −9 to −4)). There were no differences between treatment groups regarding clinical parameters and quality of life scores over time. Pump or catheter dysfunction led to ketoacidosis in 6 patients: 2 using CIPII and 4 SC insulin.ConclusionsAfter 7 years of follow-up, there is a persistent decline of hypoglycaemic events among CIPII treated T1DM patients. Besides less hypoglycaemic episodes with CIPII therapy, there are no differences between long-term CIPII and SC insulin therapy.     

Pharmacokinetics of continuous subcutaneous insulin infusion

Summary One of the reasons for the variability of blood glucose regulation in Type 1 (insulin-dependent) diabetic patients is the huge variation in subcutaneous absorption of intermediate-acting insulin. We have investigated the variation in insulin absorption during continuous subcutaneous insulin infusion in eight such patients. The content of insulin in the subcutaneous tissue was measured using ¹²⁵I-labelled insulin. The concentration of free serum insulin and blood glucose was followed from 1 h before and from 7 h after breakfast on two consecutive days. The amount of insulin absorbed during 24 h differed in all cases by less than 3% from the daily insulin dose given by the pumps. Mean insulin absorption rates and mean free insulin concentration showed peak values 30–90 min after meal bolus injections; this was sufficient to maintain near-normal blood glucose. Mean free serum insulin correlated strongly with disappearance of insulin from the subcutaneous tissue (r=0.98). From the insulin absorption rates and free insulin concentrations during basal constant insulin infusion, the half-time of serum insulin was calculated as 6 min. Compared with the known large variability in the absorption of intermediate-acting insulin, continuous subcutaneous insulin infusion offers a precise and reproducible way of insulin administration resulting in post-prandial serum insulin peaks sufficient to maintain near-normal blood glucose levels. The half-time of serum insulin during subcutaneous infusion corresponds to values for intravenous infusion given in the literature, indicating that local degradation of insulin in subcutaneous tissue is of minor importance.     

Safety of continuous subcutaneous insulin infusion: Metabolic deterioration and glycaemic autoregulation after deliberate cessation of infusion

Summary To assess the rate of metabolic deterioration and potential risks of failure of continuous subcutaneous insulin infusion during basal insulin delivery, we deliberately stopped infusion in nine insulin dependent diabetics. Plasma glucose, blood 3-hydroxybutyrate and plasma free insulin were measured for 9 h whilst the patients remained supine and fasting. Mean plasma glucose remained unchanged at normal fasting levels for the first hour, then rose to plateau at about 10 mmol/l until the end of the experiment. The final plateau level of glucose varied from patient to patient; two C-peptide secreting diabetics plateaued at low glucose levels. In contrast, blood 3-hydroxybutyrate rose progressively, without plateauing. Plasma free insulin concentrations fell during the withdrawal period and there was a highly significant negative correlation between free insulin and 3-hydroxybutyrate. No patient was more than mildly unwell after 9 h of insulin deprivation. We conclude that under these experimental conditions there is glycaemic autoregulation and that ketones may sometimes be a more appropriate monitor of insulin deficiency or loss of diabetic control than is glucose. Accidental failure of continuous subcutaneous insulin infusion and interruption of basal delivery in resting and fasting diabetics will probably not cause dangerous metabolic or clinical deterioration.     

Metabolic and hormonal responses to exercise in type 1 diabetic patients during continuous subcutaneous, as compared to continuous intraperitoneal, insulin infusion

This study was performed to determine whether metabolic and hormonal responses during moderate exercise differ between continuous intraperitoneal insulin infusion (CIPII) and continuous subcutaneous insulin infusion (CSII). In seven Type 1 diabetic patients, treatment was changed from CSII to CIPII. Prior to the change, these patients performed an ergometer exercise at 60% of VO2max for 40 min followed by a 200-min rest. About one year later, when the procedure was repeated during CIPII, HbA1c had improved from 8.5 to 7.1%. Arterial blood glucose, venous lactate and hormonal responses were analysed. Although a regimen with a higher basal insulin infusion rate was applied during the exercise test on CIPII, corresponding venous insulin levels were lower (28.0 +/- 2.2 vs. 48.1 +/- 7.9 pmol L-1, p = 0.04). Exercise caused a more marked decline in blood glucose during CIPII, with nadir blood glucose at the end of exercise (3.6 +/- 0.4 vs. 5.1 +/- 0.4 mmol L-1, p = 0.005). Both exercise tests yielded significant and similar increases in plasma levels of adrenaline, noradrenaline, cortisol and growth hormone. A significant rise in plasma glucagon (15.1 +/- 4.5 pg mL-1, p = 0.01) was observed during CIPII, but not during CSII (7.4 +/- 3.5, pg mL-1, n.s.). It is concluded that patients on CIPII should reduce their insulin infusion rate during exercise. CIPII appears to have favourable effects on counterregulatory capacity; in particular, a more prominent glucagon response to exercise may prove important.     

Intraperitoneal insulin infusion: treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia

Continuous intraperitoneal insulin infusion (CIPII) is a treatment option for patients with type 1 diabetes mellitus who fail to reach adequate glycaemic control despite intensive subcutaneous (SC) insulin therapy. CIPII has clear advantages over SC insulin administration in terms of pharmacokinetic and pharmacodynamic properties and has been shown to improve glycaemic regulation. Due to the delivery of insulin predominantly in the portal vein, as opposed to systemically, CIPII offers a unique research model to investigate the effects of insulin on endocrine and metabolic parameters in vivo. The aim of the present article is to provide an overview of the literature with respect to the effects of CIPII on glucose management, quality of life, complications and costs, with additional focus on metabolic and endocrine aspects. Finally, future use and research objectives are discussed.     

Chronic continuous intraperitoneal insulin infusion (CIPII) in type I diabetic patients non-satisfactorily responsive to continuous subcutaneous insulin infusion (CSII)

Summary Six unstable C-peptide negative type I diabetic patients who had been previously treated with continuous subcutaneous insulin infusion (CSII) for at least one year without achieving satisfactory metabolic control, were admitted to this study and switched to continuous intraperitoneal insulin infusion (CIPII). The results obtained with the two treatments have been compared from the metabolic and clinical points of view. CIPII produced a decrease in HbA_1c (p<0.05), in MAGE value (p<0.005), in the percentage of blood glucose determinations above 14 mmol/l (p<0.05) and below 3.9 mmol/l (p<0.05); an increase in serum cholesterol, and a decrease in HDL-cholesterol (p<0.05) due to a reduction of the HDL₂ fraction (p<0.01). A mean body weight reduction of 3 kg was observed during CIPII (p<0.01), not related to dietary changes or to a reduction of the daily insulin dose. Twenty-four hour metabolic profiles during CIPII showed lower mean plasma glucose (p<0.001), serum free insulin (p<0.001), blood β-OH-butyrate (p<0.001), and higher serum glycerol (p<0.001) as compared to CSII. It is concluded that CIPII may be of clinical value in the out-patient management of unstable type I diabetic patients, and that metabolic modifications induced by CIPII are not limited to changes in glucose utilization and production, but include changes in triglyceride, cholesterol and lipid metabolism which may have clinical relevance. Supported by the National Research Council (CNR), Target Project ‘Preventive Medicine and Rehabilitation’, Subproject ‘4’ and by the Juvenile Diabetes Foundation, U.S.A., file No. 184066.     

Continuous subcutaneous insulin infusion in diabetes: patient populations,safety, efficacy,and pharmacoeconomics

The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health‐related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed‐loop ‘artificial pancreas’ systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.     

Explorative study of pharmacokinetics and pharmacodynamics after change in basal insulin infusion rate

Background

The use of insulin pumps is rapidly increasing and new, technologically more advanced pumps are continuously being developed. It is of interest to assess the clinical relevance of the many technical features of these pumps, e.g., the effect on pharmacokinetics and pharmacodynamics with change in infusion rate.

Method

The aim of this study was to explore the sequence of pharmacokinetic and pharmacodynamic changes after dose doubling of the basal insulin infusion rate with subcutaneous bolus insulin injections once an hour, continuous subcutaneous insulin infusion, and continuous intravenous insulin infusion. Ten type 1 diabetes mellitus patients were included. The insulin doses were calculated based on the habitual insulin doses. The study was designed as an open-labeled, single-center, randomized, crossover exploratory trial.

Results

Dose doubling of the basal insulin infusion rate with the three different administration protocols did not result in any clinically relevant differences in the time courses of the pharmacokinetic and pharmacodynamic parameters. With all three administration protocols, we observed a time interval of more than 6 hours before a new steady state of insulin was achieved.

Conclusions

Our results indicate that frequent changes in basal subcutaneous insulin infusion rates are not of significant clinical relevance on a 24-hour basis. Regarding technological features of subcutaneous insulin pumps, no discernable advantages of increasing pump stroke frequency were found. This indicates that pump stroke frequency sophistication might not be of clinical relevance in pumps used for basal subcutaneous insulin infusion.     

Insulin responses to varying profiles of subcutaneous insulin infusion: kinetic modelling studies

Summary Refinement of continuous subcutaneous insulin infusion for diabetes therapy requires improved knowledge of subcutaneous insulin absorption kinetics. We have used kinetic modelling to quantitate systemic insulin delivery produced by subcutaneously-infused insulin (i.e. simulated meal and basal delivery). Profiles were studied in normal subjects, with endogenous insulin suppressed. Paired studies of intravenous insulin infusion enabled systemic insulin delivery to be quantitated. High rate subcutaneous delivery (10 U in 5 min) resulted in a systemic delivery of approximately 8 U in 4h. Increasing infused insulin concentration delayed systemic delivery (p<0.025). Both continuous and pulsatile low-rate infusions (2.4 U/h) gave similar slow increases in systemic delivery to 1 U after 4 h. Computer fitting to a two-pool model of the subcutaneous space suggested a low rate of insulin degradation for all profiles (rate constant <10%/h). We conclude that: (1) systemic insulin delivery following subcutaneous infusion conforms reasonably to a two-pool model, (2) subcutaneous insulin degradation is low regardless of input profile, (3) a long delay in basal systemic delivery should be taken into account when initiating or resuming interrupted subcutaneous insulin infusion. Kinetic modelling of subcutaneous insulin absorption should be useful to predict the impact of programming strategies for continuous subcutaneous insulin infusion therapy.     

Nine years' personal experience of intensified diabetes control: infusion versus injections

The author, who had been an unstable diabetic since 1948, has attempted to maintain normoglycaemia since January 1977 after developing retinopathy and painful peripheral neuropathy. After 40 months of intensified conventional therapy (ICT), blood glucose fell from 13.0 +/- 2.0 (mean +/- S.D.) to 8.6 +/- 1.5 mmol/l (p less than 0.001), but with 36% of blood glucose tests still exceeding 10.0 mmol/l. After 6 years of continuous subcutaneous insulin infusion (CSII) mean blood glucose was 6.6 +/- 0.7 mmol/l (p less than 0.001) CSII/ICT, with only 10% of tests exceeding 10 mmol/l, smoother glycaemic profiles and excellent control overnight with no hypoglycaemia. These improvements under CSII were attributed to continuous varied insulin intake, which was instantly and unobtrusively adjustable, and more reliable food/insulin/blood glucose relationships. No infusion-site abscesses or serious ketoacidosis developed. Under both therapies glycaemic control was readily disrupted by exercise, minor dietary inaccuracies, relaxing of vigilance and unknown factors. Whenever the sense of commitment faultered there was a tendency to maintain higher glycaemic values to avoid distressing hypoglycaemia. Over the nine years, retinopathy progressed, foot pains regressed slightly but no fresh complications developed. Thus, intensified conventional management alone improved control, but CSII enabled the author to remain near-normoglycaemic for years (given sufficient motivation), with a less regimented lifestyle.     

Continuous basal insulin infusion without premeal boluses in insulin-dependent diabetes mellitus therapy

Summary Six insulin-dependent diabetic patients, poorly controlled on conventional insulin therapy (CIT), underwent continuous basal insulin infusion (CBII) and continuous subcutaneous insulin infusion (CSII) during 2 subsequent periods of 1 month each, employing a Betatron II insulin infusion pump (Lilly, CPI). During CSII, insulin was infused at a continuous basal rate with 3 premeal boluses. During CBII, from 22⁰⁰ to 06⁰⁰ a continuous basal nocturnal insulin infusion rate and from 06⁰⁰ to 22⁰⁰ a diurnal one, which was approximately twice the former, were maintained and total daily calorie intake was subdivided into 6 isoglycidic and isocaloric meals, taken at regular intervals. We obtained better blood glucose control both by CSII and CBII than by CIT, with significant reduction of HbA₁ values. Mean blood glucose levels were lower during CBII than during CSII, while M-index, number of hypo- and hyperglycemic events and insulin requirement were not different. However, daily blood glucose excursions were narrower and percent blood glucose increment after the noon meal was reduced during CBII. CBII insulin profile was characterized by a plateau trend with lower levels at meals in comparison with CSII. Our data show that the subdivision of daily calorie intake into 6 isocaloric and isoglycidic meals allows to achieve good metabolic control by continuous basal insulin infusion without need for premeal boluses and could be especially useful in brittle diabetic patients, whose brittle condition may be caused by erratic absorption of subcutaneous boluses of insulin.     

Exercise-induced hypoglycaemia and subcutaneous insulin infusion

To assess whether exercise-induced hypoglycaemia could be prevented by interruption of insulin infusion (3 h) we studied diabetic patients treated with continuous subcutaneous insulin infusion (CSII). The studies were performed in 7 insulin-dependent diabetics (aged 31.4 +/- 4.8 (mean +/- SD) years, duration of diabetes 16.9 +/- 5.4 years), after an overnight fast and in the afternoon, 4 h after the last pre-meal bolus injection (exercise and control period). Bicycle exercise (45 min at 60% of maximum oxygen consumption) was started 30 min after the insulin infusion was stopped. During exercise there was a more pronounced decline in blood glucose in the afternoon (2.2 +/- 0.3 mmol/l, mean +/- SEM) than in the morning (1.4 +/- 0.4 mmol/l) (p less than 0.01). This corresponded to higher mean levels of free insulin during exercise in the afternoon (20 +/- 4.5 mU/I vs 12.0 +/- 1.0 mU/l, in the morning). Interruption of insulin delivery for 3 h resulted in a moderate increase of blood glucose, a gradual decrease of free insulin, and a moderate increase in free fatty acids and beta-hydroxybutyrate. During exercise in the afternoon 3 diabetics suffered from symptomatic hypoglycaemia (BG less than 2.8 mmol/l). In contrast with most of the other patients they showed no decline of free insulin during exercise. Thus even after interruption of basal rate insulin infusion moderate postprandial exercise may lead to hypoglycaemia if there is relative hyperinsulinism.     

Low subcutaneous degradation and slow absorption of insulin in insulin-dependent diabetic patients during continuous subcutaneous insulin infusion at basal rate

Summary As information on the absorption kinetics and local degradation of infused insulin is relevant to programming strategies for continuous subcutaneous insulin infusion, we examined the time relationship of systemic insulin appearance and quantitated subcutaneous degradation during a near-basal rate of continuous subcutaneous insulin infusion in five insulin-dependent diabetic patients. Plasma free insulin was monitored for 8 h during and 3 h after a subcutaneous (abdominal wall) infusion of neutral insulin at 2.4 U/h. An identical intravenous infusion (2–4 h) was given on a separate occasion. Plateau levels of free insulin were not significantly different during the subcutaneous (37±8 mU/l) and intravenous (40±7 mU/l) infusions. Fitting of the free insulin data to our two-pool model of the subcutaneous space gave a mean estimate of 9.2 units insulin (= 3.8 h infusion) for the subcutaneous depot after 8 h. Model estimates of systemic insulin appearance, as a percentage of subcutaneous infusion rate, were 59% and 93% after 4 and 8 h respectively, and 76% 2 h after cessation of infusion. In insulin-dependent diabetic patients subcutaneous degradation of infused insulin is negligible but local accumulation in the subcutaneous space is considerable. The delay in absorption has important clinical implications for interruption and resumption of continuous subcutaneous insulin infusion and also for programming of variable basal rates.     

Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes1

Aims To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid-acting insulin analogue and once daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. Methods Twenty-one patients with Type 2 diabetes treated with oral glucose-lowering agents were randomized in this two-period crossover study to an equivalent 24-h dose of continuous subcutaneous infusion of insulin aspart and subsequently once-daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded. Results On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre-injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra-subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra-subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic-only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period. Conclusions Basal continuous subcutaneous infusion of a rapid-acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once-daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes.     

Insulin Kinetics in Type I Diabetic Patients Treated by Continuous Intraperitoneal Insulin Infusion: Influence of Anti-insulin Antibodies

Continuous intraperitoneal insulin infusion (CIPII) is a promising therapy of patients with Type 1 (insulin-dependent) diabetes mellitus (IDDM), since it improves metabolic control and decreases frequency of severe hypoglycaemia. This could be due to more appropriate insulin kinetics. Our aim, therefore, was to compare plasma free insulin levels achieved in patients with Type 1 diabetes chronically treated with CSII or CIPII. Furthermore, as anti-insulin antibodies increase with this treatment, we wanted to assess their influence upon insulin kinetics. Plasma free insulin profiles were obtained during the night and then after the bolus for breakfast and the bolus for lunch in 11 patients with Type 1 diabetes treated successively by CSII and CIPII. In another group of 16 patients with long-term Type 1 diabetes, treated by CIPII, we examined the influence of anti-insulin antibody level on insulin kinetics after a bolus. During the night, plasma free insulin levels were lower with CIPII than with CSII (12:00 am: 10.1 ± 1.7 vs 18.5 ± 2.6 mU l⁻¹; 4:00 am: 9.1 ± 2 vs 15 ± 3 mU l⁻¹), p < 0.01. After the bolus, CIPII lead to an earlier (1h vs 3h) and higher (25.8 ± 3.3 vs 18 ± 2.7, p < 0.05) plasma free insulin peak than CSII. With CIPII, the return to baseline level was observed within 3 h. Conversely, during CSII, insulin levels did not return to baseline until the next meal. After the bolus, high insulin-antibody levels were associated with a reduced maximal value of plasma free insulin peak. Taken together, these findings suggest that CIPII provides plasma free insulin profiles which are much closer to physiology than CSII. This could explain the lower rate of severe hypoglycaemia observed with this type of treatment. But in long-term CIPII treated patients with high anti-insulin antibody level, insulin profile could be moderately modified. This emphasizes the need for a less immunogenic insulin preparation.     

短期胰岛素泵治疗初诊2型糖尿病患者的随访研究

目的 观察短期应用胰岛素泵治疗初诊2型糖尿病的中远期疗效及不良反应.方法 观察、随访、回顾性分析256例初诊2型糖尿病患者经胰岛素泵(CSII)强化治疗2周后控制血糖情况、不服用药物血糖达标(空腹血糖:3.9～7.0 mmol/L,餐后2h血糖:3.9～10.0 mmol/L)持续时间(缓解期)等.结果 CSII治疗3 d血糖达标率46.7%,7 d达标率78.4%,2周达标率92.2%;拆除胰岛素泵缓解期超过3个月的患者共192例(75%),超过6个月166例(64.8%),超过12个月137例(53.5%),超过24个月79例(30.9%),超过36个月26例(10.2%),无1例超过48个月.缓解期少于3个月的患者,其停用胰岛素时的剂量明显高于缓解期超过3个月的患者(P＜0.01),停用胰岛素时的剂量与缓解期的长度呈负相关(r=-0.63,P＜0.01).结论 CSII可迅速有效使初诊2型糖尿病患者血糖达标,消除高血糖的毒性作用,使受糖毒性损伤的残存胰岛β细胞功能得到一定程度恢复,可延缓胰岛β细胞功能的衰退.