Basal Insulin Supplementation Research Articles

Metabolic and sympathovagal effects of bolus insulin glulisine versus basal insulin glargine therapy in people with type2 diabetes: A randomized controlled study.

Aims/IntroductionThis study compares the effects of two different insulin regimens – basal versus bolus insulin – on metabolic and cardiovascular autonomic function in Japanese participants with type 2 diabetes.Materials and MethodsParticipants were randomly assigned to groups for therapy with insulin glulisine (IGlu) or insulin glargine (IGla). The primary efficacy end‐point was glycemic variability, including M‐values, mean of glucose levels, and a blood glucose profile of seven time points before and after the intervention. The secondary end‐points included pleiotropic effects, including endothelial and cardiac autonomic nerve functions.ResultsBlood glucose levels at all time points significantly decreased in both groups. Post‐lunch, post‐dinner, and bedtime blood glucose levels were significantly lower in the IGlu group than in the IGla group. Nadir fasting blood glucose levels at the end‐point were significantly lower in the IGla group than in the IGlu group. The M‐value and mean blood glucose levels were significantly decreased from baseline in both groups, although the former was significantly lower in the IGlu group than in the IGla group. IGla, but not IGlu, was found to elevate 24‐h parasympathetic tone, especially during night‐time, and it decreased 24‐h sympathetic nerve activity, especially at dawn.ConclusionsBoth IGlu and IGla regimens reduced glucose variability, with IGlu bringing a greater reduction in M‐value. IGla, but not IGlu, increased parasympathetic tone during night‐time and decreased sympathetic nerve activity at dawn. These findings shed light on the previously unrecognized role of night‐time basal insulin supplementation on sympathovagal activity in type 2 diabetes patients.

Insulin Therapy in Type 2 Diabetes.

Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available. The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines. When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases. Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future. Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.

Effect of basal insulin supplement therapy on diabetic retinopathy in short‐duration type 2 diabetes: A one‐year randomized parallel‐group trial

BackgroundIn this study, we compared the effect on diabetic retinopathy (DR) between oral antidiabetic drugs (OADs) alone and in combination with basal insulin‐supported OADs therapy (BOT). [Correction added on 11 November 2019, after first online publication: In under Background section, “DR” has been corrected into “diabetic retinopathy (DR)”.]MethodsBetween January 2015 and January 2018, this study enrolled 290 patients (age 18‐65 years) with diabetes duration between 0 and 5 years. Patients were randomly assigned to receive OADs or BOT after 14 days intensive insulin treatment. Examinations were performed at the beginning and end of the study.ResultsFewer patients developed DR in the BOT than OADs group (8 [6.06%] vs 12 [8.3%], respectively), and all cases of DR were non‐proliferative. Blood glucose concentrations were higher in the BOT than OADs group at the 3rd month, but lower in the former at the 6th and 12th month. The rate of reaching target HbA1c ≤7% was lower in the BOT than OADs group at the 3rd month (63.6% vs 72.2%, respectively), similar between the two groups at the 6th month (60.6% vs 66.6%, respectively) and higher in the BOT group at the 12th month (75.0% vs 61.1%, respectively). The SD of fasting blood glucose (FBG), coefficient of variation of FBG, SD of blood glucose (SDBG), and mean amplitude of glycemic excursions were lower in the BOT than OADs group. Changes in the levels of three cytokines (interleukin [IL]‐1β, IL‐6, and IL‐17α) were significantly less in the BOT than OADs group.ConclusionsTwelve months of BOT decreased the incidence of DR in short‐duration type 2 diabetes by reducing glycemia more effectively, stably, and completely than OADs alone.

Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy

Postprandial insulin pulsatility is impaired in patients with type 2 diabetes, but the effects of exogenous insulin therapy on pulsatile insulin secretion are not known. We addressed, whether pulsatile insulin secretion is related to glycaemic control, whether basal insulin supplementation increases postprandial insulin secretion, and if so, is this accomplished by a specific improvement in pulsatile insulin secretion? Fourteen patients with type 2 diabetes underwent a mixed meal test before and after an 8-week treatment period with insulin glargine. Glucose, insulin and C-peptide levels were measured, and insulin pulsatility was determined by deconvolution analysis. Insulin treatment lowered fasting glycaemia from 179.6 ± 7.5 mg/dl to 117.6 ± 6.5 mg/dl (p < 0.001). Postprandial insulin and C-peptide levels increased significantly after the treatment period (p < 0.0001). The total calculated insulin secretion rate increased with insulin treatment (p = 0.0039), with non-significant increases in both pulsatile and non-pulsatile insulin secretion. Insulin pulse frequency was unchanged by the intervention. There was an inverse relationship between fasting and postprandial glycaemia and insulin pulse mass (r(2) = 0.51 and 0.56, respectively), whereas non-pulsatile insulin secretion was unrelated to either fasting or postprandial glucose concentrations (r(2) = 0.0073 and 0.031). Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous β-cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes.

Efficacy and safety of insulin lispro protamine suspension as basal supplementation in patients with type 2 diabetes

The three currently marketed long-acting insulin analogs, glargine, detemir and insulin lispro protamine suspension (ILPS), represent the most significant advances in basal insulin supplementation since the 1940s and 1950s and the introduction of the intermediate-acting NPH (neutral protamine Hagedorn) insulin. As injection of NPH insulin lacks chronic maintenance of a steady-state low-level basal insulin during fasting periods, which can also expose patients to unpredictable nocturnal hypoglycemia, long-acting insulin analogs have been developed to overcome this important limitation of NPH insulin. ILPS is a protamine-based, intermediate-acting insulin formulation of the short-acting analog insulin lispro: its pharmacokinetic and pharmacodynamic characteristics are quite similar to the other basal insulin analogs glargine and detemir. In recent head-to-head randomized controlled trials of insulin-naïve patients with type 2 diabetes, ILPS achieved similar glycemic control compared with glargine or detemir. ILPS administered once daily is an effective and safe way to maintain a steady-state low-level basal insulin during night time, not dissimilar from that currently obtained with a one-day glargine or detemir administration.

New insulins and insulin therapy

New insulins and insulin therapy

Pharmacokinetics and Pharmacodynamics of Basal Insulins

The two basal insulin analogs, insulin glargine and insulin detemir, were developed to ameliorate the well-known limitations of NPH insulin. In contrast to rapid-acting analogs, which differ exclusively in terms of primary structure while sharing similar pharmacokinetics (PK) and pharmacodynamics (PD), the two long-acting insulin analogs are different chemical and structural entities, exhibiting distinct modes of protracting the insulin effect. So far, PK and PD studies of long-acting analogs have often shown conflicting results, pointing out different conclusions, thereby leading to animated controversies. The methods used in the evaluation of basal insulins might have been partially responsible as, although the euglycemic clamp technique has been broadly acknowledged to be the "gold standard" reference to assess the glucose-lowering effect of an insulin preparation, its execution and interpretation might have been substantially different across studies, in various methodological and analytical aspects, ultimately providing an explanation for some of these controversies. This review will present and describe the basic methods used in the evaluation of basal insulins and will critically summarize the points that might have been responsible for the different outcomes. The findings of glucose clamp studies demonstrate that the two long-acting insulin analogs are different, to some extent, in both their PK and PD profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well.

How Basal Insulin Analogs Have Changed Diabetes Care

How Basal Insulin Analogs Have Changed Diabetes Care

The Future of Basal Insulin Supplementation

This review presents an overview of the candidates for an improved basal insulin in the pharmaceutical pipeline. The first new basal insulin to enter the market is most likely insulin degludec (IDeg), currently reporting in phase 3 of development, from Novo Nordisk (Bagsvaerd, Denmark). IDeg has a longer duration of action than currently available analogs. Phase 2 studies show comparable efficacy and safety outcomes compared with insulin glargine once daily with less hypoglycemia in type 1 diabetes. The final results of phase 3 studies seem to confirm this, also in type 2 diabetes. Biodel (Danbury, CT) has two long-acting basal insulin formulations in the pipeline, both in the preclinical phase of development: BIOD-Adjustable Basal, a modified formulation of insulin glargine, is available in long-, medium-, and short-acting forms and could be mixed, and BIOD-Smart Basal releases insulin proportional to the subcutaneous glucose concentration. Eli Lilly (Indianapolis, IN) is also developing a basal insulin. Phase 2 trials have been completed, but no results are published yet. Clinical trials with the new patch pump from CeQur (Montreux, Switzerland) have recently started in Europe. This patch pump delivers both basal and bolus doses subcutaneously and is intended for people with type 2 diabetes who need multiple daily injection insulin therapy.

Fluctuation and reproducibility of exposure and effect of insulin glargine in healthy subjects*

Low diurnal fluctuation and high day-to-day reproducibility in exposure and effect characterize beneficial basal insulin products. Two insulin glargine (LANTUS) formulations [without (R) or with polysorbate-20 (T)], added to minimize unfolding of proteins and subsequent formation of fibril structures, were assessed for equivalence in exposure and effect, and aspects of fluctuation and reproducibility in time-concentration and time-action profiles. A dose of 0.4 U/kg was subcutaneously administered to 24 healthy subjects in a two-sequence (R-T-R-T or T-R-T-R), randomized, four-way crossover trial utilizing 30-h Biostator-based euglycaemic glucose clamps. Identical serum insulin glargine concentration and time-action profiles established average, individual and population equivalence in insulin exposure and effect. Point estimates for 24-h area under the curve for insulin (INS-AUC(0-24) (h)) and glucose infusion rates (GIR-AUC(0-24) (h)) were 97% [90% confidence interval (CI): 91-103%] and 100% (88-114%), respectively. Within-subject variability (coefficient of variation) for INS-AUC(0-24) (h) and GIR-AUC(0-24) (h) were 19% (95% CI: 14-25%) and 34% (24-43%), respectively. The diurnal relative fluctuation of the serum insulin glargine concentration was 20% (95% CI: 19-21%). Insulin glargine in either formulation presents with a high day-to-day reproducibility of a uniform release after injection enabling an effective basal insulin supplementation.

Beyond the Era of NPH Insulin—Long-Acting Insulin Analogs: Chemistry, Comparative Pharmacology, and Clinical Application

The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a duration >or=24 h, (2) a single subcutaneous dose of glargine/detemir was used, and (3) area under the curve for insulin concentrations or glucose infusion rates were calculated.

Risk of exercise-induced hypoglycaemia in patients with type 2 diabetes on intensive insulin therapy: Comparison of insulin glargine with NPH insulin as basal insulin supplement

Aim Hypoglycaemia is the most common adverse event associated with intensive conventional insulin therapy (ICT). This study compared the risk of exercise-related hypoglycaemia in type 2 diabetes patients receiving either basal insulin glargine or NPH insulin. Methods In a prospective trial, 122 ICT patients (glargine n = 60, NPH n = 62) had a standardized treadmill test, monitored by capillary lactate concentration. Blood glucose (BG) profiles were performed the day before, during and the day after the exercise test, with the patients on a strict carbohydrate-defined diet. All patients had been on a stable ICT scheme for at least three months and had an HbA1c below 7.5%. Results BG at the beginning of the exercise test, BG decline and lowest BG during the test were comparable between the two groups. The episodes of mild hypoglycaemia (BG < 3.3 mmol/l) and amounts of additional carbohydrate intake due to mild symptoms of hypoglycaemia (BG 3.3–5.0 mmol/l) were not significantly different. No episodes of hypoglycaemia occurred during several hours after the exercise. Conclusions Moderate physical activity can be recommended for well-controlled type 2 diabetes patients receiving ICT, independently of glargine or NPH as basal insulin and without risk of exercise-induced hypoglycaemia.

Efficacy of Insulin Glargine on Basal Insulin Supplementation in Japanese Type 1 Diabetes Patients Treated with Basal-bolus Injection Therapy

Efficacy of Insulin Glargine on Basal Insulin Supplementation in Japanese Type 1 Diabetes Patients Treated with Basal-bolus Injection Therapy

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.

Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Optimal insulin treatment for patients with type 2 diabetes: Basal or prandial insulin supplementation?

During the natural course of type 2 diabetes (T2D), insulin therapy is needed in order to maintain appropriate glycaemic control in a substantial part of patients. Although the definition theoretically is arbitrary, prandial and basal insulin could be used for insulin supplementation in clinical practice. To improve both prandial and basal insulin supplementation, short- and long-acting insulin analogues were recently developed. Clinical studies indicated that better prandial glucose control could be achieved by using short-acting insulin analogues, such as insulin lispro insulin, insulin aspart and glulisine than that observed by treatment with regular human insulin. Using new long-acting insulin analogues such as glargine or detemir, the risk of hypoglycaemia, especially nocturnal, could be decreased as compared with NPH insulin treatment. It is obvious that adequate prandial and basal insulin supplementation and nearly physiological insulin replacement could be carried out by using basal–bolus insulin therapy. Nevertheless, patients with T2D and stable lifestyle, or those who are unwilling to perform multiple daily insulin injections and blood glucose readings could sufficiently be treated by using premix human insulin preparations or more recently, by premix insulin analogues. Given the importance of clinical benefits of short-acting, long-acting and premix insulin analogues, the long-term effects of treatment with these relatively new insulin preparations are yet to be determined. Instead of the question whether basal or prandial insulin supplementation is more critical, the mode of treatment providing appropriate basal and prandial insulin supplementation is of importance. Using optimal insulin supplementation, all components of glucose triad (fasting glucose, postprandial glucose, HbA 1c) should be targeted by proper management of patients with T2D.

Achieving goal glycosylated hemoglobin levels in type 2 diabetes mellitus: Practical strategies for success with insulin therapy

Background:As the prevalence of diabetes mellitus (DM) continues to increase at an alarming rate, achieving glycosylated hemoglobin (AIC) target levels is crucial to prevent microvascular and macrovascular complications and to reduce the impact this disease has on individuals and society as a whole. Objective:This article discusses various approaches to intensive therapy, focusing on insulin regimens designed to mimic physiologic basal-bolus insulin secretion in type 2 DM, with the goal of helping patients with type 2 DM achieve normal glycemic control. Methods:Relevant articles were identified through a search of the English-language literature indexed on MEDLINE (1966-present) using the terms type 2 diabetes mellitus, glycemic control, glycosylated hemoglobin, postprandial hyperglycemia, insulin analogues, and continuous subcutaneous insulin pump therapy. Results:Patients with type 2 DM are often initially managed with diet modification, exercise, and oral antidiabetic agents; however, as β-cell function continues to decline, many of these individuals will require exogenous insulin supplementation. Because of the time-action profiles and large variability of the conventional insulins, including regular human and neutral protamine Hagedorn, their use makes it difficult to provide intensive treatment without significant risk of hypoglycemia, especially nocturnal hypoglycemia. The advent of recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues with improved pharmacokinetic parameters. These new insulins that can more accurately simulate endogenous insulin secretion—along with advances in insulin pump technology, improved delivery devices, and frequent glucose monitoring—make intensive treatment regimens feasible for more patients than ever before. The mealtime insulin requirement can best be met through administration of a rapid-acting insulin analogue (such as insulin lispro, aspart, or glulisine) either by SC injection or as a bolus from an insulin pump. Basal insulin supplementation can best be achieved using injections of insulin glargine or detemir or through the use of a rapid-acting insulin analogue in an infusion pump. Conclusions:For patients with type 2 DM, every effort must be made to continue achieving target A1C goals, with frequent blood glucose monitoring in conjunction with oral therapy plus basal and bolus multiple daily injection regimens, BID mixed insulins, or the use of an insulin pump.

Biochemical and Physiological Properties of a Novel Series of Long-Acting Insulin Analogs Obtained by Acylation with Cholic Acid Derivatives

This study was conducted to assess the suitability of insulin analogs acylated by various cholic acid derivatives for use as basal insulin, and to test the most promising of these, LysB29(Nepsilon-lithocholyl-gamma-Glu) des(B30) human insulin (NN344) in pigs. Circular dichroism spectroscopy and size-exclusion chromatography were used to explore the physicochemical properties of the analogs, and affinities for albumin and insulin receptors were determined. After subcutaneous injection in pigs, disappearance half-times were measured, and the plasma profile and glucose-lowering effect in a euglycemic clamp were assessed for NN344. NN344 showed glucose-lowering activity lasting more than 24 h. Glucose infusion rate was essentially constant from 5 to 19 h after injection. NN344 seemed to be a dodecamer in the presence of zinc ions and phenol. Without phenol, the apparent molecular mass was >5000 kDa. Formation of such a self-assembly at the site of s.c. injection and its subsequent slow decomposition might explain the long duration of action of NN344. A measurable affinity for albumin of the lithocholic acid ligand may also contribute to the prolonged action. NN344 is a candidate for a neutral soluble basal insulin that might offer people with diabetes a prolonged duration, smooth, and predictable basal insulin supplement.

Implantation of primary cultured adipocytes that secrete insulin modifies blood glucose levels in diabetic mice

In type 1 diabetic patients, basal insulin supplementation plays a central role in tight glycaemic control. Therefore, safe and steady supplementation of basal insulin is strongly desirable, despite the need for multiple injections. The aim of this study was to investigate a procedure for supplementation using genetically engineered, primary-cultured adipocytes in diabetic mice. Furin-cleavable human proinsulin cDNA was transferred into murine primary-cultured adipocytes using a retroviral vector. The cells were implanted subcutaneously into streptozotocin-induced diabetic mice. The transfected cells secreted substantial amounts of mature insulin, as well as C-peptide, into conditioned medium. Syngeneic implantation of the cells significantly improved hyperglycaemia and blood HbA(1)c concentrations in a manner that was dependent on cell number, without causing hypoglycaemia. The plasma insulin concentration was dependent on the implanted cell number, and the systemic effect of the circulating insulin was confirmed by marked improvement of body weight reduction and liver glycogen content. Additionally, surgical resection of the implants, in which the insulin secretion was immunologically confirmed after transplantation, diminished the glucose-lowering effect, suggesting that in vivo expression could be eliminated if necessary. These results indicate that the autotransplantation of functionalised adipocytes may lead to a clinical application in the treatment of diabetes.

An observational study comparing continuous subcutaneous insulin infusion (CSII) and insulin glargine in children with type 1 diabetes

The advantages of continuous subcutaneous insulin infusion (CSII) or insulin glargine have been demonstrated both in adult and paediatric diabetic patients; however, as no data comparing these two approaches during childhood are available, we have examined the efficacy of these two intensive approaches. We retrospectively evaluated data from 36 diabetic children, who had changed their previous insulin regimen [with isophane insulin (NPH) at bedtime] because of HbA1c levels >8.0%. Twenty patients underwent CSII, while the other 16 (significantly younger for age) started insulin glargine at bedtime. At 6 and 12 months, CSII-treated patients showed a significant reduction in HbA1c values from 8.5 +/- 1.8 to 7.4 +/- 1.1% and to 7.6 +/- 1.2%, respectively. The insulin requirement significantly decreased from 0.93 +/- 0.2 IU/kg to 0.73 +/- 0.2 IU/kg of body weight and to 0.74 +/- 0.15 IU/kg of body weight, respectively, while no significant differences were observed for BMI SDS, fructosamine and severe hypoglycaemic events. The patients treated with glargine showed a small decline in HbA1c values from 8.9 +/- 1.7 to 8.3 +/- 0.9% (not significant) in the first 6 months of treatment and to 8.2 +/- 0.9% after 12 months. The basal insulin supplementation can be supplied effectively in children with type 1 diabetes by either CSII or insulin glargine. As previously reported for adults, it is confirmed that CSII is the best current intensive approach aimed to the improvement of glycaemic control.