Short-acting Insulin Analogues Research Articles

Metabolische Störungen bei Leberzirrhose (Teil 2): Hepatogener Diabetes mellitus

Uip to 20% of patients with liver cirrhosis develop hepatogenous diabetesdue to the hepatocellular functional loss and insulin resistance. Optimizing diabetic metabolic conditions is not only important to avoid typical late complications of diabetes, but also cirrhosis-associated complications e.g. gastrointestinal bleeding, hepatic encephalopathy or the occurence of hepatocellular carcinoma. So far there have beenno recommendations orguidelines for the diagnosis and treatmentof hepatogenous diabetes. The medical teatment of a diabetic condition is mainly influenced by its side effects. The risk of hypoglycemia must be considered carefully during drug treatment, especially in patients with chronic alcohol abuse. Suitable oral antidiabetics are glinides and short-acting sulfonylureas or possibly meal-related insulin administration with short-acting insulins or rapid-acting insulin analogues. Biguanide and PPAR-gamma agonists are contraindicated because of side effects in liver cirrhosis. Regarding basic treatment, an adequate daily energy and protein supply should be ensuredbecause the majority of patients with liver cirrhosis are malnourished.

Insulin pump therapy of type 1 diabetes mellitus in children and adolescents in the Moscow region

Aim. To assess dynamics of glycated hemoglobin levels and insulin doses per kg bw in children and adolescents with poorly controlled type 1 diabetes mellitus using insulin pumps. Materials and methods. Retrospective analysis of HbA1c levels and insulin doses per kg bw in children aged 2-17 years with DM1 (mean duration 5.3?3.1) before and 18 months after onset of insulin pump therapy (Medtronic Minimed 712 and 722) with a short-acting insulin analog Novopramid (Novo Nordisk) or Humalog (Ely Lilly) given to 55 (52,4%) and 50 (47,6%) of the patients respectively. НbА1с level and mean daily insulin dose per kg bw were determined when a patient visited the doctors office every 3 months. Results. Insulin pump therapy in patients with initially poorly controlled DM1 resulted in a decrease of HbA1c from 9.8?0.8 to 7,8?0,5% within 18 months after its beginning (p

Intensification with prandial insulin

Many patients with type 2 diabetes will ultimately need insulin therapy to maintain their target for glycaemic control. This review considers how best to achieve the target for glycaemic control in primary care. Literature review and workshop discussions among participants at the Insulin Intensification Summit. Treatment aimed at reducing postprandial glucose is more effective in improving glycaemic control near target levels. Adding prandial doses of a short-acting insulin is superior to switching to a twice-daily premixed insulin. Short-acting analogue insulins offer advantages over animal insulins for intensification of basal insulin therapy, which can be achieved either by sequentially adding prandial doses or immediate introduction of three-times daily prandial dose. Each approach has benefits depending on the health care system and can be supported in primary care by a simple algorithm. Intensification of basal insulin therapy is most effectively achieved by adding a prandial short-acting insulin analogue, using a simple clinical algorithm. The regimen should be selected according to local needs.

Insulin therapy and quality of life. A review

Three central goals in the treatment of diabetes mellitus are (1) the avoidance of hyperglycaemia to prevent the development or progression of diabetes complications over time, (2) the avoidance of hypoglycaemia and (3) the maintenance or achievement of good quality of life. Insulin is the most powerful agent that can be used to control blood glucose levels. This article reviews the studies that have investigated the effects of different types of insulin and insulin delivery techniques on quality of life of patients with type 1 or type 2 diabetes. First, the concept of 'quality of life' (QoL) is defined and different ways of measuring QoL are explained. Secondly, the effects of different aspects of insulin therapy on QoL are reviewed: (1) the phenomenon of 'psychological insulin resistance'; (2) the effects of different types of insulin: regular insulin versus short-acting insulin analogues, long-acting insulin analogues or biphasic mixtures; (3) multiple daily injections versus pump therapy. Having multiple complications of diabetes is clearly associated with decreased QoL. Results from large studies such as the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) suggest that intensive treatment itself does not impair QoL. Recent findings further suggest that pump therapy, compared to multiple daily injections, has beneficial effects on QoL. The fact that multiple tools are used to assess QoL makes it difficult to draw conclusions regarding the effects of different types of insulin on QoL. More work on the standardization of the assessment of QoL in diabetes is urgently needed.

Effect of a local heating device on insulin and glucose pharmacokinetic profiles in an open-label, randomized, two-period, one-way crossover study in patients with type 1 diabetes using continuous subcutaneous insulin infusion

Background: Reducing postprandial hyperglycemia and hypoglycemia is a major challenge in the treatment of patients with diabetes. Studies suggest that heating the insulin injection site may accelerate insulin absorption. InsuPatch™ (InsuLine Medical Ltd., Petach-Tikva, Israel) is a device intended to accelerate subcutaneous insulin delivery using an insulin pump by locally warming the infusion site. Objective: The aim of this study was to assess the effect of the InsuPatch device on the pharmacokinetics of short-acting insulin analogues and on postprandial glycemia. Methods: This was an open-label, randomized, 2-period, 1-way crossover study using a meal tolerance test (MTT) protocol in subjects with type 1 diabetes mellitus aged 18 to 65 years with glycosylated hemoglobin (HbA 1c) of 6% to 12%, who were using continuous subcutaneous insulin infusion (CSII) therapy (insulin lispro or aspart). A bolus of insulin 0.15 U/kg was delivered immediately before a standardized liquid meal. The effect of the device on insulin absorption and postprandial glucose excursions was tested by measuring blood glucose and insulin concentration profiles with and without the operation of the device. Adverse events (AEs) were monitored during the 2 study visits. The infusion site was visually inspected at the end of each study. All AEs were recorded in the case-report form. Results: The MTT protocol was performed in 17 white patients with type 1 diabetes (sex, male/female, 7/10; mean age, 31.8 years [range, 18–53 years]; mean body mass index, 25.6 kg/m 2 [range, 20.0–39.4 kg/m 2]; and mean HbA 1c, 7.1% [range, 5.8%–9.3%]). The mean (SD) postprandial glucose excursion AUC at 120 minutes after the meal was significantly reduced in the group that used the device compared with the group that did not (104 [65] vs 155 [56] mg/dL/h; P < 0.005). Plasma insulin was measured randomly in 9 of the 17 subjects. Use of the device was associated with significant reductions in mean (SD) T max (45 [28] vs 78 [35] minutes) and time to half-maximum concentration (T 50%max) (20 [11] vs 28 [10] minutes; both, P < 0.05). Insulin AUC increased significantly in the group that used the device compared with the group that did not at 30 (21 [6] vs 33 [16] mU/L/h), 60 (55 [12] vs 80 [28] mU/L/h), and 90 (93 [19] vs 118 [31] mU/L/h) minutes after administration (all, P < 0.05). Cmax also increased significantly (118 [35] vs 86 [16] mU/L [38%]; P < 0.05). Conclusion: In this pilot study, use of the InsuPatch was associated with significant decreases in T max and T 50%max and increases in insulin AUC and C max of subcutaneous infused rapid-acting insulin analogues, resulting in a lower postprandial glucose excursion in these patients with type 1 diabetes mellitus treated with CSII.

Insulin Analogs Reduce Carotid Artery Intimal Hyperplasia Potentially via Insulin‐like Growth Factor‐1 Mediated Reduction in Oxidant Stress

Glargine and glulisine (long and short acting insulin analogs respectively), used in the treatment of diabetes can activate insulin‐like growth factor‐1 (IGF‐1) dependent signaling in vitro. IGF‐1 is known to decrease atherosclerotic lesion in ApoE‐null mice. Glargine or glulisine (0.45 mg/kg/d) or vehicle were sc injected in Zucker fatty rats for 7 days before and 21 days after injuring the carotid artery (CA) to study the effects on intimal hyperplasia. Intima/media ratio (I/M), in CA sections was significantly reduced in glargine group (glargine, 0.4±0.1, glulisine, 0.6±0.1, control, 0.9±0.1, P&lt;0.05). This correlated with increase in serum IGF‐1 (glargine, 1059±150 ng/ml, glulisine, 763±161 ng/ml, control, 567 ±121 ng/ml, P&lt;0.05). As IGF‐1 suppresses oxidative stress in vivo, aortic 8‐isoprostane (8IP, ELISA) and N‐tyrosine (NT, immunostaining of CA sections) were measured. Glargine and glulisine significantly reduced 8IP and NT compared to control [8IP (ng/mg protein): glargine, 0.92±0.42, glulisine, 1.12±0.29, control, 2.57±0.4, P&lt;0.05; NT immunopositivity, glargine, 55% decrease; glulisine, 34% decrease]. Glargine and to a lesser extent glulisine reduced IH in rat CA and suppressed vascular oxidative stress with an increase in IGF‐1. These effects are possibly mediated by IGF‐1, and its action as an atheroprotective agent.

HMW-Adiponectin Associates with Triglyceride Concentrations in Type 1 Diabetic Patients

The objective of this study was to investigate the relation between serum high molecular weight (HMW)-adiponectin concentration and fasting and postprandial blood glycemic and lipid parameters in type 1 diabetic patients. Type 1 diabetic patients treated with short-acting insulin analogs and healthy volunteers were recruited. The subjects were divided into two groups based on the mean HMW-adiponectin value of 12.2 mg/L: low HMW-adiponectin (men/women=7/2) and high HMW-adiponectin (men/women=3/8). Blood samples were collected after an overnight fast, and 30180 min after consuming white bread (B) or white bread with butter (BB). Type 1 diabetic patients with high HMW-adiponectin had lower triglyceride and remnant like particle (RLP)-triglyceride concentrations than those with low HMW-adiponectin (p<0.01), and had a higher lipoprotein lipase mass (p<0.01) than healthy subjects (men/women=8/6). After B and BB meals, type 1 diabetic patients with high HMW-adiponectin consistently had lower triglyceride and RLP-triglyceride concentrations for up to 180 min than those with low HMW-adiponectin (p<0.01); however, apoB48 did not differ between these two groups. Fasting and postprandial plasma glucose were higher in both diabetic groups than in healthy subjects (p<0.001), with no significant difference between patient groups. HMW-adiponectin is more strongly associated with very low density lipoprotein remnant metabolism than glucose utilization in type 1 diabetic patients receiving short-acting insulin analogs.

The management of gestational diabetes

The incidence of gestational diabetes is increasing. As gestational diabetes is associated with adverse pregnancy outcomes, and has long-term implications for both mother and child, it is important that it is recognized and appropriately managed. This review will examine the pharmacological options for the management of gestational diabetes, as well as the evidence for blood glucose monitoring, dietary and exercise therapy. The medical management of gestational diabetes is still evolving, and recent randomized controlled trials have added considerably to our knowledge in this area. As insulin therapy is effective and safe, it is considered the gold standard of pharmacotherapy for gestational diabetes, against which other treatments have been compared. The current experience is that the short acting insulin analogs lispro and aspart are safe, but there are only limited data to support the use of long acting insulin analogs. There are randomized controlled trials which have demonstrated efficacy of the oral agents glyburide and metformin. Whilst short-term data have not demonstrated adverse effects of glyburide and metformin on the fetus, and they are increasingly being used in pregnancy, there remain long-term concerns regarding their potential for harm.

Short‐acting insulin analogues vs. regular human insulin in type 2 diabetes: a meta‐analysis

Short-acting insulin analogues, in comparison with regular human insulin (HRI), provide a greater control of postprandial glucose, while their superiority on haemoglobin A1c (HbA1c) is controversial. All randomized controlled trials (RCTs) with a duration >4 weeks comparing short-acting insulin analogues (lispro, aspart or glulisine) with HRI in type 2 diabetic patients were retrieved; data on HbA1c and postprandial glucose et end-point and incidence of severe hypoglycaemia were extracted and meta-analysed. A total of 13 RCTs (7, 4 and 2 with lispro, aspart and glulisine, respectively) were retrieved and included in the analysis. Short-acting analogues reduced HbA1c by 0.4% (0.1-0.6%) (p = 0.027) in comparison with HRI. A significant improvement was observed also in self-monitored 2 h postbreakfast and dinner blood glucose. The overall rate of severe hypoglycaemia was not significantly different with short-acting analogues and HRI [Mantel-Haenszel odds ratio for 95% confidence interval 0.61 (0.25-1.45)]. In type 2 diabetic patients, short-acting insulin analogues provide a better control of HbA1c and postprandial glucose than regular human insulin, without any significant reduction of the risk of severe hypoglycaemia.

Insulin Glargine versus Neutral Protamine Hagedorn Insulin for Treatment of Diabetes in Pregnancy

We compared maternal and neonatal outcomes in diabetic pregnancies treated with either insulin glargine or neutral protamine Hagedorn (NPH) insulin. We performed a retrospective chart review of diabetic pregnant patients using the Diabetes Care Center of Wake Forest University during the years 2000 to 2005. Outcomes of interest included maternal hemoglobin A1C, average fasting and 2-hour postprandial blood sugars, mode of delivery, birth weight, 5-minute Apgar score < 7, umbilical artery pH < 7.20, incidence of neonatal hypoglycemia, and pregnancy complications. A total of 52 diabetic pregnant patients were included in this study. Twenty-seven women used insulin glargine. A total of 13 women used insulin glargine during the first trimester. Glycemic control was similar in women who used NPH insulin and insulin glargine, as determined by hemoglobin A1C levels and mean blood sugar values. There were no differences in mode of delivery, average birth weight, or neonatal outcomes. Maternal and fetal/neonatal outcomes appear similar in pregnant diabetic women who use either NPH insulin or insulin glargine in combination with a short-acting insulin analogue to achieve adequate glycemic control during pregnancy. Insulin glargine appears to be an effective insulin analogue for use in women whose pregnancies are complicated by diabetes.

Overnight CSII as supplement to oral antidiabetic drugs in Type 2 diabetes

To evaluate the potential advantages of a constant overnight subcutaneous delivery of insulin in type 2 diabetic patients who fail to achieve glycaemic control on oral antidiabetics. Ten type 2 diabetic patients treated with oral antidiabetic drugs without gaining sufficient glycaemic control were included in this three-period study. All patients received continuous subcutaneous insulin infusion (CSII) with a short-acting insulin analogue, 2 IU/h, for 8 h during three consecutive nights (period A). Based upon the results from period A, two additional dose regimens of three nights (period B and C) were studied in random order. Serum insulin aspart, human insulin and plasma glucose (PG) profiles were recorded. In period A, fasting plasma glucose (FPG) was reduced from a mean +/- s.d. (mmol/l) value of 11.6 +/- 2.9 to 5.5 +/- 1.6 (p < 0.0001) during the first night. No additional lowering of FPG was seen the two succeeding nights. FPG narrowed as the range before the infusion was 7.3-15.2 mmol/l compared with 3.6-6.1 mmol/l on the last morning after infusion. The variability in PG profile during the first and the last night of CSII was small and not significantly different. The rising insulin aspart was mirrored by a decrease in human insulin. In period B and C, similar tendencies as for period A were seen. In period A, two patients each experienced one mild hypoglycaemic episode. CSII with an insulin analogue overnight effectively reduced FPG without occurrence of major hypoglycaemia in type 2 diabetic patients who fail to achieve glycaemic control on oral antidiabetic treatment.

Evaluation of the Pituitary Function with Insulin Tolerance (Hypoglycaemia) Testing: Are There Any Differences Using Insulin Lispro Compared to Regular Insulin?

Background/Aim: The insulin tolerance test (ITT) remains the gold standard for evaluating the pituitary function, but has potential risks when hypoglycaemia is induced. There are scarce data using short-acting insulin analogs for ITTs. This pilot study compares the effects of insulin lispro (LPI) with regular insulin (RGI) during an ITT. Methods: Patients with suspected hypopituitarism (n = 103) randomly received either LPI (n = 51) or RGI (n = 52). Results: All patients reported signs and symptoms when hypoglycaemia was induced. In the LPI group, hypoglycaemia occurred sooner (23.6 ± 1.6 vs. 28.3 ± 1.4 min, p < 0.05), and duration of hypoglycaemia (25.0 ± 1.7 vs. 31.9 ± 1.9 min, p < 0.05) and time for blood glucose levels to return to a ‘safe’ level (>3.3 mmol/l; 56.5 ± 2.3 vs. 76.0 ± 2.1 min, p < 0.001) were shorter as compared with the RGI group. No differences in peak growth hormone and cortisol levels were observed between the two groups. Conclusions: Our data suggest that despite inducing similar symptomatology, LPI exerted a quicker onset and a shorter duration of hypoglycaemia as compared with RGI. Thus, using LPI might reduce the potential risks associated with an ITT by shortening the hypoglycaemic phase of the test.

A comparison of lispro and regular insulin for the management of type 1 and type 2 diabetes in pregnancy

Objective. To describe perinatal outcomes of women with pregestational diabetes treated with short-acting, regular insulin and the short-acting insulin analogue, lispro.Study design. This was a prospective observational study of women with pregestational diabetes maintained on short-acting insulin regimens over a 3-year period. Clinical characteristics, aspects of diabetic therapy, and perinatal/neonatal outcomes were collected.Results. Of 107 women, 49 were maintained on regular insulin and 58 utilized the insulin analogue, lispro. Frequency of type 1 diabetes, maternal age, overweight/obese pregravid body mass index (≥25 kg/m2), preexisting hypertension, and presence of vascular disease were similar between groups. Women treated with lispro had a longer duration of diabetes (11.4 vs. 8.3 years, p = 0.04). Glycemic control was improved in women managed with lispro compared to regular insulin (HgbA1c 5.9 vs. 6.7, p = 0.009). Total insulin requirements were lower in the lispro group in the first (0.58 vs. 0.79 units/kg, p = 0.02), second (0.75 vs. 1.10 units/kg, p = 0.002), and third (0.98 vs. 1.25 units/kg, p = 0.03) trimesters of pregnancy. Mean infant birth weight was greater in the lispro group, whereas the rate of large for gestational age infants and ponderal indices were similar between groups. Malformation rate, gestational age at delivery, neonatal intensive care unit admission, neonatal length of stay, rates of respiratory distress syndrome, and hypoglycemia were similar.Conclusions. Women treated with lispro demonstrated improved glycemic control and lower total insulin requirements during pregnancy compared to those receiving regular insulin. Perinatal outcomes were similar between women treated with both types of insulin.

Defining the Role of Insulin Lispro in??the Management of Postprandial Hyperglycaemia in Patients with Type??2 Diabetes Mellitus

The role of postprandial hyperglycaemia in contributing to the risk of both micro- and macrovascular complications in patients with diabetes mellitus is being increasingly recognized. In type 2 diabetes, there is a progressive shift in the relative contributions of postprandial and fasting hyperglycaemia to the overall glycaemic control as the disease progresses. For patients with fairly good glycaemic control (glycosylated haemoglobin [HbA(1c)] <8.5%), postprandial hyperglycaemia makes a relatively greater contribution to the overall glycaemic load than fasting hyperglycaemia, but in patients with poorer control, the relative contribution of the two states to the overall glycaemic load is reversed. This finding, coupled with epidemiological evidence that elevated postprandial glucose concentration is an independent risk factor for cardiovascular disease (CVD), and is associated with a greater CVD risk than elevated fasting glucose, points to the need to monitor and target postprandial glucose, as well as fasting glucose and HbA(1c) levels, when optimizing insulin therapy for patients with type 2 diabetes. When insulin therapy becomes necessary in patients with type 2 diabetes who can no longer be controlled with oral antihyperglycaemic therapy, use of short-acting insulin analogues with a rapid onset of action and capable of controlling postprandial glycaemic excursions when injected immediately before a meal, has advantages over regular human insulin in that they provide a more favourable time-action profile that mimics normal physiological insulin secretion. Among the available rapid-acting insulin analogues, insulin lispro has been shown to reduce postprandial glucose concentrations to a significantly greater degree than regular human insulin in patients with type 2 diabetes. Moreover, premixed combinations of insulin lispro with the longer acting analogue neutral insulin lispro protamine suspension in 25% : 75% or 50% : 50% combinations are significantly more effective in lowering postprandial blood glucose concentrations than premixed regular human insulin plus neutral protamine Hagedorn (NPH) 30% : 70%. The premixed insulin lispro combinations offer the advantage of fewer daily injections than intensive insulin therapy, and the convenience of not having to mix insulin preparations manually. Although it has yet to be conclusively established that targeting postprandial hyperglycaemia reduces CVD risk, the potential benefits of improved postprandial and interprandial hyperglycaemia favour the use of newer insulin analogues, such as insulin lispro and insulin lispro mixes, over conventional insulin therapy, whenever insulin therapy becomes necessary in patients with type 2 diabetes.

The importance of carbohydrate counting in the treatment of children with diabetes

Carbohydrate (Carb) counting is a meal planning approach for patients with diabetes mellitus that focuses on carbohydrate as the primary nutrient affecting postprandial glycemic response. The concept of carb counting is not new. In the early 1990's the Diabetes Control and Complications Trial (DCCT) used carb counting as one of its education tools. More recently, short acting insulin analogues and insulin pumps have made the role of carb counting important and popular. Carb counting can be used in conjunction with a meal plan to set carbohydrate targets at each meal and snack. It is also used, perhaps more commonly, to estimate carbohydrate intake and adjust insulin around mixed meals and snacks using insulin to carbohydrate ratio. This effectively addresses the variable eating habits of most children and adolescents. The method may be adapted for patients who use a conventional insulin regimen and may meet the needs of patients who use multiple daily injections (MDI) or an insulin pump. Carb counting can make food planning flexible and enjoyable for patients, and the meal planning approach is very important for the physical growth and psychological development of children with diabetes. This paper describes the importance of carb counting for childhood diabetes as well as some of the special aspects associated with it.

Nice insulins, pity about the evidence

In February 2006 the German Institute for Quality and Efficiency in Healthcare (IQWiG), an independent body with a mandate to assess the evidence for medical interventions, released its final report on the use of short-acting insulin analogues in the treatment of type 2 diabetes. The report found no advantage over soluble (regular) human insulin. Given that analogues cost more than soluble insulin, the report concluded that there was no evidence to support their use in patients with type 2 diabetes [1]. A subsequent report concluded that the benefits of shortacting analogues in type 1 diabetes were marginal at best [2], and a report on the long-acting analogues is on its way: many suspect that this will be almost equally negative. Although some have taken issue with the way in which the analysis was performed, for reasons to be discussed later, the conclusions of the initial report were not unexpected. It was not so much the advice that provoked controversy as the fact that it was acted upon: healthcare purchasers decided that they would no longer reimburse the costs of short-acting analogues prescribed for patients with type 2 diabetes. The response from some industry representatives, patient bodies and clinicians was one of predictable outrage. From the point of view of industry, the German pharmaceutical market is worth 37.8 billion euros per year [3], third only in importance to those of the USA and Japan, and analogues have a larger share of insulin sales in Germany than anywhere else in the world. Patients were affected at a more personal level, for many link their safety and well-being to an insulin formulation that suits them, and feel threatened if someone proposes to take this away. Some physicians were equally displeased, for clinicians notoriously dislike challenges to their autonomy and judgement. Add to this volatile mix the fact that some (but by no means all) patient organisations and clinicians are well-funded by industry, and you have a recipe for trouble. Most of the anger was directed towards IQWiG, and the debate that followed was loud and sometimes ugly. Peter Sawicki, Chairman of IQWiG, had his name dragged through the media. A petition to the government protesting at the withdrawal of the analogues was signed by 180,000 patients, and ‘independent’ commentators duly appeared in the media to discredit the report [4]. The outcome was revealing. The insulin manufacturers denied the evidence, but they did not dispute it. Instead, they simply opted to reduce the price of their quick-acting analogues to match that of human insulin, and the concerns of the healthcare providers melted away. Story over? Not quite.

Prescription of Insulin Glargine in Primary Care Practices in Germany

New classes of antidiabetic medications have been introduced, but details of their use are not well known. The aim was to assess prescription patterns and dosing for insulin glargine (market launch: 6/2000) in primary care patients. Computerized data on prescriptions (Disease Analyzer, 6/1999 to 8/2003) from 277 general and internal medicine practices throughout Germany were analysed (67,402 diabetic patients; 340 incident glargine (age: 67+/-12 years) and 378 incident NPH users (66+/-11 years). Diabetes prevalence in the practices increased over the three-year period (5.1% to 6.2%). The highest increase was observed for insulin treated patients (+29%), followed by diet (+21%) and oral antidiabetics (+19%). Premixed insulin (short-acting insulin and NPH) remained constant as largest insulin group. A continuous increase of short-acting insulin analogues was found (+70%). Long-acting insulin analogues (glargine) increased threefold. Glargine was more often prescribed in combination with oral antidiabetics than NPH (76% vs 49%; p<0.05). Only about a quarter received short-acting insulin (NPH: 61%; p<0.05). The cumulative annual dose was higher among NPH users (geometric mean; NPH: 7971 IU; glargine: 5719 IU) (p<0.01), which persisted after adjusting for age, sex, and morbidity (p<0.01). Diabetes prevalence continuously increased in German primary care practices from 1999 to 2003. The largest increase was found for insulin treatment, in particular, for short and long-acting insulin analogues. Insulin glargine was more often prescribed in combination with oral agents, whereas NPH insulin was more frequently prescribed with short-acting insulin, indicating different prescription patterns in primary care.

Maternal Metabolic Control and Perinatal Outcome in Women With Gestational Diabetes Mellitus Treated With Lispro or Aspart Insulin

Gestational diabetes mellitus (GDM) is associated with increased risk of maternal and neonatal morbidity with macrosomia being the most common neonatal complication (1). The risk of macrosomia and/or disproportionate fetal growth is closely related to 1-h postprandial glucose concentration (2). Therefore, the treatment of GDM should be aimed at normalizing maternal glycemia including the early postprandial response. Insulin therapy is needed whenever strict normoglycemia cannot be achieved by medical nutritional therapy alone (3). Because of their pharmacokinetic properties, short-acting insulin analogs (Insulin Aspart [ASP] and Insulin Lispro [LIS]) could be more effective in pregnancy than human regular insulin (HI) (4). Nevertheless, data …

When basal insulin therapy in type 2 diabetes mellitus is not enough—what next?

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by co-existing insulin deficiency (relative) and insulin insensitivity. Both fasting and post-prandial blood glucose are elevated, exposing the patient to acute and chronic complications due to micro- and macro-vascular angiopathy. Improving glycaemic control has been demonstrated to lower the risk of these complications. Owing to the progressive nature of the disease, an evolving treatment strategy is necessary to maintain glycaemic control. Insulin therapy is required when dietary and lifestyle modifications combined with oral hypoglycaemic agents fail to provide adequate glycaemic control. Adding an optimized dose of basal insulin to the existing oral therapy is a simple and widely used method for initiating insulin therapy. However, despite an effective control of fasting hyperglycaemia, further intervention to control post-prandial hyperglycaemia may become necessary to achieve HbA1c targets. Strategies for the addition of prandial insulin include administering short-acting (or rapid-acting) insulin analogues before each meal or twice-daily administration of pre-mixed insulin. As a single large meal often contributes to the greatest part of daytime hyperglycaemia, an alternative strategy is emerging with the addition of a single injection of prandial insulin prior to the meal that induces the largest post-prandial blood glucose excursion measured 2 h after the start of the meal. Over time, additional prandial boluses of insulin may be required to sustain daytime glycaemic control. This strategy offers a simple, stepwise approach to progress from basal insulin to a basal-bolus regimen. Studies are needed to validate this method and better define specific titration tactics.

Early and late onset side effects of short-acting insulin analogue in seven Japanese diabetic patients

Short-acting insulin analogue has previously shown to be equal to short-acting human regular insulin regarding in vitro characteristics, immunogenicity, and safety. But in the present study, we experienced seven patients who had mild to moderate side effects due to short-acting insulin analogue. These side effects could be divided into two types based on the appearance time; one with early onset and the other with late onset. Early onset side effects include rash, disturbances in walking and general fatigue that can not be explained by the swing in glucose levels. These symptoms appeared 2–3 days after the use of short-acting insulin analogue and disappeared several hours after switching short-acting human regular insulin. The late onset side effect is bilateral leg edema, which appeared 1–2 months after the induction of short-acting insulin analogue and disappeared after several hours by changing to short-acting human regular insulin. We should monitor the early and late onset side effects as diligently as possible when we use short-acting insulin analogue on diabetic patients.