Regular Human Insulin Research Articles

Lispro insulin in people with non-alcoholic liver cirrhosis and type 2 diabetes mellitus

AimsTo compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD). Methods108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12+12 week cross-over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12IU lispro or RHI shot ahead. ResultsCGM showed higher glycemic excursions under RHI than under lispro (p<0.01) with lower glucose levels in the late post-absorption phase (p<0.05) and even more during the night (p<0.01). Post-challenge incremental areas under the curve (ΔAUC) were undistinguishable for insulin but lower for glucose, while insulin peaked higher and earlier and glycemic excursions were lower with lispro than with RHI (0.05<p<0.001). ConclusionsLispro granted lower early postprandial glucose levels and late postprandial hypoglycemic rates and therefore might represent the treatment of choice for people with T2DM and compensated CLD. This might depend on its faster/shorter–living effects, as well as, on the lower liver glucose output expected from its earlier hepatic distribution.

Clinico-bacteriological study of diabetic foot: an observational study

Background: Diabetic foot is the most important surgical manifestation of diabetes. With foot infection a major cause of morbidity bacterial infection play an important role in diabetic foot ulcers. Aim of this study was proposed to establish the bacterial profile and anti-microbial pattern of ulcer in an attempt to evaluate the role of infection in the foot lesions of diabetic patient. Associated factors like incidence, age, sex, predisposing factors, duration of diabetes, ulcer grade, hospital stay, modes of treatment, antibiotics sensitivity and other outcomes were also evaluated. Methods: This is a Prospective cohort study. The patients were admitted in surgical ward as provisional diagnosed cases of diabetic foot, were subjected to investigations including blood sugar (fasting, P.P, random), renal function test, x-ray of affected foot, fundus examination, grading of ulcer and various modes of treatment was given. Gross examination and culture from ulcers were done. Study was done in 104 patients over 1 year period. Results: One hundred four patients with diabetic foot were evaluated. Incidence of diabetic foot was 1.26%. Majority of cases were from rural areas (82.7%). Newly diagnosed cases of diabetes at admission (22.11%), majority of cases culture was positive (94.1% of 85). Staphylococcus was the predominant organism (61.17%), there were patients who were not on any mode of treatment (29.8%). Conclusions: Staphylococcus aureus a gram positive cocci was the most common micro-organism grown on culture from the ulcer (61.17%), next common micro-organism was Klebsiella (16.47%) gram negative bacilli. Piperacillin and metronidazole were most commonly used antibiotics. Diabetes was controlled by human actrapid (human regular insulin) in majority of the patients. Majority belonging to rural areas (82.7%). Most of the cases were relieved (77.88%). Only two cases fatality (1.92%) occurred during study period.

Drug utilisation in medical intensive care unit: a retrospective analysis from a tertiary care teaching hospital

Background: The World Health Organisation has defined drug utilization study as “the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social, and economic consequences. The objective was to evaluate drug utilization pattern in medical intensive care unit (MICU) in a tertiary care teaching hospital. Methods: A retrospective observational study was conducted in MICU for adult patients admitted from October to December 2013. Data collected was analysed for demographics, indication, duration of stay, World Health Organisation (WHO) prescribing indicators including anatomical therapeutic chemical classification and defined daily dose (DDD). Results: A six hundred encounters from 63 male and 44 female patients with a mean age of 60.88±16.87 were studied. Average duration of stay was 5.61±3.88 days. The common indications for admission were dyspnoea 20 (18.69%), upper gastrointestinal bleed 16 (14.95%), cerebrovascular accident 14 (13.08%) and sepsis 13 (12.15%). Total number of drugs prescribed was 246. Total drug encounters were 7695. Average number of drugs per encounter was 12.83. Percentage of drugs prescribed by generic name was 38.21%, 44.7% and 40.65% of the drugs were prescribed from National and WHO essential medicine list respectively. Among the drugs prescribed 65.44%, 32.93% and 17.48% were oral, injectable and fixed dose combination preparations respectively. Percentage of encounters resulting in prescription of an antibiotic and an injection were 59% and 85.83% respectively. The most commonly prescribed drugs were pantoprazole (100%), human regular insulin (52.83%), piperacillin + tazobactam (45%) and ceftriaxone (38%). Their DDD/100 bed days were found to be 83.79, 12.78, 12.50, and 17.81 respectively. Conclusions: Overall the prescribing pattern seems to be rational but may be further strengthened by increasing generic drug prescription, judicious use of pantoprazole and periodic longitudinal surveillance studies.

Development of a Microsphere-Based System to Facilitate Real-Time Insulin Monitoring.

The speed of insulin absorption after subcutaneous delivery is highly variable. Incorrect assumptions about insulin pharmacokinetics compromise effective glycemic regulation. Our ultimate goal is to develop a system to monitor insulin levels in vivo continuously, allowing pharmacokinetic parameters to be calculated in real time. We hypothesize that a bead-based detection system can be run on a flow-through microfluidic platform to measure insulin in subcutaneous fluid sampled via microdialysis. As a first step in development, we focused on microsphere-based measurement of insulin. Polystyrene microspheres coated with an anti-insulin monoclonal antibody were exposed to insulin-containing solutions, and after addition of a fluorescently labeled anti-insulin monoclonal antibody with a distinct epitope, bead-associated fluorescence was detected by fluorescence microscopy in 96-well plates or in a flow-through, microfluidic platform. The bead detection system in plates had a linear range in buffer for regular human insulin (RHI), insulin lispro, and insulin aspart of 15-1115 µIU/ml, 14-976 µIU/ml, and 25-836 µIU/ml, respectively. Measurement on plasma samples demonstrated proportionality between basal and peak insulin levels similar to the laboratory reference method. Preliminary results in a polydimethylsiloxane-based, flow-through, microfluidic platform showed a strong signal at peak insulin levels. We have developed a microsphere-based system to rapidly measure levels of insulin and insulin analogs. We have further demonstrated proof of concept that this bead detection system can be implemented in a lab-on-a-chip format, which will be further developed and combined with microdialysis for real-time monitoring of insulin in vivo.

Optimized Human Regular U-500 Insulin Treatment Improves β-Cell Function in Severely Insulin-Resistant Patients with Long-Standing Type 2 Diabetes and High Insulin Requirements

To assess β-cell function and insulin sensitivity following improvement in glycemic control in severely insulin-resistant patients with poorly controlled type 2 diabetes (T2D). A subset of patients in a 24-week, open-label, randomized trial comparing thrice-daily (n = 14/162) versus twice-daily (n = 11/163) human regular U-500 insulin (U-500R) underwent mixed meal tolerance testing at baseline and endpoint. Baseline characteristics were similar between treatment groups (combined means: age, 54.0 years; diabetes duration, 13.6 years; body mass index, 38.8 kg/m(2); glycated hemoglobin [HbA1c], 8.3%; U-100 insulin dose, 287.6 units/day, 2.6 units/kg/day). Primary outcome measure was ratio of area under the curve (AUC) for C-peptide to glucose (AUCC-peptide/AUCglucose) at 24-week endpoint. Change from baseline HbA1c, daily U-500R dose, and weight were -1.17% (P = .0002), +80.8 units (P = .0003), and +5.9 kg (P = .33), respectively. β-Cell function significantly improved after 24 weeks of U-500R therapy in combined treatment groups. The AUCC-peptide/AUCglucose increased 34.0% (ratio of least-squares geometric mean, 1.34; 95% confidence interval, 1.18 to 1.52; P = .0001). Integral of total insulin secretion rate increased from 27.0 to 33.7 nmol/m(2), and glucose sensitivity improved from 18.3 to 24.0 pmol/min/m(2)/mM (both, P = .02). Matsuda index improved from 0.8 to 1.3 (P = .008). Despite long-standing diabetes and poor glycemic control at baseline, functional recovery of β-cells was observed with improved glycemic control in these severely insulin-resistant patients with T2D, possibly due to alleviation of glucotoxicity.

Insulin Aspart in the Management of Diabetes Mellitus: 15 Years of Clinical Experience.

Limiting excessive postprandial glucose excursions is an important component of good overall glycemic control in diabetes mellitus. Pharmacokinetic studies have shown that insulin aspart, which is structurally identical to regular human insulin except for the replacement of a single proline amino acid with an aspartic acid residue, has a more physiologic time–action profile (i.e., reaches a higher peak and reaches that peak sooner) than regular human insulin. As expected with this improved pharmacokinetic profile, insulin aspart demonstrates a greater glucose-lowering effect compared with regular human insulin. Numerous randomized controlled trials and a meta-analysis have also demonstrated improved postprandial control with insulin aspart compared with regular human insulin in patients with type 1 or type 2 diabetes, as well as efficacy and safety in children, pregnant patients, hospitalized patients, and patients using continuous subcutaneous insulin infusion. Studies have demonstrated that step-wise addition of insulin aspart is a viable intensification option for patients with type 2 diabetes failing on basal insulin. Insulin aspart has shown a good safety profile, with no evidence of increased receptor binding, mitogenicity, stimulation of anti-insulin antibodies, or hypoglycemia compared with regular human insulin. In one meta-analysis, there was evidence of a lower rate of nocturnal hypoglycemia compared with regular human insulin and, in a trial that specifically included patients with a history of recurrent hypoglycemia, a significantly lower rate of severe hypoglycemic episodes. The next generation of insulin aspart (faster-acting insulin aspart) is being developed with a view to further improving on these pharmacokinetic/pharmacodynamic properties.

Systematic Literature Review of Basal Bolus Insulin Analogue Therapy during Pregnancy

Currently standard insulin therapy for pregnancies complicated by diabetes mellitus (DM) is a combination of intermediate Neutral Protamine Hagedorn (NPH) and regular human insulin. In contrast, for non-pregnant individuals with diabetes, standard insulin therapy is basal bolus therapy (BBT) using a combination of rapid- and long-acting insulin analogues designed to mimic physiologic biphasic insulin secretion by the pancreatic beta cells. Although there are published reports describing use of BBT during pregnancy, due to the lack of strong clinical evidence regarding safety and efficacy of BBT during pregnancy, its use has not been adopted as standard insulin administration during pregnancies complicated by diabetes mellitus. To evaluate the evidence for this discrepant clinical management, we conducted a systematic review. Search strategy and selection criteria: PubMed, Medline, Cochrane Database of Systematic Reviews for publications between 1996 and 2014. Search terms: lispro, apart, glargine, detemir, glulisine, Humalog, NovoLog, Lantus, Levemir, Apidra, pregnancy, and diabetes. Included: randomized clinical trials, prospective and retrospective cohort analyses, case-control studies and case series and reports. Search limited to human studies and English language. Excluded: review articles. Nineteen studies were identified that assessed safety/efficacy of rapid-acting insulin analogues, lispro and aspart, and 23 studies that assessed the long-acting insulin analogues, glargine and detemir, in pregnant patients complicated with pregestational (PGDM) and gestational diabetes mellitus (GDM). The principal efficacy endpoint examined in the selected studies was glycated hemoglobin levels. Other study outcome variables to assess maternal glycemic control included fasting and postprandial glucose levels, large for gestational age (LGA) infants, mean birth weight, congenital malformations, and incidence of hypoglycemic events. Compared to conventional insulin therapy, insulin analogue use provided similar overall glycemic control in pregnancy. In addition, they contributed to greater postprandial glucose control. There was no compelling evidence that insulin analogue use was associated with any significant differences in maternal and neonatal outcomes, particularly in terms of incidences in maternal and neonatal hypoglycemia, LGA, and congenital malformations. Given the documented benefits of physiological insulin replacement, we found no reason that BBT should not be standard prenatal care for pregnancies complicated by DM.

Quantitative analysis of insulin in total parenteral nutrition bag in Taiwan

Regular insulin can reduce hyperglycemia when directly added to total parenteral nutrition (TPN) solutions. Insulin is not routinely added to all TPN solutions. For patients who require insulin prior to the initiation of TPN supplement, one-third to one-half of the usual total daily dose can be added to the TPN bag as regular human insulin. However, an incorrect dose or an interaction between insulin and the TPN bag material may affect blood sugar control in clinical practice. Therefore, it is important to quantitatively determine the final dose of insulin in the TPN bag. High performance liquid chromatography is a very powerful technique for determining the purity of proteins. The goal of this study was to use high-performance liquid chromatography to perform quantitative analysis of insulin in a TPN bag. The analysis was performed under different light conditions (UV, fluorescent, and darkness) and different temperatures (25°C and 2–8°C). The results show that adsorption of insulin on an ethylene vinyl acetate TPN bag is significantly higher than that on glass. Based on the results, it is evident that regular insulin should be administered separately from TPN to reduce cost and eliminate wasteful disposal of TPN solutions.

Use of Insulin Lispro Protamine Suspension in Pregnancy.

Maternal metabolism changes substantially during pregnancy, which poses numerous challenges to physicians managing pregnancy in women with diabetes. Insulin is the agent of choice for glycemic control in pregnant women with diabetes, and the insulin analogs are particularly interesting for use in pregnancy. These agents may reduce the risk of hypoglycemia and promote a more physiological glycemic profile than regular human insulin in pregnant women with type 1 (T1D), type 2 (T2D), or gestational (GDM) diabetes. However, there have been concerns regarding potential risk for crossing the placental barrier, mitogenic stimulation, teratogenicity, and embryotoxicity. Insulin lispro protamine suspension (ILPS), an intermediate- to long-acting insulin, has a stable and predictable pharmacological profile, and appears to have a favorable time–action profile and produce desirable basal and postprandial glycemic control. As the binding of insulin lispro is unaffected by the protamine molecule, ILPS is likely to have the same mitogenic and immunogenic potential as insulin lispro. Insulin lispro produces similar outcomes to regular insulin in pregnant women with T1D, T2D, or GDM, does not cross the placental barrier, and is considered a useful treatment option for pregnant women with diabetes. Clinical data support the usefulness of ILPS for basal insulin coverage in non-pregnant patients with T1D or T2D, and suggest that the optimal regimen, in terms of balance between efficacy and hypoglycemic risk, is a once-daily injection, especially in patients with T2D. Available data concerning use of ILPS in pregnant women are currently derived from retrospective analyses that involved, in total, >1200 pregnant women. These analyses suggest that ILPS is at least as safe and effective as neutral protamine Hagedorn insulin. Thus, available experimental and clinical data suggest that ILPS once daily is a safe and effective option for the management of diabetes in pregnant women. Funding: Eli Lilly and Company.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0244-y) contains supplementary material, which is available to authorized users.

Alternative signaling network activation through different insulin receptor family members caused by pro-mitogenic antidiabetic insulin analogues in human mammary epithelial cells.

IntroductionInsulin analogues are designed to have improved pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode of action of different insulin analogues. Insulin analogues can bind the insulin receptor and the insulin-like growth factor 1 receptor with different affinities and consequently will activate different downstream signaling pathways.MethodsHere we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR or the IGF1R. We applied a transcriptomics approach to assess the differential transcriptional programs activated in these cells by either insulin, IGF1 or X10 treatment.ResultsBased on the differentially expressed genes between insulin versus IGF1 and X10 treatment, we retrieved a mitogenic classifier gene set. Validation by RT-qPCR confirmed the robustness of this gene set. The translational potential of these mitogenic classifier genes was examined in primary human mammary cells and in mammary gland tissue of mice in an in vivo model. The predictive power of the classifier genes was evaluated by testing all commercial insulin analogues in the in vitro model and defined X10 and glargine as the most potent mitogenic insulin analogues.ConclusionsWe propose that these mitogenic classifier genes can be used to test the mitogenic potential of novel insulin analogues as well as other alternative molecules with an anticipated affinity for the IGF1R.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0600-5) contains supplementary material, which is available to authorized users.

Effectiveness of Inpatient Insulin Order Sets Using Human Insulins in Noncritically Ill Patients in A Rural Hospital

Recent guidelines recommend a physiologic approach to non-intensive care unit (ICU) inpatient glucose management utilizing basal-bolus with correctional (BBC) insulin over traditional sliding-scale insulin monotherapy. Unfortunately, few studies exist using a BBC approach restricted to human insulins (regular and neutral protamine Hagedorn [NPH]). This study evaluated changes in provider prescribing patterns, effects on blood glucose, and safety with implementation of hospital order sets for BBC using human insulins. Order sets were developed for non-ICU inpatients, consisting of basal, prandial, and correctional insulin using NPH and regular human insulins. Evaluation compared a 4-month period before (admissions, n = 274) with a 4-month period after order set availability (n = 302). Primary outcome was change in insulin prescribing patterns. Secondary outcomes included use of nonpreferred diabetes treatments, hemoglobin A1c testing, mean daily blood glucose, and incidence of hypoglycemia. Use of BBC insulin regimen increased from 10.6 to 27.5% after order set implementation (P<.001). Use of oral antihyperglycemic agents decreased from 24.1 to 14.9% after implementation (P = .006). Hemoglobin A1c testing rose from 50.0 to 62.3% after (P = .003). Mean daily blood glucose improved, with an estimated mean difference of 14.4 mg/dL (95% confidence interval, 2.2 to 26.5 mg/dL) over hospital days 3 through 9 (P = .02). There was no significant change in the incidence of moderate or severe hypoglycemia. Implementation of hospital-wide human insulin order sets led to improvements in prescribing practices and blood glucose control, without increasing the incidence of hypoglycemia. These order sets may be useful for facilities limited by formulary and cost considerations to the use of older human insulins.

Two Treatment Approaches for Human Regular U-500 Insulin in Patients With Type 2 Diabetes not Achieving Adequate Glycemic Control on High-Dose U-100 Insulin Therapy With or Without Oral Agents: A Randomized, Titration-To-Target Clinical Trial

To compare the efficacy and safety of 2 dosing regimens for human regular U-500 insulin (U-500R, 500 units/mL) replacing high-dose U-100 insulins with or without oral antihyperglycemic drugs in patients with inadequately controlled type 2 diabetes (T2D). We conducted a 24-week, open-label, parallel trial in 325 patients (demographics [means]: age, 55.4 years; diabetes duration, 15.2 years; body mass index, 41.9 kg/m(2); glycated hemoglobin [HbA1c], 8.7%; U-100 insulin dose, 287.5 units administered in 5 injections/day [median; range, 2 to 10]). Patients were randomized to thrice-daily (TID, n = 162) or twice-daily (BID, n = 163) U-500R after a 4-week lead-in period. The primary outcome was HbA1c change from baseline. After 24 weeks, both treatments demonstrated significant HbA1c reductions (TID, -1.12%; BID, -1.22%; both, P<.001) and clinical equivalence (difference, -0.10%; 95% confidence interval, -0.33 to 0.12%; noninferiority margin, 0.4%). Comparable increases in total daily U-500R dose (TID, 242.7 to 343.1 units; BID, 249.0 to 335.0 units) were observed. Incidence and rate of documented symptomatic hypoglycemia (≤70 mg/dL) were lower for TID versus BID (P = .003 and P = .02, respectively); severe hypoglycemia was similar between treatments. Weight gain was similar in both groups (TID, 5.4 kg; BID, 4.9 kg). Initiation and titration of U-500R using either algorithm (TID or BID) improves glycemic control effectively and safely with fewer injections in patients with T2D treated with high-dose/high-volume U-100 insulin. These results provide clinicians with a practical framework for using U-500R in severely insulin-resistant patients with suboptimally controlled T2D.

Practical Pearls for the Management of Patients on U-500 Regular Human Insulin

Practical Pearls for the Management of Patients on U-500 Regular Human Insulin

Optimal Dosing and Titration of U-500R Improve Glycemic Control

Human regular U-500 insulin (U-500R) is more concentrated and has a higher potency level than U-100 insulin. Dosing errors can occur in patients on concentrated insulin. This study investigates dosing and titration of U-500R insulin using a twice- or thrice-daily dosing schedule.

Abstract #265: Trends of Incident and Prevalent use of Human Regular U-500 Insulin Over A 9-Year Period in the United States

Abstract #265: Trends of Incident and Prevalent use of Human Regular U-500 Insulin Over A 9-Year Period in the United States

Safety of intravenous insulin aspart compared to regular human insulin in patients undergoing ICU monitoring post cardiac surgery: an Indian experience.

BackgroundPoor perioperative glycemic control increases risk of infection, cardiovascular accidents and mortality in patients undergoing surgery. Tight glycemic control by insulin therapy is known to yield better outcomes in such patients. Intravenous (IV) insulin therapy with or without adjunctive subcutaneous insulin therapy is the mainstay of managing hyperglycemia in perioperative period. This observational study assessed the safety of IV Insulin Aspart (IAsp) as compared to Regular Human Insulin (RHI) in patients undergone cardiac surgery at a tertiary care hospital.Methods203 patients received IV IAsp (n = 103) and RHI (n = 100) respectively. Safety was assessed by frequency and severity of adverse events (AEs) & serious adverse events (SAEs) during hospitalization.ResultsIAsp effectively controlled mean blood glucose levels to 159.87 ± 41.41 mg/dl similar to RHI (160.77 ± 44.39 mg/dl). No serious adverse event was reported. The incidence of hypoglycemia was similar in both the groups. The insulin infusion rate, time for which insulin infusion was withheld and mean blood glucose during hypoglycemia was significantly high in RHI group.ConclusionThis study has shown similar safety of IV IAsp as compared to IV RHI in the post cardiac surgery patients. However physicians preferred IAsp as it offers advantage during transition. IV IAsp offers an effective and safe option for managing hyperglycemia in patients in ICU post cardiac procedures.

Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study

AimDescribe the characteristics of patients initiating human regular U-500 insulin (U-500R) and their subsequent glycemic control in a real-world setting.MethodsUS Humedica electronic health record system data (July 2007–September 2011) were...

Afrezza: An inhaled approach to insulin delivery.

The purpose of this article is to educate nurse practitioners about Afrezza. A comprehensive literature search was conducted using MEDLINE for clinical trial data. Information from the Centers of Disease Control and Prevention, World Health Organization, clinical guidelines, Food and Drug Administration labeling, briefings, and press releases was also utilized. Afrezza represents a promising noninjectable insulin delivery option for type 1 and type 2 diabetes mellitus. According to clinical trial evidence, it appears to be efficacious and comparable to currently available prandial insulin options, and based on current data, it appears to be a safe alternative to injectable insulin with high treatment satisfaction. Afrezza may offer an alternative for insulin naïve patients who are hesitant about initiating traditional insulin. It may cause less weight gain when compared to subcutaneous mealtime insulin with a more rapid absorption and elimination profile, but more long-term studies are needed. Afrezza is limited in type 1 diabetes to use in combination with basal insulin. It is not recommended in the treatment of diabetic ketoacidosis or for patients who smoke. It is contraindicated during hypoglycemic episodes, in chronic lung diseases, or in those with hypersensitivity to regular human insulin or any of the excipients in Afrezza.

Insulin aspart for the treatment of Type 2 diabetes

SUMMARY Insulin aspart is a rapid-acting insulin analog and is approved for use in Type 1, Type 2 and gestational diabetes. Following the subcutaneous injection, it more closely mimics the physiological release of insulin in the human body with a faster onset and shorter duration of action. It also offers several advantages like flexibility in mealtime administration, better glycemic control in the form of superior control of postprandial glucose excursion and less nocturnal hypoglycemia as compared with regular human insulin. It is safe to use in patients with renal and hepatic impairment and is approved for use in pregnancy, in children above 2 years of age, in continuous subcutaneous infusion pumps and can be used intravenously in hospital settings.

Mammary gland tumor promotion by chronic administration of IGF1 and the insulin analogue AspB10 in the p53R270H/⁺WAPCre mouse model.

IntroductionInsulin analogues are structurally modified molecules with altered pharmaco-kinetic and -dynamic properties compared to regular human insulin used by diabetic patients. While these compounds are tested for undesired mitogenic effects, an epidemiological discussion is ongoing regarding an association between insulin analogue therapy and increased cancer incidence, including breast cancer. Standard in vivo rodent carcinogenesis assays do not pick up this possible increased carcinogenic potential.MethodsHere we studied the role of insulin analogues in breast cancer development. For this we used the human relevant mammary gland specific p53R270H/+WAPCre mouse model. Animals received life long repeated treatment with four different insulin (−like) molecules: normal insulin, insulin glargine, insulin X10 (AspB10) or insulin-like growth factor 1 (IGF1).ResultsInsulin-like molecules with strong mitogenic signaling, insulin X10 and IGF1, significantly decreased the time for tumor development. Yet, insulin glargine and normal insulin, did not significantly decrease the latency time for (mammary gland) tumor development. The majority of tumors had an epithelial to mesenchymal transition phenotype (EMT), irrespective of treatment condition. Enhanced extracellular signaling related kinase (Erk) or serine/threonine kinase (Akt) mitogenic signaling was in particular present in tumors from the insulin X10 and IGF1 treatment groups.ConclusionsThese data indicate that insulin-like molecules with enhanced mitogenic signaling increase the risk of breast cancer development. Moreover, the use of a tissue specific cancer model, like the p53R270H/+WAPCre mouse model, is relevant to assess the intrinsic pro-carcinogenic potential of mitogenic and non-mitogenic biologicals such as insulin analogues.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0518-y) contains supplementary material, which is available to authorized users.