Regular Human Insulin Research Articles

Concentrated insulins: History and critical reappraisal.

The earliest marketed insulins were crude acidic formulations with concentrations of ≤10 units/mL. Since the early 1920s, insulins have improved continually, via bioengineering, process, and chemical modifications. Today, most insulin formulations have a concentration of 100 units/mL (U100). However, more concentrated insulin formulations (200, 300, and 500 units/mL; U200, U300, and U500, respectively) are also available. There is a tendency to assume that concentrated insulins are similar, both to each other and to their U100 counterparts, but this is not always the case: two concentrated insulins, namely insulin degludec U200 and insulin lispro U200, are bioequivalent to their U100 counterparts, whereas regular human insulin U500 and insulin glargine U300 are not. The advent of these concentrated insulins offers greater opportunities to provide tailored therapy for patients; it also introduces potential confusion, and highlights the need for prescriber and patient education. Precise and accurate dedicated insulin delivery devices are also necessary for the safe use of these concentrated insulins. Although some clinicians only use concentrated insulin with obese and severely insulin-resistant patients, other patients would also benefit from the reduced injection volume associated with concentrated insulins, or the modified time-action profile of some concentrated insulins. The aim of this review is to enhance understanding of the historic development and the safe and effective use of concentrated insulins in clinical practice.

Pharmacokinetics and Pharmacodynamics of Human Regular U-500 Insulin Administered via Continuous Subcutaneous Insulin Infusion vs. Subcutaneous Injection in Adults with Type 2 Diabetes and High Insulin Requirements

There have been no euglycemic clamp studies on U-500R in obese patients with type 2 diabetes (T2DM) and high insulin requirements. This open-label, randomized, 2-way crossover, euglycemic clamp study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of U-500R administered by continuous subcutaneous insulin infusion (CSII; using an investigational Omnipod® U-500 Insulin Management System) compared to subcutaneous injection (SCI) (using a U-100 syringe), in adults with T2DM requiring >150 U/day of insulin.

Clinical Evaluation of MK-2640: An Insulin Analog With Glucose-Responsive Properties.

The goal of this investigation was to examine clinical translation of glucose responsiveness of MK-2640, which is a novel insulin saccharide conjugate that can bind the insulin receptor or mannose receptor C type 1 (MRC1), the latter dependent upon glucose concentration. In a rising dose study in 36 healthy adults under euglycemic clamp conditions, rising exposures revealed saturation of MK-2640 clearance, likely due to saturation of clearance by MRC1. Potency of MK-2640 was ~25-fold reduced relative to regular human insulin. In a randomized, 2-period crossover trial in 16 subjects with type 1 diabetes mellitus to evaluate glucose-responsiveness of i.v. administered MK-2640, we were unable to demonstrate a glucose-dependent change in MK-2640 clearance, although a significant glucose-dependent augmentation of glucose infusion rate was observed. These pharmacokinetic (PK) and pharmacodynamic (PD) data provide crucial insights into next steps for developing an insulin saccharide conjugate as a clinically effective glucose-responsive insulin analog.

Effect of insulin on thyroid cell proliferation, tumor cell migration, and potentially related mechanisms

ABSTRACTBackground: Diabetes has recently been identified as a risk factor for a variety of cancers, possibly due to hyperinsulinemia or exogenous insulin use. Thyroid cancer is the most common endocrine malignancy, and its incidence has been exponentially increasing worldwide at an alarming rate. The aim of this study was to establish whether insulin use affects thyroid cancer development and progression, specifically cell proliferation and migration in vitro.Methods: In this study, we investigated the effects of the insulin agents most commonly used in the clinic, regular human insulin (HI) and insulin glargine (IG), on the proliferation and migration of thyroid cells.Results: Both HI and IG affected the thyroid cells in a dose-dependent manner and at high concentrations significantly promoted thyroid cell proliferation and tumor cell migration. The promoting effect might be elicited by activation of the insulin receptor and insulin-like growth factor-1 receptor and through the downstream Akt-signaling pathway, which inhibits the activity of the tumor-suppressor FoxO3a. In particular, MAPK-signaling cascades were activated in papillary thyroid carcinoma cell-1 cells but not in follicular rat thyroid-5 cells.Conclusion: The in vitro evidence demonstrated that HI and IG can promote thyroid cell proliferation and tumor cell migration at supraphysiological concentrations, but the effect was not significant at low concentrations. Whether high-dose insulins could affect diabetic patients with thyroid cancer or undetected (pre)cancerous lesions needs further in vivo study.Abbreviations: HI: human regular insulin; IG: insulin glargine; IR: insulin receptor; IGF-1R: insulin-like growth factor-1 receptor; Akt: protein kinase B (PKB); MAPK: mitogen-activated protein kinase; FoxO3a: the forkhead box-containing protein: class O 3a

Production costs and potential prices for biosimilars of human insulin and insulin analogues

IntroductionHigh prices for insulin pose a barrier to treatment for people living with diabetes, with an estimated 50% of 100 million patients needing insulin lacking reliable access. As insulin analogues...

Human Regular 500 units/mL Insulin Therapy: A Review of Clinical Evidence and New Delivery Options.

Human regular U-500 insulin (U-500), a fivefold concentrated form of U-100 regular human insulin, was introduced to address the insulin needs of patients with severe insulin resistance (1). Severe insulin resistance has historically been characterized by patients with total daily insulin dose (TDD) requirements exceeding 200 units/day (1). With the increasing prevalence of diabetes and obesity in the United States, severe insulin resistance has become more common, increasing the need for U-500. The safe and effective use of U-500 requires careful monitoring to optimize glycemic control while minimizing the risk of hypoglycemia. The elevated risk of medication errors associated with U-500 therapy and a lack of clear guidelines for its use may have been responsible for its underutilization by both patients and health care providers (HCPs). In a survey administered to internal medicine physicians and ward nurses evaluating the inpatient use of U-500, 47% of respondents said they were “very uncomfortable” with the use of U-500 (2). A 2013 article published by the Institute for Safe Medication Practices (ISMP) reported on an increasing number of medication error reports and complaints from HCPs related to the use of U-500 (3). To address these medication errors, innovations (i.e., a dedicated U-500 syringe and a U-500 pen delivery device) have been developed to help solve dosing confusion issues and potentially enhance HCP and patient comfort with U-500 therapy. Here, we review the available evidence for U-500 and the innovations for its delivery. When considering the use of U-500, patients and HCPs must be aware of the unique pharmacokinetic/pharmacodynamic (PK/PD) profile that distinguishes it from both basal insulins and prandial insulins. Unlike other insulins, U-500 covers both the basal and prandial insulin needs of patients. This unique PK/PD profile allows for its use as monotherapy, and patients can inject smaller volumes with fewer injections …

Treatment Patterns in Patients with Type 2 Diabetes Treated with Human Regular U-500 Insulin—A Retrospective Claims Database Analysis

Human regular U-500 insulin (U-500R) is highly concentrated with both basal and prandial activity. It can be used as insulin monotherapy. This study sought to provide a better understanding of treatment patterns in a real-world environment for patients treated with U-500R. Patients with type 2 diabetes initiating U-500R between 2010 and 2013 (N=1582) were selected from Truven Health MarketScan® database. The study had 3 periods: pre-index (12 month before initiation), post-index (12 month after initiation or until U-500R discontinuation), and follow-up (12 month after post-index). U-500R treatment patterns, medication possession ratio (MPR), and persistence with its contributing baseline factors were examined. The resumption of U-500R was studied during follow-up (i.e., after a gap ≥ 60 days between ends of supply from one fill to the next). During post-index, 74.1% of patients had U-500R claims that did not overlap with other insulins. Only 7.6% had continuous U-500R claims overlapping ≥ 60 days with continuous claims of other insulins. The median U-500R average daily dose was 333 units. Among 12patients with more than one U-500R fill, 54.39% had MPR ≥80% and 26.08% patients between 60% and 80%. Within one year, 849 patients discontinued U-500R. Median time to discontinuation was 264 days. Patients 45 to 75 years old, treated with more types of insulins, or with rapid acting insulin use during pre-index were less likely to have a U-500R treatment gap (P <0.05). During follow-up, 602 (70.9%) of patients resumed U-500R. The median time from end of post-index to U-500R restart was 135 days. Out of the 733 patients with U-500R use beyond one year, 286 patients discontinued U-500R in the second year and 447 continued U-500R beyond two years. The study suggests that U-500R is commonly used as insulin monotherapy. The observed adherence/persistence could be the result of the simplicity of U-500R regimen, which might benefit high-dose insulin-treated patients. Disclosure J. Chen: None. X. He: None. C.Y. Kao: None. J.A. Jackson: Other Relationship; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Human Regular U-500 Insulin via Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Adults with T2D—The VIVID Study—All Randomized Population

VIVID is the first prospective randomized controlled trial evaluating CSII (using an investigational Omnipod U-500™ Insulin Management System) vs. MDI (TID) with U-500R (Humulin® R U-500). This was a 26-week, open-label, multicenter, parallel study in adults with T2D on high dose insulin (201-600 units/day) with or without other antihyperglycemic agents (NCT02561078). We present results for the all randomized population (N=420); results for the primary population (excluding participants on concomitant GLP-1 RAs or SGLT2 inhibitors) are reported separately. Baseline characteristics were similar between arms. Without adjusting for multiplicity, CSII demonstrated significantly greater reduction in A1C and FPG at a lower total daily dose vs. MDI at 26 weeks. Also, a higher percentage of participants on CSII reached A1C targets <7.0%, <7.5%, and <8.0%. Severe hypoglycemia rates were low. Other hypoglycemia rates were similar (documented symptomatic) or higher (nocturnal) for CSII vs. MDI. Weight gain was similar (Table). In the all randomized population, U-500R via CSII demonstrated greater efficacy at a lower dose with a higher nocturnal hypoglycemia rate vs. MDI. CSII with U-500R may be a viable option for patients with T2D on high dose insulin. Individualized dose titration will be important for safely achieving glycemic targets. Disclosure G. Grunberger: Research Support; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc.. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Janssen Pharmaceuticals, Inc.. A. Bhargava: None. T.T. Ly: Employee; Self; Insulet Corporation. H. Zisser: Employee; Self; Verily Life Sciences LLC.. Stock/Shareholder; Self; Verily Life Sciences LLC. L. Ilag: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.K. Malone: Employee; Self; Eli Lilly and Company. S. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company.

Patient Reported Outcomes (PRO) in a Study of Human Regular U-500 Insulin (U-500R) Delivered by Continuous Subcutaneous Insulin Infusion (CSII) or Multiple Daily Injections (MDI) in Patients with T2D

Persons with T2D treated with U-500R have shown improved glycemic control. This prospective analysis evaluated the impact on PRO of U-500R delivered by CSII (using an investigational Omnipod U-500TM Insulin Management System) or MDI (using a U-100 syringe). In this 26-week (week), open-label, parallel trial, 420 patients treated with >200 units/day of insulin for T2D were randomized to CSII (n=209) or MDI (n=211) treatment groups. The Treatment-Related Impact Measure for Diabetes (TRIM-D) and Diabetes Device (TRIM-DD) questionnaires were assessed at baseline, week 14, and week 26. Results are shown in Table 1. TRIM-D scores (overall score and all 5 domain scores) and TRIM-DD overall score in both groups improved significantly from baseline to week 26 (p<0.05). At week 26, change in baseline score for the CSII group was significantly higher than the MDI group in all TRIM-D measures (p<0.05). At week 26, there were no significant differences in the change from baseline score between the CSII and MDI groups in TRIM-DD overall or its domains. In summary, the U-500R CSII device scored significantly better than MDI in the perceived impact on diabetes treatment (TRIM-D) but not for diabetes device (TRIM-DD). PROs for diabetes treatment improved significantly from baseline to week 26 in patients treated with U-500R by either CSII or MDI. Disclosure X. Peng: Employee; Self; Eli Lilly and Company. J. Chen: None. L. Fan: Employee; Self; Eli Lilly and Company. L. Ilag: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. T.T. Ly: Employee; Self; Insulet Corporation. J. Johnson: Employee; Self; Eli Lilly and Company.

Pharmacokinetics and Pharmacodynamics of Human Regular U-500 Insulin (U-500R) Administered via Continuous Subcutaneous Insulin Infusion (CSII) vs. Subcutaneous Injection (SCI) in Adults with Type 2 Diabetes and High Insulin Requirements

There have been no euglycemic clamp studies on U-500R in obese patients with type 2 diabetes mellitus (T2DM) and high insulin requirements. This open-label, randomized, 2-way crossover, euglycemic clamp study (NCT02588950) evaluated PK/PD of U-500R administered by CSII (using an investigational Omnipod® U-500 Insulin Management System) compared to SCI (using a U-100 syringe), in adults with T2DM requiring >150 U/day of insulin. Subjects (N=11, mean BMI: 39.6 kg/m2, mean A1C: 10.2%) each received a 100 U dose via CSII [primed with a 12-hour (hour) U-500R basal infusion] and a single SCI, both followed by a 24 hour clamp. Serum insulin concentrations were corrected for endogenous insulin using C-peptide for both administration methods. Basal infusion values in CSII were adjusted with baseline and model corrections. Following SCI, using model corrected method, time of maximum observed drug concentration (tmax) was about 1.5 hour longer compared to CSII [LSmean ratio (90% CI): 1.46 (1.08, 1.97)]. There was no statistically significant difference between CSII and SCI in median tmax, areas under the curve [AUC(0-24), AUC(0-tlast)], and maximum concentration. There was no statistically significant difference between CSII and SCI in median time to maximum glucose infusion rate (GIR) [CSII: 7.2 hour; SCI: 8 hour], median time of 50% of maximum GIR before Rmax (tRmax50) [CSII: 2.85 hour; SCI: 3.59 hour], and median time to last GIR [CSII: 18.9 hour; SCI: 14.6 hour]. No severe hypoglycemia was reported. U-500R was well tolerated whether given by syringe or CSII. The PK/PD profiles and time action parameters were similar with both methods of administration. Disclosure X. Ma: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R.P. Prescilla: None. S. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L. Morrow: Stock/Shareholder; Self; ProSciento. Employee; Spouse/Partner; Eli Lilly and Company. J.A. Jackson: Other Relationship; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company. D. Leishman: Employee; Self; Eli Lilly and Company.

Human Regular U-500 Insulin via Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Adults with T2D—The VIVID Study, Primary Population

VIVID is the first prospective, randomized controlled trial to assess efficacy and safety of U-500R (Humulin® R U-500) administered by CSII (using an investigational Omnipod U-500™ Insulin Management System) vs. MDI (TID). This 26-week, open-label, multicenter, parallel study (NCT02561078) enrolled adults with T2D on 201-600 units of insulin/day with or without other antihyperglycemic agents. We report data for the primary population (N=340), excluding participants on concomitant GLP-1 RAs or SGLT2 inhibitors. Data for the all-randomized population are reported separately. Baseline characteristics were similar between arms. CSII showed noninferior A1C reduction vs. MDI (primary objective) and superior FPG reduction at 26 weeks with adjustment for multiplicity. CSII showed significantly greater A1C reduction at a lower total daily dose with no multiplicity adjustment. Clinically important hypoglycemia rates (<54 mg/dL) and weight gain were similar; severe and nocturnal (≤70 mg/dL) hypoglycemia rates were statistically higher for CSII vs. MDI (Table). In this population, U-500R via CSII had greater efficacy at a lower dose vs. MDI with higher hypoglycemia rates for some categories. CSII with U-500R may be a viable option for T2D patients on high-dose insulin. Individualized dose titration will be important to safely achieve A1C targets. Disclosure G. Grunberger: Research Support; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Janssen Pharmaceuticals, Inc.. A. Bhargava: None. T.T. Ly: Employee; Self; Insulet Corporation. H. Zisser: Employee; Self; Verily Life Sciences LLC.. Stock/Shareholder; Self; Verily Life Sciences LLC. L. Ilag: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.K. Malone: Employee; Self; Eli Lilly and Company. S. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company.

Impact of Endogenous Insulin Adjustment Methods on the Assessment of Insulin Pharmacokinetics and Pharmacodynamics

Assessing reliable insulin pharmacokinetics (PK) and pharmacodynamics (PD) following an exogenous insulin administration is a scientific challenge due to the circulating endogenous insulin. Effect of exogenous insulin on the endogenous insulin through the sensitive glucose homeostatic system in the body could further confound the PK/PD data. We compared results of PK/PD parameters of methods in literature for the estimation of insulin PK and PD, namely total method without adjustment (method 1), a simple baseline method (method 2), elimination rate constant method (method 3), empirical C-peptide correction method (method 4), and conventional PK/PD modeling method (method 5). We also developed new PK/PD modeling method reflecting the effect of glucose on endogenous insulin release based on C-peptide (method 6). Subject-level time-matching insulin and glucose concentrations without external glucose administration were collected from clinical trials with regular human insulin administration to healthy subjects under fasting conditions (n=23). Primary insulin PK parameters (i.e., the maximum concentration (Cmax) and area under the concentration-time profile (AUC)) were estimated using subjects’ insulin, glucose and C-peptide level data. Our results indicate that insulin AUC and Cmax differ by up to 32 and 17%, respectively, among different methods. Further, the contribution of endogenous insulin to total insulin AUC is estimated to be approximately 55% but varies depending upon estimation methods. Insulin PD parameters are apparently similar among different methods (e.g., area under the glucose concentration-time profile; 8121.4 and 8293.3 mg/dL*min for method 1-5 and method 6, respectively). The results call for a careful selection of the method for the assessment of insulin PK and PD parameters depending upon the objectives of study as the relationship between PK and PD could vary among methods and may lead to misinterpretation of data. Disclosure S.M. Chung: None. J.A. Penzenstadler: None. M. Khurana: None. C. Sahajwalla: None.

Efficacy and Safety of Rapid-Acting Insulin Analogs in Special Populations with Type 1 Diabetes or Gestational Diabetes: Systematic Review and Meta-Analysis.

IntroductionTo assess the efficacy and safety of three available rapid-acting insulin analogs (insulins lispro, aspart and glulisine, respectively) in pregnant women, children/adolescents and people using continuous subcutaneous insulin infusion (CSII) with type 1 diabetes.MethodsPubMed, EMBASE and Cochrane Reviews were searched electronically, and their bibliographies examined to identify suitable studies for review and inclusion in a meta-analysis. Eligible studies were randomized controlled trials that reported data on relevant clinical outcomes. A different reviewer abstracted data for each of the three subpopulations, and one reviewer abstracted data for all three. Any differences were resolved by consensus or by consulting a fourth reviewer.ResultsIn people on CSII, rapid-acting insulin analogs lowered postprandial plasma glucose post-breakfast to a greater extent than did regular human insulin (RHI) (mean difference: − 1.63 mmol/L [95% confidence interval − 1.71; − 1.54]), with a comparable risk of hypoglycemia and a trend for lower glycated hemoglobin. In the pediatric population, glycemic control was similar with rapid-acting insulin analogs and RHI, with no safety concerns. Meta-analysis indicated severe hypoglycemic events were comparable for rapid-acting insulin analogs versus RHI (risk difference: 0.00 [95% confidence interval − 0.01; 0.01]). In the pregnancy group, insulin lispro and insulin aspart were safe and effective for both mother and fetus, with glycemic control being at least as good as with RHI. There were no data on insulin glulisine during pregnancy.ConclusionRapid-acting insulin analogs appear generally safe and effective in these special populations; however, additional trials would be helpful.FundingNovo Nordisk A/S.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0411-7) contains supplementary material, which is available to authorized users.

Type 1 Diabetes in Children and Adolescents.

Type 1 Diabetes in Children and Adolescents.

Treating Type 1 Diabetes Mellitus with a Rapid-Acting Analog Insulin Regimen vs. Regular Human Insulin in Germany: A Long-Term Cost-Effectiveness Evaluation.

The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany. The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5years, duration of diabetes of 8.6years, and baseline glycosylated hemoglobin of 7.39%. Regular human insulin and rapid-acting analog insulin regimens reduced glycosylated hemoglobin by 0.312 and 0.402%, respectively. Compared with human insulin, hypoglycemia rate ratios with rapid-acting analog insulin were 0.51 (non-severe nocturnal) and 0.80 (severe). No differences in non-severe diurnal hypoglycemia were modeled. Discount rates of 3% were applied to future costs and clinical benefits accrued over the 50-year time horizon. In the base-case analysis, rapid-acting analog insulin was associated with an improvement in quality-adjusted life expectancy of 1.01 quality-adjusted life-years per patient (12.54 vs. 11.53 quality-adjusted life-years). Rapid-acting analog insulin was also associated with an increase in direct costs of €4490, resulting in an incremental cost-effectiveness ratio of €4427 per quality-adjusted life-year gained vs. human insulin. Sensitivity analyses showed that the base case was driven predominantly by differences in hypoglycemia; abolishing these differences reduced incremental quality-adjusted life expectancy to 0.07 quality-adjusted life-years, yielding an incremental cost-effectiveness ratio of €74,622 per quality-adjusted life-year gained. Rapid-acting analog insulin is associated with beneficial outcomes in patients with type 1 diabetes and is likely to be considered cost effective in the German setting vs. regular human insulin.

Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake in Healthy Men.

Insulin administration to the central nervous system inhibits food intake, but this effect has been found to be less pronounced in female compared with male organisms. This sex-specific pattern has been suggested to arise from a modulating influence of estrogen signaling on the insulin effect. We assessed in healthy young men whether pretreatment with transdermal estradiol interacts with the hypophagic effect of central nervous insulin administration via the intranasal pathway. According to a 2×2 design, two groups of men (n = 16 in each group) received a 3-day transdermal estradiol (100 µg/24 h) or placebo pretreatment and on two separate mornings were intranasally administered 160 IU regular human insulin or placebo. We assessed free-choice ad libitum calorie intake from a rich breakfast buffet and relevant blood parameters in samples collected before and after breakfast. Estrogen treatment induced a 3.5-fold increase in serum estradiol concentrations and suppressed serum testosterone concentrations by 70%. Independent of estradiol administration, intranasal insulin reduced the intake of carbohydrates during breakfast, attenuating in particular the consumption of sweet, palatable foods. Estradiol treatment per se decreased protein consumption. We did not find indicators of eating-related interactions between both hormones. Results indicate that, in an acute setting, estrogen does not interact with central nervous insulin signaling in the control of eating behavior in healthy men. Insulin and estradiol rather exert independent inhibiting effects on macronutrient intake.

Rethinking the Viability and Utility of Inhaled Insulin in Clinical Practice.

Despite considerable advances in pharmacotherapy and self-monitoring technologies in the last decades, a large percentage of adults with diabetes remain unsuccessful in achieving optimal glucose due to suboptimal medication adherence. Contributors to suboptimal adherence to insulin treatment include pain, inconvenience, and regimen complexity; however, a key driver is hypoglycemia. Improvements in the PK/PD characteristics of today's SC insulins provide more physiologic coverage of basal and prandial insulin requirements than regular human insulin; however, they do not achieve the rapid on/rapid off characteristics of endogenously secreted insulin seen in healthy, nondiabetic individuals. Pulmonary administration of prandial insulin represents an attractive option that overcomes limitations of SC insulin by providing more a rapid onset of action and a faster return of action to baseline levels than SC administration of rapid-acting insulin analogs. This article reviews the unique PK/PD properties of a novel inhaled formulation that support its use in patient populations with T1D or T2D.

Insulin for the treatment of women with gestational diabetes.

Insulin for the treatment of women with gestational diabetes.

Cuidados al adulto postoperado en la administración de insulina

Introducción: Los pacientes adultos postoperados de cirugía cardiaca (POCC), con o sin diabetes mellitus tipo 2 (DM T2), comúnmente presentan descontrol glucémico, favoreciendo la presencia de complicaciones que aumentan la morbimortalidad. Objetivo: Describir cuidados de enfermería al paciente adulto POCC con o sin DM T2 en la administración de insulina. Metodología: Revisión sistematizada con metodología integradora. Pasos de la enfermería basada en la evidencia: pregunta clínica; descriptores en ciencias de la salud; atención de enfermería, administración y dosificación, insulina regular humana e insulina isófana humana en español, inglés y portugués; búsqueda de la evidencia científica (SciELO, CINAHL, PubMed, LILACS, CUIDEN), artículos en texto completo publicados del 1 enero 2012 a 31 marzo 2017; lectura y evaluación de la evidencia científica con tabla de evidencia; y análisis de contenido a profundidad para integración de la evidencia. Resultados: se encontraron 20 artículos que cumplieron con los criterios de inclusión. Prevalecieron los estudios con nivel de evidencia observacionales III/C, publicados en países anglosajones en inglés del área médica. Se identificaron cinco dimensiones: valoración de enfermería, medición de la glucosa en sangre, control glucémico, las complicaciones por hipoglucemia o hiperglucemia, y recomendaciones o seguimientos para enfermería. Conclusiones: los cuidados de enfermería basados en la evidencia, pueden mejorar el control metabólico y prevenir las complicaciones por hipoglucemia e hiperglucemia.

A Diabetic Woman with Insulin Injection Abscesses

A 50-year-old diabetic woman developed multiple abscesses after daily injections of subcutaneous regular human insulin. Initial cultures from the draining fluid revealed no organisms, and the patient was unresponsive to multiple courses of antibiotics including doxycycline, amoxicillin/clavulanic acid, and intravenous vancomycin and piperacillin/tazobactam. After consulting dermatology, the patient underwent punch biopsy and tissue culture. The tissue culture grew mycobacterium fortuitum after 22 days of incubation. The patient was diagnosed with non-tuberculous mycobacterial infection and began to improve after treatment with ciprofloxacin. Non-tuberculous mycobacteria are common in the environment, although systemic manifestations of infection are rare in healthy individuals. In this paper, we discuss the risk factors, diagnostic methods, and treatment recommendations for these types of infections.