Insulin Analogues Research Articles

Cytoplasmic soluble Lispro insulin production in Escherichia coli, product yield optimization and physiochemical characterization

Lispro is an insulin analog with an accelerated action profile suitable for post-prandial injections and glycemic control in diabetes. Insulin production in Escherichia coli leads to inclusion body formation due to its reducing inner environment. This conventional platform requires refolding procedures with relatively low recovery resulting in product loss and increased production time. We introduced a novel approach for high yield cytoplasmic soluble expression of Lispro insulin in E. coli. Presence of the SUMO fusion tag and being expressed in SHuffle T7 improved the solubility of Lispro precursor to10 mg/L. Product yield increased to approximately 5-fold after the optimization procedure. The scalability of the optimized condition was confirmed in a fed-batch fermentor that resulted in high cell density and high yield soluble expression (540 mg/L). 25 mg/L bioactive Lispro insulin was generated and purified. The final product was identical to the commercial analog based on physiochemical characterization analyses.

Hyperglycemia in hospitalized patients of a tertiary care hospital: prevalence and treatment in two cross-sectional evaluations (2011-2020).

A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.

Selective N-Terminal Acylation of Peptides and Proteins with Tunable Phenol Esters.

Selective modification of peptides and proteins is of foremost importance for the development of biopharmaceuticals and exploring biochemical pathways, as well as other applications. Here, we present a study on the development of a general and easily applicable selective method for N-terminal acylation of biomolecules, applying a new type of phenol esters. Key to the success was the development of highly tunable phenol activators bearing in the ortho-position, sulfonic acid or sulfonamide, acting as a steric shield for hydrolysis, and electron-withdrawing groups in the other ortho- and para-position for controlling the reactivity of the activated phenol esters. A library of heptapeptides, testing all 20 natural amino acids positioned at the N-terminal, were acylated in a selective manner at the N-terminus. The majority showed high conversion and excellent Nα-selectivity. Several biologically relevant biomolecules, including DesB30 insulin and human growth hormone, could also be modified at the N-terminal in a highly selective way, exemplified by either a fluorophore or a fatty acid sidechain. Finally, taking advantage of the possibility to accurately adjust the reactivity of the phenol esters, we present a potential strategy for the construction of dual active biopharmaceuticals through the employment of a bifunctional acylation linker and demonstrate its use in the creation of a GLP-1 insulin analogue, coupled through the lysine residue of GLP-1 and the N-terminal PheB1 amine of DesB30 insulin.

Current Status and Emerging Options for Automated Insulin Delivery Systems.

Combining technologies including rapid insulin analogs, insulin pumps, continuous glucose monitors, and control algorithms has allowed for the creation of automated insulin delivery (AID) systems. These systems have proven to be the most effective technology for optimizing metabolic control and could hold the key to broadly achieving goal-level glycemic control for people with type 1 diabetes. The use of AID has exploded in the past several years with several options available in the United States and even more in Europe. In this article, we review the largest studies involving these AID systems, and then examine future directions for AID with an emphasis on usability.

Detection of insulin analogues and large peptides >2kDa in urine.

Insulin analogues and large bioactive peptides may be used by athletes to enhance performance and are banned by the World Anti-Doping Agency (WADA). In addition to insulin analogues, the large peptides include a structurally diverse set of peptides including analogues of growth hormone releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1), and mechano-growth factor (MGF). Detection of this class of peptides is difficult due to their absorptive losses and presence at very low concentrations in urine. In this report, a high throughput method is described that allows sensitive detection of four classes of large peptides in one assay. Sample extraction is performed by ultrafiltration to concentrate the urine followed by solid phase extraction in a 96-well micro-elution plate. Peptides in the urine samples are detected on a triple quadrupole mass spectrometer coupled to standard flow liquid chromatography. The method was validated and evaluated for limit of detection, limit of identification, specificity, precision, carryover, recovery, matrix interference, and post-extraction stability. The limit of detection for insulin analogues is between 5 and 25 pg/ml and between 5 and 50 pg/ml for the other peptide classes. Specificity was good with no detection of interfering peaks in blank urine samples. Carryover from a high concentration sample was not observed and the post-extraction stability was between 77% and 107%. The method was able to detect insulin analogues in three diabetic urine samples. Increased screening for this class of peptides will improve detection and deterrence.

Insulin aspart dimer dissociation in water

The insulin hormone is stored in the hexameric form and dissociates to the dimeric form and finally to the active monomeric form. When insulin secretion is impaired, thereby affecting various metabolic processes, as a final response, insulin analogs are subcutaneously injected before meals to facilitate glucose metabolism. Depending on the molecular details, analogs are rapid or slow acting based on the dissociation rate of the dimer to monomer. Insulin aspart is a recombinant human insulin analog, acting faster than regular human insulin. Despite its practical and elementary importance, the process of insulin aspart dimer dissociation is relatively unknown. Here, we combined molecular dynamics simulations and umbrella sampling to characterize the energetic and structural features of dissociation of the insulin aspart dimer. Like previous studies on human insulin (another well studied analog), insulin aspart can also display a wide spectrum of pathways for dimer dissociation from dissociation happening without a major change in the monomer structure to dissociation that is coupled with unfolding of a protein. Additionally, water plays a vital role in the dissociation of the insulin aspart by stabilizing the monomers in the dissociated state. Our study shows the molecular details, such as the variation in the structure and orientation and conformational changes along the minimum energy pathways in the process of dissociation of the insulin aspart dimer.

Diurnal Variation of Real-Life Insulin Sensitivity Factor Among Children and Adolescents With Type 1 Diabetes Using Ultra-Long-Acting Basal Insulin Analogs

BackgroundEstimation of insulin sensitivity factor (ISF) is essential for correction insulin doses calculation. This study aimed to assess real-life ISF among children and adolescents with type 1 diabetes using ultra-long-acting basal insulin analogs and to detect factors associated with ISF among those patients.MethodsThis prospective observational study was conducted at Sohag University Hospital, Egypt, and included 93 participants aged 6–18 years, diagnosed with T1DM for at least 1 year and using insulin glargine 300 Units/mL or insulin degludec 100 Units/mL as basal insulin. The ISF, insulin-to-carbohydrate ratio (ICR) and insulin doses were initially assessed then adjusted as required. The participants were regularly contacted throughout the follow-up period. Glycemic control parameters were assessed after 3 months.ResultsThe ISF showed diurnal variation with higher correction dose requirements for the morning than for the rest of the day (p < 0.001). This pattern of diurnal variation was found in participants with different pubertal stages and in participants using either type of ultra-long acting basal insulin analogs. There was no significant difference between the ISF calculated according to the 1800 rule [1800/Total daily insulin dose (TDD)] and the morning ISF (p = 0.25). The 1800 rule-calculated ISF was significantly lower than the actual ISF for the afternoon (p < 0.001) and the evening (p < 0.001). ISF at different times of the day were significantly correlated with age, body mass index, pubertal stage, diabetes duration, TDD, and ICR. Multiple regression analysis revealed that ICR was the most significant factor associated with ISF. Linear regression analysis revealed that the ISF (in mg/dL) for any time of the day could be estimated as 5.14 × ICR for the same time of the day (coefficient = 5.14, 95% confidence interval: 5.10–5.19, R2 = 0.95, p < 0.001).ConclusionDiurnal variation of ISF that had to be considered for proper calculation of correction doses. This diurnal variation was found in children and adolescents with different pubertal stages. The 1800 rule was appropriate for the morning correction doses but not in the afternoon or the evening. The TDD and the ICR could be used for ISF estimation.

Biosimilars are essential for sustainable healthcare systems; however, key challenges remain as seen with long-acting insulin analogues

Biosimilars are essential for sustainable healthcare systems; however, key challenges remain as seen with long-acting insulin analogues

Use of Fast-Acting Insulin Analog for Preparing a Pharmaceutical Composition for Preventing, Treating, or Alleviating Diabetes

Diabetes is the most common disease in India that mostly affects adult people and reduces physical strength. Diabetes decreases insulin production in the human body that creates various physical disturbances such as damage to the heart, stroke, and others. In the past decades, medical treatments have followed long-acting insulin that reduces life expectancy rate and increases mortality rate in India. Along with that, in the present time, India's medical treatment has adopted the pharmaceutical composition of insulin to prevent diabetes and manage blood sugar in the human body. In this regard, this research study has selected some previous research papers to understand the importance of fast-acting insulin analogue to prevent diabetes. According to the secondary information, most of the medical treatment process in India has adopted fast-acting insulin analogue to prevent diabetes. Moreover, though fast-acting insulin analogue India reduces mortality rate and increases the life expectancy of adult people in India. Keyword : Metabolic disturbances, E-bacteria, amino acids, Regular Human Insulin (RHI).

Management of Type 1 Diabetes in Children in the Outpatient Setting.

Management of Type 1 Diabetes in Children in the Outpatient Setting.

Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation.

The mutant proinsulin syndrome is a monogenic cause of diabetes mellitus due to toxic misfolding of insulin’s biosynthetic precursor. Also designated mutant INS-gene induced diabetes of the young (MIDY), this syndrome defines molecular determinants of foldability in the endoplasmic reticulum (ER) of β-cells. Here, we describe a peptide model of a key proinsulin folding intermediate and variants containing representative clinical mutations; the latter perturb invariant core sites in native proinsulin (LeuB15→Pro, LeuA16→Pro, and PheB24→Ser). The studies exploited a 49-residue single-chain synthetic precursor (designated DesDi), previously shown to optimize in vitro efficiency of disulfide pairing. Parent and variant peptides contain a single disulfide bridge (cystine B19-A20) to provide a model of proinsulin’s first oxidative folding intermediate. The peptides were characterized by circular dichroism and redox stability in relation to effects of the mutations on (a) in vitro foldability of the corresponding insulin analogs and (b) ER stress induced in cell culture on expression of the corresponding variant proinsulins. Striking correlations were observed between peptide biophysical properties, degree of ER stress and age of diabetes onset (neonatal or adolescent). Our findings suggest that age of onset reflects the extent to which nascent structure is destabilized in proinsulin’s putative folding nucleus. We envisage that such peptide models will enable high-resolution structural studies of key folding determinants and in turn permit molecular dissection of phenotype-genotype relationships in this monogenic diabetes syndrome. Our companion study (next article in this issue) employs two-dimensional heteronuclear NMR spectroscopy to define site-specific perturbations in the variant peptides.

Survival Risk Analysis of Small Cell Lung Cancer Patients with Pre-Existing Type 2 Diabetes Mellitus: A Single-Center Retrospective Cohort Study.

PurposeWe aimed to investigate the clinicopathological characteristics and survival risk factors in small cell lung cancer (SCLC) patients with preexisting type 2 diabetes mellitus (preDM).Patients and MethodsAll patients with SCLC admitted to our hospital between January 2013 and August 2018 were followed up until August 2020 and retrospectively analyzed. Clinical characteristics of SCLC patients with and without preDM were extracted. Cox proportional hazards models were conducted to identify potential independent prognostic factors.ResultsOf 628 eligible individuals, 88 individuals had preDM. preDM was independently significantly associated with distant metastasis in all SCLC patients (p =0.016, OR=1.80, 95% CI 1.11–2.91), while preDM did not affect the outcome of SCLC patients (p=0.803, HR=1.04, 95% CI 0.79–1.36) by multivariate analysis. In the preDM group, the median overall survival (OS) was shorter in the insulin group than in the non insulin group (13.93 months versus 21.77 months, p=0.024). Multivariate analysis identified that insulin treatment was an independent unfavorable factor associated with OS (p =0.009, HR=2.10, 95% CI 1.19–3.64). In addition, poorer performance status (PS) and liver metastasis were also independent unfavorable prognostic factors (all p<0.01), while thoracic therapy significantly improved OS and decreased mortality risk in diabetic patients with SCLC (p<0.05).ConclusionpreDM may promote distant metastasis of SCLC while it is insulin therapy and not preDM which adversely affects the prognosis of SCLC patients. These findings indicate that enhancing blood glucose control and reducing insulin analog use may be essential to the improvement of the long-term survival of the diabetic population with SCLC.

Peptide Model of the Mutant Proinsulin Syndrome. II. Nascent Structure and Biological Implications.

Toxic misfolding of proinsulin variants in β-cells defines a monogenic diabetes syndrome, designated mutant INS-gene induced diabetes of the young (MIDY). In our first study (previous article in this issue), we described a one-disulfide peptide model of a proinsulin folding intermediate and its use to study such variants. The mutations (LeuB15→Pro, LeuA16→Pro, and PheB24→Ser) probe residues conserved among vertebrate insulins. In this companion study, we describe 1H and 1H-13C NMR studies of the peptides; key NMR resonance assignments were verified by synthetic 13C-labeling. Parent spectra retain nativelike features in the neighborhood of the single disulfide bridge (cystine B19-A20), including secondary NMR chemical shifts and nonlocal nuclear Overhauser effects. This partial fold engages wild-type side chains LeuB15, LeuA16 and PheB24 at the nexus of nativelike α-helices α1 and α3 (as defined in native proinsulin) and flanking β-strand (residues B24-B26). The variant peptides exhibit successive structural perturbations in order: parent (most organized) > SerB24 >> ProA16 > ProB15 (least organized). The same order pertains to (a) overall α-helix content as probed by circular dichroism, (b) synthetic yields of corresponding three-disulfide insulin analogs, and (c) ER stress induced in cell culture by corresponding mutant proinsulins. These findings suggest that this and related peptide models will provide a general platform for classification of MIDY mutations based on molecular mechanisms by which nascent disulfide pairing is impaired. We propose that the syndrome’s variable phenotypic spectrum—onsets ranging from the neonatal period to later in childhood or adolescence—reflects structural features of respective folding intermediates.

Abstract 5: Similar hypoglycemia duration with once-weekly insulin icodec versus insulin glargine U100 in insulin naïve or experienced patients with T2D

Insulin icodec* (icodec) is a novel once-weekly basal insulin analog in development. This post hoc analysis explored hypoglycemia duration using double-blinded CGM (Dexcom G6®) data from 2 phase 2, randomized, open-label, treat-to-target 16-week trials. One trial compared 3 titration algorithms of icodec vs. insulin glargine U100 (IGlar U100) in 205 insulin-naïve patients with T2D (NCT03951805), the other assessed 154 basal insulin-treated patients with T2D switching from any daily basal insulin to icodec with or without a 100% loading dose vs. IGlar U100 (NCT03922750). In line with ATTD guidelines, a hypoglycemic episode was defined as a CGM period of interstitial glucose (IG) <70 mg/dL for at least 15 min, ending when IG ≥70 mg/dL for at least 15 min. In the titration trial, hypoglycemia duration was similar across all arms: median overall hypoglycemic episode duration (IQR) was 35.0 (20.0, 70.0) min for icodec titrations A (SMBG 80-130 mg/dL ±21 U/wk) and B (80-130 mg/dL ±28 U/wk) and for IGlar U100 (80-130 mg/dL ±4 U/day), and 39.0 (24.0, 70.0) min for icodec titration C (70-108 mg/dL ±28 U/wk). The distribution pattern of hypoglycemic episodes by duration was similar across all treatment arms. Results were similar for nocturnal hypoglycemic episodes. Similarly, in the switch trial, the duration of hypoglycemia was similar between arms, irrespective of loading dose use: median overall hypoglycemic episode duration (IQR) was 40.0 (20.0, 75.0) min for icodec with loading dose, 40.0 (25.0, 80.0) min for icodec without loading dose, and 35.0 (20.0, 60.0) min for IGlar U100. The distribution pattern of hypoglycemic episodes by duration was similar across treatment arms. Similar results were seen for the nocturnal period.In conclusion, CGM-derived hypoglycemic episode duration was similar with icodec vs. IGlar U100 in insulin-naïve and insulin-experienced patients with T2D, regardless of titration algorithm or initial loading dose use. *Proposed INN.

Biosimilar insulins in international and domestic practice of pharmacist

In Ukraine, people with diabetes receive insulin, including insulin biosimilars in pharmacies, so pharmacists should increase their knowledge about biosimilar because they become more available in the coming years.&#x0D; The aim of the work was to summarize current information on insulin biosimilars.&#x0D; Research materials ‒ regulatory database information and scientific publications on biosimilars. Content analysis, bibliosemantic, analytical, generalizing analyzes were used.&#x0D; The terminology related to reproducible biological drugs (biosimilars) is difference and it depend on the regulatory agency or the country that controls the approve of drugs. Insulin was the first biopharmaceutical drug which was developed. For approving biosimilars, it is necessary to establish similarity with the reference drug in terms of safety, purity and efficacy. Regulatory of biosimilars and requirements for demonstration the biosimilarity are specified in regulatory of the EMA and WHO. The regulatory of the approving of biosimilar in Ukraine is harmonized with European regulatory. The rules on interchangeability are not determined by all regulatory agency. The International Diabetes Federation emphasizes the role of the pharmacist, stating that they should be well informed about the forms of insulin, includes biosimilars. In Ukraine, pharmacists must dispense insulin, including biosimilars, exactly in accordance to the prescription in which the trade name of insulin (or biosimilars) is indicated. Insulin biosimilars can be an alternative to original insulins that have lost patent protection by increasing the availability of drugs, which can lead to increased market competition and access insulin for patients.&#x0D; Based on the analysis of current information on biosimilars, generalizations about their terminology, aspects of manufecture, regulatory, interchangeability, prospects in the treatment of diabetes and their replacement of referens insulins are presented. The potential impact of biosimilar insulins to patients and the health care system was determinated. The importance of awareness of these drugs by pharmacists as part of the diabetic team are highlighted.

Time-series analysis of recent antihyperglycemic medication prescribing trends for a diverse sample of Medicare enrollees with type 2 diabetes mellitus in an integrated health system.

Despite high type 2 diabetes mellitus (T2DM) prevalence in Medicare enrollees, newer therapeutic options, and revised treatment guidelines, little is known about US antihyperglycemic prescribing trends after 2015. This research describes recent monthly antihyperglycemic prescribing trends in a large, diverse population of Medicare enrollees from the US Mid-Atlantic region. Encounter data (July 2018-July 2020) for Medicare enrollees 65 years of age or older with T2DM were extracted from electronic health records of a large integrated health system. Descriptive time-series regression models were estimated to describe monthly prescribing rates (ie, prescription orders per 100 eligible plan members with T2DM) overall and by medication subgroups for all-eligible and continuously-eligible samples. Trends in monthly prescription orders per 100 eligible plan members with T2DM were reported. The monthly all-eligible member sample (n > 22,000) exhibited an overall positive baseline monthly prescribing rate of 23.88 T2DM medication orders per 100 members with T2DM and a significant positive monthly prescribing rate trend (ie, change) of 0.12 T2DM medication orders per 100 members with T2DM (P < 0.05). Subgroup T2DM medication order rates per 100 members with T2DM at baseline were 16.28 for first-generation medications, 3.87 for human insulins, 3.04 for insulin analogs, 0.58 for second-generation medications, and 0.11 for combination medications. Human insulins, insulin analogs, and second-generation medications had positive monthly trends (P < 0.05). Among second-generation medications, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists had positive monthly trends (P < 0.05). Continuously eligible members with T2DM (n = 19,185) had no significant overall monthly prescribing trend; however, human insulins, insulin analogs, and second-generation medications and the SGLT-2 inhibitor class had positive monthly prescribing trends (P < 0.05). In a diverse Medicare sample, this study observed increasing monthly trends for second-generation medications, human insulins, and insulin analogs consistent with emerging evidence. Among second-generation medications, SGLT-2 inhibitors became the most commonly prescribed over time.

Functionally selective signaling and broad metabolic benefits by novel insulin receptor partial agonists

Insulin analogs have been developed to treat diabetes with focus primarily on improving the time action profile without affecting ligand-receptor interaction or functional selectivity. As a result, inherent liabilities (e.g. hypoglycemia) of injectable insulin continue to limit the true therapeutic potential of related agents. Insulin dimers were synthesized to investigate whether partial agonism of the insulin receptor (IR) tyrosine kinase is achievable, and to explore the potential for tissue-selective systemic insulin pharmacology. The insulin dimers induced distinct IR conformational changes compared to native monomeric insulin and substrate phosphorylation assays demonstrated partial agonism. Structurally distinct dimers with differences in conjugation sites and linkers were prepared to deliver desirable IR partial agonist (IRPA). Systemic infusions of a B29-B29 dimer in vivo revealed sharp differences compared to native insulin. Suppression of hepatic glucose production and lipolysis were like that attained with regular insulin, albeit with a distinctly shallower dose-response. In contrast, there was highly attenuated stimulation of glucose uptake into muscle. Mechanistic studies indicated that IRPAs exploit tissue differences in receptor density and have additional distinctions pertaining to drug clearance and distribution. The hepato-adipose selective action of IRPAs is a potentially safer approach for treatment of diabetes.

Similar Pharmacokinetics and Pharmacodynamics of Biosimilar SAR342434 Insulin Lispro and Japan-Approved Humalog Insulin Lispro in Healthy Japanese Subjects.

This phase 1 study compared the pharmacokinetic (PK) and glucose pharmacodynamic (PD) characteristics of biosimilar SAR342434 insulin lispro and Japan‐reference Humalog insulin lispro. This was a randomized, double‐blind, 2‐period, crossover study. Thirty‐six healthy Japanese male subjects underwent a 10‐hour euglycemic clamp following a single subcutaneous 0.3‐U/kg dose of SAR342434 or Humalog. Insulin lispro concentration and blood glucose were measured, and the glucose infusion rate (GIR) was adjusted to maintain the target blood glucose level. Primary PK end points were maximum plasma insulin lispro concentration and area under the plasma insulin concentration–time curve (AUC) from time 0 to the last quantifiable concentration. Primary PD end points were area under the GIR–time curve from time 0 to 10 hours and maximum GIR. PK exposure (maximum plasma concentration and AUC from time 0 to the last quantifiable concentration) and PD activity (GIR‐AUC from time 0 to 10 hours and maximum GIR) were similar between treatments. Geometric mean ratios were close to 1, and the corresponding 90% and 95%CIs (PK and PD activity, respectively) were within the 0.80 to 1.25 equivalence range. SAR342434 and Humalog were well tolerated. In healthy Japanese males, SAR342434 and Humalog showed similar PK exposure profiles and PD potency, in support of SAR342434 use as a biosimilar product.

Proteomic Changes to the Updated Discovery of Engineered Insulin and Its Analogs: Pros and Cons.

The destruction of β-cells of the pancreas leads to either insulin shortage or the complete absence of insulin, which in turn causes diabetes Mellitus. For treating diabetes, many trials have been conducted since the 19th century until now. In ancient times, insulin from an animal’s extract was taken to treat human beings. However, this resulted in some serious allergic reactions. Therefore, scientists and researchers have tried their best to find alternative ways for managing diabetes with progressive advancements in biotechnology. However, a lot of research trials have been conducted, and they discovered more progressed strategies and approaches to treat type I and II diabetes with satisfaction. Still, investigators are finding more appropriate ways to treat diabetes accurately. They formulated insulin analogs that mimic the naturally produced human insulin through recombinant DNA technology and devised many methods for appropriate delivery of insulin. This review will address the following questions: What is insulin preparation? How were these devised and what are the impacts (both positive and negative) of such insulin analogs against TIDM (type-I diabetes mellitus) and TIIDM (type-II diabetes mellitus)? This review article will also demonstrate approaches for the delivery of insulin analogs into the human body and some future directions for further improvement of insulin treatment.

Pregnancy outcomes in women with type 1 diabetes using insulin degludec

AimsTo evaluate pregnancy outcomes in a real-world setting of pregnant women with type 1 diabetes using the ultra-long-acting insulin analog degludec compared to other long-acting insulin analogs throughout pregnancy. MethodsThis was a secondary analysis of a prospective cohort study. The prospective cohort included consecutive, singleton pregnant women with type 1 diabetes receiving long-acting insulin analogs both before and during pregnancy: 67 women using degludec compared to 95 women using other long-acting insulin analogs in a routine care setting. ResultsWomen using degludec had similar clinical characteristics as women using other long-acting insulin analogs including HbA1c at 9 gestational weeks [6.5 (6.2–6.9) % (48 (44–52) mmol/mol) versus 6.5 (6.0–7.0) % (47 (42–53) mmol/mol), p = 0.52] and at 35 gestational weeks [6.0 (5.6–6.5) % (42 (38–47) mmol/mol) versus 6.1 (5.6–6.5) % (43 (38–48) mmol/mol), p = 0.68]. Pregnancy outcomes were similar regarding preeclampsia [10% (7/67) versus 8% (8/95), p = 0.66] and preterm delivery before 37 gestational weeks [16% (11/67) versus 23% (22/95), p = 0.29]. There were no perinatal deaths, and neonatal outcomes as large for gestational age infants [37% (25/67) versus 39% (37/95), p = 0.83], small for gestational age infants [4% (3/67) versus 5% (5/95), p = 1.0] and neonatal hypoglycemia [32% (21/65) versus 41% (34/83), p = 0.28] were similar between women using degludec and other long-acting insulin analogs. ConclusionsThe use of degludec during pregnancy resulted in similar pregnancy outcomes as use of other long-acting insulin analogs in women with type 1 diabetes in a real-world setting. This suggests that degludec initiated before pregnancy can be continued throughout gestation.