Insulin Preparations Research Articles

B-150 Chromatographic Separation and Quantitation of Human Insulin and Lispro Analog in Serum Using Liquid Chromatography High-Resolution Mass Spectrometry

Abstract Background Factitious hypoglycemia, a deliberate attempt to induce low blood glucose levels occurring secondary to the surreptitious administration of exogenous insulin, can be difficult to diagnose due to a variety of factors including the increased use of synthetic insulin analogs in clinical practice. Traditional insulin immunoassays demonstrate variable cross-reactivity with commonly prescribed insulin analogues and their metabolites, making it difficult to measure specific analogs. The development of liquid chromatography high resolution accurate mass (LC-HRAM)-mass spectrometry (MS) assays has largely circumvented the limitations of traditional immunoassays for detection and quantitation of insulin analogs. Analytical challenges remain, however, specifically in differentiating lispro, an isomeric human insulin analog formed by the transposition of proline and lysine near the C-terminal end of the B chain, from human insulin in patient samples due to the equivalent mass-to-charge ratios of their precursor ions. Methods Immunoaffinity purification of insulin from calibrators and quality control material prepared by spiking insulin-depleted serum with pharmaceutical insulin preparations, as well as patient samples, was performed using tips coupled with anti-insulin monoclonal antibody. An automated liquid handler was programmed to perform aspiration and dispense cycles. Eluate from the purification protocol was submitted for analysis using a TLX-2 multiplex LC system paired with a Thermo Scientific Q Exactive Plus mass spectrometer. Various HPLC column chemistries were evaluated, a column passivation procedure was established, and column heater temperature was optimized to identify a combination of parameters yielding the best chromatographic separation of human insulin and lispro. Additionally, parallel reaction monitoring (PRM) targeted tandem mass spectrometry (MS/MS) analysis was utilized in combination with the full scan data to increase specificity through the monitoring of fragment ions produced from human insulin and each insulin analog. Results We found that a 1000 Å Diphenyl, 2.7 µm, 2.1 x 100 mm analytical column in a column heater maintained at a temperature of 80°C allowed for human insulin and lispro to be differentiated as two chromatographically separated extracted ion chromatographic peaks (XICs) and quantified down to 2.5 mcIU/mL with near-baseline separation. Before use, the column required passivation with a high protein buffer (0.05% bovine serum albumin in 20% acetonitrile [ACN] + 0.2% acetic acid) followed by increasingly organic buffers (20% ACN + 0.2% acetic acid and 50% ACN + 0.2% acetic acid). MS/MS was used to confirm the presence of analogs detected. Conclusions The LC-HRAM-MS method described here, coupled with optimized column chemistry, column passivation, and proper column temperature control allows for chromatographic separation of human insulin and lispro. Incorporating a PRM scan into the mass spectrometry full scan method provides confirmation of the insulin detected in the XICs. The results obtained from preliminary studies suggest this method is appropriate for use to facilitate the clinical investigation of suspected factitious hypoglycemia with the ability to differentiate isomeric compounds, such as human insulin and lispro.

PROGRESS OF KNOWLEDGE IN THE DEVELOPMENT OF CHITOSAN FORMULATIONS WITH INSULIN TO PROMOTE SKIN WOUND HEALING

The treatment of difficult-to-heal wounds is a major problem in modern medicine. The search for new materials and ways to treat wounds is important and timely. Insulin stimulates proliferation, differentiation and migration of skin fibroblasts and keratinocytes. Chitosan has beneficial biological properties and can be an effective carrier of insulin. This review discusses research into the development of chitosan formulations with insulin to aid local treatment of chronic wounds. The PubMed, Google Scholar, Scopus and Web of Science databases were searched for studies on chitosan preparations with insulin in terms of their efficacy in wound healing. Twelve original English-language articles published in peer-reviewed scientific journals were included in the analysis. Insulin preparations in a chitosan matrix in the form of gel, hydrogel, injection and non-woven dressing are highly effective at all stages of the wound-healing process. They show anti-inflammatory and antimicrobial effects. Insulin from the formulations is released in a prolonged or controlled manner. However, it seems necessary to learn more about the mechanisms of insulin action within lesions. Of note, the data are mainly from basic and preclinical studies. Only one clinical study has been conducted.

A PHARMACOECONOMIC EVALUATION OF TYPE 2 DIABETES DRUGS IN CENTRAL PHARMACIES IN SİVAS PROVINCE

Type 2 diabetes is characterized by insulin resistance in tissues such as the liver, muscle, and fat, resulting from detectable damage to pancreatic beta cells. The disease is also related to genetics, environmental factors, and lifestyle. In our country, 22.6% of the health budget is allocated to treating diabetes and its complications. Due to the increasing incidence of patients with type 2 diabetes, effective and rational treatments to reduce the burden of the disease on the healthcare budget have become an important issue for both payers and policymakers. In this study, prescriptions of 391 Type-2 diabetic patients were analyzed from pharmacies selected by mass sampling method in Sivas center, and the pharmacoeconomic suitability of these drugs was investigated, taking into account chronic complications related to diabetes. According to the data obtained, the drugs prescribed to diabetic patients with chronic diseases were found to be appropriate. However, when all diabetic patients were examined, it was determined that the prescribed amount of insulin preparations was high and not pharmaceutically appropriate. It was revealed that the cost of type 2 diabetes medications for 391 patients was 77,852,79 TRY, and the prescription price was 199.11 TRY.

Reducing insulin omission errors among patients with diabetes mellitus in general surgical wards: a best practice implementation project.

Omission of insulin, a high-alert medication with one of the highest locally reported errors, could lead to severe hyperglycemia, which could result in coma or death if not treated timeously. This study aimed to identify, evaluate, and implement strategies to reduce the occurrence of insulin omission errors in diabetic adult patients requiring insulin. This project followed the JBI Evidence Implementation Framework and conducted context analysis, strategy implementation, and evaluation of outcomes according to evidence-based quality indicators. The JBI PACES and JBI GRiP situational analysis tools were used to support data collection and implementation planning. There was one evidence-based criterion and five sub-criteria, with a sample size of 22 patients. There was increased compliance with best practices to reduce interruptions and distractions from baseline audit (50%) to follow-up audits 1 (45.4%) and 2 (31.8%), and no insulin omission incidences during the implementation period. In the post-implementation analysis, there were notable improvements in compliance with strategies related to nurses; however, reduced compliance was observed related to patients. Key barriers to implementation included patients still disturbing nurses despite the nurses wearing the medication vests and patients forgetting instructions not to disturb nurses during medication administration. Strategies to improve compliance included ensuring coverage in each cubicle during insulin preparation and administration, tending to patients' needs prior to insulin administration, and use of posters as reminders. There was an overall increase in compliance with best practice to reduce interruptions and distractions and no insulin omission incidences related to interruptions and distractions during the implementation phase. http://links.lww.com/IJEBH/A219.

Insulin Management for Gestational and Type 2 Diabetes in Pregnancy.

Insulin is preferred as the first-line agent for glucose management of gestational diabetes mellitus and type 2 diabetes in pregnancy when nutritional and lifestyle modifications are unable to achieve pregnancy-specific glucose targets. Individual heterogeneity in defects of insulin secretion or sensitivity in liver and muscle, unique genetic influences on pregnancy glycemic regulation, and variable cultural and lifestyle behaviors that affect meal, activity, sleep, and occupational schedules necessitate a personalized approach to insulin regimens. Newer insulin preparations have been developed to mimic the physiologic release of endogenous insulin, maintaining appropriate basal levels to cover hepatic gluconeogenesis and simulate the rapid, meal-related, bolus rise of insulin. Such physiologic basal-bolus dosing of insulin can be administered safely, achieving tighter glycemic control while reducing episodes of hypoglycemia. Insulin initiation and titration require understanding the pharmacodynamics of different insulin preparations in addition to a patient's glycemic profiles, effect of variable nutritional intake and mealtimes, physical activity, stress, timing of sleep cycles, and cultural habits. Educating and empowering patients to learn how their glucose responds to insulin, portion and content of meals, and physical activity can increase personal engagement in therapy, flexibility in eating patterns, and improved glycemic control. This Clinical Expert Series article is focused on optimizing insulin management (initiation, dosing, and titration) of gestational and type 2 diabetes in pregnancy.

Identifying and Reducing Insulin Errors in the Simulated Military Critical Care Air Transport Environment: A Human Factors Approach.

During high-fidelity simulations in the Critical Care Air Transport (CCAT) Advanced course, we identified a high frequency of insulin medication errors and sought strategies to reduce them using a human factors approach. Of 169 eligible CCAT simulations, 22 were randomly selected for retrospective audio-video review to establish a baseline frequency of insulin medication errors. Using the Human Factors Analysis Classification System, dosing errors, defined as a physician ordering an inappropriate dose, were categorized as decision-based; administration errors, defined as a clinician preparing and administering a dose different than ordered, were categorized as skill-based. Next, 3 a priori interventions were developed to decrease the frequency of insulin medication errors, and these were grouped into 2 study arms. Arm 1 included a didactic session reviewing a sliding-scale insulin (SSI) dosing protocol and a hands-on exercise requiring all CCAT teams to practice preparing 10 units of insulin including a 2-person check. Arm 2 contained arm 1 interventions and added an SSI cognitive aid available to students during simulation. Frequency and type of insulin medication errors were collected for both arms with 93 simulations for arm 1 (January-August 2021) and 139 for arm 2 (August 2021-July 2022). The frequency of decision-based and skill-based errors was compared across control and intervention arms. Baseline insulin medication error rates were as follows: decision-based error occurred in 6/22 (27.3%) simulations and skill-based error occurred in 6/22 (27.3%). Five of the 6 skill-based errors resulted in administration of a 10-fold higher dose than ordered. The post-intervention decision-based error rates were 9/93 (9.7%) and 23/139 (2.2%), respectively, for arms 1 and 2. Compared to baseline error rates, both arm 1 (P = .04) and arm 2 (P < .001) had a significantly lower rate of decision-based errors. Additionally, arm 2 had a significantly lower decision-based error rate compared to arm 1 (P = .015). For skill-based preparation errors, 1/93 (1.1%) occurred in arm 1 and 4/139 (2.9%) occurred in arm 2. Compared to baseline, this represents a significant decrease in skill-based error in both arm 1 (P < .001) and arm 2 (P < .001). There were no significant differences in skill-based error between arms 1 and 2. This study demonstrates the value of descriptive error analysis during high-fidelity simulation using audio-video review and effective risk mitigation using training and cognitive aids to reduce medication errors in CCAT. As demonstrated by post-intervention observations, a human factors approach successfully reduced decision-based error by using didactic training and cognitive aids and reduced skill-based error using hands-on training. We recommend the development of a Clinical Practice Guideline including an SSI protocol, guidelines for a 2-person check, and a cognitive aid for implementation with deployed CCAT teams. Furthermore, hands-on training for insulin preparation and administration should be incorporated into home station sustainment training to reduced medication errors in the operational environment.

The impact of hyperkalemia on ICU admission and mortality: a retrospective study of Chinese emergency department data

ObjectiveThis study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room.MethodsThis retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated.Results12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline.ConclusionHyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.

Synergistic quantification of mixed insulin preparations using time domain NMR techniques

Diabetes patients often rely on tailored insulin therapies, necessitating precise blends of various insulin types to achieve optimal pharmacokinetic profiles, including the quantity and action duration of insulin absorption into the bloodstream. This study aimed to develop an accurate quantification method for mixed insulin preparations, consisting of Insulin-NPH and Insulin Regular in ratios varying between 0:100–100:0. Time Domain NMR (TD-NMR) techniques, T2 relaxation times, and T1T2 maps were used to analyze the mixtures. Individually, neither technique provided a reliable determination of insulin ratios. However, the integration of both methods through chemometrics has been proven to be a synergistic approach, yielding a robust quantification technique suitable for quality control in the assessment of mixed insulin drugs. This innovative combined TD-NMR method is non-invasive, cost-effective, and user-friendly, offering at the same time a significant potential for preventing health complications associated with improper insulin dosing. Furthermore, our work elucidates the broader applicability of converging multiple TD-NMR techniques for analyzing intricate mixtures.

Most total pancreatectomies for ductal adenocarcinoma potentially can Be replaced by whipple over the splenic artery: a before and after study.

Recently, more and more total pancreatectomy (TP) has been performed for central-located pancreatic ductal cell adenocarcinoma (PDCA) which abuts or involves both gastroduodenal and splenic arteries and demands transaction of both of them for a complete resection. Spiked by Warshaw's procedure (spleen-preserving distal pancreatectomy with excision of splenic vessels), we developed a new procedure "Whipple over the splenic artery (WOTSA)" to replace TP by leftward extension of pancreatic parenchyma transaction line and preservation of pancreatic tail and spleen after excision of splenic artery. This uncontrolled before and after study assesses the safety and efficacy of a new technique "Whipple over the splenic artery (WOTSA)" as a treatment for PDAC which traditionally requires total pancreatectomy (TP) for a complete excision. The study group comprised 40 consecutive patients who underwent WOTSA for PDAC between August 2019 and September 2022. Their clinicopathological characteristics and survival were compared with those of a historical control group comprising 30 consecutive patients who underwent TP between January 2016 and July 2019. None of the 40 patients in the WOTSA group required reoperation due to infarction of the pancreas and/or spleen remnant. DM medication after WOTSA were none in 19, oral hypoglycemic agents in 19, and insulin preparations in 2 patients. Compared with TP, patients who underwent WOTSA exhibited similar rates of major operative complications, clear pancreatic parenchyma transaction margin, and number of harvested positive lymph nodes, but higher rate of adjuvant chemotherapy completion and a trend toward better median disease free survival (14 vs. 7.5mo, P=0.023). Compared to TP, WOTSA can be safely performed and have much better postoperative glycemic status without cost of higher operative risk or impaired surgical radicality. These findings indicate that most TPs for PDAC potentially can be replaced by WOTSAs.

Insulin therapy in type 2 diabetes: Insights into clinical efficacy, patient-reported outcomes, and adherence challenges.

Insulin therapy plays a crucial role in the management of type 2 diabetes as the disease progresses. Over the past century, insulin formulations have undergone significant modifications and bioengineering, resulting in a diverse range of available insulin products. These products show distinct pharmacokinetic and pharmacodynamic profiles. Consequently, various insulin regimens have em-erged for the management of type 2 diabetes, including premixed formulations and combinations of basal and bolus insulins. The utilization of different insulin regimens yields disparate clinical outcomes, adverse events, and, notably, patient-reported outcomes (PROs). PROs provide valuable insights from the patient's perspective, serving as a valuable mine of information for enhancing healthcare and informing clinical decisions. Adherence to insulin therapy, a critical patient-reported outcome, significantly affects clinical outcomes and is influenced by multiple factors. This review provides insights into the clinical effectiveness of various insulin preparations, PROs, and factors impacting insulin therapy adherence, with the aim of enhancing healthcare practices and informing clinical decisions for individuals with type 2 diabetes.

Review of data on comparative pharmacokinetics, pharmacodynamics, efficacy and safety of the superfast insulin drug lispro

Diabetes mellitus remains one of the main socially significant health problems worldwide. Glycemic control plays a key role in the prevention of all complications of diabetes mellitus. One of the most important factors in the overall control of glycemia in patients with both type 1 and type 2 diabetes mellitus is postprandial glucose levels, as a leading risk factor for delayed vascular complications. Modern possibilities for controlling postprandial glycemia include the use of not only ultrashort insulin preparations, but also ultrafast action. One of the superfast insulin preparations available today is the drug Lumzhev ® (inLisFast), which contains lyspro insulin as an active ingredient. A number of studies on the comparative pharmacokinetics and pharmacodynamics of inLisFast compared with insulin lispro consistently demonstrate a shift in the pharmacokinetic and pharmacodynamic profile to the left, which indicates faster absorption, an increase in early insulin exposure and a decrease in late insulin exposure. inLisFast provides flexibility in the regulation of food intake, which can play a significant role in optimizing glycemic control and improving the quality of life of patients with diabetes.

Acute insulin-induced hypoglycemia in twin neonates

Twin neonates with a history of exogenous insulin administration by a mother suffering from post-partum psychosis are reported. Twin 1 presented with lethargy, while twin 2 presented with apnea and bradycardia, requiring vigorous resuscitation. During their neonatal intensive care unit stay, both the babies developed multiple episodes of symptomatic refractory hypoglycemia with seizures and were managed with intravenous dextrose boluses and infusion, glucagon infusion, octreotide, diazoxide, and glucocorticoids. Although short-acting regular insulin (Actrapid, Novo Nordisk™) preparation was administered to the neonates, its effects were seen for a duration of 3–4 days, probably due to the depot effect. We highlight the importance of history taking and physical examination for early diagnosis and appropriate management.

Less is more: Validating a single method for comprehensive rh-insulin analysis

The objective of this current study is to establish a single method for potency and related proteins analysis of human insulin formulations using reverse-phase high performance liquid (RP-HPLC) chromatography technique which was validated and verified for the potency analysis in insulin formulations. Chromatographic separation was achieved using an octadecylsilane (C-18) stationary phase and a mobile phase composed of 55% (v/v) buffer (0.2 M sodium sulfate in water, {pH 2.3}) and 45% (v/v) acetonitrile. Detection was performed by UV detector at 214 nm with a flow rate of 1 ml/min and an injection volume of 20 µL, at 40°C. Currently there are separate methods available in Indian Pharmacopoeia for analysis of Potency and Related proteins in human insulin. We have validated a single method where quantitation of potency and related proteins can be performed in the same run. The method validation exhibited linearity over the concentration range of 0.08–4.5 mg/ml (r2=0.999) with limit of detection of 0.094 mg/ml The accuracy of the method was 99–102.8%. Thus, it is proposed that both potency and related proteins in insulin formulations can be precisely evaluated using a single run thus saving the time and cost for quality analysis of insulin preparations both at manufacturing and regulatory laboratories which in turn will increase the market availability of such standard quality insulin preparations for public health use.

Preparedness of diabetic patients for receiving telemedical health care: A cross-sectional study.

This study evaluates feasibility of telemedicine to deliver diabetic care among different regions of the country. Medical interns affiliated with Rotaract Club of Medicrew (RCM) organized a Free Diabetes Screening Camp called "Diab-at-ease" at multiple sites across the country. Of all beneficiaries of the camp >18 years of age, patients previously diagnosed with diabetes and undiagnosed patients with a random blood sugar level of more than 200 mg/dL were interviewed regarding their knowledge, attitude, and practice regarding diabetes care and preparedness and vigilance to receiving care through telemedicine. Random blood sugar, height, weight, and waist circumference were also documented. About 51.1% (N = 223) of female patients aged 57.57 ± 13.84 years (>18 years) with body mass index (BMI) =26.11 ± 4.63 were the beneficiaries of the health camps. About 75.3% (n = 168) of them were on oral hypoglycemic agents (OHAs), 15.7% (n = 35) were on insulin preparations, and 59.6% (n = 156) and 88.5% (n = 31) of which were highly compliant with treatment, respectively. About 35% (n = 78) and 43.9% (n = 98) of them were unaware of their frequency of hypoglycemic and hyperglycemic episodes, respectively. About 64.6% (n = 144) of the patients were equipped for receiving teleconsultation. Glucometer was only possessed by 51.6% (115) of which only 46.95% (n = 54) can operate it independently. Only 80 patients (35.9%) were aware of the correct value of blood glucose levels. While a majority of the population is compliant with treatment and aware about diabetes self-care, they lack adequate knowledge and resource equipment for the same leading to very limited utilization.

Evaluating Patient and Provider Preferences for a Once-Weekly Basal Insulin in Adults with Type 2 Diabetes.

The global burden of disease of type 2 diabetes (T2D) is significant, and insulin currently plays a central role in T2D management. This study sought to assess the preferences of patients with T2D and healthcare providers (HCPs) involved in T2D care regarding a hypothetical once-weekly basal insulin in comparison to current basal insulin options. In a survey-based study in the United States that included a discrete choice experiment (DCE), patients with T2D (insulin naïve and current insulin users) and providers who treat individuals with T2D were asked to evaluate current basal insulins and identify attributes of importance regarding a hypothetical once-weekly basal insulin. A regression analysis was conducted to identify drivers of preference by relevant demographics, attitudes, and behaviors. Most respondents (91% of patients with T2D and 89% of HCPs in the base case scenario) would choose a once-weekly basal insulin product over another type of basal insulin. Both patients with T2D and HCPs rated insulin type and delivery method to be attributes of highest importance in the discrete choice exercise. Current basal insulin users ("insulin experienced") reported higher levels of confidence that a once-weekly insulin would help them to achieve their desired blood sugar levels compared to their current basal insulin (5.7 vs 5.2 on a 7-point Likert scale). Most insulin-experienced respondents (88%) were likely to inquire about once-weekly basal insulin, and most HCPs (85%) indicated willingness to educate patients on management of their T2D using a once-weekly basal insulin. Discussing preferences for T2D medication management is important for patients and HCPs to ensure treatments are offered for patients based on their preferences. This study showed that patient and provider preferences are similar towards a once-weekly basal insulin over current basal insulin preparations.

A gluco-mindful approach to diabetic gastroparesis.

Diabetes gastroparesis is a common manifestation of autonomic neuropathy in persons with long-standing, uncontrolled diabetes. Most discussion about its management revolves around the mitigation of symptoms. Here, we share tips on choosing the right glucose-lowering medication, based upon predominant symptomatology of gastroparesis. We highlight about insulin preparations, and their timing of administration, can be tailored according to need. We also emphasize the need to choose oral glucose lowering drugs with care.

Эффективность и безопасность использования метформина у больных с сахарным диабетом, развившимся на фоне панкреатита

Pancreatogenic diabetes mellitus (DM-P) is a topical multidisciplinary problem, many aspects of which need further research. The purpose is to study the efficacy and safety of metformin as a component of hypoglycemic therapy in patients with DM–P in prospective follow-up. Material and methods. The study included 81 patients with DM-P aged 54.7 (9.3) years, with a history of pancreatic lesions from 5 months to 4.5 years. In group A (n = 37), insulin preparations were used as hypoglycemic agents, in group B (n = 44) metformin (at HbA1c levels &gt; 8% and fasting glycemia &gt; 10 mmol/l insulin preparations were added to it). The follow-up was 10.6 (2.7) months. Results. Initially, hypoglycemic treatment as metformin monotherapy was prescribed to 43.1% patients of group B, that insured adequate glycemic control in 27.3% of cases. During treatment, the average HbA1c levels decreased in group A from 9.8 (1.9) % to 8.6 (1.6) %, in group B — from 9.4 (1.8) % to 8.1 (1.4) %, respectively, p &lt; 0.05. In group B, the proportion of people who achieved the target levels of HbA1c was significantly higher (61.3%) than in group A (35.1%), p &lt; 0.05. The addition of metformin to insulin preparations in group B allowed reducing the insulin dose by ≥ 20% in 36% of patients. The treatment tolerability in both groups was satisfactory. The development of episodes of grade 1–2 hypoglycemia was noted in 20 (54.0%) and 18 (40.9%) patients in groups A and B; grade 3 — in 6 (16.2%) and 6 (13.6%), respectively, p &gt; 0.05. The development of gastrointestinal effects of metformin was noted in 29.5% of patients and was transient. Conclusions. The use of metformin in DM-P as monotherapy or in combination with insulin preparations was satisfactorily tolerated, contributed to improved glycemic control, allowed reducing insulin doses, and was associated with a decrease of pancreatitis recurrence.

Assessment of Prescribing Pattern of Anti-diabetic Drugs in a Tertiary Care Teaching Hospital

Background: There is increasing importance of PPMS because of a boost in marketing of new drugs, variations in pattern of prescribing and consumption of drugs, growing concern about delayed adverse effects, and cost of drugs and volume of prescription. Diabetes mellitus is a pandemic disease that has struck each corner of the world. According to the Indian Council of Medical Research – Indian study (ICMR), a national diabetes study, India currently has 62.4 million people with diabetes. This is set to increase to over 100 million by 2030. Objective: The aim of this study is to evaluate the prescribing pattern of drugs used to treat Diabetes Mellitus in a tertiary care teaching hospital. Methodology: A hospital based retrospective cross-sectional observational study was performed in Navodaya Medical College &amp; Hospital, Raichur over a period of 6 months from May 2022 to October 2022. The study was performed among 80 patients having diabetes mellitus and associated comorbidities that satisfy the study criteria. Results: In this study, among 80 cases of DM diseases assessed, the incidence of diabetes mellitus is common in females (51.25%) than males (48.75%). Most frequently prescribed combination was the insulin, metformin (25%) followed by metformin, glimepiride (12.5%). Among three drug combination was most prescribed metformin, glipizide, and insulin (10%) Conclusion: Diabetes should be managed properly to enhance the quality of life of patients. metformin is the most common choice of oral antidiabetic drugs, but the use of insulin preparation treatment of type 2 DM is increasing continuously. Metformin is the most prescribed antidiabetic drugs in monotherapy.

Discrimination of Human Insulin and its Analogs by Flow Injection Analysis with Mass Spectrometry

Although insulin therapy is recognized as an effective treatment for diabetes, it can lead to serious side effects and medical accidents. Since living organisms contain many foreign components, the separation of these components by liquid chromatography (LC) is essential for the identification of insulin preparations. However, it is difficult to conclude that separation by LC is indispensable because multiple components are unlikely to be mixed in a sample obtained from a vial or syringe needle. Therefore, the introduction of flow injection analysis (FIA), in which samples are analyzed with the column removed, can potentially eliminate the sample separation process and reduce analysis time. In addition, tandem mass spectrometry (MS/MS), which allows detailed analysis, requires expensive equipment, and some facilities only allow analysis by single mass spectrometry (MS). The discriminatory ability of each analysis method should also be clarified. Here, we examined the analysis time and discriminatory ability using a combination of FIA, MS, and MS/MS. The results showed that FIA reduced the analysis time, FIA-MS could not discriminate when the molecular weights of the samples were the same or similar, and FIA-MS/MS could discriminate between different amino acid sequences. FIA-MS has limitations in discrimination, whereas FIA-MS/MS is considered an analytical method that can shorten the analysis time and discriminate formulations.

Endotoxin accelerates insulin amyloid formation and inactivates insulin signal transduction

Aims and objectivesThe aim of this study is to discuss the influence of endotoxin on insulin amyloid formation, to provide guidance for therapeutic insulin preparation and storage. Materials and methodsThe ThT and ANS binding assays were applied to characterize the dynamics curve of insulin amyloid formation with the presence or absence of endotoxin. The morphological structures of intermediate and mature insulin fibrils were observed with SEM and TEM. Secondary structural changes of insulin during fibriliation were examined with CD, FTIR and Raman spectral analysis. The cytotoxic effects of oligomeric and amyloidogenic insulin aggregates were detected using a cck-8 cell viability assay kit. The influence of endotoxin on insulin efficacy was analyzed by monitoring the activation of insulin signal transduction. Key findingsThT analysis showed that endotoxin, regardless of species, accelerated insulin fibrils formation in a dose-dependent manner, as observed with a shorter lag phase. ANS binding assay demonstrated endotoxin provoked the exposure of insulin hydrophobic patches. The results of SEM and TEM data displayed that endotoxin drove insulin to cluster into dense and viscous form, with thicker and stronger filaments. Based on CD, FTIR and Raman spectra, endotoxin promoted the transition of α-helix to random coil and β-strand secondary structures during insulin aggregation. Insulins in both oligomeric and amyloidogenic forms were cytotoxic to HepG2 cells, with the former being more severe. Finally, the efficacy of endotoxin treated insulin obviously decreased. SignificanceOur studies revealed that endotoxin disrupts the structural integrity of insulin and promotes its amyloidosis. These findings offered theoretical guidance for insulin storage and safe utilization, as well as pointing up a new direction for insulin resistance research.