NPH Insulin Research Articles

Role of insulin in the management of diabetic foot

Despite insulin's well-documented benefits in wound healing over the last 70 years, challenges remain regarding the optimal method of administration. While systemic insulin therapy has significant side effects, topical insulin faces challenges with consistent delivery. This study aims to test the hypothesis that local insulin injections can provide sustained high concentrations in wounds, promoting healing with minimal systemic impact, combining the benefits of both systemic and topical insulin therapies.This study investigates the effect of local insulin injections on wound healing, focusing on enhancing the healing process in a non-healing diabetic foot ulcer. The objective is to determine whether insulin injections at the wound site can accelerate healing by promoting key processes like keratinocyte migration, differentiation, and angiogenesis.Conducted at a tertiary care center in South India, this study involved a 69-year-old male patient with a non-healing ulcer over the lateral aspect of the left foot due to Charcot's joint. The wound area was treated with a mixture of Insulin Isophane and Human Insulin (70/30) in a 4-unit to 10 ml saline ratio per 10 cm². The treatment was followed by a two-layer regenerative scaffold dressing and Negative Pressure Wound Therapy (NPWT) to support recovery.The insulin application significantly enhanced wound healing by promoting keratinocyte migration, differentiation, and angiogenesis. These effects led to a noticeable reduction in the time required for wound closure and improved tissue regeneration.The use of local insulin injections effectively improves wound healing by targeting key processes such as inflammation, re-epithelialization, and angiogenesis. This study underscores the potential of insulin as a promising therapeutic agent for chronic wound management. Further research is recommended to validate these findings and explore its application across diverse wound types.

Budget impact analysis of insulin glargine vs. isophane protamine insulin treatment for patients with type-2 diabetes and severe hypoglycemia in Thailand

ObjectiveThis study aimed to assess the financial impact of different adoption rates of insulin glargine (IGlar) treatment compared to isophane protamine (neutral protamine hagedorn [NPH]) insulin treatment for patients with type-2 diabetes (T2D) and severe hypoglycemia in Thailand from the payer’s perspective.MethodsThe budget impact analysis (BIA) model over a period of 5 years was used to estimate the net budget impact (NBI) of IGlar treatment by comparing the total budget expenditures under two scenarios: scenario 1 involved only NPH insulin and scenario 2 included the introduction of IGlar. The total budget included either the cost of insulin or a combination of the costs of insulin and the expense related to severe hypoglycemia. Scenario 2 started at 20% uptake of IGlar and a yearly increase of 20%. NBI was calculated as the difference between the total budgets of scenarios 1 and 2. NBI and one-way sensitivity analyses were conducted for evaluation.ResultsConsidering only the cost of insulin, the use of IGlar for patients with T2D and severe hypoglycemia resulted in a yearly average NBI of 174.9 million Thai baht (THB) (5.1 million USD). However, when the cost related to severe hypoglycemia was included, the total budget incurred from scenario 2 was less than that of scenario 1, leading to a negative NBI or cost savings.ConclusionThe NBI of IGlar adoption would be substantial when considering only the cost of insulin; however, the significant benefit of IGlar in terms of a lower rate of severe hypoglycemia compared with NPH insulin would clearly offset the additional cost of IGlar.

Optimization of hydroxypropyl β-cyclodextrin-isophane insulin complex-loaded thiolated chitosan/sodium alginate nanoparticles using full factorial design

Isophane insulin (N) is challenging to administer orally due to its gastrointestinal instability. Research has shown that partially complexing N with hydroxypropyl β-cyclodextrin (HPβCD-N complexes) enhances its stability. Nanoparticles (NPs) are also frequently used to encapsulate drugs to protect them from degradation. This study aimed to optimize HPβCD-N complex-loaded thiolated chitosan/alginate (TCS/ALG) NPs using a full factorial design. The HPβCD-N complexes were prepared before being loaded into the NPs. Independent variables included the concentrations of TCS, ALG, and HPβCD-N complex, while the dependent variables were particle size and zeta potential. The results demonstrated that TCS and ALG concentrations had a positive and negative effect on particle size, respectively, with smaller particles being favored. The zeta potentials of the NPs increased positively and negatively in proportion to the TCS and ALG concentrations, respectively. The HPβCD-N complexes had a minimal effect on the dependent variables. The NPs made with TCS, ALG, and HPβCD-N complex concentrations of 0.075%, 0.0375%, and 5% w/w, respectively, were the most suitable for achieving small particle size and zeta potential within +30 mV and +50 mV. TEM images showed spherical particles with nanometer diameters. The encapsulated N was found to be approximately 1% w/w, confirming successful loading of N into the NPs. Thus, the optimized formulation shows potential as an NP carriers for N delivery.

8132 Prolonged Refractory Hypoglycemia For Seven Days After Discontinuation Of Neutral Protamine Hagedorn (NPH) Insulin And Injectable Semaglutide

Abstract Disclosure: A. Musleh: None. M.T. Rauf: None. E. Afroze: None. S. Al-Bacha: None. A 75-year-old male with Type 2 Diabetes was brought to the emergency department (ED) by emergency medical services (EMS) due to altered mentation. The patient’s wife found him unresponsive with seizure-like activity. EMS was called to the scene and obtained a capillary blood glucose reading of 31 mg/dL. Despite initial treatment with 50% dextrose the patient’s capillary blood glucose came down to 21 mg/dL in the ED and was confirmed by venous glucose. Workup including Computed Tomography (CT) imaging was inconsistent with a cerebrovascular accident. Given refractory hypoglycemia and delirium, the patient was started on a dextrose 10% infusion at 150 milliliters per hour. He was admitted to the intensive care unit for closer monitoring. His wife states that the patient had a few episodes of mild hypoglycemia overnight for the past several weeks, which improved after eating. His home medications included NPH insulin 46 units twice daily, empagliflozin 25 mg once daily, and injectable semaglutide 2 mg once weekly. The last dose of NPH insulin was the night before the presentation and the last dose of semaglutide was 5 days prior to admission. Serum creatinine levels were stable at 1.3-1.5 mg/dL throughout the hospitalization, which was below his baseline creatinine of 1.7 mg/dL. Laboratory results were as follows: hemoglobin A1c 5.9%, c-peptide level was 0.3 ng/mL (normal range 0.8-3.9 ng/mL) with a glucose of 68 mg/dL (normal range 70-100 mg/dL), insulin 203.8 mcIU/mL (normal range less than 24 mcIU/mL), proinsulin 3.2 pmol/L (normal range less than or equal to 8 pmol/L), beta-hydroxybutyrate 0.06 mmol/L (normal range 0.02-0.27), cortisol 66.6 mcg/dL (normal range 6.7-22.6 mcg/dL), insulin-like growth factor 1 123 ng/mL (normal range 53-222), and hypoglycemic agent panel was negative. On ICU Day 2, his mentation improved, he was allowed to eat but continued to require dextrose infusion to prevent hypoglycemia. Repeat fasting insulin levels even four days from prior showed an incremental decrease to 59.4 mcIU/mL with a glucose of 77 mg/dL. It took 7 days before the patient was able to maintain glucose above 70 mg/dL off of dextrose infusion. After which he had hyperglycemia requiring gradual reintroduction of his diabetes medicines other than insulin. It is rare to see such prolonged refractory hypoglycemia from an exogenous source of insulin as exhibited in this case. Notably, the patient was on semaglutide and had stable chronic kidney disease without acute kidney injury. Although multiple mechanisms explain the prolonged insulin duration of action in kidney disease, the effects of semaglutide on insulin action are unknown. Presentation: 6/3/2024

6810 Successful Insulin Allergy Desensitization To Humalog During The Second Trimester Of Pregnancy

Abstract Disclosure: J. Noreña: None. S. Seav: None. S. Jiang: None. S. McGhee: None. M. Tan: None. M. Basina: None. Background: Insulin allergy is rare, occurring in only 0.1 to 3% of people with insulin-treated diabetes. During pregnancy, this incidence is even lower due to a relative immunosuppressive state. Currently, there are no standardized insulin allergy desensitization protocols for this specific patient population. Clinical Case: A 39-year-old female (G4P3003) with T2DM and multiple prior medication allergies presented to the antepartum unit in her 17th week of pregnancy due to hyperglycemia and reported insulin allergy to NPH insulin.Patient was initially diagnosed with gestational diabetes during her third pregnancy, requiring NPH insulin which she seemed to tolerate well at the time. She remained medication-free for two years post-delivery but later developed T2DM with an A1c of 6.8%. Metformin and Jardiance, previously prescribed, were discontinued upon confirmation of her current pregnancy. She opted to manage her diabetes through diet and exercise alone, but her A1c rose to 7.0%, prompting the initiation of NPH.Following the first dose of NPH at home, she experienced a localized burning sensation at the injection site associated with facial flushing, followed by a diffuse, pruritic, erythematous rash on her face, chest, abdomen, and bilateral arms. Due to her history of anaphylaxis to other drugs (mainly antibiotics), she was admitted to the hospital for monitoring. Inpatient attempts with lower doses of NPH and then a trial of glargine triggered new rash episodes. Work-up revealed negative insulin antibodies, low IgG, and a normal CBC. She was started on Humalog to cover basal dose administered every 6 hours and additional prandial injections, which she tolerated prior to discharge. One week later, she developed a new local erythematous reaction at the Humalog injection site followed by a generalized rash which led to her readmission.Allergy was consulted and facilitated a successful desensitization protocol to Humalog. The protocol included escalating doses of insulin administered every 30 minutes (0.1u, 0.2u, 0.4u, 0.8u, 1u, 2u, 3u, 3u) to achieve a pre-determined cumulative dose of 10.5 units. Patient tolerated the protocol well and was discharged with q6h Humalog for basal coverage in addition to prandial doses with plan to transition to insulin pump therapy with Humalog soon. Conclusion: This unique case demonstrates how insulin desensitization can be a safe and successful strategy to help achieve insulin tolerance and glycemic control during pregnancy. Election of an insulin, such as Humalog, that can achieve the one-hour post-prandial glucose target during pregnancy and also provide effective basal coverage should be considered as desensitization can only be done with one insulin type at a time. Presentation: 6/2/2024

Is It Time for a New Algorithm for the Pharmacotherapy of Steroid-Induced Diabetes?

Glucocorticoids (GS) are widely used in multiple medical indications due to their anti-inflammatory, immunosuppressive, and antiproliferative effects. Despite their effectiveness in treating respiratory, skin, joint, renal, and neoplastic diseases, they dysregulate glucose metabolism, leading to steroid-induced diabetes (SID) or a significant increase of glycemia in people with previously diagnosed diabetes. The risk of adverse event development depends on the prior therapy, the duration of the treatment, the form of the drug, and individual factors, i.e., BMI, genetics, and age. Unfortunately, SID and steroid-induced hyperglycemia (SIH) are often overlooked, because the fasting blood glucose level, which is the most commonly used diagnostic test, is insufficient for excluding both conditions. The appropriate control of post-steroid hyperglycemia remains a major challenge in everyday clinical practice. Recently, the most frequently used antidiabetic strategies have been insulin therapy with isophane insulin or multiple injections in the basal-bolus regimen. Alternatively, in patients with lower glycemia, sulphonylureas or glinides were used. Taking into account the pathogenesis of post-steroid-induced hyperglycemia, the initiation of therapy with glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors should be considered. In this article, we present a universal practical diagnostic algorithm of SID/SIH in patients requiring steroids, in both acute and chronic conditions, and we present a new pharmacotherapy algorithm taking into account the use of all currently available antidiabetic drugs.

Authentication of the shelf-life of NPH injectable insulins samples using NIR and MS spectral fingerprints

Insulin is essential for regulating glucose levels, and its hormonal deficiency leads to diabetes. Treatment involves the use of different types of insulin tailored to individual needs. Properly stored and transported Neutral Protamine Hagedorn (NPH) insulin remains effective and stable, highlighting the importance of quality control to ensure its efficacy and patient safety. This study aims to develop an analytical method to evaluate the shelf-life of NPH injectable insulin samples while preserving packaging integrity. The approach consisted of analyzing intact insulin samples, with and without expired shelf-life dates, using near-infrared spectroscopy (NIR) obtained from two instruments: a benchtop and a portable device. These measurements were coupled with chemometric methods, specifically single-class classification algorithms. The classifiers considered were Data Driven-Soft Independent Modeling of Class Analogy (DD-SIMCA) and One-Class Partial Least Squares (OC-PLS). For benchtop NIR, the DD-SIMCA method, with Savitzky-Golay smoothing preprocessing (41-point window) and baseline offset (BO), achieved excellent results, reaching 100% sensitivity, specificity, and efficiency in both training and test sets. As for portable NIR, the most effective methods were DD-SIMCA and OC-PLS, using datasets preprocessed with Savitzky-Golay smoothing with first derivative, second-order polynomial (SGD-1st-2nd), and 9-point windows combined with Standard Normal Variate (SNV), and Savitzky-Golay smoothing filters (SGS) using second-order polynomial and 7-point windows combined with baseline offset (BO) and Multiplicative Scattering Correction (MSC). The results were corroborated by mass spectrometry, correlating the structural changes of degraded insulin with NIR data. The proposed methodology is a promising tool for non-destructive, rapid, and cost-effective authentication of the preservation state of NPH insulin, aligning with green chemistry principles and allowing for in-situ evaluation, thereby preserving medication integrity.

A Case Report of Bardet Biedl Syndrome in a Patient from Pakistan who Presented with Osmotic Symptoms associated with Diabetes Mellitus

Background: The primary features of Bardet Biedl syndrome (BBS) are characterized by retinal degeneration, central obesity, post-axial polydactyly, intellectual impairment, hypogonadism, and renal anomalies. The secondary clinical features are syndactyly, delay in the achievement of developmental milestones, diabetes insipidus, diabetes mellitus, congenital heart disease and liver involvement. It is diagnosed when a patient has either four primary or three primary and two secondary clinical features and the management depends upon those predominant features. Case presentation: A 12-year-old boy presented with polyuria, polydipsia and polyphagia. His developmental milestones were delayed and had syndromic features on physical exmination. Ultrasound of the abdomen and pelvis showed mild right-side hydronephrosis. His BMI was 28 and HbA1c was 18.3%, and values of LH and FSH were decreased. As a result, he was diagnosed with a case of BBS. He was commenced on insulin therapy with Insulin Regular (Human Insulin)and Insulin NPH (Human Insulin). Conclusion: Patients presenting with polyuria, polydipsia, polyphagia along with the presence of syndromic features, should be assessed for BBS as osmotic symptoms associated with diabetes mellitus can be initial clinical presentation of BBS. Its management depends upon the signs and symptoms of the patient. Various options including weight loss, exercise, oral hypoglycemic drugs, and insulin are available to treat diabetes mellitus in BBS. Some cases can have very high levels of HbA1c on initial presentation, which may require insulin without trying oral hypoglycemic drugs to treat diabetes mellitus in BBS.

Study of the Relationship between Diabetic Retinopathy, Basal Insulin Therapy (Glargine or NPH) and Insulin-Like Growth Factor 1 Serum Level

Abstract Background Diabetic retinopathy (DR) is the major cause of preventable blindness worldwide. DR is a microvascular complication of diabetes mellitus that is more prevalent in patients with type 1 diabetes. Type 1 diabetes mellitus is an autoimmune disease that leads to insulin deficiency so patients require long term therapy with basal insulin for optimum glycemic control. Insulin- like growth factor 1 (IGF-1) is an important growth factor that is involved in cell proliferation and angiogenesis. There is a lot of evidence that IGF-1 is tightly related to DR development. Insulin Glargine is a long-acting insulin analogue which is peak-free and less hypoglycemic as compared to the intermediate-acting NPH insulin. Glargine has an increased affinity to IGF-1 receptor and this raised concern about its role in development of DR. The relationship between diabetic retinopathy, basal insulin therapy and IGF-1 serum level is still in debate. Aim we aimed to compare the incidence and severity of diabetic retinopathy in type 1 diabetic patients on basal insulin therapy (Glargine or NPH) and its relation to serum IGF-1 level. Methods The current study included 88 subjects with type 1 diabetes divided into 44 on basal insulin therapy with Glargine and actrapid ( Group A) and 44 on NPH and actrapid ( Group B). Hemoglobin A1c, Total cholesterol, Triglycerides, High density lipoproteins, Low density lipoproteins and serum IGF-1 levels were assessed. Full clinical examination including (weight, height, BMI), vital signs (pulse, blood pressure) was done and Fundus examination by Optomed Aurora® IQ handheld fundus camera. Results On comparing the 2 studied groups, There was no statistical significant difference as regarding fundus examination findings between studied groups (P value = 0.429). There was no statistically significant relation between diabetic retinopathy and serum IGF-1 (P value = .080 with Mean ± SD of serum IGF-1 level in patients with Normal fundus 14.8 ± 11 vs. Patients with Diabetic retinopathy 21.3 ± 16.9). There was statistically significant association between diabetic retinopathy and duration of diabetes (P value< 0.05 with Mean ± SD of diabetes duration in patients with Diabetic retinopathy 17.7 ± 6.9 vs. Patients with Normal fundus 14.6 ± 5.6). There was a statistical significant difference as regarding age (P value< 0.05 with Mean ± SD of age in Group B regimen 28.4 ± 6.7 vs. Group A 25.5 ± 4.9). Conclusion Serum IGF-1 levels showed no statistically significant difference in patients either on Glargine or NPH and also in patients either with normal fundus or with diabetic retinopathy. The incidence and severity of diabetic retinopathy in patients with type 1 diabetes mellitus is directly proportionate to duration of disease. No noted difference concerning diabetic retinopathy changes between patients on basal insulin therapy either Glargine or NPH.

1069-P: Regular Insulin vs. NPH Insulin for Controlling Hyperglycemia in Hospitalized Patients on Continuous Enteral Tube Feeding

1069-P: Regular Insulin vs. NPH Insulin for Controlling Hyperglycemia in Hospitalized Patients on Continuous Enteral Tube Feeding

Expecting factors for inadequate glycemic control in children and adolescents with type 1 diabetes mellitus: a single center experience.

Achieving an ideal glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM) is both a difficult and challenging process. We aim to highlight the expected factors contributing to inadequate glycemic control in children and adolescents with T1DM in a sample of Iraqi children and adolescents. This was a descriptive cross-sectional study that recruited 247 T1DM patients aged < 18 years & disease duration ≥ 1 year. Data collected included socio-demographic & clinical characteristics with recent HbA1c value. Each patient was examined for signs of puberty and any lipodystrophy at insulin injection sites. Factors studied using Independent-Samples T-Test, One way ANOVA & Multivariable logistic regression. Of the 247 patients, 108 (43.7%) were males, and 139 (56.3%) were females. The mean & SD of the age of patients was 10.13 ± 3.85 years. The Mean & SD of the recent HbA1c level was 9.43 ± 2.56. HbA1c ≤ 7.5 was achieved in 27.1% of patients. Using Multivariable logistic regression to study the association between variable factors and inadequate glycemic control, showed a significant association with higher odds in terms of the older age of the patient, maternal illiteracy, presence of recurrent diabetic ketoacidosis (DKA) episodes, absence of carb counting, and presence of lipodystrophy. Higher HbA1c was also associated significantly with puberty, rural residency, poor socioeconomic status, DKA presentation, and using regular + NPH insulin regimen. In the current study, inadequate glycemic control was induced by many factors, Strategies should be applied to control these factors to minimize the prospective risks of macro-vascular complications linked to T1DM in children & adolescents. The online version contains supplementary material available at 10.1007/s40200-024-01442-2.

Effect of the sodium-glucose cotransporter-2 inhibitor, DWP16001, as an add-on therapy to insulin for diabetic dogs: A pilot study.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents. This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment. Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n=10) and DWP SID group (n=9). In the DWP TOD group, 0.025mg/kg of DWP16001 was administered once every 3 days, whereas, in the DWP SID group, 0.025mg/kg of DWP16001 was administered once a day. Food intake was maintained during the trial period. Hypoglycaemia, ketoacidosis or unexpected life-threatening reactions were assessed as adverse effects before and after DWP16001 administration. We compared insulin requirement reduction and blood glucose level control between two groups. No specific adverse effects were observed during the clinical trial, and haematological parameter remained unchanged. Moreover, the fasting glucose levels and daily insulin dose in the DWP TOD group were lower than the pre-administration values, but not significantly different for 8 weeks. Systolic blood pressure, fructosamine and insulin dose decreased significantly in the DWP SID group compared to the DWP TOD group at 8 weeks (p<0.05) without affecting food consumption. Among these patients, 10 patients were monitored while receiving DWP16001 for 12 months (DWP TOD group n=5, DWP SID group n=5). The fasting glucose and fructosamine levels and daily insulin dose were reduced in both groups at 12 months compared with those before receiving DWP16001. When DWP16001, an SGLT2 inhibitor, was supplied to dogs with type 1 diabetes, no adverse effects were observed, and it was confirmed that the administered insulin dose can be reduced in controlling blood glucose.

Continuous subcutaneous insulin infusion versus multiple daily injection therapy in pregnant women with type 1 diabetes.

The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and continuous subcutaneous insulin infusion (CSII) and to compare outcomes of women treated with long-acting insulin or neutral protamine Hagedorn (NPH). This multicenter prospective cohort study involved women with pregestational T1DM treated with MDI and CSII. Primary outcome was glycated hemoglobin (HbA1c) before and during pregnancy. Secondary outcomes included maternal and neonatal outcomes and quality of life. Of the 121 studied women, the average age was 28.48 years, and the average body mass index was 21.29 kg/m2 at conception and 26.32 kg/m2 at delivery. Of the studied women, 78.51% had planned pregnancy. Women treated with MDI and CSII had comparable HbA1c before pregnancy or in the first and second trimesters. In the third trimester, women on CSII therapy had significantly lower HbA1c (6.07 ± 0.62 vs 6.20 ± 0.88%, p = .017), higher HbA1c on-target rate (71.43% vs 64.62%, p = .030), and greater decline of HbA1c from preconception to the third trimester (-0.65 vs -0.30%, p = .047). Fewer daily insulin requirements were observed in those used CSII compared with MDI-treated women (0.60 ± 0.22 vs 0.73 ± 0.25 U/kg/day, p = .004). Newborns born of mothers treated with the CSII method were more likely to have neonatal jaundice (adjusted odds ratio [OR] 2.76, 95% confidence interval [CI] 1.16-6.57) and neonatal intensive care unit (adjusted OR 3.73, 95%CI 1.24-11.16), and women on CSII had lower scores in patient-reported quality of life (p = .045). In the MDI group, those receiving long-acting insulin had nonsignificant lower HbA1c and higher HbA1c on-target rate in the second and third trimesters, compared with those treated with NPH. Insulin pump users may achieve better glycemic control than multiple daily insulin injections, which did not substantially improve pregnancy outcome.

Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

In the United States, costs of antidiabetes medications exceed $327 billion. To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. American College of Physicians. (PROSPERO: CRD42022382315).

Beyond HbA1c: Identifying Gaps in Glycemic Control Among Children and Young People with Type 1 Diabetes Using Continuous Glucose Monitoring.

To describe continuous glucose monitoring (CGM) derived glycemic variables, and study their association with HbA1c and socio-economic factors in young people with Type 1 diabetes mellitus (T1DM). Ninety-two participants [age 15.7 ± 5.0 y (mean ± SD), HbA1c 8.0 ± 1.5% (mean ± SD)] wore a professional CGM sensor for 14 d. Median (IQR) time in range (TIR) was 41 (18)%. Participants spent 41 ± 20% of their day in hyperglycemia (>180mg/dl), and 14 (13)% in hypoglycemia (<70mg/dl). High glycemic variability (percent CV >36%) was seen in 92% participants. Older age at diagnosis was associated with higher TIR (β = 0.267, p = 0.01), lower time above range (TAR) (β = -0.352, p <0.001), but higher time below range (TBR) (β = 0.274, p = 0.006). The use of NPH vs. glargine basal insulin was associated with higher TBR (β = -0.262, p = 0.009) but lower TAR (β = 0.202, p = 0.041). HbA1c showed negative correlation with TIR (r= -0.449, p <0.001) and TBR (r= -0.466, p <0.001) and positive correlation with TAR (r = 0.580, p <0.001) and mean glucose (r = 0.589, p <0.001). These data demonstrate wide gaps between the recommended vs. real world glycemic variables in patients with T1DM in thisregionon multiple daily insulin injections. CGM identifies glycemic variability and complements HbA1c in improving glycemic control.

Efficacy and safety of basal insulins in people with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.

The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation. A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach. Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses. The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.

A Cross-National Comparison of Biosimilars Pricing in Argentina, Australia, Brazil, and Italy.

Biosimilar medicines are defined as biological products highly similar to an already licensed biological product (RP). The market entry of biosimilars is expected to reduce the costs of biological treatments. This study aims to evaluate the range of differences between the prices of biosimilars and the corresponding RP for biologicals approved in four countries. This is a cross-national comparison of pricing of biosimilars in Argentina, Australia, Brazil, and Italy. The study examined online price databases provided by the national authorities of the investigated countries. Biosimilar price difference was calculated by subtracting the unit price of the biosimilar by the unit price of the RP, and then dividing it by the unit price of the RP. The results were presented as percentage. Brazil had the highest median price reduction (-36.3%) in biosimilars price, followed by Italy (- 20.0%) and Argentina (- 18.6%). All the biosimilars in Italy were priced below the RP presenting a minimum reduction of 6.3%, while in Australia, most of the prices of biosimilars were equal to the RP. In Argentina, one infliximab-biosimilar displayed price above the RP (40.7%) while the lower priced brand had a reduction of 14.4%. Brazil had four biosimilars with prices above the respective RP, including isophane insulin (1), insulin glargine (1) and somatropin (2). The study revealed a marked dispersion in the price's differences between biosimilars and RP across the studied countries. Governments should evaluate whether their policies have been successful in improving affordability of biological therapies.

Computational Approach to Elucidating Insulin-Protamine Binding Interactions and Dynamics in Insulin NPH Formulations.

Insulin NPH is an intermediate-acting insulin. Its protracted action profile is due to the formation of microcrystalline suspensions when insulin is complexed with a basic peptide protamine, zinc ion, and phenolic ligands. Despite advancements in analytical techniques, the binding epitope and binding mode of the protamine in the insulin-protamine complex are still unknown. In this study, we used bioinformatics tools such as molecular docking and molecular dynamics (MD) simulations to compute the binding sites and energetics of the insulin-protamine complex. We have taken four naturally occurring protamine peptides that are independently docked with the insulin R6 hexamer and subjected them to 200 ns MD simulations to observe the dynamics of the complexes and estimate the binding energies. The arginine-rich protamine peptides were found to bind on the surface of the insulin hexamer through hydrogen bonding, hydrophobic, and electrostatic interactions well supported by the calculated negative binding energies. The overall structure of the insulin hexamer was retained upon binding, highlighting its dynamic stability in the complex. Furthermore, the residues at the termini of the protamine peptides in the complex were seen to be highly dynamic, which stabilize toward the end of the simulation.

The effects of induced type I diabetes on developmental regulation of GDNF, NRTN, and NCAM proteins in the dentate gyrus of male rat offspring

BackgroundMaternal diabetes during pregnancy can affect the neurological development of offspring. Glial cell-derived neurotrophic factor (GDNF), neurturin (NRTN), and neural cell adhesion molecules (NCAM) are three important proteins for brain development. Therefore, this study aimed to investigate the impacts of the mentioned neurotrophic factors in the hippocampal dentate gyrus (DG) of rat offspring born to diabetic mothers. MethodsWistar female rats were randomly allocated into diabetic (STZ-D) [(45 mg/kg BW, STZ (Streptozotocin), i.p)], diabetic + NPH insulin (STZ-INS) [(4–6 unit/kg/day SC)], and control groups. The animals in all groups were mated by non-diabetic male rats. Two weeks after birth, male pups from each group were sacrificed and then protein contents of GDNF, NRTN, and NCAM were evaluated using immunohistochemistry. ResultsThe study found that the expression of GDNF and NRTN in the hippocampus of diabetic rat offspring was significantly higher compared to the diabetic+ insulin and control groups, respectively (P < 0.01, P < 0.001). Additionally, the expression of NCAM was significantly higher in the diabetic group the diabetic+ insulin and control groups (P < 0.01, P < 0.001). ConclusionsThe results of the study revealed that diabetes during pregnancy significantly impacts the distribution pattern of GDNF, NRTN, and NCAM in the hippocampus of rat neonates.

Diabetes and Instagram: Analysis of Information in Brazilian Publications

Diabetes Mellitus (DM) is a heterogeneous metabolic disorder, characterized by hyperglycemia. It is a vast disease, involving different classifications, signs, symptoms, and treatment approaches, especially pharmacological. With digital technologies, social media, and the Internet have become disseminating agents of health information, which is often incomplete and incorrect. This study aimed to evaluate the information about pharmacological treatments for DM on Brazilian publications’ Instagram social media platforms. Data from around 300 publications were collected for this study, which was conducted between 2021 and 2022. The characteristics, engagement, and quality of the information were analyzed using the Discern Questionnaire tool. Content evaluation was applied to categories not included in the quality tool. The type of information presented was classified as information disorder. Data were described using descriptive statistics, and inter-examiner agreement was calculated using the kappa coefficient. It was observed that the profiles publishing the information had an average of 6,263.3 followers. Type 2 DM was mentioned in 46.3% of the publications, and the most cited drugs were metformin (10.3%) and NPH insulin (7%). The quality of the information was classified as very poor in 68.8% of the publications. Regarding analysis of the content and type of information, indication, forms of administration, and non-pharmacological treatment presented misinformation and/or disinformation. It is, therefore, important to reinforce digital literacy, so that people can discern the content they are absorbing. Likewise, public policies aimed at regulating the content circulating in the media, are fundamental tools to ensure better information about DM through the Internet.