Insulin Group Research Articles

Evaluation of linagliptin and insulin combined therapy on unfolded protein response in type 1 diabetic mouse heart.

The aim of this study is to reveal the effects of the use of linagliptin, a DPP-4 inhibitor due to its beneficial cardiovascular effects, on endoplasmic reticulum stress (ERS) signaling, which is involved in the pathogenesis of cardiovascular complications related to type 1 diabetes. BALB/c female mice (n = 72) were divided into six groups: control, diabetes+insulin, diabetes+linagliptin, diabetes+linagliptin+insulin, diabetes+TUDCA, and diabetes+TUDCA+insulin. Immunohistochemistry and western blot method, qRT-PCR, ELISA method, and malondialdehyde (MDA) measurements were performed. Linagliptin administered to the type 1 diabetic mouse heart significantly reduced the expression levels of the total and cleaved forms of ATF6, ATF4, and p-JNK, caspase 3. Immunohistochemical and western blot analyses revealed that cleaved caspase 3 protein expression was significantly increased in the diabetes+insulin group compared to the other groups. According to ELISA findings, TUDCA was more effective in reducing NOX 1 and MDA levels than linagliptin. While linagliptin decreased the Chop mRNA level, no change was observed in the Grp78 mRNA level. Our findings showed that there was not much difference between the administration of linagliptin alone or in combination with insulin. Our study reveals that linagliptin is an effective therapeutic agent on ERS and apoptotic UPR in type 1 diabetic hearts.

Comparative Attenuating Impact of Camel Milk and Insulin in Streptozotocin-Induced Diabetic Albino Rats.

In this study, albino Wistar rats that have developed diabetes as a result of the drug streptozotocin (STZ) were treated with camel milk and insulin. For this, 36 rats were divided into six different (n = 6) groups: control, control + camel milk, diabetic control, insulin, camel milk, and combined camel milk + insulin. A 50 mg/kg intraperitoneal injection of STZ was used to induce diabetes. Rats with blood glucose levels exceeding 250 mg/dL after the induction of diabetes were taken into consideration for the study. The diabetic rats were treated with camel milk (50 mL/rat/day), insulin (6 units kg-1 b·wt/day), or their combination daily for 30 days. Throughout the course of the study, the rats' glucose levels and body weight were checked. In the diabetic control rats, a reduction in body weight and hyperglycemic condition was seen. Improvements in glycemic levels and weight gain were seen in the camel milk, insulin, and combined treatment groups compared to the diabetic control group; however, the combined treated group did not show the same degree of improvement as the alone treated group. Hematological changes in the diabetic control group included reductions in lymphocytes, platelets, total leukocyte count (TLC), and red blood cell (RBC) indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), packed cell volume (PCV), and mean cell hemoglobin concentration (MCHC)). Each group that got insulin and camel milk separately and combined showed improvement in these changes. The liver, kidney, and pancreas in the diabetic control group had worsened morphological alterations. These histopathological alternations were significantly improved in the treatment groups. Hence, this study demonstrates the antidiabetic effects of camel milk in comparison to insulin. These findings highlight the potential of camel milk as an alternative therapy for diabetes, although further research is warranted to fully understand its mechanisms of action and long-term effects.

Renal, cardiovascular, and safety outcomes of adding sodium-glucose cotransporter-2 inhibitors to insulin therapy in patients with type-2 diabetes: a meta-analysis.

To investigate the renal, cardiovascular, and safety outcomes when sodium-glucose cotransporter-2 inhibitors (SGLT2is) were added to insulin therapy in patients with type-2 diabetes mellitus (T2DM). We searched Embase, PubMed, and Cochrane libraries for reports published up to Feb 2023. Randomized controlled trials (RCTs) comparing SGLT2is and insulin combination therapy (SGLT2is + INS group) with insulin therapy alone (INS group) in T2DM were included. Fourteen RCTs involving six thousand one hundred twenty subjects with durations of 12-104weeks were included. Compared with the insulin group, the SGLT2is + INS group showed decreased glycosylated hemoglobin values and insulin dosages (P < 0.00001). Meanwhile, the SGLT2is + INS group had a reduced urinary albumin/creatinine ratio (UACR) by 25.42mg/g and uric acid concentration (P = 0.030; P = 0.001, respectively) but the estimated glomerular filtration rate (eGFR) and renal-related adverse events were unaffected (P = 0.070; P = 0.880, respectively). Blood pressure and body weight were lower in the SGLT2is + INS group (P < 0.01). However, the risk of genital infection was bigger when SGLT2is were added to insulin therapy (P < 0.00001), but the risks of severe hypoglycemia or urinary tract infection were equal between the two groups (P > 0.05). Adding SGLT2is to insulin therapy in T2DM patients showed better glucose control and decreased albuminuria, uric acid, blood pressure, and body weight without a reduction in the eGFR.

The influence of insulin resistance variables on heart rate variability indices in mature men under Russia’s North conditions

BACKGROUND: Heart rate autonomic regulation can go out of balance which is normally assessed by the heart rate variability (HRV) indices. Similarly, it is relevant to research if and how HRV fluctuations can be influenced by varying signs of insulin resistance since they are quite common in Northern men. At present, there is no evidence of this influence in the North residents of older ages.AIM: This study aimed to comparatively assess heart rate variability in mature men who do or do not feature metabolic signs of insulin resistance.MATERIALS AND METHODS: Seventy-three mature aged male residents of Magadan Region, Caucasian by origin, were examined. All the subjects were divided into two groups: Group without insulin resistance signs (HOMA-IR index &lt; 2.5 units) and Group with insulin resistance signs (HOMA-IR index &gt; 2.5 units). We used immunochemiluminescent and enzymatic methods, and heart rate variability was assessed using the Varikard (Russia).RESULTS: Our research showed that 48% of all the examinees exhibited signs of insulin resistance along with an increase in the sympathetic activity in heart rate regulation. We also identified the heart rate indicators that had proved to undergo the most significant changes depending on the HOMA-IR index and the presence or absence of signs of insulin resistance: MxDMn, pNN50, SDNN, AMo50, SI, TP, HF, LF, and Body Mass.CONCLUSION: In general, the results obtained allow for ascertaining the high proportion of male Northerners of mature age with signs of insulin resistance. We also claim that those examinees demonstrate an autonomic imbalance and a moderate dominance of the sympathetic activity with a simultaneous decrease in activation of the parasympathetic link of autonomic nervous system and high body mass variables. At the same time, the correlations and causal associations among signs of insulin resistance, activation of the sympathetic link of autonomic nervous system, and overweight remain unclear. Apparently, all the analyzed features are likely to complement each other rather than completely exclude each other. The triad of obesity, signs of insulin resistance, and activation of the sympathetic link of autonomic nervous system is a driving factor for significant health risks. This study is expected to spread the use of the method of assessing heart rate variability based on insulin resistance signs as well as in reliance on metabolic disorders in general in a sample of mature men.

Effect of insulin on bone formation ability of rat alveolar bone marrow mesenchymal stem cells.

The alveolar bone marrow mesenchymal stem cells (ABM-MSCs) play an important role in oral bone healing and regeneration. Insulin is considered to improve impaired oral bones due to local factors, systemic factors and pathological conditions. However, the effect of insulin on bone formation ability of ABM-MSCs still needs to be elucidated. The aim of this study was to determine the responsiveness of rat ABM-MSCs to insulin and to explore the underlying mechanism. We found that insulin promoted ABM-MSCs proliferation in a concentration-dependent manner, in which 10-6 M insulin exerted the most significant effect. 10-6 M insulin significantly promoted the type I collagen (COL-1) synthesis, alkaline phosphatase (ALP) activity, osteocalcin (OCN) expression and mineralized matrix formation in ABM-MSCs, significantly enhanced the gene and protein expressions of intracellular COL-1, ALP and OCN. Acute insulin stimulation significantly promoted insulin receptor (IR) phosphorylation, insulin receptor substrate-1 (IRS-1) protein expression and mammalian target of rapamycin (mTOR) phosphorylation, but chronic insulin stimulation decreased these values, while inhibitor NT219 could attenuate these responses. When seeded on β-tricalcium phosphate (β-TCP), ABM-MSCs adhered and grew well, during the 28-day culture period, ABM-MSCs+β-TCP+10-6 M Insulin group showed significantly higher extracellular type I collagen amino-terminus prolongation peptide (TPINP) content, ALP activity, OCN secretion, Ca and P concentration. When implanted subcutaneously in severe combined immunodeficient mice for 1 month, the ABM-MSCs+β-TCP+10-6 M Insulin group obtained the most bone formation and blood vessels. These results showed that insulin promoted the proliferation and osteogenic differentiation of ABM-MSCs in vitro, and enhance osteogenesis and angiogenesis of ABM-MSCs in vivo. Inhibition studies demonstrated that the insulin-induced osteogenic differentiation of ABM-MSCs was dependent of insulin/mTOR signaling. It suggests that insulin has a direct anabolic effect on ABM-MSCs.

Chemical Modification of the Amino Groups of Human Insulin: Investigating Structural Properties and Amorphous Aggregation of Acetylated Species.

The efficacy of human recombinant insulin can be affected by its aggregation. Effects of acetylation were observed on insulin structure, stability, and aggregation at 37 and 50°C and pH of 5.0 and 7.4 with the use of spectroscopy, circular dichroism (CD), dynamic light scattering (DLS), and atomic force microscopy (AFM). Raman and FTIR results were indicative of structural changes in AC-INS, and CD analyses showed a slight increase in β-sheet content in AC-INS. Melting temperature (Tm) measurements indicated an overall more stable structure and spectroscopic assessment showed a more compact one. Formation of amorphous aggregates was followed over time and kinetics parameters showed a longer nucleation phase (higher t* amount) and lower aggregates amount (lower Alim) for acetylated insulin (AC-INS) compared to native (N-INS) in all tested conditions. The results of amyloid-specific probes approved the formation of amorphous aggregates. Size particle and microscopic analysis suggested that AC-INS was less prone to form aggregates, which were smaller if formed. In conclusion, this study has demonstrated that controlled acetylation of insulin may lead to its higher stability and lower propensity toward amorphous aggregation and has provided insight into the result of this type of post-translational protein modification.

Safety and efficacy of non-insulin therapy in non-critically ill hospitalized patients with type 2 diabetes mellitus

IntroductionClinical guidelines recommend insulin as the mainstay of therapy for hospitalized patients with diabetes mellitus. The aim of the current study is to evaluate safety and efficacy of non-insulin anti-hyperglycemic therapy in hospitalized patients. Materials and methodsSystematic review and meta-analysis of randomized controlled trials (RCTs) examining treatment of hospitalized patients with type 2 diabetes with insulin vs non-insulin therapy. We searched PubMed and the Cochrane Library for RCTs published from inception to November 30, 2022. Primary outcomes were 30-day mortality and hypoglycemic events during hospitalization. This meta-analysis includes two parts, the first is a comparison between insulin and non-insulin therapy and the second is a comparison between insulin only and a combination of insulin+non-insulin therapy. ResultsA total of 14 randomized control studies and 1570 patients were included. There was a lower incidence of 30-day mortality in the insulin+non-insulin group compared with the insulin group without statistical significance, RR 0.64 (95%CI 0.30–1.35). Hypoglycemic events were significantly lower with the non-insulin therapies compared to insulin therapy, RR 0.23 (95%CI 0.09–0.55). Mean daily glucose levels were significantly lower in the insulin+non-insulin group compared to the insulin group by 10.83 mg/dL (95%CI -14.78-(-6.87)). ConclusionsNon-insulin either with or without insulin, results in lower rates of hypoglycemia. Non-insulin+insulin is more effective than insulin alone in reducing blood glucose levels. Non-insulin-based therapy is safe and effective for control of hyperglycemia. Insulin combined with non-insulin drugs seems to be the preferred treatment option for the majority of hospitalized patients with type 2 DM in the non-critical care setting.

100-LB: Dapagliflozin for Inpatient Hyperglycemia in Cardiac Surgery Patients with Type 2 Diabetes—Randomized Controlled Trial

Sodium/glucose cotransporter-2 (SGLT2) inhibitors have not been assessed extensively for the treatment of hyperglycemia in noncritically ill, hospitalized patients with type 2 diabetes (T2D). In this investigator-initiated, treat-to-target, randomized trial, 250 cardiac surgery patients with T2D were randomly assigned (1:1) to receive dapagliflozin 10 mg daily plus basal-bolus insulin (DAPA group) or basal-bolus insulin alone (INSULIN group) in the early postoperative period. The primary outcome was mean differences between groups in their daily blood glucose (BG) concentrations. The major safety outcomes were the occurrence of severe ketonemia/diabetic ketoacidosis (DKA) and hypoglycemia. All analyses were performed according to the intention-to-treat principle. There were no differences in mean daily BG concentrations (149 vs. 150 mg/dL), mean percentage of readings within the target BG of 70-180 mg/dL (82.7% vs. 82.5%), daily total insulin dose (mean, 39 vs. 40 units/day), number of daily insulin injections (median, 3.9 vs. 4), length of stay (median, 10 vs. 10 days), or hospital complications (21.6% vs. 24.8%) between the DAPA and INSULIN groups. Mean plasma ketone levels were significantly higher in the DAPA group than in the INSULIN group at day 3 (0.71 vs. 0.30 mmol/L) and day 5 (0.42 vs. 0.19 mmol/L) of randomization. Six patients in the DAPA group developed severe ketonemia, but none developed DKA. There were no differences in the proportion of patients with BG &amp;lt;70 mg/dL (9.6% vs. 7.2%) between the treatment groups. Numerically fewer patients in the DAPA group developed acute kidney injury (7.2%) than in the insulin group (12.8%). These findings indicate that dapagliflozin complementary to basal-bolus insulin does not improve glycemia further over and above the basal-bolus in hospitalized cardiac surgery patients with T2D. However, dapagliflozin is safe and does not increase the incidence of DKA or other complications during the hospital stay. Disclosure M. S. Kuchay: Other Relationship; Boehringer-Ingelheim, Novartis India, Sanofi, Novo Nordisk, Intas Pharmaceuticals Ltd., Sun Pharmaceutical Industries Ltd., USV Private Limited, MSD Life Science Foundation. C. Kohli: None. G. Bakshi: None. V. Radhika: None. S. Saheer: None. M. K. Singh: None. S. Mishra: Other Relationship; Abbott, Novo Nordisk, Sanofi, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Intas Pharmaceuticals Ltd., Sun Pharmaceutical Industries Ltd., Merck Sharp &amp; Dohme Corp., Cipla Inc. P. Khatana: None. M. Mishra: None. P. S: None. P. Kaur: Other Relationship; Abbott, AstraZeneca, Boehringer Ingelheim Inc., Eris Lifesciences Ltd., Novartis India, Sanofi. J. S. Wasir: Other Relationship; Abbott, AstraZeneca, Novartis. H. Kaur: Other Relationship; AstraZeneca, Novo Nordisk, Sanofi, Intas Pharmaceuticals Ltd., Sun Pharmaceutical Industries Ltd. A. Singh: None. R. Jain: Other Relationship; Abbott, AstraZeneca, Lilly Diabetes. Funding Diabetes and Endocrinology Foundation of India

Metformin versus insulin for gestational diabetes: Adiposity variables and adipocytokines in offspring at age of 9 years

AimsTo compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM). Methods172 offspring of 311 mothers randomized to receive metformin (n = 82) or insulin (n = 90) for GDMwere studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA). ResultsSerum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p < 0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016). ConclusionsMaternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys.

Predicting insulin use among women with gestational diabetes diagnosed in oral glucose tolerance test

BackgroundGestational diabetes mellitus (GDM) is one of the most common complications affecting pregnant women. While most women will achieve adequate glycemic levels with diet and exercise, some will require pharmacological treatment to reach and maintain glucose levels between the desired thresholds. Identifying these patients early in pregnancy could help direct resources and interventions.MethodsThis retrospective cohort of women with GDM diagnosed with an abnormal 75g-OGTT presents data from 869 patients (724 in the diet group and 145 in the insulin group). Univariate logistic regression was used to compare the groups, and multivariable logistic regression was used to identify independent factors associated with the need for insulin. A log-linear function was used to estimate the probability of requiring pharmacological treatment.ResultsWomen in the insulin group had higher pre-pregnancy BMI index (29.8 vs 27.8 kg/m2, odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03–1.09), more frequent history of previous GDM (19.4% vs. 7.8%, OR 2.84, 95% CI 1.59–5.05), were more likely to have chronic hypertension (31.7% vs. 23.2%, OR 1.54, 95% CI 1.04–2.27), and had higher glucose levels at all three OGTT points. Multivariable logistic regression final model included age, BMI, previous GDM status, and the three OGTT values as predictors of insulin requirement.ConclusionsWe can use regularly collected data from patients (age, BMI, previous GDM status, and the three OGTT values) to calculate the risk of a woman with GDM diagnosed in OGTT needing insulin. Identifying patients with a greater risk of requiring pharmacological treatment could help healthcare services to better allocate resources and offer closer follow-up to high-risk patients.

Localised insulin administration for wound healing in non-diabetic adults: A systematic review and meta-analysis of randomised controlled trials.

Insulin has the potential to restore damaged skin and due to its affordability and global availability, it is an agent of interest when it comes to pioneering new remedies to accelerate wound healing. The aim of this study was to explore the efficacy and safety of localised insulin administration on wound healing in non-diabetic adults. Studies were systematically searched, using the electronic databases Embase, Ovid MEDLINE and PubMed, screened, and extracted by two independent reviewers. A total of seven randomised controlled trials that met the inclusion criteria were analysed. Risk of bias was assessed using the Revised Cochrane Risk-of-Bias Tool for Randomised Trials and a meta-analysis was performed. The primary outcome, which explored rate of wound healing (mm2 /day), concluded that there was an overall significant mean improvement in the insulin treated group (IV = 11.84; 95% CI: 0.64-23.04; p = 0.04; I2 = 97%) compared to the control group. Secondary outcomes concluded that there is no statistical difference between the healing time (days) of the wound (IV = -5.40; 95% CI: -11.28 to 0.48; p = 0.07; I2 = 89%); there is a significant reduction in wound area in the insulin group; no adverse events were noted with the administration of localised insulin; quality of life improves drastically as the wound heals, irrespective of insulin. We conclude that although the study showed an improved wound healing rate, other parameters were not statistically significant. Therefore, larger prospective studies are warranted to fully explore the effects of insulin on different wounds, where an appropriate insulin regime can be developed for clinical practice.

The diabetes insulin self-management education (DIME) intervention for people with type 2 diabetes starting insulin: a pilot feasibility randomised controlled trial

ObjectiveTo determine the feasibility and acceptability of a diabetes insulin self-management education (DIME) group intervention for people with type 2 diabetes starting insulin.DesignSingle-centre parallel randomised pilot trial.SettingPrimary care, South London, UK.SubjectsAdults with type 2 diabetes, requiring insulin treatment, on maximum tolerated dose of 2 or more oral antidiabetic drugs with HbA1c > / = 7.5% (58 mmol/mol) on 2 occasions. We excluded people who were non-fluent in English; morbid obesity (BMI > / = 35 kg/m2); in employment that contraindicates insulin treatment; and those with severe depression, anxiety disorders, psychotic disorders, personality disorders, or cognitive impairment.MethodsParticipants were randomised using blocks of 2 or 4 to 3, 2-h group, face-to-face, DIME sessions or standard insulin group education sessions (control). We assessed feasibility according to consent to randomisation and attendance at intervention (DIME) and standard group insulin education sessions. Acceptability of the interventions was determined using exit interviews. We additionally measured change in self-reported insulin beliefs, diabetes distress and depressive symptoms between baseline and 6-month post-randomisation.ResultsThere were 28 potentially eligible participants, of which 17 consented to randomisation, 9 were allocated to the DIME group intervention and 8 were allocated to the standard group insulin education. Three people withdrew from the study (1 from DIME and 2 from standard insulin education) before the start of the first session and did not complete baseline questionnaires. Of the remaining participants (n = 14), all DIME participants (n = 8) completed all 3 sessions, and all standard insulin education participants (n = 6) completed at least 1 standard insulin education session. The median group size was 2, the mean age of participants was 57.57 (SD 6.45) years, and 64% were female (n = 9). Exit interviews demonstrated that all participants (n = 7) found the group sessions acceptable, and thematic analysis of interview transcripts indicated social support, the content of group sessions and post-group experiences were positive, especially amongst DIME participants. There was improvement on self-report questionnaires.ConclusionsThe DIME intervention was acceptable and feasible to deliver to participants with type 2 diabetes starting insulin in South London, UK.Trial registrationInternational Study Registration Clinical Trial Network (ISRCTN registration number 13339678).

Oral Health Indices in Patients With Type 2 Diabetes Receiving Insulin Treatment Compared With Metformin: A Cross-sectional Study

Objectives: Due to the important influence of glycemic control on oral health, this study aimed to compare the gingival index and decayed, missing, filled teeth (DMFT) in participants with type 2 diabetes mellitus receiving insulin and metformin. Materials and Methods: In this cross-sectional study, 130 participants with type 2 diabetes mellitus treated with insulin and metformin were studied in two groups based on the type of treatment. The information for DMFT and gingival indices were obtained using the oral examination. In the insulin group, participants received insulin Lantus 0.2 unit/kg once daily, and in the metformin group, participants received metformin tablets 500 mg every 12 hours. Glycosylated hemoglobin A1c (HbA1c) was measured by lab test in all participants. Finally, HbA1c, the information of DMFT, and gingival indices were compared between the two groups. Results: The results showed that there were no statistically significant differences in decayed, missed, and restored teeth, as well as the overall DMFT index between the two groups. The gingival index was significantly higher in the insulin group (P=0.046). Conclusions: Gingival health of insulin users is poorer than metformin users, but it seems that type of diabetes treatment does not affect the DMFT index

The effect of maternal diabetes on the expression of gamma-aminobutyric acid and metabotropic glutamate receptors in male newborn rats' inferior colliculi.

Few studies have examined the molecular alterations in the auditory pathway of infants of diabetic mothers, notwithstanding the fact that maternal diabetes may have an impact on the development of the neonatal peripheral and central nervous systems. Male newborn rats were studied to determine how maternal diabetes affected the expression of gamma-aminobutyric acid (GABAAα1 and GABAB1) and metabotropic glutamate (mGlu2) receptors in the inferior colliculus (IC) in this research. Female rats were given a single intraperitoneal injection of streptozotocin (STZ) at a 65 mg/kg dose to develop a model of diabetic mothers. The study population was split into sham, diabetes without treatment, and diabetes with insulin groups. Their male neonatal rats were anesthetized on P0, P7, and P14 after mating and delivery. The receptors' distribution pattern was studied using immunohistochemistry (IHC). Pairwise comparison in the groups revealed that the GABA receptors (Aα1 and B1) were significantly downregulated in the diabetes without treatment group (p<0.001). Furthermore, pairwise comparison in the groups indicated significant mGlu2 upregulation in the diabetes without treatment group (p<0.001). Regarding the concentration of all receptors, there was no discernible distinction between the diabetes with insulin and sham groups. This investigation showed that the concentration of GABAAα1 and GABAB1 receptors decreased significantly over time, whereas the concentration of mGlu2 receptors increased significantly over time in male neonatal rats born to streptozotocin-induced diabetic mothers.

Serum insulin concentration in dogs with insulinoma as a clinical marker for presence of metastasis at the time of diagnosis.

Information regarding serum insulin concentration in dogs newly diagnosed with insulinoma and its association with clinical stage and survival time is lacking. Examine association between serum insulin concentration and survival and clinical disease stage in dogs with insulinoma. Fifty-nine client-owned dogs with a diagnosis of insulinoma from 2 referral hospitals. Retrospective observational study. The χ2 test was used to compare the proportion of dogs with increased insulin concentration in groups with or without metastasis at the time of diagnosis. Linear mixed-effect models were built to compare differences in insulin concentration between dogs with and without evidence of metastasis at the time of original diagnosis. Cox's proportional hazards regression and Kaplan-Meier graphs were used to evaluate the association between insulin concentration and insulin groups and survival. Median serum insulin concentration was 33 mIU/L (range, 8-200 mIU/L) in dogs with World Health Organization (WHO) stage I disease and 45 mIU/L (range, 12-213 mIU/L) in dogs with WHO stage II and III disease. No difference was found in the proportion of dogs with increased insulin concentration with or without metastasis (P = .09). No association was identified between insulin concentration and survival (P = .63), and between dogs grouped by insulin concentration and survival (P = .51). Serum insulin concentrations were not different between dogs with or without metastasis at diagnosis. The degree of insulinemia does not provide further information regarding the stage of the disease and is not associated with survival time in dogs with insulinoma.

Are Insulin Mimetics Protective Against Comorbidity in Patients With Neuro-Autoimmune Disease? (P10-5.016)

<h3>Objective:</h3> To investigate the neuroprotective potential of insulin mimetics (IM) in patients with neuro autoimmune disease (NAD) and high risk comorbidities. <h3>Background:</h3> IM are used to treat patients with diabetes mellitus (DM) and have been shown to protect against progressive neurological damage. Despite their neuroprotective benefits, the extent of their neuroprotection in patients with NAD has not been completely characterized. <h3>Design/Methods:</h3> A retrospective analysis on 34464 patients hospitalized at a tertiary care center in a major metropolitan area was conducted. 168 patients were taking IM medications. 7848 patients were taking medicine other than IM for their DM (nIM). 7690 patients were taking insulin without IM medications. 26448 patients were not on any DM medication (nDM). The outcomes compared included the prevalence of NAD, diabetic neuropathy and/or retinopathy (DMNR), and the prevalence of high risk comorbidities defined as those with either heart failure, chronic kidney disease, stroke, or encephalopathy. <h3>Results:</h3> The prevalence of NAD was 0.6%, 0.52%, 0.53%, 0.56% among patients in the IM, nIM, insulin, and nDM groups respectively (p&gt;0.05). 19.5% of NAD and 23.6% of those without NAD had high risk comorbidities (p&gt;0.05). Among those with autoimmune disease, 31% of those taking any diabetic medication and 16% of nDM had high risk comorbidities (p&gt;0.05). The prevalence of DMNR was 10% and 8% in IM and nIM groups respectively (p&gt;0.05). <h3>Conclusions:</h3> These results suggest that IM medications may benefit patients with NAD against additional comorbidity as those without NAD and DM are expected to have less high risk disease. However, more studies are needed to determine whether IM medications play a role in neuro-autoimmune disease progression and mortality. <b>Disclosure:</b> Ms. Azhar has nothing to disclose. Mr. Ahmed has nothing to disclose. Mr. Ahmed has nothing to disclose. Mr. Ahmed has nothing to disclose. Mr. Azhar has nothing to disclose. Dr. Souayah has received publishing royalties from a publication relating to health care.

Diabetes-related outcomes with basal-bolus vs. premixed insulin among veterans with type 2 diabetes: A single institutional retrospective study

BackgroundThe purpose of this study was to compare diabetes (DM)-related outcomes between basal-bolus (BB) and premixed (PM) insulin regimens. MethodsRetrospective chart review including veterans with type 2 diabetes (T2DM), ≥18 years old with hemoglobin A1c (HbA1c) ≥8%. Outcomes were assessed after one year of BB or PM insulin therapy. Data were analyzed using Chi-square/Fisher exact tests and logistic regression. ResultsOut of 140 enrolled subjects (70 BB and 70 PM), 94% were males with average age and duration of DM of 65.7 ± 10.1 and 12.9 ± 9 years, respectively. The BB and PM groups were similar in age, gender distribution, HbA1c, body mass index (BMI) and DM duration at baseline. Following 1 year of treatment, there was no significant difference between the groups for change in HbA1c (-1.9 ± 1.8 vs -2.1 ± 1.9%, p = 0.3) or hypoglycemia rate (30% vs 21.4%, p = 0.3), respectively. There was similar increase in average BMI in both groups (0.84 ± 3.1 for BB vs 0.4 ± 2.2 kg/m2 for PM, p = 0.2). ConclusionsThere were no significant differences for glycemic control, hypoglycemia rate or BMI between the BB or PM insulin groups. These results suggest PM insulin is equally effective and safe as BB insulin.

Effect of Repeated Intranasal Administration of Different Doses of Insulin on Postoperative Delirium, Serum τ and Aβ Protein in Elderly Patients Undergoing Radical Esophageal Cancer Surgery.

Postoperative delirium is common after general anesthesia in older patients. However, there are currently no effective preventive measures. This study investigated the effect of repeated intranasal administration of different insulin doses before surgery on postoperative delirium in older patients with esophageal cancer, and the possible mechanism for its efficacy. In this randomized, placebo-controlled, double-blind, parallel-group study, 90 older patients were randomly assigned to either a Control (normal saline), Insulin 1 (20 U/0.5 mL intranasal insulin), or Insulin 2 (30 U/0.75 mL intranasal insulin) group. Delirium was assessed on postoperative days 1 (T2), 2 (T3), and 3 (T4) using the Confusion Assessment Method for the Intensive Care Unit. Serum τ and Aβ protein levels were measured at T0 (before insulin/saline administration), T1 (end of surgery), T2, T3 and T4. The Insulin 2 group had a significantly lower prevalence of delirium compared to the Control and Insulin 1 groups three days after surgery. Compared to baseline, τ and Aβ protein levels increased significantly at T1-T4. Compared to the Control group, the Insulin 1 and 2 groups had significantly lower τ and Aβ protein levels at T1-T4, and the Insulin 2 group had significantly lower levels than the Insulin 1 group at T1-T2. The administration of 30 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can significantly reduce postoperative delirium in older patients undergoing radical esophagectomy. It can also decrease postoperative τ and Aβ protein expression without causing hypoglycemia. This study was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier: ChiCTR2100054245; December 11, 2021).

Доказанная эффективность и безопасность применения инсулина деглудек при лечении сахарного диабета 1 типа у беременных

Diabetes mellitus (DM) remains a disease that determines the high frequency of obstetric and perinatal complications. Achieving the physiological values of glycemia as the main condition for the successful course and outcomes of pregnancy in women with diabetes remains a difficult task to date. To improve the quality of treatment of patients with DM 1 type, the method of basic bolus insulin therapy has been used for more than 30 years. Therefore, the emergence of new effective and safe insulins is extremely important for improving pregnancy outcomes in patients with diabetes. Insulin degludec is an analogue of basal insulin of the new generation with improved pharmacokinetic and pharmacodynamics profiles compared to analogues of basal insulins of the previous generation, however, there was insufficient data on its use during pregnancy. This article presents the results of an open international randomized controlled study of EXPECT no less effective use of insulin degludec during pregnancy, which took place in 14 countries in 56 research centers, 8 of them in Russia. Of the 225 women with DM 1 type who participated in the study, 67 were from Russia. The EXPECT study compared the efficacy and safety of insulin degludec with insulin detemir (both in combination with insulin aspart) in pregnant women with DM 1 type. Insulin detemir was chosen as a comparison drug, since it is the first basal insulin analog approved for use during pregnancy and most often recommended as a first-line drug when choosing long-acting insulin for the treatment of diabetes in pregnant women. Material and methods. The study included women over the age of 18 with DM 1 type, whose gestation period ranged from 8 (+0 days) to 13 (+6 days) weeks and who were just planning a pregnancy. The study participants (1:1) were randomized using an interactive Internet system for the use of insulin degludec at a dose of 100 U/ml once a day or insulin detemir at a dose of 100 U/ml once or twice a day, while both drugs were taken in combination with insulin aspart at a dose of 100 U/ml. Pregnant women received the study drug at randomization, throughout the entire period of pregnancy and up to 28 days after delivery (the end of the study). Women who were not pregnant at the time of randomization started taking the study drug before conception. The primary endpoint is the last scheduled measurement of glycated hemoglobin (HbA1c) before childbirth (a field of at least 0.4% efficiency for degludec compared to detemir). Secondary endpoints are efficacy, safety for the mother, and pregnancy outcomes. The primary endpoint was evaluated in all randomized women who were pregnant during the study. Safety – for all participants who were pregnant during the study and received at least one dose of the study drug. This study is registered on the website ClinicalTrials.gov numbered NCT03377699 and currently completed. Results. From November 22, 2017 to November 8, 2019, out of 296 screened women, 225 were randomized for insulin degludec (n = 111) or insulin detemir (n = 114). The average HbA1c value at the initial stage of pregnancy in the degludec insulin group was 6.6% with a standard deviation (SD) of 0.6%, in the detemir insulin group -6.5% with SD of 0.8%. In the degludec insulin group, the average value of the last planned measurement of HbA1c before childbirth was 6.2% (SD – 0.07%; 45 mmol/mol), in the detemir insulin group – 6.3% (SD – 0.07%; 46 mmol/mol). The estimated difference between the treatment groups is -0.11% (95% CI -0.31–0.08); -1.2 mmol/mol (95% CI -3.4–0.9); p &lt; 0.0001 which confirms the equally effective effectiveness of insulin degludec. When using insulin degludec, no additional safety-related problems were reported compared to the use of insulin detemir.

Effect of Growth Factors and Hormones during In Vitro Growth Culture of Cumulus-Oocyte-Complexes Derived from Small Antral Follicles in Pigs

This study evaluated the effect of various growth factors and hormones in an in vitro growth (IVG) medium on the in vitro maturation (IVM) and developmental competence of oocytes derived from small antral follicles (SAFs) in pigs. Cumulus-oocyte complexes (COCs) derived from SAFs were either untreated or treated with epidermal growth factor (EGF), insulin-like factor-1 (IGF-1), insulin, or growth hormone (GH) for 2 days of IVG. Following IVG, COCs were cultured for maturation, and IVM oocytes were induced for parthenogenesis (PA). During IVG, the nuclear maturation of oocytes was significantly increased by the insulin treatment compared to other treatments. Moreover, the insulin treatment significantly increased blastocyst formation after PA relative to the No-IVG, control, EGF, and GH treatments. The cumulus expansion score after IVG-IVM was significantly higher in the insulin group than in the other groups. The glutathione (GSH) contents in IVM oocytes were increased through treatment with IGF, insulin, and GH compared to those of No-IVG oocytes. The level of reactive oxygen species (ROS) in IVM oocytes in all treatment groups was significantly lower after IVG culture than in the No-IVG group. The maturation-promoting factor (MPF) activity after IVM in the insulin-treated oocytes was significantly higher than that of the oocytes treated with EGF, IGF-1, and GH. In conclusion, this study demonstrates that insulin treatment during IVG culture improves the maturational and developmental competence of oocytes derived from SAFs in pigs through its effect on cumulus cell expansion and cytoplasmic microenvironments, such as GSH, ROS, and MPF activity.