Insulin Group Research Articles

Efficacy and Safety of Intramuscular Insulin Lispro vs. Continuous Intravenous Regular Insulin for the Treatment of Dogs With Diabetic Ketoacidosis.

The use of rapid-acting insulin analogs as routes of administration other than IV has never been described for the treatment of dogs with diabetic ketoacidosis (DKA). This study aims to compare the efficacy and safety of a new protocol based on IM administration of insulin lispro with that of low-dose IV continuous rate infusion of regular insulin in the treatment of canine DKA. Client-owned dogs with naturally occurring DKA were included. Dogs treated with IM insulin lispro (Group L, n = 11) received 0.25 U/kg. The goal was to achieve a drop of at least 10% in blood glucose between 1 h and the next. If this goal was not achieved, the insulin dose was repeated hourly; otherwise, the insulin dose was not repeated up to a maximum of 3 h, after which the insulin dose was repeated anyway. When blood glucose was ≤250 mg/dL, the insulin dose was reduced to 0.125 U/kg IM every 3 h. Cases receiving IV continuous rate infusion of regular insulin (Group R, n = 13) were treated according to a previously published protocol. The median time to resolution of ketosis was significantly shorter in Group L (12 h; range, 4–27 h) compared to Group R (23 h; 10–46 h; P = 0.04). The median times to resolution of acidemia and ketoacidosis were 13 h (4–35 h) and 17.5 h (4–35 h) in Group L, and 22 h (9–80 h) and 23.5 h (10–80 h) in Group R, respectively. These differences were not significant (P = 0.06 and P = 0.09, respectively). The median length of hospitalization did not differ significantly between groups (P = 0.67). There were no differences in the frequency and severity of adverse events (hypoglycemia, hypokaliemia, and hypophosphatemia) between groups. The new protocol based on IM administration of insulin lispro preliminarily appears effective and safe for treatment of canine DKA.

Efficacy and Safety of Metformin in Gestational Diabetes Mellitus

Background: Gestational Diabetes Mellitus (GDM) is a sequence of serious unfavorable maternal and perinatal outcomes specially if uncontrolled. Although insulin is a standard therapy, Metformin can be used as an alternative medication to insulin. This study aimed to establish the efficacy, safety, and other metabolic effects of metformin in GDM due to limited studies in the local population. Methods: This quasi experimental trial was conducted on pregnant female at 24 weeks of gestation and above, presenting to Ziauddin Hospital. A total of 361 patients who were diagnosed with GDM were enrolled. Patients were divided into three groups: diet control, metformin, and metformin with insulin. The Chi Square and ANOVA were used to compare the maternal and neonatal outcomes. Further post hoc analysis of significant parameters was done using Tukey HSD test. Results: Weight gain in pregnancy and gestational age at delivery gives significant mean differences across three study groups (p=<0.01). In diet control group, weight was significantly gained as compare to metformin group. Similarly, the gestational age in diet control group was significantly higher as compare to metformin and metformin with insulin group (p=<0.01). The higher gestational age was found in patients treated with metformin as compared to metformin with insulin group (37.25±1.41). Conclusion: Metformin alone as well as in combination with insulin, is a safe, effective treatment option and more acceptable to women with GDM. Metformin has shown to cause less weight gain during pregnancy with minimal risk of maternal and neonatal hypoglycemia. Keywords: Gestational Diabetes Mellitus; Metformin; Insulin

Low-Molecular-Weight Heparin Combined With Insulin Versus Insulin Alone in the Treatment of Hypertriglyceridemic Pancreatitis (LIHTGP Trial): Study Protocol for a Multicenter, Prospective, Single-Blind, Randomized Controlled Trial.

Currently, insulin and/or heparin/low-molecular-weight heparin (LMWH) serve as an early lipid-lowering treatment for hypertriglyceridemic pancreatitis (HTGP). However, whether the clinical prognosis of combining LMWH with insulin is superior to using insulin alone remains unknown. This trial will compare the clinical outcomes of LMWH with insulin and an insulin regimen for emergency lipid-lowering treatment in HTGP patients. In total, 476 eligible participants will be recruited from 18 hospitals throughout China. Participants in the LMWH group will receive LMWH combined with insulin, whereas insulin alone will be administered to those in the insulin group. The patients will be followed up at 3 and 6 months after discharge. Adverse reactions will be evaluated by the safety monitoring committee. Safety outcomes and adverse events will also be recorded. The study is registered in the Chinese Clinical Trial Registry (No: ChiCTR1900023640). Recruitment will begin in August 2019 and will be completed in December 2021 (http://www.chictr.org.cn/index.aspx). No data are available now. The trial will investigate the efficacy of using LMWH combined with insulin as an emergency lipid-lowering treatment in reducing new organ failure, mortality, hospital stays, and expenses compared using with insulin alone for patients with HTGP.

SGLT2i as fourth-line therapy and risk of mortality, end-stage renal diseases and cardiovascular diseases in patients with type 2 diabetes mellitus

AimCurrent guideline recommends insulin as fourth-line glucose-lowering medications. However, treatment effects of sodium glucose co-transporter-2 inhibitors (SGLT2i) on the risk of complications are uncertain. This study examines risks of all-cause mortality, cardiovascular diseases (CVD) and end-stage renal diseases (ESRD) in type 2 diabetes mellitus (T2DM) patients on triple oral glucose-lowering medications initiating SGLT2i, insulin or other oral medications. MethodsA population-based retrospective cohort of patients with T2DM between 2006–2017 was extracted from Hong Kong Hospital Authority database. Patients who were initiated a fourth-line therapy with SGLT2i, insulin or other oral medications were included. Hazard ratios (HRs) for all-cause mortality, CVD and ESRD were assessed using Cox proportional hazard models. ResultsOver a median follow-up period of 18.5 months with 63,122 person-years, SGLT2i and insulin group had the lowest and highest incidence rate of all-cause mortality, CVD and ESRD (1.06, 0.65 and 0.61 vs 4.25, 5.58 and 4.39/100 person-years), respectively. Initiating SGLT2i as fourth-line medication had more benefits on CVD, in particular coronary heart disease and stroke. Insulin users had higher risks of CVD (HR=8.04, 95%CI=3.06–21.12) than SGLT2i users. SGLT2i was associated with insignificant reduction in ESRD (HR=4.62, 95%CI=0.73–29.09) and all-cause mortality (HR=3.06, 95%CI=0.75–12.45), and HF (HR=2.99, 95%CI=0.37–24.42) among patients without established HF. ConclusionAmong T2DM patients initiating fourth-line therapy, SGLT2i users had significant benefits in lowering risk of CVD, and potential benefits in lowering risks of ESRD and all-cause mortality. SGLT2i was the preferred fourth-line glucose-lowering medication least likely to be associated with complication risks.

Real-world evaluation of adverse pregnancy outcomes in women with gestational diabetes mellitus in the German health care system

AimsThis study aims to estimate the incidence of adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) in Germany. MethodsPregnant women were identified from a health claims database for the year of 2016. Three groups were defined: general population without GDM, women with GDM without treatment and women with GDM and insulin treatment. Operationalisation of outcomes was aligned with the hyperglycaemia and adverse pregnancy outcomes (HAPO) study. ResultsThe cohort consisted of 58,297 mother-child pairs. Of those, 7245 had a GDM diagnosis and 1407 had a GDM diagnosis with a prescription of insulin. Adverse pregnancy outcomes were higher in both GDM groups compared to the control group. Birthweight (OR 2.08 [95% CI 1.50–2.90]), primary caesarean section (OR 1.70 [95% CI 1.48–1.95]), intensive neonatal care (OR 1.25 [95% CI 1.04–1.50]), preeclampsia (OR 1.51 [95% CI 1.23–1.85]), and clinical neonatal hypoglycaemia (OR 5.32 [95% CI 4.27–6.62]) were higher in the GDM+insulin group in comparison to a control group after adjustment for potential confounders. ConclusionMost of the adverse pregnancy outcomes were moderately higher in both identified GDM groups in comparison to women without GDM. Women receiving insulin treatment are at an increased risk of most of the defined adverse pregnancy outcomes.

EFFICACY AND SAFETY OF IV INSULIN INFUSION FOR MANAGEMENT OF HYPERTRIGLYCERIDEMIC PANCREATITIS

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Hypertriglyceridemic pancreatitis (HTGP) portends significant morbidity and mortality, and management involves rapid lowering of serum triglycerides (TG). Both plasmapheresis (PL) and intravenous (IV) insulin infusions are effective for this purpose, although comparative analyses of these interventions have not been performed. Furthermore, the role of IV insulin in patients with HTGP without diabetes remains unknown. We aimed to investigate these questions in a cohort of patients hospitalized for HTGP at a tertiary care center. METHODS: A retrospective chart review of patients hospitalized for acute HTGP between January 1, 2001 and December 31, 2018 was performed. Patients were stratified according to treatment modality: IV insulin infusion, PL+/- IV insulin, or conservative management. Efficacy of TG-lowering and clinical outcomes were compared between groups. RESULTS: One hundred and four patients with HTGP were identified. Seventy-eight patients (75 %) were treated with IV insulin, 6 (5.8%) were treated with PL, and 20 (19.2%) received conservative management. Admission TG levels were significantly higher in the IV insulin and PL vs. conservative group (p = 0.009). The percent decline in TG levels from admission to hospital discharge was 80.8% ±13.2%, 90.0% ± 5.6%, 63.9% ± 30.5% among the IV insulin, PL, and conservative groups, respectively (p=0.0214), with no statistically significant differences seen between IV insulin and PL groups. Eighty (80.0%) patients had diabetes mellitus, the majority of whom received IV insulin (81.3%). Among patients without diabetes, 54.2% received IV insulin only. Hospital complications, hypoglycemic events, and LOS did not differ between patients with and without diabetes who received IV insulin. CONCLUSIONS: Intravenous insulin infusion is a safe and effective method for reducing serum triglyceride levels in both diabetic and non-diabetic patients diagnosed with acute HTGP. CLINICAL IMPLICATIONS: IV insulin infusion is effective and safe for management of acute HTPG when compared to conservative management or plasmapheresis. Given the challenges associated with use of plasmapheresis and its limited clinical utility, IV insulin infusion should be considered as a first line therapy for treatment of this entity in both diabetic and non-diabetic individuals. DISCLOSURES: No relevant relationships by Hasan Ahmad Hasan Albitar, source=Web Response No relevant relationships by Adham Alkurashi, source=Web Response No relevant relationships by Yahya Almodallal, source=Web Response no disclosure on file for Tiffany Cortes; No relevant relationships by Kristen Gonzales, source=Web Response No relevant relationships by Sumedh Hoskote, source=Web Response No relevant relationships by Maria Hurtado, source=Web Response No relevant relationships by vivek iyer, source=Web Response no disclosure on file for Prashant Jagtap; No relevant relationships by Vinaya Simha, source=Web Response

Maternal serum leptin, adiponectin, resistin and monocyte chemoattractant protein-1 levels in different types of diabetes mellitus

ObjectiveEvaluation of serum concentration of leptin, adiponectin, resistin, and MCP-1 in pregnant patients with different types of diabetes mellitus (DM) considering preconception planning and method of DM correction in 11–14th and 30–34th weeks of pregnancy. Study designLongitudinal, prospective study included 130 pregnant women divided into the following comparison groups: type 1 DM (T1DM, n = 40), type 2 DM (T2DM, n = 35), GDM (n = 40), and the control group (n = 15). The ELISA method defined the levels of leptin, resistin, adiponectin, and MCP-1 concentration in serum, which was assessed in 11–14th and 30–34th weeks of pregnancy. Statistical analysis was accomplished using SPSS 23.0 and "Prism 8-GraphPad" software. ResultsThe leptin level in the 1st trimester was the highest in T2DM insulin group compared to the control due to gestational age, hence in the 3rd trimester in all groups its serum concentrations appeared higher than in healthy patients (p = 0.0001). In the 1st trimester leptin levels directly correlated with women's BMI, newborns’ weight and macrosomia rate, in the 3rd trimester – with OGTT levels, HbA1c, gestational hypertension, and preeclampsia rates. Resistin levels in the 1st and 3rd trimesters were increased in almost all DM groups compared to the control group (p = 0.0001). The study established direct positive correlation between resistin and HbA1c, birth weight, and preeclampsia. In the 1st trimester, adiponectin demonstrated the lowest levels in T2DM insulin compared to T1DM and the control group (p = 0.0001) while in the 3rd trimester, adiponectin levels declined alongside gestational age in DM patients and all the groups compared to the control group (p < 0.05). Adiponectin negatively correlated with BMI, OGTT levels, and preeclampsia rate. MCP-1 levels in T2DM appeared higher than in T1DM patients and the control group in the 1st trimester, whereas in the 3rd trimester MCP-1 declined, correlating with BMI, preeclampsia and OGTT levels. ConclusionHigh rate of adverse perinatal outcomes in diabetic pregnancy might be developed due to more severe metabolic failures and further disturbances of adipokines expression.

Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis activity in diabetic mice

BackgroundThe risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia.MethodsFive-week-old male C57BL/6 J mice were divided into four groups (No insulin (Diabetes Mellitus: DM), Short-term insulin (DM), Long-term insulin (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term insulin (DM) group received insulin therapy for 6 h before the operation and the Long-term insulin (DM) group received insulin therapy for 5 days before the operation. The No insulin (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2′,7′-dichlorodihydrofluorescein diacetate) before and 24 h after the operation using FACSVerse™ with BD FACSuite™ software.ResultsBlood glucose was lowered by insulin therapy in the Short-term insulin (DM) and Long-term insulin (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term insulin (DM) group compared with those in the No insulin (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term insulin (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term insulin (DM) group or Long-term insulin (DM) group.ConclusionsPreoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 h before the operation.

Association of pregnancy outcomes in women with type 2 diabetes treated with metformin versus insulin when becoming pregnant

BackgroundMetformin use in pregnancy is controversial because metformin crosses the placenta and the safety on the fetus has not been well-established. This retrospective study aimed to compare pregnancy outcomes in women with preexisting type 2 diabetes receiving metformin or standard insulin treatment.MethodsThe cohort of this population-based study includes women of age 20–44 years with preexisting type 2 diabetes and singleton pregnancies in Taiwan between 2003 and 2014. Subjects were classified into three mutually exclusive groups according to glucose-lowering treatments received before and after becoming pregnant: insulin group, switching group (metformin to insulin), and metformin group. A generalized estimating equation model adjusted for patient age, duration of type 2 diabetes, hypertension, hyperlipidemia, retinopathy, and aspirin use was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of adverse pregnancy outcomes.ResultsA total of 1166 pregnancies were identified in the insulin group (n = 222), the switching group (n = 318) and the metformin group (n = 626). The insulin group and the switching group had similar pregnancy outcomes for both the mother and fetus, including risk of primary cesarean section, pregnancy-related hypertension, preeclampsia, preterm birth (< 37 weeks), very preterm birth (< 32 weeks), low birth weight (< 2500 g), high birth weight (> 4000 g), large for gestational age, and congenital malformations. The metformin group had a lower risk of primary cesarean section (aOR = 0.57; 95% CI, 0.40–0.82) and congenital malformations (aOR, 0.51; 95% CI; 0.27–0.94) and similar risk for the other outcomes as compared with the insulin group.ConclusionsMetformin therapy was not associated with increased adverse pregnancy outcomes in women with type 2 diabetes as compared with standard insulin therapy.

Diabetes-Related Effectiveness and Cost of Liraglutide or Insulin in German Patients with Type 2 Diabetes: A 5-Year Retrospective Claims Analysis.

IntroductionLiraglutide is a glucagon-like peptide-1 analogue used to treat type 2 diabetes mellitus (T2DM). To date, limited long-term data (> 2 years) exist comparing real-world diabetes-related effectiveness and costs for liraglutide versus insulin treatment.MethodsThis retrospective claims data analysis covered the period from 1 January 2010 to 31 December 2017 and included continuously insured patients with T2DM who initiated insulin or liraglutide and had 3.5 or 5 years’ follow-up data, identified using the German AOK PLUS dataset. Propensity score matching (PSM) was used to adjust for patient characteristics.ResultsAfter PSM, there were 825 and 436 patients in the liraglutide and insulin groups at 3.5 and 5 years’ follow-up, respectively. Baseline characteristics were similar between compared cohorts. The respective change from baseline to follow-up in mean glycated haemoglobin for liraglutide and insulin patients was − 0.88% and − 0.81% (p > 0.100) after 3.5 years and − 1.15%/ − 1.02% (p > 0.100) after 5 years. Mean respective changes in body mass index (kg/m2) were − 1.21/+ 1.14 (p < 0.001) after 3.5 years and − 1.29/+ 1.13 after 5 years (p < 0.001). Liraglutide- versus insulin-treated patients were less likely to have an early T2DM-related hospitalisation (3.5-year hazard ratio [HR]: 0.414 [95% confidence interval (CI) 0.263–0.651]; 5-year HR: 0.448 [95% CI 0.286–0.701]). At 5 years’ follow-up, there was no statistically significant difference in total direct costs between treatment groups (cost ratio: 1.069 [95% CI 0.98–1.13]; p > 0.100).ConclusionThe clinical effectiveness of liraglutide is maintained long term (up to 5 years). Liraglutide treatment is not associated with higher total direct healthcare costs.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-020-00903-0) contains supplementary material, which is available to authorized users.

Metformin versus Insulin in Treatment of Gestational Diabetes

Abstract Background: GDM affects both mother and baby during pregnancy and in the long term. Metformin was associated with a lower risk of neonatal hypoglycemia; however, met-formin may slightly increase the risk of prematurity. Aim of Study: The aim of the present study was to compare the safety and efficacy of metformin as an oral anti-diabetic drug with insulin as oral hypoglycemic drugs for management of gestational diabetes mellitus. Patients and Methods: 120 pregnant women with gesta-tional diabetes mellitus were included in this randomized controlled trial. Patients were randomly allocated into 2 groups as follows: Group I: Insulin group (n=64) and Group M: Metformin group (n=56). Follow-up was done every week by measuring fasting and post prandial blood glucose level. Maternal outcomes and neonatal outcomes were recorded. Results: There were statistically significant differences as regard mean fasting and post prandial blood glucose level and mean birth weight in insulin and metformin group. Also, increased CS rate between insulin and metformin group. There were statistically significant differences between insulin group and metformin sub-groups patients as regards birth weight, Apgar score and serum glucose level. Conclusion: We concluded that metformin is an effective and safe treatment option for women with GDM. Metformin is comparable with insulin in glycemic control, providing additional evidence for the use of metformin in GDM.

A Comparative Study on Feto-Maternal Outcome of GDM Treated by Either Insulin or Metformin

Background: Gestational Diabetes Mellitus (GDM) is linked with amplified risk of variety of maternal and perinatal complications. There have been a number of studies comparing metformin with insulin in the management of GDM.&#x0D; Methods: A clinical trial (Quasi experimental) was conducted on fifty women with GDM at their 24 – 34 weeks of gestation with the aim to compare maternal and perinatal outcomes treated by either insulin or metformin. The study population were recruited from obstetrics and gynaecology outpatient department of Medical College for Women and Hospital, Uttara, Dhaka, from July 2012 to December 2012.The patients were divided into two groups (nonrandomized), 25 patients in each, and were subjected to either injection insulin or oral metformin medication.&#x0D; Results: The patients were grouped as insulin or metformin group. They were compared in terms of age, parity and developing maternal complications like preeclampsia (p=0.24), UTI (p=0.40), polyhydramnios (p=0.70). However, the incidence of preterm birth was higher among metformin group in comparison to insulin group (P=0.007).There was no significant difference between insulin and metformin group as regard to mode of delivery. The proportion of neonatal hypoglycemia in insulin group was higher than metformin group (P=0.46) but statistically not significant. Other neonatal outcomes such as macrosomia, birth asphyxia and hyperbillirubinaemia did not differ significantly between two groups.&#x0D; Conclusion: In women with GDM, treatment with metformin is associated with higher proportion of preterm birth than with insulin. Proportion of neonatal hypoglycemia is higher with insulin use.&#x0D; Bangladesh J Obstet Gynaecol, 2019; Vol. 34(1): 8-14

Histological Study on the Effects of Allogenic Bone Marrow Derived Mesenchymal Stem Cells Along with Local Insulin Therapy on Osteosynthesis in Gap Defects of Radius in Diabetic Rabbit Model

Background: Diabetes mellitus impairs fracture healing causing bone repair abnormality which is insulin dependent. Exogenous insulin can accelerate fracture healing in diabetes by promoting bone remodeling and bone formation. Mesenchymal stem cell loaded scaffolds having osteoinductive and osteoconductive properties, may be used as an alternative for autogenous bone grafting. The current study aimed to investigate the efficacy of cultured allogenic bone marrow derived mesenchymal stem cell implantation with insulin therapy for increasing osteosynthesis in bone gap defects in experimentally induced diabetic rabbits. Methods: Thirty six, New Zealand White rabbits were divided into four groups: A, B, C and D. Diabetes was induced experimentally in all rabbits, except group A. A 5 mm bone defect was created in right radii of all rabbits and following treatment was given: hydroxyapatite granules (group A and B), hydroxyapatite granules and insulin therapy (group C), cultured allogenic BMMSCs in hydroxyapatite scaffold and insulin therapy (group D). Histologic evaluation was performed on days 30, 60 and 90. Result: Combined therapy of allogenic BMMSCs in hydroxyapatite scaffold along with local insulin (group D) provided best healing response followed by healthy control (group A), locally insulin treated group (group C) and diabetic control (group B).

Serum glypican4 and glycosylphosphatidylinositol-specific phospholipase D levels are associated with adipose tissue insulin resistance in obese subjects with different glucose metabolism status.

Glypican4 (GPC4) is a novel adipokine associated with obesity and insulin resistance. GPC4 was cleaved by the glycosylphosphatidylinositol-specific phospholipase D (GPLD1) in an anchored site of the glycosylphosphatidylinositol, and then was released into the extracellular environment. Herein, we investigated the changes of serum GPC4 and GPLD1 levels in obese subjects with different glucose metabolism status and their relationship with adipose tissue insulin resistance index (Adipo-IR) in Chinese north populations. A total of 221 obese subjects and 37 normal controls (NC) were recruited in this study. Obese subjects were divided into normal insulin (NI) group, hyperinsulinemia (HI) group, impaired glucose tolerance (IGT) group, and type 2 diabetes mellitus (DM) group. Serum GPC4, GPLD1, and adiponectin were determined by commercially available ELISA kits. Serum GPC4 levels in the HI, IGT, and DM groups were significantly higher than those in the NC and NI groups (2.27 ± 0.58ng/mL, 2.21 ± 0.60ng/mL, 2.49 ± 0.67ng/mL vs. 1.70 ± 0.33ng/mL, 1.93 ± 0.34ng/mL, P < 0.05). GPC4 was positively correlated with GPLD1, which was the most important influencing factor of GPC4. Adipo-IR was independently and positively associated with serum GPC4 and GPLD1. For GPC4, afteradjustmentforconfounders, the risk of adipose tissue insulin resistance in subjects with the highest tertile was 2.974-fold that of those with the lowest tertile (OR = 2.974, P = 0.013). For GPLD1, before adjustment for lipids, the increased probability still existed (Model 2, OR = 3.568, P = 0.003). GPC4 is an adipokine associated with adipose tissue insulin resistance, and its activitymay beregulatedby GPLD1. GPC4 may be a marker for adipose tissue insulin resistance in Chinese north obese populations.

Sodium Glucose Cotransporter-2 Inhibitor Treatment and the Risk of Diabetic Ketoacidosis in Denmark: A Retrospective Cohort Study of Five Years of Use.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with increased risk of diabetic ketoacidosis (DKA) in both people with type 1 and type 2 diabetes mellitus. Few studies using data from high-quality registries exist that attempt to determine the real- world impact of the increasing use of this drug. The aim of this study was to investigate the incidence and risk of DKA in connection with SGLT2i treatment in Denmark between 2013-2017. A nationwide retrospective cohort of people with type 2 diabetes mellitus using SGLT2i or glucagon-like peptide-1 receptor agonists (GLP1-RA) was established and analysed using both Cox-proportional hazard regression and Kaplan-Meier survival analysis. The 37,058 individuals included in the cohort, were made up of SGLT2i (10,923), GLP1- RA (18,849), SGLT2i+insulin (2,069), and GLP1-RA+insulin (10,178) users. The incidence rate (IR) of DKA was 0.84 (95% CI 0.49-1.44) and 0.53 (95% CI 0.36-0.77) for the SGLT2i and GLP1-RA groups, respectively. There was no statistically significant increase in the risk for DKA with SGLT2i use (HR 1.02, 95% CI, 0.44-2.36). However, for the SGLT2i+insulin and GLP1- RA+insulin groups, IRs were 3.47 (95% CI 1.92-6.27) and 0.97 (95% CI 0.68-1.37) respectively, and the risk was statistically significantly higher (HR 5.42, 95% CI 2.16-13.56). We observed no significant increase in the risk of DKA for SGLT2i users compared to GLP1-RA. However, a significantly higher IR of DKA was observed with concomitant insulin use, and the risk of DKA was considerably higher for the SGLT2 group using insulin.

Association of polymorphism genes LPL , ADRB2 , AGT and AGTR1 with risk of hyperinsulinism and insulin resistance in the Kazakh population.

Hyperinsulinism and insulin resistance are closely associated with several common diseases including type 2 of diabetes, cardiovascular diseases, and metabolic syndrome. The present study aimed to determine the association between hyperinsulinism, insulin resistance and the polymorphism of genes, including angiotensin II receptor type 1 (AGTR1), angiotensinogen (AGT), β2-adrenoreceptor (ADRB2) and lipoprotein lipase (LPL), in the Kazakh population. The design of the current research was a case-control study, involving 460 subjects (age range, 18-65 years). For every subject, plasma glucose, insulin, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein B and apolipoprotein A1 were examined. Moreover, reverse transcription-quantitative PCR was conducted to detect the polymorphism genes LPL Ser447Ter, ADRB2 Gln27Glu, AGT Thr174Met and AGTR1 A1166C. Hyperinsulinism was considered when the insulin level was elevated >24.9 IU/ml. The homeostasis model assessment insulin resistance (HOMA-IR) was used to evaluate insulin resistance. The subjects were divided into hyperinsulinism (17 men and 24 women) and normal level insulin (214 men and 205 women) groups, which were also split into insulin resistance group (HOMA-IR >2.7; 80 men and 105 women) and those without insulin resistance group (151 men and 124 women). The results suggested that LPL Ser447Ter (rs328) allele G was associated with a lower risk of hyperinsulinism (P=0.037). Furthermore, polymorphisms of genes ADRB2 Gln27Glu (rs1042714), AGT Thr174Met (rs4762) and AGTR1 A1166C (rs5186) were not associated with hyperinsulinism and insulin resistance in the Kazakh population. No interaction was identified between LPL Ser447Ter, ADRB2 Gln27Glu, AGT Thr174Met and AGTR1 A1166C. Therefore, the results indicated that haplotype combinations were not associated with insulin resistance.

Intensive Insulin Therapy Versus Conventional Glucose Control In Traumatic Brain Injury Patients Who Are On Parenteral Nutrition

&lt;p&gt;Parenteral nutrition (PN) is a valuable life saving intervention, which can improve the nutritional status of hospitalized malnourished patients. PN is associated with complications including hyperglycemia. This study was conducted to compare two methods of blood glucose control in traumatic brain injury patients who are on PN.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Materials &amp; Methods:&lt;/strong&gt;This study is a randomized , open-label, controlled clinical trial with blinded end assessment. This study was done in the surgical intensive care unit of Beni-Suef University hospital after obtaining approval from the ethical committee of the Institution and obtaining consent from relatives of the patients involved in the study. Seventy critically ill patients were choosen randomly according to the inclusion criteria from cases admitted to Beni-suef university hospital, then divided into two groups randomly:&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Group &lt;/strong&gt;&lt;strong&gt;?&lt;/strong&gt;&lt;strong&gt; (Intensive insulin therapy):&lt;/strong&gt;35 patients received continuous insulin infusion to maintain glucose levels between 4.4mmol/l (80 mg/dl) and 6.6mmol/l (110 mg/dl).&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Group &lt;/strong&gt;&lt;strong&gt;??&lt;/strong&gt;&lt;strong&gt; (Conventional therapy):&lt;/strong&gt;35patients not received insulin unless glucose levels greater than 10 mmol/l (&gt;180 mg/dl).&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In our study, it was shown that mean glucose concentration were significantly lower in IIT group vs conventional group. No hypoglycemic episode occurred in two groups. Triglyceride and C-reactive protein was decreased in the IIT group, significantly. There were also significant differences in the electrolytes, with magnesium and phosphorus being lower in the IIT group.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; In this study, Intensive insulin group improved some of parenteral such as hyperglycemia, hypertriglyceridemia and electrolyte imbalances compared to Conventional insulin group.&lt;/p&gt;

Diabetes up-regulated collagen IV and laminin α5 genes in mRNA and protein levels in seminiferous tubules of C57BL/6 adult mice

Diabetes is a disease associated with impairment of the male reproductive system that causes complications such as decreased testosterone, the diameter of the seminiferous tubule, libido, and fertility. Extracellular matrix (ECM) molecules are involved in testicular development and spermatogenesis. Laminin and collagen are key proteins in seminiferous tubule basement membrane and play an important role in spermatogenesis. The present study was conducted to investigate the effect of diabetes on collagen IV and laminin α5 changes in mice testis. In this experimental study, 40 mice (C57BL/6) were divided randomly into 4 groups: 1) Control group: without intervention, 2) Diabetic group: treated mice with 50 mg/kg streptozotocin (STZ), 3) Diabetic + Insulin group: treated mice with STZ and insulin, and 4) Sham group: received citrate buffer. After 35 days, the left testes of all specimens were used for Real-Time PCR while their right testes were applied for immunohistochemical study and Periodic acid-Schiff (PAS) staining. This study showed that gene expression and immunoreactivity of laminin α5 and collagen IV were significantly increased in diabetic mice compared to other groups (P&lt;0.05). Also, PAS staining showed the thickness of seminiferous tubule basement membrane in the Diabetic group compared to other group increased significantly (p&lt;0.05). In Diabetic + Insulin compared to Diabetic group, gene expression, the intensity of immunoreactivity and thickness of seminiferous tubule basement membrane decreased significantly (P&lt;0.05). Our findings indicated that diabetes causes up-regulation of collagen IV and laminin α5 in mRNA and protein levels in the seminiferous tubule basement membrane and may cause disorder in spermatogenesis in mice.

Impact of resveratrol in the reduction of the harmful effect of diabetes on peri-implant bone repair: bone-related gene expression, counter-torque and micro-CT analysis in rats

Objective Investigate the impact of resveratrol (RESV) on peri-implant repair and its effect on bone-related markers in rats with induced diabetes mellitus (DM). Material and methods Ninety rats were divided into: DM + RESV (n = 18); DM + placebo (PLAC) (n = 18); DM + insulin (INS) (n = 18); DM + RESV + INS (n = 18); Non-DM (n = 18). Diabetes was induced by streptozotocin. One screw-shaped titanium implant was inserted in each tibiae of animals. Treatments were administered during 30 days. After, one of the implants was removed for counter-torque and the peri-implant tissue was collected for mRNA quantification of BMP-2, OPN, Runx2, Lrp-5, Osx, β-catenin, Dkk1, OPG, and RANKL by Real-time PCR. The other tibia was submitted to MicroCT analysis to measure: bone volume (BV/TV), trabecular thickness (Tb.Th) and bone-implant contact (BIC). Results Higher counter-torque values were observed for implant removal in DM + RESV, DM + RESV + INS and Non-DM groups when compared to DM + PLAC (p < .05). Augmented Tb.Th was observed in DM + RESV and Non-DM when compared to DM + PLAC group (p < .05), whereas higher BIC was detected in DM + RESV, DM + RESV + INS and Non-DM animals when compared to DM + PLAC (p < .05). Levels of RANKL were downregulated by the RESV and/or INS therapy, whereas only the association of RESV and INS upregulated the levels of Runx2 (p < .05). Conclusions The therapy with RESV may favour peri-implant bone repair improving bone formation around implants.

Study of metformin in diabetes mellitus with stage 3 and 4 chronic kidney disease

Background: Chronic Kidney Disease is one of the major complications of Diabetic patients. Cardiovascular mortality increases in patient with diabetes and more so with diabetic CKD. Clinician treating diabetic CKD finds option limited as metformin is considered contraindicated when serum creatinine is greater than 1.5 mg/dl in males and greater than 1.4 mg/dl in females. The primary aim of the study is to evaluate the efficacy of metformin in terms of glycemic control in patient with diabetic stage 3 and 4 CKD.&#x0D; Methods: This is Randomised open labelled clinical trial done in the Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal. Primary end point were glycemic status at 6 months as defined by with fasting, post prandial blood sugar, glycosylated hemoglobin in comparison to baseline.&#x0D; Results: Altogether 73 diabetic patients with diabetic CKD stage 3 and 4 were included in the study. 41 patients were included in insulin group and 32 patients in metformin group. In metformin group, the fasting and past prandial blood sugar declined progressively compared to insulin group, where fasting and post prandial blood sugar declined more rapidly.&#x0D; Conclusions: Metformin is found to be efficacious in diabetic CKD as it had already proved to be effective in diabetes without CKD. In this study metformin was not associated with lactic acidosis and the level of lactate with metformin treatment was similar to that of treatment with insulin. The vast majority of case reports relating metformin to lactic acidosis report at least one other disease/illness that could result in lactic acidosis. Despite increasing disregard of contraindications to metformin by physicians, the incidence of lactic acidosis has not increased, as does the result of this study. So metformin may be safe even in patients with diabetic CKD stage 3 and 4.