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Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes. In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ from (...) trial results.To compare the rates of hypoglycemia-related emergency department (ED) visits or hospital admissions associated with initiation of long-acting insulin analogs vs human NPH insulin in patients with type 2 diabetes.A retrospective observational study using data from Kaiser Permanente of Northern California from January 1, 2006, through September 30, 2015. Patients with type 2 diabetes who initiated a long-acting insulin analog or NPH insulin were included and censored at death, loss
The Regulation of Insulin-Stimulated Cardiac Glucose Transport via Protein Acetylation Cellular catabolism is the cell capacity to generate energy from various substrates to sustain its function. To optimize this energy production, cells are able to switch between various metabolic pathways in accordance to substrate availability via a modulation of several regulatory enzymes. This metabolic flexibility is essential for the healthy heart, an organ requiring large quantities of ATP to sustain (...) substrates induces an increase in acetylation levels of proteins which is concomitant to the perturbation of glucose transport. The purpose of the present review is to gather, in a synthetic model, the different evidences that demonstrate the role of acetylation in the inhibition of the insulin-stimulated glucose uptake in cardiac muscle.
Insulin Degludec (Tresiba) - diabetes mellitus Search Page - Drug and Health Product Register Language selection Search and menus Search Search website Search Topics menu You are here: Summary Basis of Decision - - Health Canada Expand all Summary Basis of Decision (SBD) for Contact: Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The for is located below. Recent Activity for SBDs written for approved after September 1, 2012
Everolimus Directly Suppresses Insulin Secretion Independently of Cell Growth Inhibition Everolimus, an orally administered mammalian target of rapamycin inhibitor, has been widely used as an immunosuppressant and an anticancer agent. Whereas everolimus can control recurrent hypoglycemia in patients with insulinoma, possibly through tumor regression and/or the direct inhibition of insulin secretion, time-dependent changes in serum insulin levels caused by everolimus still remain unclear. Here (...) we report a clinical case of a patient with metastatic insulinoma, in which frequent monitoring of serum insulin levels demonstrated rapid and substantial changes in insulin secretion levels, a few days after the discontinuation as well as the readministration of everolimus. To further confirm the direct effect of everolimus on β-cell function, we performed in vitro experiments using mouse insulinoma cells (MIN6) and human induced pluripotent stem cell (hiPSC)-derived insulin-producing cells
Glycemic index, glycemic load and insulin response of two formulas of isoglucose with different sweeteners and dietary fiber in healthy adults and type-2 diabetes Objective: The aim of this study is to compare the glycemic index (GI) and glycemic load (GL) of two formulas with the same glucose content
with different sweeteners and dietary fiber for diabetics in healthy adults and in patients with type-2 diabetes (DM2).
Methodology: In this randomized, double-blind crossover research, eleven (...) healthy people and six with DM2 consumed two enteral formulas, Glucerna SR®, Laboratorios Abbott C.A. (GF) and Enterex Diabetic®, Victus C.A. (EF), sweetened with fructose y sucralose, with 1.2 and 1.3 g/100 ml of fiber source respectively (four times). Additionally, they consumed glucose solution once, obtaining blood samples at 0, 15, 30, 45, 60, 90 and 120 min for controls; in the diabetics, minutes 150 and 180 were added for measuring blood glucose, basal and postprandial insulin after two
Insulin in a Pill: Barriers to Development of Oral InsulinInsulin in a Pill: Barriers to Development of Oral Insulin – Clinical Correlations Search Insulin in a Pill: Barriers to Development of Oral Insulin May 8, 2018 4 min read By Nicolas Gillingham Peer Reviewed Over 30 million Americans—9.4% of the population—live with diabetes, . Insulin can be self-administered by subcutaneous injection, either classically via a syringe, an insulin pen, or using an insulin pump. However, patients (...) with diabetes report that these daily injections can feel particularly burdensome, not to mention stigmatizing, when compared to oral medications like metformin, . What if our patients could take their insulin in a capsule alongside their morning metformin? Such a formulation would eliminate a significant barrier to medication adherence and would also better mimic the physiology of endogenous insulin. Endogenous and exogenous insulin take different paths to the liver, which affects how they influence
Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study To compare the efficacy and safety of adding the glucagon-like peptide-1 receptor agonist exenatide once weekly (QW) 2 mg or placebo among patients with type 2 diabetes who were inadequately controlled despite titrated insulin glargine (IG) ± metformin.This multicentre, double-blind study (ClinicalTrials.gov identifier: NCT02229383) randomized (1:1
Hypoglycaemia incidence and recovery during home use of hybrid closed-loop insulin delivery in adults with type 1 diabetes Glucose excursion was assessed prior to and post hypoglycaemia to increase understanding of hypoglycaemia incidence and recovery during hybrid closed-loop insulin delivery. We retrospectively analysed data from 60 adults with type 1 diabetes who received, in a crossover randomized design, day-and-night hybrid closed-loop insulin delivery and insulin pump therapy, the latter (...) during control intervention (P < .01), while insulin delivery was reduced (P < .01). During both day and night, participants recovered from hypoglycaemia faster when treated by closed-loop intervention. At 120 minutes post hypoglycaemia, sensor glucose levels were higher during closed-loop intervention compared to the control period (P < .05). In conclusion, closed-loop intervention reduces the risk of hypoglycaemia, particularly overnight, with swift recovery from hypoglycaemia leading to higher 2
Safety of non-insulin glucose-lowering drugs in pregnant women with pre-gestational diabetes: A cohort study To evaluate the association between use of non-insulin antidiabetics in early pregnancy and the risk of miscarriages, stillbirths and major structural malformations.A cohort of 1511 pregnant women with pre-gestational diabetes linked to live births was identified using electronic medical records from The Health Improvement Network (THIN) for the period 1995 to 2012. Information (...) on prescriptions, foetal outcomes and potential confounders was ascertained from both codes and free text in the THIN database. Odds ratios (OR) and 95% confidence intervals (CI) of adverse foetal outcomes in women treated with non-insulin antidiabetics during the first trimester compared to those on insulin were estimated using logistic regression to adjust for type of diabetes, glycaemic control and other maternal characteristics.Among 311 pregnant women on non-insulin antidiabetics, 21.9% had a miscarriage
Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial. Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes.To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes.The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 (...) and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation.Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter
Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease Rodent and cell-culture models support a role for iron-related adipokine dysregulation and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, substantial human data are lacking. We examined the relationship between measures of iron status, adipokines, and insulin resistance in patients with NAFLD in the presence and absence of venesection. This study forms (...) part of the Impact of Iron on Insulin Resistance and Liver Histology in Nonalcoholic Steatohepatitis (IIRON2) study, a prospective randomized controlled trial of venesection for adults with NAFLD. Paired serum samples at baseline and 6 months (end of treatment) in controls (n = 28) and patients who had venesection (n = 23) were assayed for adiponectin, leptin, resistin, retinol binding protein-4, tumor necrosis factor α, and interleukin-6, using a Quantibody, customized, multiplexed enzyme-linked
Phosphoinositide 3-Kinase Is Integral for the Acute Activity of Leptin and Insulin in Male Arcuate NPY/AgRP Neurons Neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are part of a neuroendocrine feedback loop that regulates feeding behavior and glucose homeostasis. NPY/AgRP neurons sense peripheral signals (including the hormones leptin, insulin, and ghrelin) and integrate those signals with inputs from other brain regions. These inputs modify (...) both long-term changes in gene transcription and acute changes in the electrical activity of these neurons, leading to a coordinated response to maintain energy and glucose homeostasis. However, the mechanisms by which the hormones insulin and leptin acutely modify the electrical activity of these neurons remain unclear. In this study, we show that loss of the phosphoinositide 3-kinase catalytic subunits p110α and p110β in AgRP neurons abrogates the leptin- and insulin-induced inhibition of AgRP
Day-and-Night Closed-Loop Insulin Delivery in a Broad Population of Pregnant Women With Type 1 Diabetes: A Randomized Controlled Crossover Trial Despite advances in technology, optimal glucose control remains elusive and neonatal complications remain ubiquitous in type 1 diabetes (T1D) pregnancy. Our aim was to examine the safety, efficacy, and longer-term feasibility of day-and-night closed-loop insulin delivery.We recruited 16 pregnant women (mean [SD]: age 32.8 [5.0] years, T1D duration 19.4 (...) [10.2] years, HbA1c 8.0% [1.1], and BMI 26.6 [4.4] kg/m2) to an open-label, randomized, crossover trial. Participants completed 28 days of closed-loop and sensor-augmented pump (SAP) insulin delivery separated by a washout period. Afterward, participants could continue to use the closed-loop system up to 6 weeks postpartum. The primary end point was the proportion of time with glucose levels within the target range (63-140 mg/dL).The proportion of time with glucose levels within target
Effect of prandial treatment timing adjustment, based on continuous glucose monitoring, in patients with type 2 diabetes uncontrolled with once-daily basal insulin: A randomized, phase IV study To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily (...) basal insulin glargine.This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data
Sex Difference In the Effect of Fetal Exposure to Maternal Diabetes on Insulin Secretion We previously showed that fetal exposure to maternal type 1 diabetes (T1D) is associated with altered glucose-stimulated insulin secretion in adult offspring. Here, we investigated whether this β-cell defect displays a sex dimorphism. Twenty-nine adult nondiabetic offspring of T1D mothers (ODMs) were compared with 29 nondiabetic offspring of T1D fathers. We measured early insulin secretion in response (...) to oral glucose and insulin secretion rate in response to intravenous glucose ramping. Insulin sensitivity and body composition were assessed by a euglycemic, hyperinsulinemic clamp and dual-energy X-ray absorptiometry, respectively. In response to oral glucose, male and female ODMs displayed a reduced insulin secretion. In contrast, in response to graded intravenous glucose infusion, only female ODMs (not males) exhibited decreased insulin secretion. There was no defect in response to combined
Increase in hepatic and decrease in peripheral insulin clearance characterize abnormal temporal patterns of serum insulin in diabetic subjects Insulin plays a central role in glucose homeostasis, and impairment of insulin action causes glucose intolerance and leads to type 2 diabetes mellitus (T2DM). A decrease in the transient peak and sustained increase of circulating insulin following an infusion of glucose accompany T2DM pathogenesis. However, the mechanism underlying this abnormal temporal (...) pattern of circulating insulin concentration remains unknown. Here we show that changes in opposite direction of hepatic and peripheral insulin clearance characterize this abnormal temporal pattern of circulating insulin concentration observed in T2DM. We developed a mathematical model using a hyperglycemic and hyperinsulinemic-euglycemic clamp in 111 subjects, including healthy normoglycemic and diabetic subjects. The hepatic and peripheral insulin clearance significantly increase and decrease
Effect of pioglitazone on insulin resistance, progression of atherosclerosis and clinical course of coronary heart disease. Pioglitazone, a medication of thiazolidinedione group, is capable of triggering the peroxisome proliferator-activated receptors (PPAR-γ). Activation of receptor PPAR-γ regulates carbohydrate and lipid metabolism, immune and inflammatory responses in heart tissues.Our aim was to study the effect of pioglitazone on insulin resistance, the clinical course of atherosclerosis (...) , as well as increased high-density lipoprotein (p<0.05).Long-term treatment with pioglitazone at low doses against the background of standard therapy contributes to functional and clinical condition of patients, promotes the prevention of atherosclerosis and reduction of insulin resistance, thereby improving the clinical manifestations of coronary heart disease.
Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin; DUAL VII Randomized Clinical Trial In patients with uncontrolled type 2 diabetes on basal insulin, prandial insulin may be initiated. We assessed the efficacy and safety of initiating insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus basal-bolus insulin.A phase 3b trial examined patients with uncontrolled type 2 diabetes on insulin (...) glargine (IGlar U100) 20-50 units/day and metformin, randomized to IDegLira or IGlar U100 and insulin aspart ≤4 times per day.Glycated hemoglobin (HbA1c) decreased from 8.2% (66 mmol/mol) to 6.7% (50 mmol/mol) with IDegLira and from 8.2% (67 mmol/mol) to 6.7% (50 mmol/mol) with basal-bolus (estimated treatment difference [ETD] -0.02% [95% CI -0.16, 0.12]; -0.2 mmol/mol [95% CI -1.7, 1.3]), confirming IDegLira noninferiority versus basal-bolus (P < 0.0001). The number of severe or blood glucose