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Evaluation of Hypothalamicâ€“Pituitaryâ€“Adrenal Axis by the GHRP2 Test: Comparison With the Insulin Tolerance Test GH-releasing peptide 2 (GHRP2) stimulates the hypothalamic-pituitary-adrenal axis (HPA) through the GH secretagogue receptor (GHSR) in the hypothalamus, in which ghrelin is a natural ligand. Therefore, the GHRP2 test (GHRP2T) could be used instead of the insulin tolerance test (ITT).Can the GHRP2T replace the ITT for evaluation of HPA?The present retrospective study analyzed
Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care. In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancreas) can improve glucose control in patients with type 1 diabetes. We wanted to investigate whether a closed-loop system could also improve glycemic control in patients with type 2 diabetes who were receiving noncritical care.In (...) this randomized, open-label trial conducted on general wards in two tertiary hospitals located in the United Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required subcutaneous insulin therapy to receive either closed-loop insulin delivery (70 patients) or conventional subcutaneous insulin therapy, according to local clinical practice (66 patients). The primary end point was the percentage of time that the sensor glucose measurement was within the target range of 100 to 180 mg per
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.
Free and fixed-ratio combinations of basal insulin and GLP-1 receptor agonists versus basal insulin intensification in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials A meta-analysis is presented of randomized controlled trials (RCTs) comparing free or fixed combinations of a glucagon-like peptide-1 receptor agonist plus basal insulin versus insulin intensification on metabolic control in patients with type 2 diabetes. Electronic databases were searched (...) for RCTs assessing changes in HbA1c, proportion of patients at HbA1c target of <7% (53 mmol/mol), hypoglycaemia and body weight. A random-effect model was used to calculate the weighted mean difference (WMD) or relative risk (RR) with 95% CI. Eleven RCTs were identified, lasting 24-30 weeks and involving 6176 patients. In the overall analysis, the combination therapy led to a mean HbA1c decrease significantly greater than insulin up-titration (WMD -0.53%, 95% CI, -0.66, -0.40%, P < 0.001), more
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
Vitamin D Supplementation, Glycemic Control, and Insulin Resistance in Prediabetics: A Meta-Analysis Diabetes prevention is a public health priority. Vitamin D supplementation may help prevent the development of diabetes in persons at increased risk. We performed a meta-analysis of controlled clinical trials that assessed glycemic outcome measures among adults at risk for type 2 diabetes, including prediabetes, overweight, or obesity. We searched PUBMED/ MEDLINE, CINAHL, and Google Scholar (...) hemoglobin (HbA1c), fasting plasma glucose, plasma glucose after 2-hour oral glucose tolerance test, and homeostatic model assessment of insulin resistance (HOMA-IR)]. Data synthesis was conducted using random-effect models (PROSPERO registration no. CRD42017055326). Twenty-eight trials, representing 3848 participants, met the eligibility criteria. Compared with the control group, vitamin D supplementation significantly reduced HbA1c level by -0.48% (95% CI, -0.79 to -0.18), fasting plasma glucose level
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
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 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
Biosimilar vs originator insulins: Systematic review and meta-analysis Biosimilar insulins have expanded the treatment options for diabetes. We compared the clinical efficacy and safety of biosimilar insulins with those of originator insulins by conducting a meta-analysis. A random-effects meta-analysis was performed on randomized controlled trials comparing biosimilar and originator insulins in adults with diabetes. Studies were obtained by searching electronic databases up to December 2017 (...) . Ten trials, in a total of 4935 patients, were assessed (2 trials each on LY2963016, MK-1293, Mylan's insulin glargine and SAR342434, and 1 trial each on FFP-112 and Basalog). The meta-analysis found no differences between long-acting biosimilar and originator insulins with regard to reduction in glycated haemoglobin at 24 weeks (0.04%, 95% confidence interval [CI] -0.01, 0.08; P for efficacy = .14, I2 = 0%) or at 52 weeks (0.03%, 95% CI -0.04, 0.1), or reduction in fasting plasma glucose (0.08
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
Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin for type 1 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials New treatments for type 1 diabetes are an unmet need. We investigated the efficacy and safety of adding sodium-glucose co-transporter-2 (SGLT2) inhibitors to insulin for type 1 diabetes by conducting a meta-analysis of prospective randomized, placebo-controlled trials. A search of electronic databases up to October 2017 (...) identified 1361 studies, of which 14 were investigated (N = 4591). Meta-analysis showed that SGLT2 inhibitor therapy significantly reduced glycated haemoglobin (HbA1c) concentration by 0.4% (95% confidence interval [CI] 0.35, 0.46; P < .001, I2 = 0%), fasting plasma glucose by 1.14 mmol/L (95% CI 0.8,1.47), body weight by 2.68 kg (95% CI 2.0, 3.36), and systolic blood pressure by 3.37 mmHg (95% CI 1.46, 5.28). In addition, bolus insulin decreased by 3.6 units/day (95% CI 2.0, 5.3), and basal insulin
The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of To investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes.This was a post hoc pooled analysis of 5 (...) phase III randomized, 26-week, open-label, treat-to-target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories.We conducted a meta-analysis of 5 clinical
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
Continuous insulin pumps may help manage poorly controlled type 2 diabetes Continuous insulin pumps may help manage poorly controlled type 2 diabetes Discover Portal Discover Portal Continuous insulin pumps may help manage poorly controlled type 2 diabetes Published on 18 July 2017 doi: Continuous subcutaneous insulin infusions, or pumps, reduced the amount of daily insulin required by 24 units for people with advanced type 2 diabetes compared to multiple daily insulin injections. Average (...) weight did not differ between treatments. This review compared the two treatments in 590 people from five trials and found that the pumps were linked to slightly better control for people on higher doses of insulin and those with poorer glucose control. However, looking at all the people with diabetes in these studies, there was no difference in overall control between the different forms of treatment. One main challenge in controlling type 2 diabetes is the low adherence to treatment. Other studies