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Insulin Dosing

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121. In Silico Modeling of Minimal Effective Insulin Doses Using the UVA/PADOVA Type 1 Diabetes Simulator (PubMed)

In Silico Modeling of Minimal Effective Insulin Doses Using the UVA/PADOVA Type 1 Diabetes Simulator The objective of this study was to identify the minimum basal insulin infusion rates and bolus insulin doses that would result in clinically relevant changes in blood glucose levels in the most insulin sensitive subjects with type 1 diabetes.The UVA/PADOVA Type 1 Diabetes Simulator in silico population of children, adolescents, and adults was administered a basal insulin infusion rate (...) to maintain blood glucose concentrations at 120 mg/dL (6.7 mmol/L). Two scenarios were modeled independently after 1 hour of simulated time: (1) basal insulin infusion rates in increments of 0.01 U/h were administered and (2) bolus doses in increments of 0.01 U were injected. Subjects were observed for 4 hours to determine insulin delivery required to change blood glucose by 12.5 mg/dL (0.7 mmol/L) and 25 mg/dL (1.4 mmol/L) in only 5% of the in silico population.The basal insulin infusion rates required

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2017 Journal of diabetes science and technology

122. Low-dose YC-1 combined with glucose and insulin selectively induces apoptosis in hypoxic gastric carcinoma cells by inhibiting anaerobic glycolysis (PubMed)

Low-dose YC-1 combined with glucose and insulin selectively induces apoptosis in hypoxic gastric carcinoma cells by inhibiting anaerobic glycolysis This study aimed to establish a therapeutic strategy targeting hypoxic cancer cells in gastric carcinoma (GC). YC-1 is a HIF-1α inhibitor, and we revealed that low-dose YC-1 (10 µM) suppressed HIF-1α expression, and induced hypoxia-dependent apoptosis in the GC cell line 58As9. This hypoxia-specific apoptosis induction by YC-1 involved excessive (...) reactive oxygen species (ROS) generation. The apoptotic effect of 10 µM YC-1 was enhanced by additional glucose (G) and insulin (I) treatments. RT-PCR demonstrated that 10 µM YC-1 reduced hypoxia-induced expression of HIF-1α targets involved in anaerobic glycolysis. Metabolic analysis showed that YC-1 shifted glucose metabolism in hypoxic cells from anaerobic glycolysis to oxidative phosphorylation (OXPHOS). Additional GI accelerated membranous GLUT1 translocation, elevating glucose uptake

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2017 Scientific reports

123. Issues and Ideas in Bolus Advisor Research With Commentary on “A Methodology to Compare Insulin Dosing Algorithms in Real-Life Settings” (PubMed)

Issues and Ideas in Bolus Advisor Research With Commentary on “A Methodology to Compare Insulin Dosing Algorithms in Real-Life Settings” The accompanying article by Groat et al in this issue presents a methodology to compare glucose outcomes from insulin bolus dose recommendations observed retrospectively from a novel iDecide bolus calculator with glucose outcomes from the prospective bolus recommendations provided by a current insulin pump. The methodology in this article evaluates a bolus (...) merits serious consideration, yet the actual dose recommendations provided by the iDecide calculator introduce wider lessons on how bolus calculator glucose outcomes might be better optimized.

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2017 Journal of diabetes science and technology

124. Dose Accuracy, Injection Force, and Usability Assessment of a New Half-Unit, Prefilled Insulin Pen (PubMed)

Dose Accuracy, Injection Force, and Usability Assessment of a New Half-Unit, Prefilled Insulin Pen This study examines the utility of the first prefilled, rapid-acting insulin pen that can be dialed in half-unit increments. Dose accuracy and injection force were examined through a series of design-verification tests, and usability was established by human factors validation testing.Devices were tested for dose accuracy at 3 different doses and temperatures and under free fall, vibration (...) , and cold storage conditioning. Injection force was measured at the maximum dose (30 units). Both experiments used the same semiautomated testing system. Usability was validated in a human factors simulated-use study that included 60 participants (patients with type 1 or type 2 diabetes [aged 10-79 years], adult caregivers, and health care providers).The pen met the International Organization for Standardization (ISO) 11608-1:2014 requirements for dose accuracy at all settings and conditions tested

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2017 Journal of diabetes science and technology

125. Dose-Dependent Effect of Sitagliptin on Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus Receiving Insulin Treatment: A Post Hoc Analysis (PubMed)

Dose-Dependent Effect of Sitagliptin on Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus Receiving Insulin Treatment: A Post Hoc Analysis Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce blood glucose in a dose-dependent manner, but the dose-dependent effect relationship between DPP-4 inhibitors and atherosclerosis has not been investigated.Patients with type 2 diabetes mellitus (T2DM) treated with insulin were randomized to the sitagliptin (n = 137) or conventional treatment (...) compared with conventional treatment. Multiple linear regression analysis showed that changes in mean-IMT-CCA and left max-IMT-CCA decreased with higher sitagliptin dose.Addition of sitagliptin to insulin therapy might attenuate the progression of atherosclerosis in patients with T2DM in a dose-dependent manner.Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., and Novo Nordisk.UMIN000007396.

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2017 Diabetes Therapy Controlled trial quality: uncertain

126. Low Dose Insulin as an Anti-Scarring Therapy in Breast Surgery: A Randomised Controlled Trial. (PubMed)

Low Dose Insulin as an Anti-Scarring Therapy in Breast Surgery: A Randomised Controlled Trial. The role of insulin in expediting wound healing is firmly established within the context of major trauma and burns; however, only limited clinical evidence exists as to its effects on scar formation. This study aims to build on previous laboratory work to examine the potential antiscarring properties of insulin in a clinical environment.Ninety-one patients undergoing bilateral aesthetic breast (...) operations were recruited to receive low-dose insulin and placebo injections to the medial 3 cm of their submammary incisions within the context of a randomized, intrapatient, placebo-controlled trial, and scar quality was assessed at 3-, 6-, and 12-month reviews using the Manchester Scar Scale.Across the cohort at 12-month review, the insulin-treated scars had lower scar scores (p = 0.055) compared with placebo. Subgroup analysis of individuals with heavier scars showed that median scar scores were

2017 Plastic and reconstructive surgery Controlled trial quality: uncertain

127. Erratum to: An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial. (PubMed)

Erratum to: An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial. After publication of the original article [1] it was noted that both the figures and captions and relating to Figs. 1 and 2 had been interchanged.

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2017 Medical Informatics and Decision Making Controlled trial quality: uncertain

128. Dose dependent effects of intranasal insulin on resting-state brain activity. (PubMed)

Dose dependent effects of intranasal insulin on resting-state brain activity. Insulin action in the human brain influences eating behavior, cognition, and whole-body metabolism. Studies investigating brain insulin rely on intranasal application.To investigate effects of three doses of insulin and placebo as nasal sprays on the central and autonomous nervous system and analyze absorption of insulin into the bloodstream.Nine healthy men received placebo or 40 U, 80 U, and 160 U insulin spray (...) in randomized order. Before and after spray, brain activity was assessed by functional magnetic resonance imaging, and heart rate variability (HRV) was assessed from electrocardiogram. Plasma insulin, C-peptide, and glucose were measured regularly.General community.Nasal insulin administration dose-dependently modulated regional brain activity and the normalized high-frequency component of the HRV. Post hoc analyses revealed that only 160 U insulin showed a considerable difference from placebo. Dose

2017 Journal of Clinical Endocrinology and Metabolism Controlled trial quality: uncertain

129. A Randomized Controlled Study of an Insulin Dosing Application That Uses Recognition and Meal Bolus Estimations. (PubMed)

A Randomized Controlled Study of an Insulin Dosing Application That Uses Recognition and Meal Bolus Estimations. Throughout the insulin pump therapy, decisions of prandial boluses programming are taken by patients individually a few times every day, and, moreover, this complex process requires numerical skills and knowledge in nutrition components estimation. The aim of the study was to determine the impact of the expert system, supporting the patient's decision on meal bolus programming (...) requirement in both groups was comparable-the average difference in total daily insulin dose between two groups was 0.26 (SD 7.06 IU, P = .9).The expert system in meal insulin dosing allows improvement in glucose control without increasing the rates of hypoglycemia or the insulin requirement.

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2017 Journal of diabetes science and technology Controlled trial quality: uncertain

130. Cross-Over Study Comparing Postprandial Glycemic Increase After Addition of a Fixed-Dose Mitiglinide/Voglibose Combination or a Dipeptidyl Peptidase-4 Inhibitor to Basal Insulin Therapy in Patients with Type 2 Diabetes Mellitus. (PubMed)

Cross-Over Study Comparing Postprandial Glycemic Increase After Addition of a Fixed-Dose Mitiglinide/Voglibose Combination or a Dipeptidyl Peptidase-4 Inhibitor to Basal Insulin Therapy in Patients with Type 2 Diabetes Mellitus. BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated (...) with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6

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2017 Medical science monitor basic research Controlled trial quality: uncertain

131. Impact of ELKa, the Electronic Device for Prandial Insulin Dose Calculation, on Metabolic Control in Children and Adolescents with Type 1 Diabetes Mellitus: A Randomized Controlled Trial. (PubMed)

Impact of ELKa, the Electronic Device for Prandial Insulin Dose Calculation, on Metabolic Control in Children and Adolescents with Type 1 Diabetes Mellitus: A Randomized Controlled Trial. Background. The ELKa system is composed of computer software, with a database of nutrients, and a dedicated USB kitchen scale. It was designed to automatize the everyday calculations of food exchanges and prandial insulin doses. Aim. To investigate the influence of the ELKa on metabolic control in children (...) with type 1 diabetes mellitus (T1DM). Methods. A randomized, parallel, open-label clinical trial involved 106 patients aged <18 years with T1DM, HbA1C ≤ 10%, undergoing intensive insulin therapy, allocated to the intervention group, who used the ELKa (n = 53), or the control group (n = 53), who used conventional calculation methods. Results. After the 26-week follow-up, the intention-to-treat analysis showed no differences to all endpoints. In per protocol analysis, 22/53 (41.5%) patients reporting ELKa

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2017 Journal of diabetes research Controlled trial quality: uncertain

132. Combined low-dose spironolactone plus vitamin E vs. vitamin E monotherapy on insulin resistance, noninvasive indices of steatosis and fibrosis and adipokine levels in nonalcoholic fatty liver disease: A randomized controlled trial. (PubMed)

Combined low-dose spironolactone plus vitamin E vs. vitamin E monotherapy on insulin resistance, noninvasive indices of steatosis and fibrosis and adipokine levels in nonalcoholic fatty liver disease: A randomized controlled trial. The beneficial effects of mineralocorticoid receptor blockade by spironolactone have been shown in animal models of non-alcoholic fatty liver disease (NAFLD). The aim of the present 52-week randomized controlled trial was to compare the effects of low-dose (...) in the combination treatment group (P = .028), but not in the vitamin E group, and the difference for group*time interaction was significant (P = .047). Alanine aminotransferase-to-platelet ratio index, an index of fibrosis, did not change. Insulin levels and HOMA-IR decreased significantly only within the combination group (P = .011 and P = .011, respectively). In conclusion, the combined low-dose spironolactone plus vitamin E regimen significantly decreased NAFLD liver fat score. Larger-scale trials are needed

2017 obesity & metabolism Controlled trial quality: uncertain

133. An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial. (PubMed)

An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial. A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection (...) of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity

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2017 Medical Informatics and Decision Making Controlled trial quality: uncertain

134. The effect of baseline characteristics on clinical efficacy of liraglutide in patients treated with high-dose insulin. (PubMed)

The effect of baseline characteristics on clinical efficacy of liraglutide in patients treated with high-dose insulin. In patients requiring high-dose insulin treatment, a randomized, double-blind, placebo-controlled study showed that liraglutide improved glycaemic control and treatment satisfaction while promoting weight loss. We performed a post hoc analysis to evaluate if patients' baseline characteristics impact the efficacy of liraglutide, and which outcomes correlate with treatment (...) satisfaction. We used regression analysis to model the change in HbA1c and weight, with treatment assignment and baseline characteristics [HbA1c, age, body mass index (BMI), total daily dose (TDD) of insulin, duration of insulin treatment, and type of insulin regimen] as independent variables. Improvement in HbA1c was best predicted by treatment with liraglutide, followed by higher baseline HbA1c, BMI and age. Changes in weight were only associated with liraglutide treatment, independent of all baseline

2017 obesity & metabolism Controlled trial quality: uncertain

135. Effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles of Insulin-Resistant Patients with Polycystic Ovary Syndrome (PubMed)

Effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles of Insulin-Resistant Patients with Polycystic Ovary Syndrome This study was carried out to evaluate the effects of vitamin D supplementation on the metabolic profiles of insulin-resistant subjects with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was conducted on 90 insulin-resistant women with PCOS. Participants were randomly assigned to three groups to intake either (...) vitamin D administration for 12 weeks to insulin-resistant women with PCOS had beneficial effects on total testosterone, SHBG, FAI, serum hs-CRP and plasma TAC levels compared with low-dose vitamin D and placebo groups.

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2017 Nutrients Controlled trial quality: predicted high

136. Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naive adults with Type 2 diabetes (PubMed)

mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions (...) Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naive adults with Type 2 diabetes To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin.In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat

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2016 EvidenceUpdates Controlled trial quality: uncertain

137. Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease. (PubMed)

peptide-1 (GLP-1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due (...) Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease. Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose

2018 Cochrane

138. Comparison of morning basal + 1 bolus insulin therapy (insulin glulisine + insulin glargine 300 U/ml vs. insulin lispro + insulin glargine biosimilar) using continuous glucose monitoring (CGM): a randomized crossover study. (PubMed)

on admission after glucose levels were stabilized by morning long-acting and ultra-rapid-acting insulins were randomly allocated to groups who received G + G300 on days 1 and 2, and the same dose L + GB on days 3 and 4, or vice versa. Data collected on days 2 and 4 (mean amplitude of glycemic excursion, mean of daily differences: all days) were analyzed. Insulin was injected at 08.00 h. A day was defined as the period from 08.00 h one day, to 08.00 h the next day. Test meals were given.Increased post (...) Comparison of morning basal + 1 bolus insulin therapy (insulin glulisine + insulin glargine 300 U/ml vs. insulin lispro + insulin glargine biosimilar) using continuous glucose monitoring (CGM): a randomized crossover study. We compared the effects of morning administration of insulin glulisine + insulin glargine 300 U/mL (G + G300) with that of insulin lispro + insulin glargine biosimilar (L + GB).A total of 30 patients with type 2 diabetes who wore a continuous glucose monitoring device

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2017 Journal of Diabetes Investigation Controlled trial quality: uncertain

139. 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

FPG <5.5 mmol/L). Significantly lower insulin doses were observed with IDegAsp vs comparators in all baseline characteristic and half of the category groups, and significantly lower rates of confirmed and nocturnal confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline variable and category groups.IDegAsp retains a consistent safety and efficacy profile in patients with different baseline characteristics.© 2018 The Authors. Diabetes, Obesity and Metabolism published (...) 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

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2018 EvidenceUpdates

140. A randomized, open-label, multicentre, parallel-controlled study comparing the efficacy and safety of biphasic insulin aspart 30 plus metformin with biphasic insulin aspart 30 monotherapy for type 2 diabetes patients inadequately controlled with oral anti

A randomized, open-label, multicentre, parallel-controlled study comparing the efficacy and safety of biphasic insulin aspart 30 plus metformin with biphasic insulin aspart 30 monotherapy for type 2 diabetes patients inadequately controlled with oral anti To confirm non-inferiority of biphasic insulin aspart 30 (BIAsp 30) plus metformin to BIAsp 30 in lowering glycated haemoglobin (HbA1c) in Chinese patients with inadequately controlled type 2 diabetes using oral antidiabetic drugs.In this 16 (...) dose (P < 0.001) and weight gain were significantly lower (P < 0.05) in the BIAsp 30 plus metformin group compared with the BIAsp 30 group. No between-group differences in number of hypoglycaemic events were observed.BIAsp 30 plus metformin was non-inferior to BIAsp 30 in safely reducing HbA1c in this study.© 2018 John Wiley & Sons Ltd.

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2018 EvidenceUpdates

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