Dynamic changes in insulin requirements with post-operative time using bedside artificial pancreas to maintain normoglycemia without hypoglycemia after cardiac surgery.

It is difficult to manage postoperative blood glucose levels without hyperglycemia and hypoglycemia in cardiac surgery patients even if continuous intravenous insulin infusion is used. Therefore, the insulin requirements for maintaining normoglycemia may be difficult to evaluate and need to be elucidated. In this single-center retrospective study, 30 adult patients (age 71.5 ± 9.0 years old, men 67%, BMI 22.0 ± 3.1 kg/m2, diabetes 33%) who underwent cardiac surgery and used bedside artificial pancreas (STG-55) as a perioperative glycemic control were included. We investigated the insulin and glucose requirements to maintain normoglycemia until the day after surgery. The bedside artificial pancreas achieved intensive glycemic control without hypoglycemia under fasting conditions for 15 h after surgery (mean blood glucose level was 103.3 ± 3.1 mg/dL and percentage of time in range (70-140 mg/dL) was 99.4 ± 2.0%). The total insulin requirement for maintaining normoglycemia differed among surgical procedures, including the use of cardiopulmonary bypass during surgery, while it was not affected by age, body mass index, or the capacity of insulin secretion. Moreover, the mean insulin requirement and the standard deviation of the insulin requirements were variable and high, especially during the first several hours after surgery. Treatment using the bedside artificial pancreas enabled intensive postoperative glycemic control without hypoglycemia. Furthermore, the insulin requirements for maintaining normoglycemia after cardiac surgery vary based on surgical strategies and change dynamically with postoperative time, even in the short term.

Effects of 6-month eicosapentaenoic acid treatment on postprandial hyperglycemia, hyperlipidemia, insulin secretion ability, and concomitant endothelial dysfunction among newly-diagnosed impaired glucose metabolism patients with coronary artery disease. An open label, single blinded, prospective randomized controlled trial.

BACKGROUND: Recent experimental studies have revealed that n-3 fatty acids, such as eicosapentaenoic acid (EPA) regulate postprandial insulin secretion, and correct postprandial glucose and lipid abnormalities. However, the effects of 6-month EPA treatment on postprandial hyperglycemia and hyperlipidemia, insulin secretion, and concomitant endothelial dysfunction remain unknown in patients with impaired glucose metabolism (IGM) and coronary artery disease (CAD). METHODS AND RESULTS: We randomized 107 newly diagnosed IGM patients with CAD to receive either 1800 mg/day of EPA (EPA group, n = 53) or no EPA (n = 54). Cookie meal testing (carbohydrates: 75 g, fat: 28.5 g) and endothelial function testing using fasting-state flow-mediated dilatation (FMD) were performed before and after 6 months of treatment. The primary outcome of this study was changes in postprandial glycemic and triglyceridemic control and secondary outcomes were improvement of insulin secretion and endothelial dysfunction. After 6 months, the EPA group exhibited significant improvements in EPA/arachidonic acid, fasting triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The EPA group also exhibited significant decreases in the incremental TG peak, area under the curve (AUC) for postprandial TG, incremental glucose peak, AUC for postprandial glucose, and improvements in glycometabolism categorization. No significant changes were observed for hemoglobin A1c and fasting plasma glucose levels. The EPA group exhibited a significant increase in AUC-immune reactive insulin/AUC-plasma glucose ratio (which indicates postprandial insulin secretory ability) and significant improvements in FMD. Multiple regression analysis revealed that decreases in the TG/HDL-C ratio and incremental TG peak were independent predictors of FMD improvement in the EPA group. CONCLUSIONS: EPA corrected postprandial hypertriglyceridemia, hyperglycemia and insulin secretion ability. This amelioration of several metabolic abnormalities was accompanied by recovery of concomitant endothelial dysfunction in newly diagnosed IGM patients with CAD. Clinical Trial Registration UMIN Registry number: UMIN000011265 ( https://www.upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013200&language=E ).

Effects of insulin degludec and insulin glargine on day-to-day fasting plasma glucose variability in individuals with type 1 diabetes: a multicentre, randomised, crossover study.

AIMS/HYPOTHESIS: We compared the effects of insulin degludec (IDeg; Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin) and insulin glargine (IGlar; A21Gly,B31Arg,B32Arg human insulin) on the day-to-day variability of fasting plasma glucose (FPG) levels in individuals with type 1 diabetes treated with basal-bolus insulin injections. METHODS: The effects of basal-bolus insulin therapy for 4 weeks with either IDeg or IGlar as the basal insulin in adult C-peptide-negative outpatients with type 1 diabetes were investigated in an open-label, multicentre, randomised, crossover trial. Randomisation was conducted using a centralised allocation process. The primary endpoints were the SD and CV of FPG during the final week of each treatment period. Secondary endpoints included serum glycoalbumin level, daily dose of insulin, intraday glycaemic variability and frequency of severe hypoglycaemia. RESULTS: Thirty-six randomised participants (17 in the IDeg/IGlar and 19 in the IGlar/IDeg groups) were recruited, and data for 32 participants who completed the trial were analysed. The mean (7.74 ± 1.76 vs 8.56 ± 2.06 mmol/l; p = 0.04) and SD (2.60 ± 0.97 vs 3.19 ± 1.36 mmol/l; p = 0.03) of FPG were lower during IDeg treatment than during IGlar treatment, whereas the CV did not differ between the two treatments. The dose of IDeg was smaller than that of IGlar (11.0 ± 5.2 vs 11.8 ± 5.6 U/day; p < 0.01), but other secondary endpoints did not differ between the treatments. CONCLUSIONS/INTERPRETATION: IDeg yielded a lower FPG level and smaller day-to-day variability of FPG at a lower daily dose compared with IGlar in participants with type 1 diabetes. IDeg serves as a good option for basal insulin in the treatment of type 1 diabetes. TRIAL REGISTRATION: University Hospital Medical Information Network 000009965. FUNDING: This research recieved no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Effects of exenatide and liraglutide on postchallenge glucose disposal in individuals with normal glucose tolerance.

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are categorized as short- or long-acting types, but information regarding differences in the effects of these two types on postprandial glucose disposal has been limited. We have now investigated the effects of exenatide and liraglutide (short- and long-acting GLP-1RAs, respectively) on glucose disposal during an oral glucose tolerance test (OGTT). METHODS: Fourteen healthy volunteers with normal glucose tolerance underwent three OGTTs, which were performed without pharmacological intervention or after a single administration of exenatide or liraglutide at 30 min and 10 h, respectively, before test initiation. The three OGTTs were performed with intervals of at least 7 days between successive tests and within a period of 2 months. RESULTS: Exenatide, but not liraglutide, markedly decelerated the peak of both plasma glucose and serum insulin levels during the OGTT, with the peaks of both glucose and insulin concentrations occurring at 150 min after test initiation with exenatide compared with 30 min in the control condition or with liraglutide. Exenatide and liraglutide reduced the area under the curve for plasma glucose levels during the OGTT by similar extents, whereas that for serum insulin levels was reduced only by exenatide. CONCLUSIONS: Our results suggest that exenatide decelerates the increase in plasma glucose levels through inhibition of glucose absorption and that it exerts an insulin-sparing action after glucose challenge.

Diurnal variation of carbohydrate insulin ratio in adult type 1 diabetic patients treated with continuous subcutaneous insulin infusion.

To estimate the carbohydrate-to-insulin ratio (CIR), a formula dividing a constant, usually 300-500, by the total daily dose (TDD) of insulin, is widely utilized. An appropriate CIR varies for each meal of the day, however. Here, we investigate diurnal variation of CIR in hospitalized Japanese type 1 diabetic patients treated with continuous subcutaneous insulin infusion. After optimization of the insulin dose, TDD and total basal insulin dose (TBD) were 34.9 ± 10.2 and 9.3 ± 2.8 units, respectively, with a percentage of TBD to TDD of 27.3 ± 6.0%. The products of CIR and TDD at breakfast, lunch and dinner were 311 ± 63, 530 ± 161, and 396 ± 63, respectively, suggesting that in the formula estimating CIR using TDD, the constant should vary for each meal of the day, and that 300, 500, and 400 are appropriate for breakfast, lunch, and dinner, respectively.

C-peptide response to glucagon challenge is correlated with improvement of early insulin secretion by liraglutide treatment.

The amelioration of glucose tolerance by liraglutide was associated with a significant improvement of early insulin-response during OGTT. The serum C-peptide response to glucagon challenge strongly correlated with the improvement of the early insulin-response. The C-peptide response to glucagon challenge would be useful to predict therapeutic response to liraglutide.