Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects.

Normal beta-cells adjust their function to compensate for any decrease in insulin sensitivity. Our aim was to explore whether a prolonged fast would allow a study of the effects of changes in circulating free fatty acid (FFA) levels on insulin secretion and insulin sensitivity and whether any potential effects could be reversed by the antilipolytic agent acipimox. Fourteen (8 female, 6 male) healthy young adults (aged 22.8-26.9 yr) without a family history of diabetes and a body mass index of 22.6 +/- 3.2 kg/m(2) were studied on three occasions in random order. Growth hormone and FFA levels were regularly measured overnight (2200-0759), and subjects underwent an intravenous glucose tolerance test in the morning (0800-1100) on each visit. Treatment A was an overnight fast, treatment B was a 24-h fast with regular administrations of a placebo, and treatment C was a 24-h fast with regular ingestions of 250 mg of acipimox. The 24-h fast increased overnight FFA levels (as measured by the area under the curve) 2.8-fold [51.3 (45.6-56.9) vs. 18.4 (14.4-22.5) *10(4) micromol/l*min, P < 0.0001], and it led to decreases in insulin sensitivity [5.7 (3.6-8.9) vs. 2.6 (1.3-4.7) *10(-4) min(-1) per mU/l, P < 0.0001] and the acute insulin response [16.3 (10.9-21.6) vs. 12.7 (8.7-16.6) *10(2) pmol/l*min, P = 0.02], and therefore a reduction in the disposition index [93.1 (64.8-121.4) vs. 35.5 (21.6-49.4) *10(2) pmol/mU, P < 0.0001]. Administration of acipimox during the 24-h fast lowered FFA levels by an average of 20% (range: -62 to +49%; P = 0.03), resulting in a mean increase in the disposition index of 31% (P = 0.03). In conclusion, the 24-h fast was accompanied by substantial increases in fasting FFA levels and induced reductions in the acute glucose-simulated insulin response and insulin sensitivity. The use of acipimox during the prolonged fast increased the disposition index, suggesting a partial reversal of the effects of fasting on the acute insulin response and insulin sensitivity.

[Pilot study to evaluate blood glucose control by a model predictive control algorithm with variable sampling rate vs. routine glucose management protocol in peri- and postoperative period in cardiac surgery patients]. / Pilotní studie pro srovnání pocítacového algoritmu s variabilním intervalem merení glykémie a standardního protokolu pro intenzivní inzulínovou terapii v peri- a pooperacním období u kardiochirurgických pacientu.

BACKGROUND: Increased blood glucose levels are frequently observed in critically ill patients. Recent studies have shown that the normalization of glycemia by intensive insulin therapy decreases mortality, length of the hospitalization and number of complications. METHODS AND RESULTS: The aim of this pilot study was to compare blood glucose control by an automated model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RP) in peri- and postoperative period in cardiac surgery patients. 20 patients were included into this study (14 men and 6 women, mean age 68 +/- 10 let, BMI 28.3 +/- 5.0 kg/m2). 10 patients were randomized for treatment using eMPC algorithm and 10 patients for routine protocol. All patients underwent elective cardiac surgery and were treated with continuous insulin infusion to maintain glycemia in target range 4.4-6.1 mmol/l. The study duration was 24 hours. Mean blood glucose was significantly lower in eMPC vs. RP group (5.80 +/- 0.45 vs. 7.23 +/- 0.84 mmol/l, p < 0.05). Percentage of time in target range was significantly higher in eMPC vs. RP group (67.6 +/- 8.7% vs. 27.6 +/- 15.8%, p < 0.05). Percentage of time above the target range was higher in RP vs. eMPC group. Average insulin infusion rate was higher in eMPC vs. RP group (4.18 +/- 1.19 vs. 3.24 +/- 1.43 IU/hour, p < 0.05). Average sampling interval was significantly shorter in eMPC vs. RP group (1.51 +/- 0.24 vs. 2.03 +/- 0.16 hour, p < 0.05). No severe hypoglycaemia in either group occurred during the study. CONCLUSIONS: The results of our pilot study suggest that eMPC algorithm is more effective in maintaining euglycemia in peri- and post-operative period in patients after cardiac surgery and comparably safe as compared to RP.

On-line adaptive algorithm with glucose prediction capacity for subcutaneous closed loop control of glucose: evaluation under fasting conditions in patients with Type 1 diabetes.

AIMS: To evaluate an algorithm with glucose prediction capacity and continuous adaptation of patient parameters-a model predictive control (MPC) algorithm-to control blood glucose concentration during fasting conditions in patients with Type 1 diabetes. In the subcutaneous (sc) route within a closed loop system. METHODS: Paired experiments were performed in six patients. Over 8 h the MPC algorithm was used to control glucose with s.c. insulin administration and two different glucose monitoring protocols: first, the algorithm was provided with intravenous (i.v.) glucose values for insulin dosage calculation directly (i.v.-s.c. route). Then, in the second experiment, i.v. glucose values were fed to the MPC with a delay of 30 min to simulate s.c. glucose measurements ('s.c.'-s.c. route). In both experiments plasma glucose, insulin dosage, and serum insulin levels were analysed. RESULTS: Glucose concentration was brought from hyper- to normoglycaemia and kept in the physiological range (6-7 mmol/l) with both routes in all subjects. Mean glucose concentration reached the threshold of 7 mmol/l approximately 2 (i.v.-s.c. route) and 3 ('s.c.'-s.c. route) hours after the start of glucose control with the MPC. During the last 2 h of automated glucose control, mean glucose concentration was 6.3 +/- 0.2 mmol/l and 6.6 +/- 0.3 mmol/l for i.v.-s.c. and 's.c.'-s.c. route, respectively. Glucose concentration, insulin doses, and serum insulin levels did not differ significantly between routes (P > 0.05). CONCLUSIONS: The MPC algorithm is suitable for glucose control during fasting within an extracorporeal artificial beta-cell in the subcutaneous route Type 1 diabetic patients.