Oral glucose has little or no effect on appetite and satiety sensations despite a significant gastrointestinal response.

OBJECTIVE: The effect of oral glucose-induced release of gastrointestinal hormones on satiety and appetite independently of prevailing plasma glucose excursions is unknown. The objective is to investigate the effect of oral glucose on appetite and satiety sensations as compared to isoglycemic IV glucose infusion (IIGI) in healthy volunteers. DESIGN: A crossover study involving two study days for each participant. PARTICIPANTS: Nineteen healthy participants (6 women, mean age 55.1 [SD 14.2] years; mean body mass index 26.7 [SD 2.2] kg/m2). INTERVENTIONS: Each participant underwent a 3-h 50-g oral glucose tolerance test (OGTT) and, on a subsequent study day, an IIGI mimicking the glucose excursions from the OGTT. On both study days, appetite and satiety were indicated regularly on visual analog scale (VAS), and blood was drawn regularly for measurement of pancreatic and gut hormones. PRIMARY OUTCOMES: Difference in appetite and satiety sensations during OGTT and IIGI. RESULTS: Circulating concentrations of glucose-dependent insulinotropic polypeptide (P < .0001), glucagon-like peptide 1 (P < .0001), insulin (P < .0001), C-peptide (P < .0001), and neurotensin (P = .003) increased significantly during the OGTT as compared to the IIGI, whereas glucagon responses were similarly suppressed (P = .991). Visual analog scale-assessed ratings of hunger, satiety, fullness, thirst, well-being, and nausea, respectively, were similar during OGTT and IIGI whether assessed as mean 0-3-h values or area under the curves. For both groups, a similar, slow increase in appetite and decrease in satiation were observed. Area under the curve, for prospective food consumption (P = .049) and overall appetite score (P = .044) were slightly lower during OGTT compared to IIGI, whereas mean 0-3-h values were statistically similar for prospective food consumption (P = .053) and overall appetite score (P = .063). CONCLUSIONS: Despite eliciting robust responses of appetite-reducing and/or satiety-promoting gut hormones, we found that oral glucose administration has little or no effect on appetite and satiety as compared to an IIGI, not affecting the release of appetite-modulating hormones. TRIAL REGISTRY NO: ClinicalTrials.gov: NCT01492283 and NCT06064084.

Sustained heart rate-corrected QT prolongation during recovery from hypoglycaemia in people with type 1 diabetes, independently of recovery to hyperglycaemia or euglycaemia.

AIM: To investigate changes in cardiac repolarization abnormalities (heart rate-corrected QT [QTc ] [primary endpoint], T-wave abnormalities) and heart-rate variability measures in people with type 1 diabetes during insulin-induced hypoglycaemia followed by recovery hyperglycaemia versus euglycaemia. METHODS: In a randomized crossover study, 24 individuals with type 1 diabetes underwent two experimental clamps with three steady-state phases during electrocardiographic monitoring: (1) a 45-minute euglycaemic phase (5-8 mmol/L), (2) a 60-minute insulin-induced hypoglycaemic phase (2.5 mmol/L), and (3) 60-minute recovery in either hyperglycaemia (20 mmol/L) or euglycaemia (5-8 mmol/L). RESULTS: All measured markers of arrhythmic risk indicated increased risk during hypoglycaemia. These findings were accompanied by a decrease in vagal tone during both hyperglycaemia and euglycaemia clamps. Compared with baseline, the QTc interval increased during hypoglycaemia, and 63% of the participants exhibited a peak QTc of more than 500 ms. The prolonged QTc interval was sustained during both recovery phases with no difference between recovery hyperglycaemia versus euglycaemia. During recovery, no change from baseline was observed in heart-rate variability measures. CONCLUSIONS: In people with type 1 diabetes, insulin-induced hypoglycaemia prolongs cardiac repolarization, which is sustained during a 60-minute recovery period independently of recovery to hyperglycaemia or euglycaemia. Thus, vulnerability to serious cardiac arrhythmias and sudden cardiac death may extend beyond a hypoglycaemic event, regardless of hyperglycaemic or euglycaemic recovery.

Hypoglycaemia and rebound hyperglycaemia increase left ventricular systolic function in patients with type 1 diabetes.

AIM: To investigate echocardiographic changes during acute hypoglycaemia followed by recovery to hyperglycaemia or euglycaemia in patients with type 1 diabetes. MATERIALS AND METHODS: In a randomized crossover study, 24 patients with type 1 diabetes took part in two experimental study days, consisting of a hyperinsulinaemic-euglycaemic phase (5.0-8.0 mmol/L) for 45 minutes followed by a hyperinsulinemic-hypoglycaemic phase (2.5 mmol/L) for 60 minutes, and a recovery phase in either hyperglycaemia (20 mmol/L) or euglycaemia (5.0-8.0 mmol/L) for 60 minutes. Cardiac function was evaluated with echocardiography during each phase. RESULTS: Acute hypoglycaemia increased all markers of left ventricular (LV) systolic function, including LV ejection fraction (LVEF), global longitudinal strain (GLS), GLS rate and peak systolic velocity of mitral annular longitudinal movement (s'; P < 0.001 for all). During the recovery phases, all markers of LV systolic function were increased during hyperglycaemia (P < 0.01 for all), and LVEF and GLS remained increased during euglycaemia (P = 0.0116 and P = 0.0092, respectively). The increment in LVEF during the recovery phase was greater during hyperglycaemia than euglycaemia (P = 0.0046). CONCLUSIONS: Hypoglycaemia, recent hypoglycaemia, and overcorrection of hypoglycaemia to rebound hyperglycaemia increased LV systolic function in type 1 diabetes and may imply consideration of plasma glucose when evaluating LV function in patients with type 1 diabetes. An increase in LV systolic function may cause increased strain on the heart and partly explain the link between hypoglycaemia, high glycaemic variability and cardiovascular disease.