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Andreas Andersen, Jonatan I Bagger, Maria Pa Baldassarre, Mikkel B. Christensen, Kirsten U Abelin, Jens Faber, Ulrik Pedersen-Bjerregaard, Jens J Holst, Tommi B Lindhardt, Gunnar Hilmar Gislason, Filip K. Knop, and Tina Vilsbøll

Objective. Hypoglycemia is associated with increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes.

Design. A non-randomised, mechanistic intervention study

Methods. Insulin-treated patients with type 2 diabetes (n=21, [mean±SD] age 62.8±6.5 years, BMI 29.0±4.2 kg/m2, HbA1c 6.8±0.5% [51.0±5.4 mmol/mol]) and matched controls (n=21, age 62.2±8.3 years, BMI 29.2±3.5 kg/m2, HbA1c 5.3±0.3% [34.3±3.3 mmol/mol]) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: 1) fasting plasma glucose, 2) hyperglycemia (fasting plasma glucose+10 mmol/L) and 3) hyperinsulinemic hypoglycemia (plasma glucose<3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained.

Results. Both groups experienced progressively increasing heart rate corrected QT (Fridericia’s formula)) interval prolongations during hypoglycemia ([∆mean (95% CI)] 31 ms [16, 45] and 39 ms [24, 53] in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P=0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P=0.033 and P<0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia.

Conclusions. In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrythmias and sudden cardiac death.

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Mia Demant, Malte P Suppli, Signe Foghsgaard, Lise Gether, Magnus F G Grøndahl, Niels B Dalsgaard, Sigrid S Bergmann, Amalie R Lanng, Lærke S Gasbjerg, Martin Thomasen, Jonatan I Bagger, Charlotte Strandberg, Merete J Kønig, Henning Grønbæk, Ulrik Becker, Nicolai J Wewer Albrechtsen, Jens J Holst, Joachim Knop, Matthew P Gillum, Tina Vilsbøll, and Filip K Knop

Aims/hypothesis

Metabolic effects of intermittent unhealthy lifestyle in young adults are poorly studied. We investigated the gluco-metabolic and hepatic effects of participation in Roskilde Festival (1 week of binge drinking and junk food consumption) in young, healthy males.

Methods

Fourteen festival participants (FP) were studied before, during and after 1 week’s participation in Roskilde Festival. Fourteen matched controls (CTRL) who did not participate in Roskilde Festival or change their lifestyle in other ways were investigated along a similar timeline.

Results

The FP group consumed more alcohol compared to their standard living conditions (2.0 ± 3.9 vs 16.3 ± 8.3 units/day, P < 0.001). CTRLs did not change their alcohol consumption. AUC for glucose during OGTT did not change in either group. C-peptide responses increased in the FP group (206 ± 24 vs 236 ± 17 min × nmol/L, P = 0.052) and the Matsuda index of insulin sensitivity decreased (6.2 ± 2.4 vs 4.7 ± 1.4, P  = 0.054). AUC for glucagon during oral glucose tolerance test (OGTT) increased in the FP group (1037 ± 90 vs 1562 ± 195 min × pmol/L, P = 0.003) together with fasting fibroblast growth factor 21 (FGF21) (62 ± 30 vs 132 ± 72 pmol/L, P < 0.001), growth differentiation factor 15 (GDF5) (276 ± 78 vs 330 ± 83 pg/mL, P = 0.009) and aspartate aminotransferase (AST) levels (37.6 ± 6.8 vs 42.4 ± 11 U/L, P = 0.043). Four participants (29%) developed ultrasound-detectable steatosis and a mean strain elastography-assessed liver stiffness increased (P = 0.026) in the FP group.

Conclusions/Interpretation

Participation in Roskilde Festival did not affect oral glucose tolerance but was associated with a reduction in insulin sensitivity, increases in glucagon, FGF21, GDF15 and AST and lead to increased liver stiffness and, in 29% of the participants, ultrasound-detectable hepatic steatosis.