Soraya de Kam¹, Jeroen HPM van de Velde², Anna Veelen¹, Vera B. Schrauwen-Hinderling^{1, 3, 4}, Joris Hoeks¹ and Patrick Schrauwen^{2, 3, 4}

¹ Maastricht University, Universiteitssingel 50, Maastricht, The Netherlands, ² Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, ³ Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany, ⁴German Center for Diabetes Research (DZD e,V), München-Neuherberg, Germany

soraya.dekam@maastrichtuniversity.nl

Background: We previously showed that nocturnal respiratory exchange ratio (RER) was elevated in older metabolically compromised individuals compared to young healthy individuals. However, it remains unknown whether nocturnal substrate oxidation is altered by age or glycemic state in type 2 diabetes (T2D), and which traits contribute to these changes. This study examined RER and substrate metabolism across several groups and explored baseline characteristics that may influence these parameters.

Methods: Baseline data were pooled from 18 clinical trials. Nocturnal RER and substrate metabolism were measured via whole-room indirect calorimetry. Additional assessments included fasting glucose, insulin, free fatty acids, triglycerides and body composition (BodPod/DEXA).

Results: Study populations were included from four subpopulations: young lean (n=37,age=23.0 ±3.0, BMI=22.6 ±2.0), older lean (n=10,age=65.0 ±7.0, BMI=23.6 ±2.0), older overweight/obese without T2D (n=90,age=64.0 ±9.0,BMI=29.9 ±3.4) and older T2D (n=52,age=65.0 ±6.0,BMI=29.3 ±3.4). Nocturnal RER and carbohydrate oxidation were higher in overweight/obese (0.83 and 1.92 kJ/min, respectively) and T2D groups (0.82 and 1.77 kJ/min, respectively) compared to the young lean group (0.81 and 1.43 kJ/min, respectively; p<0.01). Fat oxidation was lower in the overweight/obese group (2.25 kJ/min) compared to young lean group (2.59 kJ/min; p<0.05). Fasting triglycerides correlated positively with nocturnal RER (r=0.376, p<0.01). Additionally, fasting insulin, triglycerides, fat mass and fat-free mass correlated positively with carbohydrate oxidation (r=0.205, 0.368, 0.222 and 0.413, respectively; p<0.05). Fat-free mass correlated positively with fat oxidation (r=0.312; p<0.001), whereas fasting triglycerides correlated negatively with fat oxidation (r= -0.282; p<0.001).

Conclusion: Besides correlations with body weight, fasting insulin and triglyceride may be determinants of elevated nocturnal carbohydrate oxidation in overweight/obese and T2D individuals.