Meal skipping has become an increasing trend of the modern lifestyle that may lead to obesity and type 2 diabetes. We investigated whether the timing of meal skipping impacts these risks by affecting circadian regulation of energy balance, glucose metabolism, and postprandial inflammatory responses. In a randomized controlled crossover trial, 17 participants [body mass index (in kg/m): 23.7 ± 4.6] underwent 3 isocaloric 24-h interventions (55%, 30%, and 15% carbohydrate, fat, and protein, respectively): a breakfast skipping day (BSD) and a dinner skipping day (DSD) separated by a conventional 3-meal-structure day (control). Energy and macronutrient balance was measured in a respiration chamber. Postprandial glucose, insulin, and inflammatory responses in leukocytes as well as 24-h glycemia and insulin secretion were analyzed. When compared with the 3-meal control, 24-h energy expenditure was higher on both skipping days (BSD: +41 kcal/d; DSD: +91 kcal/d; both < 0.01), whereas fat oxidation increased on the BSD only (+16 g/d; < 0.001). Spontaneous physical activity, 24-h glycemia, and 24-h insulin secretion did not differ between intervention days. The postprandial homeostasis model assessment index (+54%) and glucose concentrations after lunch (+46%) were, however, higher on the BSD than on the DSD (both < 0.05). Concomitantly, a longer fasting period with breakfast skipping also increased the inflammatory potential of peripheral blood cells after lunch. Compared with 3 meals/d, meal skipping increased energy expenditure. In contrast, higher postprandial insulin concentrations and increased fat oxidation with breakfast skipping suggest the development of metabolic inflexibility in response to prolonged fasting that may in the long term lead to low-grade inflammation and impaired glucose homeostasis. This trial was registered at clinicaltrials.gov as NCT02635139.

Background Weight control is hypothesized to be improved when physical activity and energy intake are both high [high energy turnover (ET)]. Objective The impact of three levels of ET on short-term appetite control is therefore investigated at fixed levels of energy balance. Design In a randomized crossover trial, 16 healthy adults (25.1 ± 3.9 y of age; body mass index, 24.0 ± 3.2 kg/m2) spent three daylong protocols for four times in a metabolic chamber. Four conditions of energy balance (ad libitum energy intake, zero energy balance, −25% caloric restriction, and +25% overfeeding) were each performed at three levels of ET (PAL 1.3 low, 1.6 medium, and 1.8 high ET; by walking on a treadmill). Levels of appetite hormones ghrelin, GLP-1, and insulin (total area under the curve) were measured during 14 hours. Subjective appetite ratings were assessed by visual analog scales. Results Compared with high ET, low ET led to decreased GLP-1 (at all energy balance conditions: P < 0.001) and increased ghrelin concentrations (caloric restriction and overfeeding: P < 0.001), which was consistent with higher feelings of hunger (zero energy balance: P < 0.001) and desire to eat (all energy balance conditions: P < 0.05) and a positive energy balance during ad libitum intake (+17.5%; P < 0.001). Conclusion Appetite is regulated more effectively at a high level of ET, whereas overeating and consequently weight gain are likely to occur at low levels of ET. In contrast to the prevailing concept of body weight control, the positive impact of physical activity is independent from burning up more calories and is explained by improved appetite sensations.

Objective Sedentary lifestyle increases the risk of type 2 diabetes. The aim of this study was to investigate the impact of different levels of energy turnover (ET; low, medium, and high level of physical activity and the corresponding energy intake) on glucose metabolism at zero energy balance, caloric restriction, and overfeeding. Methods Sixteen healthy individuals (13 men, 3 women, 25.1 ± 3.9 years, BMI 24.0 ± 3.2 kg/m 2 ) participated in a randomized crossover intervention under metabolic ward conditions. Subjects passed 3 × 3 intervention days. Three levels of physical activity (PAL: low 1.3, medium 1.6, and high 1.8 achieved by walking at 4 km/h for 0, 3 × 55, or 3 × 110 min) were compared under three levels of energy balance (zero energy balance (EB): 100% of energy requirement (Ereq); caloric restriction (CR): 75% Ereq, and overfeeding (OF): 125% Ereq). Continuous interstitial glucose monitoring, C-peptide excretion, and HOMA–IR, as well as postprandial glucose and insulin were measured. Results Daylong glycemia and insulin secretion did not increase with higher ET at all conditions of energy balance (EB, CR, and OF), despite a correspondingly higher CHO intake (Δ low vs. high ET: +86 to 135 g of CHO/d). At CR, daylong glycemia ( p = 0.02) and insulin secretion ( p = 0.04) were even reduced with high compared with low ET. HOMA–IR was impaired with OF and improved with CR, whereas ET had no effect on fasting insulin sensitivity. A higher ET led to lower postprandial glucose and insulin levels under conditions of CR and OF. Conclusion Low-intensity physical activity can significantly improve postprandial glycemic response of healthy individuals, independent of energy balance.

Sugar-containing beverages like orange juice can be a risk factor for obesity and type 2 diabetes although the underlying mechanisms are less clear. We aimed to investigate if intake of orange juice with or in-between meals differently affects energy balance or metabolic risk. Twenty-six healthy adults (24.7 ± 3.2 y; BMI 23.2 ± 3.2 kg/m2) participated in a 4-week cross-over intervention and consumed orange juice (20% of energy requirement) either together with 3 meals/d (WM) or in-between 3 meals/d (BM) at ad libitum energy intake. Basal and postprandial insulin sensitivity (primary outcome), daylong glycaemia, glucose variability and insulin secretion were assessed. Body fat mass was measured by air-displacement plethysmography. After BM-intervention, fat mass increased (+1.0 ± 1.8 kg; p < 0.05) and postprandial insulin sensitivity tended to decrease (ΔMatsudaISI: −0.89 ± 2.3; p = 0.06). By contrast, after WM-intervention fat mass and gamma-glutamyl transferase (GGT) decreased (−0.30 ± 0.65 kg; −2.50 ± 3.94; both p < 0.05), whereas glucose variability was higher (ΔMAGE: +0.45 ± 0.59, p < 0.05). Daylong glycaemia, insulin secretion, changes in basal insulin sensitivity, and triglycerides did not differ between WM- and BM-interventions (all p > 0.05). In young healthy adults, a conventional 3-meal structure with orange juice consumed together with meals had a favorable impact on energy balance, whereas juice consumption in-between meals may contribute to a gain in body fat and adverse metabolic effects.

The 'carbohydrate-insulin theory of obesity' is used to justify popular health claims stating that carbohydrates make you fat or a high glycemic load and consumption of sugar-sweetened beverages (SSBs) and breakfast skipping increase fat gain. According to this theory, the elevated postprandial insulin secretion to a high glycemic challenge is blamed as a causal mechanism by directing nutrients away from oxidation in muscle towards storage in adipose tissue. Scientific evidence is however largely disagreeing with an adverse effect of postprandial hyperinsulinemia on fuel partitioning. Possible reasons for this disagreement are differences in insulin sensitivity and energy balance. Diet-induced hyperinsulinemia may lead to a higher fat storage only at a positive energy balance. A shift in fuel partitioning towards fat storage requires improved or maintained insulin sensitivity in adipose tissue when compared with skeletal muscle. This may be the case during refeeding (after weight loss), physical inactivity or in metabolically healthy obese subjects (relative to insulin-resistant subjects). The adverse effect of a high-glycemic diet, SSBs consumption or breakfast skipping on body weight is likely due to increased energy consumption rather than to increased fat storage.