Background Caloric restriction is an effective way to treat Type 2 diabetes (T2D). However, chronic and severe restriction of food intake is difficult to sustain and is known to promote slower... Show moreBackground Caloric restriction is an effective way to treat Type 2 diabetes (T2D). However, chronic and severe restriction of food intake is difficult to sustain and is known to promote slower metabolism. Intermittent and frequent fasting can exert similar metabolic effects, but may be even more challenging for most patients. A fasting-mimicking diet (FMD) is low in calories, sugars and proteins, but includes relatively high levels of plant based complex carbohydrates and healthy fats. The metabolic effects of such a diet mimic the benefits of water-only fasting. The effects of a FMD applied periodically in T2D patients are still unknown. The Fasting In diabetes Treatment (FIT) trial was designed to determine the effect of intermittent use (5 consecutive days a month during a year) of a FMD in T2D patients on metabolic parameters and T2D medication use compared to usual care. Methods One hundred T2D patients from general practices in the Netherlands with a BMI >= 27 kg/m(2), treated with lifestyle advice only or lifestyle advice plus metformin, will be randomised to receive the FMD plus usual care or usual care only. Primary outcomes are HbA1c and T2D medication dosage. Secondary outcomes are anthropometrics, blood pressure, plasma lipid profiles, quality of life, treatment satisfaction, metabolomics, microbiome composition, MRI data including cardiac function, fat distribution and ectopic fat storage, cost-effectiveness, and feasibility in clinical practice. Discussion This study will establish whether monthly 5-day cycles of a FMD during a year improve metabolic parameters and/or reduce the need for medication in T2D. Furthermore, additional health benefits and the feasibility in clinical practice will be measured and a cost-effectiveness evaluation will be performed. Show less
In this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was... Show moreIn this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was impaired in obese individuals. At baseline, mitochondrial protein content in skeletal muscle of obese subjects was significantly reduced compared to lean individuals. We assessed the neuronal response to fasting by fMRI scanning. We found a different neuronal response to fasting between lean and obese individuals in terms of functional connectivity between the hypothalamus and respectively the dACC and insula. Since these regions are part of the saliency network, these differences may reflect distinct perception of calorie imbalance between lean and obese subjects. The effects of fasting on sympathetic tone (estimated by heart rate variability) were studied. Our data suggests that fasting decreases sympathetic tone in lean subjects, whereas it increases sympathetic activity in obese individuals. Weight loss in obese individuals increased HRV parameters that reflect the postprandial sympathetic tone. Finally, we studied the effects of fasting in the presence and absence of food-odors since this has been shown to reduce the fasting-induced increase in life span in fruit flies __ no differences were found in our human subjects. Show less
