We are what we don’t eat: fasting and diabetes
Intermittent fasting is the diet industry’s hot new kid on the block, dominating headlines and bestseller lists. But for all the books and column inches, evidence of its benefits from clinical trials - particularly human trials – is in relatively short supply. Which made the presentations at the ‘Fasting and diabetes’ session at the EASD’s Annual Meeting especially welcome.
Intermittent fasting is an umbrella term, covering a range of fasting protocols that includes alternate-day fasting, fasting one or two days a week (the ‘5:2 diet’) and time-restricted feeding (TRF) where eating is restricted to 4-10 hour window. What these approaches hold in common is the belief that because our bodies evolved to cope with periods of going without, unlimited food availability inevitably leads to dysfunction – manifested in conditions such as obesity and type 2 diabetes. An eminently reasonable hypothesis, but what evidence is there that intermittent fasting is effective at reversing those dysfunctions?
Suheda Erener presented results from studies that examined the effect of different types of fasting on different organs – comparing the effect in mouse models of alternate day fasting versus TRF. Both approaches improved insulin sensitivity in the liver. Strikingly, when looking at the underlying protein signaling pathways, there was a clear distinction between genes upregulated by alternate-day fasting (which tended to be associated with fatty acids) and those upregulated by TRF (which tended to be associated with amino acids).
Studies looking at pancreatic islets held still more surprises, with fasting mice shown to have reduced insulin secretion and beta cell mass. Suheda hypothesised that these results were evidence that fasting in young mice predisposes them to diabetes. Additional studies are planned using older mice to illuminate these findings further.
Age, then, may significantly influence fasting’s effects. Gender too, according to another set of results, these presented by Satchidananda Panda. Satchidananda’s research, also using mouse models, found that while TRF helped improve glucose control in male and female mice, it only protected the males against body weight gain and fat accumulation. Nevertheless, the females in the TRF group showed reduced adipose tissue inflammation and were actually better protected by TRF against lipopolysaccharide challenge than the males.
But what about people? Krista Varady presented results from a 12-week study of TRF (specifically, 16:8 – which allows eating only within an 8-hour window) in a group of people with obesity. One of the best things about the TRF approach, according to Krista, is that no calorie monitoring is required, making compliance less burdensome than other approaches. Sure enough, participants showed good adherence (they stuck to the rules for 6 out of every 7 days). And their diligence reaped rewards with mild to moderate weight loss (7-8 lb/3 kg) and energy intake reduced by 350 calories a day. No change in adverse events was reported. A further 8-week study, conducted to gauge the effect of shorter eating windows (four and six hours, instead of eight), showed little difference on any of these outcomes – although the shorter window did have a more significant effect on fasting insulin and insulin resistance. A further study comparing alternate-day fasting (ADF) and calorie restriction diets showed that weight loss over one year between the two groups was pretty much identical. Interestingly, though, ADF produced greater reductions in insulin resistance and fasting insulin in participants with insulin resistance – suggesting a potential role for fasting regimens in pre-diabetes.
A new EASD e-Learning course on insulin resistance is currently in development and will be launching in 2021.
The opinions expressed in this blog are those of the author, Dr Eleanor D Kennedy.
Sessions at the EASD 56th Annual Meeting 2020
We are what we don’t eat
Suheda Erener. Organ-specific responses to intermittent fasting.
Krista Varady. Clinical application of intermittent fasting.
Satchidananda Panda. Circadian clocks, metabolism and fasting.