Thread by @Dr__Guess

High protein and low glycaemic diet to prevent type 2 diabetes.

A tweetorial.

The PREVIEW study primary results came out last month.

This was a large international trial looking at the effect of diet on the prevention of T2D (an endpoint OMG!!)

It didn't get much traction which is weird, so I wanted to review.

First of all, some history.

We know lifestyle changes can help prevent T2D in people who are at high risk (ie, have prediabetes/ non-diabetic hyperglycaemia).

This is because we have >10 large scale trials which have looked at this.

This is the basis on which we in the 🇬🇧 have the NHS Diabetes Prevention Programme.

National screening takes place for high risk groups, and if people are identified with elevated blood glucose, they can be referred onto the programme.

The evidence from these trials is that modest weight loss of 5-7% can help prevent/delay T2D.

(There are caveats based on type of prediabetes, ethnic group, whether exercise adds further benefit, baseline BMI but bottom line is that it's mostly weight loss driving this effect)

However, what's not been looked at well is whether different dietary patterns could optimise the preventive effect.

This is because all the major trials pretty much looked at the same diet: low fat, low saturated fat, high fibre.

(Except PREDIMED).

What was great about PREVIEW is they looked at a different and quite experimental approach -

High protein and reduced glycaemic index diet!

I think the rationale for this is good.

Increasing protein and lowering the glycaemic load lowers blood glucose in established T2D even if a person does not lose weight.

(Note: This effect has been well- studied up to 10 weeks, whether the effect is maintained over time is unknown)

The effect might be due to the effect of amino acids on the pancreas - they can help the pancreas produce more insulin which helps lower glucose.

The glucose reduction itself might help further as glucose at high concentrations is toxic including to pancreatic B-cells.

Note - again, whether the "insulinogenic" effect of the amino acids lasts over time is also not known.

This is why this study was pretty cool - b/c participants randomised to the high protein groups were encouraged to consume 25%kcal from protein for the whole 3 -year period.

Also note, the PREVIEW study was a 2x2 factorial study - comparing different protocols to each other.

HP was high protein (25%kcal).
MP was medium protein (15%kcal).
MI was medium intensive exercise
HI was high intensive exercise

Finally - BEFORE participants started on their assigned diet - ALL of them took part in an 8-week weight loss phase using meal replacement. They only continued in the study if the lost 8kg or more.

(@KCKlatt don't @ me about error bars)

So what did the investigators find? Did more protein and less available carb (low GI) help prevent more cases of T2D than the medium protein and higher GI group?

NO

However, I do not think this means a high protein reduced carb diet could not help protect against T2D in people at high risk.

Here's why:

Firstly, the initial weight loss phase (10kg weight loss!!) would probably be enough to "reboot" the pancreas.

So if protein mediates its effects via helping the pancreas produce more insulin, this probably would have been nulled by the marked and rapid weight loss effect.

The baseline A1c was 36 mmol/L and what we see from other trials is that if the baseline risk of developing T2D is LOW, you don't see a protective effect during the trial (cos ppl weren't going to develop T2D during this timeframe anyway).

The loss to follow-up was high - just under 50% lost at the 3 year endpoint - so the study did not have the power to see a difference (notwithstanding the nullifying effects of low baseline risk + initial weight loss phase)

Note: running long-term dietary trials is HARD.

Although the diet was low GI its hard to know whether participants did this - also the diet was fairly high in available carb (~38%kcal from carb).

It's speculation but maybe the combo of high protein + high carb puts too much demand on the beta-cell?

So congratulations to the investigators for running an ambitious, novel dietary intervention for the prevention of T2D (they also measured urinary nitrogen and did MR on a subsample 👏👏)

But I think in some ways this study leaves more questions than answers.

I would love to see the effect of rapid weight loss on T2D incidence - ie have people lose 6% weight loss but over 2 weeks as opposed to 2 months & see if this makes a difference.

And let's properly test a high protein reduced carb T2D prevention programme.

THE END.