That was heralded in media reports like this one:  Low-calorie diet offers hope of cure for type 2 diabetes

It just so happened that I had a journal article open in my browser dealing with pancreatic fat content and diabetes when I received an email about this from a reader.  So I sort of had this topic on my mind and was probably more receptive to what the study found vis a vis this factor than others might have been.

Peter/Hyperlipid, in a post entitled Diabetic and Hungry,  jumped on the fact that this was a very low calorie diet, therefore a low carbohydrate diet and that’s why it worked to reverse diabetes.   He writes:

It is really too bad that Peter is so steeped into the insulin hypothesis that it appears he’ll never acknowledge the role of calories in the equation.  That won’t stop me from trying to tell him, and others of like mind, that were the participants to have done so, they would not have lost the weight they did, and likely not have unloaded the fat from their pancreata (I think that’s the plural there) either, in the 8 relatively short weeks in which they did.  Since all diets are high fat diets in his mind anyway — because he counts the fatty acids liberated from body fat and oxidized as “calories in” (??this just makes no sense to me??)   — what’s the point anyway?

Jenny Ruhl of Diabetes 101 weighed in with her own take with the exaggerated entitled:  Idiotically Dangerous Diet “Reverses Diabetes” but So Does Moderate Carb Restriction Without Calorie Restriction

I don’t really know what to make of Jenny’s take on a lot of things regarding scientific studies, low carbing and treating diabetes.  She’s a diabetic herself who manages her disease with, near as I can tell, a rather bit more moderate than some, low carb diet.  And yet, this study “cured” diabetes — as in proper insulin secretion by the beta cells was restored — it did not simply manage hyperglycemia.  As my regular readers know, I’ll repeat that I consider hyperglycemia a symptom of the underlying problem which is impaired pancreatic beta cell function.  If memory serves, Jenny is amongst those who took Dr. Davis to task for making claims of “curing” diabetes with low carb and giving diabetics false hope.  I took him to task on this blog around a year ago for his put-downs of other doctors, most of whom are advising their patients in good conscience and based on success they’ve achieved with others, I believe.  Davis has walked that back a bit, now claiming that low carb only puts diabetes into remission.  (This was admitted to in comments on his blog sometime circa March/April of this year if anyone can find me the link.)    I would go a step further and say all it does is manage hyperglycemia in the long run for the bulk of folks following his advice  One is certainly well served by avoiding the ravages of hyperglycemia, but there’s no evidence that carbohydrate restriction improves beta cell function (more on this later).  

Jenny ratchets up the hyperbole with this statement on the study:

Now, I don’t care if only one out of the 11 was actually cured of their diabetes for the long term, and the gent interviewed for the article was free of his diabetes a year and a half later after six years of taking medications to manage his disease, so I’d say he qualifies.  That’s a big deal.  This diet did not damage that diabetic!  It actually CURED him!!!  A year and a half out.  Nor, apparently did it damage the 7 of the 11 who were still diabetes free three months later despite regaining an average of roughly 3kg.  

Jenny goes on:

Sorry, but the urge to go yada yada at the whole it’s so low in calories it’s LC schtick  overwhelms me.  Really?  At 12 weeks post intervention, we had the following results:

Hepatic triacylglycerol remained low and unchanged (2.9±0.2 vs 3.0±0.3%; p=0.80), and pancreatic triacylglycerol decreased further to a small extent (6.2±1.1 vs 5.7±1.1%; p=0.005). HbA1c was unchanged (6.0±0.2 vs 6.2±0.1% [42±2 vs 44±1 mmol/mol]; p=0.10) and fasting plasma glucose increased modestly (5.7±0.5 vs 6.1± 0.2 mmol/l; p<0.01), with a 2 h OGTT plasma glucose of 10.3±1.0 mmol/l. Three participants had recurrence of diabetes as judged by a 2 h post-load plasma glucose >11.1 mmol/l. Fasting plasma insulin concentrations were unchanged (57±11 vs 65±15 pmol/l) and fasting plasma NEFA decreased further (0.72±0.06 vs 0.54±0.05 mmol/l;p<0.02).

Again, this is 3 months after returning to a “normal” diet and gaining back around 7 lbs on average.  The fasting NEFA — which are elevated in diabetes (although not that much in this group) went predictably up during the dramatic 8 weeks of weight loss, but later went down to lower than the non-diabetic controls.

Jenny also makes a, frankly, ridiculous analogy between  this diet — essentially a protein sparing modified fast (PSMF) —  and the Minnesota “starvation” diet.  C’mon now!  I actually find myself in agreement with commenter “blogblog” over at Peter’s on this one.  We’ve discussed here before the utterly irrelevancy of that study, and as blogblog pointed out, starving normal weight people on a protein and likely many micro deficient diet for six months is nowhere near the same as putting an overweight/obese person on a PSMF for a couple of months.  Yes, as was the case here, a PSMF is best done under medical supervision as there are potential dangers, but apparently none of the participants became suicidal psychotics!

Now they don’t measure such things as pancreatic or hepatic fat on The Biggest Loser, but TBL consultant Dr. Michael Dansinger says that they basically halve the caloric intake of the participants on the show.  Couple that with all those hours of exercise and you’re talking a similar very large/sustained caloric deficit.  It’s my understanding that one consumes a totally liquid diet — relatively low fat at that as well — for a while following gastric bypass surgery … IOW dramatic/sustained caloric deficit.  And guess what?  Whether they want to admit it or not,  especially the first time around, the spontaneous caloric reduction on a low carb diet  is often rather significant.  There’s a formerly almost 400 lb guy who used to participate at Jimmy’s who believed all the “high calorie” lore, yet when he averaged his intake on LC he was eating less than 1200 cal/day.  That’s a pretty significant deficit!

Yoni Freedhoff weighed in on this over on his Weighty Matters blog with a post entitled Amazing, shocking, unbelievable news about type 2 diabetes and diet!   His take, that I agree with,  is  basically that there’s nothing new about the advice or knowledge that diet/lifestyle change can actually cure diabetes.

I’m guessing if you’ve got type 2 diabetes, you caught that news from your doctor. In fact I’d be shocked to learn if there were a single type 2 diabetic on the planet who wasn’t told at diagnosis that weight loss and/or lifestyle change could reverse the course of their disease, and while they’d need to maintain their losses/changes to maintain the reversal, that lifestyle can have at least as great an impact on disease course as drugs.

Dr. Davis, of course, contends that all those other doctors, who advise patients to go on a traditional weight loss diet and increase their activity to lose weight are just doing that to hook them on medications.  Surely they don’t have their patients’ well-being in mind.  I’m guessing most aren’t ratcheting up the hyperbole because they’re coming out with their own line of gluten free products to hawk, but I digress …  Back to Yoni for one more excerpt:

Wanna know what else disappeared for the participants?

Weight. In the first week they lost nearly 10lbs, or 5% of their presenting body weights. By the end of 8 weeks, they lost nearly 30lbs or 13% of their presenting body weights.

So is it surprising that a recently diagnosed type 2 diabetic who loses 30lbs living off an extremely low calorie, low carb diet, can come off of their oral hypoglycemics?

What would be interesting, to me at least, is for this group to repeat the study (measuring pancreatic fat and insulin response) in another group of subjects put on a 1200 cal/day diet for however long it takes for them to lose the same average 30 lbs and compare the results to these.  Is it just the weight loss after all?  After all, in long term intervention studies such as Shai, the average weight losses weren’t all that impressive – about 10 lbs at 1yr to 2yrs in both the Mediterranean and LC groups, and even the max loss around 4 months for LC was only avg of around 15 lbs.  (See graphic here).

But maybe there’s something to this aside from the weight, or maybe the speed of the weight loss matters?  After all, what do SAD-to-VLC-or-Paleo converters, 600 cal/day dieters (which includes such plans as KK, Medifast, HCG injections, and a caloric intake Gary Taubes’ Diet Doctor friend would be delighted to see), TBL contestants, and many many “crash” diets have in common?   The establishment of a substantial and sustained caloric deficit.  This of course leads to rapid weight loss.  Does the rate of the loss, however, impact the fat content of the pancreas?  I’ll speculate on that in my closing comments.

Getting back to Jenny’s contention that lowering pancreatic fat had nothing to do with it, and the paper that was open in my browser when this story landed in my Inbox, let’s talk pancreatic fat content for a bit. It is not controversial that the pancreas requires fatty acids for the secretion of insulin.  It’s often not known by most because we focus on what elicits an acute insulin response — that being glucose (and the oft forgotten amino acids) — but we’ve discussed this here before (and I’ll have more to come).  The long story short of it is that fatty acids fuel the ß-cell for glucose-stimulated insulin secretion, but they also stimulate basal insulin secretion, e.g. in the fasted state.  When exposure to fatty acids is excessive, lipid accumulates in the ß-cell and causes lipotoxicity and/or cell death (apoptosis).  The direct relationship between circulating free fatty acid (NEFA) levels and lipid accumulation in the pancreas (or any organ for that matter) is somewhat complicated.  It appears to me that when our bodies are in a state of negative energy balance or increased usage of fatty acids as fuel, the elevated levels do not contribute to such accumulation and/or the accumulation is not detrimental but acts more as a local storage depot for the cells.  But in the context of chronic energy surplus and/or the failure of adipose tissue to adequately trap and store NEFA, elevated NEFA lead to detrimental accumulation of lipid in the cells.  And it appears one such cell type most affected are the ß-cells.

The paper I had open in my browser was this one:  (A more detailed analysis is forthcoming in a separate post)
Pancreatic Fat Content and ?-Cell Function in Men With and Without Type 2 Diabetes

This group used an analytical method to assess the pancreatic lipid content in diabetic men and non-diabetic controls.  Here’s what they found:

Median pancreatic fat content was significantly higher in diabetic compared with nondiabetic men: 20.4% (13.4–43.6 [interquartile range]) vs. 9.7% (7.0–20.2)

Note:  Interquartile range (IQR) is the range of levels for the middle half of the sample.  One quarter of each group had levels less than the minimum of the IQR, and one quarter of them had levels exceeding the maximum.  Clearly there’s no absolute relationship between fat content (25% of the non-diabetics had fat content greater than roughly half of the diabetics), but …

This is the first report to show that, in addition to liver fat, pancreatic fat content is increased in men with type 2 diabetes, relative to nondiabetic men. In nondiabetic men, the pancreatic fat content was inversely associated with various features of ?-cell function.

Although pancreatic fat was associated with all but one model/parameter of ?-cell function, ?-cell glucose sensitivity correlated most strongly with pancreatic fat. This parameter of ?-cell function has been demonstrated to be most reproducible (14) and a good predictor of progression to type 2 diabetes in nondiabetic subjects (18).

Also,

The association of pancreatic fat and ?-cell function was found in nondiabetic but not in diabetic men. This may be explained by both methodological (relatively small number of diabetic men and low numerical values for the ?-cell parameters assessed with too little variation to allow detection of any association) and pathophysiological factors, which are more likely to account for the findings. In diabetes, the presence of pancreatic fat may be permissive to the deleterious action of hyperglycemia on the ?-cell (glucolipotoxicity) (2). Thus, because of the simultaneous activation of many deleterious cascades, including oxidative stress, inflammation, and apoptosis but also hypoperfusion of the islets, ?-cell function deterioration may develop at a rate disproportional to that of pancreatic fat accumulation. Conversely, hyperglycemia via malonyl-CoA inhibits carnitine palmitoyltransferase-1, leading to a decrease in mitochondrial ?-oxidation and further stimulation of intracellular triglyceride accumulation. As stated above, this mechanism may, among others, contribute to the higher pancreatic fat content observed in diabetic relative to nondiabetic men.

Translation:  When some degree of normal function exists, pancreatic fat content correlates with the extent of that function in an inverse manner.  In non-diabetics, higher pancreatic fat content is associated with reduced ß-cell function.  But once some threshold has been exceeded — e.g. we now have ß-cell impairment and frank diabetes — further accumulations of fat don’t seem to exacerbate things much.  That kind of makes sense to me.  If someone adds dirt to  a wheelbarrow, the speed with which I can move it declines as the amount of dirt increases.  But once it’s filled with a certain weight I can no longer push it at all.  My inability to push the wheelbarrow is not impacted further by adding even more dirt.  The amount of dirt that renders a wheelbarrow immovable varies with the person trying to push it. 

One other note:

Interestingly, no correlation was found between hepatic and pancreatic fat content … [and] we found no association between pancreatic and visceral fat. 

I’ll leave that for another day except to say that essentially any intervention that has been demonstrated to alter body composition, or reduce hepatic (liver) or visceral (around abdominal organs)  fat will not necessarily impact pancreatic fat.

So let’s go back one last time to the study that caused the splash and what was novel about it after all.  Here’s what the authors state in their intro: