Mice and humans with certain types of cancer lose a lot of weight, a condition known as cachexia. Besides causing a major decline in quality of life, this usually predicts mortality. But tumor-burdened ATGLko mice exhibit none of this (closed bar = control; open bar = mice with tumors):
Unfortunately, much of this weight is type II muscle (left), while type I muscle is largely spared (right). ATGLko mice are immune to muscle loss.
Type II muscle is white, burns sugar, and flexes fast and strong (that’s why I said “unfortunately,” above). Type I muscle is red, burns fat, and flexes slow and weak.
You wanna burn fat? ATGL (Adipocyte Triacylglycerol Lipase) is your man. ATGL is responsible for breaking down fat, a necessary precondition for fat burning. Mice lacking ATGL accumulate tons of fat: 20x more in the heart, 10x more in testis, 3x more in skeletal muscles, 2x more in the GI tract, etc., etc. Not surprisingly, they’re overweight.
Part 1. The importance of the ability to un-store fat: appetite, body composition, and insulin.
I’ve been known to rave about the phenomenon of metabolically obese normal weight (MONW), or fat skinny people. In brief, this population exhibits insulin resistance, metabolic syndrome, hypertension… all things usually associated with obesity… but they’re lean. In fat skinny people, I wrote about two epidemiological studies on markedly different populations (Americans and Koreans); these two peoples have virtually nothing in common (culture, foods, genetics, etc.). Despite these differences, there was a strong similarity in the macronutrients associated with metabolic dysregulation in otherwise lean individuals (aka fat skinny people): in the first study, high carb and low protein diets were the major culprits, with a smaller contribution of low fat. In the second study, high carb and low fat were at fault (protein intake wasn’t analyzed).
A new study that is about to hit the presses didn’t intend to say anything about fat skinny people, but they weren’t counting on ME.
This study included over 50,000 people aged 18-90. Between the years 2000 and 2005 about 3% died, which was statistically just enough to ask “why?” In brief, they compared body weight, blood pressure, smoking, and diabetes with mortality risk.
In each BMI category, the square is higher than the circle. DM = diabetes (the squares). Diabetes increases mortality risk independent of BMI. Now just focusing on the squares; as you move from left to right, body weight is increasing but mortality risk in diabetics is decreasing. A 150 pound diabetic has a higher mortality risk than a 200 pound diabetic, who has a higher mortality risk than a 250 pound diabetic. Huh?
Perhaps the lean diabetics are fat skinny people, the elusive MONW? If so, according to the research discussed HERE, their diet might have made them that way. The lean diabetics (aka fat skinny people aka MONW aka NOD [non-obese diabetics]) eat less protein, more carbs, and less fat. This might be a reach, but collectively (1 + 2 + 3) these data imply a poor diet might be worse than obesity for diabetics.
disclaimer: this is not true in most circumstances, i.e., skinny people can usually whatever they want. There areskinny diabetics, but they are significantly rarer than obese diabetics. In other words, most type II diabetics are obese, the lean ones just eat a crappier diet. You might be wondering: “how are they skinny if they eat so poorly?” My guess is that they just haven’t eaten enough of it [yet]; it’s rare to stay lean on a “crappier diet.”
So is skinny the new fat? Being lean with type II diabetes is an indicator of EMPTY CALORIES; it could be riskier for all-cause mortality than obesity in diabetics.
“Attention endocrinologists, diabetologists, and general practitioners: don’t assume diet is not a problem in your skinny diabetics because they are skinny. Indeed, diet might be THE problem.”
And no, if you’re a skinny diabetic, this DOESN’T mean gaining weight will make you live longer. it just doesn’t.
Figuring out how best to eat, physiological insulin resistance, and an homage to pioneering nutrition research.
Insulin resistance, as we know it today, is associated with poor nutrition, obesity, and the metabolic syndrome. But it’s FAR more interesting than that. Indeed, it could even save your life. At the time when the pioneering studies discussed below were occurring, the researchers had no idea insulin resistance was going to become one of the most important health maladies over the course of the following century. Furthermore, these somewhat-primitive studies also shed some light, possibly, on how weshould be eating. hint: it might all come down to physiological insulin resistance.
Rats were fed either a normal starch-based diet (low fat), or a high butter diet (low carb) for one month, then fasted overnight and injected with a whopping dose of insulin (4 U/kg). First, take a guess, what do you think happened and why. Then, click on the table below.
To make a long story short, all the starch-fed rats died while all the butter-fed rats lived.
On a high-fat zero-carb diet, plasma insulin levels are low. Insulin is low because there no carbs (i.e., it’s supposed to be low). Under conditions of low insulin, unrestrained adipose tissue lipolysis leads to a mass exodus of fatty acids from adipose tissue. These fatty acids accumulate in skeletal muscle and liver rendering these tissues insulin resistant. But this doesn’t matter, because insulin sensitivity is unnecessary when there aren’t any carbs around. So if that rogue research scientist who’s always trying to jab you with a syringe filled with insulin actually succeeds, you won’t die. The high-fat diet prevents insulin-induced hypoglycemic death. This is physiological and absolutely critical insulin resistance.
To determine if this was specific to dairy (butter) or a general effect of a high fat zero carb diet, Bainbridge repeated the experiments with lard. Lo-and-behold, lard-fed rats were just as fine as those dining on butter.
To be sure, these studies exhibited a high degree of animal cruelty… but their simplicity is laudable. And Bainbridge’s findings are not an isolated case.
Instead of starch, lard, and butter, Hynd and Rotter used milk and bread, cheese, and casein. And their findings were essentially identical to Bainbridge’s: mice, rats, or rabbits fed carbohydrate-free diets were insulin resistant and protected against insulin-induced tragedies.
The interesting finding was in kittens, who sadly maintained insulin sensitivity when fed fish (high protein) or cream (high fat).
You’re probably thinking: why would I say any state of heightened insulin sensitivity is “sad?” WELL, I say “sad” because we’re talking about physiological insulin resistance; a condition when resistance to the hypoglycemic effect of insulin is essential, and lack thereof is incompatible with survival. To be clear: 1) kittens remain insulin sensitive on high fat and protein diets; and 2) this is OK because there aren’t any rogue research scientists running around trying to jab them with insulin. While I can’t say for sure, this might have something to do with what kittens are supposed to eat, i.e., their natural diet. High protein and fat diets won’t make them insulin resistant because unlike rodents, that is their normal diet. (real mice eat fruits and seeds; laboratory mice eat pelleted rodent chow; cartoon mice eat cheese.) Lard causes ectopic lipid deposition in insulin sensitive tissues in rodents because they aren’t accustomed to it. Mice are optimized to eat a high carb diet. Kittens eat protein and fat, usually in the form of mice. But when given bread, kittens develop insulin resistance. There is no bread in mice.
While we shouldn’t base our diet around the possibility of turning a corner and being jabbed with a syringe filled with insulin, perhaps we are simply more similar to kittens. Hypercaloric diets loaded with sugar, excess carbohydrates, and empty calories cause [pathological] insulin resistance (which could theoretically save your life if a rogue research scientist jabbed you with insulin), whereas the opposite is true for diets high in fat and protein. This is repeatedly demonstrated in diet intervention studies, most recently in the notorious Ebbeling study (Missing: 300 kilocalories). When people were assigned to the very low carbohydrate diet, insulin sensitivity was significantly higher than when they were on low fat diets:Soapbox rant: I’m not saying low carb is what we are supposed to eat. Nor am I saying it is the optimal diet. IMHO any diet which excludes processed junk food and empty calories is “healthy.” The Paleo diet isn’t healthy because some nutritionista says it’s what we are supposed to eat; Paleo is healthy for the same reason as Atkins, Zone, South Beach, and a million others: no junk food.
Maybe the diet we’re supposed to eat has nothing to do with the healthiest diet. Maybe not. But it probably isn’t bad for you. just sayin’
In this CROSSOVER study, different doses of coconut flour were incorporated into common test foods to see how they impacted the blood glucose response to said test foods. The total carbohydrate load of each food was 50 grams and to make a long story short, coconut flour dose-dependently reduced the glycemic index.
There’s a lot happening in that figure, but basically the foods with the least coconut flour (e.g., white bread) elicited far greater increases in blood glucose than foods with the most coconut flour (e.g., coconut flour brownies). Mechanistically, this is most likely due to coconut flour’s fiber and/or fat content (both of which slow down glucose absorption and both of which are markedly higher in coconut flour compared than white flour).
Coconut flour: anti-hyperglycemic
Moving on,
the lipid component of coconut flour, coconut oil, is kind-of-amazing in itself.
1) Coconut oil is a perfectly suitable substitute for butter if you’re following a casein-free diet (e.g., GFCF). You don’t need to be a molecular gastronomer or food scientist to try it; refined coconut oil can be used just like butter (“virgin” coconut oil, on the other hand, retains a strong coconut flavor).
2) Coconut oil is rich in the magical ketogenic medium chain fatty acids (e.g., C12 laurate) and to over-simplify a series of very elegant studies on diet and diabetes (detailed in Diet, diabetes, and death [oh my] [highly recommended reading if you’re into fatty acids, etc.]), coconut oil is remarkably protective against diabetic pathophysiology; a property not shared with lard, corn oil, or shortening.
Indirect confirmation of the presence of ketogenic medium chain fatty acids in coconut oil can be seen in this study by Romestaig. Rats fed a diet rich in coconut oil ate more calories but gained less weight than rats fed a high butter or low fat diet:
Coconut oil-fed rats (solid black circles) ate more than the butter group but weighed less. Coconut oil-fed rats ate WAY more than the low fat group but weighed just as much. Nice, huh? Getting back to the point, this is virtually identical to what happens on bona fide ketogenic diets (see Episode 2 of the ketosis series and Ketosis, III), where carbohydrates are kept below 5% of calories (which is phenomenally low, 25 grams on a 2000 kcal diet).
Coconut flour: anti-hyperglycemic Coconut oil: ketogenic
Coconut protein ? … calorie for calorie, coconut flour has more protein than most other flours.
In recent study on diabetic rats, Salil showed that coconut protein completely protected against alloxan-induced diabetes (this study was published in 2011; unlike the earlier studies referenced above, researchers are no longer allowed to give fatal doses of alloxan to rats and count the days until they die. Nowadays they just look at the surrogate marker blood glucose [it goes up very high in diabetes]). Alloxan is a pancreatic toxin which destroys insulin-producing beta cells.
Group 1 (open bar) = controls group. Group II (black bar) = fed coconut protein. Group III (vertical stripes) = diabetic. Group IV (diagonal stripes) = diabetic and fed coconut protein. A diet high in coconut protein made these rats invincible to alloxan… just like coconut oil. Coincidence? (to be continued)
Coconut oil and coconut protein are both present in coconut flour. While it’s not as expensive as almond flour, coconut flour is still pricier than regular white flour. But people love their baked goods, pastas, and breads. If there is ever going to be a way for these foods exit the realm of “empty calories,” the first step is abandoning white flour. Maybe your muffins won’t be so big and fluffy, but neither will your ass.
(it’s a “drupe,” not a nut. [Thank you Wikipedia.])
Should almonds be upgraded from “snack” to food? Should almond flour be used in place of some or all white flour? Yes and yes, IMHO.
In 2007, Josse and colleagues did a quick-and-dirty study on almonds and glucose tolerance. They fed a group of volunteers 50 grams of carbs from white bread and either 0, 30, 60, or 90 grams of almonds and then measured blood glucose over the following two hours. “Quick” because they probably had almonds and bread in the refrigerator, and glucometers in their desk drawers; “dirty” because there were a lot of uncontrolled variables; for example: fiber, protein, and fat content of the test meals differed wildly:In a proper study, they might have tried to feed everyone the same amount of fiber, protein, and fat, because each of these is known to affect blood glucose. In any case, the result was pretty cool:
Whole almonds dose-dependently blunted the blood glucose response to the test meal. Conclusion: almonds = anti-hyperglycemic. But almonds are complex lil’ things; they’re made of protein, fat, fiber, and a lot of nutrients; so what’s responsible for all the anti-hyperglycemic effect? this post is not simply an academic pursuit; indeed, almond flour and almond oil are commercially available, affordable, widely used, and are comprised of different fractions of the almond. So Mori and colleagues decided to study.
In this excessively high quality study, the effect of 4 different types of almond preparations on glucose tolerance was assessed.
What was tested (in a FIVE-WAY crossover study):
WA = whole almonds
AB = almond butter
AF = defatted almond flour (remember this stuff? lacks all the bifidogenicity of regular almond flour )
AO = almond oil
V = vehicle: negative control.
Basically, the participants were fed a breakfast of OJ and Cream of Wheat with the equivalent of 33 almonds (42.5 grams) for a total of 75 grams of carbs, and blood glucose was measured over the next 2 hours.
Notable nutritional differences between the almond preparations: they all contain a similar fat content except for the defatted almond flour; whole almonds and almond butter have 2-3 times more fiber than almond flour and almond oil; almond oil has half the protein as all the others.
In brief, no almond preparation affected insulin or free fatty acids.
Whole almonds, almond butter, and almond oil, on the other hand, all blunted the glycemic response. Defatted almond flour, which only really differs in its lack of almond fat, did not. Thus, according to last post, almond fat is a potent bifidogen (i.e., good for gut bacteria); and now we see it’s also responsible for the anti-hyperglycemic effect of almonds. These two effects are probably unrelated, however, as any effect on gut bacteria will take significantly longer than a few hours as the almond fat hasn’t even reached the large intestine by then… (the anti-hyperglycemic effect is evident within 2 hours; the bifidogenic effect noted by Mandalari was 8-24 hours).
OK, almond fat slows the absorption of glucose, so what? this is not exciting… it’s common among most fats- “dietary fat reduces the glycemic index of food.” But this has a greater implication: one could alternatively conclude that almond flour’s lack of fiber was at fault, as dietary fiber is also known to slow glucose absorption. However, almond oil, which has even less fiber than defatted almond flour, was also anti-hyperglycemic. So it’s not the fiber (… perhaps because almond fiber is predominantly insoluble).
With regard to all-things-almonds: almond fat, not almond fiber, is anti-hyperglycemic and bifidogenic (what can’t it do?).
Almond fat: +2
Solution: whole almonds (with meals?), almond oil (with whatever), and regular [non-defatted] almond flour (for baking?). WRT the latter, get all the benefits, a boost for the gut microbiota, and significantly fewer carbs than with white flour (while actually attenuating the glycemic impact of said white flour).
An argument for almond flour: most baked goods are made with white flour. These foods are predominantly empty calories, the bane of human health and well-being. Substituting almond flour for white flour is one way to decrease the emptiness of those calories, and thus of life itself (it’s gluten-free too).
It takes more sugar in the form of “date paste” (Cranberry Almond, 19 g sugar) to compensate for the lack of “invert evaporated cane juice” (Peanut Crunch, 14 g sugar) or “invert dried cane syrup” (Toasted Coconut, 16 g sugar). Invert sugar is basically table sugar (sucrose) that has been broken down into glucose & fructose. 1) It’s sweeter, which is why you need less of it; and 2) it’s essentially identical to high fructose corn syrup = used in everything from candy and crackers to cigarettes and soda. Not good.
Pro’s: less sugar and more fiber than ZonePerfect’s Perfectly Simple.
These bars rely on the sweetener brown rice syrup which is primarily glucose (significantly less fructose than invert sugar), but it’s complimented with agave (significantly more fructose than invert sugar)… end result? Organic high fructose corn syrup (a polished turd).
High protein, moderate sugar, and preservative-free.
These bars are sweetened with honey, brown rice syrup, invert sugar, and a little coconut sugar. These bars have more protein and less sugar than both Perfectly Simple and ActiveX.
Last but not least, my personal favorite in the “coolness” department: Chapul.
Pro #1: they owned it! “sugar” actually appears in the list of ingredients.
Pro #2: while it’s only 6 grams of protein, you’ll never guess where it comes from… crickets! Yes crickets. Baked, then ground into a fine powder.
Con: the most sugar and least protein of all.
To put this all into perspective: relative to the nutritional profile of Quest protein bars, these noobs pale in comparison.
“Weight-loss maintenance” is a critical part in the battle against obesity because losing weight is much easier and significantly more successful than keeping it off. The difference lies predominantly in duration: a few months of dieting to lose weight vs. keeping it off for the rest of your life. Two diet studies on the topic were recently published, and while neither study really addressed the issue proper, some interesting points can be gleaned from both.
16 weeks of weight loss followed by 16 weeks of “weight-loss maintenance.”
In brief, the weight loss was accomplished by one of two hypocaloric (1400 kcal/d) isocaloric pseudo-Dukan Diets (higher protein & lower fat than Atkins)
The catch: Breakfast for the people in HCPb (High Carbohydrate and Protein breakfast) had twice the calories, 6x the carbs, and half more protein than LCb (Low Carb breakfast). This was compensated, calorically, by a much smaller dinner. In other words, they ate like a King for breakfast, a Prince for lunch, and a Pauper for dinner… with the added bonus of a “sweet food… chocolate, cookies, cake, ice cream, chocolate mousse or donuts.” For breakfast.
People in both groups lost roughly similar amounts of weight in the weight loss phase:
During the first 16 weeks (weight loss phase), a strict 1400 kcal diet was implemented. During the second 16 weeks (“weight-loss maintenance” phase), macronutrient composition was supposed to be kept similar, but subjects were “free to eat as motivated by hunger or cravings.” Critique #1a: this study would’ve greatly benefitted by food intake questionnaires to know more accurately what these people were eating; the importance of this becomes more apparent soon.
At three times throughout the study (baseline, week 16, and week 32), a “Breakfast meal challenge” was administered to assess Hunger, Hatiety, and Food Cravings. Unfortunately, however, the “Breakfast meal challenge” was administered… after… breakfast. HCPb binged on a high calorie 3-course meal which included dessert while LCb nibbled on a lite breakfast… And the researchers needed a 100-millimeter Visual Analog Scale and 28-item Food Craving Inventory Questionnaire to figure out who would be hungrier afterwords? Really?
Divide and conquer
Table 2. There were no major differences between the groups, and between those who completed or didn’t complete the study except for weight loss in those who withdrew. Apparently, people who didn’t lose any weight on the hypocaloric weight loss diet decided to quit (was it the diet or the dieter that didn’t work? [sorry, no offense]). In any case, this would’ve introduced a systematic bias except the non-weight-losers were similar in both diet groups. But Hunger & Satiety was also similar between completers and dropouts… I wonder why… i.e., the diet was working for those who were losing weight, because Hunger was low and Satiety high; in the dropouts who didn’t lose weight, Hunger was low and Satiety high because they were eating more (which is why they didn’t lose weight). IOW: “not hungry -> eat less -> lose weight -> complete the study” vs. “eat more -> not hungry -> don’t lose weight -> dropout of the study.” People are “not hungry” in both groups, but for different reasons.
Critique 1b: this is another place where a food intake questionnaires would come in handy.
During the weight loss phase, LCb lost a little bit more weight and became a little bit more insulin sensitive than HCPb, which is interesting only because the macronutrients were so similar. Thus, it may have been an effect of “meal-size-timing.” In other words, don’t eat like a King for breakfast, a Prince for lunch, and a Pauper for dinner.
Ghrelin, a hunger hormone, was significantly higher in LCb and this actually correlated very well with measured Hunger levels (unlike leptin, the far more popular anti-hunger hormone, discussed in depth HERE). And insulin, a theorized yet controversial hunger hormone, did not: insulin was lower at week 16 while Hunger was 2x higher; and insulin was 2x higher at week 32 compared to week 16 while Hunger was the same at those time points (Table 3). Thus, for those interested (which is admittedly probably only me), neither leptin nor insulin correlate with Hunger levels; but this study showed that ghrelin does. Furthermore, similar to those leptin data mentioned above, Hunger was not correlated with weight loss (which is kind-of-fascinating).
The second half of the study (“weight-loss maintenance”) was complete bollocks and made no sense whatsoever (you’ll see it on the evening news). What you can conclude from this study, however: people following the moderately higher protein and lower carb pseudo-Dukan Diet (LCb) lost modestly more weight during the first 16 weeks than those following the more traditional higher carb version (HCPb). BOTH diets were “high protein” and “low carb,” and people in BOTH groups lost a lot of weight (~30 pounds in 4 months). The media hasn’t had their way this study [yet], but when they do, I’m sure the they’ll disagree.
Don’t eat doughnuts for breakfast, you heard it here first.
Altered gut bacteria can cause a whole host of problems, anywhere from depression and fatigue to ADHD and heartburn. Thus, while running my daily search for “bifidobacteria,” I happened across these little goodies:
The Attune Foods Dark Chocolate Probiotic Bar. Combining probiotics (e.g., bifidobacteria, acidophilus, etc.) with chocolate?! And with 68% cocoa, I’d expect this bar to deliver at least some of the benefits of dark chocolate (e.g., improved insulin sensitivity). They’re gluten-free and even contain inulin! (my second favorite bifidogenic prebiotic.)
And it packs a big, or rather huge, probiotic punch (6.1 billionB. lactis HN019, L. acidophilus NCFM, & L. casei LC-11). Attune loses a little cred by trying to disguise their sugar as “evaporated cane juice,” like it’s something inherently healthier than plain old sugar… just like all-natural agave syrup, honey, and organic coconut blossom sugar. just own it for crying out loud. On the other hand, at only 6 grams, the sugar in Attune’s bar is harmless especially in the context of the high cocoa content, inclusion of inulin, and whopping dose of probiotics.
But, chocolate & probiotics? Alas, the curiousity bug had bitten.
Apparently, a lot of companies think dark chocolate is a good vehicle for probiotic delivery.
GI Health’s Probiotic Chocolate is gluten-free and contains a half billion L. helveticus R0052 and B. longum R0175 per serving. A half-billion is low by conventional standards*, but such standards might be irrelevant if the delivery vehicle (i.e., chocolate) is superior.
*Most probiotic products are rated (by me) by the number of live bacteria per serving, or “colony forming units (cfu).” This is usually in the billions because most die in transit, thus the importance of the delivery method. Yogurt and apparently now chocolate seem to be good delivery vehicles, however, yogurt and most probiotic pills require refrigeration; these chocolate products do not. And neither do Nature’s Way Probifia Pearls, although they are the only pill that doesn’t (I suspect alien technology).
Possemiers (2010) set out to test how well probiotics survived in a robot gut simulator when mixed in chocolate. 1 billion L. helveticus CNCM I-1722 and B. longum CNCM I-3470 were mixed with either chocolate or milk. An astounding 85% of the probiotics survived when administered in chocolate compared to only 25% with milk. FYI the study was funded by Barry Callebaut, a fancy Belgian chocolate maker who is currently developing their own line of probiotic chocolates … it’s not a conflict of interest, it’s what companies should be doing IMO (while an independent third party would be optimal, any data are better than none). I have no idea how well their robot gut simulator emulates actual human digestion, but these results suggest that chocolate is [at least] potentially a good candidate to deliver probiotics.
An additional benefit of loading probiotics into chocolate is that cocoa itself can function as a prebiotic. Tzounis (2011) gave real-life live humans cocoa every day for 4 weeks and showed that bifidobacteria increased dramatically. These findings were confirmed by Fogliano (2011), who showed (via another robotic gut simulator) that water-insoluble cocoa fractions (e.g., cocoa fiber) alone markedly stimulated the growth of bifidobacteria.
So: 1) chocolate is a good vehicle to deliver exogenous bifidobacteria; and 2) cocoa promotes the growth of endogenous bifidobacteria. win-win.
Why is this relevant? because probiotics by themselves don’t survive the trip! They die off somewhere between the factory and your large intestine. In a study by Prilassnig (2007), 7 people were fed one of 6 different commercially available probiotics for a week. 2 of the products contained bifidobacteria, Omniflora and Infloran. None of the bifido in Omniflora survived in any of the volunteers, and the bifido in Infloran was detectable in only 1 out of 4. Feeling lucky?
Thus, chocolate may be not only viable, but an optimal way to administer probiotics. The bifidobacteria can feed on the cocoa while in transit (from the factory to your cupboard to your bowels), and the cocoa can directly stimulate them along with your native gut flora.
And chocolate with GOS?! according to Davis (2010), chocolates enriched with 10 grams of GOS increased endogenous bifidobacteria a whopping 3-fold.
Formula for the healthiest chocolate on Earth? >70% cocoa, a billion bifidobacteria, and a few grams of GOS… don’t get your hopes up, however, this won’t likely be made any time soon. Despite all of the data showing the remarkable health-promoting properties of GOS, it’s still not widely commercially available. In the meantime, Attune’s use of inulin will have to suffice.
The goal was to see if nightly insulin injections could prevent pre-diabetics from becoming real diabetics. ORIGIN was monstrous: >12000 participants, 40 countries, 6 years, etc. FYI the subjects included in this study, mostly pre-diabetics, are not usually candidates for insulin injections (diet and lifestyle modification seem to work OK for this group). If ORIGIN showed a positive result, then the number of patients to receive this treatment, and therefore the number of prescriptions written for Sanofi’s Insulin Glargine, would increase dramatically = $anofi 🙂
IMHO, Sanofi is hunting for a new bunch of people to whom they can market their same old drug. (Not a good practice.) To stay alive in the fiercely competitive pharmaceutical industry, companies have to either invent new drugs to treat old diseases or invent new diseases that use old drugs. In this case, they are saying that pre-diabetes, or “dysglycemia,” should be a new indication for insulin. Pre-diabetes is not a new disease, but insulin was never warranted (Rx = diet and lifestyle modification).
I have no financial disclosures to report (but I’m open to offers). Of moral disclosures, on the other hand, I’ve got but one. Insulin injections are fraught with side effects and should be reserved for people who need them. I don’t believe these people need them.
divide and conquer
After 6 long years of insulin injections (or standard care in the control group), the researchers tested for diabetes. Lo and behold, diabetes was present in 35% of controls and 30% of the insulin-treated group; i.e., insulin-treated patients had a 20% lower chance of developing diabetes (odds ratio [OR] of 0.80, p = 0.05). Apparently, insulin prevents diabetes.
Or not.
Exhibit A. There’s a caveat to these diabetes rates. The subjects were tested for diabetes at the end of the study. Anyone whodidn’thave it was re-tested a few weeks later; only those who didn’t have it were re-tested a few weeks later (during which time they received no treatment). The researchers claim they were trying to assess the “durability of diabetes prevention.” Here’s the rub: 25% of the patients on insulin tested positive for diabetes at the end of the study. A few weeks later (during which time they weren’t being treated) some of the people who initially tested negative for diabetes (insulin obviously must have been protecting them), now tested positive, increasing the total to 30%. This must have happened because they were no longer protected by insulin! Err, no. Diabetes in the control group, the group who was deprived of insulin from the start, went from 31% to 35% during the same exact time period. It’s not “durability of diabetes prevention,” it’s experimental bias: by only RE-testing people who were initially negative, the total could only stay the same (if there were no false negatives) or go up (if there werefalse negatives). The fact that it went up in both groups could simply mean that the re-test either: 1) detected diabetes in some people who falsely tested negative the first time around; and/or 2) generated some new false positives. To correct for this, they should have also re-tested anyone who tested positive for diabetes. *The importance of this difference is described below.
Exhibit B. Disclaimer: statistics are the bane of my existence.
The rate of disease was rather high in both groups (>>10%); if you calculated the “relative risk (RR)” instead of “odds ratio (OR),” you’d get 0.857. An RR of 0.857 is not as pretty as an OR of 0.80 (lower is better). Their “OR of 0.80” was barely statistically significant (p = 0.05); I’d be willing to bet that an “RR of 0.857” would not have been so lucky… so why did they choose to publish the OR? OK, no suspense necessary: I think if this measurement turned out non-significant, then the entire study would’ve been a waste of time and a LOT of money. And they would have no shot at an entirely new market for their same old drug. *This is precisely why proper diabetes diagnoses and statistical analyses were so critical in this study. To be clear: this is going to come down to a numbers game, and the numbers don’t support a new indication for insulin in pre-diabetics. But fuzzy math and biased testing makes this appear as though it is a debatable conclusion.
Moving on.
HbA1c, a marker of long-term glucose control was 6.4% at baseline in both groups. Insulin therapy lowered this to 6.3% (not exactly something to write home about) while it drifted to 6.5% in controls. This insignificant effect of insulin on HbA1c didn’t come cheap, however. The insulin treated group experienced a huge number of severe hypoglycemic episodes:
Not surprisingly, the severity of hypoglycemia was totally downplayed in Sanofi’s press release despite it being the most robust and statistically significant finding in the entire study.
People in the insulin-treated group got a little heavier (by about 5 pounds), and surprisingly, the control group lost a little weight (about a pound). I say “surprisingly” because this population is expected to be weight stable or gaining weight.
Lastly, fortunately, there was no difference in mortality. This is not unexpected because the intervention was mild and the patients were relatively healthy (i.e., not people who need nightly insulin injections). When a more intensive insulin intervention was tested on frank diabetics, the study was halted because too many people died. Enter: The ACCORD study.
Intensive insulin therapy lowered HbA1c waay more in ACCORD than mild insulin therapy did in ORIGIN:
but it also lowered lifespan:
In conclusion: YES, high blood glucose is the culprit, and YES, it needs to be lowered. But NO, insulin injections are not the answer. If you have lactose intolerance, you stop eating lactose. These people have glucose intolerance; they need to stopeatingglucose.
is healthy for the same reason as 
, 
, 
, and a million others: no junk food.
, it’s gluten-free and anti-hyperglycemic (i.e., the opposite of white flour).
dose-dependently reduced the glycemic index.
can be used just like butter (
: ketogenic
and bread in the refrigerator, and 
in their desk drawers; “dirty” because there were a lot of uncontrolled variables; for example: fiber, protein, and fat content of the test meals differed wildly:
dose-dependently blunted the blood glucose response to the test meal. Conclusion: almonds = anti-hyperglycemic. But almonds are complex lil’ things; they’re made of protein, fat, fiber, and a lot of nutrients; so what’s responsible for all the anti-hyperglycemic effect? this post is not simply an academic pursuit; indeed, 
and 
are commercially available, 
, these noobs pale in comparison.
(higher protein & lower fat than 
)
. Combining probiotics (e.g., bifidobacteria, acidophilus, etc.) with 
is gluten-free and contains a half billion L. helveticus R0052 and B. longum R0175 per serving. A half-billion is low by conventional standards*, but such standards might be irrelevant if the delivery vehicle (i.e., chocolate) is superior.
, although they are the only pill that doesn’t (I suspect alien technology).
, 
; the list goes on and on. Apparently, I was late to the game… (expect to see these in your local grocer soon.)
every day for 4 weeks and showed that bifidobacteria increased dramatically. These findings were confirmed by 
use of inulin will have to suffice.
.