Macro Ratios & Glucose Management: Eating Lower GI Carbs and Higher Protein Alone is Less Effective in Blood Sugar Normalization Than You May Have Thought

Macronutrient ratios matters, but food quality does, too. And so do exercise, laziness, sleep, .... the list is endless, so can we be surprised that modulating GI and protein is not helping much?

We all "know" that going low(er) carb is good for your blood glucose management, right? Nice! So, we probably don't need studies like the Marleen A. van Baak's conducted only recently, right? I mean, carbs are bad! So why would we even be interested to hear how much the subjects of the Diogenes Study lost on one of four different diets with varying protein content and glycemic index? Or who would want to know what the subjects' 24-h glucose profiles on one out of four diets differing in carbohydrate content by 10 energy % and glycemic index by 20 units during three days. No one would like to know that, right!?

In view of the fact that you're still there, I suppose that I was wrong and you are interested in the effects of different marconutrient ratios and types of carbohydrates (low vs. high glycemic index) on weight loss and glucose management. Let's take a closer look at the design of the Diogenes Trial (learn more), then.

Use alternatives to sugar sweetened beverages if you want to improve your blood glucose!

Unsatiating Truth About Sweeteners?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Sweeter Than Your Tongue Allows!

Stevia, Much More Than Sweet?

Artif. Sweetened Foods Good, Not Bad for Fat Loss.

The Diogenes Study was a field study, in the course of which subjects were randomized into 5 different diets: lower protein (LP)/lower GI(LGI), higher protein (HP)/LGI, LP/higher GI (HGI),HP/HGI and a control diet according to national recommendations for a healthy diets.

• The intended difference in protein content of the LP and HP diets was 10%–12% of energy intake.
• The intended difference in glycemic index between the LGI and HGI diets was 15. 

All diets were reduced in fat (<30 energy%) to make room for significant differences in the CHO to PRO ratios. All subjects had to keep food diaries and monitor their glucose levels continuously.

Table 1: Examplary diet composition in the Diogenes Trial (van Baak. 2014)

As some of you will probably remember (I've written about the Diogenes Study and its results in the Facebook News, previously), the total amount of weight the subjects lost from the start of the Diogenes Study was 8.8 ± 8.4 kg. The subsequent weight regain since the start of the randomized diet intervention was 1.6 ± 7.3 kg, with no significant differences between the diet groups (in spite of a marginal advantage for those who kept eating a high(er) protein diet).

Lifestyle changes are more powerful than supplements: So don't forget that it's imperative to realize the lifestyle changes described in the first installment of the "Improve Your Glucose Sensitivity"-series. Otherwise the best you can hope to achieve with supplements (and drugs) is to slow the progression from insulin resistance to full-blown diabetes.

The analysis of the three-day dietary records showed the expected differences in carbohydrate content and glycemic index between the diet groups, but the differences were smaller than intended (a bummer in view of the fact that they were not large to begin with). Much in contrast to what our initially phrased prejudice would say, there were no significant differences in mean 24-h, daytime or nighttime glucose concentrations between the diet groups.

Table 2: Self-reported dietary macronutrient composition in the field study (a) and macronutrient
composition of the diet in the lab study (b) (van Baak. 2014)

Moreover, the absence of at least a deviation in standard deviations (SD) signifies that the lack of statistical significance is not due to extreme outliers who may not have adhered to their dietary prescription (macronutrient make-up / reported / see Table 2).

"Post hoctesting did not reveal differences between the LP/HGI diet and any of the other diets for the glucose parameters studied. Adjustment for BMI, HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) index, minutes of exercise performed by the subjects, total weight loss or weight regain did  not change this outcome (data not shown)." (Van Baak. 2014)

Still, in a relatively uncontrolled scenario like the one in the Diogenes Study it's always possible that someone cheated twice, i.e. he deviated from the diet and reported to have stuck to it to the literal "T". Against that background, the results of van Baak's three-day follow up in a very controlled scenario is all-the-more interesting.

Figure 1: Parameters of glucose homeostasis means (left) and standard deviations (right)
on the different diets in the lab study (van Baak. 2014)

It's a study in which we see the same non-significant effects of the macronutrient ratio on ability of the study participants to keep their glucose in check. With goodwill you could say that protein seems to buffer the glucose excursions, but with p-values of p >> 0.05, this effect is everything but statistically significant.

To find an effect that is statistical significant we do thus have to take a look at the continuous overlapping net glycemic action over 1 h periods (CONGA1) values over 24 h on the different diets in the lab study, where the high protein + low GI group finally shows the statistically significant advantage we've been waiting for all along (see Figure 2). Still, as the scientists point out, overall their data does not support the hypothesis that "glucose concentrations would be highest on the reference diet (LP/HGI) compared to all other diets and especially compared to the HP/LGI diet." (van Baak. 2014). As the author points out, the study did yet provide support for the hypothesis regarding glucose variability was found, since both 24-h and daytime variability of glucose concentrations were lower on the HP/LGI diet than on the LP/HGI diet.

Learn how to improve and maintain your insulin sensitivity in a previous article and the corresponding series about ways to improve your insulin sensitivity, naturally.

Bottom line: I am not sure what to make of this study, but I guess that the fact that the macronutrient manipulation had a relatively minor impact on the glucose levels of the overweight subjects confirms that "hitting your macros" is by far not all you've got to do if you want to get away from the road to diabesity | What's your take on this study - comment on Facebook!

That being said, there is no doubt that a high(er) protein, low(er) GI will make it much easier to return to the realms of the few non-pre-diabetics. In that, the effects will probably be even more profound if you increase the protein intake by more than 10% over the reference value of 0.8g/kg.

Doubling the protein intake, for example, would necessarily require a reduction in carbohydrate and fat intake of 3.2kcal/body weight. For a person who weighs 100kg that would be 320kcal and 80g of carbs or 40g of fat - with the former usually being the better idea for anyone who's still significantly overweight and not already eating less than 180g of carbs per day.

Reference:

• van Baak, Marleen. "24-Hour Glucose Profiles on Diets Varying in Protein Content and Glycemic Index." Nutrients 6 (2014):3050-3061

What Diogenes Has To Say About Weight Loss: Study Investigates "Optimal" Macronutrient Compositions for Weight Loss & Maintenance

Image 1: Diogenes, a critical thinker
of the ancient world and eponym of
a European research project; a man
right after my liking, who would not tire
questioning common "wisdom".

I must forewarn you: Being part of the pan-European Diogenes Project, the study I am going to tell you about in the following is not something you can read or understand in a few minutes. Aimed at elucidating the intricate relationship(s) between Diet Obesity and Genes [the acronym DIOGENES was aptly chosen, for there is little doubt that Diogenes, if he lived today, would certainly feel inclined to debunk many of the nutritional idiocies of our age, cf. image 1], the project that is financially supported by the European Union, is literally epic. Its newest spin-off, an investigation into the "blood profiles of proteins and steroids during weight maintenance with manipulation of dietary protein level and glycaemic index" (Wang. 2011), is no exception to this rule. I will thus try my best to summarize the study design along with the most important findings, as comprehensively as possible.

From the participants of previous weight loss trials, Ping Wang from the Department of Human Biology at the NUTRIM School for Nutrition in the Netherlands, and 15 colleagues from other European institutions that cooperate under the roof of the Diogenes Consortium selected 96 overweight/obese, but otherwise healthy female subjects (age 29-49y), who had experienced a pronounced, but not extreme weight loss and/or regain in the course of previous trials. According to the weight loss, respectively regain the subjects had experienced after an initial 8-week low calorie (800-1000kcal/day) weight loss phase, the group of participants was further divided into "continued weight losers" (WL; n= 48) and "weight regainers" (WR; n= 48). All subjects were instructed to eat ad-libitum, while trying to maintain their weight at a constant level for the subsequent 6 month weight maintenance phase. Each of these groups was then further subdivided into four groups, the participants of which were instructed to consume one out of four diets that were characterized by high, respectively low protein intake and high or low GI carbohydrate content (cf. figure 1)

Figure 1: Schematic illustration of the 2x4 groups à 12 subjects whose endocrine responses during weight loss/regain after an 8-week low-calorie dietary intervention were analyzed in the study.

Despite the names of the groups, a closer look at the actual macronutrient composition consumed by the participants of each of the groups (cf. figure 2) does reveal a that the actual differences in protein intake (as measured by dietary questionnaires) in the low vs. high protein groups were modest, at best - a fundamental drawback of the study, which is also acknowledged by the authors, themselves.

Figure 2: Relative macronutrient composition of the diets of 'continous weight losers' (WL) and 'weight regainers' (WG) on low (LP) or high (HP) diets with reference to a standard 2.000kcal/day diet (calculated based data from on Wang. 2011)

As can be seen in figure 2, the difference in protein intake for the weight loss groups (LP(WL) and HP(WL)) amounts to about 23g, while the low protein weight regain (LP(WR)) group consumed only 11g less protein than the high protein weight loss group. Unquestionably, the conclusions about the effects of high vs. low protein content in the subjects' diets on the outcome of the dietary intervention would certainly have been more reliable, if the scientists had not been satisfied by these "modest differences", as they themselves describe them, but had specified an absolute or relative amount of protein the subjects in the high protein groups had to consume every day.

That being said, there were nevertheless certain differences in dietary success/failure and serum parameters that correlated well with the macronutrient compositions of the respective diets:

Figure 3: Overview of hormones and
peptides measured in Wang. 2011

• previous studies from the Diogenes Project had already established that "both a modestly higher protein content and a modest reduction in GI in the context of an ad libitum diet improve weight-loss maintenance" (Larssen. 2010); these results were confirmed in the study at hand
• in terms of the measured serum markers all groups experienced what the scientists label "a ‘return-back’ effect of the body to keep the homeostasis" in the course of the ad-libitum fed 6-month weight maintenance phase of the study, but...
• interestingly, "return-back regulation of IL-6 failed in the WR group", indicating that despite an increase in fat mass, the associated inflammatory marker remained relatively low
• on the other hand, "Leptin (LEP) and pancreatic polypeptide showed [the return-back effect] significantly more profoundly in the WR group", which would have been expected in view of the increase in fat mass these subjects experienced
• the observation that subjects who kept losing weight had "less increase in diastolic blood pressure, cholesterol, TAG [triglycerides] and glucose" corroborates the undesirable side effects of weight regain (WR)
• a slight increase in C-reactive protein (CRP; a marker generally associated with increased risk of heart diesease) in the subjects who regained weight on a high protein diet, warrants further investigation [in view of the fact that the high protein WR group consumed about the same amount of protein as its weight loss counterpart, I do yet highly doubt that the protein intake is to blame for this]

Other results worth mentioning were that while high protein intake and a low GI diet were associated with more weight loss in the weight loss group, in the weight regain group group, however, only the protein intake had a exhibited an ameliorative effects on the amount weight the subjects regained. Overall, "[t]here was no analyte [cf. figure 3] for which the fold change did significantly reflect the dietary GI level", and "for fat mass, no significant dietary effect in both groups could be detected", at all.

In figure 4 I've also compiled the data on body composition changes in the course of the weight maintenance phase [indicated by parameter 'm' as in 'maintenance'] relative to the BMI, body fat and waist circumference after the initial 8-week low-calorie weight loss interference.

Figure 4: Changes in body composition during the 6-month weight "maintenance"-phase relative to BMI, body fat and waist circumference after the initial 8-week weight loss phase; abbreviations: LP=low protein, HP=high protein; LGI=low glycemic index, HGI=high glycemic index; WL=subjects who continuously lost weight, WR=subjects who regained weight (data calculated on the basis of Wang. 2011)

In view of the quest for an optimal [I am honestly asking myself whether this even exists] macronutrient composition, mentioned in the title of this post, the most intriguiging finding of this study may thus be summarized as follows:

A "high" (remember 18%, see above) protein low-GI diet is optimal for weight loss and at least as effective to ward of weight regain as the other diets evaluated in this study

In that, the most reasonable explanations for the beneficial effects on weight loss and regain are reductions in  glucagon and insulin, the promotion of an anabolic state and lipolysis via the upregulation of testosterone and generally lower plasma levels of plasminogen activator inhibitor 1, a well known modulator of adipose tissue development on a high protein, low glycemic index diet.