Food Matrices: Protein & Fat Ameliorate Glucose Spikes After Standardized Glucose Load | Plus: Timing Matters if You Want to Turn Regular into Resistant Starch

This is what it's all about. Real food does not come in form of "macros". It comes in form of complex food matrices that determine its effect on one's health - including one's glycemic health.

You will probably remember that I have touched on a specific aspect of the effects of and interactions between different macronutrients in what scientists often refer to as "food matrices" on the glycemic response to standardized glucose loads in previous articles like the famous "True or False?" article that dealt with the question: "Will Adding Fat to A Carby Meal Lower the Insulin Response?" (read it).

You don't remember this or any of the other articles? Well, in that case, I probably have to tell you again that the mere fact that the postprandial glucose are lower does not mean that a certain food or combination of certain macronutrients would increase your insulin sensitivity (adding fat to a high carbohydrate meal certainly doesn't do that, believe me).
While this is possible for certain supplements like berberine and other AMPK activators, it is mandatory that we differentiate the following three cases:

1. Reduced postprandial blood glucose levels in response to an increase in insulin sensitivity as it is triggered by exercise or AMPK activators,
2. Reduced postprandial blood glucose levels in response to increased insulin levels as they occur with the co-ingestion with whey protein and
3. Reduced postprandial blood glucose levels in response to increased insulin levels and a decreased rate of absorption of glucose as it is the case if you add fat to carbohydrates.

That was too fast? Too complicated? Or both? Never mind. The discussion of two recent articles from the Lund University and the Yong Loo Lin School of Medicine (see blue box) will hopefully help you understand the difference - I promise ;-)

Let's take a look at study design, results and implications

In their study, Wathik Alsalim and his colleagues from the Lund University in Sweden and the Consiglio Nazionale delle Ricerche in Italy investigated the integrative impact of macronutrients on postprandial glycemia, β-cell function, glucagon and incretin hormones in man. The subjects were male and female Caucasian subjects, aged 30-70 years and BMI 20-35 kg/m², without diabetes (normal fasting glucose and normal HbA1c) or with T2D without any pharmacological glucose-lowering therapy and HbA1c <60 mmol/mol (<7.8%).

"Exclusion criteria were liver disease, diabetic nephropathy, proliferative diabetic retinopathy, pregnancy or breast feeding, treatment with oral antidiabetic or insulin, previous myocardial infarction, coronary heart disease or angina pectoris, previous surgery on the gastrointestinal tract, larger surgical intervention the last 12 weeks or treatment with oral steroids or thiazide diuretics" (Alsalim. 2015).

Participants were studied at the Lund University's Clinical Research Center on four occasions in a randomized cross-over design, separated by at least four and maximally eight weeks. After overnight-fast (no food after 10pm), subjects were provided with antecubital vein catheter. After two baseline samples at 5, and 2 mins, they ingested in randomized order either one of the macronutrients alone

• glucose - 330kcal = 83g; Skåne University Hospital Pharmacy, Lund, Sweden,
• protein mixture - 110kcal = 30g; ISO WHEY protein consisting of milk and egg protein
• fat emulsion - 110kcal = 24ml; 50% long-chain triglycerides and 50% water;

The response to the individual macros was then compared to the ingestion of a 550kcal meal containing 330kcal (60%) from glucose, 110kcal (20%) from protein and 110kcal (20%) fat - a proportion of which the scientists say that it "was selected to represent a common meal with 60% carbohydrate, 20% protein and 20% fat" (Alsalim. 2015).

Figure 1: To allow for maximal control, the "meal" (macro composition on the right) was a shake (Alsalim. 2015).

Water was ingested at the same time of each load to standardize the ingested volume to 400ml; all ingestions were consumed within 5 min. Blood samples were taken throughout a 300min period after each challenge test.
Now, guess what? Yes, yes, and no ... the glucose meal was not the most insulinogenic one. Accordingly, we have to be careful not to mistake the scientists' conclusion that "[a]dding protein and fat macronutrients to glucose in a mixed meal diminishes glucose" (Alsalim. 2015) as evidence that fat and protein will reduce the potential obesogenic effect of carbohydrates. After all, the data in Figure 2 leaves no doubt that we are not talking about effect (a) from our list at the beginning of the article, i.e. a reduction in glucose excursions in response to "an increase in insulin sensitivity as it is triggered by exercise" (see introduction).

Figure 2: Glucose and insulin response as well as corresponding insulinogenic index and insulin clearance of the individual macros and the mixed meal - all data expressed relative to the values of 110kcal of glucose (Alsalim. 2015).

Rather than that, the reduced glucose AUC was a result of (c), i.e. an increase in insulin levels due to increased insulin production, as well as a decreased clearance of insulin and a decreased rate of absorption of glucose (-16%, -52%, -59% and -70% reduced glucose influx through the portal vein at 30, 45, 60 and 90 min after the meal) - and with the increased insulin levels you will also run an increased "risk" of fat storage (whether you gain weight will still depend on your overall energy intake not your insulin levels, though).

Figure 3: Insulin is not always the bad guy. A 2004 study by Hallschmid, et al. shows that it's centrally mediated effects in the brain can actually help men (but not women) lose weight effortlessly, when they administer it cyclically (only chronically elevated insulin levels are truly problematic) intranasally.

At this point, it may be necessary to point out that the increase in insulin in response to the co-ingestion of protein and fat does not imply that guzzling glucose on its own would be healthier than eating a mixed meal. In conjunction with the increases in the important (fat burning) satiety hormone GLP1, which were observed only in the diabetic subjects, though, these changes are yet far more beneficial for the average type II diabetic than they are for the lean athlete, who doesn't need the extra-insulin to maintain normal blood glucose levels and may even consider them an obstacle on his / her way to single-digit body fat levels.
References:

• Alsalim et al. "Mixed meal diminishes glucose excursion compared to glucose by several adaptive mechanisms in man." Diabetes, Obesity and Metabolism (2015): Accepted article.
• Collier G, O'Dea K. The effect of coingestion of fat on the glucose, insulin, and gastric inhibitory polypeptide responses to carbohydrate and protein. Am J Clin Nutr. 1983 Jun;37(6):941-4.
• Hallschmid, Manfred, et al. "Intranasal insulin reduces body fat in men but not in women." Diabetes 53.11 (2004): 3024-3029.
• Kaur B, Ranawana V, Teh AL, Henry CJ. "The Glycemic Potential of White and Red Rice Affected by Oil Type and Time of Addition." J Food Sci. (2015).
• Robertson, R. Paul, et al. "Glucose toxicity in β-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection." Diabetes 52.3 (2003): 581-587.
• Steen, Eric, et al. "Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease-is this type 3 diabetes?." Journal of Alzheimer's disease 7.1 (2005): 63-80.