The Insulin / Glucagon Ratio and Why Diabetics and People W/ Severe Insulin Resistance Must be Careful With Protein

Now, back in the day these observations were mainly used to support the concept of a "protein sparing action" of glucose. Today, the effect on gluconeogenesis, i.e. the production of glucose from proteins / amino acids in the liver, has moved to the center of attention of a number of scientists. Calbet and MacLean, for example, investigated how the plasma glucagon and insulin responses of humans would depend on the rate of appearance of amino acids after ingestion of very fast vs. fast protein sources.

Figure 2: Glucose and glucagon levels in the blood of healthy volunteers after ingesting either 25g glucose or protein solutions containing whey protein hydrolysate (WPH), pea peptide hydrolysate (PPH) or milk protein (MS | Calbet. 2002).

Their results (see Figure 2) indicate the obvious: Even in healthy individuals and even upon co-administering protein sparing and 25 g of anti-gluconeogenic glucose, the fastest protein sources (whey protein, WPI; pea peptide hydrolysate; PPH) produce the highest increase in glucagon, gluconeogenesis and thus serum glucose levels in the first 20 minutes after the ingestion of the 25 g of glucose plus ~30g of the different proteins.
What may not be a major problem for healthy individuals, though, can be a deal-breaker for diabetics, in whom studies into the inter-organ flux of substrates after a protein-rich meal (slow digesting beef 3g/kg body weight) show that the normally non-significant effect on glycemia (<5% in healthy subjects) was exuberant in the diabetic subjects in whom you will see a greater rise in blood glucose, and a three-to-fourfold increment in splanchnic glucose output at 30-90 min that was triggered by a doubling of arterial glucagon, which was not compensated for by an concomitant increase in insulin as it occurred in the healthy test subjects (Wahren. 1976).

Figure 3: Rel. changes in blood glucose after ingestion of 3g/kg lean meat in healthy and diabetic subjects (Wahren. 1976).

Whether an increase in protein intake will have beneficial or ill effects on your ability to control your glucose levels will thus clearly depend on the degree of hepatic insulin resistance / pancreatic dysfunction you expose.

• If you are severely diabetic and/or insulin resistance, i.e. you either don't produce enough or no insulin in response to the ingestion of protein or your body does not react to the insulin, as it would be the case in type I diabetes and progressive type II diabetes, your glycemia may be impaired by high protein meals.
• If you are only slightly insulin resistant, you will probably benefit from the insulinogenic effects of protein and the ability to replace carbohydrates in your meals with protein. You may nevertheless want to test your individual glucose response to fast-digesting proteins like whey or amino acid supplements, which may still result in an uncontrolled gluconeogenic response.
• If you are healthy and insulin sensitive, you won't have to worry about the gluconeogenic effects of high protein intakes - regardless of whether we are talking about fast or slow protein sources, because the former will spike insulin enough to blunt any pro-gluconeogenic effects of the concomitant increase in glucagon to keep the rates of gluconeogenesis and thus your glucose levels in check.