Insulin Response of Long Term Type 2 Diabetics Improved with Amino Acids

Amino Acid Ingestion Strongly Enhances Insulin Secretion in Patients With Long-Term Type 2 Diabetes

ABSTRACT:

OBJECTIVE—Insulin secretion in response to carbohydrate intake is blunted in type 2 diabetic patients. However, it is not clear whether the insulin response to other stimuli, such as amino acids, is also diminished. Recently, we defined an optimal insulinoptropic mixture containing free leucine, phenylalanine, and a protein hydrolysate that substantially enhances the insulin response in healthy young subjects when coingested with carbohydrate. In this study, we aimed to investigate the insulinotropic capacity of this mixture in long-term type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Ten type 2 diabetic patients (aged 59.1 ± 2.0 years, BMI 26.5 ± 0.7 kg/m²) and 10 healthy control subjects (58.8 ± 2.1 years, 26.5 ± 0.7 kg/m²) visited our lab twice, during which insulin responses were determined following ingestion of carbohydrate only (CHO) or carbohydrate with the free amino acid/protein mixture (CHO+PRO). All subjects received 0.7 g · kg⁻¹ · h⁻¹ carbohydrate with or without 0.35 g · kg⁻¹ · h⁻¹ of the amino acid/protein mixture.

RESULTS—Insulin responses were dramatically increased in the CHO+PRO trial in both the type 2 diabetic and control groups (189 and 114%, respectively) compared with the CHO trial (P < 0.01). Plasma glucose, glucagon, growth hormone, cortisol, IGF-I, and IGF binding protein 3 responses were not different between trials within the 2-h time frame.

CONCLUSIONS—The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal.

My Summary:  10 adult males with Type 2 diabetes >8 yrs and ready to switch to insulin therapy were compared to 10 normal adult males.  Each group was fed either a standardized carbohydrate only meal (CHO) or the carb along with a protein mixture containing free amino acids.  The insulin responses were increased in both groups given the protein/AA mixture.

So ... what was the composition of this magical protein mixture?   The dose was 0.35 g · kg⁻¹ · h⁻¹ of an amino acid/protein hydrolysate mixture.  The mixture consisted of a wheat protein hydrolysate (50%, 0.17 g · kg⁻¹ · h⁻¹), free leucine (25%, 0.09 g · kg⁻¹ · h⁻¹), and free phenylalanine (25%, 0.09 g · kg⁻¹ · h⁻¹).  This was administered  in 3 mL/kg boluses  at 0, 30, 60, and 90 min.

For "A", the open symbols are the CHO only, the black symbols are the CHO/PRO group.  The circles are the T2's the squares are the normal controls.  

Remember, these are T2's who are about to become insulin dependent.  We see that the T2's had less than half the insulin response to CHO that the normal controls have (clear bars in "B").  We also see that using the protein along with the CHO, the T2's had an insulin response similar or even a little better than that mounted by the normal "unstimulated" controls as evidenced in both "A" and "B" above.

The results don't impact glucose levels a whole lot, however.

The shape of the normal control curve does show a lower max BG (something that might show up better but for the scale to accomodate the BG levels of the T2's).  The glucose clearance does not seem to be improved by the insulin response in the T2's.  Things that make you go hmmmmmmmmm.  Seems the IR of the T2's is still "in force".  For this treatment to reduce hyperglycemia, it seems the underlying resistance to insulin needs to be addressed.  

However this does demonstrate that long term T2's may not have "worn out" their pancreases with their hyperinsulinemia after all, but rather than chronically elevated BG's may reduce the pancreas' response to acute BG rises.  

Still, this points to me that even long-ongoing T2 diabetes could theoretically be reversed.  The subjects in this study were only mildly overweight.  What is the underlying cause of the IR in these Type 2's?

More Biochemistry Animations

Boyer - Interactive Biochemistry

A screen shot of the Menu:

Protein in optimal health: heart disease and type 2 diabetes

Protein in optimal health: heart disease and type 2 diabetes

Aside:  The lead author (I believe), is affiliated with the Australian CSIRO research group that is well regarded in the LC community -- except when, in the end, CSIRO's highly successful weight loss plan does not advocate for high fat  VLC after all.  I would also point out that the authors and the summit from which this article originated were highly subsidized by "Big Egg", "Big Dairy", "Big Beef" and "Big Pork".  I point this out not because I question the findings that seem pretty sound, but to point out that discounting research based on the sponsor just because one doesn't like the outcome is common practice amongst "debunkers".

So, that said, on to this article.  I won't repeat the whole thing.  It is a review, and although requires slow reading to digest, it's not overly clouded with technical lingo.  Some highlights of interest in no particular order:

• Regardless of dietary makeup, LDL seems to be ultimately related to one's weight status  both in terms of degree of excess weight and whether one is maintaining, losing or gaining weight.
• Protein's  "power" in weight loss may and glycemic control may well be its insulin stimulating action (particularly, leucine and glycine) -- this goes counter to LC theory, but makes sense to me.  If the post prandrial insulin response is increased by protein with reduced carb intake, BG's will not rise as high, and will fall more rapidly.  Protein seems to help insulin sensitivity.  If this occurs, chronic (basal) insulin levels should go down b/c the insulin manufactured in response to food is more effective, hence the pancreas is not pumping out more and more insulin in response to chronically elevated BG's.  Eggs, BTW, are particularly high in leucine.  Carbs and fats are still the prefered energy substrates, so insulin in-and-of-itself does NOT drive net fat storage, it merely directs energy traffic to the priority of available glucose or more towards fats when carbs are restricted.
• Infused amino acids raised BG levels and insulin, while ingested whole proteins seem to have the opposite effect.  I've seen many studies demonstrating similar effects for infused vs. ingested fats, and liquid glucose vs. whole carbs.  As the review points out, this underscores the involvement of our digestive systems and livers in the whole picture.

High protein is not defined here.  But there is some info on diets in which carbs are replaced with protein (as opposed to fats as is highly recommended in the LC world these days).  For me, this seems to be where it's at for weight loss.