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?