ABSTRACT
BACKGROUND: We tested whether ingestion of whey protein can induce greater post-prandial amino acid (AA) levels in the plasma and a higher beta-cell response than casein ingestion in type 2 diabetes mellitus patients. METHODS: The study was designed as a double-blind, randomized, and controlled cross-over clinical trial. Twelve post-absorptive type 2 diabetic subjects who were withdrawn from their usual hypoglycemic therapy were studied. A medium calorie (approximately 6 kcal/kg BW), high protein (approximately 50% of total kcal) mixed meal, containing whey protein, casein, or a free amino acid (FREE AA) mixture matching the casein AA composition, was randomly administered on three different occasions. RESULTS: Following ingestion of whey protein, plasma concentrations of total, branched chain, and essential AA were 25-50% greater than after ingestion of casein (p < 0.0001), and were similar to those observed after the FREE AA meal. With whey protein, C-peptide, insulin, and pro-insulin concentrations were greater by 12-40% (p < 0.02 or less) than with casein, and similar to those with FREE AA. Glucagon-like polypeptide 1 (GLP-1) response tended to be lower with casein than with whey protein. Glucose-dependent insulinotropic polypeptide (GIP) response was greater with either whey protein or casein than with FREE AA. Post-prandial glucose concentrations were similar after whey protein and casein ingestion, but lower after the FREE AA meal. CONCLUSIONS: In type 2 diabetes, the ingestion of a fast-absorbable protein results in a greater post-prandial aminoacidemia and a higher beta-cell secretion than the ingestion of a 'slow' protein. Whether these changes can be maintained chronically in combination with hypoglycemic therapy, possibly also resulting in better glycemic control, remains to be established.
Subject(s)
Amino Acids/blood , Caseins/pharmacology , Caseins/pharmacokinetics , Diabetes Mellitus, Type 2/physiopathology , Insulin-Secreting Cells/physiology , Milk Proteins/pharmacology , Milk Proteins/pharmacokinetics , Body Mass Index , Cross-Over Studies , Diabetes Mellitus, Type 2/metabolism , Digestion , Double-Blind Method , Female , Humans , Insulin-Secreting Cells/drug effects , Intestinal Absorption , Kinetics , Male , Middle Aged , Whey ProteinsABSTRACT
Fibrinogen is an acute-phase reactant and an independent cardiovascular risk factor. Insulin without amino acid replacement acutely suppressed fibrinogen production in nondiabetic and type 1 diabetic individuals. Fibrinogen production and plasma concentration increase in insulin-resistant type 2 diabetes. It is not known whether altered response to insulin contributes to hyperfibrinogenemia in type 2 diabetes. Fibrinogen fractional (FSR) and absolute (ASR) synthesis rates were measured using a leucine isotopic model in type 2 diabetic men (n = 7; age = 51 +/- 3 years; BMI = 26.7 +/- 1 kg/m(2)) compared with matched nondiabetic subjects under basal conditions and following a 4-h euglycemic-, euaminoacidemic-hyperinsulinemic clamp. Basal fibrinogen concentration (+35%, P < 0.05) and ASR (+35%, P < 0.05) were greater in the diabetic subjects. Following clamp, fibrinogen FSR and ASR were unchanged in the control subjects. In contrast, fibrinogen FSR and ASR increased by 41 and 43%, respectively (P < 0.05), in the diabetic subjects. Thus, fibrinogen production is acutely increased by insulin when euglycemia and euaminoacidemia are maintained in type 2 diabetic individuals but not in nondiabetic individuals. Enhanced fibrinogen production by insulin is likely to be a key alteration contributing to hyperfibrinogenemia and therefore cardiovascular risk in type 2 diabetes. Unchanged fibrinogen production in nondiabetic individuals suggests a role of plasma amino acids in regulating fibrinogen production in humans.
