Protein Hydrolysate/Leucine Co-Ingestion Reduces the Prevalence of Hyperglycemia in Type 2 Diabetic Patients

Eleven long-standing type 2 diabetic patients (aged 58 ± 1 years, BMI 28 ± 1 kg/m², HbA_1c 7.4 ± 0.3%) and 11 matched healthy control subjects (aged 59 ± 2 years, BMI 28 ± 1 kg/m², HbA_1c 5.5 ± 0.1%) participated in this study. All subjects were screened for type 2 diabetes according to American Diabetes Association guidelines (11). Type 2 diabetic patients had been diagnosed for 8 ± 1 years and were using metformin with (n = 8) or without (n = 3) a sulfonylurea derivative. Blood glucose–lowering medication was continued throughout the experimental trials. Subjects maintained normal dietary and physical activity patterns but refrained from exhaustive physical labor and exercise training for 3 days before each trial.

Each subject participated in a crossover study with two trials during which blood glucose concentrations were recorded for 40 h under free-living conditions using a continuous glucose monitoring system (CGMS) (GlucoDayS; A. Menarini Diagnostics, Firenze, Italy) (12). Subjects received three beverages containing a protein hydrolysate/leucine mixture or a placebo beverage. Prepacked beverages were consumed directly after each main meal. All meals, snacks, and beverages were provided in preweighed packages and were ingested at predetermined time points to ensure fully standardized dietary modulation during both trials. The standardized diet provided 121 kJ · kg⁻¹ · day⁻¹ (64% carbohydrate, 25% fat, and 11% protein). Beverages contained 4 ml/kg water (PLA) or water containing 0.3 g/kg casein protein hydrolysate and 0.1 g/kg leucine (PRO). Both trials were performed in a randomized and double-blind manner.

The acquired data were downloaded from the CGMS onto a personal computer with GlucoDay software (version 3.0.5). Values reported by the CGMS were converted into glucose values using self-monitoring blood glucose (SMBG) values. To quantify and compare the prevalence of hyperglycemia between groups and trials, the amount of time during which glucose concentrations were >10 mmol/l was calculated. A multiway ANOVA or a Student’s t test for paired or unpaired observations were applied where applicable. All data are expressed as means ± SE and significance was set at P = 0.05.

Total 24-h glucose concentrations were higher in the diabetic group versus the control subjects group (10.2 ± 0.4 vs. 6.2 ± 0.6 mmol/l, respectively, P < 0.01). In the diabetic patients, 24-h glucose concentrations in the PRO trial were significantly lower compared with the PLA trial (9.6 ± 0.6 vs. 10.8 ± 0.5 mmol/l, respectively, P < 0.05) (Fig. 1). PRO ingestion resulted in a 11 ± 3% decline in the overall glucose response in the diabetic patients (P < 0.05). In the control subjects, differences between trials did not reach statistical significance (6.2 ± 0.4 vs. 6.3 ± 0.2 mmol/l).

Despite a healthy standardized diet and the continued use of oral blood glucose–lowering medication, hyperglycemia (>10 mmol/l) was prevalent during 55 ± 7% of the 24-h period in the diabetic patients in the PLA trial. In the control group, hyperglycemia was hardly present (2 ± 1% or 25′ ± 15′ min). In the diabetic patients, the prevalence of hyperglycemia was significantly lower in the PRO versus PLA trial (39 ± 6 vs. 55 ± 7%, respectively, P < 0.05). The latter represented a 26 ± 9% reduction in the prevalence of hyperglycemia from 1318′ ± 0140′ in the PLA trial to 0942′ ± 0154′ in the PRO trial (P < 0.05).

The prevalence of elevated postprandial glucose excursions in type 2 diabetic patients imposes a direct and independent risk for the development of cardiovascular complications (6,7,13). In accordance, both the Diabetes Control and Complications Trial (1) and the U.K. Prospective Diabetes Study (2–4) report that improving glycemic control effectively reduces the risk of developing micro- and macrovascular complications and cardiovascular disease.

The present study shows that long-standing type 2 diabetic patients who receive standard primary medical care experience hyperglycemia throughout the greater part of the day. Co-ingestion of a protein hydrolysate/leucine mixture following each main meal substantially reduces the prevalence of hyperglycemia in these patients. This is accompanied by a significant reduction in average 24-h blood glucose concentration. Although the use of continuous glucose monitoring devices in an applied setting does not allow for concomitant insulin measurements, numerous other studies (8–10,14,15) have repeatedly shown that protein hydrolysate/amino acid co-ingestion stimulates insulin secretion, resulting in improved glucose disposal and reduced postprandial glucose concentrations.

These data extend on previous findings and provide evidence that protein hydrolysate/leucine co-ingestion represents an effective dietary strategy to improve daily blood glucose homeostasis under free-living conditions in long-standing type 2 diabetic patients.

This study was supported by a grant from DSM Food Specialties (Delft, the Netherlands).

We thank A. Menarini Diagnostics BENELUX and Hanneke van Milligen for her technical assistance.

This study was presented at the American Diabetes Association 66th Scientific Sessions in Washington DC, 9–13 June 2006.