TABLE 2.
Clinical studies of dairy proteins (whey and casein) in subjects with T2DM1
| Dairy protein tested and reference | Study population and design | Intervention | Findings |
| Casein | |||
| Manders et al., 2005 (57) | 10 male subjects | Subjects were given continuous glucose infusions + repeated boluses of 2 mL/kg BW every 15 min for 165 min of either of the following: | Plasma glucose responses were lower in the carbohydrate + protein (casein + leucine + phenylalanine) group than in the carbohydrate alone group. |
| Age: 62 ± 2 y | 1) 0.7 g carbohydrate ⋅ kg BW−1 ⋅ h−1 | Plasma insulin responses were higher in the carbohydrate + protein group than in the carbohydrate alone group. | |
| BMI: 27 ± 1 kg/m2 | 2) 0.7 g carbohydrate ⋅ kg BW−1 ⋅ h−1 + 0.35 g ⋅ kg−1 ⋅ h−1 of a mixture consisting of 50% casein protein hydrolysate, 25% leucine, and 25% phenylalanine | ||
| Acute challenge study; randomized, double-blind, placebo-controlled, crossover | |||
| Manders et al., 2006 (59) | 10 male subjects | Subjects were given a single bolus of one of the following: | The glucose responses were lower in both the carbohydrate + casein, and the carbohydrate + casein + leucine groups, compared with the carbohydrate control. Plasma insulin responses were greater in the carbohydrate + casein, and carbohydrate + casein + leucine groups, compared with those in the carbohydrate control. |
| Age: 59.7 ± 2.6 y | 1) 0.7 g carbohydrate/kg BW | ||
| BMI: 26.8 ± 0.82 kg/m2 | 2) 0.7 g carbohydrate/kg BW + 0.35 g casein hydrolysate/kg BW | ||
| Acute challenge study; randomized, double-blind, placebo-controlled, crossover | 3) 0.7 g carbohydrate/kg BW + 0.35 g casein hydrolysate/kg BW + 0.1 g leucine/kg BW | ||
| Manders et al., 2006 (58) | 11 male subjects | Subjects ingested 3 meals/d in a single 24 h period containing either of the following: | The 24-h glucose concentrations in the casein + leucine group were significantly lower than with the water placebo group.The prevalence of hyperglycemia was significantly lower in the casein + leucine group than in the placebo group. Insulin was not measured in this study. |
| Age: 58 ± 1 y | 1) flavored water placebo | ||
| BMI: 28 ± 1 kg/m2 | 2) 0.3 g casein protein hydrolysate/kg BW + 0.1 g leucine/kg BW | ||
| Acute challenge study; randomized, double-blind, placebo-controlled, crossover | |||
| Manders et at., 2008 (60) | 10 male subjects | Subjects were given continuous glucose infusions + repeated boluses every 30 min for 6 h of either of the following: | Over 6 h, plasma glucose responses were lower after carbohydrate + casein ingestion than after the carbohydrate control.Plasma insulin concentrations were significantly higher in the carbohydrate + casein group than in the carbohydrate control. |
| Age: 68 ± 2 y | 1) 0.6 g carbohydrate ⋅ kg BW−1 ⋅ h−1 | ||
| BMI: 24.9 ± 0.4 kg/m2 | 2) 0.6 g carbohydrate ⋅ kg BW−1 ⋅ h−1 + 0.3 g ⋅ kg BW−1 ⋅ h−1 casein protein hydrolysate | ||
| Acute challenge study; randomized, double-blind, placebo-controlled crossover | |||
| Manders et al., 2009 (53) | 13 male subjects | Subjects ingested 3 meals/d in a single 24 h period containing either of the following: | The 24-h glucose concentrations were similar between groups. Casein coingestion with each main meal did not reduce the prevalence of hyperglycemia. Insulin response was not reported in this study. |
| Age: 62 ± 2 y | 1) flavored water placebo | ||
| BMI: 28 ± 1 kg/m2 | 2) 0.4 g casein/kg BW | ||
| Acute challenge study; randomized, double-blind, placebo-controlled crossover | |||
| Brader et al., 2010 (49) | 11 subjects (7 male, 4 female) | Subjects were assigned to consume one of the following: | The 45-g carbohydrate meal and the 45-g casein + 45-g carbohydrate meal caused a higher 8-h postprandial glucose response than the control or 45-g casein meals. The 45-g casein meal and the 45-g casein + 45-g carbohydrate meals increased 8 h insulin responses compared with the control meal. The largest insulin response was seen with the 45-g carbohydrate + 45-g casein meal. |
| Age: 62.4 ± 3.9 y | 1) 80 g fat (control) | ||
| BMI: 28.9 ± 3.6 kg/m2 | 2) 80 g fat + 45 g carbohydrate | ||
| Acute challenge study; randomized, controlled, crossover | 3) 80 g fat + 45 g casein | ||
| 4) 80 g fat + 45 g carbohydrate + 45 g casein | |||
| Geerts et al., 2011 (50) | 36 subjects (27 male, 9 female) | Subjects were assigned to consume one of the following: | Both casein hydrolysate treatments (with leucine and without) caused lower 4-h postprandial plasma glucose concentrations compared with the placebo and unhydrolyzed casein meals. All casein meals caused higher 4-h postprandial insulin secretion than the placebo meal. The casein hydrolysate + leucine group showed the greatest insulin response. |
| Age: 61.5 ± 5.1 y | 1) 35 g carbohydrate + 5 g fat placebo | ||
| BMI: 28.1 ± 3.6 kg/m2 | 2) placebo + 15 g unhydrolyzed casein | ||
| Acute challenge study; randomized, double-blind, placebo-controlled, partial crossover | 3) placebo + 15 g casein hydrolysate | ||
| 4) placebo + 15 g casein hydrolysate + leucine | |||
| Jonker et al., 2011 (51) | 13 subjects (8 male, 5 female) | Subjects were assigned to consume one of the following: | The 12-g casein meal decreased the 4-h postprandial glucose response compared with the control, whereas the 6-g dose did not. The 12-g casein dose increased peak insulin concentrations and the 4-h postprandial insulin response compared with the control, but the 6-g dose did not. |
| Age: 58 ± 1 y | 1) 50 g carbohydrate + 0 g casein (control) | ||
| BMI: 27.9 ± 0.9 kg/m2 | 2) 50 g carbohydrate + 6 g casein | ||
| Acute challenge study; randomized, placebo-controlled, double-blind | 3) 50 g carbohydrate + 12 g casein | ||
| Manders et al., 2014 (61) | 60 male subjects | Subjects were assigned to consume one of the following: | The plasma glucose responses were lower in both the carbohydrate + intact casein group and the carbohydrate + casein hydrolysate group than in the carbohydrate control. There was no difference in 4-h postprandial glucose response between casein groups. The insulin response was greater in the carbohydrate + intact casein group and the carbohydrate + casein hydrolysate group than in the carbohydrate control. There was no difference in 4-h postprandial insulin response between casein groups. |
| Age: 60 ± 1 y | 1) 0.7 g carbohydrate/kg BW | ||
| BMI: 30.2 ± 0.4 kg/m2 | 2) 0.7 g carbohydrate/kg BW + 0.3 g intact casein/kg BW | ||
| Acute challenge study; randomized, placebo-controlled, double-blind | 3) 0.7 g carbohydrate/kg BW + 0.3 g casein hydrolysate/kg BW | ||
| Whey and casein | |||
| Tessari et al., 2007 (24) | 12 subjects (7 male, 5 female) | Subjects consumed a 6-kcal/kg BW, 50% protein mixed meal containing 0.7 g protein/kg BW of one of the following: | 3-h postprandial glucose AUCs were similar after whey protein and casein ingestion.Insulin response was greater with whey protein than with casein. GLP-1 response tended to be lower with casein than with whey protein. GIP concentrations were similar after whey and casein protein ingestion. |
| 1) mixture of free amino acids resembling the amino acid composition of micellar casein (amino acid control) | |||
| Age: 56.6 ± 2.3 y | 2) sweet whey protein isolate | ||
| BMI: 24.3 ± 0.8 kg/m2 | 3) micellar casein | ||
| Acute challenge study; randomized, double-blind, controlled, crossover | |||
| Mortensen et al., 2009 (54) and Mortensen et al., 2010 (56) | 12 subjects (6 male, 6 female) | Subjects consumed a meal containing 100 g butter, 45 g carbohydrates, and one of the following: | The 8-h postprandial glucose AUC was lower after the whey meal than after the other protein meals. There were no significant differences reported in insulin, glucagon, GLP-1, and GIP responses between meals. |
| Age: 64.6 ± 3.3 y | 1)1) 45 g casein protein | ||
| BMI: 28.9 ± 3.7 kg/m2 | 2) 45 g whey protein | ||
| Acute challenge study; randomized, crossover | 3) 45 g cod protein | ||
| 4) 45 g gluten protein | |||
| Whey | |||
| Frid et al., 2005 (25) | 14 subjects (8 male, 6 female)Age: 27–69 yBMI: 26.2 ± 3.1 kg/m2Acute challenge study; randomized, crossover | Subjects consumed a breakfast meal consisting of 102 g white wheat bread and, 4 h later, a lunch meal containing 52.2 g mashed potatoes and 50 g meatballs, with one of the following at both meals: | There was no difference between groups in 3-h glucose AUC after breakfast. However, after lunch, the 3 h blood glucose AUC for the whey group was significantly reduced compared with the ham + lactose group. The insulin AUCs were higher after both breakfast and lunch when whey was included in the meal than with ham + lactose. Two-hour postprandial breakfast GIP AUC and 3-h postprandial lunch GIP AUCs were higher after whey ingestion than with ham + lactose. There were no differences reported in GLP-1 concentrations. |
| 1) 27.6 g whey protein | |||
| 2) 96 g lean ham + 5 g lactose | |||
| Ma et al., 2009 (52) | 8 subjects (7 male, 1 female) | Subjects consumed a preload meal of 350 mL beef soup and, 30 min later, a potato meal, with one of the following: | The 5-h postprandial blood glucose response was similar between the whey protein preload and whey protein with meal. Both whey trials resulted in lower blood glucose responses than the no whey group. The 5-h postprandial insulin AUC was similar between the whey protein preload and whey protein with meal. Both whey protein trials resulted in higher insulin responses than the no whey protein group.GIP concentrations were higher in the whey protein preload and whey protein meal than in the no whey protein group. GLP-1 was greatest during the 90 min after the whey protein preload. |
| Age: 58 ± 3 y | 1) 55 g whey protein with preload meal | ||
| BMI: 28.6 ± 1.3 kg/m2 Acute challenge study; randomized, controlled, crossover | 2) 55 g whey protein with potato meal | ||
| 3) no whey protein at either meal (control) | |||
| Mortensen et al., 2012 (55) | 12 subjects (5 male, 7 female) | Subjects consumed a meal containing 100 g butter, 45 g carbohydrates, and one of the following: | Over 3 h, the glucose response was significantly lower after the whey + caseinoglycomacropeptide meal than with the whey protein hydrolysate meal. Over 8 h, 45 g whey protein isolate and 45 g whey protein hydrolysate led to higher insulin responses compared with 45 g whey + α-lactalbumin or 45 g whey + caseinoglycomacropeptide. |
| Age: 65.8 ± 5.3 y | 1) 45 g whey protein isolate | ||
| BMI: 28.2 ± 5.3 kg/m2 | 2) 45 g whey protein hydrolysate | ||
| Acute challenge study; randomized, single-blind, crossover | 3) 45 g whey protein with α-lactalbumin | ||
| 4) 45 g whey protein with caseinoglycomacropeptide | |||
| Jakubowicz et al. 2014 (62) | 15 subjects (9 male, 6 female) | Subjects were assigned to consume either of the following, followed by a 353 kcal high glycemic index breakfast: | Over 3 h, glucose concentrations were reduced after whey protein preload compared with the placebo. Insulin response was higher with whey protein preload than with the placebo. Both total GLP-1 and intact GLP-1 concentrations were significantly higher with the whey protein preload than with the placebo. |
| Age: 64.1 ± 1.4 y | 1) 50 g whey protein | ||
| BMI: 26.7 ± 1.2 kg/m2 | 2) water-placebo | ||
| Acute challenge study; randomized, open label, placebo-controlled, crossover |
1
Sixteen publications produced from 15 different clinical studies, 2005–2014. BW, body weight; GLP-1, glucagon-like peptide 1; GIP, glucose-dependent insulinotropic peptide; T2DM, type 2 diabetes mellitus.