Table 6.

Protein intake and outcome glucose-insulin metabolism (2 clinical trials)

Author, year (ref no.) Country Study design (study name if applicable)	No. of participants	Exposure (incl age)	Outcome (incl age)	Effect/association	Study quality comments
Hoppe, 2009, (27)Denmark CT	831 invited, 89 agreed to participate.	2×2 factorial design: 540 ml milk-based drinks, either: 1) whey with low mineral content (Ca and P) (Whey-low), 2) whey with high mineral content (Whey-high), 3) casein with low mineral content (Case-low), 4) casein with high mineral content (Case-high) RQ: To examine the effects of the two major n milk protein fractions, whey and casein, and milk minerals (Ca and P) in a 2×2 factorial design on IGFs and glucose-insulin metabolism	Serum IGF-1, IGFBP, fasting insulin, C-peptide, index of insulin resistance, glucose	No interactions between milk mineral groups (high, low) and milk protein groups (whey, casein). The milk protein intervention groups were combined. Average daily protein intake was increased by 17% by the whey drink, from 58 g/day (2.23 g/kg per day, 12.98 PE%) to 68 g/day (2.56 g/kg per day, 15.42 PE%) (p<0.001), and by 51% by the casein drink, from 68 g per day (2.30 g/kg per day, 14.30 PE%) to 103 g per day (3.44 g/kg per day, 23.40 PE%) (p<0.001). In the whey group, fasting insulin increased by 21% (p=0.006), with no change in IGF-1 (p=0.27). In the casein group, serum IGF-1 increased by 15% (p<0.0001), whereas there was no change in fasting insulin (p=0.36). No independent effects of a high milk mineral intake on IGF-1 and insulin. Increase in serum urea nitrogen (SUN), and the molar ratio of IGF-1/IGFBP-3 was significantly higher in the combined casein-group than in the combined whey group. Conversely, whey increased fasting insulin more than did casein.	B 36% drop-out. No details given. Remaining diet unclear. Energy intake at baseline reported and credible level. Measurement errors not considered Can′t find that they say very much about compliance. They state in Discussion that ‘However, the diet was appropriately recorded, and this has been controlled for in the analysis.’ Intake of energy, protein and milk,+SUN (biomarker for protein intake) was controlled for in the analysis (but how?). Nothing more is said. 2e) They use SUN as a biomarker for protein intake, but don′t say anything about the rest of the dietary intake.
Sandström, 2008 (31) Sweden CT Partly RCT	80 (Healthy GA:36–42 weeks BWT: 2500–5000 g)	Standard vs. two formulas varying in G Lycomacropeptide (GMP) and α-lactalbumin i.e. 3 formulas w. bovine whey fractions rich in α-lactalbumin w. varying GMP vs. breast feeding (as control) All formulas: 1,96 g prot/ 100 kcal.	–Growth –General health –Plasma leptin, insulin, urea nitrogen, amino acids	Formula intake was similar in different groups. Weight gain in the alpha-lactalbumin-enriched formula groups was similar to that of the breastfed infants. The standard formula group gained significantly more weight than did the breastfed infants.All formula-fed infants had significantly higher plasma concentrations of most essential amino acids at 4 and 6 months than did the breastfed infants, and serum urea nitrogen was also higher in the formula-fed infants. Insulin and leptin concentrations did not differ between groups.	B No power calculation reported, compliance unclear, energy intake unclear, results not analysed blind, unclear about between-measurments errors