Which protein is best for blood glucose and insulin?

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Hi All,

The below appears to provide much protein food for thought.

See Table 3 data especially for this pdf-available paper.

Am J Clin Nutr. 2004 Nov;80(5):1246-53.

Glycemia and insulinemia in healthy subjects after lactose-equivalent

meals of

milk and other food proteins: the role of plasma amino acids and

incretins.

Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM.

BACKGROUND: Milk products deviate from other carbohydrate-

containing foods in

that they produce high insulin responses, despite their low GI. The

insulinotropic mechanism of milk has not been elucidated. OBJECTIVE:

The

objective was to evaluate the effect of common dietary sources of

animal or

vegetable proteins on concentrations of postprandial blood glucose,

insulin,

amino acids, and incretin hormones [glucose-dependent insulinotropic

polypeptide

(GIP) and glucagon-like peptide 1] in healthy subjects. DESIGN:

Twelve healthy

volunteers were served test meals consisting of reconstituted milk,

cheese,

whey, cod, and wheat gluten with equivalent amounts of lactose. An

equicarbohydrate load of white-wheat bread was used as a reference

meal.

RESULTS: A correlation was found between postprandial insulin

responses and

early increments in plasma amino acids; the strongest correlations

were seen for

leucine, valine, lysine, and isoleucine. A correlation was also

obtained between

responses of insulin and GIP concentrations. Reconstituted milk

powder and whey

had substantially lower postprandial glucose areas under the curve

(AUCs) than

did the bread reference (-62% and -57%, respectively). Whey meal was

accompanied

by higher AUCs for insulin (90%) and GIP (54%). CONCLUSIONS: It can

be concluded

that food proteins differ in their capacity to stimulate insulin

release,

possibly by differently affecting the early release of incretin

hormones and

insulinotropic amino acids. Milk proteins have insulinotropic

properties; the

whey fraction contains the predominating insulin secretagogue.

PMID: 15531672 [PubMed - indexed for MEDLINE]

...

Subjects and study design

Twelve healthy nonsmoking volunteers (6 men and 6 women aged 20–28 y)

with normal body

mass indexes (21.9±1.26 kg/m2; ±SD) and not receiving drug treatment

participated in the

study. All subjects had normal fasting blood glucose concentrations

(4.1±0.03 mmol/L; ±SEM)

and no history of lactose malabsorption. The meals were provided as

breakfasts, on 7

different occasions, in random order with 1 wk between each.

...

TABLE 1 Nutrient composition and serving size of the test meals

and the

white-wheat-bread (WWB) reference meal1

---------------------------------------------

Meal Amount of product Added lactose2 Total carbohydrate Total

protein Serving quantity

of liquid

----------------------------------------------------------------------

----------

WWB 58.4 — 25.0 2.8 2503

GL 4.0 25.0 25.0 2.8 5504

GH 25.2 25.0 25.0 18.2 5504

Cod 74.7 25.0 25.0 18.2 2505

Milk 51.3 — 25.0 18.2 5506

Whey 28.0 19.4 25.0 18.2 5506

Cheese 52.6 25.0 25.0 18.2 2505

-------------------------------------

1 GL, gluten low; GH, gluten high.

2 Amount of lactose added to reach 25 g carbohydrate in the meals.

3 Tap water was served in addition to the bread.

4 Gluten and lactose were mixed in tap water.

5 Lactose dissolved in tap water was served along with the protein

source.

6 Powder was dissolved in tap water.

RESULTS

Amino acid content in the test meals

Concentrations of the amino acids in the test meals are presented in

Table 2. The

concentrations of branched-chain amino acids in the milk-based

products and the cod meal were in

the same range. However, the content of leucine was somewhat lower in

cod than in milk,

whey, and cheese. The cod meal contained almost the same amount of

valine as milk and

cheese, whereas the whey showed a considerably higher amount. Lysine

was slightly more

represented in cod than in the dairy products. GH contained somewhat

lower amounts of lysine

and the branched-chain amino acids compared with the other test meals.

TABLE 2 Content of amino acids in the different meals1

------------------------------------

---------------------Meal (mg/serving)

----------------------------------------------------------------------

----------

Amino acid-----WWB GL GH Cod Milk Whey Cheese

----------------------------------------------------------------------

----------

Asp 198 92 580 1831 1395 1848 1249

Thr 102 71 446 849 800 1268 665

Ser 198 142 895 877 1077 1005 1033

Glu 1546 658 4158 2493 3868 3024 3635

Pro 529 245 1550 644 1754 1148 1823

Gly 173 90 570 752 385 395 368

Ala 173 89 559 752 657 1053 368

Val 198 122 774 1097 1170 1725 1195

Ile 166 97 610 774 852 1016 798

Leu 318 191 1207 1364 1775 1764 1652

Tyr 148 95 600 627 816 549 963

Phe 215 148 937 709 867 652 882

Lys 138 48 305 1836 1395 1596 1414

His 106 66 418 397 487 381 522

Arg 176 100 630 1167 641 437 557

------------------------------------

1 WWB, white-wheat-bread reference meal; GL, gluten low; GH, gluten

high.

Postprandial blood glucose and insulin responses

Milk powder and whey had lower postprandial glucose responses (P <

0.05), expressed as

AUC (0-90min), than did the reference (Table 3). No significant

differences in the AUC

for blood glucose were found between the reference and the GL, GH,

cod, and cheese meals.

TABLE 3 Postprandial blood glucose and insulin areas under the

curve (AUCs) and the

insulinogenic index after the test meals and the white-wheat-bread

(WWB) reference meal1

----------------------------------------------------------------------

----

Meal Glucose AUC (0 –90 min) Change2 Insulin AUC (0 –90 min) Change2

Insulinogenic index

(0 –45-min AUC)

----------------------------------------------------

WWB 50.2±7.6a,3 — 8.0±0.7b,c — 0.16±0.03b

GL 42.4±6.8a,b,c –16 6.2±0.7c –23 0.17±0.03b

GH 35.4±5.9a,b,c –30 8.2±0.9b,c +3 0.25±0.06b

Cod 43.9±8.4a,b –13 7.1±1.0b,c –11 0.14±0.01b

Milk 19.3±4.5c –62 9.9±1.2b +24 0.55±0.08a

Whey 21.8±5.6b,c –57 15.2±1.6a +90 0.72±0.2a

Cheese 39.3±10.1a,b,c –22 10.0±0.9b +25 0.27±0.05b

----------------------------------------------------------------

1 n = 12. GL, gluten low; GH, gluten high. Values in the same column

with different

superscript letters are significantly different, P < 0.05 (ANOVA

followed by Tukey's test).

2 Change in postprandial response as a percentage of the WWB

reference meal.

3 ±SEM (all such values).

Significant differences between treatments over the entire time

course (P < 0.0001)

and a significant treatment x time interaction (P < 0.0001) were

found for blood glucose

concentrations. A post hoc analysis showed that the blood glucose

responses at 30 min were

higher after milk and whey than after the cod meal (Figure 1). At the

same time point, GH

and GL had significantly higher glucose responses than did the whey

meal (P < 0.05).

Forty-five minutes after eating commenced, a higher blood glucose

response was observed after

the reference meal than after all test meals, except for cod. At 60

min, all test meals

elicited lower glucose values than did the reference (P < 0.05).

Although the blood glucose responses after the whey meal were

considerably lower than

those after the reference meal (–57%), the serum insulin AUC (Table

3) was significantly

higher (90%) (P < 0.05). The insulin response registered after whey

deviated from all

other test meals by being significantly higher. The milk and cheese

meals showed

significantly higher insulin AUCs than did the GL.

Significant differences between treatments over the entire time

course (P < 0.0001)

and a significant treatment x time interaction were found for insulin

concentrations (P <

0.0001). Compared with the reference, whey resulted in increased

insulin concentrations at

15, 30, 45, and 75 min (Figure 2). Also at 30 min, the insulin

responses after the milk

and the cheese meals were significantly higher than after the

reference (P < 0.05). Serum

insulin concentrations increased 15, 45, 60, and 75 min after whey

ingestion compared

with all other test meals. At 30 min, insulin concentrations were

higher after the whey meal

than after the other test meals, excluding milk.

Postprandial plasma amino acids

After the reference meal, only proline reached 0.02 mmol/L in

postprandial blood.

After the other meal with a low protein concentration (GL), glutamine

and alanine were the

only amino acids that had a plasma concentration >0.02 mmol/L. The

other gluten meal (GH)

elicited higher (>0.04 mmol/L) plasma amino acids concentrations of

proline, glutamine,

and alanine. Proline and glutamine reached peak values at 120 min,

whereas alanine reached

the highest concentration between 75 and 120 min.

After the cheese meal, proline and alanine had the highest plasma

concentrations, with

peaks at 0.12 mmol/L and 0.10 mmol/L, respectively. The milk meal

resulted in the highest

responses for leucine, proline, glutamine, valine, lysine,

isoleucine, and alanine, with

peak concentrations from 0.07 to 0.14 mmol/L.

Of all the test meals, the whey meal resulted in the most

pronounced amino acid

responses in postprandial blood; leucine, alanine, lysine, valine,

threonine, isoleucine, and

proline yielding the highest peaks, which ranged from 0.13 to 0.17

mmol/L.

After the cod meal, plasma concentrations of all amino acids were

<0.06 mmol/L,

except for lysine and alanine, which reached their highest values

after 120 min: 0.12 and 0.10

mmol/L, respectively.

The 45-min AUC for each amino acid after the different test meals

and WWB reference

meal are shown in Table 4. A positive correlation was seen between

all amino acids and the

insulinogenic index (Table 5). The postprandial amino acid responses

in plasma after the

WWB and GL meals were almost negligible. The highest correlation

coefficients were found

for leucine, valine, lysine, and isoleucine.

TABLE 4 Incremental postprandial areas under the curve (AUCs) for

the different amino

acids from 0 to 45 min after the meals1

-----------------------------

----------------------------Meal (mmol · min/L)

----------------------------------------------------------------------

---------

-------------WWB GL GH Cod Milk Whey Cheese

---------------------------

Amino acid AUC ---------------------------------------------------

---------------------------------------------------------------------

-----------

Thr 0.2±0.04b 0.3±0.1b,c 0.5±0.2b,c 0.3±0.1b 1.4±0.2b,c,d

2.9±0.3b,c,d 1.0±0.2b,c,d,e

Ser 0.2±0.1b 0.1±0.1b,c 0.6±0.2b,c 0.3±0.1b 0.9±0.9c,d 1.7±0.2e,f

0.8±0.2c,d,e

Gln 0.5±0.1a 1.0±0.5a 1.6±0.4a 0.9±0.2a 2.0±1.4a,b 2.2±0.4d,e

1.6±0.3a,b,c

Pro 1.3±0.5a 0.6±0.2a,b 1.3±0.3a 0.5±0.2b 2.6±0.5a 2.8±0.4c,d,e

2.4±0.4a

Gly 0.2±0.05b 0.2±0.1b 0.4±0.1c 0.4±0.1b 0.7±0.2d 1.2±0.6g 0.3±0.1c

Ala 0.3±0.1a,b 0.8±0.2a 1.1±0.3a,b 1.1±0.2a 1.9±0.3a,b 3.2±0.5a,b,c

1.9±0.3a,b

Val 0.3±0.1a,b 0.2±0.1b,c 0.5±0.1b,c 0.3±0.1b 2.3±0.3a,b

3.1±0.3a,b,c,d 1.8±0.4a,b,c

Ile 0.4±0.1a,b 0.1±0.02b,c 0.4±0.1c 0.2±0.1b 2.1±0.4a,b,c

3.2±0.3a,b,c 1.8±0.6a,b,c,d

Leu 0.3±0.1a,b 0.2±0.1b,c 0.5±0.1c 0.2±0.1b 2.8±0.3a 3.9±0.3a

1.8±0.4a,b,c

Tyr 0.2±0.1b 0.3±0.1b,c 0.3±0.1c 0.2±0.1b 0.9±0.2c,d 0.7±0.1g

0.5±0.2d,e

Phe 0.1±0.04b 0.1±0.03c 0.3±0.1c 0.1±0.02b 0.5±0.1d 0.4±0.07g

0.6±0.2d,e

Lys 0.1±0.05b 0.2±0.1b,c 0.3±0.1c 0.5±0.1b 2.1±0.4a,b 3.7±0.3a,b

1.9±0.4a,b

His 0.1±0.02b 0.1±0.04b,c 0.3±0.05c 0.2±0.04b 0.5±0.1d 0.4±0.1g

0.4±0.1d,e

Arg 0.5±0.2a,b 0.2±0.05b,c 0.6±0.2b,c 0.4±0.1b 0.8±0.2c,d 1.1±0.2f,g

0.7±0.3d,e

----------------------------------------------------------------------

--

1 All values are ±SEM; n = 12; WWB, white-wheat-bread reference meal;

GL, gluten low; GH,

gluten high. Values in the same column with different superscript

letters are

significantly different, P < 0.05 (ANOVA followed by Tukey's test).

TABLE 5 Spearman's correlation coefficients and P values for the

relations between

plasma amino acids [45-min area under the curve (AUC)] and the

insulinogenic index (45-min

AUC)

-------------------------------------------------

Amino acid r P

----------------------------------------------------------------------

----------

Thr 0.53 0.022

Ser 0.49 0.009

Gln 0.37 0.013

Pro 0.55 0.005

Gly 0.35 0.030

Ala 0.47 0.013

Val 0.63 0.005

Ile 0.58 <0.001

Leu 0.67 0.003

Tyr 0.48 0.003

Phe 0.47 0.007

Lys 0.62 0.005

His 0.32 0.054

Arg 0.38 0.020

GLP-1 and GIP

The postprandial AUCs for GLP-1 were not significantly different

(P < 0.05) between

the test meals (Table 6). No significant treatment effect (P = 0.92)

or treatment x time

interaction (P = 0.67) was seen after GLP-1 over the entire time

period (Figure 3).

However, the AUCs for plasma GIP concentrations were significantly

higher after the whey meal

than after the other test meals and the reference meal (Table 6).

An examination of GIP over the entire time period showed that both

the treatment

effect and the treatment x time interaction were significant (P <

0.0001 and P = 0.0068,

respectively). A post hoc analysis showed that the GIP concentration

after whey was

significantly higher than that after milk and the reference meal 15

min after ingestion (P < 0.05;

Figure 4). At 30 min, a higher GIP concentration was found after whey

than after cod.

Between 45 and 60 min, whey induced a greater GIP response than did

both cod and milk. At 60

min, the milk and cod meals resulted in lower GIP concentrations than

did the reference

bread (P < 0.05). An evaluation of the data for all meals, including

the reference meal,

showed a positive correlation between the GIP and insulin responses

between 0 and 30 min

(Table 7).

DISCUSSION

Although the postprandial blood glucose response after the test

meal with

reconstituted skim milk powder was low, the insulin response after

milk was not significantly

distinguishable from that after the WWB reference. Thus, the present

results confirm those from

a previous study in which the ingestion of pasteurized milk resulted

in a discrepancy

between blood glucose (GI = 30) and the insulin response (II = 90),

which was not present

after a carbohydrate equivalent load of pure lactose (GI = 68; II =

50) (9). In that study,

it was hypothesized that some milk component in addition to lactose

appears to stimulate

insulin secretion. As judged from similar and high IIs for

reconstituted skim milk (<0.1%

fat, present study) and pasteurized 3%-fat milk (9, 10), neither the

fat content per se

nor the drying process appears to be involved in the insulinotropic

mechanism. Instead, we

supposed an involvement of milk proteins. About 80% of milk proteins

are casein and 20%

are whey.

When

rennet (used in cheese making) is added to milk, casein proteins

aggregate and form a

gel but whey proteins remain soluble. Also, when the pH is decreased,

casein proteins clot;

hence, the acidity in the stomach makes casein, but not whey, to

aggregate into a gel.

It was previously observed that the ingestion of milk and other

food proteins may

stimulate insulin secretion (11, 12, 35). In the current study, the

insulin response to the

whey meal was even more pronounced than that to milk, which indicated

that the

insulinotropic component may be connected to the soluble milk

proteins. Assuming that the protein

fraction of milk contains an insulin secretagogue, the stimulating

effect might be mediated

through bioactive peptides or by specific amino acids released during

digestion. Several

amino acids are potent stimulators of insulin release, either when

taken as a protein

orally or when infused intravenously (21), and certain amino acids

(eg, the branched-chain

amino acids) are more insulinogenic than are others. van Loon et al

(36) showed that the

insulin response in healthy subjects was positively correlated with

plasma leucine,

phenylalanine, and tyrosine when ingested orally in the form of

drinks in combination with

glucose. Furth

ermore,

it was concluded that protein hydrolysates stimulate insulin

secretion to a higher

extent than do intact protein because of a more rapid increase in

postprandial plasma amino

acid concentrations. In addition, Calbet and MacLean (37) described a

close relation

between the insulin response and the increase in plasma amino acid

response, especially for

leucine, isoleucine, valine, phenylalanine, and arginine. These

findings indicate that the

postprandial pattern of plasma amino acids may be an important entity

for the

insulinogenic properties of food proteins.

Of the 7 amino acids that reached the highest increments after the

whey meal in the

current study, the branched-chain amino acids (leucine, valine, and

isoleucine), lysine,

and threonine are all known to stimulate insulin secretion (20, 36,

38). Alanine might also

have insulinotropic effects under select experimental conditions (39).

Whereas whey, milk, and to some extent cheese ingestion resulted

in obvious amino acid

responses, the remaining meals (GH, GL, cod, and WWB) resulted in

only small increases in

plasma amino acids. Generally, the amino acid responses to the cod

meal occurred 60 min

after ingestion. In contrast, peak amino acid responses to milk,

whey, and cheese occurred

more rapidly—within 30–45 min after ingestion—which indicated that

milk proteins are

highly digestible and result in a rapid release of amino acids into

the circulation.

Instead of being related to amino acids per se, the insulinotropic

effect of milk

proteins might be related to bioactive peptides either present in the

milk or formed during

digestion in the small intestine. A possible pathway in the case of

peptides may include

the activation of the incretin system (24). Previous studies showed a

protein-stimulated

insulin response in type 2 diabetic patients (40) and healthy

subjects (41) that did not

parallel the rise in amino acids in the circulation, which suggests

the involvement of the

incretin hormones in protein-stimulated insulin release.

Conversely, Schmid et al (22) concluded that gut factors are only

of minor importance

and that amino acids are the major insulin secretagogue in the

absence of carbohydrates.

Whereas the GLP-1 responses to all of the test meals were similar in

the current study,

whey induced a particularly elevated GIP response. Thus, the higher

GIP response after

whey may have been one contributing factor to the observed elevated

postprandial insulin

response. The degree to which the GIP response explains the

insulinotropic effect of whey

proteins can, however, not be elucidated from the present data.

Surprisingly, the GIP

response to the milk meal was not elevated compared with the response

to the reference meal.

Similarly to whey, milk also showed an insulinogenic effect, although

it was of a lower

magnitude. This finding indicates that the stimulation of the

incretin system may not

solely explain the insulinotropic effects of whey.

In contrast with milk and whey, the postprandial blood glucose

response after the meal

consisting of cheese and lactose was not significantly different from

that obtained after

the WWB meal. However, serum insulin concentrations after the cheese

meal were not

significantly different from those after milk, although they were

lower than those after whey.

It is likely that cheese contains not only casein but also the

remnants of whey proteins,

and either this small amount of whey in the cheese curd is capable of

enhancing insulin

concentrations or the casein fraction itself may contain an insulin

secretagogue. However,

it is known that casein is more slowly digested than is whey (42,

43), and the different

digestion rates of the proteins may effect the insulin response.

Wheat gluten in high and low amounts (the GH and GL meals,

respectively) and cod

affected glycemia and insulin response similarly to the reference

meal, which suggests that

both wheat gluten and cod have a poor capacity to stimulate insulin

secretion. The lack of

effect of wheat protein on the insulin response agrees with the

consistency reported in

GIs and IIs for a range of wheat products (6).

A synergistic effect of carbohydrates and proteins in stimulating

insulin has been

reported in diabetic subjects (44), whereas this effect was not seen

in healthy persons

(41). Although an additive effect of protein and carbohydrates (45)

after the cod meal would

be possible, the rise in plasma amino acids after the cod meal was

modest compared with

that after the milk and whey meals and presumably was too low to

evoke an amino

acid–induced insulin response.

Although whey and cod proteins are similar with respect to the

content and

distribution of amino acids, the postprandial plasma pattern of amino

acids differed substantially

after the test meals containing these proteins, most probably because

of the different

digestion and absorption rates of these proteins. It is especially

interesting that several

of the known insulinotropic amino acids (leucine, valine, isoleucine,

lysine, and

threonine) were among those amino acids that were observed to

increase after the whey meal.

It can be concluded that food proteins differ in their capacity to

stimulate insulin

release, possibly by affecting the early postprandial concentrations

of insulinotropic

amino acids and incretin hormones differently. It cannot be excluded

that an elevated plasma

amino acid response is merely an indicator of the rapid digestion and

absorption of whey

proteins.

The results of the current study show that milk proteins have

insulinotropic

properties, with the whey fraction being a more efficient insulin

secretagogue than casein. It

remains to be shown whether the insulinotropic effect of whey and

milk depends on an optimal

and rapid postprandial release of certain amino acids to the blood,

the release of a

bioactive peptide, or an activation of the incretin system,

particularly by enhancing GIP

secretion. Also, the potential long-term effects of a noncarbohydrate–

mediated insulin

stimulus on metabolic variables should be evaluated in healthy

persons and in persons with a

diminished capacity for insulin secretion.

Cheers, Al Pater, PhD;

email: old542000@...