SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 11 NUMBER 1 • MARCH 2014
21
period in 12 subjects with diet-controlled type 2 diabetes.
33
While
macroalbuminuria was an exclusion criteria, as no subject was
receiving pharmaceutical treatment for diabetes it is likely that
subjects did not have any degree of renal impairment. All food and
meals were provided to participants in this trial to ensure a protein
intake of 30% in the intervention group. No significant differences
were noted between diets for urinary creatinine clearance or urinary
microalbuminuria.
In the first of the two weight-loss trials, Sargrad
et al
. reported an
increase in protein intake from 15% of total energy to 27% in the
high-protein group (
n
= 12).
34
No difference was reported between
groups for either serum creatinine or blood urea nitrogen. No pre-
treatment description of participants’ renal status was provided.
In the second, the Diabetes Excess Weight Loss Trial (
n
= 419) in
patients with type 2 diabetes, a high-protein diet was compared
with a low-fat diet. This study included some participants (
n
= 77)
with a urinary albumin–creatinine ratio (ACR) between 2.5 and
30 mg/mmol. Protein intake in the high-protein group was
significantly higher than in the high-carbohydrate group at six
months but did not reach the goal of 30% of total energy (it
increased from 19 to 22% of total energy).
6
At this level of protein
intake there was no difference between groups in serum creatinine
or urinary ACR after two years.
In conclusion, very little literature is available to enable an
assessment of the impact of a high protein diet on renal function in
patients with type 2 diabetes.
Discussion
While there may be some short-term benefit of protein restriction
in patients with type 2 diabetes and nephropathy, it appears that
this dietary approach is difficult to maintain past six months, and
that any benefits are not sustained. The most benefit is gained
in those with the greater degree of renal deterioration, namely
macroalbuminuria. Substituting plant protein and/or chicken for
red meat may be an easier and equally effective long-term option
for those with renal impairment, and this approach warrants further
long-term investigation.
While there is some evidence for the treatment of existing
nephropathy with protein restriction, there is no evidence that an
increase in protein intake accelerates diabetic nephropathy in those
with microalbuminuria, or causes it in those with normal renal
function. The limited literature in this area may be confounded by
the effects of weight loss on blood pressure, glycaemic control and
lipid profile, which in turn protect against nephropathy. There is also
difficulty in comparing studies of protein restriction – where protein
intake is usually reported in g/kg/day – and high-protein weight-loss
studies – where protein intake is reported as a percentage of total
energy, and is therefore very dependent on total caloric intake.
Evidence from the UK Prospective Diabetes Study (UKPDS)
35
in
type 2 diabetes and the Diabetes Control and Complications Trial
(DCCT)
36
in type 1 diabetes, supports the importance of achieving
tight glycaemic and blood pressure control in reducing the incidence
of nephropathy. Higher dietary protein intake has been related
to improvements in glycaemic control in weight-stable patients
with type 2 diabetes over five weeks in a cross-over trial.
37
Similar
benefits of increased protein intake have been observed on blood
pressure.
34
Thus, while these improvements may translate into
benefits in reduced microalbuminuria, longer term studies have not
been in universal agreement on these benefits.
6
In contrast, there are studies linking the greater net acid load
of diets with higher animal protein intake, to an increased risk of
hypertension, which in turn would adversely affect nephropathy.
29,38
In the Nurses Health Study, women in the highest decile of net
acid load (based on animal protein intake) had an increased risk
of hypertension [HR 1.14 (CI 1.05–1.24)], compared with those
in the lowest decile.
29
In contrast, the Rotterdam study found no
association between acid load and blood pressure.
39
Furthermore
no high-protein weight-loss study in type 2 diabetes has reported
an increase in blood pressure in the high-protein group, so whether
a dose–response relationship exists and the real impact of this on
changes in protein intake remains to be determined.
Data from longitudinal observational studies in the general
population raise some concerns about increased mortality
associated with higher protein diets. The EPIC study reported a
non-significant increase in total mortality for the highest intake of
protein (20% TE) (1.02, 95% CI 0.98–1.07)
40
However, this was
exaggerated by combining the high protein score with the low
carbohydrate score, leading to an increased mortality ratio of 1.22
(95% CI 1.09–1.36). A similar observation is made in the Women’s
Lifestyle and Health study.
41
The risk of mortality for every decile less
carbohydrate was 1.06 for all causes (1.00–1.12) while the risk was
1.10 for every decile higher protein (1.01–1.2) for cardiovascular
mortality. While the study controlled for saturated fat intakes, the
reduction of fruit, vegetables and fibre with a possible increase in
red meat consumption may explain these findings.
41
While epidemiological studies can only identify questions and
examine associations, this does suggest that other hallmarks of
healthy diets should not be ignored, and that increases in protein
should be accompanied by a high-fibre diet, high in fruits and
vegetables, low in saturated fat and with an emphasis on chicken,
fish and plant proteins.
Conclusion
There is remarkably little evidence to inform policy for optimal dietary
protein intake in patients with type 2 diabetes, with or without
evidence of diabetic nephropathy. There appears to be a short-term
benefit of protein restriction in patients with macroalbuminuria,
but the benefit is difficult to sustain past six months. Substituting
chicken and vegetable protein sources for red meat may be an
effective treatment that is easier to sustain long term, but more
evidence is required. However, there is no evidence that increasing
dietary protein in those with normal renal function, or even
microalbuminuria, causes any deterioration in renal function. A well-
designed, randomised, controlled trial is required to answer this
question specifically. However, based on current evidence, adopting
a high-protein weight-loss diet under medical supervision is an
acceptable option for these individuals. Because of the potential link
between a high animal protein diet and increases in blood pressure
and nephropathy, regular monitoring is important. Finally, retaining
a focus on other healthy diet markers, such as a high fibre and high
plant intake, will ensure any potential risks are minimised.
Declaration of conflicting interest
The authors declare that there are no conflicts of interest.
Funding
This research received no specific grant from any funding agency in
the public, commercial, or not-for-profit sectors.
