1
Jessica McConnellogue
Sarah Neguse
ARG-1
December 7, 2005
The Effect of a Low- Carbohydrate Diet on Insulin & Glucose Levels in Type 2 Diabetic
Patients:
A Position Paper for Type 2 Diabetic Adults
Fall 2005
A paper for Time Magazine
The number of diabetics worldwide grows every year at a high rate. Right now
there are over 151 million people in the world that are diagnosed with diabetes. It is
predicted that by 2010, 221 million people will be diabetic (Cheng, 2005). The World
Health Organization estimated that by 2025, 300 million people will be afflicted with this
disease all over the world (Lai, 2002). Figure 6 depicts the progression of diabetes from
1990-1999. The cost of the disease has also skyrocketed. In the U.S. alone $132 billion
dollars are spent on diabetes; this includes $92 billion going to medical costs and $40
billion going to disability, work loss and premature mortality (Cheng, 2005). Type 2
diabetes alone is closely associated with obesity, which contributes to cardiovascular
morbidity and even mortality rates. The mortality rates were at their highest in 2002
when diabetes was diagnosed as the fifth leading cause of death by disease in the United
States (Hogan, P., Dall T., Nikovlov P., 2003). The treatment of type 2 diabetes will
provide both positive effects on the quality of your life and long-term cost savings.
Therefore, it is important to understand what treatment method is most effective in
alleviating Type 2 diabetes.
To determine whether low-carbohydrate diets have an effect on glucose levels and
insulin sensitivity in diabetic patients we compared many studies’ methods of going
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about determining what affects low carbohydrate diets have. The amount of
carbohydrates in the diet was compared to the specific results that they came to. This
paper is based upon eight studies and two reviews. The administration of these studies
ranged from 2002 to present day. We were curious to see what effects a low carbohydrate
diet had on glucose and insulin levels in type 2 diabetic patients. All of the studies we
have either used glucose or insulin levels to be tested against a low carbohydrate diet.
The most common method in measuring these variables was feeding a patient either a
low or high carbohydrate diet and then comparing their insulin and glucose levels after
the duration of the study. All subjects were adults who have type 2 diabetes. From the
studies, we found that possible answers could be that in diabetic patients, a low
carbohydrate diet resulted in: glucose and insulin levels remain the same, only insulin
sensitivity improves while glucose remains the same or both glucose control and insulin
sensitivity increase.
In type 2 diabetes, the body suffers from a term known as insulin resistance.
(Sievenpiper, Jenkins, Witham, and Vuksan, 2002). The process through which this
occurs happens in the following manner: your pancreas has the ability to make insulin
and attach that insulin to receptors on your liver and muscle cells. Even though the
pancreas still has the ability to produce insulin, it is either not making it in sufficient
amounts or it is not being used to its fullest capabilities on the target tissue (e.g. there is
trouble moving glucose into the cells where it can be used). Therefore, what we see is
the body being functionally resistant to this insulin. After time this results in glucose,
which is the main source of fuel for the body, to build up in the blood since the pancreas
is not making enough insulin to overcome the resistance. Consequently, now the body is
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unable to use glucose (blood sugar) for fuel. This continual cycle of elevated glucose
eventually destroys your receptor cells making it impossible to make insulin anymore
therefore resulting in Type 2 diabetes. The entirety of this process if illustrated in a more
simplistic manner as seen in Figure 7.
Reducing glucose levels and increasing insulin sensitivity may be a way to
alleviate type 2 diabetes; however there is a disagreement on whether low carbohydrate
diets can be used to achieve this. Many studies argue that a low carbohydrate diet has
either no effect or an inconsistent effect (meaning only glucose or insulin but not both) on
reducing glucose or insulin levels. Referring to figure 2, all text highlighted in red
illustrates these studies. For example, Sievenpiper et al. (2002) shows that a decrease of
over 40% in the risk of diabetes was seen when using a high carbohydrate diet versus a
low carbohydrate diet. Additionally, in the Sargard, K., Mozzoli, M., Homko, C., and
Boden, G., (2005) study, a low carbohydrate diet showed no effects on either glucose or
insulin levels. In the Stern, L., Iqbal, N., Seshandri, P., Chicano, K., Daily, D., McGrory,
J., Williams, M., Gracely, E., and Samaha, F., (2004) study insulin levels decreased by
33% but glucose levels had an unusual, slight increase.
On the contrary to all of these results listed above, it is oppositely argued that a
low carbohydrate diet is an effective approach to decrease glucose and insulin levels in
type 2 diabetes. Several studies have agreed with this conclusion which you can see on
Figure 2 as the studies in blue text. Although each study presented varying changes in the
amount of improvement, there was a general theme of an overall decrease in glucose
levels and increase in insulin sensitivity which you can see in Figure 1. For instance, in
the Boden, G., Sargrad, K., Homko, C., Mozzoli, M., and Stein, T., (2005) study a very
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significant decrease in glucose of 16% was observed along with a 75% decrease in
insulin levels. In comparison, the Samaha, F., Iqbal, N., Seshadri, P., Chicano, K., Daily,
D., McGrory, J., Williams, T., Williams, M., Gracely, E. and Stern, L., (2003) study
showed that glucose decreased by nine percent and insulin levels by 6% . It is evident
that there a distinct link between the maintenance of glucose and insulin levels and
carbohydrate intake, however, according to the range of data from both sides of this
argument, it is clear that the issue at hand is still unresolved.
After weighing both sides of this issue, we see that the strongest evidence
supports that a low carbohydrate diet can improve both insulin sensitivity and glucose
levels in type 2 diabetic patients. Its counterargument is that one variable improved while
the other was affected in a negative manner leading to the conclusion that low
carbohydrate diets are not one hundred percent effective in improving both insulin and
glucose. The studies supporting our position all have the strongest measurement
techniques in relation to measuring glucose and insulin improvement. Another reason this
position is the strongest is because the amount of carbohydrate intake for the subjects was
strictly controlled so that there were no discrepancies between how much was being
consumed by the subjects. Lastly, the data showed more consistency versus the opposite
side.
Reason 1: Strongest measurement techniques. Studies using the techniques we
will be describing showed an improvement in both insulin and glucose levels giving us
reason to believe this it the most concrete reason for why low carbohydrate diets work for
type 2 diabetics. The study done by Boden G., Sargrad, K., Homko, C., Mozzoli, M., and
Stein P. (2005) produced data that clearly showed the most improvement in both
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variables out of all the data that we looked at (75% improvement in insulin sensitivity
and 16% improvement in glucose levels). To collect consecutive measurements of
insulin and glucose, euglycemic hyperinsulinemic clamps were performed on days 1, 8
and 22 after an overnight fast. A euglycemic clamp is the most effective way to take
insulin and glucose measurements because it analyses the preventative and therapeutic
effects of diets/food additives on glucose metabolism under conditions of obesity, insulin
resistance and type 2 diabetes. It is a good method because it gathers results in a short
period of time and only small amounts of sample from participant are needed (The
Euglycemic Clamp Technique in Mouse Model for Type 2 Diabetes). Another technique
that was used to gather insulin and glucose levels was collecting blood for 24 hours
(every hour between 8 am and 1 am and at 4 am and 6 am) on days 7 and day 21. This is
more effective than the studies that support our counterargument because although they
also took blood samples, they were not taken consistently for 24 hours like the Boden, et
al. (2005) did. Boden, et al (2005) also used Steele’s equation to calculate rates of
glucose appearance and disappearance. To measure blood glucose they used a glucose
analyzer (YSI, Yellow Springs, Ohio). A glucose analyzer is an instrument that provides
accurate results for whole-blood glucose. The YSI model provides the highest precision
and more accurate results than any other model. (YSI glucose analyzers, blood gas
analysis). Last, they collected data on serum insulin level by radioimmunoassay with a
specific antibody that cross-reacts only minimally (<.2%) with pro-insulin. We found
this technique to be effective because of its specificity and attempt to block interfering
mechanisms (by using things such as a particular antibody) which would alter data.
Studies within this pile showed similar if not identical techniques of measurement for
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both glucose and insulin. In addition to these methods, a commonly used approach, as in
the Samaha, et al. (2003) study, was estimating insulin sensitivity with the use of the
quantitative insulin sensitivity index, a standard and effective method of measurement
because of its strong correlation with the results of glucose clamp studies in diabetic
patients. Figure 3 depicts a more concise description of the variety of methods used
within the pile of studies supporting the effectiveness of low carbohydrate diets in
improving insulin sensitivity and glucose levels.
In the counterargument, the piles of studies collectively have several
measurement techniques, however, individually each study is lacking both in quantity
and quality. Beginning with the Dansinger, M., Gleason, J., Griffith, J., Selker, H., and
Schaefer, E., (2005) study, glucose and insulin measurements were only taken through
blood samples after an overnight fast. This is not as affective as a euglycemic clamp for
taking glucose measures because it solely takes the glucose level measurement whereas
the clamp analyses the glucose and insulin content more precisely. In the Foster, G.,
Wyatt, M., O’Hill, J., McGukin, B., Brill, B., Mohammed, M., Szapary, P., Rader, D.,
Edman, D., and Klein, S., (2003) study, a radioimmunoassay was used to measure plasma
insulin and the quantitative insulin sensitivity check for insulin sensitivity. Although
similar to techniques used in our supportive studies to take insulin measurements, it was
the glucose measurements that were not as strong because only a glucose oxidase auto
analyzer was used to measure glucose whereas several different ways were used in our
posisiton’s studies in order to ensure conclusiveness. The Stern, L. et al., (2004) study
only used blood samples to calculate glucose levels and a radioimmunoassay for insulin.
From the previous description of measurements from the studies in our position you can
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see that although they had some of the same techniques, the counterargument lacks in the
amount of methods they use to measure glucose and insulin.
Reason 2: Pattern in our pile of studies showing a strict control of
carbohydrate intake for all subjects so as not to cause altered results. In these
studies, patients were given a specific low carbohydrate diet rather than choosing their
own food, with the exception of the Samaha et al., (2003) study. However, in this study,
precaution was taken by supplying subjects with pamphlets discussing what to eat and
how to count the amount of carbohydrates consumed. Specifically, in the Boden et al.,
(2005) all consumed food was measured by the Mettler balance to the nearest gram.
Caloric and nutrient value was determined using Version 8.1 of The Food Processor
program.
Conversely, in the pile of studies counter arguing our position, carbohydrate
intake was not strictly monitored. For example, in the Foster et al., (2003) study subjects
were encouraged to read Dr. Atkins New Diet Revolution and follow the diet as
described, however no attempts were made to ensure this was occurring. In addition,
subjects participating in the Stern et al., (2004) study were recorded as not having
followed the mandatory carbohydrate intake of less than 30g per day and rather
consuming more than recommended. In general, the entire pile of studies reflect that
subjects were not given food by the conductors of the study but rather given dietician
advice or cookbooks to work from. Participants were told to “aim” for the recommended
amount (usually 30g/day) however not forced to. Figure 4 depicts a graph comparing
results of the amount of carbohydrates consumed by subjects as compared to their
percentage improvement of glucose levels and insulin sensitivity.
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Reason 3: Pile of studies all collectively supported the same conclusion that
insulin and glucose levels can significantly improve when given a low carbohydrate
diet. All results were definitive leaving no room for question as to the effectiveness of
carbohydrates. Insulin sensitivity showed an improvement ranging from 6% to 75% and
glucose levels showed an approximate average decrease of 10%. Even though it may look
as though insulin sensitivity showed such variable improvement, it is still supported by
the fact that the studies all had an overall improvement whether it was 6% or 75%.
Studies on the other side of our position did not prove to have a collective
agreement on both glucose levels and insulin sensitivity improvement. Results ranged
from one variable improving to the other not improving, as well as neither being affected.
Referring back to Figure 2, after one year, in the Dansinger, M. et al., (2005) study, mean
glucose levels went from 127 mg/dL to 128.4 mg/dL. Insulin changed from 22 micro IU
to 20.8 micro UI. Mean values at the year mark where significantly different from the
mean values collected at the 6 month period. Even though glucose increased by 1.4
mg/dL at one year, a 7.8 mg/dL decrease was seen at six months. Contrary to these
results, Stern, et al., (2004) reported that insulin levels decreased by 33% (153+/-139 to
104+/-49 pmol/L) but glucose levels increased from 5.61+/-.72 to 5.66+/-.56 mmol/L.
Yet in another study, contradictory evidence was seen in the Foster, et al., (2003) study in
which glucose was not changed in either group however insulin sensitivity was
significantly increased at 6 months, returning to baseline at on year. The variability of
these results is seen throughout the studies within this pile of evidence. These results
show varying findings that do not support a conclusive idea of carbohydrates role in
glucose levels especially since this does not make physiological sense. By this we mean
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that it does not make sense for just glucose levels or just insulin levels to decrease
because normally they function as a unit in type 2 diabetic patients. More specifically, in
order for insulin sensitivity to improve it is normally in conjunction with maintaining
proper glucose levels that are low enough for this to happen.
Though our position holds much strength, no study comes without limitations. A
common limitation to all of the studies tended to be a relatively high attrition rate
resulting in a low number of participants. The highest number of participants was in the
Boden, et al., (2005) study which had a total number of 79. The other two studies
combined had a total of 22 participants. Though a limit to our position, this attrition
(dropout) rate was also seen in studies supporting our counterargument, leading us to
believe that dropout rates are common in most studies. In addition, our studies performed
their research for a short duration ranging from 3-4 weeks. Lastly, in the Samaha, et al.,
(2003) study, subjects were given a diet consisting of 40% of their daily intake coming
from carbohydrates, which is arguable as to whether this can be considered a “low
carbohydrate” diet when compared to RDA standards.
Our counterargument contained several limitations as mentioned throughout this
paper; however several studies did show strengths that our strongest pile did not have.
Unlike the duration of our studies, the Stern, et al., (2004) study is noted as the longest
and largest study to date on the effects of carbohydrates on glucose levels and/or insulin
sensitivity. Preliminary characteristics were taken into consideration before the actual
study was conducted. More specifically, things such as fat composition, gender, race, etc.
were matched for each group in the Sargrad, et al., (2005) study. This was seen in some
of the studies of our strong pile as well, however not to the same extent. Lastly, in the
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Dansinger, et al., (2005) study, all measurements were taken at two months, six months
and then at one year to obtain an overall trend and distinguish between short and long
term effects.
As you can see, the debate between whether or not low carbohydrate diets are
effective in improving glucose levels and insulin sensitivity is unresolved. It is in our
opinion that a low carbohydrate diet is indeed effective for the three reasons we have
stated previously in this paper. To summarize, our position demonstrated stronger
measurement techniques, strict carbohydrate intake control, and more studies that
collectively supported this conclusion. Therefore, after reading this paper we would hope
that diabetic people like you would be willingly to try a low carbohydrate to aid in the
management of diabetes.
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Percentage of Glucose vs. Insulin
decrease
80
70
60
50
Percent
40
decrease
30
20
10
0
Insulin
Glucose
Insulin
Glucose
Samaha,
Boden,
et al
et al
Figure 1: Comparison of glucose levels and insulin sensitivity in the Samaha et al. (2003)
and Boden et al. (2005) studies. Results both show a general improvement in both
variables after low carbohydrate diets however at different amounts.
Reference
Foster, G.D., et al., A
randomized trial of a
low- carbohydrate
diet for obesity.
Hung et al., Fat vs.
Carbohydrate in insulin
resistance, obesity, diabetes
and cardiovascular disease.
Boden, G et al., Effects of a
low carbohydrate diet on
appetite, blood glucose
levels, and insulin resistance
in obese patients with type 2
diabetes.
Population
Participant
Number
Results
Adults with
Type 2
diabetes
63
Significant increase in insulin
sensitivity at six months but
values not significantly
different from base line at one
year
Review
Review
Type 2 diabetes can be
prevented with modification of
carbohydrates
Obese with
type 2 diabetes
10
Insulin sensitivity improved by
75% and glucose levels
normalized after effects of low
carbohydrate diet
12
Miyashita, Y. et al.,
Beneficial effect of low
carbohydrate in low
calorie diet on visceral
fat reduction.
Sievenpiper, JL el al., Insulin
Resistance: concepts,
controversies and the role of
nutrition.
Samaha, F.F. et al., A lowcarbohydrate as compared
to a low fat diet in sever
obesity.
Sargrad, K.R. et al., Effect of
high protein versus high
carbohydrate intake on
insulin sensitivity, body
weight, hemoglobin A1c, and
blood pressure in patients
with Type 2 diabetes
mellitus.
Dansinger, M. et al.,
Comparison of the Atkins,
Ornish, Weight Watchers
and Zone diets for weight
loss and heart disease risk
reduction.
Stern, K. et al., The effects of
low-carbohydrate versus
conventional weight loss diet
in severely obese adults: one
year follow up of a
randomized trial.
Obese adults
with Type 2
diabetes
22
30% reduction in serum insulin
levels, homeostasis model
assessment ratio changed
from 3.06 to .77
Review
Review
High carbohydrate, low fat diet
with high amount of fiber can
decrease the risk of diabetes
by over 40%.
Severely obese
adults with a
high
prevalence of
diabetes
Adults with
Type 2
diabetes
79
Insulin sensitivity increased
6+/-9%, glucose levels
decreased by 9+/-19% in a low
carb diet
12
Neither glucose or insulin was
affected by the lowcarbohydrate diet
Overweight or
obese adults
160
Obese adults
with diabetes or
metabolic
syndrome
132
Mean glucose to start was
127mg/dL: at 2 months a
decrease by 9.8; at 6 months a
decrease of 7.8 from baseline;
at 12 months an increase of
1.4mg/dL from baseline.
Insulin to start was 22 micro
IU/mL: at 2 months a decrease
by 5.1; at 6 months a decrease
by 2.3 from baseline; at 12
months a decrease by 1.2 from
baseline.
Insulin levels decreased by
33% (153+/-139 to 104+/-49
pmol/L) but glucose levels
increased from 5.61+/-.72 to
5.66+/-.56 mmol/L
Figure 2: Table comparing several results from different studies showing that issue of
low carbohydrate diet and its effect on glucose levels and insulin sensitivity remains
unresolved. Red indicates the studies that were for the counterargument while the blue
text indicates the studies for our position.
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Results
Samaha
Boden
Sargrad
Stern
Insulin
sensitivity
increased
6+/-9%,
glucose
levels
decreased
by 9+/-19%
Insulin
sensitivity
improved
by 75% and
glucose
levels
decreased
from 7.5
mmol/L to
6.3 mmol/L
Neither
glucose nor
insulin were
significantly
effected
(insulin
decreased
from 94+/-11
to 75+/-25
pmol/L; P <
.02 of plasma
glucose)
Insulin levels
decreased by
33% (153+/139 to 104+/49 pmol/L)
but glucose
levels
increased
from 5.61+/.72 to 5.66+/.56 mmol/L
Length of
Study
4 weeks
followed by
one hourly
monthly
sessions for 5
months
# of
Subjects
79
7 days of
normal diet
followed by
14 days of
lowcarbohydrate
diet
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Measurement Technique

Blood sample after an
overnight fast
 Radioimmunoassay
 Quantitative insulin
sensitivity check index
 Euglycemic clamp



Glucose analyzer
Radioimmoassay with
specific antibodies
Euglycemichyperinsulinemic
clamp
Blood sampling for 24
hours
Steele’s equation


Once a
week for
eight
weeks
12


Euglycemic clamp
Blood sampling (once)
6 month
study, 6
month
follow up (
year total)
87 ( less
than half
received
follow up
after 6
months)


Radioimmunoassay
QUICK index
14
Figure 3: Variety of method techniques used to measure the variables (glucose levels and
insulin sensitivity) both from studies that agree or disagree with our position.
Collectively, the two counterargument studies (bottom two) that we looked at had four
measurement techniques where as you can see that for our position the two studies (top
two) had nine.
Comparison of variable carbohydrate intakes versus
insulin and glucose improvement
80
70
% improvement
60
50
40
Insulin sensitivity
30
Glucose levels
20
10
0
-10
Boden, et al.
(4.2%)
Stern, et al.
(6%)
Samaha, et al. Sargrad, et al.
(6%)
(40%)
Reference along with percent dietary intake of
carbs
Figure 4: Comparison of amount of carbohydrate intake and its relationship to
percentage improvement of both glucose levels and insulin sensitivity. Results were taken
from two studies against our position and two in support. Note the lowest amount of
carbohydrates correlates with the highest percentage of improvement while the higher
percentage of carbohydrate intake correlates with a lower improvement if any at all.
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Figure 7: Progression of Type 2 Diabetes
Figure 6: Trend of Diabetes progression from 1990-1999
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References:
Boden, G., Sargrad, K., Homko, C., Mozzoli, M. & Stein, T.P. (2005). Effect of a low
Carbohydrate diet on appetite, blood glucose levels, and insulin resistance in
obese Patients with type two diabetes. Annals of Internal Medicine Journal 142,
403-411.
Cheng, D. (2005). Prevalence, predisposition and prevention of type 2 diabetes.
Nutrition and Metabolism 2, 29.
Dansinger, M., Gleason, J., Griffith, J., Selker, H., Shaefer, E., (2005). Comparison of
the Atkins, Ornish, Weight Watchers and Zone diets for weight loss and heart
disease risk reduction: A randomized trial. JAMA 293, 43-53.
Foster, G.D., Wyatt, M.D., O’Hill, J., McGukin, B.G., Brill, B.S., Mohammed, M.D.,
Szapary, P., Rader, D.J., Edman, D.S., Klein, S. (2003). A Randomized trial of a
Low carbohydrate diet for obesity. New England Journal of Medicine. 348, 282390.
Hogan, P., Sievenpiper, J., Marchie, A., Kendall, C., and Jenkins, D., (2003). Fat versus
carbohydrate in insulin resistance, obesity, diabetes, and cardiovascular disease.
Current Opinion in clinical nutrition in metabolic care 6, 165-176.
Hung, T., Sievenpiper, J.L., Marchie, A., Kendall, C., Jenkins, D. (2003). Fat versus
Carbohydrate in insulin resistance obesity diabetes and cardiovascular disease.
Current Opinion in clinical nutrition in metabolic care 6, 165-176.
Lai, L.C., (2002). Prevention of type 2 diabetes. Malays J Pathology 24, 71-76
Miyashita, Y., Koide, N., Ohtsuka, M., Ozaki, H., Itoh, Y., Oyama, T., Utekae, T., Ariga,
K & Shirai, K. (2004) Beneficial effect of low carbohydrate in low calorie diets
on Visceral fat reduction in type 2 diabetic patients with obesity. Diabetes
Researach and Clinical Practice 65, 235-241
Samaha, F.F., Iqbal, N., Seshadri, P., Chicano, K., Daily, D., McGrory, J., Williams, T.,
Williams, M., Gracely, E & Stern, L. (2003). Low carbohydrate as compared with
A low fat diet in severe obesity. New England Journal of Medicine 348, 20742081.
Sargrad, K.R., Homko, C., Mozzoli, M & Boden, G. (2005). Effect of high protein vs.
High carbohydrate intake on insulin sensitivity, body weight, hemoglobin A1c,
and Blood pressure in patients with type 2 diabetes mellitus. Journal of the
American Dietetic Association 105, 573-580
17
Sievenpiper, J.L., Jenkins, A.L., Whitham, D.L & Vuksan, V. (2002). Insulin resistance:
Concepts, controversies and the role of nutrition. Canadian Journal of Dietetic
Practice and Research 63, 20-32
Stern, L., Iqbal, N., Seshadri, P., Chicano, K., Daily, D., McGrory, J., Williams, M.,
Gracely, E & Samaha, F.F. (2004). Effects of a low carbohydrate versus
Conventional weight loss diets in severly obsese adults: one year followup
Of a randomized trial. Annals of Internal Medicine 140, 778-785
The Euglycemic Clamp Technique in Mouse Model for Type 2 Diabetes. (2001).
[Online] In TNO Pharma. Available:
http://www.tno.nl/kwaliteit_van_leven/toegepaste_biotechnologie/biomedical_re
earch/the_euglycemic_clamp/LE114_Euglycemic%20clamp%20diab.pdf
YSI glucose analyzers, blood gas analysis. (2001). [Online] In YSI Life Sciences.
Available: http://www.ysi.com/life/blood-gas-analysis.htm