A low-carbohydrate, ketogenic diet to treat type 2 diabetes

Abstract

The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes.
From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A1c.
Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [+/- SD] age was 56.0 +/- 7.9 years and BMI was 42.2 +/- 5.8 kg/m2. Hemoglobin A1c decreased by 16% from 7.5 +/- 1.4% to 6.3 +/- 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 +/- 18.3 kg to 122.7 +/- 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A1c. Fasting serum triglyceride decreased 42% from 2.69 +/- 2.87 mmol/L to 1.57 +/- 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly.
The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.

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Nutrition & Metabolism
Open Access
Research
A low-carbohydrate, ketogenic diet to treat type 2 diabetes
William S Yancy Jr*1,2, Marjorie Foy1, Allison M Chalecki1, Mary C Vernon3
and Eric C Westman2
Address: 1Center for Health Services Research in Primary Care, Department of Veterans' Affairs Medical Center (152), 508 Fulton Street, Durham,
NC, USA 27705, 2Department of Medicine, Duke University Medical Center, Durham, NC, USA and 3Private Bariatric and Family Practice, and
Clinical Faculty, University of Kansas School of Medicine, Lawrence, KS, USA
Email: William S Yancy* - yancy006@mc.duke.edu; Marjorie Foy - foy00005@mc.duke.edu; Allison M Chalecki - allisonchalecki@yahoo.com;
Mary C Vernon - mvernonmd@yahoo.com; Eric C Westman - ewestman@duke.edu
* Corresponding author
Abstract
Background: The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving
glycemia and reducing medications in patients with type 2 diabetes.
Methods: From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes
for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial
goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation.
Participants returned every other week for measurements, counseling, and further medication
adjustment. The primary outcome was hemoglobin A1c.
Results: Twenty-one of the 28 participants who were enrolled completed the study. Twenty
participants were men; 13 were White, 8 were African-American. The mean [± SD] age was 56.0
± 7.9 years and BMI was 42.2 ± 5.8 kg/m2. Hemoglobin A1c decreased by 16% from 7.5 ± 1.4% to
6.3 ± 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7
participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight
decreased by 6.6% from 131.4 ± 18.3 kg to 122.7 ± 18.9 kg (p < 0.001). In linear regression analyses,
weight change at 16 weeks did not predict change in hemoglobin A1c. Fasting serum triglyceride
decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38 mmol/L (p = 0.001) while other serum lipid
measurements did not change significantly.
Conclusion: The LCKD improved glycemic control in patients with type 2 diabetes such that
diabetes medications were discontinued or reduced in most participants. Because the LCKD can
be very effective at lowering blood glucose, patients on diabetes medication who use this diet
should be under close medical supervision or capable of adjusting their medication.
Background
Prior to the advent of exogenous insulin for the treatment
of diabetes mellitus in the 1920's, the mainstay of therapy
was dietary modification. Diet recommendations in that
era were aimed at controlling glycemia (actually, glycosu-
ria) and were dramatically different from current low-fat,
high-carbohydrate dietary recommendations for patients
with diabetes [1,2]. For example, the Dr. Elliot Joslin Dia-
betic Diet in 1923 consisted of "meats, poultry, game,
fish, clear soups, gelatin, eggs, butter, olive oil, coffee, tea"
Published: 01 December 2005
Nutrition & Metabolism 2005, 2:34 doi:10.1186/1743-7075-2-34
Received: 10 August 2005
Accepted: 01 December 2005
This article is available from: http://www.nutritionandmetabolism.com/content/2/1/34
© 2005 Yancy et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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and contained approximately 5% of energy from carbohy-
drates, 20% from protein, and 75% from fat [3]. A similar
diet was advocated by Dr. Frederick Allen of the same era
[4].
Recently, four studies have re-examined the effect of car-
bohydrate restriction on type 2 diabetes. One outpatient
study enrolled 54 participants with type 2 diabetes (out of
132 total participants) and found that hemoglobin A1c
improved to a greater degree over one year with a low-car-
bohydrate diet compared with a low-fat, calorie-restricted
diet [5,6]. Another study enrolled 8 men with type 2 dia-
betes in a 5-week crossover outpatient feeding study that
tested similar diets [7]. The participants had greater
improvement in glycohemoglobin while on the low-car-
bohydrate diet than when on a eucaloric low-fat diet. The
third study was an inpatient feeding study in 10 partici-
pants with type 2 diabetes [8]. After only 14 days, hemo-
globin A1c improved from 7.3% to 6.8%. In the fourth
study, 16 participants with type 2 diabetes who followed
a 20% carbohydrate diet had improvement of hemo-
globin A1c from 8.0% to 6.6% over 24 weeks [9]. Only
these latter three studies targeted glycemic control as a
goal, and two of these were intensely-monitored efficacy
studies in which all food was provided to participants for
the duration of the study [7,8]. Three of the studies [6,8,9]
mentioned that diabetic medications were adjusted but
only one of them provided detailed information regard-
ing these adjustments [9]. This information is critical for
patients on medication for diabetes who initiate a low-
carbohydrate diet because of the potential for adverse
effects resulting from hypoglycemia.
The purpose of this study was to evaluate the effects of a
low-carbohydrate, ketogenic diet (LCKD) in overweight
and obese patients with type 2 diabetes over 16 weeks.
Specifically, we wanted to learn the diet's effects on glyc-
emia and diabetes medication use in outpatients who pre-
pared (or bought) their own meals. In a previous article,
we reported the results observed in 7 individuals [10]; this
report includes data from those 7 individuals along with
data from additional participants enrolled subsequently.
Methods
Participants
Participants were recruited from the Durham Veterans
Affairs Medical Center (VAMC) outpatient clinics. Inclu-
sion criteria were age 35–75 years; body mass index (BMI)
>25 kg/m2; and fasting serum glucose >125 mg/dL or
hemoglobin A1c >6.5% without medications, or treatment
with oral hypoglycemic agents (OHA) and/or insulin.
Exclusion criteria were evidence of renal insufficiency,
liver disease, or unstable cardiovascular disease by history,
physical examination, and laboratory tests. All partici-
pants provided written informed consent approved by the
institutional review board. No monetary incentives were
provided.
Intervention
At the first visit, participants were instructed how to fol-
low the LCKD as individuals or in small groups, with an
initial goal of ≤20 g carbohydrate per day. Participants
were taught the specific types and amounts of foods they
could eat, as well as foods to avoid. Initially, participants
were allowed unlimited amounts of meats, poultry, fish,
shellfish, and eggs; 2 cups of salad vegetables per day; 1
cup of low-carbohydrate vegetables per day; 4 ounces of
hard cheese; and limited amounts of cream, avocado,
olives, and lemon juice. Fats and oils were not restricted
except that intake of trans fats was to be minimized. Par-
ticipants were provided a 3-page handout and a hand-
book [11] detailing these recommendations. Participants
prepared or bought all of their own meals and snacks fol-
lowing these guidelines.
In addition, on the day the diet was initiated, diabetes
medications were reduced – generally, insulin doses were
halved, and sulfonylurea doses were halved or discontin-
ued. Due to the possible diuretic effects of the diet soon
after initiation, diuretic medications were discontinued if
of low dosage (up to 25 mg of hydrochlorothiazide or 20
mg of furosemide) or halved if of higher dosage. Partici-
pants were also instructed to take a standard multivitamin
and drink 6–8 glasses of water daily, and were encouraged
to exercise aerobically for 30 minutes at least three times
per week.
Participants returned every other week for 16 weeks for
further diet counseling and medication adjustment. When
a participant neared half the weight loss goal or experi-
enced cravings, he or she was advised to increase carbohy-
drate intake by approximately 5 g per day each week as
long as weight loss continued. Participants could choose
5 g carbohydrate portions from one of the following foods
each week: salad vegetables, low-carbohydrate vegetables,
hard or soft cheese, nuts, or low-carbohydrate snacks. Dia-
betes medication adjustment was based on twice daily
glucometer readings and hypoglycemic episodes, while
diuretic and other anti-hypertensive medication adjust-
ments were based on orthostatic symptoms, blood pres-
sure, and lower extremity edema.
Measurements
Participants completed take-home food records (4 con-
secutive days, including a weekend) collected at baseline
and at weeks 2, 8, and 16 during the study. Participants
were given handouts with examples of how to complete
the records. A registered dietician analyzed the food
records using a nutrition software program (Food Proces-
sor SQL, ESHA Research, Inc., Salem, OR).

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The following measurements were made every other
week: anthropometric and vital sign measurements; urine
testing for ketones; and assessment for hypoglycemic epi-
sodes and other symptomatic side effects. Weight was
measured on a standardized digital scale while the partic-
ipant was wearing light clothes and shoes were removed.
Skinfold thickness was measured at 4 sites – the average of
2 measurements at each site was entered into an equation
to calculate percent body fat [12]. Waist circumference
was measured at the midpoint between the inferior rib
and the iliac crest using an inelastic tape; 2 measurements
were averaged in the analysis. Blood pressure and heart
rate were measured after the participant had been seated
quietly without talking for 3 minutes. Certified laboratory
technicians assessed urine ketones from a fresh specimen
using the following semi-quantitative scale: none, trace
(up to 0.9 mmol/L [5 mg/dL]), small (0.9–6.9 mmol/L
[5–40 mg/dL]), moderate (6.9–13.8 mmol/L [40–80 mg/
dL]), large80 (13.8–27.5 mmol/L [80–160 mg/dL]),
large160 (>27.5 mmol/L [160 mg/dL]). Hypoglycemic
episodes and symptomatic side effects were assessed by
direct questioning of the participant and by self-adminis-
tered questionnaires.
Blood specimens were obtained at weeks 0, 8, and 16 after
the participant had fasted overnight. The following serum
tests were performed in the hospital laboratory using
standardized methods: complete blood count, chemistry
panel, lipid panel, thyroid-stimulating hormone, and uric
acid. A non-fasting specimen was also drawn at weeks 4
and 12 to monitor electrolytes and kidney function.
The primary outcome was the change from baseline to
week 16 in hemoglobin A1c. Changes in all variables were
analyzed by the paired t-test or Wilcoxon signed-ranks
test, as appropriate. Linear regression analysis was used to
examine predictors of change in hemoglobin A1c. A p
value of 0.05 or less was considered statistically signifi-
cant. Statistical analysis was performed using SAS version
8.02 (SAS Institute, Cary, NC).
Results
Of the 28 participants enrolled in the study, 21 completed
the 16 weeks of follow-up. Reasons for discontinuing the
study included unable to adhere to study meetings and
unable to adhere to the diet; no participant reported dis-
continuing as a result of adverse effects associated with the
intervention. All but one of the 21 participants were men;
62% (n = 13) were Caucasian, 38% (n = 8) were African-
American (Table 1). The mean age was 56.0 ± 7.9 years.
Adequate food records were available for analysis in a pro-
portion of participants at each of the 4 timepoints (Table
2). Participants completed food records at a mean of 2.5
and a median of 3 timepoints. In general, comparing
baseline to subsequent timepoints, mean carbohydrate
intake decreased substantially and energy intake
decreased moderately while protein and fat intake
remained fairly constant.
From baseline to week 16, the mean body weight
decreased significantly from 131.4 ± 18.3 kg to 122.7 ±
18.9 kg, BMI decreased from 42.2 ± 5.8 kg/m2 to 39.4 ±
6.0 kg/m2, and waist circumference from 130.0 ± 10.5 cm
to 123.3 ± 11.3 cm (Table 3). The percent change in body
weight was -6.6%. The mean percent body fat decreased
from 40.4 ± 5.8% to 37.0 ± 6.0%. Systolic and diastolic
blood pressures did not change significantly over the 16
weeks. The mean heart rate decreased from 81.2 ± 12.9
beats per minute to 74.6 ± 14.0 beats per minute (p =
0.01).
Urine ketone data were missing in a median of 4 partici-
pants (range 0–8) at any given visit. The proportion of
participants with a urine ketone reading greater than trace
was 1 of 17 participants at baseline, 5 of 17 participants at
week 2, and similar frequencies at subsequent visits until
week 14 when 2 of 18 participants had readings greater
than trace and week 16 when 2 of 21 participants had
Table 1: Baseline characteristics (n = 21)
Characteristic Summary
Age, years, mean (SD) 56.0 (7.9)
Gender, male, n (%) 20 (95%)
Race, White, n (%) 13 (62%)
African-American, n (%) 8 (38%)
Weight, kg, mean (SD) 131.4 (18.3)
BMI, kg/m2, mean (SD) 42.2 (5.8)
Table 2: Diet composition
Nutrient Week 0
Mean (SD)
Week 2
Mean (SD)
Week 8
Mean (SD)
Week 16
Mean (SD)
n 141515 8
Carbohydrate, g 204.4 (118.4) 44.6 (27.4) 44.0 (29.1) 33.8 (24.6)
Protein, g 95.8 (23.9) 111.7 (38.6) 114.8 (57.0) 98.5 (52.5)
Fat, g 95.5 (27.3) 95.1 (47.2) 106.6 (47.6) 93.5 (63.7)
Energy, kcal 2031.5 (521.4) 1515.5 (587.2) 1603.4 (713.0) 1418.7 (756.9)

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readings greater than trace. During the study, only 27 of
151 urine ketone measurements were greater than trace,
with one participant accounting for all 7 occurrences of
the highest urine ketone reading (large160).
In regard to serum measurements, the mean fasting glu-
cose decreased by 17% from 9.08 ± 4.09 mmol/L at base-
line to 7.57 ± 2.63 mmol/L at week 16 (p = 0.04) (Table
4). Serum sodium and chloride levels increased signifi-
cantly, but only by 1% and 3%, respectively. Uric acid
level decreased by 10% (p = 0.01). Serum triglyceride
decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38
mmol/L (p = 0.001). Increases occurred in both high-den-
sity lipoprotein (HDL) cholesterol (8%) and low-density
lipoprotein (LDL) cholesterol (10%) but these changes
were of borderline statistical significance (p = 0.08 and p
= 0.1, respectively). The following blood tests did not
change significantly: total cholesterol, potassium, bicar-
bonate, urea nitrogen, creatinine, calcium, thyroid-stimu-
lating hormone, and hemoglobin.
The primary outcome, hemoglobin A1c, decreased from
7.5 ± 1.4% at baseline to 6.3 ± 1.0% at week 16 (p <
0.001), a 1.2% absolute decrease and a 16% relative
decrease (Table 4). All but two participants (n = 19 or
90%) had a decrease in hemoglobin A1c (Figure 1). The
absolute decrease in hemoglobin A1c was at least 1.0% in
11 (52%) participants. The relative decrease in hemo-
globin A1c from baseline was greater than 10% in 14
(67%) participants, and greater than 20% in 6 (29%) par-
ticipants. In regression analyses, the change in hemo-
globin A1c was not predicted by the change in body
weight, waist circumference, or percent body fat at 16
weeks (all p > 0.05).
Table 3: Anthropometric and vital sign measurements (n = 21)
Measurement Week 0
Mean (SD)
Week 16
Mean (SD)
Change
%
p value*
Body weight, kg 131.4 (18.3) 122.7 (18.9) -6.6 <0.001
Body mass index, kg/m242.2 (5.8) 39.4 (6.0) -6.6 <0.001
Waist circumference, cm 130.0 (10.5) 123.3 (11.3) -5.2 <0.001
Percent body fat, % 40.4 (5.8) 37.0 (6.0) -8.4 <0.001
Systolic blood pressure, mm Hg 135.1 (14.8) 135.4 (17.6) 0.2 0.9
Diastolic blood pressure, mm Hg 79.2 (14.9) 74.1 (13.0) -6.4 0.1
Heart rate, beats/min 81.2 (12.9) 74.6 (14.0) -8.1 0.01
*By paired t-test or Wilcoxon signed-ranks test.
Table 4: Serum test results (n = 21)
Measurement Week 0
Mean (SD)
Week 16
Mean (SD)
Change
%
p value*
Hemoglobin A1c, % 7.5 (1.4) 6.3 (1.0) -16.0 <0.001
Glucose, mmol/L 9.08 (4.09) 7.57 (2.63) -16.6 0.04
Total cholesterol†, mmol/L 4.61 (1.40) 4.54 (1.26) -1.5 0.7
Triglyceride†, mmol/L 2.69 (2.87) 1.57 (1.38) -41.6 0.001
HDL-C†, mmol/L 0.92 (0.20) 0.99 (0.22) 7.6 0.08
LDL-C†, mmol/L 2.51 (0.64) 2.77 (0.89) 10.4 0.1
Sodium, mmol/L 138.2 (3.4) 140.2 (3.4) 1.4 0.02
Potassium, mmol/L 4.2 (0.4) 4.2 (0.3) 0 0.2
Chloride, mmol/L 101.0 (3.4) 103.8 (2.8) 2.8 0.001
Bicarbonate, mmol/L 28.8 (2.0) 28.2 (2.5) -2.1 0.3
Urea nitrogen, mg/dL 5.90 (1.90) 6.27 (1.81) 6.3 0.3
Creatinine, µmol/L 82.8 (20.4) 79.9 (19.1) -3.5 0.3
Calcium†, mmol/L 2.32 (0.11) 2.33 (0.08) 0.4 0.8
Uric acid†, µmol/L 403.5 (94.6) 352.1 (85.4) -10.3 0.01
TSH†, mIU/L 1.6 (1.0) 1.4 (0.7) -12.7 0.2
Hemoglobin, g/L 142 (11) 141 (10) -0.7 0.8
Legend: TSH = thyroid-stimulating hormone, HDL-C = high-density lipoprotein cholesterol, LDL-C = low-density lipoprotein cholesterol.
* By paired t-test or Wilcoxon signed-ranks test.
† Serum calcium, TSH, total cholesterol, triglyceride, and HDL-C results are based on n of 20 because one participant did not have these tests at
baseline. Uric acid is based on n of 19. LDL-C is based on n of 17 because triglyceride levels were too high at baseline to calculate LDL-C in 3
participants.

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The improvement in glycemic control occurred while
medications for diabetes were discontinued or reduced in
most participants (Table 5). During the study, hyperten-
sion and hyperlipidemia medication doses were not
increased from baseline nor were new agents added,
except in 3 individuals. No serious adverse effects related
to the diet occurred. One participant had a hypoglycemic
episode requiring assistance from emergency services after
he skipped a meal but the episode was aborted without
need for transportation to the emergency room or hospi-
talization.
Discussion
In this single-arm, 4-month diet intervention, an LCKD
resulted in significant improvement of glycemia, as meas-
ured by fasting glucose and hemoglobin A1c, in patients
with type 2 diabetes. More importantly, this improvement
was observed while diabetes medications were reduced or
discontinued in 17 of the 21 participants, and were not
changed in the remaining 4 participants. Participants also
experienced reductions in body weight, waist circumfer-
ence, and percent body fat but these improvements were
moderate and did not predict the change in hemoglobin
A1c in regression analyses.
Several recent studies indicate that a low-carbohydrate
diet is effective at improving glycemia. A few studies have
shown that in non-diabetic individuals, low-carbohydrate
diets were more effective than higher carbohydrate diets at
improving fasting serum glucose [13,14] and insulin
[6,14-16], and at improving insulin sensitivity as meas-
ured by the homeostasis model [6]. One of these studies
also included diabetic patients and noted a comparative
improvement in hemoglobin A1c after 6 months (low fat
diet: 0.0 ± 1.0%; low carbohydrate diet: -0.6 ± 1.2%, p =
0.06) [6] and 12 months (low fat diet: -0.1 ± 1.6%; low
carbohydrate diet: -0.7 ± 1.0%, p = 0.019) duration [5]. In
a 5-week crossover feeding study, 8 men with type 2 dia-
betes had greater improvement in fasting glucose, 24-hour
glucose area-under-the-curve (AUC), 24-hour insulin
AUC, and glycohemoglobin while on the low-carbohy-
drate diet than when on a eucaloric low-fat diet [7]. In a
14-day inpatient feeding study, 10 participants with type
2 diabetes experienced improvements in hemoglobin A1c
and insulin sensitivity as measured by the euglycemic
hyperinsulinemic clamp method [8]. Hemoglobin A1c
also improved in an outpatient study of 16 participants
who followed a 20% carbohydrate diet for 24 weeks [9].
Similar to our results, three studies noted that diabetes
medications were reduced in some participants[6,8,9],
although details were provided in only one study. We also
discontinued diuretic medications during diet initiation
because of concern for additional diuresis incurred by the
diet. This concern was based on the theoretical effects of
the diet [17], observed effects of the diet on body water by
bioelectric impedance [18], and practical experience with
the diet [19]. Until we learn more about using low carbo-
hydrate diets, medical monitoring for hypoglycemia,
dehydration, and electrolyte abnormalities is imperative
in patients taking diabetes or diuretic medications.
While body weight decreased significantly (-8.5 kg) in
these 21 diabetic participants, the mean weight loss was
less compared with what we observed in the LCKD partic-
ipants of an earlier trial (-12.0 kg) [18]. Given that the dia-
betic participants had a higher baseline mean weight than
the LCKD participants of our previous trial (131 kg vs. 97
kg), this translates into an even more dramatic disparity in
percent change in body weight (-6.6% vs. -12.9%). This
lesser weight loss might result from several factors. First,
in the current study, most of the participants were taking
insulin and/or oral hypoglycemic agents that are known
to induce weight gain[20,21] Second, these same agents,
particularly insulin, inhibit ketosis, which is strived for in
the earliest phases of the LCKD; while it remains unclear
whether ketones actually play a role in weight loss on the
LCKD, previous research in non-diabetic patients has
shown a positive correlation between level of ketonuria
and weight loss success [22]. Lastly, compared with our
previous study the participants in the current study had
more comorbid illness, lower socioeconomic status, and a
shorter duration of follow-up (16 weeks versus 24 weeks),
all of which are associated with reduced success on any
weight loss program [23].
The main limitations of our study are its small sample
size, short duration, and lack of control group. That the
main outcome, hemoglobin A1c, improved significantly
despite the small sample size and short duration of fol-
low-up speaks to the dramatic and consistent effect of the
LCKD on glycemia. For other effects, however, such as the
Hemoglobin A1c for each participantFigure 1
Hemoglobin A1c for each participant. *Red line is the
group mean. P value is for the mean change from baseline.
4
5
6
7
8
9
10
11
12
13
Week 0
Week 16
Hemoglobin A1c, %
Mean= 7.4%
Mean= 6.3%,
*P<0.001

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rises in serum LDL and HDL cholesterol, the small sample
size might be the reason statistical significance was not
reached. Future studies of larger samples and containing a
control group are needed to better address questions
about the effect of the LCKD on serum lipids in patients
with type 2 diabetes.
Conclusion
In summary, the LCKD had positive effects on body
weight, waist measurement, serum triglycerides, and glyc-
emic control in a cohort of 21 participants with type 2 dia-
betes. Most impressive is that improvement in
hemoglobin A1c was observed despite a small sample size
and short duration of follow-up, and this improvement in
glycemic control occurred while diabetes medications
were reduced substantially in many participants. Future
research must further examine the optimal medication
adjustments, particularly for diabetes and diuretic agents,
in order to avoid possible complications of hypoglycemia
and dehydration. Because the LCKD can be very effective
at lowering blood glucose, patients on diabetes medica-
tion who use this diet should be under close medical
supervision or capable of adjusting their medication.
Competing interests
Dr. Vernon has held a consulting relationship with Atkins
Nutritionals, Inc.
Table 5: Diabetes medication changes
Participant Week 0
Total daily dose
Week 16
Total daily dose
Participants with diabetes medications discontinued (n = 7 of 21)
5 glipizide 10 mg
metformin 1000 mg
none
6 glipizide 20 mg
metformin 1500 mg
none
7 metformin 2000 mg
rosiglitazone 8 mg
none
9 metformin 1000 mg none
15 metformin 1000 mg none
22 metformin 1000 mg none
24 metformin 1000 mg none
Participants with diabetes medications reduced (n = 10 of 21)
3 70/30 insulin 50 units
metformin 1000 mg
metformin 1000 mg
11 metformin 2000 mg
glyburide 20 mg
metformin 2000 mg
16 metformin 2000 mg
pioglitazone 45 mg
glipizide 20 mg
metformin 2000 mg
21 metformin 1500 mg
pioglitazone 30 mg
metformin 1000 mg
8 NPH 145 units
metformin 1000 mg
NPH 25 units
metformin 1000 mg
13 70/30 insulin 70 units
metformin 2550 mg
70/30 insulin 35 units
metformin 2550 mg
23 70/30 insulin 110 units
pioglitazone 45 mg
70/30 insulin 80 units
pioglitazone 45 mg
metformin 1000 mg
25 NPH 70 units, R 30 units
metformin 2000 mg
pioglitazone 45 mg
NPH 8 units
metformin 2000 mg
pioglitazone 45 mg
27 70/30 insulin 86 units
metformin 2000 mg
70/30 insulin 18 units
metformin 2000 mg
28 NPH insulin 110 units
lispro insulin 90 units
glipizide 20 mg
NPH insulin 30 units
glipizide 20 mg
Participants with diabetes medications unchanged (n = 4 of 21)
1 none none
2 metformin 1700 mg metformin 1700 mg
10 none none
26 metformin 2000 mg metformin 2000 mg

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Authors' contributions
WY conceived, designed, and coordinated the study; par-
ticipated in data collection; performed statistical analysis;
and drafted the manuscript. MF assisted with study
design, performed data collection, and helped to draft the
manuscript. AC analyzed the food records. MV assisted
with study/intervention design and safety monitoring. EW
participated in the conception and design of the study,
and assisted with the statistical analysis. All authors read
and approved the final manuscript.
Acknowledgements
Dr. Yancy is s uppor ted by a VA He alth Services R esear ch Career Devel op-
ment Award (RCD 02-183-1).
References
1. Klein S, Sheard NF, Pi-Sunyer S, Daly A, Wylie-Rosett J, Kulkarni K,
Clark NG: Weight management through lifestyle modifica-
tion for the prevention and management of type 2 diabetes:
rationale and strategies. A statement of the American Dia-
betes Association, the North American Association for the
Study of Obesity, and the American Society for Clinical
Nutrition. Am J Clin Nutr 2004, 80:257-263.
2. Arora SK, McFarlane SI: The case for low carbohydrate diets in
diabetes management. Nutr Metab (Lond) 2005, 2:16.
3. Osler W, McCrae T: The Principles and Practice of Medicine.
New York, Appleton and Co.; 1923.
4. Allen FM, Stillman E, Fitz R: Total dietary regulation in the treat-
ment of diabetes: monograph No. 11. New York, The Rockefel-
ler Institute for Medical Research; 1919.
5. Stern L, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Wil-
liams M, Gracely EJ, Samaha FF: The effects of low-carbohydrate
versus conventional weight loss diets in severely obese
adults: one-year follow-up of a randomized trial. Ann Intern
Med 2004, 140:778-785.
6. Samaha FF, Iqbal N, Seshadri P, Chicano K, Daily D, McGrory J, Wil-
liams T, Williams M, Gracely EJ, Stern L: A low-carbohydrate as
compared with a low-fat diet in severe obesity. N Engl J Med
2003, 348:2074-2081.
7. Gannon MC, Nuttall FQ: Effect of a high-protein, low-carbohy-
drate diet on blood glucose control in people with type 2 dia-
betes. Diabetes 2004, 53:2375-2382.
8. Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP: Effect of a low-
carbohydrate diet on appetite, blood glucose levels, and
insulin resistance in obese patients with type 2 diabetes. Ann
Intern Med 2005, 142:403-411.
9. Nielsen JV, Jonsson E, Nilsson AK: Lasting improvement of
hyperglycaemia and bodyweight: low-carbohydrate diet in
type 2 diabetes. A brief report. Ups J Med Sci 2005, 110:179-183.
10. Yancy WS Jr, Vernon MC, Westman EC: Brief report: a pilot trial
of a low-carbohydrate, ketogenic diet in patients with type II
diabetes. Metabolic Syndrome and Related Disorders 2003, 1:239-244.
11. The Atkins Trial Kit Handbook: A Simple Guide to Doing
Atkins. Ronkonkoma, NY, Atkins Nutritionals, Inc.; 2001.
12. Durnin JVGA, Womersley J: Body fat assessed from total body
density and its estimation from skinfold thickness: measure-
ments on 481 men and women aged from 16 to 72 years. Br
J Nutr 1974, 32:77-97.
13. Sharman MJ, Gomez AL, Kraemer WJ, Volek JS: Very low-carbohy-
drate and low-fat diets affect fasting lipids and postprandial
lipemia differently in overweight men. J Nutr 2004,
134:880-885.
14. Volek JS, Sharman MJ, Gomez AL, DiPasquale C, Roti M, Pumerantz
A, Kraemer WJ: Comparison of a very low-carbohydrate and
low-fat diet on fasting lipids, LDL subclasses, insulin resist-
ance, and postprandial lipemic responses in overweight
women. J Am Coll Nutr 2004, 23:177-184.
15. Meckling KA, O'Sullivan C, Saari D: Comparison of a low-fat diet
to a low-carbohydrate diet on weight loss, body composition,
and risk factors for diabetes and cardiovascular disease in
free-living, overweight men and women. J Clin Endocrinol Metab
2004, 89:2717-2723.
16. Volek JS, Sharman MJ, Love DM, Avery NG, Gomez AL, Scheett TP,
Kraemer WJ: Body composition and hormonal responses to a
carbohydrate-restricted diet. Metabolism 2002, 51:864-870.
17. Denke MA: Metabolic effects of high-protein, low-carbohy-
drate diets. Am J Cardiol 2001, 88:59-61.
18. Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC: A low-
carbohydrate, ketogenic diet versus a low-fat diet to treat
obesity and hyperlipidemia: a randomized, controlled trial.
Ann Intern Med 2004, 140:769-777.
19. Vernon MC, Mavropoulos J, Yancy WS Jr, Westman EC: Brief
report: clinical experience of a carbohydrate-restricted diet:
effect on diabetes mellitus. Metabolic Syndrome and Related Disor-
ders 2003, 1:233-238.
20. Intensive blood-glucose control with sulphonylureas or insu-
lin compared with conventional treatment and risk of com-
plications in patients with type 2 diabetes (UKPDS 33). UK
Prospective Diabetes Study (UKPDS) Group. Lancet 1998,
352:837-853.
21. Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA,
Brunzell JD: Effect of excessive weight gain with intensive
therapy of type 1 diabetes on lipid levels and blood pressure:
results from the DCCT. Diabetes Control and Complica-
tions Trial. JAMA 1998, 280:140-146.
22. Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE: Effect of
six-month adherence to a very-low-carbohydrate diet pro-
gram. Am J Med 2002, 113:30-36.
23. Yancy WS Jr, Boan J: Adherence to Diet Recommendations. In
Patient Treatment Adherence: Concepts, Interventions, and Measurement
Mahwah, NJ, Lawrence Erlbaum Associates, Inc.; 2005.