Luke Shealy 1

The Ketogenic Diet as Treatment for Type 2 Diabetes

Introduction:
Type 2 diabetes mellitus (T2DM) has no cure and its complications can be deadly and
debilitating. Uncontrolled blood-glucose levels due to insulin resistance or lack of insulin can
lead to nerve damage, heart disease, kidney damage, and eye damage (Mayo, 2016). Too much
glucose in the blood damages the walls of capillaries that supply these organs and nerves with
blood (class, 2016). Controlling and maintaining healthy blood-glucose levels is important for
treatment of T2DM (Mayo, 2016). From 2007 to 2012, the cost of diabetes and its complications
has risen from $174 billion to $245 billion in the United States (CDC, 2014). Almost ten percent
of the U.S. population has diabetes and a third of the U.S. population has prediabetes (CDC,
2014).
Although there are pre-established methods used for treating type 2 diabetes, could a lowcarbohydrate, ketogenic diet (LCKD) be effective as a form of treatment with someone
diagnosed with type 2 diabetes mellitus? Per the American Diabetes Association, some of the
most common forms of treating type 2 diabetes include: carbohydrate counting, regular exercise,
medications (Metformin), and the use of exogenous insulin (Medication, 1995-2016). The
ketogenic diets focus is on limiting carbohydrates to levels of under 50g/day, so it could be a
potentially effective diet for controlling and slowing the progression of T2DM.
Metabolic Basis:
Because blood-glucose levels must be maintained at a healthy level, the pancreas produces
the hormone insulin to help cells take glucose out of the blood and into cells for storage and
anabolic needs (Gropper, et al., 2013, p.76). Insulin plays a primary role in moving glucose out
of the blood and into cells found in muscles, fat, and the liver. When insulin resistance is present
due to pre-diabetes or T2DM, muscle cells, fat cells, and liver cells fail to respond to insulin with

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GLUT4 transporters, and they cannot absorb glucose from the blood. This causes the pancreas
beta cells to produce more insulin to keep the blood-glucose levels in a healthy range (NIDDK,
2009). Eventually, the beta cells cannot keep up with the insulin demand, and without proper
diet, exercise, medications, or insulin injections, blood-glucose levels cannot be maintained at
healthy levels.
The ketogenic diet is a way for the body to bypass the need for carbohydrates and glucose
as the bodys main source of energy. Instead of glucose being used as the primary energy source
for the body, the ketogenic diet causes the body to utilize acetyl coenzyme A (AcCoA) as the
primary energy source for the TCA cycle (Paoli, et al., 2013).
The AcCoA comes from the beta oxidation of fatty acids and the metabolism of certain
amino acids. Beta oxidation of one palmitic acid yields eight AcCoAs (Gropper, et al., 2013, p.
166). Leucine and lysine are the only two completely ketogenic amino acids. When catabolized,
they create AcCoA. Several other amino acids are both glucogenic and ketogenic, and they
include phenylalanine, tyrosine, tryptophan, threonine, methionine, and isoleucine. Leucine,
tyrosine, and phenylalanine can all three be converted directly to the ketone body acetoacetate
(Gropper, et al., 2013, p. 196-197).
Both the beta oxidation of fatty acids and the metabolism of amino acids, gained from a
diet high in fats and protein and low in carbohydrates, lead to the overproduction of ketone
bodies. The three main ketone bodies are: acetoacetate, beta-hydroxybutyric acid, and acetone
(Paoli, et al., 2013). Acetyl Coenzyme A is used to make ketone bodies when it is overproduced
in the liver due to a shortage of glucose. The ketone bodies (acetoacetate and betahydroxybutyrate) are then transported from the liver to peripheral tissues, so the ketone bodies

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can be taken up and broken back down to AcCoA which is then used as an energy source in the
TCA cycle (Paoli, et al., 2013).
Research Hypothesis and Rationale:
In each of the three clinical trials, the main variable being studied for outcomes was
hemoglobin A1C (HbgA1C). Some other variables observed include: weight loss, waist
circumference, medication discontinuation, While the hypotheses were somewhat different, they
were also similar. The basic hypothesis for each study was: The low-carbohydrate, ketogenic diet
will be effective at lowering HbgA1C as well as improving other outcomes in type 2 diabetic
patients. Vital signs, including heart rate, blood pressure, and blood panels with lipid panels,
kidney function and liver function tests were also performed in each of the three studies. Each
studys hypothesis predicted that the hemoglobin A1C levels of the participants would be
positively affected by a low-carbohydrate, ketogenic diet (Yancy Jr., et al., 2005, Hussain, et al.,
2012, Westman, et al., 2008).
The 2005 and 2008 clinical trials, authored respectively by Yancy Jr., et al., and Westman,
et al., state their hypotheses as: The LCKD may be effective for improving blood-glucose levels
and reducing medications in patients with type 2 diabetes. The primary outcomes measured were
hemoglobin A1C (Yancy Jr., et al., 2005, Westman, et al., 2008). Finally, the third, 2012 clinical
trial, authored by Hussain et al., does not state a specific hypothesis but has the purpose of
understanding the beneficial effects of LCKD) in improving glycemia as measured by
hemoglobin A1C (Hussain, et al., 2012).
Participants:
The three clinical trials included in this paper had varying participants, including different
genders, ethnicities, races, and health indicators. The 2008 and 2012 clinical trials included

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comparison diets. Since this paper is focused on the benefits of the LCKD for people diagnosed
with T2DM, the participants from the LCKD intervention will be the only participants
considered. Because the three studies covered a diverse group of participants, the findings are
relatively generalizable to the public but still have limitations, including age since most
participants are aged from 30 to 60 years old (Yancy Jr., et al., 2005, Westman, et al., 2008,
Hussain, et al., 2012).
In the 2005 clinical trial, 21 participants completed the trial while the 2008 study had 21
complete the LCKD, and the 2012 study had 220 participants complete the trial following the
LCKD. The 2005 and 2012 studies had participants recruited from hospitals, while the 2008
study recruited participants through newspaper advertising and phone screenings. Out of the 21
participants in the 2005 study, 20 of them were male and one was female (Yancy Jr., et al., 2005).
This contrasted significantly from the 2008 and 2012 studies where most participants were
women. 14 out of the 21 in the 2008 trial were women, and 161 were women and 59 were men in
the 2012 trials (Westman, et al., 2008, Hussain, et al., 2012). 13 participants in the 2005 clinical
trial were Caucasian and eight were African American (Yancy Jr. et al., 2005). 14 were
Caucasian and five were African American in the 2008 study with two unspecified, and the
ethnicities and races were left unspecified in the 2012 clinical trial (Westman, et al., 2008,
Hussain, et al., 2012).
The three studies had similar pre-requisites for participants including: being overweight
(BMI over 25kg/m2, fasting serum glucose of over 125mg/dL, and all the participants were
between the ages of 30 and 60 years old. Another key similarity included the three studies
precluding participants with renal insufficiency, liver disease, or unstable cardiovascular disease
(Yancy Jr., et al., 2005, Westman, et al., 2008, Hussain, et al., 2012).

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One of the key differences between the studies includes: the first two studies (2005 and
2008) requiring that participants be diagnosed type 2 diabetic while some of the participants in
the 2012 clinical trial were not diagnosed with type 2 diabetes (Yancy Jr., et al., 2005, Westman,
et al., 2008, Hussain, et al., 2012).
Interventions:
Each of the three clinical trials varied in their interventions, but they also had many
similarities in their design, including: setting of the intervention (free living), diet education,
food records (kept and maintained throughout the studies), and regular check-ins where labs and
bloodwork were collected (Yancy Jr., et al., 2005, Westman, et al., 2008, Hussain, et al., 2012).
The first clinical trial which took place in 2005 included only one group of participants,
and it took place over 16 weeks, while the second two clinical trials from 2008 and 2012 both
lasted 24 weeks and included comparison diets. All trials included participants living freely but
following a low-carbohydrate, ketogenic diet that they received education and guidelines for
effective adherence. The initial carbohydrate goal for each of the three diets included eating less
than 20g of carbohydrates a day. These interventions included unlimited amounts of meats,
poultry, fish, shellfish, and eggs. It also included two cups of salad vegetables, one cup of lowcarbohydrate vegetables, four ounces of hard cheese, no restrictions on fats and oils, and limited
amounts of avocado, cream, lemon juice, and olives. Each of the 21 participants lived freely, but
they were given low-carbohydrate, ketogenic diet counseling, so they could successfully follow a
diet that started off with an initial goal of less than 20g of carbohydrates a day. Medications were
also reduced with insulin doses halved and sulfonylurea doses also halved or stopped altogether.
Each participant was also told to drink six to eight glasses of water a day, exercise aerobically for
30 minutes a day for at least three days a week, and to take a standard multi-vitamin each day. If

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participants in any of the three studies reached half of their goal weight or experienced cravings,
they could increase their carbohydrate intake by five grams a day (Yancy Jr., et al., 2005,
Westman, et al., 2008, Hussain, et al., 2012).
Differences in the interventions between the three studies included: The 2008 study
included the participants receiving nutritional supplements (Vanadyl sulfate, chromium
dicotinate glycinate, and alpha-lipoic acid) (Westman, et al., 2008). The check-in dates also
slightly varied between the three studies, but ultimately each study had the participants check-in
at least every other week for testing and labs.
Results:
Since this paper is focusing on the effects of the low-carbohydrate, ketogenic diet, this
section will focus on the results from the LCKD interventions in each of the three studies. Each
of the three studies found that the LCKD made significant improvements in the primary
outcomes (HbgA1C) measured for patients diagnosed with type 2 diabetes mellitus (Yancy Jr., et
al., 2005, Westman, et al., 2008, Hussain, et al., 2012).
In the 2005 clinical trial, the primary outcome, HbgA1C, decreased relatively by 16% and
absolutely by 1.2%. The baseline HbgA1C of the participants was measured at 7.5% plus or
minus 1.4%, and at the final measurement after the study was concluded, it was measured at
6.3% plus or minus 1.0% (Yancy Jr., et al., 2005). The baseline mean HbgA1C of 7.5% was in
the diabetic range, while the final mean HbgA1C of 6.3% was in the pre-diabetic range. Seven of
the 21 participants discontinued their diabetes medication altogether, and 10 reduced their
diabetes medication substantially. Four participants did not change their diabetes medication
(Yancy Jr., et al., 2005).

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The mean reduction in HbgA1C in the 2008 study was from 8.5% at baseline to 7.5% at the
end of the 24-week study. The American Diabetes Association recommends an HbgA1C of 7%.
The decrease in this study due to the low-carbohydrate, ketogenic diet places the participants
closer to the healthy range. Out of the 21 participants on the LCKD, eight of them were on
diabetes medications at the start of the study. Out of those eight, two were able to discontinue
diabetes medication entirely, and the remaining six were able to decrease their medications
significantly (Westman, et al., 2008).
The mean hemoglobin A1C at the start of the 2012 study was close to 7.9%, and by the
end, it was close to 6.4%, placing it in the pre-diabetic range and in a healthy range for managing
type 2 diabetes. With regards to medications reduction, this clinical trial only states: some
antidiabetic medications were decreased to half in the LCKD group (Hussain, et al., 2012).
Discussion:
The low, carbohydrate, ketogenic diet appears to be an effective way to improve health
status and maintain healthy blood-glucose levels in people diagnosed with type 2 diabetes
mellitus. Each of the three clinical trials discussed in this paper reached this conclusion with men
and women of different backgrounds, races, and ethnicities, aged 30 to 60 years old (Yancy Jr., et
al., 2005, Westman, et al., 2008, Hussain, et al., 2012).
The low, carbohydrate, ketogenic diet appears to not only improve blood-glucose levels, it
also appears to stabilize these levels and reduce the need for exogenous insulin and/or oral
medications such as Metformin. The bodys ability to use ketone bodies as energy in the place of
glucose, appears to limit the bodys production or need for insulin to take glucose out of the
blood since there is a limited amount of glucose being used. Because carbohydrate intake is
restricted, less glucose is ingested and less glucose must travel from the enterocytes of the small

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intestine through the portal vein to the liver and to other tissues in the body. This means less
glucose enters the bloodstream after meals and during times of fasting (Class, 2016). Less
glucose in the blood means it may be easier to establish healthy blood-glucose levels and
maintain them. Still, blood glucose levels must be checked routinely since there is a danger of
hypoglycemia, especially with patients who remain on T2DM medications (Yancy Jr., et al.,
2005).
Another reason the LCKD may be successful in treating people with T2DM could have to
do with the LCKD successfully addressing several of the comorbidities of T2DM. Several of
these comorbidities and how this diet treats them include: obesity by decreasing weight and body
fat, dyslipidemia by improving HDL levels, and hypertension by improving participants blood
pressures (AACE, n.d., Yancy Jr. et al., 2005, Westman, et al., 2008, Hussain, et al., 2012).
Typically, when someone diagnosed with T2DM reduces their weight, improves their blood
pressure, and improves their cholesterol, they also improve their blood glucose levels and help
with disease management (AACE, n.d.). The LCKD accomplished these improvements in each
of the three clinical trials (Yancy Jr., et al., 2005, Westman, et al., 2008, Hussain, et al., 2012).
Something to note with these studies is the number of participants who started out the
clinical trials on the LCKD and the number who dropped out of the trial due to the difficulty of
adhering to the LCKD diet. Seven participants in the 2005 study did not complete the study due
to difficulty adhering to the diet or scheduling conflicts, and five participants in the 2008 study
did not complete the study due to being dissatisfied with the diet or refusing the assigned diet
(Yancy Jr., et al., 2005, Westman, et al., 2008). The difficulty with starting and maintaining the
LCKD should be considered when weighing the diets advantages and disadvantages with
treating people diagnosed with T2DM.

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References Cited:
American Association of Clinical EndocrinologistsAACE Diabetes Resource Center. (n.d).
Retrieved December 5, 2016, from http://outpatient.aace.com/type-2diabetes/management-of-common-comorbities-of-diabetes
By Mayo Clinic Staff Print. (2016). Type 2 diabetes. Retrieved November 26, 2016, from
http://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/dxc20169861
Diabetes Latest. (2014). Retrieved November 26, 2016, from
http://www.cdc.gov/features/diabetesfactsheet/
Gropper, S.S., Smith, J.L., (2013). Advanced Nutrition and Human Metabolism, Sixth Edition.
Belmont, CA: Wadsworth.
Hussain, T.A., Mathew, T.C., Dashti, A.A., Asfar, S., Al-Zaid, N., Dashti, H.M. (2012). Effect of
low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition, 28 (10):
1016-1021.
http://www.sciencedirect.com.proxybz.lib.montana.edu/science/article/pii/S08999007120
00731
Medication. (1995-2016). Retrieved November 25, 2016, from http://www.diabetes.org/livingwith-diabetes/treatment-and-care/medication/
Paoli, A., Rubini, A., Volek, J.S., Grimaldi, K.A. (2013). Beyond weight loss: a review of the
therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of
Clinical Nutrition, 67 (8): 789-796.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826507/
Prediabetes and Insulin Resistance I NIDDK. (2009). Retrieved November 27, 2016, from
https://www.niddk.nih.gov/health-information/diabetes/types/prediabetes-insulinresistance
Westman, E.C., Yancy Jr., W.S., Mavropoulos, J.C., Marquart, M., McDuffie, J.R. (2008). The
effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on
glycemic control in type 2 diabetes mellitus. Nutrition and Metabolism (London), 5 (36)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633336/
Yancy Jr., W.S., Foy, M., Chalecki, A.M., Vernon, M.C., Westman, E.C. (2005). A lowcarbohydrate, ketogenic diet to treat type 2 diabetes. Nutrition and Metabolism (London),
2 (34). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325029/

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