Keywords
ketogenic diet - evolution - diet in diabetes
Introduction
Importance of lifestyle changes, including diet and exercise, has always been undermined
in the management of diabetes, especially in the western literature. The main reason,
often cited, is nonsustainability of these measures. There has been recent evolution
in the literature to challenge this notion. A new approach and a fresh look into the
role of lifestyle change in diabetes care is needed in view of suboptimal response
to current care standards. Even in the best-case scenario, average hemoglobin A1c
(HbA1c) in India among people with diabetes vary between 8.1 and 9.5%, which is far
from optimal levels.[1] This assumes even more significance in view of much earlier onset of diabetes and
increasing life expectancy in India.
Spectrum of Diet
Diets in diabetes care vary in different geographies of world and have been listed
in [Table 1].
Table 1
Macronutrient distribution (as percentage of total daily calories) in different diets
|
Carbohydrates (%)
|
Proteins (%)
|
Fats (%)
|
|
Abbreviations: NIN, National Institute of Nutrition; SAD, standard American diet.
|
|
SAD[2]
|
50–60
|
10–20
|
25–35
|
|
NIN[3]
|
70–80
|
10–20
|
10–20
|
|
Mediterranean[4]
|
30–40
|
20–30
|
30–35
|
|
Paleolithic[5]
|
20–30
|
25–35
|
35–45
|
|
Ketogenic Diet[6]
|
10–20
|
10–20
|
65–70
|
Calorie Restriction
Most common diet that is followed worldwide is the so-called balanced diet with 50
to 70% carbohydrate, 20% proteins, and rest fats.[2] It has been endorsed by institutions such as American Diabetes Association and National
Institute of Nutrition, India.[3] To be effective in the management of diabetes and obesity, it has to be low in calorie.
In a recent study, diet with this macronutrient proportions given with very low caloric
value, has been shown to be very effective.[7] A total of 306 individuals between 20 and 65 years of age, duration of diabetes
less than 6 years, and with body mass index of 27 to 45 kg/m[2] were recruited from National Health Service centers in England and Scotland. Participants
were started on meal replacements with approximately 850 Kcal/day and were subjected
to stepped food reintroduction. At the end of 1 year of intervention, 46% of the participants
achieved diabetes remission, defined as HbA1c < 6.5% for at least 2 months without
any antidiabetic medication. This remission was strongly correlated with weight loss.
Participants who lost 15 kg, 86% of them achieved remission. This study is a significant
step toward establishing diet intervention as a potent tool in the management of diabetes.
It has already been advocated that diet interventions should have a definite role
in the algorithm of diabetes care at par with drugs.[8] However, sustainability of high carb, low calorie diet has always been an issue
and its biological basis for the same are proposed in [Fig. 1].
Fig. 1 Biological basis of failure and nonsustainability of low calorie diet.
Carbohydrate Restriction: Ketogenic Diet
Carbohydrate Restriction: Ketogenic Diet
Evolutionary Endocrinology
Ketogenic diet may turn out be pathophysiologically the most sound way of treating
people with diabetes. Fundamentally, diabetes is the inability of the human body to
take carbohydrate metabolism to its conclusion. This results in the accumulation of
glucose in blood and starvation at the muscle level due to the inability to metabolize
it due to resistance to action of insulin. Diabetes can be forced into remission if
we change the fuel type from carbohydrate to fats. Human body has enough molecular
mechanisms to switch between the fuels. In fact, carbohydrates are the only nutrient
in diet for which no safe lower limit has ever been defined.[9]
Ketogenic Age
Over the periods of evolution, adapting to a particular fuel type has been advantageous.
Right from the eternity till some 8,000 years back, every human being was on ketogenic
diet. People used to hunt and gather and eat food whenever it was available.[10] There was general scarcity of food, and human beings were somewhere in the middle
of the food chain. During lean months with harsh weather, humans would perish of malnutrition
([Fig. 2]).
Fig. 2 Energy metabolism in the preagricultural ketogenic era.
Eumetabolic Carbohydrate Age
As humans started cultivation and included more grains in their food, it gave them
a distinctive survival advantage. It protected them in two ways. First, increased
carb intake allowed their insulin levels to go up and this, in turn, allowed their
bodies to store energy in the form of increased fat generation (lipogenesis) and fat
storage. Second, cultivation allowed them to stay together and at one place; thus,
avoiding other predators on the move ([Fig. 3]).
Fig. 3 Insulin offered survival advantage in the agricultural era.
Cultivation, led by its biological, social, and environmental advantages, changed
the course of human history, and humans thrived to reach on top of the food chain
on this planet. Taking more carbohydrates became ingrained in almost all civilizations
worldwide. This biological switch (from fat as a fuel to carbohydrate as a fuel) continued
to serve a useful purpose till food availability was limited. This all changed with
herald of the industrial era.
Maladaptive Carbohydrate Age
After the industrial revolution, in early 20th century, food scarcity had not been
a problem. We are now living in a world with surplus food. But the same advantageous
biological switch (from fat as a fuel to carbohydrate as a fuel) that was developed
over thousands of year cannot really be switched off in few decades. People held on
to their traditions and carbohydrates stayed as their staple food. But now it is working
to our disadvantage ([Fig. 4]).
Fig. 4 Maladaptive carbohydrate metabolism in modern era.
Pragmatism for the Future
Actually, from this point of view, we do not need insulin anymore as a survival tool.
Insulin would still be required as an essential ingredient of metabolic milieu of
the human body. But taking more carbohydrates and making more insulin inside our bodies
is not helping us anymore. Of course, evolution is going to take its own time to turn
this biological switch off. There are two ways to handle this now. One, we can make
food scarce for everybody and turn the clock back to the preindustrial era. This sounds
a little too harsh and illogical. But, looking around, that is exactly what we have
been doing so far by restricting calories that people eat.
Second option to turn off that switch is by cutting down on carbohydrates that we
take in our diets. Lowering insulin lowers the energy overload in the system and reverses
all metabolic abnormalities ([Fig. 5]).
Fig. 5 Lowering the carbohydrate may hold the key.
Evidence Base
Slowly, but steadily, the literature documenting the efficacy of ketogenic diet in
the management of diabetes has been gathering. Very low carbohydrate ketogenic diets
have consistently showed greater reduction in Hba1c as well as in weight. Few notable
studies have been compiled in [Table 2].
Table 2
Compilation of studies on ketogenic diet for the treatment of diabetes
|
Serial no.
|
Author, country, journal, year of publication
|
No. of patients
|
Intervention
|
Results
|
Adverse effects
|
|
Abbreviation: SAR, serious adverse reaction.
|
|
1
|
Yancy et al, United States, Nutrition and Metabolism, 2005[11]
|
21
|
Low carbohydrate ketogenic diet (LCKD) for 16 wk
|
Hemoglobin A1c decreased from 7.5 ± 1.4% to 6.3 ± 1.0% (p < 0.001). The mean body weight decreased by 6.6% from 131.4 ± 18.3 to 122.7 ± 18.9
kg (p < 0.001)
|
No serious adverse effects reports. One episode of hypoglycemia after missing meal
|
|
2
|
Westman et al, United States, Nutrition and Metabolism, 2008[12]
|
49
|
LCKD versus low calorie diet (LCD)
|
The LCKD group had greater improvements in hemoglobin A1c (–1.5% vs.–0.5%, p = 0.03), body weight (–11.1 kg vs.–6.9 kg, p = 0.008). Diabetes medications were reduced or eliminated in 95.2% of LCKD versus
62% of low–glycemic index diet (LGID) participants (p < 0.01)
|
Headache (LCKD: 53.1%, LGID: 46.3%), constipation (LCKD: 53.1%, LGID: 39.0%), diarrhea
(LCKD: 40.6%, LGID: 36.6%), insomnia (LCKD: 31.2%, LGID: 19.5%), and back pain (LCKD:
34.4%, LGID: 39.0%) (p> 0.05 for all comparisons)
|
|
3
|
Davis et al, United States, Diabetes Care, 2009[13]
|
110
|
Low carb versus low fat diet for 12 mo
|
Weight loss occurred faster in the low–carbohydrate group than in the low–fat group
(p = 0.005), but at 1 y a similar 3.4% weight reduction was seen in both dietary groups.
There was no significant change in A1C in either group at 1 y
|
None reported
|
|
4
|
Saslow et al, United States, JMIR, 2017[14]
|
25
|
LCKD versus American Diabetes Association (ADA) Plate method diet for 32 wk; online
|
At 32 wk, participants in the intervention group reduced their HbA levels1c levels more (–0.8%) than participants in the control group (–0.3%). Participants
in the intervention group lost more weight
|
No SAR reported
|
|
5
|
Hussain et al, Kuwait, Nutrition, 2012[15]
|
363
overall, 102 with diabetes mellitus type 2 (DM2)
|
LCKD versus LCD for 24 wk
|
12% weight loss in LCKD versus 7% in LCD. HbA1c level significantly decreased with
the low-carbohydrate ketogenic diet from 7.8% to < 6.5%
|
No SAR reported
|
|
6
|
Saslow et al, United States, PLOS ONE, 2014[16]
|
44
|
Medium carbohydrate, low fat, calorie–restricted, carbohydrate counting diet (MCCR)
(n = 18) or LCKD, noncalorie– restricted diet (n = 16) for 3 mo
|
Mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased
by 0.6% in the LCK group. Forty-four percent of the LCK group discontinued one or
more diabetes medications, compared with 11% of the MCCR group (p = 0.03)
|
No serious adverse effects reports
|
In a recent study, 262 participants with 8 years duration of diabetes and a baseline
HbA1c of 7.6% were given very low carbohydrate ketogenic diet.[17] Eighty-four percent participants complied with the program at the end of 1 year.
HbA1c decreased from 7.6 to 6.29% and that too with large reduction in the requirement
of antidiabetic drugs. Insulin was eliminated in 47.6% of patients, sulfonylureas
were eliminated in 100% of patients, and other drugs, including SGLT2 inhibitors,
DPP4 inhibitors, and pioglitazone, were eliminated in large proportion of patients.
There was also a reported weight loss of 13.6% at the end of 1 year.[17] A subsequent publication also reported almost 12% risk reduction in 10 years atherosclerotic
cardiovascular disease risk in same the cohort of people.[18]
Even in the general population (without diabetes), decrease in carbohydrate intake
has been shown to be associated with lower all-cause and noncardiovascular mortality
while cardiovascular mortality was unaffected.
Caveats and Concerns
While ketogenic diet seems to be a very attractive alternative for diabetes care,
lack of availability of expertise especially in the Indian subcontinent is a matter
of concern. Common issues faced include low energy levels during the initial 2 weeks
representing the transition phase for fuel switch from carbohydrates to fats. As most
of the treatment algorithms for drug usage in diabetes management are based on presumptive
intake of carbohydrate predominant diet, protocols for using the same drugs on ketogenic
diet are practically nonexistent in the literature. In the long term, proper supplementation
of micronutrients is warranted.
Conclusion
Ketogenic diet is emerging as a powerful lifestyle tool in the treatment of diabetes.
Ketogenic diet seems to have very strong pathophysiological basis to be used as a
therapeutic modality in the treatment of diabetes. This involves inducing a fuel switch
from a dysfunctional carbohydrate metabolism to fat metabolism, for which necessary
molecular mechanisms are already present in the human biological ecosystem. However,
expertise and consensus on nutrition and medicinal protocol need to be developed and
standardized to apply this approach on population in general.
