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Ketogenic Diets for Diabetes Mellitus and Obesity

By: Anna Chen, PharmD Candidate c/o 2020

Every day the public faces an onslaught of a new fad diet that promises to prevent boredom and the feelings of restriction that regular diets are famous for. One example is the banana diet that promises to keep one satiated with the high volume and fiber content of bananas to kill cravings for unhealthy snacks. Some followers have taken this diet to the extreme of eating only bananas to quickly reduce weight. However, one famous fad diet, the Atkin’s Diet, has shown great potential to be a primary option of therapy for patients suffering from obesity or diabetes. The Atkin’s Diet is a type of ketogenic diet that focuses on a low carbohydrate and high protein and fat intake to induce the body to utilize ketosis to burn fat when the supply of readily available carbohydrates is low. There is evidence that the unique aspects of drastically reducing carbohydrate intake help patients with glucose metabolism and decrease lipid levels more so than traditional low calorie diets that do not restrict carbohydrate intake. When used appropriately, ketogenic diets have shown to be safe to use and tolerable in addition to being more effective than traditional low calorie diets.

A controlled study of 9 lean men placed on a ketogenic diet for 4 weeks, showed a 15% reduction in blood glucose and 30% reduction in whole body glucose metabolism.1 Since the bulk of the experiment diet consisted of protein and fats, meals were prepared with chicken breast, tuna fish, eggs, cheddar cheese, ground beef, sour cream, cream cheese, and mayonnaise.1 Thus, the sources of protein and fat in ketogenic diets are still chosen in a health conscious way in that dieters would still stray away from trans fats and unhealthy junk food. However, the main pillar of such ketogenic diets are reducing carbohydrate intake to less than 20g per day. Studies were then made to see whether it was ketosis, the burning of fat over carbohydrates, that was responsible for the beneficial effects of ketogenic diets. One study hypothesized that ketosis was responsible for a reduced hepatic glucose output in patients with Type 2 diabetes when placed on ketogenic diets. The study observed 13 obese Type 2 patients over 6 weeks with two diets of equal caloric intake and high protein intake (55%) but different carbohydrate intake. One of the diets incorporated a low amount of carbohydrates and the other a high amount of carbohydrates to induce high levels of ketosis and low levels of ketosis respectively.1 Overall even with similar weight loss, the low carbohydrate diet had beneficial effects of lowered blood glucose, better glucose tolerance without affecting plasma insulin, and faster decrease in hepatic glucose output. With the only difference being that the diet having lower carbohydrates and therefore higher levels of ketosis activity indicates that the effects of ketosis and low carbohydrate intake are crucial in improving glucose metabolism in patients regardless of weight loss.

A study of 64 obese subjects all having a body mass index (BMI) greater than 30 were divided into two groups based on whether they had a normal blood glucose levels (5.127 ± 0.440 mmol/l) or high blood glucose levels (10.481 ± 3.026).2 Both groups were  put on the same ketogenic diet for 56 weeks. Similar to the previously mentioned studies, the group with high blood glucose levels observed fasting blood glucose levels decreased from 10.481 ± 3.026 mmol/l to 4.874 ± 0.556 mmol/l;2 thus, solidifying ketogenic effects on high blood glucose. The levels of HDL cholesterol were shown to increase from 1.033 ± 0.264 mmol/l to 1.586 ± 0.211 mmol/l and levels of LDL cholesterol decreased from 5.160 ± 0.892 mmol/l to 3.379 ± 0.608 mmol/l.2 These results put the subjects at a lower risk of cardiovascular disease as well as events such as myocardial infarctions. Similar increase in HDL and decrease in LDL were shown in those with normal blood glucose levels and with relatively no change in blood glucose levels in the same patients.2 The unchanged glucose levels in the group with normal blood glucose levels calls into question the claim that diets low in carbohydrates and high in fat may be harmful and induce insulin resistance. The lowered risk of cardiovascular disease is strongly correlated from the changed body composition as subjects showed “a preferential loss of fat mass and preservation of lean body mass following the administration of ketogenic diet.”2

In regards to the safety and tolerability of ketogenic diets, a study in Spain was done on 89 patients with Type 2 Diabetes in a randomized weight loss intervention program that included lifestyle support to compare the effects of a very low carbohydrate-ketogenic diet (VLCK) as compared to a standard low calorie (LC) diet. The study extended for a period of 4 months and showed that the VLCK group showed more significant improvements in weight loss, insulin sensitivity, triglyceride levels, and HbA1c levels than the LC group.3 Since a main pillar of the ketogenic diet consists of large protein intake, there are concerns that the high protein content would exacerbate patients with albuminuria or nephropathy to renal failure. Although the exact macro nutrient goals of patients with diabetes are yet to be known, the 30-53% protein in the daily ketogenic patient diet showed no negative effects on albuminuria nor on plasma creatinine levels within the 4 month period.3

The one possible drawback identified in the Spain study was the 80% of the VLCK patients reporting mild adverse events compared to only 41% of the LC patients.3 The mild adverse events consisted of headache, nausea, orthostatic hypotension, and constipation.3 However, more patients were able to stick through the VLCK diet to the end compared to the LC diet and 92.5% of VLCK patients deemed the program satisfactory compared to just 68.5% of the LC patients.3 A similar study comparing the effects of traditional low calorie vs. low carbohydrate in patients with Type 2 diabetes in Kuwait found a low carbohydrate diet to give more significant benefits but recommended that patients be placed on strict medical supervision as glucose levels start decreasing in patients.4 The same study found that physicians  were able to decrease anti-diabetic medications in patients on the low carbohydrate diet due to better glycemic control.4 Thus, in addition to the previous study that extended for 56 weeks, a ketogenic diet is acceptable for both short and long term use in patients with diabetes.

Contrary to the previous three studies mentioned, a ketogenic diet can be utilized as a treatment plan without extensive observation or doctor visits. An online intervention study randomized 25 patients with type 2 diabetes into a ketogenic diet (n=12) or a standard low fat diet (n=13) for 32 weeks.1

Through patient self-reporting, researchers found no statistically significant signs of diabetes related distress nor depressive symptoms within the two groups.1 However, patients in the ketogenic diet reported that they would be less likely to cheat on their diets compared to those in the standard diet and gave high ratings in categories including better attitudes on the ketogenic diet and beneficial outlooks to their improved physical health.1 Not unlike the studies previously described, the online intervention study found more significant results in the ketogenic diet compared to the standard diet that include reduced HbA1c levels, greater weight loss, and reduced triglycerides.1 The limitations to online studies and patient self-reporting notwithstanding, the data obtained and particularly its congruence with evidence from the other studies, asserts that ketogenic diets are a substantial form of therapy.

The win-win situation with both improved glucose metabolism and decreased triglyceride levels from a ketogenic diet is phenomenal for treating patients suffering from obesity or diabetes. A ketogenic diet is also compatible with regular medications as the patients in the online intervention study were still on prescribed metformin while on the ketogenic diet. Only one patient experienced an adverse event due to hypoglycemia from taking a dose of metformin.5 Moreover, the ketogenic diet does not have to be a permanent lifestyle commitment as the patients in the Goday A, Bellido D, Sajoux I, et al. study were transitioned to a less restrictive lifestyle with nutritional counseling after reaching weight loss goals.3 This novel diet is an answer to the call for a diet that is more effective than standard diets in granting long term results while being satisfying enough to keep patients both interested and committed to a form of therapy.

SOURCES:

  1. Mobbs CV, Mastaitis J, Isoda F, Poplawski M. Treatment of diabetes and diabetic complications with a ketogenic diet. J Child Neurol. 2013;28(8):1009-14. doi: 10.1177/0883073813487596
  2. Dashti HM, Mathew TC, Khadada M, et al. Beneficial effects of ketogenic diet in obese diabetic subjects. Mol Cell Biochem. 2007;302(1-2):249-56. Epub 2007 Apr 20.
  3. Goday A, Bellido D, Sajoux I, et al. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr Diabetes. 2016;6(9):e230. doi: 10.1038/nutd.2016.36.
  4. Hussain TA, Mathew TC, Dashti AA, Asfar S, Al-Zaid N, Dashti HM. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition. 2012;28(10):1016-21. doi: 10.1016/j.nut.2012.01.016
  5. Saslow LR, Mason AE, Kim S, et al. An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial. J Med Internet Res. 2017;19(2):e36. doi: 10.2196/jmir.5806.
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