Ketogenic Diet for the Management of T2D and Associated Long-Term Complications

The ketogenic diet has been a mainstay for the management of multiple chronic conditions dating back to the 1920s, when prior to the introduction of anticonvulsant drugs, a diet consisting of increased fat and low carbohydrates was used as a treatment for epilepsy in children.¹  Dietary restriction was also used in diabetes prior to the discovery of insulin for the management of both type 1 (T1D) and type 2 diabetes (T2D), as the 2 types were indistinguishable from one another at the time.² Once insulin was discovered, the need for dietary interventions decreased. Over the years, numerous pharmacologic agents have been introduced and widely touted for their superiority in managing this chronic condition. Despite the variety of therapeutic and curative roles foods have, it seems that diet has become a last resort rather than a first-line treatment in disease management.

With obesity reaching epidemic proportions and its known association with T2D, dyslipidemia, hypertension, and atherosclerosis, it is worthwhile to consider nutritional approaches to managing these chronic conditions. With such heavy reliance on and cost attributed to the pharmaceutical industry, chronic disease management through diet could prove to be a relevant area for ongoing research and clinical practice.

Although in prior years the standard approach to diabetes management from the American Diabetes Association (ADA) included dietary interventions, caloric restriction, and low-fat food choices, more evidence supports promising results in individuals who consume various versions of a ketogenic diet, characterized by low-carbohydrate intake, moderate protein intake, and high-fat intake.

The rationale for using a high-fat, low-carbohydrate diet in the management of a chronic disease such as diabetes is that it places the body in a state of ketosis causing fat — rather than sugar — to be used as a primary source of fuel for the brain and other organs, thus decreasing reliance on glucose as a fuel source. The ketogenic diet produces metabolic changes often associated with the starvation state, a mechanism that was used in biblical times for seizure management.^3-5 When the body is deprived of carbohydrates, fatty acids and ketones (from dietary fat and adipose stores) become the body’s main fuel source. If the body does not consume dietary carbohydrates, the liver and kidneys can produce about 200 g/d of glucose from dietary protein and fats and will serve as a source of energy for glucose-dependent tissues, while the rest of the body will use ketones and fatty acids.^3,4

The purpose of this review is to evaluate the current research in diabetes management with a ketogenic diet and to explore its effectiveness, as well as any opportunities for future research.

Systematic literature searches were conducted to explore the correlation between diabetes mellitus and ketogenic diets. Searches were performed in Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Biomedical Reference Collection, PubMed, and Google Scholar databases. Keywords used in the searches included ketosis and metabolic changes; impact of ketogenic diet; diabetes management; and variations of ketogenic diets, diabetes management, and uses of ketogenic diet. Articles reviewed were from 2008 through 2017.

Types of Ketogenic Diets

There are 4 distinct variations of the ketogenic diet (Table 1).⁶ First is the classic ketogenic diet, which is high in fat and low in carbohydrates. The classic ketogenic diet is usually a 4:1 or 3:1 ratio of fat to carbohydrate with almost 90% of the total required calories derived from fat. The classic ketogenic diet has been defined as <130 g of carbohydrate (or 26% of caloric intake).^3,4,6

A second variation of the ketogenic diet is the medium-chain triglyceride (MCT) diet, which allows more liberal amounts of carbohydrates. MCT are used instead of long-chain triglycerides (LCTs) as the major source of fat. MCT oil supplements (such as coconut) are most commonly used because they yield more ketones per unit and are more efficiently absorbed and carried directly to the liver. The main concern with the use of MCT oil is that it is expensive and not palatable.^3,6,7

A third type of ketogenic diet is the low-glycemic-index treatment (LGIT) in which selected carbohydrates are restricted, allowing for liberal fat and protein intake. LGIT (considered more tolerable than the classic ketogenic diet) recommends the consumption of carbohydrates that have a glycemic index of less than 50, achieved by the consumption of more lentils, whole wheat bread, and citrus fruits rather than potatoes and white bread.^3,6,7 There is no restriction of fluids, protein, or calories, and ketones are not monitored.^3,6,7

A fourth variation of the ketogenic diet is the modified Adkins Diet (MAD), which restricts consumption of carbohydrates and endorses liberal consumption of fats and proteins.  First used in 2003, the MAD was found to be less restrictive than the classic ketogenic diet.³ With the MAD, carbohydrates are restricted to 15 to 20 g/d with most dietary intake focused on high-fat foods. Typically the caloric breakdown of MADs is 65% from fats, 30% from proteins, and 6% from carbohydrates.^3,4,6,7

Each variation is designed to create a state of ketosis, which is most effectively determined through physiologic testing.  It is also important to keep in mind that ketosis is very different from ketoacidosis, which is a complication of T1D resulting from dangerously high levels of ketones and blood sugar. In ketosis, higher levels of ketones can be detected in the urine or blood. Although urine testing for ketosis is the most common and feasible approach for assessing diet adherence, there is widespread disagreement regarding which method of assessment is more effective. In an experimental intervention conducted by Urbain and Bertzt to determine the best time to test for ketone concentrations, it was found that stable ketosis can be most reliably detected in the first morning urine and several hours after dinner late in the evening.⁸