Ketogenic Diets in the Management of Type 1 Diabetes: Safe or Safety Concern?

Editor’s note: This is an abridged version of an article originally published in the Cleveland Clinic Journal of Medicine. The article in its entirety, including a complete list of references, can be found here.

By Lauren Anne Buehler, MD, MPH, Dawn Noe, RDN, LD, CDCES, Shannon Knapp, BSN, RN, CDCES, Diana Isaacs, Pharm D, CDCES and Kevin M. Pantalone, DO, ECNU, FACE

Ketogenic diet and diabetes type

Ketogenic diets have risen in popularity in recent years as a strategy for weight loss and treatment of a variety of diseases. For patients with Type 2 diabetes mellitus (T2DM), the diet can lead to clinical improvement, including better glycemic control, lower cholesterol and weight reduction.

The diet is also becoming popular among patients with Type 1 diabetes, but its clinical impact remains unclear, as much of the literature consists of retrospective case reports and series. The subject has not been well investigated, likely because of concern about inducing ketoacidosis and hypoglycemia in patients already at high risk for these complications.

This article reviews potential risks and benefits of a ketogenic diet for managing Type 1 diabetes based on available evidence.

Ketogenic diet parameters

Ketogenic diets are generally high in fat (60%–85%), moderate in protein (15%–30%), and low in carbohydrates (5%–10%). This leads to the body using fat as its principal energy source.

Common misconceptions about ketogenic diets are that followers can consume few vegetables and must eat excessive amounts of meat. But a well-formulated diet can incorporate a variety of protein-containing foods, including fish, cheese and Greek-style yogurt. The diet may also include four or five servings of vegetables daily, which contain about 20 to 30 grams of carbohydrate in total; hence, the low amount of allowable carbohydrate may be obtained entirely from vegetables. Fat calories can also come from plants and fish that are on the Mediterranean diet, such as olives, olive oil, nuts, seeds, avocado, tuna and salmon.

Biochemistry of ketosis

Under normal physiologic circumstances, glucose is the main substrate for glycolysis, resulting in the production of adenosine triphosphate (ATP), the body’s main energy source. Under circumstances of starvation or dietary carbohydrate restriction, the body breaks down glycogen (i.e., the storage form of glucose) in the liver to provide the body with glucose.

In a prolonged fasting or carbohydrate-restricted state (> 48–72 hours), liver glycogen stores become depleted. Without glucose as a substrate for ATP production, the liver breaks down triglycerides to make ketone bodies that travel to target tissues (e.g., brain, muscles) and ultimately generate ATP. This process of ketogenesis is regulated by insulin; low carbohydrate intake leads to low insulin levels, promoting ketosis.

Monitoring ketones

For patients with Type 1 diabetes, monitoring ketones is important to identify and prevent diabetic ketoacidosis (DKA). Three types of ketone bodies, resulting from the liver metabolizing fatty acids, are measured in different ways, each with advantages and disadvantages: acetone, acetoacetic acid and beta-hydroxybutyrate.

Diligent and more frequent blood glucose monitoring should be a mainstay in patients with diabetes on a ketogenic diet. Although euglycemic DKA is possible while following a ketogenic diet, blood glucose levels above 250 mg/dL may be seen and are a sign of potential DKA.

Glucose monitoring can also be helpful for preventing hypoglycemia, a potential consequence of reduced carbohydrate intake. Clinical studies indicate that a continuous glucose monitor (CGM) can be a useful tool in reducing hypoglycemia.

Adjusting diabetes therapies

In clinical practice, it is not uncommon to escalate basal insulin rather than add or increase bolus doses, thus allowing the long-acting insulin to cover some or all of a patient’s post-meal insulin needs. In such cases, excessive basal coverage can increase the risk of hypoglycemia when a patient reduces mealtime carbohydrate intake when starting a ketogenic diet. Furthermore, many people with Type 1 diabetes have an elevated BMI, and insulin resistance is expected to improve and insulin requirements decrease as weight is lost on a ketogenic diet.

How to adjust insulin

Insulin dosages usually need to be reduced after starting a ketogenic diet; in Type 1 diabetes, this usually entails decreasing the amount of insulin received per gram of carbohydrate. The following strategy can be used:

• If a patient’s HbA1c is near target, the daily dosage of basal insulin may need to be decreased by 10% to 20%.
• If the HbA1c is elevated, no adjustments may be required.
• It is often safest to adjust insulin with the aim of reducing the risk of hypoglycemia; the patient can be instructed to take additional correction doses of short-acting insulin to address hyperglycemia.
• Insulin dosages often need to be adjusted weekly in the initial stages as weight loss and adherence to the ketogenic diet will impact the necessary insulin adjustments, and these factors are highly individual.

Other diabetes medications

Usually with the aim of weight loss, many patients with Type 1 diabetes also take medications off-label that are approved by the US Food and Drug Administration for Type 2 diabetes, including metformin, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists.

SGLT-2 inhibitors are associated with an increased risk of euglycemic DKA, particularly in Type 1 diabetes. This may occur through multiple mechanisms, including reduction in insulin-mediated suppression of lipolysis and ketogenesis, volume contraction, promotion of glucagon secretion and decrease in renal clearance of ketone bodies. Accordingly, SGLT-2 inhibitors should be stopped before starting a ketogenic diet owing to the risk of DKA that often presents as euglycemic, making it difficult to recognize.

GLP-1 receptor agonists, when used in Type 1 diabetes, may increase the risk of hypoglycemia and DKA. They can be continued with close monitoring in patients following a ketogenic diet, although some providers prefer to stop them.

Metformin is generally considered safe to continue.

Blood glucose control: A balancing act

Optimizing glycemic control in Type 1 diabetes can be extremely challenging but is essential to prevent life-threatening, short-term complications such as DKA. Long-term glycemic control is also important to reduce the risk of microvascular complications (neuropathy, retinopathy and nephropathy) and perhaps macrovascular complications (stroke, coronary artery disease and peripheral vascular disease). However, preventing hyperglycemia comes with the risk of inducing frequent or severe hypoglycemia, which can lead to lower quality of life, hospitalization, coma and death.

Much of the challenge in maintaining euglycemia in patients with diabetes lies in the difficulty in matching carbohydrate intake with insulin administration, owing to errors in estimating the carbohydrate content in meals, variable insulin absorption, timing of insulin administration and gastroparesis. Given these complicating factors, it is plausible that low carbohydrate intake and resulting lower prandial insulin bolus requirements may lead to better glycemic control, less blood glucose variability and improved quality of life.

Efficacy and safety

Before the adoption of insulin as the gold standard treatment for Type 1 diabetes, diet was one of the few therapy options available. In the early 20th century, the use of a very low-calorie, low-carbohydrate diet was used experimentally to manage it.

The existing literature regarding the use of the ketogenic diet in Type 1 diabetes is limited and has yielded mixed results. Many of the publications are case reports, and the majority are from the pediatric population for the treatment of medication-refractory epilepsy. The few studies are mostly observational and vary considerably in terms of the dietary macronutrient composition, making it difficult to generalize their results. Data on long-term cardiometabolic effects are also limited.

Further research is needed on the efficacy and safety of the ketogenic diet in patients with Type 1 diabetes. The diet may be appropriate for select patients, but only after a thorough discussion between patient and care team about the risks and benefits. A registered dietitian and specialists in diabetes care, education, endocrinology and pharmacy should be part of any discussion. For patients on the diet, extra monitoring is critical, preferably with a CGM.