Article Summary

In the intricate tapestry of human existence, few challenges test one’s resilience and strength like the battle against diabetes. Yet, within the labyrinth of this chronic condition lies a fascinating realm of scientific discovery that may offer hope for those who seek to unlock new avenues of empowerment and control – ketones. 

From taking even a quick look on social media, it’s clear that the “keto” diet is all the rage. It consistently ranks as one of the most popular diets year after year. 

While it has proven successful when followed by otherwise healthy individuals—typically for—the clinical evidence is starting to catch up. Positive findings have been noted for cognitive performance and certain neurological conditions (e.g., concussion, seizure disorder, Alzheimer’s), with recent evidence mounting in support of the ketogenic diet for blood glucose (sugar) control in those with diabetes. 

The one main problem with this plan is the lack of long-term compliance, as many individuals cannot adhere to the requirement of severe carbohydrate restriction. Somewhat less restrictive, modified versions of the ketogenic diet have been proposed, which allow the user to enter into a state of ketosis, but to a lesser degree than when following a strict ketogenic plan.

When adopting a modified approach, exogenous ketone use (ketone supplements) may be considered. These ketone aids can rapidly elevate blood ketones, reduce blood glucose, and possibly enhance insulin sensitivity (which is vital for optimal glucose control). 

Additionally, exogenous ketones have been reported to reduce hunger and the desire to eat, which may lead to weight/fat loss over time—a highly desired outcome for an individual with diabetes. 

If choosing to use exogenous ketones, the ester form results in a greater elevation in blood ketone levels as compared to ketone salts, and the monoester form may also result in greater effects pertaining to blood glucose lowering. 
Tecton’s ketone esters have been reported to be safe for oral ingestion at relatively high dosages and appear well-tolerated even when used multiple times daily.

Introduction to Ketones and Diabetes

Diabetes (mellitus) is a condition in which the body cannot produce enough (or any) insulin or cannot properly utilize the insulin that is produced. 

Insulin is a hormone that serves multiple bodily functions, one of which is to promote glucose uptake from the bloodstream into cells. It works through a complex series of “signaling” events that ultimately allow transport proteins to bind glucose and transport it inside the cell to be used as fuel or stored for later use.

Hence, having inadequate or poorly functioning insulin (or the “signaling” of insulin) can lead to defects in glucose disposal, resulting in elevated glucose within the blood and cells without adequate energy to function properly.

Chronically elevated fasted blood sugar leads to the diagnosis of pre-diabetes (100-125 mg/dL) or diabetes (≥126 mg/dL). 

There are multiple health complications of diabetes, including compromised blood flow, amputations, impaired vision and blindness, kidney damage, peripheral neuropathy, elevated risk for heart disease, sexual dysfunction and skin problems. 

The good news is that most individuals (those with Type 2 diabetes in particular) can avoid these problems through lifestyle modifications. 

Types of Diabetes

Diabetes presents in three primary forms: Type 1, Type 2 and Gestational. Type 1 diabetes is thought to be an autoimmune condition where the pancreatic beta cells—those that produce the hormone insulin—are damaged. This typically manifests early in life. Those with Type 1 diabetes use supplemental insulin daily to stay alive. Type 1 diabetes accounts for approximately 5% of cases in the United States. 

Type 2 diabetes usually starts as a state of insulin resistance. That is, the pancreas produces insulin, but it does not work very well (there are many reasons for this). The result is elevated blood sugar. This typically occurs later in life (over age 45), but younger people can also be diagnosed. This may be due to various factors, including a sedentary lifestyle, high sugar and saturated fat intake, and an obese state. Type 2 diabetes accounts for approximately 95% of cases in the United States. 

Gestational diabetes is diagnosed during pregnancy. It is thought to be caused by the hormonal milieu seen during pregnancy. Approximately 6-8% of pregnant women develop gestational diabetes. Of those, an estimated 50% of women go on to develop Type 2 diabetes. 

Finally, although not associated with a defect in blood sugar regulation, we should mention diabetes insipidus. This is an uncommon disorder stemming from kidney dysfunction that leads to an imbalance of fluids within the body. This results in the production of large amounts of urine, which increases the risk of dehydration and electrolyte loss. 

Lifestyle Factors to Control Diabetes and Aid Blood Glucose Regulation

It has been well-documented that certain lifestyle factors can significantly aid in the control of elevated blood sugar and associated signs and symptoms of diabetes, including:

• Reducing stress (as stress can impair insulin sensitivity)
• Obtaining adequate sleep (as fatigue can impair insulin sensitivity)
• Consuming little or no alcohol
• Quitting smoking 
• Being physically active
• Engaging in a program of structured exercise, and 
• Consuming a nutrient-dense diet. 
• Avoiding sugary, caffeinated drinks 

While these factors can help those with Type 1 diabetes, most research has concentrated on people with Type 2 diabetes. And while all of the above are important, those that appear to receive the greatest attention from clinicians and the lay press alike are physical activity/exercise and dietary intake.

Physical Activity and Exercise for Diabetes

First, we must remember that physical activity and exercise are not necessarily the same. The intensity at which the activity is performed is the differentiator. 

For example, taking a leisurely walk, doing chores around the house, and gardening outdoors are examples of physical activity. They allow for bodily movement and some caloric expenditure. However, they are performed at such a low perceived effort that they do not meet the definition of exercise for most individuals (which has been cited as approximately 50% or more of one’s VO_2max—or the maximum aerobic capacity). 

On the other hand, exercise is planned, structured, repetitive and performed at a level of effort much higher than physical activity. This may include running, indoor cycling, stair climbing, lifting weights and similar activities. The effort is high, and the work is continuous for 30 minutes or more, ideally performed four or more days per week. The goal of exercise is to improve one’s fitness level (e.g., muscular strength or power, muscular endurance, cardiovascular endurance).

Both exercise and physical activity should be a part of every person’s routine, particularly if they have a diagnosis of pre-diabetes or diabetes. This is because skeletal muscle contraction has an “insulin-mimicking” action or insulin-independent effect that allows glucose to be taken up from the blood into cells. The degree of glucose clearance seems dependent on the amount of muscle mass used and the type, intensity and duration of exercise.

Because exercise reliably improves insulin sensitivity, in addition to favorably impacting other cardiovascular risk factors associated with diabetes, The American College of Sports Medicine views it as one of the principal therapies in diabetes treatment and should be a first-line defense strategy for anyone diagnosed with this disease. 

While this effect of exercise is welcome, the changes are short-lived. Regular exercise (perhaps daily or multiple short daily sessions) is warranted for optimal glucose control and disease management.  

Dietary Intake for Diabetes Management

Aside from exercise, dietary intake is viewed as most important in preventing and managing diabetes. Much research has focused on the role of dietary manipulation in improving blood sugar control and insulin resistance.

Specific to this, multiple dietary approaches have been used with success, including the consumption of small and frequent macronutrient-balanced meals throughout the day, plant-based diets, low-fat/high-carbohydrate diets and the high-fat ketogenic diet. While favorable effects have been observed with many different plans, and each person needs to determine what works best for them and their lifestyle, the ketogenic diet has received considerable attention in recent years from both clinicians and scientists. 

Let us explore an overview of work in this area. 

The Ketogenic Diet and Diabetes

Most people are familiar with the word “keto” in reference to the well-studied ketogenic diet. While there are variations of the plan, the standard ketogenic diet involves severe restriction of dietary carbohydrates (e.g., bread, rice, pasta, fruit) to approximately 30-50 grams per day. This small amount of carbohydrate will usually be ingested as part of other fat- and protein-containing foods, with the exception of some green vegetables. 

The majority of the keto diet is comprised of fat (usually about 60% or more), with protein adding the balance and a small amount of carbohydrates. Therefore, the diet usually consists of meat, fish, eggs, certain cheeses, plain yogurt, oil, avocado, nuts, seeds and some green vegetables.

The ketogenic diet has increased considerably in popularity over the past few years. Millions of individuals use it for weight loss, cardio-metabolic benefits, and enhanced mental focus. 

Although a very high-fat diet by definition, the keto diet has many proven health benefits, including: 

• Favorable changes in cardio-metabolic parameters
• Improvements in glycemic control 
• Possible increased genetic diversity of the microbiome 

The diabetic community is particularly interested in restricted carbohydrate intake, which is a hallmark of the keto diet. In fact, lower carbohydrate ketogenic diets have been used to treat diabetes since the late 19^th century.

When adhering to such a plan, a low and stable concentration of blood glucose and insulin is observed, which is helpful for people with diabetes. When carbs are restricted, blood glucose and insulin levels naturally lower. Then, the body breaks down stored fats and releases the fatty acids into the bloodstream. From there, they are transported to the liver to be converted into ketones. 

The ketones can then be released from the liver and travel in the bloodstream to various tissues to be used as a fuel source. This is what most people desire when adopting a ketogenic diet—to burn their stored body fat as a fuel source rather than consuming additional calories in the form of carbohydrates. 

For people with diabetes, a reduction in stored body fat may lead to an improvement in insulin sensitivity, which should aid overall blood glucose control. 

The efficacy of the ketogenic diet extends beyond acute blood glucose, with benefits observed for long-term glucose regulation (HbA1c), body weight and blood lipids. 

Moreover, the overall disease treatment cost may be less when incorporating this dietary approach than routine medical therapy alone, as many patients may require less medication because of their diet-induced glucose control. 

Many ketogenic diets have been very low calorie and met with excellent results. Studies have shown people to maintain muscle mass and strength, preserve resting metabolic rate, and experience no negative impacts on hunger and mood. A recent systemic review and meta-analysis concluded that the ketogenic diet is more effective than a traditional low-carbohydrate diet. However, people with diabetes should practice them with caution, ideally under the guidance of a qualified healthcare provider.

While the data are encouraging for people with diabetes seeking improved blood sugar control, one concern has been repeatedly raised: Many people cannot adhere to a strict ketogenic diet, because it is extremely difficult to avoid carbs – they are in almost every processed food.

So, some have considered adopting a modified form of the ketogenic diet, which is not as restrictive. Such an approach may consider using external “exogenous” ketones to aid their success.

Exogenous Ketones and Diabetes

So, what is the connection between diabetes and ketones that are produced exogenously, meaning outside the body?

Similar to the ketogenic diet, ketone aids have gained a great deal of attention in recent years. These are often referred to as dietary exogenous ketones (those coming from outside the body) instead of endogenous ketones (those produced in the liver). 

Exogenous ketones have a great deal of clinical potential. For example, they may lower blood glucose, which may serve as an impetus for endogenous ketone production. 

The glucose-lowering effect appears related to enhanced insulin signaling, an effect that has been known for many years. The therapeutic potential of exogenous ketones was highlighted in a recent review, in which the authors stated, “The recent advent of exogenous oral ketone supplements represents a novel, non-pharmacological approach to improving Type 2 diabetes pathophysiology and potentially protecting against cardiovascular disease risk.”

While many studies have focused on glucose control in a fasted state, what may be more relevant is how exogenous ketones can impact blood glucose in a fed state. 

A recent study addressed this. Investigators noted a significant reduction in the glucose area under the curve when participants consumed ketone esters 30 minutes before a standard glucose tolerance test (75 grams). 

The glucose-lowering effect appeared related to an improvement in markers of insulin sensitivity—a welcome finding, particularly for those with diabetes. However, this study used a sample of healthy men and women. Such work needs to be replicated in a sample of people with diabetes. 

Lastly, if using exogenous ketones, it may be best to use what is known as the ester form, as these have been reported to result in a more rapid and significant elevation in blood ketone levels as compared to ketone salts. In addition, greater effects pertaining to blood glucose-lowering have been observed with ketone monoesters as compared to ketone salts. 

What about Diabetic Ketoacidosis and Other Concerns?

The ketogenic diet and the use of exogenous ketones may be considered components of a diabetes treatment plan. Still, a few things need to be considered. 

First, it is crucial to start any new diet or supplemental aid under strict medical supervision, as blood glucose will likely be altered. Your doctor may need to modify the dosage of diabetic medications.

Second, people with diabetes must consider how a daily dose may impact their blood sugar and interact with current medications. Regarding the safety of ketone ester use, Tecton’s esters have been evaluated and reported to be safe for oral ingestion at very high dosing. 

Third, some have suggested that a ketogenic diet or using ketone aids could lead to “ketoacidosis.” For those who are not familiar with this term, ketoacidosis is a serious medical complication of diabetes in which excess endogenous ketones are produced, leading to a buildup in the body, which can lead to various pathological complications.

While ketoacidosis is most prevalent in those with Type 1 diabetes, particularly those younger, it can also develop in those with Type 2 diabetes. This is one reason why those with diabetes must speak with a medical professional before changing their diet.

Beyond ketoacidosis, when adhering to a ketogenic diet or using ketone aids, there is a risk for hypoglycemia (blood sugar being too low), as well as dyslipidemia (altered blood lipids). For those interested in the manipulation of ketones, it is essential to test blood sugar regularly in addition to testing for ketones, which can easily be done by using a personal test kit. 

As mentioned earlier, adjusting the dosage of insulin and other oral diabetic drugs may be necessary when taking exogenous ketone. It should only be done under the guidance of a qualified healthcare provider. 

Finally, it is important to remember that not all exogenous ketones are the same. For example, ketone salts may lead to an abundance of sodium intake, which may negatively impact the health of those with diabetes. When considering diabetes and ketones, remember that quality matters greatly in choosing an exogenous ketone.