Objective
The Steno 1 Continuous Ketone Monitoring (CKM) substudy is designed to better understand ketone levels in adults with type 1 diabetes (T1D), especially those receiving modern heart- and kidney-protective treatments such as SGLT inhibitors (SGLTi) and GLP-1 receptor agonists (GLP-1RA).
Primary goal:
To describe how ketone levels change over time under different treatment strategies and how often moderate to high ketone levels occur.
Secondary goals:
To compare the frequency of elevated ketones between people receiving standard care and those on intensified treatment.
To compare ketone patterns within different treatment approaches among those receiving intensified therapy.
To assess whether certain ketone thresholds can predict the risk of developing diabetic ketoacidosis (DKA).
To explore how ketone levels relate to blood sugar patterns.
To investigate whether long-term exposure to ketones is linked to heart or kidney health outcomes.
By achieving these objectives, the CKM substudy will provide new, real-world knowledge about ketone patterns in people with T1D. This will help doctors and patients use newer therapies more safely, prevent complications like DKA, and improve long-term heart and kidney health.
Background Rationale
Adults with type 1 diabetes (T1D) face a high risk of serious heart and kidney problems, even when their blood sugar is well controlled. These complications can lead to hospitalizations, reduced quality of life, and premature death. Newer treatments have been shown in type 2 diabetes to protect the heart and kidneys. Early evidence suggests that people with T1D may also benefit from these medications. However, these therapies carry a risk of diabetic ketoacidosis, a potentially life-threatening condition caused by high levels of ketones in the blood. Currently, ketone levels are only measured when symptoms occur, using intermittent blood or urine tests. This approach can miss early or symptom-free rises in ketones, making it difficult to fully understand the safety of these medications in T1D.
The Steno 1 study is investigating whether an intensified, multifactorial treatment approach can reduce heart and kidney complications in adults with T1D. The CKM substudy, embedded within this larger study, focuses specifically on continuous ketone monitoring. By tracking ketone levels around the clock in participants’ daily lives, the substudy aims to provide a detailed understanding of how ketones behave under different treatment strategies.
This information is critical for improving safety and guiding clinical decisions. Understanding ketone patterns will help identify early warning signs of DKA, inform the safe use of newer therapies, and ultimately support better long-term heart and kidney health for people with T1D. The CKM substudy addresses a major knowledge gap and provides real-world data that are urgently needed by clinicians, researchers, and regulators.
Description of Project
Adults with type 1 diabetes (T1D) and established cardiovascular or kidney disease are at very high risk of serious complications and premature mortality. Novel glucose-lowering and organ-protective therapies have the potential to substantially reduce this risk. However, their implementation in T1D is limited by concerns regarding diabetic ketoacidosis (DKA), a rare but potentially life-threatening complication associated with elevated ketone levels.
Currently, ketone monitoring in T1D is largely symptom-driven and based on intermittent blood or urine measurements initiated by the individual. This approach provides limited and unsystematic information on ketone dynamics in daily life and may fail to detect early or asymptomatic ketonaemia, particularly during intensified treatment regimens.
The Steno 1 Continuous Ketone Monitoring (CKM) substudy is designed to address this critical evidence gap and is embedded within the national Steno 1 study. The Steno 1 study is an ongoing national study conducted across Denmark, Greenland and the Faroe Islands. It examines whether a more intensive treatment approach—using a combination of newer heart- and kidney-protective diabetes medications—can better prevent serious heart complications and hospitalizations for heart failure in adults with type 1 diabetes at high risk, compared with today’s standard treatment. The CKM substudy has a distinct scientific focus on ketone safety. By applying continuous ketone monitoring in a real-world setting, the substudy will generate data on ketone levels over time in adults with T1D receiving modern multifactorial treatment strategies.
The primary objectives are to characterize ketone profiles and evaluate the potential of CKM to identify patterns associated with increased DKA risk. In addition, the substudy will explore associations between chronic ketone exposure and the effect on heart and kidney.
By providing robust, real-world data on ketone dynamics in high-risk T1D, the CKM substudy may support safer implementation of novel cardio-renal protective therapies. The findings have the potential to inform clinical practice, improve patient safety, and guide future regulatory and clinical recommendations for ketone monitoring in type 1 diabetes.
Anticipated Outcome
The Steno 1 Continuous Ketone Monitoring (CKM) substudy is expected to provide important new knowledge about ketone levels in adults with type 1 diabetes (T1D), especially those receiving SGLT inhibitors (SGLTi) and GLP-1 receptor agonists (GLP-1RA). By using continuous ketone monitoring, the study will generate detailed information on how ketone levels change in daily life and how often moderate or high ketone levels occur under different treatment strategies.
The data collected will help identify early warning signs of diabetic ketoacidosis (DKA), a rare but serious complication, making it possible to intervene earlier and improve patient safety. The study will also explore how ketone levels relate to blood sugar patterns and whether long-term ketone exposure is linked to heart and kidney outcomes.
Overall, the CKM substudy is anticipated to:
Improve understanding of ketone patterns in people with T1D receiving modern treatments.
Provide evidence to guide safer use of SGLTi and GLP-1RA therapies.
Support clinical decision making and patient education on ketone monitoring.
Inform future guidelines and regulatory recommendations for the safe implementation of intensified treatment strategies in T1D.
By generating real-world, ketone data, the CKM substudy will help balance the benefits of new therapies with safety, ultimately aiming to reduce complications and improve long-term heart and kidney health in adults with type 1 diabetes.
Relevance to T1D
Type 1 diabetes (T1D) is a lifelong condition in which the body cannot produce insulin, making people dependent on insulin therapy to control blood sugar. Despite advances in treatment, adults with T1D remain at high risk for serious complications, including heart disease, kidney disease, and diabetic ketoacidosis (DKA). These complications can lead to hospitalizations, reduced quality of life, and premature death.
The Steno 1 Continuous Ketone Monitoring (CKM) substudy is highly relevant to people with T1D because it addresses a major safety concern associated with modern therapies, such as SGLT inhibitors (SGLTi) and GLP-1 receptor agonists (GLP-1RA). While these medications can protect the heart and kidneys, they can also increase the risk of DKA, which is triggered by elevated ketone levels. Currently, ketone monitoring is intermittent and symptom-driven, which may miss early warning signs.
By using continuous ketone monitoring, the CKM substudy will provide detailed, real-world information on how ketone levels fluctuate in daily life under different treatment strategies. This knowledge will help doctors and individuals with type 1 diabetes use newer therapies more safely, prevent DKA, and better manage long-term heart and kidney health.
Ultimately, the findings will directly benefit people with T1D by improving treatment safety, supporting informed decision making, and contributing to evidence-based guidelines for ketone monitoring and the safe implementation of modern diabetes therapies.