Yearlong Study Leverages Ketosis for Cardiometabolic Disease Management

by Lewis Chang, PhD

A yearlong lifestyle intervention that utilized a ketogenic diet significantly improved HbA1c, body weight, and multiple cardiovascular disease (CVD) risk factors in patients with type 2 diabetes (T2D), according to data from a clinical study published in two journals.^1,2

CVD is the leading cause of death among patients with T2D.³ As the prevalence of T2D continues to increase rapidly worldwide, effective interventions to address T2D and CVD risk are critical. A low-carbohydrate diet is one of the approaches for T2D management. In a 2017 study, a 10-week carbohydrate-restricted intervention that achieved nutritional ketosis (the metabolic state in which ketone bodies are produced and utilized as the main energy source for the body instead of glucose) demonstrated improved glycemic control for outpatients with T2D.⁴

In order to understand the long-term effects of this novel intervention, a research team led by Virta Health (San Francisco, CA) and Indiana University Health (Lafayette, IN) recruited 262 outpatients with T2D to participate in a 1-year clinical study (Clinicaltrials.gov Identifier NCT02519309). Patients received individualized nutrition recommendations from a remote care team (including health coach and physician) to achieve and sustain nutritional ketosis. Social support was also offered via an online peer community. A web-based app was provided to patients for biomarker reporting and monitoring, including body weight, blood glucose and blood ketone level. A comparison group of patients (n=87) received their usual care from their own medical providers and diabetes education program. Various biomarkers of glycemic control and CVD risk were assessed in both groups at baseline and at the end of the study.

After one year, patients receiving the usual care showed no changes in all assessed biomarkers. Contrarily, patients who received the novel intervention achieving nutritional ketosis showed numerous, clinically meaningful improvements:^1,2

• Mean HbA1c was reduced from 7.6% to 6.3%
• Mean body weight decreased 13.8 kg (30.4 lb)
• T2D medication prescription use (other than metformin) declined from 57% to 30%, insulin therapy was reduced or discontinued in 94% of users, and sulfonylureas were discontinued in all users
• Homeostatic model assessment for insulin resistance (HOMA-IR) was reduced by 55%
• High-sensitivity C-reactive protein (hs-CRP) was reduced by 39%
• Small low-density lipoprotein particle number (small LDL-P) decreased by 21%
• Apolipoprotein A1 (apoA1) increased by 9.8% and apoB:apoA1 ratio decreased by 9.5%
• Triglycerides decreased by 24%, high-density lipoprotein cholesterol (HDL-C) increased by 18%, and triglyceride:HDL-C ratio decreased by 29%
• LDL-P size increased by 1% and large very low-density lipoprotein particle number (large VLDL-P) decreased by 39%
• Low-density lipoprotein cholesterol (LDL-C) increased by 10%, but appeared limited to the large LDL subfraction
• The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased by 12%
• Antihypertensive medications were discontinued in 11% of patients

These data demonstrate that an intervention delivered in an outpatient setting featuring technology-enabled remote care with individualized recommendations to achieve and sustain nutritional ketosis can improve glycemic control, support weight management, and reduce many CVD risk factors in patients with T2D.

Why is this Clinically Relevant?

• A low-carbohydrate ketogenic diet can help the body utilize fat as the primary fuel source instead of sugar
• Nutritional ketosis may be beneficial for glycemic control, weight loss, and CVD risk management^1,2
• Clinicians and health coaches can play an important role in helping patients achieve nutritional ketosis

View the Cardiocascular Diabetology abstract

View the Diabetes Therapy abstract

References

1. Bhanpuri NH, Hallberg SJ, Williams PT, et al. Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study. Cardiovasc Diabetol. 2018;17(1):56.
2. Hallberg SJ, McKenzie AL, Williams PT, et al. Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study. Diabetes Ther. 2018;9(2):583-612.
3. Matheus AS, Tannus LR, Cobas RA, Palma CC, Negrato CA, Gomes MB. Impact of diabetes on cardiovascular disease: an update. Int J Hypertens. 2013;2013:653789.
4. McKenzie LA, Hallberg JS, Creighton CB, et al. A novel intervention including individualized nutritional recommendations reduces hemoglobin A1c level, medication use, and weight in type 2 diabetes. JMIR Diabetes. 2017;2(1):e5.