ABSTRACT
More than 15% of U.S. adults with type 2 diabetes have poorly controlled blood sugar, here defined as a
glycated hemoglobin (HbA1c) level of 9.0% or higher. These adults have an elevated health risk of a variety of
outcomes, including amputation and mortality from cardiovascular disease and from all causes. Nutrition-
focused interventions can be effective for improving glycemic control, reducing anti-hyperglycemic
medications, and reducing body weight, all of which are critical outcomes for adults with type 2 diabetes.
However, typical nutrition-focused interventions can be burdensome, often requiring complex instructions and
a complete overhaul of one’s diet. Additionally, adults with poorly controlled type 2 diabetes are more likely to
have low literacy levels, which can be a barrier for adherence to complex interventions. Therefore, an effective
intervention for adults with poorly controlled diabetes who may have lower health literacy levels is necessary to
reduce both HbA1c levels and anti-hyperglycemic medications. Carbohydrate intake has the strongest impact
on post-prandial glycemia of any dietary factor, and a very low-carbohydrate diet—due to its ability to improve
glycemic control—is now recommended by the American Diabetes Association (ADA) for the treatment of type
2 diabetes. We hypothesize that some of the benefits of a very low-carbohydrate diet may be available to
individuals who change only their breakfasts to be very low-carbohydrate, rather than modifying their entire
diet. Thus, we propose an acceptability, feasibility, preliminary effectiveness trial of a 4-month, online, small-
steps, low-literacy, very low-carbohydrate breakfast-focused program in 120 adults with poorly controlled type
2 diabetes. We will measure acceptability and feasibility, plus critical efficacy outcomes, such as changes in
HbA1c, anti-hyperglycemic medications, glycemic variability, body weight, blood pressure, and lipids. We will
also test whether factors such as sex, health literacy level, and baseline insulin resistance significantly
moderate the impact of the intervention on change in HbA1c and change in anti-hyperglycemic medications.
These moderation analyses will contribute to a nascent research approach for personalized nutrition, which
responds to Objective 2-5 of the NIH’s May 2020 Strategic Plan for NIH Nutrition Research. This submission is
in response to PAS-20-160, Small R01s for Clinical Trials Targeting Diseases within the Mission of NIDDK,
which does not require preliminary data. If results are promising, our goal is to conduct a follow-up, powered,
longer randomized trial of this approach. As the prevalence of type 2 diabetes and the understanding of
personalized interventions continue to increase, there is a critical need to provide additional effective options
for population-level type 2 diabetes treatment strategies, especially for adults with poorly controlled type 2
diabetes.
