A Randomized Controlled Pilot Study of the Food Order Behavioral Intervention in Prediabetes

Intensive diet and lifestyle modifications have been shown to reduce the risk of progression
to T2DM in several randomized controlled trials. Key components of standard nutritional
counseling include reducing calorie intake and glycemic load. Sequential nutrient ingestion
is a novel strategy found to attenuate the glycemic effect of a meal. Investigators have
previously shown that ingestion of carbohydrates after protein or vegetables results in
reduced glucose and insulin excursions over 180 min in patients with T2DM. In addition,
investigators also found that levels of the hunger hormone ghrelin were more suppressed at
the end of 3 hours after a meal. Furthermore, investigators found that the glycemic effects
of food order apply to individuals with prediabetes as well. This study follows previous
research on nutrient order and seeks to determine the metabolic effects of this behavioral
intervention in the real world. The study will include two randomized groups who are
overweight or obese and are diagnosed with prediabetes. The control group will receive
standard nutritional counseling at the start of the study and no instructions to change food
order behavior. The intervention group will receive regularly scheduled food order counseling
over a period of 16 weeks in addition to standard nutritional counseling at baseline.
Anthropometric and metabolic parameters, including insulin sensitivity, will be assessed at
baseline and at 16 weeks. The primary aim of this study is to determine the proportion of
subjects who achieve reversal of prediabetes at study completion and/ or who achieve a 0.2%
reduction in hemoglobin A1c. If shown to be effective, this data will inform the design of
larger study focused on diabetes prevention.

Inclusion Criteria:

- Male and female subjects who are 21 years of age or older

- BMI 25-40 kg/m2

- Pre-diabetes defined by an HbA1c of 5.7-6.4% and 2 hour glucose between 140 - 199
mg/dl on OGTT

- Weight stable (< 5% body weight change over preceding 6 months)

- Provide valid informed consent

Exclusion Criteria:

- Previous diagnosis of T2DM or Hb1A1c greater than or equal to 6.5% or fasting glucose
> 125mg/dl on screening or 2 hour glucose greater than or equal to 200 mg/dl on OGTT

- Patients who are on any oral/ injectable medications used to treat diabetes including
metformin, sulfonylureas, DPP-4 inhibitors, GLP-1 analogs, SGLT2 inhibitors,
glitazones and insulin

- Patients on over the counter or approved weight loss medications

- Pregnant or lactating females

- Previous bariatric surgery

- Psychotropic and/or other medications known to significantly impact weight unless on
stable dose for 6 months

- eGFR < 45ml/min

- Significant hepatic, cardiac, gastrointestinal, neurologic or other medical illness
that would preclude participation in the study

- Untreated hypothyroidism or other endocrine disorders

- Non-English speaking patients

- Any patient deemed unsuitable in the investigator's opinion