Processing Responses of Grains (PRO-Grains) Study

In this pilot study, the investigators will access feasibility and generate preliminary data
to systematically address a major question in nutrition: Does food processing, specifically
with regard to whole grains (WGs), have an independent effect on outcomes related to
diabetes and cardiovascular disease? Whole grains are defined as intact, ground, cracked, or
flaked caryopsis (kernel or seed), where the principal components (bran, endosperm, germ)
are present in the same proportion as the intact caryopsis. In contrast, refined grains
(RGs) are milled to remove the bran and germ, leaving only the endosperm and resulting in
lower fiber, iron, and many B vitamins. Several previous studies have shown that consumption
of WGs vs. RGs improves insulin sensitivity and decreases risk for chronic disease. However,
the effects of consuming WGs may differ depending on degree of processing. While whole grain
products contain the three components of the kernel, we hypothesize that consuming the food
containing the least processed (and least pulverized) kernels may have beneficial effects on
metabolism that decrease disease risk through plausible physiological mechanisms.

The investigators propose a partial feeding study using a randomized 3-period crossover
design to compare the effects of 1) intact or minimally processed whole grains, 2) highly
processed whole grains, and 3) refined grains, each fed for 4 weeks. The primary outcome
will be change in peripheral insulin sensitivity. Secondary outcomes include hepatic insulin
sensitivity, components of the metabolic syndrome and other cardiometabolic risk factors,
arterial stiffness, gut microbiome and fecal short chain fatty acids, and ratings of hunger,
satiation, palatability, and acceptability (gastrointestinal symptoms).

Inclusion Criteria:

- Aged 18 to 35 years

- Body mass index ≥ 25 and <40 kg/m2

- Serum fasting insulin >10 uIU/mL and one of the following metabolic syndrome
components: waist circumference, men: ≥102 cm, women: ≥88 cm; triglycerides, ≥150
mg/dL; HDL-C, men: <40 mg/dL , women: <50 mg/dL; systolic blood pressure ≥130 or
diastolic blood pressure ≥85 mmHg; or fasting glucose, ≥100 mg/dL

- Medical clearance from a primary care provider to rule out any major medical illness,
disability, or disorder (e.g., liver disease, renal failure, cancer)

- Access to a working telephone or cell phone

- Willingness to eat the grain foods provided during participation

- If female, regular menstrual cycles (defined as 26-30 days, ±1 day full flow, i.e. 26
to 30 days between cycles; no more than one day variation in the duration of
menstrual flow)

Exclusion Criteria:

- Pre-existing major medical illness by medical history or laboratory screening tests

- Allergy or sensitivity to gluten (self-reported or physician diagnosed)

- >5% change in weight within previous 6 months

- Current smoking (1 cigarette in the past week)

- Major surgery within the previous 6 months

- Physical, mental, or cognitive handicaps that prevent participation.

- Alcohol intake >7 drinks per week

- Use of medications that may affect study outcomes

- Use of antibiotics within the previous 3 months (in those who agree to complete the
analyses of gut microbiome and fecal short chain fatty acids)

- Use of illegal drugs

- Plans to be away from home for 1 week or longer during the study period (e.g.,
vacation, relocation)

- Another member of the family (first degree relative) or household participating in
the study

- If female, pregnancy or lactation during prior 12 months, plans to become pregnant
during the study period, change in oral contraceptives within 3 months, or irregular
menstrual cycle frequency (<10 bleeds/year)