Milk for Diabetes Prevention

Purpose

Individuals with lactase non-persistence (LNP; determined by a functional variant in the LCT gene [rs4988235, GG genotype]) are susceptible to lactose intolerance in adulthood due to deficiency of lactase, the enzyme which digests milk lactose sugars. However, many LNP individuals still drink ≥1 cup of milk daily. Recent analysis in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) found that consumption of 1 serving (cup) of milk/day was associated with ~30% lower risk of type 2 diabetes among LNP individuals, but not among individuals with lactase persistence (LP). This beneficial effect might be partially explained by favorable alterations in gut microbiota and related metabolites associated with higher milk consumption among LNP individuals. Based on these observational study findings, the investigator team proposes to conduct a randomized, controlled trial of lactose-containing vs. lactose-free milk in LNP individuals with pre-diabetes, to comprehensively investigate the effects of milk intake on the gut microbiome and glycemic outcomes.

Conditions

  • Lactose Intolerance
  • Lactose Intolerant
  • Lactase Persistence
  • Pre-Diabetes
  • Diabetes Mellitus, Type 2

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • LNP genotype (LCT gene rs4988235, GG genotype) - History of pre-diabetes, defined as fasting blood glucose 100-125 mg/dL and/or hemoglobin A1c (HbA1c) 5.7-6.4% and have not been diagnosed with diabetes nor take diabetes medication (pre-diabetes determined at most recent study visit [for HCHS/SOL participant] or most recent medical chart or self-report [for other participant]) - Drink ≤1 cup milk/day - Basic computer or smartphone skills - Can speak and read English fluently

Exclusion Criteria

  • Diabetes diagnosis - Taking anti-diabetes medication - Cancer, cardiovascular disease (CVD), or life-threatening illness - Known milk allergy - Has severe GI symptoms after drinking milk - History of GI surgery - Had a double mastectomy - Smoking - More than 1 alcoholic beverage/day - Pregnant or breastfeeding - Colonoscopy in last 2 weeks - Antibiotics in last 3 months - Taking probiotics or fiber supplements (if taking, must be able to stop taking during study) - Taking laxatives, stool softeners, anti-diarrheal (if taking, must be able to stop taking during study) - Taking lactase pills (if taking, must be able to stop taking) - Participating in extreme dieting program - Planning extended travel that would prevent participation in study - Taking medication that must be taken separate from calcium or dairy products

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Lactose-Containing Milk 		Participants will be randomized to lactose-containing milk in strata of age (<60, ≥60) and sex (female, male). Within each age and sex stratum, 10 participants will be randomized into two intervention groups in a 1:1 ratio
  • Dietary Supplement: Lactose-Containing Milk
    Participants will be asked to drink regular milk (1% or 2%) for 12 weeks as follows: - Weeks 1-4: ½ cup milk per day - Weeks 5-8: 1 cup milk per day - Weeks 9-12: 2 cups milk per day Participants will continue drinking 2 cups milk/day for 2 weeks after the 12-week follow-up visit.
Active Comparator
Lactose-Free Milk 		Participants will be randomized to lactose-free milk in strata of age (<60, ≥60) and sex (female, male). Within each age and sex stratum, 10 participants will be randomized into two intervention groups in a 1:1 ratio
  • Dietary Supplement: Lactose-Free Milk
    Participants will be asked to drink 1% or 2% lactose-free milk for 12 weeks as follows: - Weeks 1-4: ½ cup milk per day - Weeks 5-8: 1 cup milk per day - Weeks 9-12: 2 cups milk per day Participants will continue drinking 2 cups milk/day for 2 weeks after the 12-week follow-up visit.

Recruiting Locations

HCHS/SOL Bronx Field Center
The Bronx, New York 10458
Contact:
718-584-1563
milkstudy@einsteinmed.edu

More Details

Status
Recruiting
Sponsor
Albert Einstein College of Medicine

Study Contact

Brandilyn Peters-Samuelson, PhD
718-430-3281
brandilyn.peterssamuelson@einsteinmed.edu

Detailed Description

The trial will feature a 2-week milk washout period, followed by 1:1 randomization to lactose-containing (1% or 2%) or lactose-free (1% or 2%) milk for 12 weeks (4 weeks each of ½ cup, 1 cup, and 2 cups milk). Before and after the 12 weeks, visits will entail lactose challenge hydrogen breath tests (HBT; i.e., lactose tolerance tests) and blood tests for fasting glucose, hemoglobin A1c, and metabolomics; while stool samples and continuous glucose monitoring (CGM) data will be collected at home using provided kits/devices. Specific aims of the study are to: (1) establish feasibility and tolerability of a randomized trial of lactose-containing vs. lactose-free milk; (2) to examine the effect of lactose-containing milk on gut microbiome species, functions, and metabolites in LNP individuals with pre-diabetes; and (3) to examine the effect of lactose-containing milk on glycemic outcomes in LNP individuals with pre-diabetes.