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.
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
Diabetes diagnosis
Taking anti-diabetes medication
Cancer, cardiovascular disease (CVD), or life-threatening illness
Known milk allergy
Parallel
Lactose-Containing Milk
Dietary supplementParticipants 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.
Lactose-Free Milk
Dietary supplementParticipants 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.
Gastrointestinal symptoms
Gastrointestinal symptoms, specifically abdominal pain, bloating, flatulence, and diarrhea, will be recorded daily from screening visit through 12 weeks of milk intervention. The occurrence and severity of these four adverse events will be summarized and reported by study arm. Average frequencies of none-mild vs. moderate-severe symptoms will be compared between treatment groups by week of study, as well as for specific time intervals corresponding to milk doses (weeks 1-4, 5-8, 9-12).
Change in Expired Breath Hydrogen
Expired breath hydrogen after lactose challenge will be measured during the baseline visit and after 12 weeks of milk intervention at the time of the follow-up visit using Hydrogen Breath Test (HBT) kits. Breath tubes will be mailed to an external laboratory where stable isotope analysis for expired breath hydrogen will be conducted. Expired breath hydrogen will be expressed as incremental Area Under the Curve (iAUC). Change in iAUC from baseline to week 12 will be summarized using basic descriptive statistics (group means and standard deviations), and change in iAUC will be compared between treatment groups.
Change in gut microbiome features - Relative Abundance of Species
Stool samples will be collected using home stool microbiome kits at baseline, 4-, 8-, and 12-week timepoints. Shotgun sequencing will be conducted. Change in relative abundance of species (with \>1% mean relative abundance) from baseline will summarized, using basic descriptive statistics (group means and standard deviations). Change in relative abundance of species from baseline will be compared between the treatment groups.
Change in gut microbiome features - Functional Pathway Relative Abundance
Stool samples will be collected using home stool microbiome kits at baseline, 4-, 8-, and 12-week timepoints. Shotgun sequencing will be conducted. Change in relative abundance of functional pathways (with \>1% mean relative abundance) from baseline will summarized, using basic descriptive statistics (group means and standard deviations). Change in relative abundance of functional pathways from baseline will be compared between the treatment groups.
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Albert Einstein College of Medicine
Lead sponsor
National Dairy Council
Collaborator
University of Minnesota (UM) Advanced Research and Diagnostic Laboratory (ARDL)
Collaborator
Azenta Life Sciences
Collaborator
Metabolic Solutions Inc.
Collaborator
