Milk for Diabetes Prevention

Albert Einstein College of Medicine

Status: Not yet enrolling

Conditions: Lactose Intolerant; Lactase Persistence; Lactose Intolerance; Diabetes Mellitus, Type 2; Pre-Diabetes

Treatments: Dietary Supplement: Lactose-Containing Milk; Dietary Supplement: Lactose-Free Milk

Study type: Interventional

Funder types: Other

Identifiers

NCT06513026

2024-16045

Details and patient eligibility

About

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.

Full description

The trial will feature a 2-week milk washout period, followed by 1:1 randomization to lactose-containing or lactose-free 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18
• 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. If blood test over 3 years ago, pre-diabetes will be confirmed using finger-stick HbA1c.
• Drink ≤1 cup milk/day
• Basic computer or smartphone skills
• English or Spanish speaking

Exclusion criteria

• No diabetes diagnosis
• No anti-diabetes medication
• Blood test with history of pre-diabetes conducted >3 years ago and finger-stick HbA1c is normal (≤5.6%).
• No cancer, cardiovascular disease (CVD), or life-threatening illness
• No known milk allergy
• Does not have severe GI symptoms after drinking milk
• No history of GI surgery
• No smoking
• ≤1 alcoholic beverage/day
• Not pregnant or breastfeeding
• No colonoscopy in last 2 weeks
• No antibiotics in last 3 months
• Not taking probiotics or fiber supplements (or can stop taking during study)
• Not taking laxatives, stool softeners, anti-diarrheal (or can stop taking during study)
• Not participating in any extreme dieting programs

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

40 participants in 2 patient groups

Lactose-Containing Milk

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: Lactose-Containing Milk

Lactose-Free Milk

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: Lactose-Free Milk