NCT03860558

Impact of Metabolic Health on Sperm Epigenetic Marks in Humans

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Joslin Diabetes Center · Academic / Other
• Sex: Male
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This study is designed to evaluate whether epigenetic markers in overweight men with type 1 diabetes (T1D) or type 2 diabetes (T2D) can be improved with a 3 month lifestyle intervention or program focused in glycemic intervention.

Detailed description

Parental history of diabetes confers substantial individual risk for development of obesity and diabetes. Obesity risk can be transmitted across generations, from parents or grandparents to children. Genomic variation explains only a portion of this risk. Epigenetic modulation through DNA methylation, histone modification, or by noncoding RNAs, provide mechanisms to regulate gene activity independent of DNA sequence by determining which genes are turned on or off in response to environment or disease. Epigenetic changes can be stable over the lifespan providing a mechanism through which environmental exposures may impart long-term effects on gene expression and phenotypic outcome. The maternal intrauterine environment is now well recognized to modify obesity and T2D disease risk of offspring. Fetuses carried by women who are obese, have diabetes, or suffer from suboptimal nutrition are at increased risk of insulin resistance, obesity, T2D, and cardiovascular disease risk as adults. Studies in rodents also show that the health, metabolism, and prior environmental exposures of the male can also influence health of his offspring. Existing data provide powerful support for the hypothesis that current glucose levels and overall metabolic health of males can alter epigenetic marks in sperm and suggest a novel modifiable mechanism of transmission. However, much less is known about how human sperm epigenetic patterns change with nutritional and metabolic health, and whether these may ultimately impart differences in health of future generations. Thus, we are studying the impact of both type 1 and type 2 diabetes, and elevations in glucose common to both conditions, on human reproductive health and the sperm epigenome.

Conditions

• Overweight
• Type 2 Diabetes Mellitus
• Type 1 Diabetes Mellitus

Interventions

Type	Name	Description
OTHER	Lifestyle Intervention	Participants will undergo a 12-week multidisciplinary program for weight control and intensive diabetes management. The program includes adjustments to diabetes medications to enhance weight reduction and improve glycemia, dietary modification, and activity instructions.
OTHER	No Intervention	Participants will not undergo an intervention.

Timeline

• Start date: 2018-05-01
• Primary completion: 2026-07-01
• Completion: 2026-07-01
• First posted: 2019-03-04
• Last updated: 2026-02-06

Locations

1 site across 1 country: United States