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Objective <p>This study investigated the longitudinal impact of intensive medical intervention (IMI) and bariatric surgery procedures on indirect measures of pancreatic β-cell death and function.</p> Methods <p>Eighty-four participants (28 non-type 2 diabetes [T2D], 56 T2D) from the HEADS UP study were assessed at baseline and 1-year post-intervention. Circulating unmethylated and methylated insulin gene [<i>INS</i>] DNA were quantified from blood samples via droplet digital polymerase chain reaction (PCR). Metabolic biomarkers, including fasting plasma glucose, HbA1c, proinsulin-to-insulin ratio, insulin, and C-peptide, were analyzed.</p> Results <p>At baseline, participants with T2D had significantly higher levels of unmethylated <i>INS</i> DNA and higher unmethylated-to-methylated <i>INS</i> DNA ratios than individuals without T2D. After 1-year, significant reductions in these biomarkers were observed primarily in the T2D group. Bariatric surgeries yielded greater improvements in metabolic profiles and reductions in unmethylated <i>INS</i> DNA than IMI. Despite substantial metabolic improvement, participants with T2D maintained elevated proinsulin-to-insulin ratios, indicating alterations to β-cell function.</p> Conclusions <p>Circulating unmethylated <i>INS</i> DNA is a non-invasive index of β-cell death and responds to weight-loss interventions. Metabolic surgeries are more effective than IMI in preserving β-cell mass and function, highlighting their potential in diabetes management. Long-term studies are necessary to confirm these initial findings.</p>

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Non-invasive islet β-cell markers track with weight-loss interventions for type 2 diabetes: a prospective cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月8日

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  • Hongyan Sun,
  • Yun Shen,
  • Susan J. Burke,
  • Phillip Brantley,
  • Ricky Brock,
  • Dachuan Zhang,
  • Shengping Yang,
  • Gang Hu,
  • J. Jason Collier

摘要

Objective

This study investigated the longitudinal impact of intensive medical intervention (IMI) and bariatric surgery procedures on indirect measures of pancreatic β-cell death and function.

Methods

Eighty-four participants (28 non-type 2 diabetes [T2D], 56 T2D) from the HEADS UP study were assessed at baseline and 1-year post-intervention. Circulating unmethylated and methylated insulin gene [INS] DNA were quantified from blood samples via droplet digital polymerase chain reaction (PCR). Metabolic biomarkers, including fasting plasma glucose, HbA1c, proinsulin-to-insulin ratio, insulin, and C-peptide, were analyzed.

Results

At baseline, participants with T2D had significantly higher levels of unmethylated INS DNA and higher unmethylated-to-methylated INS DNA ratios than individuals without T2D. After 1-year, significant reductions in these biomarkers were observed primarily in the T2D group. Bariatric surgeries yielded greater improvements in metabolic profiles and reductions in unmethylated INS DNA than IMI. Despite substantial metabolic improvement, participants with T2D maintained elevated proinsulin-to-insulin ratios, indicating alterations to β-cell function.

Conclusions

Circulating unmethylated INS DNA is a non-invasive index of β-cell death and responds to weight-loss interventions. Metabolic surgeries are more effective than IMI in preserving β-cell mass and function, highlighting their potential in diabetes management. Long-term studies are necessary to confirm these initial findings.