Aims/hypothesis <p>To identify distinct metabolic subtypes among Japanese men with prediabetes and evaluate their association with the future risk of type 2 diabetes.</p> Methods <p>A data-driven cluster k-means cluster analysis was conducted in 2,172 men with prediabetes, defined as a fasting plasma glucose (FPG) concentration of 100–125&#xa0;mg/dL (5.6–6.9 mmol/L) from the JDOIT-1 cohort. Four biochemical indicators—body mass index (BMI), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and non-HDL cholesterol—were standardized and used for clustering. The optimal number of clusters (k = 3) was determined using the elbow method. The association between cluster membership and 5-year diabetes-free survival was examined.</p> Results <p>Three metabolic phenotypes were identified: Cluster 1 (MRP, <i>n</i> = 1,149), metabolically resilient; Cluster 2 (OFIP, <i>n</i> = 581), obesity- and insulin-resistant; and Cluster 3 (NOHP, <i>n</i> = 442), non-obese hyperglycemic. Annual diabetes incidence rates were 0.70%, 2.73%, and 6.73% in the MRP, OFIP, and NOHP groups, respectively (<i>p</i> &lt; 0.001). Compared with MRP, adjusted hazard ratios were 3.95 (95% CI 2.64–5.92) for OFIP and 9.81 (95% CI 6.75–14.26) for NOHP. Lifestyle interventions significantly reduced diabetes risk only in the OFIP group (HR 0.59, 95% CI 0.36–0.97, <i>p</i> = 0.037).</p> Conclusions/interpretation <p>Unsupervised clustering identified distinct metabolic subtypes predictive of diabetes onset. Diabetes risk increased progressively from metabolically resilient to insulin-resistant and hyperglycemic phenotypes. Targeted lifestyle interventions may be particularly effective in individuals with obesity- and dyslipidemia-related insulin resistance.</p> Trial registration <p>University hospital Medical Information Network (UMIN) Center UMIN000000662)、Approval date 11 December 2006.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Identification of distinct metabolic subtypes among Japanese men with prediabetes: a data-driven cluster analysis from the J-DOIT1 study

  • Naoki Sakane,
  • Kaoru Takahashi,
  • Masayuki Domichi,
  • Akiko Suganuma,
  • Hideshi Kuzuya

摘要

Aims/hypothesis

To identify distinct metabolic subtypes among Japanese men with prediabetes and evaluate their association with the future risk of type 2 diabetes.

Methods

A data-driven cluster k-means cluster analysis was conducted in 2,172 men with prediabetes, defined as a fasting plasma glucose (FPG) concentration of 100–125 mg/dL (5.6–6.9 mmol/L) from the JDOIT-1 cohort. Four biochemical indicators—body mass index (BMI), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and non-HDL cholesterol—were standardized and used for clustering. The optimal number of clusters (k = 3) was determined using the elbow method. The association between cluster membership and 5-year diabetes-free survival was examined.

Results

Three metabolic phenotypes were identified: Cluster 1 (MRP, n = 1,149), metabolically resilient; Cluster 2 (OFIP, n = 581), obesity- and insulin-resistant; and Cluster 3 (NOHP, n = 442), non-obese hyperglycemic. Annual diabetes incidence rates were 0.70%, 2.73%, and 6.73% in the MRP, OFIP, and NOHP groups, respectively (p < 0.001). Compared with MRP, adjusted hazard ratios were 3.95 (95% CI 2.64–5.92) for OFIP and 9.81 (95% CI 6.75–14.26) for NOHP. Lifestyle interventions significantly reduced diabetes risk only in the OFIP group (HR 0.59, 95% CI 0.36–0.97, p = 0.037).

Conclusions/interpretation

Unsupervised clustering identified distinct metabolic subtypes predictive of diabetes onset. Diabetes risk increased progressively from metabolically resilient to insulin-resistant and hyperglycemic phenotypes. Targeted lifestyle interventions may be particularly effective in individuals with obesity- and dyslipidemia-related insulin resistance.

Trial registration

University hospital Medical Information Network (UMIN) Center UMIN000000662)、Approval date 11 December 2006.