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Unequal distribution of plasma glucagon levels among clustering-based diabetes subtypes: a Japanese cohort #MMPMID41388999
Tanabe H; Shimajiri Y; Shiroma K; Higa M; Masuzaki H; Shimabukuro M
J Clin Endocrinol Metab 2025[Dec]; ? (?): ? PMID41388999show ga
CONTEXT: Hyperglucagonemia contributes to disturbances in glucose metabolism. Data-driven diabetes clustering reflects risk of diabetic complications better than classical classification, type 1 diabetes (T1D) vs. type 2 diabetes (T2D); however, the pathophysiological features have not been clarified. OBJECTIVE: To assess the distribution of plasma glucagon levels among clustering-based diabetes subtypes. METHODS: A total of 546 Japanese participants with T1D or T2D were categorized into five diabetes subtypes. Plasma glucagon levels were compared across subtypes and factors associated with hyperglucagonemia were evaluated using logistic regression analyses. RESULTS: Plasma glucagon levels differed significantly among diabetes subtypes. Among the five subtypes, plasma glucagon levels and the frequency of hyperglucagonemia were highest in the severe insulin-resistant diabetes (SIRD) subtype (45.6%). The SIRD subtype was an independent risk factor for hyperglucagonemia (adjusted odds ratio 2.17, 95%CI 1.03-4.54, P=0.041), even after adjusting for other risk factors, such as body mass index, HbA1c, and metabolic dysfunction-associated steatotic liver disease. CONCLUSION: The distribution of plasma glucagon levels differed among the clustering-based diabetes subtypes. SIRD is a subtype of diabetes with a hyperglucagonemic phenotype. Elucidating the reason for hyperglucagonemia in SIRD may help to clarify the mechanisms underlying the unfavorable clinical phenotype.
J+Clin+Endocrinol+Metab 2025 ; ? (?): ?
