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Blood glucose homeostasis in patients with mild to moderate Spinocerebellar Ataxia type 2

Aguilera-Rodriguez, R.; Almaguer-Gotay, D.; Alvarez-Sosa, A.; Anidos-Machado, M.; Silva-Ricardo, Y.; Cuello-Almarales, D.; Estupinan-Rodriguez, A.; Almaguer-Mederos, L. E.

2026-01-27 physiology
10.64898/2026.01.25.701567 bioRxiv
Show abstract

BackgroundSpinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder that shows cerebellar glucose hypometabolism, systemic hypermetabolism and weight loss. This study aimed to explore novel molecular biomarker candidates for SCA2, based on the assessment of blood glucose homeostasis. MethodsA case-control and correlational study was conducted in 79 Cuban patients with SCA2 and 83 sex- and age-matched control subjects during a fasting state. A subset of 20 SCA2 patients and 19 control individuals underwent an oral glucose tolerance test (OGTT). Several indices for assessing blood glucose homeostasis, derived from the fasting state or the OGTT, were included in the study. ResultsFasting glucose levels showed a small increase, whereas the QUICKI index for insulin sensitivity was slightly decreased among patients. Markers of glucose homeostasis derived from the OGTT were no different between patients and controls. Fasting insulin levels, QUICKI, McAuleys, HOMA2-%S, HOMA2-IR, and HOMA2-%{beta} indices showed weak to moderate correlations with markers of body composition. McAuleys, TyG, HOMA2-IR, and HOMA2-%{beta} indices correlated with the age at onset, progression rate, or INAS count. ConclusionsSCA2 patients with mild to moderate ataxia do not have any major alteration in blood glucose homeostasis. Markers of glucose homeostasis associate with body composition and has modifying effects on disease severity and progression rate in patients with SCA2, with McAuleys index showing effects more consistently. Further studies are needed to describe the changes in blood glucose homeostasis in the different stages of disease, and to confirm the validity of McAuleys index as a candidate biomarker for SCA2 clinical severity and progression.

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