Temporal Progression of Microvascular Alterations in the Nailfold and Skeletal Muscle of Non-Obese Type 2 Diabetic...

Diabetes is associated with microvascular complications in multiple tissues. Nailfold capillaries (NFCs) provide a noninvasive window for assessing microvascular alterations; however, their temporal association with skeletal muscle microvascular changes during diabetes progression remains unclear. This study aimed to determine whether NFC structural changes reflect skeletal muscle microvascular alterations and muscle-type-specific vulnerability in a non-obese type 2 diabetes model.

Spontaneously Diabetic Torii (SDT) rats, a non-obese type 2 diabetes model, and age-matched Sprague-Dawley rats were studied. NFC morphology was evaluated by capillaroscopy at 12, 18, and 28 weeks of age. Soleus and plantaris muscles were collected for histological and gene expression analyses, and glucose tolerance was evaluated by oral glucose tolerance testing at each time point.

At 12 weeks of age, SDT rats exhibited mild glucose intolerance without significant abnormalities in NFC morphology or skeletal muscle capillary indices. At 18 weeks, when glucose intolerance became evident in the absence of persistent hyperglycemia, NFC narrowing and reduced density were observed, accompanied by capillary rarefaction in the predominantly fast-twitch plantaris muscle, whereas the slow-twitch soleus muscle remained relatively preserved. By 28 weeks, persistent hyperglycemia was present, and overt muscle atrophy was observed exclusively in the plantaris muscle.

NFC structural alterations emerge alongside skeletal muscle microvascular rarefaction at the stage of glucose intolerance and precede overt muscle atrophy in fast-twitch muscle. NFC assessment may serve as a noninvasive indicator of early microvascular alterations relevant to diabetes-associated skeletal muscle deterioration.