Cardiovascular Autonomic Neuropathy in Hypertensive Patient With Prediabetes

Sitorus, Gustaf D.S.; Pangaribuan, Mariska; Ismugi, I.; Soerarso, Rarsari; Hersunarti, Nani; Siswanto, Bambang Budi

doi:10.1097/01.hjh.0000539808.76921.b9

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“…CAN development was linked to glycemic control (67); however, several large trials also proposed an association between CAN and inflammation, especially in new onset of T2D (31). Interestingly, CAN was also found to be associated with prediabetes (52). Indeed, a previous study in our laboratory showed that metabolically challenged rats with hyperinsulinemia, but not hyperglycemia or obesity, developed localized perivascular adipose tissue (PVAT) inflammation together with parasympathetic CAN (2).…”

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confidence: 98%

Worsening baroreflex sensitivity on progression to type 2 diabetes: localized vs. systemic inflammation and role of antidiabetic therapy

Bakkar

Mougharbil

Mroueh

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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Cardiac autonomic neuropathy (CAN) is an early cardiovascular manifestation of type 2 diabetes (T2D) that constitutes an independent risk factor for cardiovascular mortality and morbidity. Nevertheless, its underlying pathophysiology remains poorly understood. We recently showed that localized perivascular adipose tissue (PVAT) inflammation underlies the incidence of parasympathetic CAN in prediabetes. Here, we extend our investigation to provide a mechanistic framework for the evolution of autonomic impairment as the metabolic insult worsens. Early metabolic dysfunction was induced in rats fed a mild hypercaloric diet. Two low-dose streptozotocin injections were used to evoke a state of late decompensated T2D. Cardiac autonomic function was assessed by invasive measurement of baroreflex sensitivity using the vasoactive method. Progression into T2D was associated with aggravation of CAN to include both sympathetic and parasympathetic arms. Unlike prediabetic rats, T2D rats showed markers of brainstem neuronal injury and inflammation as well as increased serum levels of IL-1b. Experiments on PC12 cells differentiated into sympathetic-like neurons demonstrated that brainstem injury observed in T2D rats resulted from exposure to possible pro-inflammatory mediators in rat serum rather than a direct effect of the altered metabolic profile. CAN and the associated cardiovascular damage in T2D only responded to combined treatment with insulin to manage hyperglycemia in addition to a non-hypoglycemic dose of metformin or pioglitazone providing an anti-inflammatory effect, coincident with the effect of these combinations on serum IL-1b. Our present results indicate that CAN worsening upon progression to T2D involves brainstem inflammatory changes likely triggered by systemic inflammation.

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