Cardiac autonomic neuropathy: impact on severe hypoglycemic unawareness and orthostatic hypotension in diabetic dysautonomia, a case series and review

Abstract

Diabetic autonomic neuropathy (DAN) and its associated cardiovascular autonomic neuropathy (CAN) can lead to potentially fatal complications. We analyzed two distinct cases of DAN/CAN based on comprehensive cardiovascular autonomic reflex tests (CARTs). Case 1 involves a 27-year-old patient with T1DM suffering from recurrent severe hypoglycemic unawareness due to DAN. After implementing an automated insulin delivery system, the glucose management improved significantly. Case 2 describes a 60-year-old patient with type 2 diabetes experiencing debilitating orthostatic hypotension. The initiation of Midodrine and Fludrocortisone markedly improved symptoms and capacity of daily activities. This observational study highlights the critical yet frequently overlooked severe manifestations of DAN/CAN, specifically hypoglycemic unawareness and orthostatic hypotension. CARTs play a pivotal role in confirming the diagnosis and guiding therapeutic decisions. Tailored interventions, including advanced technologies like automated insulin delivery systems for T1DM and pharmacotherapy targeting neurogenic orthostasis, can significantly improve patient outcomes and quality of life.

Keywords: cardiac autonomic neuropathy; diabetes; dysautonomia; hypoglycemia unawareness; orthostatic hypotension.

Fig. 1

Key clinical events and findings. IAH, impaired awareness of hypoglycemia; SHEs, severe hypoglycemic events; T1D, type 1 diabetes mellitus.

Fig. 2

Work model. Diabetic autonomic neuropathy (DAN) is involved in severe hypoglycemia events (SHEs) and impaired awareness of hypoglycemia (IAH), hypoglycemia-associated autonomic failure (HAAF) and cardiovascular autonomic neuropathy (CAN) with neurogenic orthostatic hypotension (nOH). DAN causes impaired glucagon response with sympathetic and sympathoadrenal response leading to SHEs/IAH. There is a reciprocal relationship between SHEs and IAH. DAN and the impacted hypothalamic–pituitary–adrenal (HPA) axis cause HAAF. The SHEs/IAH and HAAF compose a vicious cycle, which perpetuates itself and leads to exacerbated neuroglycopenic symptoms of hypoglycemia leading to severe SHEs-related events like coma and death. CAN, as a crucial component of DAN, has a wide spectrum of disorders. The nOH is debilitating and also links to the other adverse disorders of CAN, collectively leading to death-in-bed syndrome (DIB) and all-cause mortality.