October 14, 2019

Just Set It, And Forget It?

By Alan L Wagner, MD, FACS, FICS


Our existence, and survival, is an amazing balancing act of homeostasis. Most of the time, our hormonal, neurological and structural systems work “automatically” without a thought on our part. Yet when the wheels come off, all heck breaks loose.

These days, we’re understanding the antecedent events to an organ system’s decompensation better than ever. Yet most of our colleagues have a blind spot. I want to bring your attention to a major problem that was brought to light more than 20 years ago yet is rarely discussed: the diabetic patient possessing autoimmune autonomic dysfunction and associated autonomic neuropathy – Diabetic Autonomic Neuropathy (DAN). With DAN, our “automatic systems” are broken, and multiple life-threatening problems develop. 

Groundbreaking research regarding both the autoimmune nature of autonomic neuropathy and the significant disease burden associated with this condition was accomplished by EVMS’s own Aaron I. Vinik, MD, PhD, FCP, MACP.  

My earliest exposure to autonomic neuropathy was over 25 years ago. After attending several of the Diabetes Institutes’ grand rounds, where leading-edge autonomic neuropathy research was presented, I had a hunch that a challenging diabetic patient had the multiple system hallmarks of the recently-described DAN. Together, Dr. Vinik and I collaborated on the patient’s behalf regarding his intractable, progressively blinding, diabetic macular edema owing to autonomic neuropathy. Aggressive, minimally responsive, multi-system compromise was also present.

Why was his macula swollen and degenerating? The first clue was finding that one random evening, his blood pressure was very high. At that time, his problem was called “paradoxical nocturnal hypertension.” We found that it was secondary to underlying autonomic neuropathy. Every night, he went from a relatively hypotensive state while spending the day sitting to having significant hypertension once he was recumbent in bed! This was confirmed with a positive tilt table test. To address this issue, we used a trial of the patient sleeping with his head moderately elevated and short-acting blood pressure control agents immediately prior to bedtime, along with selectively suppressing his autoimmune rheologic profile. His macular edema quickly resolved, and his lower limb edema also improved.

Dr. Vinik and his team penned a landmark “must read” article regarding DAN (Diabetes Care 2003 May; 26(5): 1553-1579), describing it as a “serious and common complication of diabetes”.  However, DAN is still grossly underappreciated and often undiagnosed. Preventable complications, or misidentification of root causes, abound.

For the benefit of both your Type 1 and 2 diabetic patients, please review what DAN is all about and become familiar once again with the importance of irregular heart rate variability (HRV) as a negative prognostic sign for survival. Genitourinary tract pathology (infections, dysfunctions, etc.) are not always structural in origin. Dry, cracking skin that ultimately leads to infections and limb loss has inappropriate pseudomotor tone as its origin, and it won’t be improved by just a bit more lotion or fish oil. Rapidly advancing diabetic retinopathy from nocturnal hypertension can frequently be seen as orthostatic hypotension as an early clinical complaint. 

In our practice, we see friends and neighbors ravaged by end-stage diabetic disease accelerated by autonomic neuropathy, much of it preventable. Early awareness of, and the need to interdict with, autoimmune DAN is crucial. Together, we can prevent a multitude of disabling and life-threatening complications of limb loss, cardiac death, renal failure and blindness, to name but a few.

Alan L. Wagner, MD, FACS founded the Wagner Macula & Retina Center in 1987. A Board certified ophthalmologist specializing in vitreoretinal surgery, Dr. Wagner received his medical degree from Vanderbilt University School of Medicine. He completed his residency in Ophthalmology at EVMS, and furthered his training as the Dyson Fellow in vitreoretinal disease and surgery at Weill Cornell University Medical Center.  wagnerretina.com