Association of Cardiovascular Autonomic Neuropathy and Distal Symmetric Polyneuropathy with All-Cause Mortality: A Retrospective Cohort Study

Background. People with diabetic cardiovascular autonomic neuropathy (CAN) have increased cardiovascular mortality. However, the association between distal symmetric polyneuropathy (DSPN) or CAN with all-cause mortality is much less investigated. Thus, we set out to examine the effect of CAN and DSPN on all-cause mortality in a well-phenotyped cohort. Methods. All diabetes cases ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>n</a:mi> <a:mo>=</a:mo> <a:mn>1,347</a:mn> </a:math> ) from the catchment area of a secondary diabetes care centre who had medical examination including neuropathy assessment between 1997 and 2016 were followed up for all-cause mortality in the NHS Hungary reimbursement database until 2018. We investigated the association of CAN (Ewing tests) and DSPN (Neurometer) with all-cause mortality using Cox models stratified by diabetes type. Results. Altogether, <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>n</c:mi> <c:mo>=</c:mo> <c:mn>131</c:mn> <c:mo>/</c:mo> <c:mn>1,011</c:mn> </c:math> persons with type 1/type 2 diabetes were included. Of the participants, 53%/43% were male, mean age was <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mn>46</e:mn> <e:mo>±</e:mo> <e:mn>12</e:mn> <e:mo>/</e:mo> <e:mn>64</e:mn> <e:mo>±</e:mo> <e:mn>10</e:mn> </e:math> years, diabetes duration was <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mn>13</g:mn> <g:mo>±</g:mo> <g:mn>10</g:mn> <g:mo>/</g:mo> <g:mn>7</g:mn> <g:mo>±</g:mo> <g:mn>8</g:mn> </g:math> years, 42%/29% had CAN, and 39%/37% had DSPN. During the <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mn>9</i:mn> <i:mo>±</i:mo> <i:mn>5</i:mn> <i:mo>/</i:mo> <i:mn>8</i:mn> <i:mo>±</i:mo> <i:mn>5</i:mn> </i:math> -year follow-up, <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>n</k:mi> <k:mo>=</k:mo> <k:mn>28</k:mn> <k:mo>/</k:mo> <k:mn>494</k:mn> </k:math> participants died. In fully adjusted models, participants with type 1 diabetes patients with versus without DSPN had an increased mortality (HR 2.99, 95% CI 1.4-8.63), while no association with CAN was observed. In type 2 diabetes, both DSPN and CAN independently increased mortality (HR 1.32, 95% CI: 1.07-1.64, and HR 1.44, 95% CI: 1.17-1.76). Conclusions. Our results are compatible with an increased risk of mortality in people with type 1 diabetes and DSPN. Furthermore, we report a similarly strong association between DSPN and CAN and all-cause mortality in type 2 diabetes mellitus.