Uszkodzenie nerwów autonomicznych

Uszkodzenie nerwów autonomicznych
Epidemiologia

Neuropatia autonomiczna, szczególnie sercowo-naczyniowa (CAN), jest istotnym powikłaniem cukrzycy, z częstością występowania wahającą się od 1% do 90% w zależności od typu cukrzycy i metod diagnostycznych. W cukrzycy typu 1 roczny wzrost częstości CAN wynosi około 2%, a w typie 2 – około 6%. Neuropatia autonomiczna może być obecna u 7% pacjentów już w momencie rozpoznania cukrzycy, a po 15 latach jej częstość może wzrosnąć do 50-60%. W stanie przedcukrzycowym częstość CAN wynosi od 9% do 38%, a w populacji z łączonym IFG i IGT – 11,4%. Diagnostyka opiera się na testach odruchów autonomicznych sercowo-naczyniowych (bateria Ewinga), które oceniają funkcję współczulnego i przywspółczulnego układu nerwowego. Neuropatia autonomiczna wiąże się ze zwiększonym ryzykiem śmiertelności całkowitej (RR 3,17; 95% CI 2,11-4,78; p<0,00001) oraz sercowo-naczyniowej, a także z powikłaniami takimi jak przewlekła choroba nerek, gastropareza, zaburzenia motoryki jelit, dysfunkcje seksualne i pęcherza moczowego.

Epidemiologia uszkodzenia nerwów autonomicznych

Uszkodzenie nerwów autonomicznych (autonomiczna neuropatia) jest poważnym i często pomijanym powikłaniem wielu chorób, przy czym cukrzyca stanowi najczęstszą przyczynę tego schorzenia. Częstość występowania neuropatii autonomicznej różni się znacząco w zależności od populacji badanej, zastosowanych metod diagnostycznych oraz niejednolitych definicji, co utrudnia porównywanie danych epidemiologicznych między różnymi badaniami.¹²

Częstotliwość występowania w populacji ogólnej

W populacji ogólnej częstość występowania neuropatii obwodowej, która może obejmować komponenty autonomiczne, wynosi od 1% do 7%, z wyższymi wskaźnikami wśród osób powyżej 50. roku życia.³ Schorzenie to może dotyczyć osób obu płci i w każdym wieku, chociaż wiek zachorowania jest ściśle związany z podstawową patofizjologią.⁴

Częstotliwość występowania w cukrzycy

Diabetyczna neuropatia autonomiczna (DAN) jest najczęstszą postacią neuropatii autonomicznej. Metaanaliza badań obejmujących dorosłych pacjentów z lat 1966-2001 wykazała, że częstość występowania sercowo-naczyniowej neuropatii autonomicznej (CAN) waha się między 1% a 90%.⁵ Dimitropoulos raportował częstość występowania CAN między 1% a 90% u pacjentów z cukrzycą typu 1 oraz 20-70% u pacjentów z cukrzycą typu 2.⁶

W badaniach populacyjnych częstość występowania neuropatii autonomicznej, definiowanej jako co najmniej jeden nieprawidłowy wynik testu zmienności rytmu serca, wynosiła 16,7%.⁷ Potwierdzona CAN (definiowana jako nieprawidłowość w co najmniej dwóch wynikach testów częstości akcji serca) w badaniach klinicznych w nieselektywnych populacjach, obejmujących zarówno pacjentów z cukrzycą typu 1, jak i typu 2, waha się od 16,6% do 20%, a częstość ta może wzrosnąć do 65% wraz z wiekiem i czasem trwania cukrzycy.⁸

Występowanie neuropatii autonomicznej w różnych populacjach

Sercowo-naczyniowa neuropatia autonomiczna jest wykrywana u około 7% pacjentów zarówno z cukrzycą typu 1, jak i typu 2 w momencie diagnozy.⁹¹⁰ W badaniu DCCT (Diabetes Control and Complications Trial) stwierdzono, że 1,65% pacjentów z 5-letnim czasem trwania cukrzycy miało nieprawidłową zmienność rytmu serca. Częstość wzrastała do 6,2% u pacjentów z czasem trwania cukrzycy powyżej 5 lat, ale poniżej 9 lat, oraz do 12,2% po 9 latach trwania cukrzycy.¹¹

Roczny wzrost częstości występowania CAN wynosi około 6% w cukrzycy typu 2 i 2% w cukrzycy typu 1.¹²¹³ Badania CAN w populacji pediatrycznej z cukrzycą typu 1 wykazały częstość występowania od 16% do 75% w testach funkcji nerwów sercowo-naczyniowych oraz od 8% do 16% w badaniach pupilometrycznych.¹⁴

Neuropatia autonomiczna u pacjentów ze stanem przedcukrzycowym

Dane na temat częstości występowania neuropatii autonomicznej w stanie przedcukrzycowym są bardzo skąpe. Według badania epidemiologicznego z wiarygodnym podejściem diagnostycznym, częstość występowania u osób z łączonym IFG (nieprawidłowa glikemia na czczo) i IGT (nieprawidłowa tolerancja glukozy) wynosiła 11,4%.¹⁵¹⁶

Eleftheriadou i wsp. wykazali w kompleksowym przeglądzie systematycznym, że częstość CAN jest wyższa u osób ze stanem przedcukrzycowym (9-38%) niż u osób z prawidłową tolerancją glukozy (0-18%).¹⁷ Badanie KORA S4 określiło częstość występowania CAN w populacji ze stanem przedcukrzycowym i wykazało rosnącą częstość wraz ze wzrostem nasilenia dysglikemii: 4,5% dla normoglikemii, 5,9% dla upośledzenia tolerancji glukozy, 8,1% dla nieprawidłowej glikemii na czczo oraz 11,4% dla kombinacji nieprawidłowej glikemii na czczo i upośledzonej tolerancji glukozy.¹⁸

Czynniki ryzyka i zmienność występowania

Głównym czynnikiem ryzyka neuropatii autonomicznej u pacjentów z cukrzycą jest hiperglikemia.¹⁹ W badaniu DCCT (Diabetes Control and Complications Trial) roczna częstość występowania neuropatii wynosiła 2% rocznie, ale spadła do 0,56% przy intensywnym leczeniu cukrzycy typu 1.²⁰

Czas trwania cukrzycy i kontrola glikemii

Częstość występowania neuropatii autonomicznej wzrasta wraz z czasem trwania cukrzycy. Może być zidentyfikowana u pacjentów w momencie diagnozy cukrzycy u nawet 7% pacjentów, ale może wzrosnąć nawet do 50% po 15 latach.²¹ Słaba kontrola glikemii i dłuższy czas trwania choroby wiążą się z wyższą częstością występowania CAN w cukrzycy typu 2.²²

Zgodnie z badaniem ACCORD, częstość występowania CAN u osób z cukrzycą typu 2 waha się od 1,8% do 7,6%. Jednakże badania pacjentów z ponad 15-letnim czasem trwania cukrzycy wykazały częstość występowania sięgającą nawet 60%.²³

Wpływ płci, wieku i pochodzenia etnicznego

Wpływ płci na epidemiologię CAN jest kontrowersyjny.²⁴ W wieloośrodkowym, przekrojowym badaniu obejmującym 3250 pacjentów z cukrzycą, częstość występowania CAN nie różniła się między mężczyznami a kobietami. Jednakże w badaniu ACCORD obejmującym ponad 8000 pacjentów z cukrzycą typu 2, CAN była częstsza u kobiet.²⁵

Wpływ pochodzenia etnicznego na częstość występowania CAN również był szeroko dyskutowany w literaturze. Zasugerowano, że Azjaci Południowi mają niższe wskaźniki neuropatii obwodowej niż biali Europejczycy z cukrzycą.²⁶ Jednak stosując analizę spektralną zmienności rytmu serca, a także analizę częstotliwości i domeny czasowej, nie wykazano różnicy w częstości występowania CAN między Azjatami Południowymi a białymi Europejczykami.²⁷

Nadzór i monitorowanie neuropatii autonomicznej

Ze względu na poważne konsekwencje neuropatii autonomicznej, w tym zwiększoną śmiertelność i chorobowość, zaleca się wczesne rozpoznanie klinicznej lub subklinicznej neuropatii autonomicznej, co jest przydatne do stratyfikacji ryzyka i ukierunkowania konkretnych celów glikemicznych, lipidowych i wartości ciśnienia krwi.²⁸

Rekomendacje dotyczące badań przesiewowych

Podkomisja CAN Panelu Konsensusu w Toronto dotycząca neuropatii cukrzycowej zaleca, aby pacjenci z cukrzycą typu 2 byli badani w kierunku CAN w momencie diagnozy, a pacjenci z cukrzycą typu 1 w ciągu 5 lat od rozpoznania, szczególnie u pacjentów wykazujących wiele czynników ryzyka, takich jak słaba kontrola glikemii, palenie tytoniu, nadciśnienie tętnicze lub dyslipidemia.²⁹

Według Amerykańskiego Towarzystwa Diabetologicznego, jeśli masz cukrzycę typu 2, zaleca się coroczne badania przesiewowe w kierunku neuropatii autonomicznej, począwszy od momentu otrzymania diagnozy. W przypadku osób z cukrzycą typu 1 stowarzyszenie zaleca coroczne badania przesiewowe, począwszy od pięciu lat po rozpoznaniu.³⁰

Istnieją jednak pewne kontrowersje dotyczące wytycznych dotyczących badań przesiewowych w kierunku CAN. Na przykład, stanowisko Amerykańskiego Towarzystwa Diabetologicznego (ADA) uznaje pacjenta za kwalifikującego się do oceny CAN tylko wtedy, gdy ma powikłania mikronaczyniowe i/lub brak świadomości hipoglikemii. Z drugiej strony, Włoskie Towarzystwo Diabetologiczne (SID) i Włoskie Stowarzyszenie Klinicznych Diabetologów (AMD) podały, że pacjenci powinni być oceniani, jeśli mają wysokie ryzyko sercowo-naczyniowe i powikłania, podczas gdy Konsensus z Toronto podkreśla, że badania przesiewowe w kierunku objawów i oznak CAN powinny być powszechne.³¹

Badania diagnostyczne i metody oceny

Standardowe diagnostyczne miary CAN to testy odruchów autonomicznych sercowo-naczyniowych, składających się z pięciu nieinwazyjnych testów (powszechnie znanych jako bateria Ewinga), które oceniają zarówno współczulny, jak i przywspółczulny układ nerwowy.³²

Duża zmienność w raportowanych częstościach występowania CAN może być spowodowana heterogenicznością metod oceny używanych do klasyfikacji CAN, co utrudnia porównywanie danych epidemiologicznych między różnymi badaniami.³³

Wpływ na zdrowie publiczne i prognozy

Neuropatia autonomiczna sercowo-naczyniowa jest związana ze zwiększoną śmiertelnością, chorobami układu sercowo-naczyniowego, przewlekłą chorobą nerek i chorobowością u pacjentów z cukrzycą.³⁴

Wpływ na śmiertelność i choroby układu krążenia

Badania kliniczne wykazały zwiększone ryzyko śmiertelności u pacjentów z neuropatią autonomiczną. W badaniu ACCORD pacjenci z CAN, zidentyfikowani na podstawie miar takich jak odchylenie standardowe odstępów normalnych od normalnych i odstęp QT, doświadczyli około dwukrotnego wzrostu ryzyka śmiertelności z wszystkich przyczyn i trzykrotnego wzrostu ryzyka śmiertelności z przyczyn sercowo-naczyniowych.³⁵

Badanie ONTARGET/TRANSCEND wykazało, że utrata lub odwrócenie nocnego spadku ciśnienia krwi jest znacząco związane ze zwiększonym ryzykiem poważnych zdarzeń sercowo-naczyniowych, śmiertelności z przyczyn sercowo-naczyniowych i śmiertelności ogólnej.³⁶

Losowy efekt oszacowania Mantela-Haenszela dla zbiorczego RR dla śmiertelności z wszystkich przyczyn u pacjentów z CAN wynosił 3,17 (95% CI 2,11 do 4,78; p<0,00001, I²=89%).³⁷

Prognozy epidemiologiczne

Przewiduje się wzrost częstości występowania CAN równolegle z rosnącym obciążeniem cukrzycą typu 1 i 2.³⁸ Oczekuje się wzrostu zachorowalności na CAN ze względu na postęp cukrzycy jako globalnej epidemii. W 2019 roku cukrzyca dotknęła 463 miliony ludzi na całym świecie. Przewiduje się, że scenariusz ten wzrośnie do ponad 592 milionów do 2035 roku; według Międzynarodowej Federacji Diabetologicznej liczba ta wzrośnie do 700 milionów (10,9% częstości występowania) do 2045 roku.³⁹

Łącznie występowanie z innymi powikłaniami cukrzycy

Diabetyczna neuropatia autonomiczna może również powodować zaburzenia żołądkowo-jelitowe, wpływając na każdą część przewodu pokarmowego: opóźniony przejście przełyku (50%), gastropareza (40%), zaburzenia motoryki jelita cienkiego i grubego z biegunką (20%) i zaparcia (25%).⁴⁰

Częstość występowania organicznej dysfunkcji seksualnej jest również wysoka, z zaburzeniami erekcji (35-90%) i wytrysk wsteczny (32%). Dysfunkcja pęcherza moczowego wykrywana jest u 43-85% pacjentów z cukrzycą typu 1 i u 25% pacjentów z cukrzycą typu 2.⁴¹

W grupie pacjentów z cukrzycą typu 1 i 2 ryzyko rozwoju CAN wzrastało w obecności neuropatii obwodowej, retinopatii i przyspieszonej miażdżycy (odzwierciedlonej przez zwiększoną IMT i zmniejszone ABI). Te związki między dysfunkcją autonomiczną serca a powikłaniami mikro- i makronaczyniowymi były bardziej widoczne w cukrzycy typu 2.⁴²

Regionalne różnice w występowaniu

Badania neuropatii autonomicznej sercowo-naczyniowej wykazały znaczne różnice regionalne w jej częstości występowania. W jednym z badań przeprowadzonych w Ugandzie wśród dorosłych w ambulatoryjnej opiece diabetologicznej, CAN wykryto u 156/299 (52,2%) uczestników na podstawie jednego lub więcej nieprawidłowych testów odruchów autonomicznych sercowo-naczyniowych. Z 299 uczestników, 88 (29,4%) zostało sklasyfikowanych jako wczesne CAN, podczas gdy 61/299 (20,4%) i 7/299 (2,3%) zostało sklasyfikowanych jako definitywne i ciężkie (zaawansowane) CAN.⁴³

Badanie wśród pacjentów z cukrzycą typu 1 i 2 wykazało, że częstość występowania CAN wynosiła 39,1% w cukrzycy typu 2 i 61,8% w cukrzycy typu 1.⁴⁴ W innym niedawnym badaniu łączna częstość występowania CAN wynosiła 85,7% wśród badanych pacjentów z cukrzycą typu 2.⁴⁵

Badanie w community-based populacji ludzi z cukrzycą typu 2, obserwowanych przez średnio 10 lat, wykazało, że definite CAN było znacząco związane z zapadalnoścvią na chorobę niedokrwienną serca i niewydolność serca w porównaniu zarówno z brakiem CAN, jak i możliwym CAN w analizach przeżycia.⁴⁶

Obecne badanie nie dostarczyło dowodów na to, że możliwe lub definitywne CAN oceniane przez zakres zalecanych testów CART jest niezależnym predyktorem zapadalności na chorobę niedokrwienną serca lub niewydolność serca podczas stosunkowo długoterminowej obserwacji u pacjentów z cukrzycą typu 2 żyjących w społeczności.⁴⁷

Wyzwania w diagnozowaniu i nadzorze

Neuropatia autonomiczna sercowo-naczyniowa jest nadal niedodiagnozowana u pacjentów z cukrzycą. Intensywna interwencja wieloczynnikowa ukierunkowana na styl życia, kontrolę glikemii i czynniki ryzyka chorób układu krążenia zapobiega rozwojowi i spowalnia postęp CAN.⁴⁸

Szacuje się, że około 50% osób z cukrzycą pozostaje niezdiagnozowanych, a wśród tych zdiagnozowanych, diagnoza zazwyczaj pojawia się bardzo późno, około 20 lat po wystąpieniu choroby. Biorąc pod uwagę, że CAN może występować nawet przed wystąpieniem cukrzycy, jest to znacznie niedodiagnozowane i niedoszacowane powikłanie mikronaczyniowe.⁴⁹

Naturalna progresja CAN obejmuje bezobjawową, subkliniczną i odwracalną fazę, która reprezentuje stadium początkowe. Następnie CAN postępuje do bardziej zaawansowanych stadiów, z objawami i większym upośledzeniem autonomicznych włókien sercowych.⁵⁰

Typ cukrzycy	Częstość występowania CAN	Roczny wzrost częstości	Występowanie przy diagnozie
Cukrzyca typu 1	1-90%	2%	7%
Cukrzyca typu 2	20-73%	6%	7%
Stan przedcukrzycowy	9-38%	Brak danych	11,4% (w łączonym IFG i IGT)

Choroba układu sercowo-naczyniowego jest główną przyczyną śmierci wśród pacjentów z cukrzycą, podkreślając znaczenie wczesnych badań przesiewowych, stratyfikacji osób wysokiego ryzyka i terminowych interwencji w celu zapobiegania i zarządzania początkiem i progresją chorób. Neuropatia autonomiczna, która jest ściśle związana z chorobami układu krążenia, występuje częściej niż powszechnie uznawane. Jednakże złożoność testowania i trudność w interpretacji wyników często prowadzą do jej niedostatecznego rozpoznania w warunkach klinicznych.⁵¹

CAN jest poważnym, ale czasami niedodiagnozowanym powikłaniem cukrzycy. Pomimo jej znaczącego wpływu na kliniczne wyniki, neuropatia autonomiczna jest nadal niedodiagnozowana z powodu braku rutynowych badań przesiewowych i nieświadomości pracowników służby zdrowia.⁵²

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Materiały źródłowe

#1 Autonomic Neuropathy: Causes, and Treatment | Doctor
https://patient.info/doctor/autonomic-neuropathy
How common is autonomic neuropathy? (Epidemiology) In general, these can occur in men and women at any age, but the epidemiology will depend on the particular cause. Some causes are very rare. However, one of the most common causes of autonomic neuropathy is likely to be diabetes mellitus. Progressive autonomic failure usually becomes apparent in the sixth decade of life. Typically it manifests with genitourinary symptoms and orthostatic hypotension but without somatic symptoms.
#2 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. […] The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. […] A meta-analysis of adult patients including 15 studies from 1966 to 2001 reported prevalence rates of CAN between 1 and 90%, while Dimitropoulos reported a prevalence of CAN that varies between 1 and 90% in patients with T1DM and 20-70% in patients with T2DM. […] In a community-based population study, the prevalence of autonomic neuropathy, defined by one or more abnormal HR variability test results was 16.7%. […] The prevalence of confirmed CAN (defined as the abnormality of at least two cardiovascular HR results) in clinical studies in unselected populations, including both T1DM and T2DM patients, varies from 16.6 to 20%, and this prevalence may increase to 65% with increasing age and diabetes duration.
#3 Peripheral Neuropathy: Evaluation and Differential Diagnosis | AAFP
https://www.aafp.org/pubs/afp/issues/2020/1215/p732.html
The prevalence of peripheral neuropathy in the general population ranges from 1% to 7%, with higher rates among those older than 50 years. The most common identifiable causes of peripheral neuropathy include diabetes mellitus, nerve compression or injury, alcohol use, toxin exposure, hereditary diseases, and nutritional deficiencies. […] Peripheral neuropathy affects 25% to 50% of patients with diabetes, depending on factors such as the patient’s age, number of years with diabetes, and level of diabetes control. Peripheral neuropathy is idiopathic in 25% to 46% of cases, and this is more common with increasing patient age. […] Small nerve fibers mediate pain, temperature, and autonomic functions. […] Autonomic symptoms may include orthostatic intolerance, gastroparesis, bowel and bladder changes, erectile dysfunction, and blurry vision.
#4 Autonomic Neuropathy: Background, Pathophysiology, Inherited Autonomic Neuropathies
https://emedicine.medscape.com/article/1173756-overview
Falls and loss of consciousness are significant contributors to morbidity associated with autonomic neuropathies. They may lead to injury, particularly in the elderly. Often, an autonomic neuropathy manifests with orthostatic hypotension, which has been associated with increased mortality in the middle aged and elderly. […] Many cases of autonomic neuropathy have a gradually progressive course, leading to a poor outcome. Patients with severe dysautonomia are at risk for sudden death secondary to cardiac dysrhythmia, as has been documented in GBS and diabetic neuropathy. […] Autonomic neuropathies may be seen in all races and ethnicities. Certain subtypes may demonstrate an increased incidence in specific ethnic groups. […] In general, no predilection for autonomic neuropathies exists with regard to sex. POTS and connective tissue diseases are more common among females. Fabry disease is inherited as an X-linked recessive disorder; therefore, it manifests predominantly in males. […] In general, no predilection for autonomic neuropathies exists with regard to age. Age of onset is highly dependent upon the underlying pathophysiology. Patients with most forms of HSAN (except HSAN I) present at birth or in childhood.
#5 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. […] The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. […] A meta-analysis of adult patients including 15 studies from 1966 to 2001 reported prevalence rates of CAN between 1 and 90%, while Dimitropoulos reported a prevalence of CAN that varies between 1 and 90% in patients with T1DM and 20-70% in patients with T2DM. […] In a community-based population study, the prevalence of autonomic neuropathy, defined by one or more abnormal HR variability test results was 16.7%. […] The prevalence of confirmed CAN (defined as the abnormality of at least two cardiovascular HR results) in clinical studies in unselected populations, including both T1DM and T2DM patients, varies from 16.6 to 20%, and this prevalence may increase to 65% with increasing age and diabetes duration.
#6 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. […] The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. […] A meta-analysis of adult patients including 15 studies from 1966 to 2001 reported prevalence rates of CAN between 1 and 90%, while Dimitropoulos reported a prevalence of CAN that varies between 1 and 90% in patients with T1DM and 20-70% in patients with T2DM. […] In a community-based population study, the prevalence of autonomic neuropathy, defined by one or more abnormal HR variability test results was 16.7%. […] The prevalence of confirmed CAN (defined as the abnormality of at least two cardiovascular HR results) in clinical studies in unselected populations, including both T1DM and T2DM patients, varies from 16.6 to 20%, and this prevalence may increase to 65% with increasing age and diabetes duration.
#7 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. […] The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. […] A meta-analysis of adult patients including 15 studies from 1966 to 2001 reported prevalence rates of CAN between 1 and 90%, while Dimitropoulos reported a prevalence of CAN that varies between 1 and 90% in patients with T1DM and 20-70% in patients with T2DM. […] In a community-based population study, the prevalence of autonomic neuropathy, defined by one or more abnormal HR variability test results was 16.7%. […] The prevalence of confirmed CAN (defined as the abnormality of at least two cardiovascular HR results) in clinical studies in unselected populations, including both T1DM and T2DM patients, varies from 16.6 to 20%, and this prevalence may increase to 65% with increasing age and diabetes duration.
#8 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. […] The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. […] A meta-analysis of adult patients including 15 studies from 1966 to 2001 reported prevalence rates of CAN between 1 and 90%, while Dimitropoulos reported a prevalence of CAN that varies between 1 and 90% in patients with T1DM and 20-70% in patients with T2DM. […] In a community-based population study, the prevalence of autonomic neuropathy, defined by one or more abnormal HR variability test results was 16.7%. […] The prevalence of confirmed CAN (defined as the abnormality of at least two cardiovascular HR results) in clinical studies in unselected populations, including both T1DM and T2DM patients, varies from 16.6 to 20%, and this prevalence may increase to 65% with increasing age and diabetes duration.
#9 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Cardiovascular autonomic neuropathy is detected in about 7% of both T1DM and T2DM at the time of diagnosis. […] Discussing about pediatric population, a systematic review by Tang including 19 studies about young people with T1DM, reported a prevalence of DAN that varied between 16 and 75% for cardiovascular nerve function tests and between 8 and 16% in pupillometry studies. […] The Diabetes Control and Complications Trial (DCCT) found that 1.65% had abnormal HR variability at baseline in patients with 5 years duration of diabetes. The prevalence increased to 6.2% in patients with more than 5 but 9 years duration of diabetes and to 12.2% by 9 years duration of diabetes. […] The annual increase in prevalence of CAN has been reported about 6% in T2DM and 2% in T1DM. […] Diabetic autonomic neuropathy may also cause GI disturbances, affecting every part of the GI tract: delayed esophageal transit (50%), gastroparesis (40%), disordered small and large intestinal motility with diarrhea (20%) and constipation (25%). […] The prevalence of organic sexual dysfunction is also high with erectile dysfunction (35-90%) and retrograde ejaculation (32%). […] Bladder dysfunction is detected in 43-85% of patients with T1DM and in 25% of T2DM.
#10 Diabetic autonomic neuropathy – UpToDate
https://www.uptodate.com/contents/diabetic-autonomic-neuropathy
Diabetic autonomic neuropathy (DAN) is a common form of neuropathy in patients with diabetes mellitus characterized by dysfunction due to impairment of peripheral autonomic nerves. A wide spectrum of manifestations can affect many different organ systems, including the cardiovascular, gastrointestinal, genitourinary, sudomotor and vasomotor, and neuroendocrine systems (table 1). […] DAN is a common form of neuropathy in patients with diabetes mellitus. The prevalence of DAN increases with the duration of diabetes. It may be identified in patients at the time of diabetes diagnosis in up to 7 percent but can be as high as 50 percent after 15 years. DAN occurs in patients with type 1 or type 2 diabetes mellitus. […] We recommend assessing all patients with diabetes mellitus for DAN. Some patients with DAN may not have overt symptoms. Early recognition of clinical or subclinical DAN is useful for risk stratification and to guide specific glycemic, lipid, and blood pressure targets.
#11 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Cardiovascular autonomic neuropathy is detected in about 7% of both T1DM and T2DM at the time of diagnosis. […] Discussing about pediatric population, a systematic review by Tang including 19 studies about young people with T1DM, reported a prevalence of DAN that varied between 16 and 75% for cardiovascular nerve function tests and between 8 and 16% in pupillometry studies. […] The Diabetes Control and Complications Trial (DCCT) found that 1.65% had abnormal HR variability at baseline in patients with 5 years duration of diabetes. The prevalence increased to 6.2% in patients with more than 5 but 9 years duration of diabetes and to 12.2% by 9 years duration of diabetes. […] The annual increase in prevalence of CAN has been reported about 6% in T2DM and 2% in T1DM. […] Diabetic autonomic neuropathy may also cause GI disturbances, affecting every part of the GI tract: delayed esophageal transit (50%), gastroparesis (40%), disordered small and large intestinal motility with diarrhea (20%) and constipation (25%). […] The prevalence of organic sexual dysfunction is also high with erectile dysfunction (35-90%) and retrograde ejaculation (32%). […] Bladder dysfunction is detected in 43-85% of patients with T1DM and in 25% of T2DM.
#12 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Cardiovascular autonomic neuropathy is detected in about 7% of both T1DM and T2DM at the time of diagnosis. […] Discussing about pediatric population, a systematic review by Tang including 19 studies about young people with T1DM, reported a prevalence of DAN that varied between 16 and 75% for cardiovascular nerve function tests and between 8 and 16% in pupillometry studies. […] The Diabetes Control and Complications Trial (DCCT) found that 1.65% had abnormal HR variability at baseline in patients with 5 years duration of diabetes. The prevalence increased to 6.2% in patients with more than 5 but 9 years duration of diabetes and to 12.2% by 9 years duration of diabetes. […] The annual increase in prevalence of CAN has been reported about 6% in T2DM and 2% in T1DM. […] Diabetic autonomic neuropathy may also cause GI disturbances, affecting every part of the GI tract: delayed esophageal transit (50%), gastroparesis (40%), disordered small and large intestinal motility with diarrhea (20%) and constipation (25%). […] The prevalence of organic sexual dysfunction is also high with erectile dysfunction (35-90%) and retrograde ejaculation (32%). […] Bladder dysfunction is detected in 43-85% of patients with T1DM and in 25% of T2DM.
#13 Cardiac autonomic neuropathy in patients with diabetes mellitus
https://www.wjgnet.com/1948-9358/full/v5/i1/17.htm
The prevalence of CAN varies between 1%-90% in patients with type 1 DM (T1DM) and 20%-73% in patients with T2DM. This huge variation in CAN prevalence is due to the inconsistency in the criteria used to diagnose CAN and significant differences in the study populations, particularly in relation to CAN risk factors (such as age, gender and DM duration amongst others). […] CAN has been detected at time of diagnosis of diabetes in patients with either T1DM or T2DM irrespective of age, suggesting that CAN presentation is not limited by age or type of diabetes and can occur before DM is evident clinically. However, the duration of diabetes is an independent factor for developing CAN irrespective to diabetes type. CAN is detected in about 7% of both T1DM and T2DM at the time of initial diagnosis, and it is estimated that the risk for developing CAN increases annually by approximately 6% and 2% in patients with T1DM and T2DM respectively.
#14 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Cardiovascular autonomic neuropathy is detected in about 7% of both T1DM and T2DM at the time of diagnosis. […] Discussing about pediatric population, a systematic review by Tang including 19 studies about young people with T1DM, reported a prevalence of DAN that varied between 16 and 75% for cardiovascular nerve function tests and between 8 and 16% in pupillometry studies. […] The Diabetes Control and Complications Trial (DCCT) found that 1.65% had abnormal HR variability at baseline in patients with 5 years duration of diabetes. The prevalence increased to 6.2% in patients with more than 5 but 9 years duration of diabetes and to 12.2% by 9 years duration of diabetes. […] The annual increase in prevalence of CAN has been reported about 6% in T2DM and 2% in T1DM. […] Diabetic autonomic neuropathy may also cause GI disturbances, affecting every part of the GI tract: delayed esophageal transit (50%), gastroparesis (40%), disordered small and large intestinal motility with diarrhea (20%) and constipation (25%). […] The prevalence of organic sexual dysfunction is also high with erectile dysfunction (35-90%) and retrograde ejaculation (32%). […] Bladder dysfunction is detected in 43-85% of patients with T1DM and in 25% of T2DM.
#15 Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet
https://e-dmj.org/DOIx.php?id=10.4093/dmj.2018.0259
CAN affects at least 20% of unselected patients, and up to 65% of those with increasing age and diabetes duration. […] Data on the prevalence of autonomic neuropathy in pre-diabetes are very scarce; according to an epidemiological study with a reliable diagnostic approach, the prevalence in subjects with combined IFG and IGT was 11.4%. […] This prevalence is not far from that of CAN at diagnosis in T2DM, which according to CARTs is reported to be around 7% and increases with diabetes duration by 4.6% to 6% per year. […] The prevalence of confirmed CAN (based on at least two abnormal CARTs) increased from 9.0% to 15.1% with an annual incidence of 1.8%, which is lower than previously documented. […] However, the early screening-based diagnosis of T2DM, high intensity treatment from diagnosis, and overall good control of glycaemia and risk factors during the 13 years of follow-up might have mitigated CAN progression.
#16
https://link.springer.com/article/10.1007/s00125-024-06242-0
Prevalence figures vary according to the aetiology of diabetes, with prevalence reported as being between 29% and 54% for type 1 diabetes and between 12% and 73% for type 2 diabetes. […] Eleftheriadou et al demonstrated through a comprehensive systematic review that CAN prevalence is higher in those with prediabetes (9-38%) than in those with normal glucose tolerance (0-18%). […] The KORA S4 survey determined the prevalence of CAN in a population with prediabetes and demonstrated increasing prevalence with increasing severity of dysglycaemia: 4.5% for normoglycaemia, 5.9% for impaired glucose tolerance, 8.1% for impaired fasting plasma glucose and 11.4% for a combination of impaired fasting plasma glucose and impaired glucose tolerance.
#17
https://link.springer.com/article/10.1007/s00125-024-06242-0
Prevalence figures vary according to the aetiology of diabetes, with prevalence reported as being between 29% and 54% for type 1 diabetes and between 12% and 73% for type 2 diabetes. […] Eleftheriadou et al demonstrated through a comprehensive systematic review that CAN prevalence is higher in those with prediabetes (9-38%) than in those with normal glucose tolerance (0-18%). […] The KORA S4 survey determined the prevalence of CAN in a population with prediabetes and demonstrated increasing prevalence with increasing severity of dysglycaemia: 4.5% for normoglycaemia, 5.9% for impaired glucose tolerance, 8.1% for impaired fasting plasma glucose and 11.4% for a combination of impaired fasting plasma glucose and impaired glucose tolerance.
#18
https://link.springer.com/article/10.1007/s00125-024-06242-0
Prevalence figures vary according to the aetiology of diabetes, with prevalence reported as being between 29% and 54% for type 1 diabetes and between 12% and 73% for type 2 diabetes. […] Eleftheriadou et al demonstrated through a comprehensive systematic review that CAN prevalence is higher in those with prediabetes (9-38%) than in those with normal glucose tolerance (0-18%). […] The KORA S4 survey determined the prevalence of CAN in a population with prediabetes and demonstrated increasing prevalence with increasing severity of dysglycaemia: 4.5% for normoglycaemia, 5.9% for impaired glucose tolerance, 8.1% for impaired fasting plasma glucose and 11.4% for a combination of impaired fasting plasma glucose and impaired glucose tolerance.
#19 Diabetic neuropathy – Wikipedia
https://en.wikipedia.org/wiki/Diabetic_neuropathy
Globally diabetic neuropathy affects approximately 132 million people as of 2010 (1.9% of the population). […] Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes. A systematic review has found that diabetic peripheral neuropathy affects 30% of diabetes patients. […] The main risk factor for diabetic neuropathy is hyperglycemia. In the DCCT (Diabetes Control and Complications Trial, 1995) study, the annual incidence of neuropathy was 2% per year but dropped to 0.56% with intensive treatment of Type 1 diabetics. The progression of neuropathy is dependent on the degree of glycemic control in both Type 1 and Type 2 diabetes. Duration of diabetes, age, cigarette smoking, hypertension, height, and hyperlipidemia are also risk factors for diabetic neuropathy.
#20 Diabetic neuropathy – Wikipedia
https://en.wikipedia.org/wiki/Diabetic_neuropathy
Globally diabetic neuropathy affects approximately 132 million people as of 2010 (1.9% of the population). […] Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes. A systematic review has found that diabetic peripheral neuropathy affects 30% of diabetes patients. […] The main risk factor for diabetic neuropathy is hyperglycemia. In the DCCT (Diabetes Control and Complications Trial, 1995) study, the annual incidence of neuropathy was 2% per year but dropped to 0.56% with intensive treatment of Type 1 diabetics. The progression of neuropathy is dependent on the degree of glycemic control in both Type 1 and Type 2 diabetes. Duration of diabetes, age, cigarette smoking, hypertension, height, and hyperlipidemia are also risk factors for diabetic neuropathy.
#21 Diabetic autonomic neuropathy – UpToDate
https://www.uptodate.com/contents/diabetic-autonomic-neuropathy
Diabetic autonomic neuropathy (DAN) is a common form of neuropathy in patients with diabetes mellitus characterized by dysfunction due to impairment of peripheral autonomic nerves. A wide spectrum of manifestations can affect many different organ systems, including the cardiovascular, gastrointestinal, genitourinary, sudomotor and vasomotor, and neuroendocrine systems (table 1). […] DAN is a common form of neuropathy in patients with diabetes mellitus. The prevalence of DAN increases with the duration of diabetes. It may be identified in patients at the time of diabetes diagnosis in up to 7 percent but can be as high as 50 percent after 15 years. DAN occurs in patients with type 1 or type 2 diabetes mellitus. […] We recommend assessing all patients with diabetes mellitus for DAN. Some patients with DAN may not have overt symptoms. Early recognition of clinical or subclinical DAN is useful for risk stratification and to guide specific glycemic, lipid, and blood pressure targets.
#22 Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus | Scientific Reports
https://www.nature.com/articles/s41598-021-80962-w
The poorer glycemic control and the longer the duration of the disease, the higher the prevalence of CAN in T2DM. […] Age, duration of disease, WHR, and HbA1c are well correlated with the severity of CAN. […] CAN is common among people with diabetes (52.82%), the poorer the glycemic control and the longer the duration of the disease, the higher the incidence of CAN in T2DM. […] Parasympathetic impairment is more sensitive to the detection of autonomic dysfunction.
#23 Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes
https://www.e-jcpp.org/journal/view.php?number=98
This review explores the complex relationship between diabetic neuropathy and cardiovascular disease (CVD). Neuropathy, a common complication of type 1 and type 2 diabetes, is divided into autonomic and peripheral types, each impacting cardiovascular health. Cardiovascular autonomic neuropathy, a form of autonomic neuropathy, is associated with various CVD complications, including arrhythmias, impaired nocturnal blood pressure regulation, and increased mortality. The prevalence of cardiovascular autonomic neuropathy varies depending on the type and duration of diabetes and is influenced by factors like glycemic control and metabolic stress. […] The prevalence of autonomic neuropathy among individuals with diabetes varies based on the type of diabetes, the duration of the disease, and the effectiveness of blood glucose control. The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study indicated that the prevalence of cardiovascular autonomic neuropathy (CAN) in those with type 2 diabetes ranges from 1.8% to 7.6%. However, studies of patients who have had diabetes for more than 15 years have reported prevalence rates as high as 60%.
#24 Cardiac autonomic neuropathy in patients with diabetes mellitus: curre | DMSO
https://www.dovepress.com/cardiac-autonomic-neuropathy-in-patients-with-diabetes-mellitus-curren-peer-reviewed-fulltext-article-DMSO
The prevalence of CAN is often reported to be higher in T2DM compared to T1DM, despite the longer diabetes duration in patients with T1DM; this is likely a reflection of patients with T2DM often being older and more likely to have more CVD risk factors for CAN than patients with T1DM. […] The impact of sex on CAN epidemiology is controversial. […] The impact of ethnicity on CAN prevalence has also been widely discussed in the literature, being cited as a possible risk factor for CAN, as lower rates of peripheral neuropathy (PN) were detected in South Asians when compared to white Europeans with DM. […] CAN is very common and often undiagnosed in patients with DM. Intensive multifactorial intervention targeting lifestyle, glycemic control, and CVD risk factors prevents the development and slows the progression of CAN. Identifying patients with CAN is important, as CAN is associated with increased mortality, CVD, CKD, perioperative morbidity, and lower-limb complications.
#25 Cardiac autonomic neuropathy in patients with diabetes mellitus
https://www.wjgnet.com/1948-9358/full/v5/i1/17.htm
The impact of gender on CAN is controversial. In a multi-centre, cross sectional study of 3250 patients with DM, CAN prevalence was no different between men and women. However, in the action to control cardiovascular risk in diabetes trial including more than 8000 patients with T2DM CAN was more prevalent in women. […] Ethnicity has also been postulated to be a risk factor for CAN as South Asians seem to have lower rates of peripheral neuropathy than White Europeans with DM. More specifically, the prevalence of small fibre neuropathy was significantly lower in Indian Asians than in Europeans and mean nerve conduction velocity Z scores (measuring large fibre neuropathy) were superior in Asians compared to Europeans. However, using heart rate variability (HRV) spectral analysis as well as frequency and time domain analysis showed no difference in CAN prevalence between South Asians and white Europeans.
#26 Cardiac autonomic neuropathy in patients with diabetes mellitus
https://www.wjgnet.com/1948-9358/full/v5/i1/17.htm
The impact of gender on CAN is controversial. In a multi-centre, cross sectional study of 3250 patients with DM, CAN prevalence was no different between men and women. However, in the action to control cardiovascular risk in diabetes trial including more than 8000 patients with T2DM CAN was more prevalent in women. […] Ethnicity has also been postulated to be a risk factor for CAN as South Asians seem to have lower rates of peripheral neuropathy than White Europeans with DM. More specifically, the prevalence of small fibre neuropathy was significantly lower in Indian Asians than in Europeans and mean nerve conduction velocity Z scores (measuring large fibre neuropathy) were superior in Asians compared to Europeans. However, using heart rate variability (HRV) spectral analysis as well as frequency and time domain analysis showed no difference in CAN prevalence between South Asians and white Europeans.
#27 Cardiac autonomic neuropathy in patients with diabetes mellitus: curre | DMSO
https://www.dovepress.com/cardiac-autonomic-neuropathy-in-patients-with-diabetes-mellitus-curren-peer-reviewed-fulltext-article-DMSO
The prevalence of CAN is often reported to be higher in T2DM compared to T1DM, despite the longer diabetes duration in patients with T1DM; this is likely a reflection of patients with T2DM often being older and more likely to have more CVD risk factors for CAN than patients with T1DM. […] The impact of sex on CAN epidemiology is controversial. […] The impact of ethnicity on CAN prevalence has also been widely discussed in the literature, being cited as a possible risk factor for CAN, as lower rates of peripheral neuropathy (PN) were detected in South Asians when compared to white Europeans with DM. […] CAN is very common and often undiagnosed in patients with DM. Intensive multifactorial intervention targeting lifestyle, glycemic control, and CVD risk factors prevents the development and slows the progression of CAN. Identifying patients with CAN is important, as CAN is associated with increased mortality, CVD, CKD, perioperative morbidity, and lower-limb complications.
#28 Diabetic autonomic neuropathy – UpToDate
https://www.uptodate.com/contents/diabetic-autonomic-neuropathy
Diabetic autonomic neuropathy (DAN) is a common form of neuropathy in patients with diabetes mellitus characterized by dysfunction due to impairment of peripheral autonomic nerves. A wide spectrum of manifestations can affect many different organ systems, including the cardiovascular, gastrointestinal, genitourinary, sudomotor and vasomotor, and neuroendocrine systems (table 1). […] DAN is a common form of neuropathy in patients with diabetes mellitus. The prevalence of DAN increases with the duration of diabetes. It may be identified in patients at the time of diabetes diagnosis in up to 7 percent but can be as high as 50 percent after 15 years. DAN occurs in patients with type 1 or type 2 diabetes mellitus. […] We recommend assessing all patients with diabetes mellitus for DAN. Some patients with DAN may not have overt symptoms. Early recognition of clinical or subclinical DAN is useful for risk stratification and to guide specific glycemic, lipid, and blood pressure targets.
#29 Cardiac Autonomic Neuropathy in Diabetes Mellitus | Methodist DeBakey Cardiovascular J
https://journal.houstonmethodist.org/articles/10.14797/mdcj-14-4-251
Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of patients with type 1 diabetes. […] The prevalence of CAN is variable based on published studies and ranges from 2 to 91 in type I diabetes mellitus (T1DM) and 25 to 75 in type 2 diabetes (T2DM). […] Based on the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, the prevalence of CAN in T1DM after 15 years was close to 60. […] The CAN Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy recommends that patients with T2DM be screened for CAN at the time of diagnosis and those with T1DM within 5 years of their diagnosis, especially in patients exhibiting multiple risk factors, such as poor glycemic control, smoking, hypertension, or dyslipidemia. […] Some studies suggest that CAN may be seen in prediabetes as well; however, the prevalence and association have not been well studied. […] The Panel also recommends that screening be part of a perioperative risk assessment in patients with coronary artery disease.
#30 Autonomic neuropathy – Symptoms & causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/autonomic-neuropathy/symptoms-causes/syc-20369829
Autonomic neuropathy occurs when there is damage to the nerves that control automatic body functions. […] Diabetes is the most common cause of autonomic neuropathy. […] If you have type 2 diabetes, the American Diabetes Association recommends annual autonomic neuropathy screening beginning when you receive your diagnosis. For people with type 1 diabetes, the association advises annual screening beginning five years after diagnosis. […] Many health conditions can cause autonomic neuropathy. […] Factors that might increase your risk of autonomic neuropathy include: Diabetes, especially when poorly controlled, increases your risk of autonomic neuropathy and other nerve damage. […] Certain inherited diseases that put you at risk of developing autonomic neuropathy can’t be prevented.
#31 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications
https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm
Currently, it is estimated that about 50% of people with diabetes mellitus remain undiagnosed and, among those diagnosed, the diagnosis usually happens very late, approximately 20 years after the onset of the disease. Thus, considering that CAN may present even before the onset of diabetes, it is a markedly underdiagnosed and underestimated microvascular complication. The natural progression of CAN comprises an asymptomatic, subclinical, and reversible phase, which represents the initial stage. Subsequently, CAN progresses to more advanced stages, with symptoms and a greater impairment of cardiac autonomic fibers. […] According to the position statement of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE), CAN screening should be performed at the time of diagnosis in patients with type 2 diabetes mellitus and five years after diagnosis in patients with type 1 diabetes mellitus. Nevertheless, there are still some controversies regarding the guidelines for CAN screening. For instance, the position statement of the American Diabetes Association (ADA) considers a patient eligible for CAN assessment only if they have microvascular complications and/or hypoglycemia unawareness. On the other hand, the Italian Society of Diabetology (SID) and the Italian Association of Clinical Diabetologists (AMD) reported that patients should be evaluated if they have high cardiovascular risk and complications, while the Toronto Consensus emphasizes that screening for symptoms and signs of CAN should be universal.
#32 Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis | BMJ Open Diabetes Research & Care
https://drc.bmj.com/content/9/2/e002480
The reference standard diagnostic measures of CAN are cardiovascular autonomic reflex tests, consisting of five non-invasive tests (commonly known as Ewings battery) that assesses both the sympathetic and parasympathetic nervous system. […] The random effects Mantel-Haenszel estimate for the pooled RR for all-cause mortality in patients with CAN was 3.17 (95%CI 2.11 to 4.78; p0.00001, I2=89%). […] CAN is a major prognostic indicator of CVE and mortality and as such simple, quick and non-invasive testing for autonomic dysfunction should be incorporated into population screening, especially considering its preventability and reversibility with lifestyle and pharmacological interventions.
#33 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications
https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm
Cardiovascular autonomic neuropathy (CAN) is a microvascular complication defined as the impairment of cardiovascular autonomic control in persons with diabetes, with no other causes. The prevalence of CAN varies from nearly 2% in patients with newly diagnosed or well-controlled diabetes, up to 60% of patients with long-standing type 2 diabetes mellitus and 90% of pancreas transplantation candidates with type 1 diabetes. The heterogeneity of evaluation methods used to classify CAN is a possible cause of this wide variation in prevalence, making it difficult to compare epidemiological data across different studies. CAN prevalence also increases with age, duration of diabetes, and poor glycemic control. […] Despite CAN manifesting as a subclinical condition for several years until the development of symptoms, it is a risk factor for silent myocardial ischemia, chronic kidney disease, myocardial dysfunction, major cardiovascular events, cardiac arrhythmias, and sudden death. Moreover, it is associated with increased morbidity and mortality risk and poor long-term diabetes prognosis. The etiology of CAN is multifactorial, and several conditions are associated with CAN, such as hyperglycemia, insulin resistance, prediabetes, obesity, hypertension, dyslipidemia, metabolic syndrome, and obstructive sleep apnea (OSA). However, it is mainly recognized as a major complication of type 1 and type 2 diabetes mellitus, since diabetic neuropathies are the most prevalent chronic microvascular complications of diabetes. Of these, autonomic neuropathies (mainly CAN) and distal symmetric polyneuropathy are the most studied to date.
#34 Cardiac autonomic neuropathy in patients with diabetes mellitus: curre | DMSO
https://www.dovepress.com/cardiac-autonomic-neuropathy-in-patients-with-diabetes-mellitus-curren-peer-reviewed-fulltext-article-DMSO
Cardiac autonomic neuropathy (CAN) is a common and often-underdiagnosed complication of diabetes mellitus (DM). CAN is associated with increased mortality, cardiovascular disease, chronic kidney disease, and morbidity in patients with DM, but despite these significant consequences CAN often remains undiagnosed for a prolonged period. […] The aim of this manuscript is to review the latest developments related to the epidemiology, pathogenesis, diagnosis, consequences, and treatment of CAN in patients with DM. […] Several studies examined the prevalence of CAN in patients with type 1 DM (T1DM) and type 2 DM (T2DM). These studies showed a large variation in CAN prevalence: 17%66% in patients with T1DM and 31%73% in patients with T2DM. […] Diabetes duration is a major risk factor for the development of CAN in patients with T1DM and T2DM.
#35 Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes
https://www.e-jcpp.org/journal/view.php?number=98
Autonomic neuropathy can result in arrhythmias, including life-threatening conditions such as QT prolongation, atrial fibrillation, and ventricular fibrillation, all of which can lead to cardiovascular abnormalities. CAN is also linked to the occurrence and progression of severe hypoglycemia, which is strongly associated with the development of CVD and progressive kidney disease. Thus, autonomic neuropathy is closely connected with the incidence of CVD and cardiovascular mortality. […] Clinical studies have demonstrated an increased risk of mortality in patients with autonomic neuropathy. In the ACCORD study, patients with CAN, identified by measures such as the standard deviation of normal-to-normal intervals and the QT interval, experienced an approximately twofold increase in the risk of all-cause mortality and a threefold increase in the risk of cardiovascular mortality.
#36 Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes
https://www.e-jcpp.org/journal/view.php?number=98
The ONTARGET/TRANSCEND (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease) investigation has demonstrated that the loss or reversal of nocturnal blood pressure dipping is significantly associated with an increased risk of major cardiovascular events, cardiovascular mortality, and overall mortality. […] CVD is the leading cause of death among patients with diabetes, underscoring the importance of early screening, stratification of high-risk individuals, and timely interventions to prevent and manage the diseases onset and progression. Autonomic neuropathy, which is closely associated with CVD, occurs more frequently than commonly recognized. However, the complexity of testing and the difficulty in interpreting results often lead to its under-recognition in clinical settings.
#37 Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis | BMJ Open Diabetes Research & Care
https://drc.bmj.com/content/9/2/e002480
The reference standard diagnostic measures of CAN are cardiovascular autonomic reflex tests, consisting of five non-invasive tests (commonly known as Ewings battery) that assesses both the sympathetic and parasympathetic nervous system. […] The random effects Mantel-Haenszel estimate for the pooled RR for all-cause mortality in patients with CAN was 3.17 (95%CI 2.11 to 4.78; p0.00001, I2=89%). […] CAN is a major prognostic indicator of CVE and mortality and as such simple, quick and non-invasive testing for autonomic dysfunction should be incorporated into population screening, especially considering its preventability and reversibility with lifestyle and pharmacological interventions.
#38
https://link.springer.com/article/10.1007/s00125-024-06242-0
Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. CAN affects approximately 20% of people with diabetes, with recent studies highlighting the presence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose), indicating early involvement of the autonomic nervous system. […] The prevalence of CAN is expected to rise in parallel with the increasing burden of type 1 and type 2 diabetes. Strategies are required for clinicians and health professionals to manage patients adequately. In this review, we aim to provide an up-to-date clinical reference for CAN, for healthcare professionals practising in diabetes, with a focus on management in the real-world setting. […] There is wide variability in the reported prevalence of CAN because of the heterogeneous populations that have been studied and the diverse definitions of CAN used. The risk of developing CAN increases with age, duration of diabetes and suboptimal glycaemic/metabolic control.
#39 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications
https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm
An increase in the incidence of CAN is expected to occur due to the progression of diabetes as a global epidemic. In 2019, diabetes mellitus affected 463 million people worldwide. This scenario is predicted to grow to over 592 million by 2035; based on the International Diabetes Federation, this number will rise to 700 million (10.9% prevalence) by 2045. These projections are worrying considering that, in 2016, diabetes was directly responsible for 1.6 million deaths, representing the seventh leading cause of death worldwide. In addition, diabetes commonly coexists with obesity, and nearly 85% of people with diabetes are type 2 diabetics; of those, 90% are obese or overweight. The burden of these chronic diseases leads to a cardiometabolic epidemic, with a staggering increase in the global prevalence of diabetes mellitus, obesity, and metabolic syndrome. Therefore, early identification and treatment of CAN could be a key point to minimize the morbidity and mortality associated with this long-lasting pandemic. The aim of this study was to review the latest content on the epidemiology, pathophysiology, and clinical assessment of CAN and to encourage healthcare workers to be aware of this clinical entity, considering that CAN is still an under-recognized condition.
#40 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Cardiovascular autonomic neuropathy is detected in about 7% of both T1DM and T2DM at the time of diagnosis. […] Discussing about pediatric population, a systematic review by Tang including 19 studies about young people with T1DM, reported a prevalence of DAN that varied between 16 and 75% for cardiovascular nerve function tests and between 8 and 16% in pupillometry studies. […] The Diabetes Control and Complications Trial (DCCT) found that 1.65% had abnormal HR variability at baseline in patients with 5 years duration of diabetes. The prevalence increased to 6.2% in patients with more than 5 but 9 years duration of diabetes and to 12.2% by 9 years duration of diabetes. […] The annual increase in prevalence of CAN has been reported about 6% in T2DM and 2% in T1DM. […] Diabetic autonomic neuropathy may also cause GI disturbances, affecting every part of the GI tract: delayed esophageal transit (50%), gastroparesis (40%), disordered small and large intestinal motility with diarrhea (20%) and constipation (25%). […] The prevalence of organic sexual dysfunction is also high with erectile dysfunction (35-90%) and retrograde ejaculation (32%). […] Bladder dysfunction is detected in 43-85% of patients with T1DM and in 25% of T2DM.
#41 Autonomic Neuropathy in Diabetes Mellitus
https://pmc.ncbi.nlm.nih.gov/articles/PMC4249492/
Cardiovascular autonomic neuropathy is detected in about 7% of both T1DM and T2DM at the time of diagnosis. […] Discussing about pediatric population, a systematic review by Tang including 19 studies about young people with T1DM, reported a prevalence of DAN that varied between 16 and 75% for cardiovascular nerve function tests and between 8 and 16% in pupillometry studies. […] The Diabetes Control and Complications Trial (DCCT) found that 1.65% had abnormal HR variability at baseline in patients with 5 years duration of diabetes. The prevalence increased to 6.2% in patients with more than 5 but 9 years duration of diabetes and to 12.2% by 9 years duration of diabetes. […] The annual increase in prevalence of CAN has been reported about 6% in T2DM and 2% in T1DM. […] Diabetic autonomic neuropathy may also cause GI disturbances, affecting every part of the GI tract: delayed esophageal transit (50%), gastroparesis (40%), disordered small and large intestinal motility with diarrhea (20%) and constipation (25%). […] The prevalence of organic sexual dysfunction is also high with erectile dysfunction (35-90%) and retrograde ejaculation (32%). […] Bladder dysfunction is detected in 43-85% of patients with T1DM and in 25% of T2DM.
#42 Cardiac autonomic neuropathy in type 1 and type 2 diabetes patients | BMC Neurology | Full Text
https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-018-1125-1
In the group of T1DM and T2DM patients, the risk for developing CAN increased in the presence of peripheral neuropathy, retinopathy and accelerated atherosclerosis (reflected by increased IMT and decreased ABI). These associations between cardiac autonomic dysfunction and micro- and macrovascular complications were more evident in T2DM. […] As the incidence of diabetes rises, so too does the requirement for healthcare, and in order to prevent CAN in patients with T1DM, we must focus on glycaemic control, but in T2DM we should focus not only on glycaemic control but also on improving adherence to cardiovascular risk factor intervention.
#43 Prevalence and Correlates of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes in Uganda: A Hospital-Based Cross-sectional Study | Global Heart
https://globalheartjournal.com/articles/10.5334/gh.765
Cardiovascular autonomic neuropathy (CAN) is a common complication in individuals with diabetes mellitus (DM) but often overlooked in clinical practice. The burden and correlates of CAN have not been extensively studied in low-income countries, particularly in sub-Saharan Africa. […] To determine the prevalence and correlates of CAN among adults in ambulatory diabetes care in southwestern Uganda. […] We enrolled 299 individuals. The mean age was 50.1 years (SD 9.8), mean HbA1c was 9.7 (SD 2.6) and 69.6% were female. CAN was detected in 156/299 (52.2%) of the participants on the basis of one or more abnormal cardiovascular autonomic reflex tests. Out of 299 participants, 88 (29.4%) were classified as early CAN while 61/299 (20.4%) and 7/299 (2.3%) were classified as definite and severe (advanced) CAN respectively. In multivariable regression models, age over 50 years (aOR 3.48, 95%CI 1.35 8.99, p = 0.010), duration of diabetes over 10 years (aOR 4.09, 95%CI 1.78 9.38, p = 0.001), and presence of diabetic retinopathy (aOR 2.25, 95%CI 1.16 4.34, p = 0.016) were correlated with CAN.
#44 Cardiac autonomic neuropathy in type 1 and type 2 diabetes patients | BMC Neurology | Full Text
https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-018-1125-1
Cardiac autonomic neuropathy (CAN) in diabetes is among the strongest risk markers for future global and cardiovascular mortality. The aim of this study was to analyse CAN prevalence and to compare the associations between CAN, the glycaemic control, cardiovascular risk factors, peripheral neuropathy, retinopathy and macroangiopathy in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). […] The prevalence of CAN was 39.1% in T2DM and 61.8% in T1DM patients. […] This study indicated that CAN is a more frequent complication in T1DM. Apart from glycaemic control, the existence of CAN is associated with potentially modifiable cardiovascular risk only in T2DM patients. The presence of other micro- and macrovascular complications increases the probability of having CAN in both types of DM (but more pronounced in T2DM).
#45
https://journals.lww.com/jfmpc/fulltext/2023/12090/prevalence_of_cardiac_autonomic_neuropathy_in.52.aspx
Out of the 42 patients, a total of 36 patients (85.7%) were diagnosed with CAN. Among those with CAN, 24 patients had early CAN (57.1%), and 12 were diagnosed with definite CAN (28.6%). […] Recognizing the prevalence of CAN in patients with T2DM is crucial for primary care physicians as it guides screening, diagnosis, and management strategies. […] Our findings revealed that among the 42 subjects included in the study, a significant proportion exhibited signs of CAN. The classification of patients based on the severity of CAN indicated that the majority of individuals had early CAN (57.1%), followed by definite CAN (28.6%), whereas only a small percentage did not show any signs of CAN (14.3%). […] The prevalence of CAN in patients with T2DM underscores the importance of primary care physicians role in screening, diagnosis, and management. The high prevalence of CAN necessitates routine screening to identify patients at risk, initiate appropriate interventions, and collaborate with specialists when needed.
#46 Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II | Cardiovascular Diabetology | Full Text
https://cardiab.biomedcentral.com/articles/10.1186/s12933-024-02185-3
The aim of this study was, therefore, to assess the prevalence and prognostic significance of CAN in well characterised, representative, community-based participants from the Fremantle Diabetes Study Phase II (FDS2). […] The present study involving representative, community-based people with type 2 diabetes followed for an average of 10 years, showed that definite CAN was significantly associated with incident IHD and HF compared to both no CAN and possible CAN in survival analyses. […] However, when CAN category was included in multivariable models of these two incident events, it did not add to other independent predictors. […] In both KaplanMeier and Cox proportional hazard analyses, there was a significant and graded relationship between CAN category and all-cause mortality, with definite CAN associated with a more than doubling of risk at 10 years after adjustment for the presence of other recognised significant independent predictors of death.
#47 Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II | Cardiovascular Diabetology | Full Text
https://cardiab.biomedcentral.com/articles/10.1186/s12933-024-02185-3
The present study has provided no evidence that either possible or definite CAN assessed by the range of recommended CARTs is an independent predictor of incident IHD or HF during relatively long-term follow-up in community-based people with type 2 diabetes. […] Possible and especially definite CAN were associated with all-cause mortality.
#48 Cardiac autonomic neuropathy in patients with diabetes mellitus: curre | DMSO
https://www.dovepress.com/cardiac-autonomic-neuropathy-in-patients-with-diabetes-mellitus-curren-peer-reviewed-fulltext-article-DMSO
The prevalence of CAN is often reported to be higher in T2DM compared to T1DM, despite the longer diabetes duration in patients with T1DM; this is likely a reflection of patients with T2DM often being older and more likely to have more CVD risk factors for CAN than patients with T1DM. […] The impact of sex on CAN epidemiology is controversial. […] The impact of ethnicity on CAN prevalence has also been widely discussed in the literature, being cited as a possible risk factor for CAN, as lower rates of peripheral neuropathy (PN) were detected in South Asians when compared to white Europeans with DM. […] CAN is very common and often undiagnosed in patients with DM. Intensive multifactorial intervention targeting lifestyle, glycemic control, and CVD risk factors prevents the development and slows the progression of CAN. Identifying patients with CAN is important, as CAN is associated with increased mortality, CVD, CKD, perioperative morbidity, and lower-limb complications.
#49 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications
https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm
Currently, it is estimated that about 50% of people with diabetes mellitus remain undiagnosed and, among those diagnosed, the diagnosis usually happens very late, approximately 20 years after the onset of the disease. Thus, considering that CAN may present even before the onset of diabetes, it is a markedly underdiagnosed and underestimated microvascular complication. The natural progression of CAN comprises an asymptomatic, subclinical, and reversible phase, which represents the initial stage. Subsequently, CAN progresses to more advanced stages, with symptoms and a greater impairment of cardiac autonomic fibers. […] According to the position statement of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE), CAN screening should be performed at the time of diagnosis in patients with type 2 diabetes mellitus and five years after diagnosis in patients with type 1 diabetes mellitus. Nevertheless, there are still some controversies regarding the guidelines for CAN screening. For instance, the position statement of the American Diabetes Association (ADA) considers a patient eligible for CAN assessment only if they have microvascular complications and/or hypoglycemia unawareness. On the other hand, the Italian Society of Diabetology (SID) and the Italian Association of Clinical Diabetologists (AMD) reported that patients should be evaluated if they have high cardiovascular risk and complications, while the Toronto Consensus emphasizes that screening for symptoms and signs of CAN should be universal.
#50 Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications
https://www.wjgnet.com/1948-9358/full/v12/i6/855.htm
Currently, it is estimated that about 50% of people with diabetes mellitus remain undiagnosed and, among those diagnosed, the diagnosis usually happens very late, approximately 20 years after the onset of the disease. Thus, considering that CAN may present even before the onset of diabetes, it is a markedly underdiagnosed and underestimated microvascular complication. The natural progression of CAN comprises an asymptomatic, subclinical, and reversible phase, which represents the initial stage. Subsequently, CAN progresses to more advanced stages, with symptoms and a greater impairment of cardiac autonomic fibers. […] According to the position statement of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE), CAN screening should be performed at the time of diagnosis in patients with type 2 diabetes mellitus and five years after diagnosis in patients with type 1 diabetes mellitus. Nevertheless, there are still some controversies regarding the guidelines for CAN screening. For instance, the position statement of the American Diabetes Association (ADA) considers a patient eligible for CAN assessment only if they have microvascular complications and/or hypoglycemia unawareness. On the other hand, the Italian Society of Diabetology (SID) and the Italian Association of Clinical Diabetologists (AMD) reported that patients should be evaluated if they have high cardiovascular risk and complications, while the Toronto Consensus emphasizes that screening for symptoms and signs of CAN should be universal.
#51 Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes
https://www.e-jcpp.org/journal/view.php?number=98
The ONTARGET/TRANSCEND (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease) investigation has demonstrated that the loss or reversal of nocturnal blood pressure dipping is significantly associated with an increased risk of major cardiovascular events, cardiovascular mortality, and overall mortality. […] CVD is the leading cause of death among patients with diabetes, underscoring the importance of early screening, stratification of high-risk individuals, and timely interventions to prevent and manage the diseases onset and progression. Autonomic neuropathy, which is closely associated with CVD, occurs more frequently than commonly recognized. However, the complexity of testing and the difficulty in interpreting results often lead to its under-recognition in clinical settings.
#52 Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review. | EBSCOhost
https://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=20770383&AN=182987577&h=rSN0Jv508h9yKrICr8hn%2FTkeg67NxMUTdGypof125vd2o90mfl%2BAs2KUZR25LqnPVMHd6GUo3aqnVNKsn3ZSQw%3D%3D&crl=f
Cardiac autonomic neuropathy (CAN) is a serious but sometimes underdiagnosed complications of Diabetes Mellitus (DM). […] The objective of this review article is to highlight the reasons why CAN is underdiagnosed and its association with decreased cardiovascular risk and promote clinical awareness. […] This review summarizes the epidemiology, influence on the cardiovascular system and diagnostic methods of CAN, and the clinical implications of diabetic neuropathy. […] Conclusions: CAN is still underdiagnosed despite its clinical impact because routine screening is lacking, and healthcare providers are not aware of it.