Cardiovascular Autonomic Reflex Tests Research Articles

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study

ObjectiveThe study aimed to explore risk stratification approaches for cardiovascular autonomic neuropathy (CAN) in individuals with prediabetes and type 2 diabetes (T2DM) over a three-year follow-up period. MethodsParticipants underwent evaluations of autonomic function encompassing cardiovascular autonomic reflex tests (CARTs), baroreflex sensitivity (BRS), heart rate variability (HRV) in time domains (standard deviation of all normal RR intervals (SDNN)) and frequency domains (high frequency/low frequency ratio), and electrochemical skin conductance (ESC). The diagnosis of CAN relied on abnormal CART results. Subjects were categorized into 4 groups, based on their assessment of cardiac autonomic function at 3-year follow-up, relative to the presence or absence of CAN at baseline assessment: Persistent absence of CAN; Resolution of CAN; Progression to CAN; and Persistent CAN. ResultsParticipants with T2DM/prediabetes (n = 91/7) were categorized as: Persistent absence of CAN (n = 25), Resolution of CAN (n = 10), Progression to CAN (n = 18), and Persistent CAN (n = 45) groups. The Persistent absence of CAN group showed significant associations with SDNN. The Resolution of CAN group exhibited notable associations with mean HbA1C (follow-up), while the Progression to CAN group displayed a significant link with baseline estimated glomerular filtration rate. The Persistent CAN group demonstrated significant associations with SDNN and Sudoscan CAN risk score. Screening recommendations involve biennial to annual assessments based on risk levels, aiding in CAN detection and subsequent comprehensive and time-intensive autonomic function tests for confirmation. The study's findings offer improved risk categorization approaches for detecting CAN, which has relevance for shaping public health strategies.

The Composite Autonomic Symptom Score 31 Questionnaire: A Sensitive Test to Detect Risk for Autonomic Neuropathy.

Autonomic neuropathy is a common but often neglected complication of diabetes, prediabetes, and even in individuals with an elevated risk of diabetes. The Composite Autonomic Symptom Score (COMPASS) 31 is a validated and easy-to-use questionnaire regarding autonomic symptoms. We aimed to use a digitally, Norwegian version of the COMPASS 31 in people with different durations of diabetes and healthy controls to consider feasibility and to investigate if scores could discriminate between positive and negative outcomes for established tests for diabetic neuropathy, including cardiovascular autonomic neuropathy (CAN) and a novel method of examining the gastrointestinal visceral sensitivity. We included 21 participants with longstanding type 2 diabetes, 15 with early type 2 diabetes, and 30 matched controls. The mean age for all groups was 69 years. Participants were phenotyped by cardiovascular autonomic reflex tests, electrical skin conductance, sural nerve electrophysiology, and the monofilament test. As a proxy for gastrointestinal visceral and autonomic nerve function, evoked potentials were measured following rapid rectal balloon distention. Participants with longstanding diabetes scored a median (IQR) of 14.9 (10.8-28.7) points, early diabetes of 7.3 (1.6-15.2), and matched controls of 8.6 (4.1-21.6), p = 0.04. Women and men scored 14.4 (5.5-28.7) and 7.8 (3.6-14.6) points, respectively, p = 0.01. Participants with definite or borderline CAN scored 14.3 (10.4-31.9) points, compared to participants with no CAN, 8.3 (3.2-21.5), p = 0.04. Lowering the diagnostic cut-off from 16 to 10 points increased the sensitivity from 0.33 to 0.83, with a decreased specificity from 0.68 to 0.55. We successfully used COMPASS 31 in Norwegian. Thus, following the guidelines, we suggest clinical implementation for the assessment of autonomic neuropathy. Participants with longstanding diabetes had an increased likelihood of symptoms and signs of autonomic neuropathy. For screening purposes, the sensitivity was improved by lowering the cut-off to 10 points, with a lower score nearly excluding the diagnosis.

Cardiac autonomic neuropathy as risk factor of diabetic complications progression

Introduction. Diabetes mellitus (DM) is the most common and incapacitating endocrine disorder. Diabetic foot syndrome (DFS) is one of the most serious complications of DM, which is the main cause of nontraumatic lower-extremity amputations. Despite the efforts of the entire medical community, the survival rate of DFS patients with non-healing ulcers and after foot surgery does not exceed 50% over 5 years and is comparable to the survival rates of patients with colorectal cancer.Aim. It has been demonstrated that postsurgical diabetic foot wounds tend to chronization of inflammatory process. The diabetic autonomic neuropathy can be involved in diabetic foot damages. We hypothesized that progression of cardiovascular autonomic neuropathy (CAN) leads to aggressive microvascular complications of diabetes and delay the postsurgical wound healing in diabetic foot patients during 2 years of observation.Materials and methods. We examined 94 outpatients with postsurgical diabetic foot wounds and observation period of two years. The clinical neurological examination and standard cardiovascular autonomic reflex tests with identification of severe/advanced abnormalities were performed at baseline and after 2 years. The progression of CAN was diagnosed in cases of an increase in the amount of cardiovascular autonomic reflex tests by 1 score and more. The unsatisfactory result of wound treatment was detected in patients with wound healing delay and new cases of surgery debridement, foot amputations and Charcot foot during 2 years of observation.Results. The mean duration of diabetes was 10.7 year, HbA1c 8.3%, LDL-Chol 3.3 mmol/l, TG 1.8 mmol/l. The 51.1% patients had been amputated in the level of foot, 48.9% patients had surgery debridement. All patients had CAN, confirmed/severe forms in 57.4% cases. The progression of CAN was found in 22.3% patients, the most of them with functional stage at baseline. The aggressive course of CAN increased the risk of progression of diabetic sensomotor neuropathy (OR = 14.6; 95% CI 3.0–70.5; p = 0.0006), nephropathy (OR = 22.4; 95% CI 3.4–147.4; p = 0.0009) and unsatisfactory result of wound treatment (OR = 40; 95% CI 6.0–268.5; p = 0.0001).Conclusions. The patients with diabetic foot surgery wounds has high risk of confirmed/severe CAN and its progression during 2 years. The aggressive course of CAN associates with unsatisfactory result of wound treatment and progression of microvascular diabetic complications.

487-P: Cardiovascular Autonomic Function in Long COVID-19 Individuals With and Without Diabetes

Coronavirus disease 2019 (COVID-19) has been associated with a broad spectrum of long-term complications. These include the development and progression of severe autonomic dysfunction, particularly among people with diabetes. We evaluated cardiovascular autonomic (CAN) function in a cross-sectional study in 47 adults with long COVID-19 with (N=21, mean age 61 years, 43% women, mean A1c 6.2%) and without type 2 diabetes mellitus (T2DM) (N=26, mean age 58 years, 65% women) and compared them with T2DM without COVID-19 (N=45, mean age 57 years, 42% women, mean A1c 7.8%). CAN was assessed with cardiovascular autonomic reflex tests (30:15 ratio, E.I ratio, Valsalva ratio) and indices of heart rate variability (SDNN, RMSSD). We used pairwise comparison and Analysis of Covariance (ANCOVA) both adjusted for age, gender, race, and BMI to compare the groups. In a pairwise comparison higher heart rate (HR) and lower CAN measures (SDNN, RMSSD, Valsalva) were found in T2DM with COVID-19 compared to T2DM without COVID-19. Lower HR and lower Valsalva were found in COVID-19 individuals without T2DM compared to T2DM without COVID-19. When comparing the three groups, lower Valsalva were found in COVID-19 individuals with and without T2DM compared to T2DM without COVID-19 (Figure). These data suggest that COVID-19 exacerbates CAN in patients with T2DM and impacts CAN in people without T2DM at a magnitude similar to that of T2DM patients. Disclosure J.Fleischer: None. A.Vasbinder: None. S.Hayek: None. R.Busui: Board Member; American Diabetes Association, Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Novo Nordisk, Roche Diagnostics, Procter & Gamble, Research Support; Novo Nordisk, Medtronic, National Institutes of Health. S.V.G.Gunaratnam: None. Y.Huang: None. L.Ang: None. M.Charles: Research Support; Novo Nordisk Foundation, Speaker's Bureau; Novo Nordisk A/S, Boehringer-Ingelheim. A.Katona: None. N.Baker: None. K.R.Mizokami-stout: None. Y.Lin: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK119083, P30DK020572); Steno North American Fellowships 2021; Novo Nordisk Foundation (21OC0072180)

Cardiovascular autonomic neuropathy is associated with increased glycemic variability driven by hyperglycemia rather than hypoglycemia in patients with diabetes

AimCardiac autonomic neuropathy (CAN) has been suggested to be associated with hypoglycemia and impaired hypoglycemia unawareness. We have assessed the relationship between CAN and extensive measures of glucose variability (GV) in patients with type 1 and type 2 diabetes. MethodsParticipants with diabetes underwent continuous glucose monitoring (CGM) to obtain measures of GV and the extent of hyperglycemia and hypoglycemia and cardiovascular autonomic reflex testing. ResultsOf the 40 participants (20 T1DM and 20 T2DM) (aged 40.70 ± 13.73 years, diabetes duration 14.43 ± 7.35 years, HbA1c 8.85 ± 1.70%), 23 (57.5%) had CAN. Despite a lower coefficient of variation (CV) (31.26 ± 11.87 vs. 40.33 ± 11.03, P = 0.018), they had a higher CONGA (8.42 ± 2.58 vs. 6.68 ± 1.88, P = 0.024) with a lower median LBGI (1.60 (range: 0.20–3.50) vs. 4.90 (range: 3.20–7.40), P = 0.010) and percentage median time spent in hypoglycemia (4 (range:4–13) vs. 1 (range:0–5), P = 0.008), compared to those without CAN. The percentage GRADEEuglycemia (3.30 ± 2.78 vs. 5.69 ± 3.09, P = 0.017) and GRADEHypoglycemia (0.3 (range: 0 – 3.80) vs. 1.8 (range: 0.9–6.5), P = 0.036) were significantly lower, while the percentage median GRADEHyperglycemia (95.45 (range:93–98) vs. 91.6 (82.8–95.1), P = 0.013) was significantly higher in participants with CAN compared to those without CAN. ConclusionCAN was associated with increased glycemic variability with less time in euglycemia attributed to a greater time in hyperglycemia but not hypoglycemia.

"Arterial stiffness is not associated with changes in the circadian pattern of blood pressure in patients with type 1 diabetes mellitus and cardiovascular autonomic dysfunction".

Cardiovascular autonomic neuropathy (CAN) associates an abnormal circadian pattern in blood pressure (BP) regulation that might be aggravated by the coexistence of arterial stiffness. We aimed to evaluate the effect of arterial stiffness in the circadian rhythm of BP in patients with type 1 diabetes and CAN. Cross-sectional study including 56 consecutive patients with type 1 diabetes and CAN, with (n = 28) or without (n = 24) arterial stiffness as defined by an ankle-brachial index above 1.2. CAN was diagnosed by BP and heart rate responses to active standing and cardiovascular autonomic reflex tests. Absence of nocturnal decrease in BP-"non-dipping" pattern- was defined by a daytime to nighttime decrease in mean BP smaller than 10%. The study's subjects mean age was 40 ± 11 years-old, their mean duration of diabetes was 22 ± 10 years, and their mean A1c was 7.9 ± 1.5%. A "non-dipping" pattern was observed in 28 patients (54%) regardless of the presence or absence of arterial stiffness. Age, waist circumference, body mass index, and A1c, were introduced as independent variables into a multiple regression analysis. The stepwise model (R2: 0.113, p = 0.016) retained only A1c levels (β: ‒ 0.333, 95% confidence interval [CI]: -3.10 to -0.33) as significant predictor of the percentage of nighttime decrease in mean BP. A non-dipping pattern in BP is very common in patients with type 1 diabetes presenting with subclinical CAN and is associated with a poorer metabolic control. On the contrary, coexistence of arterial stiffness is not associated with abnormalities in circadian BP regulation.

Cardiovascular autonomic reflex tests using a handheld device in the diagnosis of cardiovascular autonomic neuropathy in patients with schizophrenia

Study objectiveThis study investigated whether schizophrenia and the duration of schizophrenia were associated with cardiovascular autonomic neuropathy (CAN) by using heart rate variability (HRV) as a marker. DesignCross-sectional study. SettingThe examinations were conducted at the Centre for Psychosis Research and at the Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. Participants240 patients with first-episode and chronic schizophrenia and 180 controls. InterventionsCAN was assessed by the cardiovascular reflex tests (CARTs): HR, RS ratio, E:I ratio, and VM using a handheld device. Main outcome measuresOne abnormal CART was interpreted as borderline CAN and ≥2 abnormal CARTs established definitive CAN. Borderline CAN and definitive CAN together was categorized as overall CAN. Analyses were adjusted for age, sex, smoking, overweight, and hypercholesterolemia. ResultsA total of 240 patients with schizophrenia (median age 42.5 [28.8, 52.3], 42.9 % women) and 180 controls (median age 45.8 [24.0, 60.1], 47.8 % women) were included, with 50.8 % of patients with schizophrenia having overall CAN compared to 27.2 % among controls. Dividing patients into patients with first-episode and chronic schizophrenia, 32.9 % vs 10 % (p < 0.001) and 59.1 % vs 41 % (p < 0.001) had overall CAN compared with controls, respectively. Schizophrenia was significantly associated with overall CAN (OR, 2.80; 95%CI, 1.75–4.50), with an OR of 2.31 (95%CI, 1.14–4.68) for first-episode schizophrenia and an OR of 2.97 (95%CI, 1.81–4.87) for chronic schizophrenia. ConclusionIt was demonstrated that a diagnosis of schizophrenia was associated with CAN. Patients with chronic schizophrenia had a significantly higher prevalence of CAN compared to patients with first-episode schizophrenia, suggesting an association between the duration of schizophrenia and CAN.

Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). Autonomic dysfunctions are frequent in subjectswith ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Cardiac Autonomic Neuropathy in Prediabetes: A Case-Control Study.

Early detection and diagnosis of diabetic autonomic neuropathy, especially cardiac autonomic neuropathy (CAN), have gained attention recently because of their elevated cardiovascular mortality risk. Although the connection between type 2 diabetes mellitus and autonomic neuropathy is well established, evidence is emerging that the association might predate the stage of prediabetes. The present study was undertaken to compare the prevalence of CAN in prediabetes versus that in normoglycemic controls. The study population was selected by purposive sampling from individuals attending a tertiary care hospital from January 2018 to June 2019. Fifty individuals with prediabetes diagnosed by the American Diabetes Association's glycated haemoglobin criteria and 50 age- and gender-matched healthy controls were recruited. CAN was assessed by standard cardiovascular reflex tests, as described by Ewing and Clarke. Changes in R-R with deep breathing, Valsalva manoeuver, and changes in blood pressure (BP) in response to standing and sustained handgrip were evaluated. Three-time domains [standard deviation of normal-to-normal intervals (SDNN), root mean square of successive RR intervals (rMSSD) and percentage of successive normal to normal R-R (NN) intervals that differ by more than 50 ms (pNN50)] and four frequency domain indices [very low-frequency band (VLF), low-frequency band (LF), high-frequency band (HF), LF/HF ratio) of heart rate variability (HRV)] were examined. The mean heart rate was 71.37 ± 7.94 and 65.59 ± 8.73 beats/min in patients with prediabetes and controls, respectively (P < 0.05). All three-time-domain indices of HRV were significantly lower in persons with prediabetes compared to controls. The peak frequency of LF, peak power of LF, normalised unit of LF, and LF/HF ratio was significantly lower in subjects with prediabetes than in controls. There was no difference in the traditional cardiovascular autonomic reflex testing. Our study demonstrates the presence of subclinical autonomic dysfunction in persons with prediabetes. Early detection of CAN in prediabetes can have future implications for cardiovascular risk reduction.

Skin advanced glycation end products as a screening tool of neuropathy in type 2 diabetes mellitus

Aim of the studyTo examine the diagnostic utility of skin advanced glycation end products (AGEs) as screening tool of neuropathy in type 2 diabetes mellitus (T2DM). Patients and methodsWe included 132 participants (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm and were interpreted as normal vs. elevated. Distal sensorimotor polyneuropathy (DSPN) was diagnosed by the Neuropathy Disability Score. Cardiovascular autonomic neuropathy (CAN), sympathetic and parasympathetic nervous system impairment were diagnosed by cardiovascular autonomic reflex tests. ResultsFor DSPN, AGEs yielded high sensitivity (82.8%) and NPV (80.4 %) with moderate specificity (55.4 %). For CAN, they yielded relatively high sensitivity (75.0 %) and NPV (74.5 %) with low specificity (48.7 %). For sympathetic nervous system impairment, AGEs yielded relatively high sensitivity (75.0 %) and high NPV (84.3 %) with low specificity (43.9 %). For parasympathetic nervous system impairment, they yielded high PPV (81.0 %) with moderately high sensitivity (66.7 %) and moderate specificity (55.9 %). ConclusionsIn a simplified approach, skin AGEs may be used as a screening tool of DSPN and CAN (including sympathetic and parasympathetic nervous system impairment) in T2DM.

Dapagliflozin Improves Cardiac Autonomic Function Measures in Type 2 Diabetic Patients with Cardiac Autonomic Neuropathy.

Cardiac autonomic neuropathy is a frequent complication of type 2 diabetes mellitus. Cardiac autonomic neuropathy, in which sympathetic tone predominates over parasympathetic activity, increases both cardiovascular morbidity and mortality and unfortunately has no definitive treatment. Sodium-glucose cotransporter-2 inhibitors have been suggested to reduce sympathetic nervous system activity, based on the results from previous studies. In this study, we aimed to investigate the effect of 24-week treatment with dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, on cardiac autonomic function measures in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy. Dapagliflozin 10 mg/day (n=42) or non-sodium-glucose cotransporter-2 inhibitor oral antidiabetic(s) (n=38) was added to the treatment of patients whose glycemic control could not be achieved with existing treatments. The patients with definite or confirmed cardiac autonomic neuropathy diagnosed by cardiovascular autonomic reflex tests underwent 24-hour Holter-electrocardiogram recordings to obtain heart rate variability and heart rate turbulence parameters before starting additional medication and after a 24-week treatment period. In-group analyses showed that dapagliflozin 10 mg/day for 24 weeks improved heart rate variability and heart rate turbulence parameters and decreased the frequency of ventricular premature beats relative to their baseline values. No such findings were observed in the control group despite similar glycemic control. Comparisons between dapagliflozin group and the control group showed that these effects of dapagliflozin were significantly better than non-sodium-glucose cotransporter-2 inhibitor oral antidiabetics. Dapagliflozin improves measures of cardiac autonomic function compared to the control group in type 2 diabetic patients with cardiac autonomic neuropathy. This intergroup benefit, demonstrated for the first time, may be promising for the regression of cardiac autonomic neuropathy with sodium-glucose cotransporter-2 inhibitors.

Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.

Aims/hypothesisAdvanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).MethodsThis cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) “glycolytic dysfunction”, ii) “lipid peroxidation”, iii) “oxidative stress”, and iv) “glucotoxicity”.ResultsA higher z-score of “glycolytic dysfunction” was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), “lipid peroxidation” was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and “glucotoxicity” was associated with lower SDNN (−4.20% (95% CI −8.1416; −0.0896), p = 0.047). No significance remained after adjustment for multiple testing.Conclusions/interpretationsIn young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.

Post-Acute Effect of SARS-CoV-2 Infection on the Cardiac Autonomic Function.

BackgroundRecent studies reported a long-lasting effect of COVID-19 infection that extends beyond the active disease and disrupts various body systems besides the respiratory system. The current study aims to investigate the post-acute effect of SARS-CoV-2 infection on cardiovascular autonomic activity, reactivity and sensitivity in patients who had the infection at least 3 months before.MethodsThis was a comparative cross-sectional observational study. Fifty-nine subjects were allocated into two groups, controls (n=31), who had no history of positive COVID-19 infection, and the post-COVID patients (n=28) who were recruited 3 to 8 months after testing positive for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). Baseline cardiovascular autonomic activity was evaluated through recording of baseline heart rate variability (HRV), autonomic reactivity was determined through standard cardiovascular autonomic reflex tests (CART), and cardiac autonomic sensitivity was assessed through cardiac baroreceptor sensitivity (cBRS).ResultsHigher incidence of orthostatic hypotension was observed in post-COVID patients compared to controls (39.3% and 3.2%, respectively, p <0.001). Additionally, significantly reduced handgrip test, and heart rate response to head-up tilt was illustrated in the post-COVID group (p <0.001). About 85.7% of post-COVID participants had at least one abnormal cardiovascular reflex test (CART) compared to the control group (p <0.001). Although HRV parameters (TP, LF, HF, SDRR, RMSSD, pRR50), and the cBRS were numerically lower in the post-COVID-19 group, this did not reach the level of significance.ConclusionThe results of the present study are suggestive of altered cardiovascular reactivity in post-acute COVID patients and demand further investigation and longer term follow up.

Sexual dysfunction among men with diabetes; a cross-sectional study at a specialised diabetes clinic in Sri Lanka

BackgroundMale sexual dysfunction in diabetes is often an unrevealed clinical issue. Though many publications report the prevalence, there is limited data on its associations, impact, and health-seeking behaviour. The objectives were to assess the prevalence of male sexual dysfunction, its associations, impact and treatment-seeking among men with diabetes in a selected tertiary care Diabetes Clinic.MethodsA cross-sectional study was conducted at the Diabetes Clinic, National Hospital of Sri Lanka, from January to September 2020. Men with diabetes aged 18 to 70 years undergoing annual assessment were recruited consecutively. Socio-demographic and clinical information were collected using an interviewer-administered questionnaire. Erectile dysfunction (ED), premature ejaculation, mental health and quality of life were assessed using validated self-administered questionnaires. Cardiovascular autonomic reflex tests and total testosterone levels were performed. Penile colour Doppler ultrasonography was performed on consenting participants with erectile dysfunction. Associations were assessed using the chi-square test or Fisher’s exact for dichotomous variables and independent sample t-test for continuous variables.ResultsTwo hundred and twelve participants were recruited with a mean age of 54.1 (SD = 10.1) years. Erectile dysfunction was present in 168 (79.2%), (mild: 45, mild-moderate: 56, moderate: 26, severe: 41). Premature ejaculation was present in 26 (18.7%). Libido was low among 16%. Sexual dysfunction was not revealed to a health provider by 85.6% despite 60.5% experiencing psychological and/or relationship effects. Out of 18 who sought treatment, only 4 achieved a good response. Mean age (55.4 ± 9.5 vs 48.7 ± 10.6 years, p < 0.001) and duration of diabetes (10.9 ± 7.6 vs 5.8 ± 4.6 years, p < 0.001) were higher while eGFR was lower (73.9 ± 27.7 vs 100.51 ± 28.08 years, p < 0.008) among those with ED compared to those without. Diabetic retinopathy (4% vs 42%, p < 0.001), peripheral neuropathy (17.9% vs 38.4%, p = 0.041) and lower limb arterial disease (0% vs 12.2%, p = 0.04) were associated with ED. Arterial insufficiency was seen among 50% of the participants who underwent penile colour Doppler ultrasonography.ConclusionsMale sexual dysfunction is a pervasive yet underappreciated problem in diabetes care despite its effect on the individual. Patient and disease characteristics would guide the identification of high-risk individuals for targeted screening in clinical practice.

Research for correlation between heart rate variability parameters and bone mineral density in patients of type 2 diabetes mellitus.

The relationship of CAN and BMD, fracture risk is still unclear in T2DM. The aim of the present study is to investigate the correlation between heart rate variability (HRV) and BMD in T2DM. The study included 276 patients with T2DM aged ≥ 50years, and Cardiovascular Autonomic Reflex Tests (CARTs) were applied to divide patients into two groups: CAN ( ±). 24h Ambulatory ECG was assessed for HRV, BMD was measured by dual-energy X-ray bone densitometry, and FRAX scores were calculated for 10-year hip fracture risk (HF1) and major osteoporotic fracture risk (MOF). Adjusted regression analysis was performed to investigate influence factors for BMD and fracture risk. ROC curve was used to analyze the optimal cut-off point of LF/HF for screening osteoporosis. Baseline data showed significant differences in the duration of T2DM, insulin resistance index (HOMA-IR), 25-hydroxyvitamin D[25(OH)D], femoral neck BMD, hip BMD, lumbar BMD, HF1, and MOF between the CAN ( +) and CAN (-) groups. The proportion of patients with osteoporosis increased as the degree of CAN lesion increased. Correlation analysis showed that LF/HF was significantly correlated with BMD, especially with hip (r = -0.534, p < 0.001). Regression analysis showed that LF/HF was a risk factor for reduced BMD and increased fracture risk. The optimal cut-point value for LF/HF to predict osteoporosis by ROC curve analysis was 3.17. CAN is associated with reduced BMD and increased fracture risk in patients with T2DM, and LF/HF may have the potential to be a predictor of diabetic osteoporosis and have some clinical value in early diagnosis of diabetic osteoporosis and non-traumatic fractures in T2DM.

458-P: Inflammatory Markers and Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Objective: We aimed to assess the role of chronic inflammation in the pathogenesis of cardiovascular autonomic neuropathy (CAN) , a serious complication of type 1 diabetes (T1D) . Methods: We leveraged an ongoing randomized, placebo-controlled clinical trial targeting inflammation with salsalate in individuals with T1D, to measure a panel of 40 inflammatory markers (Figure) in baseline samples. Measures of CAN included standardized cardiovascular autonomic reflex tests (CARTs) (E/I, Valsalva, 30/15 ratios) and indices of heart rate variability (HRV) . We used Spearman-rank to assess the correlations between inflammatory markers and CAN measures, and linear regression to adjust for age and hemoglobin A1c. Results: The Figure displays the correlation between biomarkers and CAN measures in 58 T1D participants (mean age 51 ± 13 years, and HbA1c 8.4 ± 1.8%) . Amongst all biomarkers, we noted a singular negative correlation between soluble urokinase plasminogen activator receptor (suPAR) and measures of CAN, which remained significant in multivariable analysis (E/I ratio p=0.005, Valsalva p=0.037, RFA p=0.019, LFA p=0.023) . Conclusion: Amongst a large panel of inflammatory markers, we found suPAR to have a notable association with CAN. SuPAR is an immune-mediated signaling glycoprotein which levels are strong predictors of risk in patients with diabetes, thus its role in CAN warrants further exploration. Disclosure L.Ang: None. L.Zhao: None. E.L.Feldman: None. S.Hayek: n/a. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. S.V.G.Gunaratnam: None. Y.Huang: None. K.R.Mizokami-stout: None. C.Martin: Advisory Panel; Nevro Corp. J.Reiss: n/a. A.Burant: None. A.Vasbinder: None. C.Launius: None. Funding NIH/NIDDK-1-R01-DK-107956-01

Cardiovascular Autonomic Reflex Tests and 7 Heart Rate Variability Indices for Early Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Individuals.

Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Thermal quantitative sensory testing as a screening tool for cardiac autonomic neuropathy in patients with diabetes mellitus.

IntroductionElectrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN.MethodsEighty‐five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed.ResultsCAN was diagnosed in 46 patients with diabetes (54%). CAN‐positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value.ConclusionTQST can be used as a screening tool for CAN before CART.

Elevated levels of interleukin-12/23p40 may serve as a potential indicator of dysfunctional heart rate variability in type 2 diabetes

BackgroundSystemic inflammatory processes plausibly contribute to the development of cardiovascular complications, causing increased morbidity and mortality in type 2 diabetes. Circulating inflammatory markers, i.e., interleukin (IL)-6 and tumour necrosis factor-α, are associated with neurocardiac measures. We examined a broad panel of various inflammatory and inflammation-related serum markers to obtain more detailed insight into the possible neuro-immune interaction between cardiovascular regulation and systemic level of inflammation.MethodsSerum samples from 100 participants with type 2 diabetes were analysed. Heart rate variability, cardiovascular autonomic reflex tests, and cardiac vagal tone tests were performed based on electrocardiographic readings. Data regarding covariates (demographic-, diabetes-, and cardiovascular risk factors) were registered.ResultsIncreased serum levels of IL-12/IL-23p40 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.007) were associated with diminished heart rate variability measures. After all adjustments, the associations between IL-12/23p40, SDANN and VLF persisted (p = 0.001). Additionally, serum levels of vascular endothelial growth factor (VEGF)-C were associated with response to standing (p = 0.005).DiscussionThe few but robust associations between neurocardiac regulation and serum markers found in this study suggest systemic changes in proinflammatory, endothelial, and lymphatic function, which collectively impacts the systemic cardiovascular function. Our results warrant further exploration of IL-12/IL-23p40, ICAM-1, and VEGF-C as possible cardiovascular biomarkers in T2D that may support future decisions regarding treatment strategies for improved patient care.

A Study of Cardiovascular Autonomic Neuropathy in Adult Patients with Diabetes Mellitus at Levy Mwanawasa University Teaching Hospital

Cardiac autonomic neuropathy (CAN) is the diminished capacity of autonomic regulation of the cardiovascular system occurring in the presence of diabetes mellitus (DM) and in the absence of other aetiologies. Diabetes mellitus is a well- known cause of peripheral neuropathy. However, in comparison to somatic neuropathy, autonomic neuropathy is an under-diagnosed and under-treated chronic complication of diabetes mellitus despite its serious and significant contribution to morbidity and mortality in the diabetes mellitus population. A variety of tests, based on evaluation of the cardiovascular reflexes triggered by performing specific provocative manoeuvres, have been proposed to measure autonomic function. This study used four cardiovascular reflex tests to estimate appropriate autonomic function by examining heart rate, heart rate variation and the baroreceptor reflex. The aim of this study was to determine the presence of cardiovascular autonomic neuropathy in adult patients with diabetes mellitus at Levy Mwanawasa University Teaching Hospital in Lusaka, Zambia. Adult patients with diabetes mellitus, aged between 21 and 70 years, participated in this cross-sectional study. Four, non-invasive, cardiac autonomic reflex tests to assess for cardiac autonomic neuropathy were employed according to Ewing’s method. The parasympathetic function was analysed based on the heart rate response to paced deep breathing and to Valsalva manoeuvring. The sympathetic function was assessed by measuring heart rate and blood pressure response to postural change. Ewing`s criteria was used for the categorisation of cardiac autonomic neuropathy. Data were analysed using SPSS version 20. Continuous data were presented as means and standard deviation. Categorical data were analysed using a Fishers’ Exact Test (χ2) and a logistic regression was performed to verify the effects of diabetes mellitus’ duration, sex and age on the probability that the participants have cardiac autonomic neuropathy. A total of 52 patients participated in the study. The prevalence of Cardiac autonomic neuropathy was 48.1%. Out of 52 patients, 42.3% had definite cardiac autonomic neuropathy and 5.8% had severe cardiac autonomic neuropathy. Early cardiac autonomic neuropathy was observed in 34.6% of patients while 17.3% had no signs of cardiac autonomic neuropathy. The mean age of patients with cardiac autonomic neuropathy was 54.44 ± 10.90 years and the mean duration of diabetes mellitus from diagnosis was 5.36 ± 6.78 years. The probability of developing cardiac autonomic neuropathy increased with increasing age and hypertensive participants were more likely develop cardiac autonomic neuropathy (ѵ = 5.82, p = .001). In conclusion, cardiac autonomic neuropathy was present in a significant proportion of adult patients with diabetes mellitus at Levy Mwanawasa University Teaching Hospital, reflecting the increased morbidity encountered by this population. In order to improve patient quality of life and reduce disease burden, screening for cardiac autonomic neuropathy should be implemented using cardiovascular autonomic reflex tests which are relatively simple, safe and affordable.