Risk Of Cardiac Autonomic Neuropathy Research Articles

Lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with type 1 diabetes. A case-control study among UAE population

BackgroundType 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation and cause of endothelial dysfunction (ED). Heart rate variability (HRV) is a marker of sympathetic and parasympathetic autonomic nervous system dysfunction. We investigated the association of lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with T1DM among UAE population. MethodIn this case-control study we recruited 126 adolescents (13–22 years) from Abu Dhabi, UAE (United Arab Emirates). Demographic, anthropometric, blood and urine samples were collected after an overnight fasting. HRV measurements were determined per Task Force recommendations. Independent t-test or Mann-Whitney U test and Pearson's Chi-squared test were used to compare groups. Adjusted conditional logistic regression model was used to identify the determinants independently associated with T1DM. ResultsThe mean ages in control (n = 47) and patient (n = 79) groups were 17.5 ± 4.6 and 18.6 ± 4.8 years, respectively. A family history of diabetes and waist and hip circumferences significantly differed between the groups (p = 0.030 and 0.010). The patients with T1DM exhibited significantly higher levels of atherogenic markers than control. Endothelial dysfunction biomarkers such as levels of sICAM-1 (p < 0.001), adiponectin (p < 0.001) and 25-hydroxyvitamin D (p < 0.001) were significantly different in the control group compared with those in the T1DM group. There was a significant difference in SDNN intervals, NN50, pNN50, and SD1/SD2 among the two groups. In adjusted analysis, total cholesterol (adjusted Odds Ratio (aOR): 2.78, 95 % CI:1.37–5.64; p = 0.005), LDL (2.66, 95%CI:1.19–5.92; p = 0.017), and triglycerides (5.51, 95%CI:1.57–19.41; p = 0.008) were significantly associated with developing T1DM. The HRV indicators were significantly associated with decrease odds of T1DM after controlling for SBP, BMI, and family history of DM. ConclusionIn this study, adolescents with T1DM showed a significant association with lipid profile, ED, and HRV compared with controls. Thus, an early attention to diabetes control is required to reduce the risk of cardiac autonomic neuropathy leading to various cardiovascular diseases.

The Importance of Evaluating Sudomotor Function in the Diagnosis of Cardiac Autonomic Neuropathy.

Cardiac autonomic neuropathy (CAN) is a disorder affecting the autonomic nerves that regulate the cardiovascular system, leading to irregular heart rate and blood pressure control. It is commonly associated with diabetes mellitus but can also result from other conditions such as autoimmune disorders, chronic kidney disease, alcohol abuse, and certain medications. Screening for CAN is essential, particularly in individuals with poor glycemic control, cardiovascular risk factors, or complications. Early identification of CAN is vital for timely intervention to prevent or manage cardiovascular complications effectively. Regular screening helps detect CAN before symptoms emerge, enabling early intervention to slow or halt its progression. This study examined the relationship between sudomotor function and cardiovascular reflex tests. This was a cross-sectional study conducted between June 2019 and June 2020. The study included 271 subjects aged 18 years and above who provided informed consent, were diagnosed with type 2 diabetes mellitus (T2DM), and were overweight or obese. Exclusion criteria encompassed patients with other types of diabetes, pregnant women, those with recent neoplasm diagnoses, stroke sequelae, history of myocardial infarction, or pelvic limb amputations. The assessment of cardiac autonomic neuropathy involved conducting an electrocardiogram and evaluating the QTc interval in the morning before taking medication. Additionally, cardiovascular reflex tests (CART) were conducted, including assessments of heart rate variability during deep breathing, the Valsalva maneuver, and changes in orthostatic position. Simultaneously, the diagnosis of CAN was assessed by performing a sweat test using a Sudoscan assessment (Impeto Medical, Moulineaux, France). Results: More than half of the participants (52%, n=143) were female. Significant differences in statistical measures were noted between females and males regarding age, systolic blood pressure, fasting blood glucose, A1c level, total cholesterol, triglycerides, gamma-glutamyl transferase, and bilirubin levels. Within the CAN-diagnosed group (CAN+), 40.92% were classified as mild cases (n=90), 47.27% as moderate cases (n=104), and 11.81% as severe cases (n=26). Among the CAN+ group, 54% (n=119) were women. Electrochemical skin conductance was lower in the CAN+ group than the CAN- group in hands (67.34±15.51 μS versus 72.38±12.12 μS, p=0.008) and feet (73.37±13.38 μS versus 82.84 ±10.29 μS, p<0.001). The Sudoscan-CAN score significantly correlated with Ewing scores (r= 0.522, p<0.001). In multiple linear regression analysis, the Sudoscan-CAN score remained significantly associated with age, high BMI, long-standing diabetes, and Ewing score. Sudoscan demonstrates potential in identifying patients with an increased risk of CAN. Its integration into clinical practice can improve patient outcomes through early detection, risk stratification, and personalized treatment approaches. Its non-invasive, portable, and user-friendly features render it suitable for utilization in outreach programs or resource-constrained settings as part of screening efforts designed to pinpoint high-risk individuals for additional assessment.

A Cross-Sectional Study to Determine the Association of Corrected QT Interval With Microalbuminuria in Type 2 Diabetes Mellitus.

Introduction Cardiac autonomic neuropathy (CAN) is a frequent and life-threatening complication of type 2 diabetes. Failure to diagnose can lead to high mortality and morbidity. In patients who have diabetes mellitus, microalbuminuria is an independent marker for cardiovascular disease. This study aimed to assess the corrected QT interval with microalbuminuria in type 2 diabetes mellitus. The objective of this study was to estimate the corrected QT interval in subjects with type 2 diabetes mellitus and to determine the association of the corrected QT interval with microalbuminuria type 2 diabetes mellitus. Methodology Ninety-five adult patients (>18 years to 65 years) diagnosed with type 2 diabetes mellitus with microalbuminuria were included in this study. Data were collected on the proforma through history taking and a general physicalandsystemic examination. An electrocardiograph was taken on the day of admission; the most prolonged QT interval was measured, and the RR interval was calculated. The data were statistically analyzed using IBMSPSSStatistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York, United States). Results There was a significant difference in the corrected QT interval prolongation prevalence between diabetic patients with microalbuminuria and without microalbuminuria(P-value <0.001). The mean corrected QT interval distribution did not differ significantly across various age groups of cases studied with microalbuminuria(P-value 0.98). The distribution of mean corrected QT interval did not differ significantly between the group of male cases and group of female cases studied with microalbuminuria(P-value 0.66). The mean corrected QT interval distribution did not differ significantly across various duration of diabetes groups among the cases studied with microalbuminuria(P-value 0.60). The mean corrected QT interval distribution did not differ significantly across different types of anti-diabetic treatment groups among the cases studied with microalbuminuria(P-value 0.64). Conclusion Type 2 diabetes has been prevalent in Indian and Asian populations. The early management of type 2 diabetes is necessary since the early stages of the disease can reduce the risk of CAN. Therefore, these patients should be diagnosed as early as possible and treated to reduce associated mortality and risk and to improve quality of care.

Association between plasma apolipoprotein M and cardiac autonomic neuropathy in type 1 diabetes

AimDiabetes may lead to severe complications e.g. cardiac autonomic neuropathy (CAN) characterized by an increased risk of cardiovascular mortality. CAN is diagnosed by a decreased heart rate viability (HRV). Sphingosine-1-Phosphate (S1P) carried by the HDL-associated apolipoprotein M (apoM) is linked to a reduction in the heart rate, and treatment with an S1P-agonist increases HRV. The present study aimed to investigate if plasma apoM was associated with an increased risk of CAN. MethodsThe study includes 278 individuals with Type 1 Diabetes recruited from Steno Diabetes Center in Copenhagen from 2010 to 2012. ResultsA change of 0.1 µM plasma apoM was associated with the diagnosis of CAN (Odds ratio: 1.11 (1.02; 1.21), p = 0.013). ApoM plasma levels were also positively associated with CAN when adjusted for age and gender (Odds ratio: 1.11 (1.02; 1.21), p = 0.013) as well as lipids, beta-blockers, blood pressure, and alcohol (Odds ratio: 1.14 (1.04; 1.26), p = 0.005) and Hbga1c and time with diabetes (Odds ratio: 1.13 (1.02; 1.25), p = 0.01). Plasma apoM was also associated with a significantly lower SDNN as well as high frequency power in all adjusted models. ConclusionIncreased plasma apoM was associated with an increased risk of CAN as well as a significant reduction in HRV indices. This could represent changes in parasympathetic activity, but, further studies are needed to also explore additional molecular alterations behind such observations.

Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances.

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that can predispose patients to higher risk for cardiovascular death. The aim of the present study was to evaluate the presence of cardiac autonomic neuropathy and sudomotor dysfunction in patients with newly diagnosed carbohydrate disturbances (prediabetes or diabetes) and to assess their relationship to metabolic disturbances and cardiovascular risk. In the present study, we included 160 patients -78 with obesity without carbohydrate disturbances, 52 with prediabetes, and 30 with newly diagnosed diabetes. CAN was diagnosed using cardiovascular reflex tests and sudomotor function was evaluated by SUDOSCAN. Cardiovascular risk was calculated using SCORE and FRMINGHAM risk scores. The prevalence of cardiac autonomic neuropathy was significantly higher in patients with newly diagnosed diabetes. Independently of their glycemic status, the patients who had blood glucose on the 60th-minute of OGTT>8.5 mmol/l had significantly higher prevalence of cardiac autonomic neuropathy (30.2% vs 15.6%, р=0.044). Patients with high cardiovascular risk according to FRAMINGHAM and SCORE had worse heart rate variability scores. Autonomic neuropathy risk assessed by SUDOSCAN was a good predictor for the presence of CAN. In conclusion, CAN has a higher prevalence on patients with newly diagnosed diabetes compared to prediabetic and normoglycemic subjects, while the patients with blood glucose>8.5 mmol/l on the 60th-minute of OGTT have higher prevalence of CAN independently of their glycemic status. SUDOSCAN testing can be used to assess the risk of CAN and to select patients that should undergo further testing.

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.

Arrhythmias and diabetes: heart block, ventricular arrhythmias, and death

Arrhythmias and diabetes: heart block, ventricular arrhythmias, and death

Relationship between cardiac autonomic neuropathy and cardio-metabolic risk profile in adults with type 1 diabetes

AimThe present study aims to determine the prevalence and association of cardiac autonomic neuropathy (CAN) with some traditional cardio-metabolic risk factors in adults with type 1 diabetes (T1D). Material and methods235 adults with T1D, divided into three groups according to diabetes duration, were recruited in this cross-sectional study from May 2017 till December 2018. Anthropometric parameters and blood pressure were measured. Lipids, liver enzymes, uric acid, creatinine, HbA1c and high sensitive C-reactive protein (hsCRP) were measured at fasting. Albumin/creatinine ratio (ACR) was measured in a first spot urine sample. Body composition was evaluated using bio-impedance analysis, Inbody720 (Biospace, USA). Advanced glycation end products (AGEs) were assessed by autofluorescence method, AGE Reader (Diagnoptics, The Netherlands). CAN was assessed by ANX-3.0 monitoring technology (ANSAR Medical Technologies, Inc., Philadelphia, PA), applying standard clinical tests. 2005 IDF and 2009 JIS definitions were used to define Metabolic Syndrome (MetS). ResultsThe prevalence of CAN was 23% and increased with diabetes duration. Sympathetic activity was independently related to age, albumin/creatinine ratio (ACR) and total body fat mass, and parasympathetic activity - to age and ACR. Elevated hsCRP, AGEs and body fat, diabetic retinopathy and nephropathy, as well as hypertension, dyslipidemia and metabolic syndrome were found to increase the risk of CAN in T1D. ConclusionCAN appears to be a common complication of T1D, especially with longer duration, and is found to be related to diabetic microvascular disease and metabolic syndrome components.

Assessment of sudomotor function in hypertensive with/without type-2 diabetes patients using SUDOSCAN: An electrophysiological study

ObjectiveElectrochemical skin conductance (ESC) test is a simple and non-invasive screening test can detect dysfunction of the peripheral sudomotor, and indirectly estimates the function of cardiac autonomic nerves. This study aimed to assess the ESC values in hypertensive patients with/without type-2 diabetes by using SUDOSCAN technology. Moreover, this study evaluated the role of cardiometabolic risk factors on the results of ESC test. MethodsThis cross-sectional study was carried on three groups of participants, includinghealthy subjects (Group I, n = 49), hypertensive without type-2 diabetes (Group II, n = 75) patients, and hypertensive with type-2 diabetes (Group III, n = 76) patients. Body mass index (BMI), blood pressure (systolic, diastolic and pulse pressure index), fasting serum glucose, and lipid profile were determined. ESC test as a measurement sudomotor function was determined by applying a small direct current at low voltage to hands and feet sensor plates through SUDOSCAN device. ResultsESC values of the peripheral sudomotor nerves in the Group II and III patients were significantly lower than the corresponding values of Group I. SUDOSCAN results of Group II and III. Significant discriminators of cardiac autonomic neuropathy (≥30 score) that determined by the area under the curve (AUC) with 95% confidence interval (95% C.I.) were, duration of the disease, BMI, and mean blood pressure in Group II, while the duration of the disease and the BMI were significant discriminators in Group III. ConclusionsSUDOSCAN is a simple, useful device, which can detect the impairment of peripheral autonomic small nerve fibers and the risk of cardiac autonomic neuropathy in hypertension. Moreover, the duration of the disease and the associated cardiometabolic risk factors are important predictors of significant SUDOSCAN findings. SignificanceESC test is useful in detecting subclinical neuropathy in hypertensive patients as well as in type 2 diabetes.

Risk of cardiac autonomic neuropathy in latent autoimmune diabetes in adults is similar to type 1 diabetes and lower compared to type 2 diabetes: A cross-sectional study.

Microvascular complications' risk differs between people with latent autoimmune diabetes in adults (LADA) and people with type 2 diabetes. We aimed to investigate whether the prevalence of cardiac autonomic neuropathy, a life-threatening complication of diabetes, also varies depending on diabetes type. In this cross-sectional study, 43 adults with LADA, 80 with type 1 diabetes and 61 with type 2 diabetes were screened for cardiac autonomic neuropathy with recommended tests. Logistic regression models were used to test differences between diabetes types adjusting for confounders. Cardiac autonomic neuropathy was diagnosed in 17 (40%) participants with LADA, 21 (26%) participants with type 1 diabetes and 39 (64%) participants with type 2 diabetes (p<0.001). The odds ratio (OR) for cardiac autonomic neuropathy in type 1 diabetes and in type 2 diabetes compared to LADA were 0.54 (95% CI: 0.25-1.20, p-value: 0.13) and 2.71 (95% CI: 1.21-6.06, p-value 0.015) respectively. Smoking (adj OR 3.09, 95% CI: 1.40-6.82, p-value: 0.005), HDL cholesterol (adj OR 0.29, 95% CI: 0.09-0.93, p-value: 0.037) and hypertension (adj OR 2.11, 95% CI: 1.05-4.24, p-value: 0.037) were independent modifiable risk factors for cardiac autonomic neuropathy. Differences among diabetes types did not change after correction for confounders. This is the first study offering a comparative evaluation of cardiac autonomic neuropathy among LADA, type 1 and type 2 diabetes, showing a lower risk of cardiac autonomic neuropathy in LADA compared to type 2 diabetes and similar compared to type 1 diabetes. This disparity was not due to differences in age, metabolic control or cardiovascular risk factors.

Angiotensin-converting enzyme insertion/deletion (I/D) gene polymorphism in Iraqi type 2 diabetic patients: association with the risk of cardiac autonomic neuropathy

BackgroundStudies have shown a direct association between angiotensin-converting enzyme (ACE) and diabetic neuropathies. As such, ACE gene polymorphisms could be a risk factor for cardiac autonomic neuropathy (CAN) in patients with diabetes. The objective of our study was to investigate the association of the ACE I/D gene polymorphism with the development of CAN in Iraqi patients with type 2 diabetes mellitus (T2DM).ResultsThis is a cross-sectional study that included 142 patients with T2DM comprising 62 males and 80 females, and 100 volunteers served as a healthy control group. Cardiac autonomic functions were tested using four standard Ewing’s noninvasive tests. Blood samples were taken for genetic evaluation of an ACE gene I/D polymorphism.Analyzing ACE gene polymorphism revealed that the D allele was far more frequent among patients with diabetes than healthy control subjects (76.07% vs. 62.67%). The frequency of I/I, I/D, and D/D genotypes in patients with diabetes was 8.55%, 30.77%, and 60.68%, respectively, compared with 18.67%, 37.33%, and 44%, respectively, in controls with a significant difference in mutant homozygous genotype. However, there were no significant differences in these genotypes between patients with and without CAN. Although patients with CAN showed a much higher frequency of D allele than those without CAN, the difference did not reach significance (p = 0.054).ConclusionThe DD genotype and D allele of the ACE I/D gene polymorphism can be a risk factor for T2DM, and the D allele of this polymorphism can even be associated with the development of CAN in these patients.

Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type1 diabetes.

Aims/IntroductionEpigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications.Material and MethodsWe assessed the frequency of five single‐nucleotide polymorphisms in the gene encoding deoxyribonucleic acid methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414 and rs10854076), and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy in 359 individuals with long‐term type 1 diabetes.ResultsNone of the single‐nucleotide polymorphisms studied was significantly associated with the presence of chronic complications in the overall population. However, after sex stratification, the minor allele C of rs11085721 conferred risk for cardiovascular neuropathy in women after adjustment for confounding variables (odds ratio 2.32; 95% confidence interval 1.26–4.33; P = 0.006).ConclusionsThe fact that heterozygous mutations in DNMT1 are associated with hereditary sensory autonomic neuropathy provides plausibility to the present finding. If confirmed in independent samples, it suggests that genetic variants in epigenetic genes might predispose to more or fewer epigenetic changes in the face of similar metabolic derangements triggered by hyperglycemia, constituting the “genetics of epigenetics” for microvascular diabetes complications.

Ezscan: A new non-invasive technology to evidence cardiac autonomic neuropathy in diabetes

Objective To assess the efficacy of Ezscan in evaluating the risk of cardiac autonomic neuropathy (CAN) in diabetes. Methods This study included 144 patients with diabetes. Their serum lipid profile and HbA1c were determined. The heart rate variability was assessed by Holter, and the cardiac autonomic neuropathy by classic experiments. Meanwhile, Ezscan was carried out. Results There was a positive correlation between low frequency (LF) measurements by Holter and Ezscan score( r=0. 39, P＜0. 01 ), so did LF/HF and Ezscan score( r=0. 28, P＜0. 01 ). Correlations between Ezscan score and other Holter parameters were weaker. There was no correlation between HbA1c and LF measurements. In patients with positive classic experiments, the sensitivity and specificity of Ezscan were 58. 3% and 57.8% respectively. Conclusions Ezscan test is a valuable screening procedure for detecting diabetic complications. It is more facilitative and takes shorter time than does the classical autonomic function assessment. Key words: Ezscan; Sudomotor function; Diabetes mellitus; Diabetic autonomic neuropathy; Heart rate variability

Metabolic Memory in the Autonomic Neuropathy of Diabetes

Metabolic memory, the concept that historical glycemic control is a major determinant of diabetes complications, is of considerable interest not only to those involved in the care of people with diabetes mellitus but also to a wider audience, those wishing to understand the pathogenesis of hyperglycemia-related target organ damage. This phenomenon has been popularized clinically by the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), which has repeatedly demonstrated the long-term impact of metabolic memory on nephropathy, retinopathy, cardiovascular disease, and peripheral neuropathy in type 1 diabetes mellitus.1–3 An article in this issue of Circulation from the DCCT/EDIC Research Group demonstrates the same phenomenon for cardiac autonomic neuropathy (CAN).4 In the DCCT, intensive glycemic control over an average of 6.5 years achieved a marked reduction in hemoglobin A1c, 1.7% lower than that achieved on conventional therapy, and a reduction in CAN incidence of 53%.5 At the termination of DCCT, all participants were encouraged to adopt intensive glycemic control such that 5 years after DCCT termination, there was no significant difference in hemoglobin A1c between the originally randomized groups. At 13 to 14 years of follow up, CAN incidence subsequent to DCCT termination in those initially randomized to intensive control was reduced by a third compared with those randomized to conventional therapy, even though glycemic control had been identical in these groups for decade before the CAN assessment. Statistical adjustment for historical glycemic control, specifically that achieved during the DCCT itself, abolished the group difference in CAN, supporting the assertion that metabolic memory explained the persistent lower risk of CAN in those originally randomized to intensive glycemic control. Article see p 2886 CAN is frequently observed in diabetes mellitus. The majority of previous studies identify diabetes duration and glycemic control as …

Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus

Cardiac autonomic neuropathy (CAN) is associated with increased morbidity and mortality in type 1 diabetes. Apart from glycaemic control, risk factors for CAN have not been extensively studied. As part of the EURODIAB Prospective Complications Study, CAN--defined as either a loss of heart rate variability or postural hypotension on standing--was assessed at baseline and follow-up (7.3+/-0.6 years from baseline) in patients with type 1 diabetes. Follow-up measurements were available for 956 participants without CAN at baseline (age at baseline 31.3+/-8.9 years, duration of diabetes 13.5+/-8.3 years). During follow-up, 163 (17%) subjects developed CAN, yielding an incidence of 23.4 per 1,000 person-years. Blood pressure, weight, the presence of cardiovascular disease, albuminuria, distal symmetrical polyneuropathy (DSP) and retinopathy at baseline were associated with the incidence of CAN after adjustment for sex, duration of diabetes and HbA(1)c. In a multivariate regression model, baseline factors associated with an increased risk of developing CAN were age [odds ratio (OR)=1.3 per decade, 95% CI 1.1-1.7], HbA(1)c (OR=1.2 per percentage point, 95% CI 1.1-1.4), systolic blood pressure (OR=1.1 per 10 mmHg, 95% CI 1.0-1.3), feeling faint on standing (OR=2.0, 95% CI 1.2-3.2), DSP (OR=1.9, 95% CI 1.2-3.0) and retinopathy (OR=1.7, 95% CI 1.1-2.6). This study confirms the importance of exposure to hyperglycaemia as a risk factor for CAN. A small set of variables, including HbA(1)c, hypertension, DSP and retinopathy, predict the risk of CAN. Clinical trials are needed to address the impact of intensive antihypertensive treatment on CAN in type 1 diabetes.

High prevalence and early onset of cardiac autonomic neuropathy among South Indian Type 2 diabetic patients with nephropathy

Objective: This study was conducted to assess the adverse effects of diabetic nephropathy on cardiovascular autonomic neuropathy (CAN) in South Indian Type 2 diabetic patients. Methods: Comparison was made between Type 2 diabetic patients with nephropathy (group 1, n=25), Type 2 diabetic patients without nephropathy (group 2, n=25) and non-diabetic, non-hypertensive control subjects ( n=20). All had a detailed clinical and biochemical work-up and cardiac assessment by ECG. Cardiac dysautonomia was assessed by a battery of five non-invasive autonomic function tests (ANF) as recommended by Ewing and Clarke [D.J. Ewing, B.F. Clarke, Diagnosis and Management of autonomic neuropathy. Br. Med. J. 285 (1982) 916–918]. Results: Group 1 patients showed a higher percentage of abnormal CAN function and a more severe form of CAN compared with patients in group 2. Group 1 patients showed early development of the abnormalities. They also had a higher prevalence of peripheral neuropathy compared with the patients without nephropathy. Conclusions: The present study showed that the presence of nephropathy was associated with the risk of cardiac autonomic neuropathy in Type 2 diabetic patients and it probably had an earlier onset also in them.