Usefulness of ambulatory blood pressure monitoring in predicting the presence of autonomic neuropathy in type I diabetic patients.

This study investigated whether nondipping (defined as a day–night change in blood pressure (BP) <=0%) could be assumed as a diagnostic index for autonomic neuropathy, and assessed its accuracy in discriminating between type I diabetic patients with and without autonomic neuropathy. In 87 type I diabetic patients with normal renal function (age 36+-11, duration 17+-9 years, serum creatinine 67.2+-15.9 mcmol/l), four cardiovascular tests and 24-h BP monitoring were performed, and the percentage day–night change (Delta) in systolic (SBP) and diastolic BP (DBP) was calculated. Sixteen patients had Delta SBP and/or Delta DBP <=0%. In a multiple logistic regression with adjustment for sex, age, and body mass index, the odds ratio for having autonomic neuropathy was seven times higher in patients with DSBP <=0% as opposed to those without (odds ratio 6.97, CI 1.4–34.9, P=0.018). Using Receiver Operating Characteristic (ROC) analysis, DBP showed an acceptable accuracy in discriminating between patients with and without autonomic neuropathy (area under the ROC curve 0.69+-0.06 and 0.72+-0.05 for Delta SBP and Delta DBP, respectively). Adequate cutoff values were 0% for Delta SBP (sensitivity, 26%; specificity, 95%; positive predictive value, 87%) and 5% for Delta DBP (sensitivity, 26%; specificity, 92%; positive predictive value, 81%). In type I diabetic patients with normal renal function, a value of Delta SBP p0% identifies the presence of autonomic neuropathy with a very high chance. Nondipping at the cutoff proposed could be considered an adjunctive marker of autonomic neuropathy provided with a high specificity and low sensitivity

Does autonomic neuropathy play a role in erythropoietin regulation in non-proteinuric Type 2 diabetic patients?

Aims Erythropoietin (EPO)-deficient anaemia has been described in Type 1 diabetic patients with both severe autonomic neuropathy (AN) and proteinuria. This study was aimed at distinguishing between the effects of AN and nephropathy on haemoglobin and EPO levels in Type 2 diabetic patients at an early stage of diabetic nephropathy. Methods In 64 Type 2 diabetic patients (age 52 +/- 10 years, duration 10 +/- 9 years) without overt nephropathy and other causes of anaemia or EPO deficit, we assessed cardiovascular tests of AN, 24-h blood pressure (BP) monitoring, urinary albumin excretion rate (UAE), a full blood count, and serum EPO. Results Although the Type 2 diabetic patients with AN did not show differences in haemoglobin and EPO when compared with patients without AN, the presence of haemoglobin < 13 g/dl was associated with the presence of AN (chi(2)= 3.9, P < 0.05) and of postural hypotension (chi(2)= 7.8, P < 0.05). In a multiple regression analysis including as independent variables gender, body mass index, duration of diabetes, smoking, creatinine, 24-h UAE, 24-h diastolic BP, ferritin, erythrocyte sedimentation rate, and autonomic score, we found that the only variables independently related to haematocrit were autonomic score, ferritin and erythrocyte sedimentation rate. Finally, the physiological inverse relationship between EPO and haemoglobin present in a control group of 42 non-diabetic non-anaemic subjects was completely lost in Type 2 diabetic patients. The slopes of the regression lines between EPO and haemoglobin of the control subjects and the Type 2 diabetic patients were significantly different (t = 14.4, P < 0.0001). Conclusion This study documents an early abnormality of EPO regulation in Type 2 diabetes before clinical nephropathy and points to a contributory role of AN in EPO dysregulation

Autonomic neuropathy and cardiovascular risk factors in insulin-dependent and non insulin-dependent diabetes

In 97 IDDM and 64 NIDDM patients aged under 65 years, we evaluated the relationship between autonomic neuropathy (AN) and retinopathy, nephropathy, glycemic control and cardiovascular risk factors. Diabetes duration and HbA(1) were significantly higher and; body mass index was significantly lower in IDDM patients with AN compared to those without. In NIDDM only age was significantly higher in neuropathic patients. AN was associated with retinopathy in both IDDM (chi(2) = 10, P < 0.03) and NIDDM patients (chi(2) = 14, P < 0.007), while only in IDDM albumin excretion was significantly higher in patients with AN. Blood pressure (BP) was significantly higher in both IDDM and NIDDM patients with AN compared to those without. There were no differences in smoking and serum lipids between patients with and those without AN. We performed a multiple regression analysis using autonomic score, index of cardiovascular tests impairment, as the dependent variable and age, diabetes duration, body mass index, HbA(1), albumin excretion, cholesterolemia, triglyceridemia, systolic BP, and retinopathy as independent variables. With this model in IDDM autonomic-score was only related to body mass index (r = -0.29, P < 0.05), to HbA, (r = 0.46, P < 0.001), and to systolic BP (r = 0.24, P < 0.05), while in NIDDM it was only related to systolic BP (r = 0.54, P < 0.001). In conclusion, AN was related to age in NIDDM, and to diabetes duration and glycemic control in IDDM. AN was associated with retinopathy, with nephropathy (only in IDDM), and with BP levels, but not with dyslipidemia, smoking, or obesity. Excess mortality rate observed in diabetic AN cannot be referred to an association with cardiovascular risk factors. (C) 1997 Elsevier Science Ireland Ltd

Reappraisal of the diagnostic role of orthostatic hypotension in diabetes

OBJECTIVE: Given the controversial aspects of orthostatic hypotension (OH) testing in diabetes, we evaluated the diagnostic role for cardiac autonomic neuropathy (CAN) and for nondipping of OH, defined according to a fall in systolic blood pressure (BP) > or = 30 (30-OH) or > or = 20 mmHg (20-OH). METHODS: 164 diabetic patients underwent 24 hours BP monitoring, three heart rate cardiovascular tests, and OH test. RESULTS: Compared to 30 mmHg, the 20 mmHg criterion increased the frequency of OH from 11 to 19.5%. Both 30-OH and 20-OH were associated with CAN (chi(2)=30.5, P <0.0001, and chi(2)=45.1, P <0.0001, respectively) and nondipping (chi(2)=31.7, P <0.0001, and chi(2)=17.2, P=0.0001, respectively). ROC curve for orthostatic systolic BP fall provided an AUC of 0.79 +/- 0.04 (95% CI 0.70-0.86) for diagnosing CAN and of 0.77 +/- 0.05 (95% CI 0.66-0.86) for diagnosing nondipping. Both 30-OH and 20-OH showed a low sensitivity and high specificity for CAN [sensitivity 31%, specificity 98%, Likelihood Ratio for a positive result (LR(+)) 17.1; and sensitivity 50%, specificity 95%, LR(+) 9.3, respectively], and for nondipping (sensitivity 40%, specificity 96%, LR(+) 8.9, and sensitivity 47%, specificity 87%, LR(+) 3.5, respectively), having 30-OH a higher LR(+) in both cases. INTERPRETATION: OH had only moderate diagnostic accuracy, with high specificity and low sensitivity, for CAN, diagnosed on the basis of heart rate cardiovascular tests, and-as a novel finding-also for nondipping. A different definition of OH did not substantially affect its diagnostic characteristics, with just a slightly greater ability of the 30 mmHg criterion to estimate the probability of CAN and nondipping

Relationship between autonomic neuropathy, 24-h blood pressure profile, and nephropathy in normotensive IDDM patients

OBJECTIVE - To evaluate the relationship between autonomic neuropathy, nephropathy, and 24-h blood pressure (BP) pattern in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS - We studied 30 normotensive IDDM patients without overt nephropathy, divided into two groups and matched for age, duration of diabetes, and HbA(1), according to the presence of cardiovascular autonomic neuropathy. We simultaneously measured 24-h BP and urinary albumin excretion rate (UAE) on urine collections timed overnight and at 2-h intervals during the day. RESULTS - Mean day and night systolic and diastolic BP values did not significantly differ between the groups. Mean night albuminuria was significantly higher in patients with autonomic neuropathy than in those without (61.4 +/- 104.6 [mean +/- SD] vs. 16 +/- 25.2 mu g/min, P < 0.04). The percentages day-night changes in systolic BP, diastolic BP, and UAE were significantly lower in neuropathic patients (systolic BP: 2.4 +/- 7.7 vs. 9.6 +/- 4.2%, P < 0.001; diastolic BP: 8.4 +/- 6.9 vs. 15.5 +/- 5.4%, P < 0.002; UAE: -8 +/- 99.4 vs. 49.3 +/- 29.4%, P < 0.02) and were inversely related to autonomic score, index of autonomic neuropathy degree (r = - 0.54, P < 0.002; r = -0.58, P < 0.001; and r = -0.53, P < 0.005, respectively). In patients with autonomic neuropathy, 2-h day periods and day and night UAE were more strongly related, respectively, to mean 2-h day periods (r = 0.58, P < 0.0001), day systolic BP (r = 0.67, P < 0.04), and night systolic BP (r = 0.69, P < 0.04) than in patients without autonomic neuropathy (2-h day periods: r = 0.32, P < 0.001; day: r = 0.37, NS; night: r = 0.35, NS). CONCLUSIONS - Autonomic neuropathy in IDDM patients is associated with reduced nocturnal falls in BP and UAE and with a stronger relationship of UAE to systolic BP. We suggest a pathogenetic role of autonomic neuropathy in the development of diabetic nephropathy through changes in nocturnal glomerular function and by enhanced kidney vulnerability to hemodynamic effects of BP

Neuropad as a diagnostic tool for diabetic autonomic and sensorimotor neuropathy

Aims The aim of the present study was to determine the diagnostic accuracy of the Neuropad sudomotor test for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN), the latter assessed using a multi-level diagnostic approach. Methods In 51 diabetic patients, CAN, symptoms and signs of DPN, vibration perception threshold (VPT), cold (CTT) and warm thermal perception thresholds (WTT) were measured. Neuropad response was determined as normal (complete colour change) or abnormal (absent or incomplete colour change). The time until the complete colour change (CCC time) was recorded. Results CCC time showed significant correlations with all the neurological parameters, the strongest of which were with Valsalva ratio (rho=-0.64, P<0.0001), symptoms of DPN (rho=0.66, P<0.0001), postural hypotension (rho=0.54, P=0.0001) and CTT (rho=-0.54, P=0.0001). CCC time showed moderate diagnostic accuracy for both CAN and DPN: the areas under the receiver operating characteristic (ROC) curves were 0.71 and 0.76, respectively. The diagnostic characteristics of three cut-off values of CCC time, identified by ROC analysis (i.e. 10, 15 and 18 min), were analysed. Compared with 10 min, the 15-min cut-off value provided better specificity (from 27% to 52% and from 31% to 62% for CAN and DPN, respectively) and a better likelihood ratio for negative result (from 0.67 to 0.34 and from 0.58 to 0.33) without lowering sensitivity (from 82% to 82% and from 85% to 80%). Conclusions Neuropad is a reliable diagnostic tool for both CAN and DPN, albeit of only moderate accuracy. Extending the observation period to 15 min provides greater diagnostic usefulness