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

Diagnosis of cardiovascular autonomic neuropathy in diabetes

The utility of standard cardiovascular tests for diagnosis of cardiac autonomic neuropathy in diabetes has been well documented. Attention must be paid to standardizing the procedure with regard to time of day, metabolic status, distance from meal and insulin, coffee and smoking avoidance, and patient's collaboration. In the presence of cardiovascular disease or drugs affecting the cardiovascular or autonomic nervous system, some caution is needed in interpreting the results. More recent reflex tests, which evaluate mainly sympathetic or baroreflex activity, despite their ability to detect early autonomic involvement, lack sufficient standardization and still need to be proved as valid alternatives. Of the different methods of measuring heart rate variability, spectral analysis has a greater ability to differentiate vagal and sympathetic modulation of heart rate than do time- domain methods. However, since these latter methods are easier and more widely available, they can be used as a screening approach. Twenty-four-hour evaluation of heart rate variability provides data on the circadian rhythm of sympathovagal activity, which can be affected earlier than and differently from cardiovascular reflex tests. Information obtained could have prognostic implications in terms of cardiovascular morbidity and mortality and offer therapeutic opportunities. However, a wide consensus on many technical aspects of both time-domain and frequency-domain methods is needed. Furthermore, large prospective studies in the diabetic population to assess the prognostic value of 24-h heart rate variability parameters on cardiovascular morbidity and mortality are lacking. Recently, I123 meta- iodobenzylguanidine (MIBG) scintigraphy has documented abnormalities of sympathetic myocardial innervation also in newly diagnosed IDDM. The meaning of this finding, whether it is an expression of functional or structural defects, needs to be clarified. Preliminary data point to a possible pathogenetic meaning of the known association between autonomic neuropathy and other diabetic complications. This area of investigation could provide useful insights into the complex and multifactorial pathogenesis of diabetic complications

Diagnosis of cardiovascular autonomic neuropathy in diabetes

The utility of standard cardiovascular tests for diagnosis of cardiac autonomic neuropathy in diabetes has been well documented. Attention must be paid to standardizing the procedure with regard to time of day, metabolic status, distance from meal and insulin, coffee and smoking avoidance, and patient's collaboration. In the presence of cardiovascular disease or drugs affecting the cardiovascular or autonomic nervous system, some caution is needed in interpreting the results. More recent reflex tests, which evaluate mainly sympathetic or baroreflex activity, despite their ability to detect early autonomic involvement, lack sufficient standardization and still need to be proved as valid alternatives. Of the different methods of measuring heart rate variability, spectral analysis has a greater ability to differentiate vagal and sympathetic modulation of heart rate than do time- domain methods. However, since these latter methods are easier and more widely available, they can be used as a screening approach. Twenty-four-hour evaluation of heart rate variability provides data on the circadian rhythm of sympathovagal activity, which can be affected earlier than and differently from cardiovascular reflex tests. Information obtained could have prognostic implications in terms of cardiovascular morbidity and mortality and offer therapeutic opportunities. However, a wide consensus on many technical aspects of both time-domain and frequency-domain methods is needed. Furthermore, large prospective studies in the diabetic population to assess the prognostic value of 24-h heart rate variability parameters on cardiovascular morbidity and mortality are lacking. Recently, I123 meta- iodobenzylguanidine (MIBG) scintigraphy has documented abnormalities of sympathetic myocardial innervation also in newly diagnosed IDDM. The meaning of this finding, whether it is an expression of functional or structural defects, needs to be clarified. Preliminary data point to a possible pathogenetic meaning of the known association between autonomic neuropathy and other diabetic complications. This area of investigation could provide useful insights into the complex and multifactorial pathogenesis of diabetic complications

Autonomic neuropathy: Clinical and instrumental findings

The development of sensitive techniques evaluating functions under autonomic control has allowed the early detection of widespread abnormalities in diabetes mellitus. However, despite a high frequency of functional abnormalities, an overt clinical syndrome develops slowly and is quite rare. Characteristic clinical features, more recent methods for evaluating autonomic function, diagnostic procedures, and main instrumental findings in a diabetic population are reported. Emphasis is given to more promising techniques evaluating autonomic control of the cardiovascular system, such as myocardial scintigraphy and assessment of 24-h blood pressure and heart rate variability. The clinical meaning of the number of functional abnormalities observed in diabetic patients s considered. While the role of autonomic neuropathy in the pathogenesis of gastrointestina motor disorders, hypoglycaemia unawareness or diabetic impotence needs to be revised, the importance of autonomic-related sweating and blood flow abnormalities in the pathogenesis of diabetic foot lesions is now better documented. Moreover, growing evidence of the importance of autonomic control of cardiovascular system, together with cardiovascular dysfunction linked to diabetic autonomic neuropathy, supports the hypothesis of a possible role of autonomic neuropathy in the increased cardiovascular morbidity and mortality observed in diabetic patients

Diabetic autonomic neuropathy

[No abstract available