Pulse pressure is independently associated with sensorimotor peripheral neuropathy in patients with type-2 Diabetes

Background:The mechanisms responsible for the onset and progression of sensorimotor peripheral neuropathy (SMPN )in type-2 diabetes remain largely unknown.Although a link between hypertension and SMPN has been observed, it is not clear which blood pressure component ( i.e. systolic,SBP;diastolic,DBP;or pulse pressure,PP )is primarily involved. Aim:To determine the relationship between different blood pressure components and parameters of nerve function in type 2 diabetes. Methods: In 55 consecutive ambulatory patients with stable type 2 diabetes ( age 62.6+-8.0 years, mean+-SD) we measured clinic blood pressure and 10 neurophysiologic parameters: motor nerves conduction velocity ( median,ulnar,posterior tibial and peroneal nerve ),sensory amplitude, and latency ( median,ulnar and sural nerve ). Results:Univariate analysis showed that age,diabetes duration, SBP and PP were negatively correlated with nerve function.Regression analysis showed that, after correcting for age, duration of diabetes, glycated haemoglobin, body mass index, microalbuminuria, and SBP, PP was independently and negatively associated with nerve conduction velocity ( median, P= 0.011; ulnar, P= 0.001; peroneal, P= 0.006; and posterior tibial , P= 0.005 and signal amplitude ( ulnar, P =0.027; sural, P =0.055 ) and positively associated with signal latency ( median,P =0.083; sural, P=0.021 ). SBP was negatively associated with signal amplitude ( median, P= 0.012 ) and positively associated with latency ( ulnar, P= 0.018 ). By contrast, DBP failed to show any significant correlation with nerve function. Conclusion: PP is strongly associated with neurophysiologic parameters of nerve function in patients with type 2 diabetes. This relationship is independent of traditional risk factors and other BP components

Interplay of peripheral neuropathy and hypertension in Type- 2 diabetes of short duration

Our understanding of the IGF-I system has increased dramatically in recent yr due in part to the advances in molecular and cellular biology. Not only can we now measure circulating levels of the members of this axis in order to address the possibly pathophysiological changes, but genetic alterations can now be identified as the underlying cause of specific clinical situations. In normal children, circulating levels of IGF-I and the IGF binding proteins (IGFBPs) change throughout development and in some cases are gender dependent. Children and adolescents with a variety of illnesses and metabolic disorders have altered circulating IGF-I and IGFBP levels. Hence, in children or adolescents with exogenous obesity, anorexia nervosa, coeliac disease, leukaemia and other types of cancer, as well as in cases of GH deficiency, this axis can be altered. These data may help us to understand the physiology and pathophysiology of this system, but the clinical or diagnostic utility of these measurements is still largely debated. Indeed, in most of the above mentioned illnesses, circulating IGF and IGFBP levels overlap with normal values. Furthermore, these measurements do not provide data concerning levels of these factors at target tissues or of local synthesis and autocrine-paracrine effects. However, measurements of IGF-I and its binding proteins, as well as GH and its binding proteins, can help us to focus our analysis of patients suspected to have genetic abnormalities on the GH receptor, IGF-I, its receptor, IGFALS, or intracellular signalling proteins such as STAT5b or ERK. Possibly, the most clear clinical utility of circulating IGF-I measurements in children is in cases of GH deficiency or insensitivity or under GH treatment. However, the fact there are cases of children with non-detectable levels of circulating IGF-I that yet normal height and growth velocity, or with non-detectable levels of GH yet normal growth and IGF-I levels, raises many questions. Furthermore, circulating IGF-I levels may be within the normal control levels and the child may have a pathological growth pattern. Hence, just how useful are these measurements? Another clinically important question pertains to GH treatment in patients, such as in the Turner Syndrome, where supraphysiological levels of serum IGF-I are reached in order to induce growth. The interpretation and clinical utility of measurements of circulating IGF-I and its BPs are currently being widely discussed. As our knowledge of this system increases, with the identification of new members of this family and its intracellular mechanisms of action, as well as new genetic alterations in patients, the interpretation of laboratory results will also improve and help to better our diagnostic capability

Predictors of impaired blood pressure homeostasis during acute and sustained orthostasis in patients with type 2 diabetes

Aim. Sympathetic failure with acute postural hypotension is a common feature of advanced autonomic neuropathy in type 2 diabetes. It is unknown, however, whether: a) the presence of sympathetic autonomic neuropathy is also a powerful predictor of postural blood pressure changes during sustained orthostasis and b) other factors affecting baroreceptor and neuro-hormonal control might play a role. Methods. Systolic blood pressure (SBP) was measured during supine rest and after 2, 5, and 20 min of active orthostasis in 45 males with type 2 diabetes (age 56.4 +/- 8.2 years, mean +/- SD) and different degrees of autonomic neuropathy (absence of neuropathy, n=26, parasympathetic neuropathy, n=9, and sympathetic neuropathy, n=10). Eight healthy subjects (50.1 +/- 11.6 years) served as controls. A multiple backward regression analysis was performed to identify independent predictors of SBP changes during orthostasis. The regression model included presence/absence of sympathetic autonomic neuropathy, age, diabetes duration, presence/absence of hypertension, baseline SBP and neuro-hormonal parameters (plasma adrenaline, noradrenaline, plasma renin activity, and aldosterone). Results. Sympathetic autonomic neuropathy (P=0.005), baseline SBP (P=0.001), and adrenaline (P=0.003) independently predicted SBP changes after 2 min (R-2=0.64); sympathetic autonomic neuropathy (P < 0.001), baseline adrenaline (P=0.008), and plasma renin activity (P=0.006) predicted SBP changes after 5 min (R-2=0.58); whereas sympathetic autonomic neuropathy (P < 0.001) and baseline SBP (P < 0.001) predicted SBP changes after 20 min orthostasis (R-2=0.65). Conclusion. The presence of sympathetic autonomic neuropathy and higher supine SBP values remain strong and independent predictors of SBP fall not only during the acute transition from supine to standing position but also during sustained orthostasis in type 2 diabetes. Lower baseline plasma adrenaline concentrations and plasma renin activity are also involved, though to a lesser extent, in the genesis of this haemodynamic response

Hypertension and Sensorimotor Peripheral Neuropathy in Type 2 Diabetes

Background: The mechanisms responsible for the onset of sensorimotor peripheral diabetic neuropathy (SMPN) remain largely unknown. To address this issue, we studied the relationship between traditional cardiovascular risk factors, parameters of metabolic control, and the presence of SMPN in patients with type 2 diabetes of relatively short duration. Methods: Blood pressure, glycated hemoglobin, lipid profile, and the presence of micro- and macrovascular complications were assessed and monitored in 31 consecutive ambulatory patients with type 2 diabetes (age 60.7 ± 7.5 years, mean ± SD) within 10 years of diagnosis (mean diabetes duration 6.0 ± 2.3 years). Results: Clinical and neurophysiological features of SMPN were present in 10 patients (SMPN+, 32%). There were no significant differences in age, gender distribution, diabetes duration, body mass index, metabolic control, and serum cholesterol between SMPN- and SMPN+ patients. However, the prevalence of hypertension (i.e. blood pressure ≥140/90 mm Hg) was higher in SMPN+ patients (10/10 vs. 13/21, χ2 = 5.13, p = 0.025). Regression analysis showed that, after correcting for age, gender, duration of diabetes, glycated hemoglobin, and cholesterol, the presence of hypertension was independently associated with SMPN (R2 = 0.17, p = 0.023). Conclusions: There is a strong association between hypertension and SMPN in type 2 diabetic patients with relatively short duration of disease. This relationship is independent of other risk factors. Copyrigh