Electrophysiological and clinical study of type-2 diabetic patients with short duration of disease and normal generalized nerve conductions.

AIM: To evaluate the presence of clinical and electrophysiological abnormalities in type-2 diabetic patients with short duration of diabetes and normal systemic nerve conduction. METHODS: Twenty-three consecutive type-2 diabetes patients (age 59.1±8.1 years, range 43-75 years, duration of diabetes 6.6±2.6 years, range 3-11 years) in good metabolic balance, of whom 15 were hypertensive on antihypertensive therapy and 8 were normotensive. Patients were regularly followed in the outpatient clinics. Serum C-peptide, lipids, glycosylated haemoglobin, glucose, Body Mass Index (BMI), and blood pressure were regularly monitored. A detailed neurological examination including a questionnaire on symptoms was performed followed by a complete electrophysiological study including sensory and motor nerve conduction studies and electromyography (EMG). RESULTS: In the whole population motor conduction in both upper (median and ulnar) and lower (peroneal and posterior tibial) limbs and sensory conductions of the median, ulnar, and sural nerve were within normal range. Patients were classified in the following groups: I) no clinical symptoms and signs and no electrophysiologic abnormalities (N=3, age 50.0±5.7 years, diabetes duration 7.3±3.3 years); IB) no clinical symptoms and signs but abnormal EMG (N=5, age 66.4±6.5 years, duration of diabetes 9.0±1.1 years); II) presence of clinical symptoms and signs and abnormal electrophysiological investigation (N=12, age 59.2±5.7 yrs, diabetes duration 5.9±2.2 yrs with chronic neurogenic disorder without active denervation on the EMG; N=3 cases with chronic neurogenic pattern with active denervation, age 55.3±8.0 yrs, diabetes duration 3.5, 6.0, and 4.0 yrs respectively). We observed a higher frequency of hypertension in diabetics with axonal damage than in patients with normal systemic EMG and ENG and in patients with "mixed" pattern on EMG, χ2=3.725, P=0.05. CONCLUSION: These results demonstrate a link between high sensitivity of the electrophysiologic studies and presence of a great variability of neurologic clinical symptoms and signs mainly in multiple associations. Both nerve conduction studies and EMG showed no generalized abnormalities and no clinical symptoms and signs only in 3 patients (13% of population) and presence of neurophysiologic abnormalities in 77% and some symptoms or signs in 65% of population studied with relatively short duration of diabetes.

ACE inhibitor-based treatment and antihypertensive effects in patients with type 2 diabetes.

AIM: The presence of hypertension significantly increases cardiovascular risk in diabetic patients. Different classes of antihypertensive drugs, by targeting different pathophysiological mechanisms and therapeutic targets, might provide different antihypertensive effects. The authors speculated that drugs specifically targeting the renin-angiotensin-aldosterone system provide better antihypertensive control than other therapeutic agents. METHODS: Fifty consecutive type 2 diabetic patients with hypertension (M:F 29:21) were followed for 3-9 yrs. Antihypertensive treatment was stable for the last 12 months and included angiotensin convertying enzyme (ACE) inhibitors (ACEI) alone in 8 patients (group IA), ACEI combined with other drugs in 11 patients (group IB) and non-ACEI treatment in 31 patients (group II), 23 of whom were treated with Ca-channel blockers and 8 were treated with beta-blockers alone or with diuretics. During the last month of the study a 3-7 days antihypertensive drugs wash-out was performed. Measurements were performed in sitting position in the same ambulatory conditions, in supine position after 20 min of absolute rest, and in motionless standing station after quickly rising up from sitting rest. RESULTS: Groups IA, IB, and II had similar blood pressure values during antihypertensive therapy within the last year. However, blood pressure values after antihypertensive drug wash-out were significantly higher in groups IA and IB vs. group II (SBP and DBP resting sitting position, P=0.039 and P=0.014 respectively; SBP and DBP in standing position, P=0.001 and P=0.016, respectively). CONCLUSION: These data show that the underlying condition in terms of pathophysiologic mechanisms is more severe in groups IA and IB, including a greater increase of peripheral resistance. Thus we may conclude that the antihypertensive effect of ACEI is greater than other classes of antihypertensive drugs.

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, chi(2 =) 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 (R(2) = 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.

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 (R2=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 (R2=0.58); whereas sympathetic autonomic neuropathy (P<0.001) and baseline SBP (P<0.001) predicted SBP changes after 20 min orthostasis (R2=0.65). CONCLUSIONS: 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.

Pulse pressure is independently associated with sensorimotor peripheral neuropathy in patients with type 2 diabetes.

OBJECTIVES: 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 (BP) component (i.e. systolic, SBP; diastolic, DBP; or pulse pressure, PP) is primarily involved. We sought to determine the relationship between BP components and parameters of nerve function in type 2 diabetes. DESIGN: Cross-sectional study. SETTING: Academic medical centre. SUBJECTS: A total of 55 consecutive ambulatory patients with type 2 diabetes (age 62.6 +/-8.0 years, mean +/- SD). INTERVENTIONS: Measurement of clinic BP and 10 neurophysiological parameters: motor nerve conduction velocity (NCV; median, ulnar, posterior tibial and peroneal nerve), sensory amplitude (AMP) and latency (LAT; 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 NCV (median, P =0.011; ulnar, P = 0.001; peroneal, P = 0.006 and posterior tibial, P = 0.005) and signal AMP (ulnar, P = 0.027; sural, P = 0.055), and positively associated with signal LAT (median, P = 0.083; sural, P = 0.021). SBP was negatively associated with signal AMP (median, P = 0.012) and positively associated with LAT (ulnar, P = 0.018). By contrast, DBP failed to show any significant correlation with nerve function. CONCLUSIONS: The PP is strongly associated with neurophysiological parameters of nerve function in patients with type 2 diabetes. This relationship is independent of traditional risk factors and other BP components.

High rate of neoplasia and other co-morbid conditions in type-2 diabetic patients with longer duration of disease and poor metabolic control.

AIM: The aim of the study was to assess the rate of neuroendocrine malignancies in the gastrointestinal tract, other malignancies and mitotic processes, in type-2 diabetic patients. In particular, we tested the hypothesis that a poor metabolic control is associated with a higher rate of neoplasms and other co-morbid conditions, such as hypertension and peripheral neuropathy. METHODS: Forty-one consecutive asymptomatic type-2 diabetic outpatients were followed for 8 years and clustered in 2 groups, according to disease duration, insulin need, and dose of oral antidiabetic agents. Physical examination, blood pressure measurements, and neurophysiologic studies were serially performed during the follow-up. In each subject, a general biochemistry was performed, aspecific and specific antigens (alpha-fetoprotein, carcinoembrionic-antigen and prostate specific antigen PSA and F-PSA) levels were measured, and invasive and non-invasive procedures were carried out, when necessary, to detect a neoplastic process. RESULTS: The rate of malignancies and mitotic processes was significantly higher in patients with longer duration of disease and poor diabetes control (72% vs 13%, p=0.02). Hypertension (83% vs 54%) and peripheral neuropathy (67% vs 21%) were also more common in this group. CONCLUSION: These data, although obtained in a relatively small population, highlight the importance of closely monitoring type-2 diabetic patients with poor diabetes control as this might be associated with the presence of malignancy or other co-morbid conditions. This may be particularly true when the poor glycemic control is characterised by a sudden onset or significant worsening despite streghtening of antidiabetic therapy.

Relative preservation of the renin-angiotensin-aldosterone system response to active orthostatism in type 2 diabetic patients with autonomic neuropathy and postural hypotension.

OBJECTIVE: The pathophysiological mechanisms involved in the progression of autonomic neuropathy (AN) and development of postural hypotension (PH) in type 2 diabetes (T2D) are largely unknown. The aim of this study was to address this issue by investigating the neurohormonal responses during active orthostatism (O) in T2D patients with and without PH. METHODS: Plasma noradrenaline (NA, pmol/L), adrenaline (A, pmol/L), plasma renin activity (PRA, angiotensin I, nmol/L/h) and aldosterone (ALD, pmol/L) were measured in the supine position (baseline) and after 2, 5, and 20 min O in 10 healthy subjects (C), 9 T2D patients without AN (D), 14 T2D patients with AN and without PH (DAN), and 7 T2D patients with AN and PH (DAN-PH). RESULTS: NA concentrations were significantly increased in the C. D and DAN groups during O. In the DAN-PH group, NA increased less markedly with no significant changes at 20 min O (+ 354 +/- 89 pmol/L at 2 min, p < 0.05; + 756 +/- 171 at 5 min, p < 0.05; + 656 +/- 295 at 20 min, p = NS). Absolute NA increments in the DAN-PH group were significantly lower than those in the C, D and DAN groups at 2 and 20 min. Concentrations of A increased significantly in the C and D groups whereas no significant changes were observed in the DAN (+ 27 +/- 27 pmol/L at 2 min, p = NS: + 22 +/- 22 at 5 min, p = NS; + 76 +/- 33 at 20 min, p = NS) and DAN-PH group (+ 16 +/- 11 pmol/L at 2 min, p = NS: + 71 +/- 27 at 5 min, p = NS; + 76 +/- 22 at 20 min, p = NS). Absolute A increments in the DAN and DAN-PH groups were significantly lower than those in controls at 2 and 20 min. By contrast, PRA and ALD increased significantly in all four groups. Absolute PRA increments were similar across the four groups, whereas ALD increments in the D, DAN and DAN-PH groups were significantly lower than those in the C group. CONCLUSIONS: In the DAN-PH group, the renin-angiotensin-aldosterone system response to O was relatively preserved compared with A and NA responses. The impairment of NA response was limited to the DAN-PH group, whereas the reduced A response was a feature of DAN regardless of PH.

[Study of the onset and progression of peripheral neuropathy and hypertension in NIDDM]. / Studio dell'esordio e della progressione della neuropatia periferica e dell'ipertensione nei NIDDM.

BACKGROUND: Diabetic neuropathy is the most common pathology affecting the peripheral nervous system. In prognostic terms, it is the most devastating complication of diabetes. About 50% of diabetics suffer from neuropathy between 25-30 years after the diagnosis of diabetes, even if over the past few decades there has been a considerable improvement in the diagnostic methods and criteria used to classify peripheral neuropathies, many of which are related to the development of neurophysiology. However, we still do not know enough about the incidence, prevalence and natural history of peripheral neuropathy diagnosed using clinical and electrophysiological criteria in non-insulin dependent diabetic patients. METHODS: The authors carried out a randomized study of the relationship between glucose intolerance, hyperglycemia, hyperinsulinemia, hypertension and early and manifest forms of peripheral neuropathy in 32 patients with NIDDM (aged 41-72 years old, duration of diabetes 1-27 years) over a 24-month period. In 11 patients diabetes was almost at onset (Group 1): 8 cases with diabetes for 1-2.5 years (4 hypertensives and 4 normotensives) and 3 cases with diabetes for 4 years (all normotensive). Twenty-one patients (Group 2) had had diabetes for longer (5-27 years): 5 were hypertensive and 16 normotensive. A full longitudinal neurophysiological study (EMG and ENG) was performed. In 11 NIDDM in Group 1, at basal conditions carpal tunnel syndrome (right CTS) was revealed in 1 case, right CTS with diffuse radiculopathy in 1 case, diffuse radiculopathy in 2 cases, lumbosacral radiculopathy in 1 case, and 1 right CTS with "mixed" symptoms. EMG-ENG were normal in 2 patients. RESULTS: The following developments were noted during the follow-up: rapid deterioration due to the onset of motor sensitive polyneuropathy (MSPN) in 1 patient, 3 cases of chronic neurogenic disorder with active denervation, 2 cases of "mixed" type symptoms. The results were only comparable in 2 cases. In 3 NIDDM with diabetes for 4 years, 1 patient presented MSPN and 2 were affected by chronic neurogenic disorders; during the follow-up the conduction of MSPN and active denervation deteriorated into chronic neurogenic syndrome. Moreover, 6 initially normotensive NIDDM developed hypertension. In 21 NIDDM of Group 2, 7 of the 16 who were initially normotensive became hypertensive. Three new cases of polyneuropathy were also reported in this group, and 5 already had MSPN but showed a deterioration of conduction during the follow-up in 1 case. One patient presented active denervation in chronic neurogenic symptoms and chronic neurogenic symptom was comparable in 1 case. One patient presented a normal EMG-ENG at both the start and end of the study. "Mixed" type of symptoms were recorded at the basal level in 11 patients (defined as the presence on the EMG of muscular areas with multiphase potentials of brief duration and low amplitude, first recruited under slight voluntary effort, isolated or mixed with areas of neurogenic potentials). Over the course of 12-24 months, eight patients deteriorated with chronic neurogenic symptoms without active denervation in 5 and present in 2 cases. One case also showed a deterioration of carpal tunnel syndrome. CONCLUSIONS: These results show that 1) metabolic control and a complete neurophysiological examination are essential for preventing and identifying the onset and progress of neuromuscular damage; 2) the onset or deterioration of these two complications mainly had a less well known common cause which was less studied and described.