Nerve Function In Diabetes Research Articles

Phrenic nerve diabetic neuropathy in rats: unmyelinated fibers morphometry

We have demonstrated that phrenic nerves' large myelinated fibers in streptozotocin (STZ)-induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ-model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin-treated and untreated STZ-diabetic rats and non-diabetic control animals over a 12-week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ-diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes.

Acetyl- l-carnitine deficiency as a cause of altered nerve myo-inositol content, Na,K-ATPase activity, and motor conduction velocity in the streptozotocin-diabetic rat

Defective metabolism of long-chain fatty acids and/or their accumulation in nerve may impair nerve function in diabetes by altering plasma or mitochondrial membrane integrity and perturbing intracellular metabolism and energy production. Carnitine and its acetylated derivatives such as acetyl- l-carnitine (ALC) promote fatty acid β-oxidation in liver and prevent motor nerve conduction velocity (MNCV) slowing in diabetic rats. Neither the presence nor the possible implications of putative ALC deficiency have been definitively established in diabetic nerve. This study explored sciatic nerve ALC levels and the dose-dependent effects of ALC replacement on sciatic nerve metabolites, Na,K-ATPase, and MNCV after 2 and 4 weeks of streptozotocin-induced diabetes (STZ-D) in the rat. ALC treatment that increased nerve ALC levels delayed (to 4 weeks) but did not prevent nerve myo-inositol (MI) depletion, but prevented MNCV slowing and decreased ouabain-sensitive (but not-insensitive) ATPase activity in a dose-dependent fashion. However, ouabain-sensitive ATPase activity was also corrected by subtherapeutic doses of ALC that did not increase nerve ALC or affect MNCV. These data implicate nerve ALC depletion in diabetes as a factor contributing to alterations in nerve intermediary and energy metabolism and impulse conduction in diabetes, but suggest that these alterations may be differentially affected by various degrees of ALC depletion.

Validation and Evaluation of Test for Sympathetic Cholinergic Function in Diabetes Mellitus

Skin potential response (SPR), an electrodermal measure of sudomotor nerve function, was shown in this study to examine specifically sympathetic cholinergic fibers by abolition of the response during atropine infusion but not during propranolol infusion. The difference between responses in the left and right arms (SPR-D) was used to assess autonomic nerve function in 136 patients with diabetes and 52 control subjects. In 82% of the diabetic population (112 of 136), SPR-D was greater than 2SD above the mean control response compared with 42% (57 of 137) greater than 2SD below the mean control age-related value for a standard autonomic test predominantly of parasympathetic function, the R-R interval variation with breathing. Of 15 patients with clinical diabetic autonomic neuropathy, SPR wave forms were bizarre or absent in 5 patients compared with 18 of 121 patients' without clinical autonomic neuropathy (chi 2 = 3.5, P = 0.062). Measurement of SPR-D provides an easily determined measure of sympathetic cholinergic nerve function and may be a useful component of a group of tests for autonomic nerve function in diabetes.

The relationship between peripheral nerve resistance to ischaemia and diabetic control.

The cause of the abnormal resistance to ischaemia of peripheral nerve function in diabetes is unknown. Median nerve function was more resistant to ischaemia in diabetic patients than in control subjects. In diabetic patients the degree of resistance to ischaemia correlated closely with HbAlc but not with the coincident blood glucose level, the duration of diabetes, the vibration perception threshold at the thumb or the initial median nerve action potential amplitude. Thus in diabetes the resistance of peripheral nerve function to ischaemia is dependent on medium term metabolic control and is not directly related to the presence or absence of neuropathy.

Quantitative evaluation of diabetic autonomic neuropathy by using heart rate variations: relationship between cardiac parasympathetic or sympathetic damage and clinical conditions.

It was previously suggested that respiratory heart rate (HR) variations were predominantly affected by the parasympathetic nerve and HR increase to standing was predominantly affected by the sympathetic nerve. To compare parasympathetic and sympathetic nerve function in diabetics, these two tests were performed in 95 diabetics and 38 controls by use of an instantaneous-HR-change continuous recorder. All subjects were between 40 and 59 years-old. As indices of autonomic nerve function, the mean difference between maximal and minimal HR during deep breathing (delta I-E) and the HR increase on standing (delta HR) were determined. The mean delta I-E and delta HR in the diabetics were 9.4 beats/min and 15.1 beats/min, respectively. These values were significantly lower than those in the controls (delta I-E 14.4, delta HR 20.5 beats/min). delta I-E correlated negatively to duration of diabetes and mean fasting blood glucose during the last 6 months in the diabetics, but delta HR did not correlate to them at all. Diminished delta I-E was found in the patients with insulin treatment, retinopathy or persistent proteinuria. Diminished delta HR, however, was found only in the patients with long-standing complicated diabetes. Thus, both cardiac parasympathetic and sympathetic nerve function were significantly impaired in the diabetics as compared with the controls and that parasympathetic nerve damage occurred early whereas sympathetic innervation was preserved.

Cardiac beat-to-beat variation as an indicator of neuropathy and the frequency of its abnormality in diabetes mellitus.

The cardiac beat-to-beat variation and the maximum constriction velocity and acceleration of the pupillary light reflex have been considered indices of parasympathetic neuropathy. The abnormality of these indices was evaluated in 191 non-diabetics and 151 diabetics. The cardiac beat-to-beat variation decreased gradually with age in non-diabetics as well as diabetics. It was small in diabetics compared to non-diabetics in corresponding age group between 10 and 59 years. In diabetics it was still smaller in the presence of peripheral neuropathy than in its absence. The overall prevalence of this abnormality was 30.1% in diabetics but only 3.0% in non-diabetics. In diabetics it rose to 40.0, 42.6 and 52.2% in the presence of motor, sensory and motor plus sensory nerve neuropathy, respectively. In 63 diabetics examined for both cardiac beat-to-beat variation and pupillary light reflex, no statistical difference was observed between the frequency of these abnormalities. These observations indicate an extremely high prevalence of abnormality in autonomic nerve function in diabetics especially in the presence of abnormality in autonomic nerve function in diabetics especially in the presence of other types of neuropathy, so that diabetics with peripheral neuropathy should be carefully examined for autonomic neuropathy and vice versa. Besides, the measurement of the cardiac beat-to-beat variation is similar in sensitivity in the detection of neuropathy to the measurement of pupillary light reflex.

Peripheral and autonomic nerve function in newly diagnosed diabetes mellitus.

Peripheral and autonomic nerve function was assessed in 10 newly diagnosed male diabetics (six insulin-treated and four sulfonylurea-treated) with repeated observations over the subsequent six months. There was significant impairment of motor-conduction velocity in the common peroneal nerve at diagnosis in both treatment groups, with improvement following treatment in only the insulin-treated patients. In contrast, although the blood glucose level fell in both groups, the mean level was significantly lower in the sulfonylurea-treated patients at two months and at each subsequent visit. In the autonomic function tests significant abnormality was found in the electrocardiographic R-R-interval (beat-to-beat) variation in resting heart rate in two of the insulin-treated patients and all of the sulfonylurea-treated group, with improvement in only one of the latter. One patient in the sulfonylurea-treated group also showed an abnormal response to the Valsalva maneuver (expressed as the Valsalva ratio), and this remained abnormal throughout the period of study. All other patients had normal responses to the Valsalva maneuver and sustained handgrip test. None of the patients had postural hypotension. Abnormalities in autonomic nerve function in diabetics at diagnosis have not been previously reported.