Structural abnormalities do not explain the early functional abnormalities in the peripheral nerves of the streptozotocin diabetic rat.
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The streptozotocin (STZ)-diabetic rat, the most commonly employed model of experimental diabetic neuropathy, is characterised by a reduction in nerve conduction velocity, pain threshold and blood flow. Whether or not structural abnormalities underlie these functional abnormalities is unclear. 10 adult male Sprague-Dawley STZ-diabetic rats (diabetes duration 27 d) and 10 age-matched (23 wk) control animals were studied. Motor nerve conduction velocity (m s(-1)) was significantly reduced in diabetic (41.31 +/- 0.8) compared with control (46.15 +/- 1.5) animals (P < 0.001). The concentration of sciatic nerve glucose (P < 0.001), fructose (P < 0.001) and sorbitol (P < 0.001) was elevated, and myoinositol (P < 0.001) was reduced in diabetic compared with control animals. Detailed morphometric studies demonstrated no significant difference in fascicular area, myelinated fibre density, fibre and axon areas as well as unmyelinated fibre density and diameter. Endoneurial capillary density, basement membrane area and endothelial cell profile number did not differ between diabetic and control animals. However, luminal area (P < 0.03) was increased and endothelial cell area (P < 0.08) was decreased in the diabetic rats. We conclude there is no detectable structural basis for the reduction in nerve conduction velocity, pain threshold or blood flow, observed in the streptozotocin diabetic rat. (+info)
Impaired diurnal cardiac autonomic function in subjects with type 2 diabetes.
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OBJECTIVE: To assess diurnal cardiac sympathetic and parasympathetic nerve functions in diabetic subjects with variable diabetic neuropathy. RESEARCH DESIGN AND METHODS: Frequency domain analysis of 24-h Holter ECG was done for 132 diabetic subjects (84 without any symptomatic neuropathy; 37 with only symptomatic peripheral neuropathy; 11 with symptomatic autonomic neuropathy) and 57 normal volunteers to calculate the low frequency (LF) component representing the beta-adrenoceptor function and the high frequency (HF) component representing the cardiac parasympathetic nerve function. RESULTS: Cardiac LF and HF components in diabetic subjects without peripheral neuropathy showed values comparable to those of normal volunteers and a similar circadian rhythm. Diabetic subjects with peripheral neuropathy or autonomic neuropathy showed significantly depressed LF and HF components and loss of the circadian rhythm of LF and HF components compared with diabetic subjects without neuropathy. Impairment of the LF component in the afternoon could be accounted for by the duration of diabetes and elevated HbA1c level. Impairment of the HF component at night could be accounted for by the duration of diabetes but not an elevated HbA1c level. CONCLUSIONS: These data indicated that diabetic subjects with peripheral neuropathy and diabetic subjects with symptomatic autonomic neuropathy, but not diabetic subjects without neuropathy, showed a marked decrease in cardiac sympathetic and parasympathetic nerve functions and loss of circadian rhythm. (+info)
Risk factors for progression of distal symmetric polyneuropathy in type 1 diabetes mellitus. Sorbinil Retinopathy Trial Research Group.
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In a prospective cohort study, the authors examined risk factors for progression of distal symmetric polyneuropathy (DSP) in type 1 (insulin-dependent) diabetes mellitus. The study population consisted of participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18-56 years with type 1 diabetes mellitus of 1-15 years' duration. Diagnosis of DSP was based on standardized clinical neurologic evaluation. A total of 407 participants who did not have definite DSP at randomization and had at least one follow-up visit were included in the analysis. Stepwise Cox proportional hazards models were used to examine the independent contribution of baseline variables to progression of DSP. During follow-up (median, 40 months), 68 participants (17%) showed progression to definite DSP. After adjustment for age and treatment assignment, independent predictors of progression to definite DSP were total glycosylated hemoglobin (relative risk (RR) for increase of one percentage point = 1.25; 95% confidence interval (CI) 1.12, 1.39), height (RR associated with being one inch (2.54 cm) taller = 1.15; 95% CI 1.05, 1.26), cigarette smoking (ever vs. never) (RR = 1.87; 95% CI 1.09, 3.21), and female gender (RR = 2.26; 95% CI 1.09, 4.67). These data indicate that, in addition to the previously established role for total glycosylated hemoglobin, other factors including height, cigarette smoking, and female gender may also be independent risk factors for progression of DSP in type 1 diabetes mellitus. (+info)
Acetyl-L-carnitine.
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Acetyl-L-carnitine (ALC) is an ester of the trimethylated amino acid, L-carnitine, and is synthesized in the human brain, liver, and kidney by the enzyme ALC-transferase. Acetyl-L-carnitine facilitates the uptake of acetyl CoA into the mitochondria during fatty acid oxidation, enhances acetylcholine production, and stimulates protein and membrane phospholipid synthesis. ALC, similar in structure to acetylcholine, also exerts a cholinomimetic effect. Studies have shown that ALC may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, diabetic neuropathies, ischemia and reperfusion of the brain, and cognitive impairment of alcoholism. (+info)
Prevention of nerve conduction deficit in diabetic rats by polyunsaturated fatty acids.
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The influence of diets containing gamma-linolenic acid (GLA; 18:3n-6) on sciatic nerve conduction velocity (NCV) was determined in diabetic rats. NCV was lower in diabetic rats fed diets supplemented with olive oil or sunflower seed oil than in nondiabetic rats; rats supplemented with GLA during a 5-wk diabetic period, however, did not exhibit significantly lower NCV. The mean proportion of the phospholipid fatty acid linoleic acid (18:2n-6) was higher in the sciatic nerves of diabetic rats than in the nondiabetic groups irrespective of dietary lipid treatment. Additionally, the proportion of linoleic acid was higher in the diabetic rats fed sunflower oil than in all other groups. Dietary GLA supplementation did not significantly influence the fatty acid composition of nerve membrane phospholipids and there was no obvious correlation between the fatty acid composition of nerve membrane phospholipids and NCV. The content of fructose and glucose in sciatic nerves was higher, whereas that of myo-inositol was lower, in diabetic rats than in nondiabetic rats; however, this was not significantly influenced by dietary GLA. GLA administration did not significantly influence Na(+)-K(+)-exchanging ATPase or ouabain binding activity in sciatic nerve preparations, both of which remained nonsignificantly different in the diabetic and nondiabetic groups. The results suggest that dietary GLA can prevent the deficit in NCV induced by diabetes and that this effect is independent of the nerve phospholipid fatty acid profile, sugar and polyol content, Na(+)-K(+)-exchanging ATPase activity, and ouabain binding. GLA may prevent the deficit in NCV indirectly, possibly by its role as a precursor of vasodilatory prostaglandins. These results confirm that GLA is the active component of evening primrose oil. (+info)
Foot screening technique in a diabetic population.
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Foot complications are a well known factor which contribute to the morbidity of diabetes and increases the chance of amputation. A total of 126 consecutive diabetic patients were evaluated by diabetic foot screening. Forty-one patients showed an impaired protective sense when tested with Semmes-Weinstein monofilament 5.07 (10 g), and 92% of them showed peripheral polyneuropathy in nerve conduction study (NCS). The mean vibration score of the Rydel-Seiffer graduated tuning fork in patients with peripheral polyneuropathy in nerve conduction (NCV) study was 5.38+/-2.0, which was significantly different from that of patients without polyneuropathy in NCS. Among the deformities identified on examination, callus, corn, and hallux valgus were the greatest. While checking the ankle/ brachial index (ABI), we also evaluated the integrity of vasculature in the lower extremities. After extensive evaluation, we classified the patients into eight groups (category 0,1,2,3,4A,4B,5,6). The result of this study suggested that the Semmes-Weinstein monofilament test, Rydel-Seiffer graduated tuning fork test, and checking the ankle/brachial index were simple techniques for evaluating pathologic change in the diabetic foot by office screening, and that this screening based on treatment-oriented classification helps to reduce pedal complications in a diabetic population. (+info)
Early detection of cardiovascular autonomic neuropathy in diabetic pigs using blood pressure and heart rate variability.
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Cardiac autonomic neuropathy is a common complication in insulin dependent diabetes mellitus. Nevertheless, little is known about when this impairment occurs during the time course of the disease. Analysis of blood pressure (BP) and heart rate (HR) variability could be used to detect early signs of autonomic alteration. To test this proposal, twelve sexually mature male Yucatan miniature pigs were equipped with an arterial catheter for telemetric BP analysis, and with a venous access. BP and HR were recorded together with respiratory movements while the animals were resting in a sling. After the first recording session performed when the pigs were 5 months old, streptozotocin (STZ) was used to induce diabetes in seven pigs, while the five others were controls. BP and HR were measured 3 and 6 months after the onset of diabetes and at a similar age in the controls. BP and HR oscillated at the respiratory range (0.19 Hz). Spectral analysis showed this respiratory component was the main determinant of the short-term variability of BP and HR. Atropine increased HR and BP and markedly diminished the respiratory sinus arrhythmia. Propranolol diminished HR and the respiratory peak of HR. A reduced respiratory oscillation of BP paralleled the diminution of the respiratory peak of HR. Baroreceptor-HR reflex was estimated using injections of phenylephrine and nitroprusside, and by cross-spectral analysis between BP and HR. Atropine shifted the curve to higher HR values, while propranolol reduced the level of the upper plateau. Atropine decreased both the coherence and gain of the cross-spectral analysis. STZ injection resulted in a type 1 diabetes. At 3 months, diabetic pigs exhibited low levels of BP and a reduced overall variability of HR and BP. Spectral analysis indicated the respiratory sinus arrhythmia was markedly reduced. In addition, the sensitivity of the baroreceptor-HR reflex was reduced. At a latter stage of diabetes these alterations were marked and the level of the resting HR was increased. These data demonstrate the dual (vagal and sympathetic) control of HR in pigs and the dominant role of respiration in the genesis of HR and BP fluctuations. The spectral and cross-spectral analysis of BP and HR were altered after 3 months of diabetes and could be proposed as early detectors of cardiac autonomic neuropathy. (+info)
Asymptomatic electrophysiologic carpal tunnel syndrome in diabetics: entrapment or polyneuropathy.
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Electrophysiologic carpal tunnel syndrome (CTS) is common and is frequently asymptomatic in diabetics. In order to evaluate the clinical significance of asymptomatic electrophysiologic CTS, the nerve conduction studies (NCS) of 48 diabetics with asymptomatic electrophysiologic CTS were compared with those of 56 age and gender-matched controls, as well as 50 patients with symptomatic CTS without diabetes. Nerve conduction velocities of the ulnar, peroneal, and posterior tibial nerves were significantly slower in diabetics with asymptomatic electrophysiologic CTS than in normal controls. Compared to symptomatic non-diabetic CTS, there was also significant slowing of the median and ulnar nerve conduction velocities in asymptomatic diabetic CTS. However, in diabetics with asymptomatic CTS, abnormalities of the distal segment of the median NCS were more prominent compared with those of all the other tested nerves. These findings suggested that asymptomatic electrophysiologic CTS in diabetics is a manifestation of increased vulnerability to the entrapment of the peripheral nerve. (+info)