Twenty-four hour blood pressure and heart rate profiles of diabetic patients with abnormal cardiovascular reflexes.

Twenty-four hour ambulatory blood pressure and heart rate profiles of 24 patients with diabetes were monitored in order to assess the effect of autonomic neuropathy on 24-h haemodynamic profiles. Eighteen patients had abnormal cardiovascular reflexes. Mean arterial pressure rose at night in six of the patients with autonomic neuropathy and fell by less than or equal to 5 mmHg in seven. In the remaining five patients with autonomic neuropathy and in the six diabetic patients with normal cardiovascular reflexes, the fall in nocturnal mean arterial pressure was comparable to that of 11 non-diabetic patients with essential hypertension. Median 24-h mean arterial pressure was similar in all four groups of diabetic patients. Prevalence of autonomic symptoms was not related to the change in blood pressure in those with autonomic neuropathy. Twenty-seven months after monitoring, three fatal and five severe non-fatal cardiovascular or renal events had occurred in four of the six patients with a rise in nocturnal blood pressure, compared with one non-fatal event in those with a small fall and no severe events in those with a pronounced fall (p = 0.02). Blood pressure rises at night in certain diabetic patients with abnormal cardiovascular reflexes and the nocturnal rise appears to be associated with a poor prognosis.

The Thermocross: a simple tool for rapid assessment of thermal sensation thresholds.

We have developed the Thermocross, a simple device for rapid assessment of thermal sensitivity, tested it on healthy subjects and diabetic patients and evaluated its use in identifying patients whose sensation loss may expose them to the risk of neuropathic foot injury. Thermal discrimination deteriorated with age (P less than 0.001) in healthy subjects, but all the controls could detect a temperature difference less than or equal to 10 degrees C. In diabetic patients, the deficit in thermal sensation detected by the Thermocross paralleled the decline of nerve conduction. Thermocross thermal sensation was impaired in 87% of 38 ulcerated feet of 26 diabetic patients. We conclude that the Thermocross is a suitable tool for screening for sensation loss and that diabetic patients with impaired thermal sensation are vulnerable to ulceration. The Thermocross could also serve a useful educational purpose, the implications of reduced thermal sensation probably being more meaningful to patients and health care personnel than those of a reduction in the traditionally tested vibration sensation.

The tuning fork revisited.

The performance of the Rydel-Seiffer graduated tuning fork was examined in healthy subjects and in various groups of diabetic patients in order to evaluate its efficacy for identifying patients whose loss of vibration sensation may expose them to the risk of foot injury. Vibration perception score measured with the tuning fork declined with age (p less than 0.001) in the control subjects. It correlated well (r = -0.90, p less than 0.001) with the thresholds obtained with an electromagnetic instrument (Vibrameter) in diabetic patients, in whom vibration perception score was impaired compared with control subjects (4.0 +/- 1.8 (+/- SD) vs 5.4 +/- 1.4, p less than 0.001). Age-related Rydel-Seiffer tuning fork vibration sensation was impaired in 79% of 38 ulcerated feet of 26 patients. The tuning fork score was less than or equal to 4.0 in 95% of the ulcerated feet. We conclude that the Rydel-Seiffer graduated tuning fork is a suitable tool for screening for sensation loss and that diabetic patients with a tuning-fork score of less than or equal to 4.0 are vulnerable to ulceration.

[Diabetic neuropathy]. / La neuropathie diabétique.

Neuropathy is a frequent late complication of diabetes. The severity and duration of hyperglycaemia are probably the principal causal factor. The consequences of the effects of neuropathy on the lower-limb and the autonomic nervous system are major causes of morbidity. Apart from glycaemic control, no specific treatment is yet available, but measures for symptomatic alleviation of certain painful and visceral manifestations of diabetic neuropathy exist and are outlined in these guidelines. The guidelines also describe simple diagnostic strategies for detecting potentially threatening neurological signs, notably reduction or loss of lower-limb sensation which expose the patient to the risk of ulceration, unnoticed trauma and amputation. The guidelines also summarize the preventive educational measures required to minimize these risks.

Effect of gangliosides on diabetic peripheral neuropathy.

The effect of subcutaneously injected gangliosides on diabetic peripheral neuropathy was assessed in 26 diabetic patients with neuropathy, 20 of whom received 100 mg daily 5 days per week for 12 weeks in a randomised single-blind cross-over placebo-controlled study and six of whom, with painful neuropathy, received the same quantity of gangliosides for the same length of time but no placebo. Subjective symptoms of lower limb neuropathy improved on gangliosides but not on placebo (P = 0.01). The amplitude of the peroneal nerve muscle action potential increased on gangliosides and declined on placebo (P = 0.05), but no other significant changes were observed in nerve conduction or in any other measurable sign of lower limb somatic nerve function or of cardiovascular autonomic function.

[Long-term complications in diabetes mellitus]. / Les complications a long terme dans le diabete sucre.

Diabetes mellitus is a chronic disease with early and late complications. In the clinical care provided to diabetics, prevention of late complications is as important as good metabolic control. To achieve these goals education of the diabetic subject is essential. Eye and nervous system complications are particularly highlighted.

Additional factors associated with plantar ulcers in diabetic neuropathy.

Patients can only examine and handle their own feet if they have adequate visual acuity and joint mobility. We therefore studied the physical capacity of patients with neuropathy to perform the preventive footcare measures previously taught. The study included three groups of diabetic outpatients, comparable for age and duration of diabetes: (1) 38 patients with neuropathic ulcers; (2) 21 patients with neuropathy, but no ulcers; (3) 30 patients without neuropathy. Visual acuity and joint mobility, expressed as minimum eye-metatarsum and heel-buttock distances, did not differ between uncomplicated neuropathic and non-neuropathic patients: visual acuity was sufficient in 95% of neuropathic patients without ulceration and in 87% of non-neuropathic patients; joint mobility was in the normal range in both groups. However, 71% of complicated neuropathic patients had insufficient visual acuity for correct foot examination, and their joint mobility was reduced compared with uncomplicated neuropathic and non-neuropathic patients.

[Nyctohemeral arterial pressure profile and heart rate in autonomic diabetic neuropathy]. / Profil nycthéméral de la pression artérielle et de la fréquence cardiaque dans la neuropathie diabétique autonome.

Autonomic failure reduces the physiological nocturnal decline of blood pressure (BP) and heart rate (HR). To assess the effect on circadian hemodynamic rhythms of sympathetic (s) and parasympathetic (ps) impairment in diabetic autonomic neuropathy (DAN), we measured BP automatically every 15 min and HR continuously for 24 hour in 11 diabetic patients. They were divided into 3 groups according to the results of cardiovascular reflex tests: a) DAN s + ps, b) DAN ps, c) no DAN. Nine of the patients were hypertensive. Eleven non-diabetic hypertensives served as controls. The disturbance of the circadian BP profile was related to the severity of the DAN, nocturnal BP tending to rise in group a, to fall in group b, and falling markedly in group c and in the control group. FC fell to a similar extent in all the groups. We conclude that the circadian BP profile is more affected by DAN than the FC profile, and that study of the circadian BP profile could reveal the presence of predominantly nocturnal hypertension.

Interference of dimethyl alpha-(dimethoxyphosphinyl) p-chlorobenzyl phosphate (SR-202) in thyroid hormone metabolism: evidence of inhibition of monodeiodination.

SR-202 is a non-iodinated potential lipid-altering agent. When administered (100 mg) three times per day for 3 days to six euthyroid subjects it was associated with a 30 +/- 3% (mean +/- S.E.M.) fall in 3,3',5-triiodothyronine (T3) (P less than 0.001), a reciprocal 104 +/- 14% rise in 3,3',5'-tri-iodothyronine (reverse T3, rT3) (P less than 0.01), and a 37 +/- 7% rise in thyroxine (T4) (P less than 0.001). Basal and TRH-stimulated TSH did not change. These results suggested that SR-202 was acting as an inhibitor of the peripheral monodeiodination of T4 to T3. During a second study the same subjects received the same dose of SR-202 for a further 3 days following 15 days of progressive substitutive treatment with L-T4, which they continued to take at 200 micrograms/day until the end of the study. Despite higher levels of thyroid hormones in the substituted subjects, similar results were observed, serum T3 falling by 40 +/- 2% (P less than 0.001), serum rT3 and T4 rising by 168 +/- 24% (P less than 0.01) and 37 +/- 9% (P less than 0.01) respectively. These changes provide compelling evidence that SR-202 is an inhibitor of the peripheral conversion of T4 to T3 that acts on thyroid hormone metabolism without provoking a counter-regulatory pituitary response. It might prove to be a useful tool for the clinical investigation of thyroid function.

Effects of bopindolol on renal function.

The effect of the long-acting beta-blocking agent bopindolol on renal function was assessed in 10 healthy normotensive volunteers and 10 hypertensive patients. The subjects received 1 mg bopindolol at 8 p.m. for 21 days. The following determinations were made at 8 a.m. on recumbent, fasting subjects before day 0 (D0) and 12 h after day 1 (D1) the first dose of bopindolol, and on the 21st day of treatment (D21): blood pressure (diastolic = DBP), glomerular filtration rate (GFR) and renal plasma flow (RPF) as reflected by the plasma disappearance of 51Cr-EDTA and 125I-hippuran, plasma concentrations and 2- and 24-h urinary excretion of electrolytes, creatinine, and proteins and osmolality of the urine. Plasma renin activity was assessed on standing subjects. Following bopindolol administration GFR, RPF, and filtration fraction remained stable, in spite of a fall of DBP from 80 +/- 7 to 76 +/- 4 and to 72 +/- 9 mm Hg in normotensives (p less than 0.05) and from 106 +/- 11-96 +/- 10 and to 91 +/- 8 mm Hg in hypertensives (p less than 0.05) on D1 and D21, respectively. The drops in DBP at D1 correlated weakly with the pretreatment renin levels (p = 0.074, p less than 0.05). All the other variables remained stable, including diuresis, free water clearance, and fractional sodium excretion. It is concluded that in contrast to many other anti-hypertensive drugs including several beta blockers, bopindolol does not reduce renal function during short- or medium-term treatment in normal volunteers or hypertensive patients.