[Peripheral diabetic neuropathy. Recommendations of ALFEDIAM (French Language Association for the Study of Diabetes and Metabolic Diseases)].
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Biomedical subjects
Publications and source records attributed to S Halimi.
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The role of serotonin in the insulin hypoglycemia (IH) stimulated secretion of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) and cortisol (F) was studied in a group of 12 normal subjects during the control period after placebo and a consecutive six-day treatment with 20 mg ritanserin (RIT) per day. RIT failed to affect the baseline levels of all the four hormones as well as the PRL response to IH (p > 0.5). The serum GH response to IH was moderately diminished after RIT, the reduction of integrated trapezoidal area under hormone curves (nAUC) being 50.7% +/- 6.9% (p < 0.005). Furthermore, RIT was found to slightly decrease the plasma ACTH response to IH, the reduction of nAUC being 36.3% +/- 2.6% (p < 0.005). Decrease in the corresponding plasma F response to IH was accompanied by 29.1% +/- 2.4% reduction of nAUC (p < 0.005). According to our results, serotonin-S2 receptors appeared to be moderately involved in IH-induced release of GH, but slightly in that of ACTH, leaving unaffected that of PRL.
DESIGN: Placebo for 3 months, followed by 30 mg/day zinc gluconate in identical capsules. SETTING: Diabetic out patients clinic at the University Hospital, Grenoble. SUBJECTS: Diabetic patients cared for type I diabetes mellitus. 22 patients began the study, 4 dropped out. 10 patients suffered of an early retinopathy, 8 patients had no retinopathy. INTERVENTIONS: In this order: T0 biological measurements, 3 months placebo treatment, T1 biological measurements, 3 months zinc gluconate treatment, T2 biological measurements. Plasma Zn, Cu, Se, thiobarbituric acid reactants and antioxidant enzymes were measured [plasma and red glutathione peroxidase (Se-GPx), red cell superoxide dismutase (Cu-Zn-SOD)]. RESULTS: Lower plasma zinc level in the two groups. An increase in zinc level was observed and was more important in diabetic patients with no retinopathy (P = 0.05). The thiobarbituric acid reactants were above the reference values in all the patients, and were decreased at T2 (P < 0.05). Increase of GPx activity after zinc supplementation in patients with retinopathy. CONCLUSIONS: Zinc deficiency in insulin-dependent diabetic patients is corrected by a zinc supplementation. Moreover this supplementation decreases lipid peroxidation. The effects of zinc are different in diabetic patients with or without retinopathy. The increase in Se-GPx activity observed in patients with retinopathy could be linked to the protective effect of zinc on the protein itself.
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We report a case of 47 years old patient who was admitted to hospital because of bilateral leg ulcers for 6 years. Chromosome analysis revealed XXY karyotype, confirming the clinical diagnosis of Klinefelter's syndrome. Testosterone level was low and Plasminogen Activator Inhibitor (PAI-1) was elevated. The patient was given androgen therapy which resulted in a normalization of the PAI-1 activity. The frequency of leg ulcers in patients with Klinefelter syndrome is between 6 and 12% according to studies. Different causes would explain the tendency towards leg ulcers in Klinefelter's syndrome: conjunctive tissues abnormalities were revealed in some studies. A higher frequency of venous insufficiency is reported in patients with Klinefelter's syndrome, either due to the particular morphology (obesity, taller size) or due to an androgen deficiency. A few arterial dysplasias cases of arteries's legs were described in patients with leg ulcers and Klinefelter syndrome. Haemostasis disorders presented in this case and normalized after androgen therapy will contribute to the physiopathologic discussion.
We have previously reported that zinc deficiency could increase in vivo lipid peroxidation and decrease rat insulin sensitivity. In the present paper, we address the hypothesis of the role of zinc on insulin molecule in relation to free radical damage. From native recombinant human insulin, we prepared a zinc-depleted insulin. Both preparations were subjected to controlled free radical attack by incubation in the presence of 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). To obtain minimally oxidized insulin, the oxidation process was monitored by measuring the intrinsic fluorescence of the insulin preparations. For 2.5 mM of AAPH, the autofluorescence of zinc-depleted insulin markedly decreased as compared to that of native insulin. These data are in favor of conformational changes of the insulin molecule which were further studied by quenching of fluorescence by means of potassium iodide. Using the euglycaemic hyperinsulinic glucose clamp technique in rats, the in vivo activities of the different insulin preparations, showed that oxidized zinc-depleted insulin had a marked reduced activity as compared to oxidized native insulin. From our results, we suggest that structural modification of the insulin molecule took place after zinc depletion and free radical treatment. Moreover, zinc depletion appeared to increase the susceptibility of insulin to free radicals.
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The availability of a new potent and selective serotonin-S2 antagonist, ritanserin (RIT), encouraged us to further investigate the effect of serotonin on the basal secretion of anterior pituitary hormones in normal humans. Administered in a single 30-mg dose to group 1 consisting of 10 normal women, RIT failed to affect the baseline LH, FSH, GH or TSH levels. In group 2 consisting of 20 normal subjects (ten males and ten females), the same dose of RIT decreased in parallel both ACTH and cortisol levels but only at 180 min. Group 3 consisting of 8 normal men was studied on three separate occasions seven days apart: each subject received graded doses of 10 mg, 20 mg and 30 mg RIT. The mean baseline PRL concentration at 180 min as well as the net integrated area under the hormone curve (nAUC) decreased only after the highest dose, while the baseline cortisol concentrations at 180 min as well as the corresponding nAUC values displayed a clear dose-dependent response. The findings indicated the serotonin-S2 receptors to be only partially involved in the basal secretion of ACTH in normal humans.
The aim of this study was to establish the concentration of insulin-like growth factor-I (IGF-I) in saliva of acromegalic patients, and to compare it with the basal levels of serum IGF-I and growth hormone. IGF-I was determined in extracted serum or neat saliva by a disequilibrium RIA using antibodies and iodinated ligand from Amersham and WHO 87/518 as standard. The detection limit of the assay was 0.5 microgram/l, and the intra- and interassay coefficients of variations were 7.9% and 15% respectively. Our study included 13 healthy adult individuals and 17 acromegalics. Compared with healthy adult subjects, acromegalics had significantly higher salivary IGF-I concentrations (mean +/- SEM 5.4 +/- 2.64 vs. 10.5 + -5.69 micrograms/l; p < 0.01), as well as serum IGF-I (176 +/- 42.9 vs. 520 +/- 98.8 micrograms/l; p < 0.0001) and somatotropin levels (1.2 +/- 1.02 vs. 15.4 +/- 9.89 micrograms/l; p < 0.0001). However, 47.1% patients (8 out of 17) with active acromegaly had salivary IGF-I concentrations within the normal range. Serum IGF-I and somatotropin concentrations were found to follow more closely the disease activity after adenomectomy, compared with the concentrations of salivary IGF-I. These results suggest that the IGF-I levels in serum and saliva are somatotropin-dependent. According to our results, measurement of IGF-I in saliva cannot be considered as an additional measure for evaluation of the disease activity in acromegaly, being less reliable than the determination of IGF-I and somatotropin in serum.
Urinary tract infections rank first among the infections of patients with diabetes mellitus. They are encouraged by chronic hyperglycaemia and occur more frequently in diabetic women aged over 50 who suffer from disorders of the autonomic nervous system responsible for disturbances of bladder voiding. Another facilitating factor in younger women is pregnancy. Acute pyelonephritis is more dangerous than in non-diabetic populations, being often painless and therefore neglected. An unexplained blood glucose imbalance may be the only manifestation of acute pyelonephritis. In these patients, pyelonephritis is more frequently complicated by pyonephritis or papillary necrosis, both capable of threatening the patient's life or renal function. Moreover, since the diabetic kidney is exposed to a specific glomerulopathy with nephroangiosclerosis and interstitial lesions, all infections may aggravate these lesions, and they must be treated vigorously. Antibiotics may be less effective due to reduction of their tissue levels, and relapses, more frequent and resistant to treatment, may call for prophylactic treatment in certain patients. This is why urinary tract infections must be detected systematically and with a frequency which depends on the presence or absence of facilitating factors: female sex, age, neuropathy, mechanical causes and pregnancy. Using dipsticks that detect urinary leucocytes and nitrates makes detection easier and less costly.
The prevalence of diabetes mellitus among patients treated for end-stage renal failure by dialysis in France was studied in two stages (UREMIDIAB Study). The first stage consisted of a questionnaire which was mailed to all dialysis centres in mainland France. The response rate was 80.8%, resulting in a study population of 12,903 patients. Of these patients 884 were declared diabetic (6.9%). Later 295 of them were interviewed by seven specially-trained physicians who checked the medical records together with the nephrologist in charge. Plasma C-peptide was measured in almost all of the patients. Effectively, 1.4% were found to have Type 1 diabetes and 5.5%, Type 2. Diabetic nephropathy was found to be the only primary renal diagnosis among 93.9% of Type 1 diabetic patients and 36.8% of Type 2. Of the latter 51.6% had a non-diabetic cause of renal failure. In the second stage a survey was later conducted in 13 of 14 dialysis centres located in the remote overseas French territories. Among 934 patients 1.04% were Type 1 diabetic and 19.67% Type 2 (22.9% altogether). Type 2 diabetic patients treated overseas were essentially non-Caucasians (92.6%). The sex ratio was 0.54 in the overseas territories vs 1.4 in the mainland. We conclude that the prevalence of diabetes among people on dialysis is low in mainland France. But there are striking differences in the prevalence of Type 2 diabetes among dialysis patients in mainland France and its overseas territories. These differences are not related to access to dialysis facilities.
OBJECTIVE: To study the structural modifications of a muscular and medium-size radial artery as regards age, in normal subjects (NT) and HT and DTI. MATERIAL AND METHODS: Transverse study with 39 NT aged 48 +/- 16 years, were compared to 22 HT, aged 50 +/- 11 years, and to 22 DT aged 37 +/- 12 years. An echo-tracking system (NIUS 01, Asulabs, Neuchatel, Switzerland) were used to measure the systolic (Ds) and diastolic diameter (Dd) and derive three indices of compliance and storage capacity: systolo-diastolic variation of cross sectional area VSCA = tau [(Ds2/4)-(Dd2/4)] mm2, operative arterial compliance CA = tau Dd (Ds-Dd)/2 (PAS-PAD) in mm2/mmHg. RESULTS: 1. In NT, Ds and Dd increased significantly with age (p < 0.01), likewise the VSCA, and CA (p < 0.002). 2. In HT and DTI, when age was taken into account, the Ds and Dd were significantly greater than in control but VCSA and CA were higher in HT and lower in DT. CONCLUSION: Similar to ageing changes in NT, HT lead to increase in medium-size radial artery the diameter and storage capacity, while to decrease in DT. This suggests that opposite cardiovascular load induce opposite modifications in arterial wall structure leading to reduce the wall stress.
Among the long term complications of diabetes, leg and foot problems frequently associated with chronic nonhealing wounds constitute a heavy economic cost previously evaluated in some countries. This specific cost has not yet been calculated in France. This study represents the first "estimation" of the frequency and cost of these complications in our country. Methodological obstacles must be considered related to a large variety of clinical situations all covered by the word "diabetic foot", neurotrophic or ischemic origin, and the heterogeneity of the therapeutical approach more or less expensive. We have estimated the incidence of leg and foot problems about 50,000 to 60,000 per years, 20,000 to 25,000 requiring an inpatient treatment for a neurotrophic complication and 10,000 to 15,000 for an ischemic problem (frequently followed by a limited or a large amputation). The annual total cost, direct plus indirect, calculated on this basis should be: 3,750 millions of francs/year (about 700 millions of US $). This value must be compared to the total cost of diabetes in France 12,000 to 18,000 millions of francs/year when considering 1 to 1.5 million diabetic patients. Thus leg and foot problems appear to constitute a prominent part of the economical cost of diabetes in our country as in others developed countries. Multidisciplinary and specialized structures for the care and prevention of such complications of diabetes must be developed as new therapeutical approaches to reduce this incidence, the duration of healing and the risk of relapse.
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Lipid peroxidation is known to accelerate aging and microvascular lesions in diabetic patients. We studied the acute influence of improved glycemic control on the concentrations of plasma lipid peroxidation intermediates [malondialdehydes (MDA), organic hydroperoxides (OHP)] in ketotic insulin-dependent diabetic patients, as well as the interplay of enzymes such as glutathione peroxidase (GPX) and CuZn superoxide dismutase (CuZn-SOD), and trace elements (Zn, Se, Cu) postulated to be involved in free radical protection. These plasma components were measured on the first day of hospitalization (T0) and when the patient had attained a stable glycemic state after continuous insulin treatment (T1). Plasma MDA and OHP concentrations were high at the beginning of the study but approached reference values after glycemic equilibration. Plasma zinc concentrations were significantly (P < 0.05) decreased during the ketotic state, but also approached reference values with glycemic equilibration. Plasma selenium concentrations and GPX activity were relatively unchanged between T0 and T1. Erythrocyte GPX activity measured at T1 in six patients was below the reference values, whereas CuZn-SOD activity was not affected. Our results show that enhanced lipid peroxidation is associated with decreased zinc plasma concentrations in ketotic patients and underline the beneficial effects of continuous insulin infusion. The mechanisms involved are still unclear but may indicate the importance of extracellular zinc transfer secondary to glycemic disorders.
Diabetes is a chronic disease requiring a compelling and permanent treatment which has repercussions on the patient's daily activities, tempo of life, feeding habits and physical exercises. This treatment also carries a risk of acute metabolic complications dreaded by the patient, the main one being hypoglycaemia. These constraints and fears have important effects on the patient's state of mind and must be taken into consideration by all those who look after him. For a strict and global handling of the diabetics' medical problems, it has been found necessary to institute an educational approach aimed at informing the patient, teaching him practical actions, facilitating his autonomy and reducing his anxiety and isolation. This approach is called diabetes education. It requires special training, as well as time and means, and must be subjected to evaluation. It is now well established that diabetes education is able to reduce the constraints of the disease, the frequency of metabolic accidents and the cost of diabetes. It is usually developed in hospital structures, but it also concerns private diabetologists and other medical helpers. This should convince the State authorities to recognize this teaching activity as a genuine therapeutic activity.
OBJECTIVE: To compare 24-h ABP in normotensive type 1 diabetic patients with and without microalbuminuria. RESEARCH DESIGN AND METHODS: The study was a retrospective comparison of cases and matched control subjects. The first phase included 35 type 1 diabetic patients, normotensive by OMS criteria. The 23 patients with normoalbuminuria (< 15 micrograms/min) were compared with 12 patients with microalbuminuria (> or = 15 micrograms/min). In the second phase, the 12 microalbuminuric patients were paired by sex- and age-matched with 12 normoalbuminuric patients and 12 nondiabetic healthy control subjects. We measured casual systolic and diastolic BP and HR, 24-h ABP and AHR (recorded with a Spacelabs automatic recorder), and microalbuminuria. RESULTS: No correlation between microalbuminuria and casual BP was observed. Microalbuminuria was correlated significantly with diastolic 24-h APR and nocturnal systolic and diastolic ABP (r = 0.35, 0.38, and 0.33, respectively; P < 0.05) and with AHR during all time periods (24-h, r = 0.46; day, r = 0.39; night, r = 0.39; P < 0.05). Normo- and microalbuminuric patients did not differ in casual BP and HR. However, microalbuminuric patients had a significant increase in systolic 24-h ABP (119.1 +/- 8.2 vs. 113.1 +/- 8.1, P = 0.05), diastolic 24-h ABP (74.9 +/- 7.5 vs. 70.2 +/- 5.7, P = 0.04), nocturnal systolic ABP (112.8 +/- 7.1 vs. 105.8 +/- 7.9, P = 0.01), and AHR during all time periods. The same results were observed when patients were paired by age and sex. CONCLUSIONS: Normotensive microalbuminuric type 1 patients, although strictly comparable with normoalbuminuric patients for casual BP and HR, have an increased ABP and HR, especially during the night. This difference might reflect dysautonomia. Ambulatory measurement of BP and HR is more appropriate than casual measurements in hemodynamic studies of incipient diabetic nephropathies and could be proposed as an interesting tool for an early prediction of diabetic nephropathy.
The prevalence of diabetes mellitus among patients treated for end-stage renal failure was studied using a questionnaire mailed to all dialysis units of mainland France in 1989. With a response rate of 80.8%, the study population amounted to 12,903 dialysed patients of whom 884 were declared diabetic (6.9%). In a second phase, the study focused on the diabetic patients treated in the 63 largest units (those with at least four diabetic patients). Seven specially trained physicians completed questionnaires after having interviewed the patients and checked their medical records. All this material was reviewed by the same diabetologist. The conflict of diabetes type declared by both sources of information (the nephrologists and the diabetologist) showed a misclassification rate of 31.2%. Using these new data, the prevalence of type 1 diabetes mellitus was estimated at 1.4% of patients on dialysis therapy in mainland France, and 5.5% for type 2 diabetes mellitus. A north-south declining trend was suggested for type 2 diabetes mellitus. Diabetic nephropathy was the only primary renal diagnosis among 93.9% of type 1 diabetic patients, but only for 36.8% of type 2 diabetic patients. Of the latter, 51.6% had a non-diabetic cause of renal failure. These data show that the proportion of diabetics among patients receiving dialysis, while steadily increasing in France, remains lower than in other countries in Europe and in North America. However, the validity of international comparisons depends on diabetes ascertainment. Heterogeneity in selection of patients and in diabetes type classification by dialysis units may account to a considerable degree for the differences between diabetes mellitus prevalence across countries.