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Biomedical subjects

G Slama

Publications and source records attributed to G Slama.

At least 19 recordsLinked to original sources

[Insulin administration systems. Possibilities and difficulties].

Conventional insulin therapy, particularly when intensive, dose not provide all the comfort and effectiveness desired. The new insulin therapy methods that are, or will soon be, available are described in this review paper. The new types of subcutaneous insulin administration include the so-called "fountain-pens"--in fact ready-to-use syringes--and portable insulin pumps, which are helpful to some patients. Pancreas and islets transplantations are limited by the problem of tissue harvesting and by the necessity of chronic immunosuppression. Nasal insulin sprays will replace rapid insulin injections when the problem of bioavailability is solved and the lack of toxicity is demonstrated. The implantable artificial pancreas is still awaiting the development of long-term reliable glucose sensors, but one of its elements, the implantable insulin pump, is already operational; its safety and reliability have now been proven; its effectiveness seems to result from a better stabilization of blood glucose level variations; it will not supersede conventional injections, but it is the only alternative for patients with poor glycaemia control and notably for those at high risk of hypoglycaemia.

Administration, Inhalation

Severe early-onset polyneuropathy in insulin-dependent diabetes mellitus. A clinical and pathological study.

BACKGROUND AND METHODS: The pathophysiologic features of diabetic neuropathy, a common and disabling long-term complication of diabetes mellitus, are poorly understood. We studied five patients, 22 to 34 years old, in whom an uncommonly severe symmetric polyneuropathy developed soon after the onset of insulin-dependent diabetes. Their autonomic function and nerve conduction were studied, and sural-nerve biopsy specimens were examined by light and electron microscopy. Other causes of neuropathy were carefully excluded. RESULTS: Four patients had autonomic dysfunction with postural hypotension, fainting, diarrhea, and Argyll Robertson pupils and peripheral neuropathy with loss of sensation of pain and changes in temperature that followed a pattern suggestive of a length-dependent degeneration of nerve fibers. In contrast, the fifth patient had muscle weakness and atrophy of limb extremities, with "glove and stocking" sensory loss, but little autonomic dysfunction. In the biopsy specimens of sural nerves, the mean (+/- SD) density of myelinated fibers was reduced to 20 +/- 14 percent of that measured in five control patients, and the density of unmyelinated fibers was reduced to 6 +/- 4 percent of that in the controls. Regenerating fibers accounted for 38 +/- 11 percent of the myelinated axons. Abnormalities of the myelin sheath affected 33 +/- 21 percent of the isolated fibers, and axonal degeneration 11 +/- 8 percent. Dying-back fibers, a characteristic of the centripetal degeneration of peripheral axons, were also identified. The dying-back process progressed at the rate of a few hundred micrometers per day. CONCLUSIONS: Early-onset symptomatic polyneuropathy in patients with diabetes mellitus is characterized by the loss of both myelinated and unmyelinated nerve fibers. Spontaneous axonal regeneration is remarkably frequent, even when neuropathy is severe.

Action Potentials

[Administration of insulin in type 1 diabetes].

Insulin therapy by subcutaneous injection is not satisfactory: it rarely brings down glycaemia to its normal level, exposes to the risk of hypoglycaemia and hyperinsulinism, is difficult to endure for a long period and requires full patient's involvement. Improvements are being achieved in the route of insulin administration (intraperitoneal and nasal routes), the type of insulin (analogues) and the material used to administer the hormone (insulin pens and implantable pumps).

Diabetes Mellitus, Type 1

Comparative effects of 6 week fructose, dextrose and starch feeding on fat-cell lipolysis in normal rats: effects of isoproterenol, theophylline and insulin.

The precise effects of fructose feeding on adipose tissue is not clearly known. Consequently, we studied the effects of fructose feeding on stimulated and inhibited in vitro lipolysis. Twenty seven male Sprague Dawley rats, 5 weeks of age, were fed for 6 weeks on one of three diets containing 57% CHO as fructose (F), dextrose (D) or starch (S). At week 6 the epididymal fat pad weights showed no difference between groups. Stimulation of lipolysis by isoproterenol or theophylline showed: decreased sensitivity of adipocytes to isoproterenol, but not to theophylline, in F (p less than 0.05); the maximal responses were decreased, but NS, after stimulation by either isoproterenol or theophylline. The maximal antilipolytic responses to insulin were increased in F (27%) and D (29%) when compared to S (16%), (p less than 0.05). Only, in F there was an increase (NS) in ED50 (0.63 +/- 0.23 ng/ml) compared to D (0.45 +/- 0.18) and S (0.29 +/- 0.18), indicating decreased sensitivity. Nonfasting plasma insulin and triglycerides were increased at the 6th week in F (p less than 0.01), without any change in plasma glucose levels. However, there was no difference in 12 h fasting plasma glucose, insulin or triglycerides. In conclusion, a 6 week 57% fructose containing diet in normal rats led to: 1) decreased lipid mobilization in the epididymal adipose tissue; and 2) increased nonfasting plasma insulin and triglycerides. Thus fructose, under these experimental conditions, seems to have adverse metabolic effects in normal rats.

Adipose Tissue

Exercise is not associated with better diabetes control in type 1 and type 2 diabetic subjects.

In the clinical setting, the impact of educational efforts on the amount of regular exercise and its effects on diabetes control are unclear. Fifty type 1 diabetic, 50 type 2 diabetic and 70 non-diabetic subjects were evaluated using a questionnaire for type, duration and intensity of exercise to assess weekly energy expenditure. Diabetic subjects did not exercise more than controls: 36% of the type 1, 46% of the type 2 and 46% of the control subjects admitted no physical activity, and those exercising regularly had similar energy expenditure: 1808 +/- 320, 2722 +/- 617, 2523 +/- 304 (mean +/- SEM) kcal/week respectively (P = NS). There was no correlation between the degree of activity and HbA1c levels, or hypoglycaemic events. HbA1c levels were less than 6,8% in 31% of nonactive patients versus 21% of active patients (P = NS). A negative correlation was found between physical activity and daily insulin usage (r = 0.27, P less than 0.05), but differences between patients averaged only 4IU/1000 kcal energy expenditure/day. We conclude that patients' attitude towards exercise was not improved by our educational methods and that physical exercise was not necessarily associated with good blood glucose control.

Body Mass Index

Neither dietary fructose, dextrose nor starch modifies in vitro glycerol release by adipocytes from streptozotocin-diabetic rats.

Because we found previously that fructose feeding could alter lipolytic responses to isoproterenol and insulin in normal rats, we studied the effects of the same diet in neonatal, streptozotocin-diabetic rats. Twenty-seven 5-wk-old diabetic Sprague-Dawley rats were fed a diet containing 57% carbohydrate as either fructose, dextrose or starch for 6 wk. At the end of the nutritional period, plasma glucose and insulin concentrations in fed rats were similar in the three diabetic groups. Plasma triacylglycerol concentrations were higher in the fructose-fed group than in the other two groups (P < 0.05). Neither the maximal adipocyte lipolytic response (fructose = 1147 +/- 165%, starch = 1823 +/- 329% and dextrose = 1287 +/- 239% of basal values) nor the sensitivity to isoproterenol (ED50) was changed by the dietary carbohydrate exchange. The maximal antilipolytic action of insulin (starch = 68 +/- 10%, dextrose = 41 +/- 13%, fructose = 95 +/- 29% of stimulated lipolysis values) was comparable in the three diet groups. Thus, 6 wk of fructose feeding in diabetic rats increased plasma triacylglycerol concentrations, but had no detectable effect on plasma glucose or insulin concentrations, isoproterenol-induced lipolysis or the antilipolytic action of insulin.

Adipose Tissue

The use of low glycaemic index foods improves metabolic control of diabetic patients over five weeks.

The aim of the present study was to determine whether any benefit might occur from lowering the glycaemic index of diet in the medium term in diabetic patients. Eighteen well-controlled diabetic patients (12 Type 1 and 6 Type 2 non-insulin-treated), were assigned to either a high mean glycaemic index or low mean glycaemic index diet for 5 weeks each in a random order using a cross-over design. The two diets were equivalent in terms of nutrient content and total and soluble fibre content. The glycaemic indices were 64 +/- 2 (mean +/- SD) % and 38 +/- 5% for the two diets. The high glycaemic index diet was enriched in bread and potato and the low glycaemic index diet in pasta, rice, and legumes. At the end of the study periods, the following variables were improved on the low compared to the high glycaemic index diet: fructosamine (3.9 +/- 0.9 vs 3.4 +/- 0.4 mmol l-1, p less than 0.05); fasting blood glucose (10.8 +/- 2.8 vs 9.6 +/- 2.7 mmol l-1, p less than 0.02); 2-h postprandial blood glucose (11.6 +/- 2.9 vs 10.3 +/- 2.5 mmol l-1, p less than 0.02); mean daily blood glucose (12.0 +/- 2.5 vs 10.4 +/- 2.7 mmol l-1, p less than 0.02); serum triglycerides (1.5 +/- 0.9 vs 1.2 +/- 0.6 mmol l-1, p less than 0.05). No significant differences were found in body weight, HbA1C, insulin binding to erythrocytes, insulin and drug requirements, and other circulating lipids (cholesterol, HDL-cholesterol, phospholipids, Apolipoprotein A1, Apolipoprotein B). Thus the inclusion of low glycaemic index foods in the diet of diabetic patients may be an additional measure which slightly but favourably influences carbohydrate and lipid metabolism, requires only small changes in nutritional habits and has no known deleterious effects.

Adult

Initiation of insulin treatment after 70 years of age: patient status 2 years later.

The present study assessed 106 diabetic patients 2 years after beginning insulin treatment at or after 70 years of age. Ten patients (9%) had had the therapy discontinued after 2-4 months, 26 (25%) had died of causes unrelated to insulin therapy, 12 (11%) were lost to follow-up, and 58 (55%) were still alive and insulin treated. Fifty-one were at home and seven institutionalized for reasons unrelated to insulin therapy. Of these 58 patients, 50 were available for further study. Except for frequency of travel, which had decreased, lifestyle either improved or did not change. Patients' perceptions of the goals of treatment were more appropriate to a younger population of patients, who are less vulnerable to hypoglycaemic reactions. Mean fasting blood glucose was considered by the medical staff to be too low in 42% of cases. Adding insulin to the treatment of the elderly did not negatively affect their lifestyle, and indeed, insulin therapy appeared to create or strengthen the patients' existing social support network. Educational interventions must attempt to extend the effect of the specialized unit outside the hospital, to families, visiting nurses as well as general practitioners.

Age Factors

The insulin sparing effect of metformin in insulin-treated diabetic patients.

Since metformin became available for therapeutic utilisation, more than 30 years ago, it has been found that the compound was able to reduce hyperglycaemia in diabetic subjects without any stimulation of B cell secretion. The mechanism(s) of action of this drug has been better clarified these last 5-10 years even if all its aspects are not yet fully elucidated. What has been established, however, since the beginning of its clinical use, is that metformin can act in the presence of insulin in "facilitating" its effects. This had lead some authors to investigate the possible synergistic effect of metformin added to insulin therapy. Some studies have thus shown that insulin requirements were significantly decreased during the administration of biguanides, and effect which seemed to be maximal shortly after commencing the drug. Some authors have also claimed that biguanides smooth out blood glucose profiles in brittle diabetes, but this is denied by others. A decrease in insulin requirements may be of interest in diminishing peripheral hyperinsulinism and its possible consequences. It remains questionable whether the addition of metformin in the long term is to be recommended in Type 1 diabetic patients. However, such a clarification of decrease insulin requirements can help in the understanding of the clinical significance of metformin's actions in diabetes (impact on insulin resistance, receptor and post-receptor effects).

Diabetes Mellitus, Type 1

[Erythrocyte aggregation in vascular disease. Influence++ of hypertension].

In vascular diseases, when the vasomotor reserve is exhausted, microcirculation is strongly dependent on blood fluidity. For patients with vascular disorders, it was therefore decided to evaluate red blood cells (RBC) aggregation and disaggregation (SEFAM erythro-aggregometer) which are important factors determining blood viscosity in low flow areas. Our results show that, in essential hypertension (EH), RBC aggregation is significantly increased (+15%), and disaggregation is decreased (-20%). The highest frequency of troubles was found in EH. This observation led to exclusion of EH subjects in all the other studied pathological groups. When EH is excluded from a group of 70 patients with cerebrovascular disorders (CVD), we did not observe significant changes in RBC aggregation. However, in essential and post-thrombotic venous insufficiency there remains a significant increase in RBC aggregation (+10%) and a decrease in disaggregation (-13%). In diabetes, disaggregation is more disabled than for controls (-16%). In all these pathologies presence of EH magnifies the abnormalities, or makes them appear like in CVD. This study underlines the critical importance of taking the influence of hypertension into consideration when evaluating RBC aggregation in vascular pathology. The increase in RBC aggregability and in the shear resistance of the aggregates, when present in vascular pathology, is likely to add a burden to the circulatory system already hindered by a deficient vasomotor regulation system.

Adult

A new non-invasive method for treating insulin-reaction: intranasal lyophylized glucagon.

The main therapeutic indication for glucagon is the treatment of hypoglycaemia in insulin overdosed Type 1 (insulin-dependent) diabetic patients. We have previously shown that an intranasal spray of 7.5 mg glucagon with deoxycholic acid as surfactant was able to correct an i.v. insulin-induced hypoglycaemia in diabetic patients. However, bioavailability and stability needed to be improved before intranasal glucagon could be introduced into clinical practice. This has now been achieved with a freeze-dried mixture of glucagon (1 mg) and glycocholic acid (1 mg) as a surfactant. Kinetics and efficacy have been controlled by (1) comparing subcutaneous and intranasal glucagon in 12 healthy non-hypoglycaemic subjects; (2) testing intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by an i.v. bolus of insulin and (3) comparing subcutaneous and intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by adding extra subcutaneous regular insulin to their usual morning dosage. Our results show that 1 mg of intranasal glucagon is as effective as 1 mg of subcutaneous glucagon in terms of the rise in blood glucose. Differences in kinetics between the subcutaneous and the intranasal routes may be observed: intranasal glucagon initiates the blood glucose rise earlier than does the subcutaneous form but the effect of the latter is more sustained. Glycocholic acid appears to be a perfectly tolerated agent in acute conditions. The use of intranasal lyophylized glucagon, for the reversal of hypoglycaemia in Type 1 diabetes, seems to be a clinically relevant alternative to its parenteral equivalent and should now be ready to be introduced in the market.

Administration, Intranasal