Comparative effects of simvastatin and pravastatin on cholesterol synthesis in patients with primary hypercholesterolemia.

The effects of simvastatin and pravastatin on cholesterol biosynthesis were compared in 26 hypercholesterolemic patients who were randomly allocated to either simvastatin or pravastatin treatment (20 mg once daily) for 6 weeks in a crossover trial. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) lathosterol (latho) concentrations and lathosterol/cholesterol (latho/chol) ratios (the latter two are considered as reliable indices of whole body cholesterol synthesis) were evaluated at the beginning and end of each therapeutic sequence. Reductions in TC and LDL-C were more pronounced (P < 0.001) with simvastatin (TC = -28.0%, LDL-C = -35.6%) than with pravastatin (TC = -19.6%, LDL-C = -25.2%). These results were associated with concomitant decreases in both latho concentrations (-59.0% with simvastatin and -37.0% with pravastatin) and latho/chol ratios (-43.0% with simvastatin and -20.3% with pravastatin). Simvastatin resulted in more marked diminutions of latho concentrations (P < 0.01) and latho/chol ratios (P < 0.05) than pravastatin. These results suggest that the better efficacy of simvastatin on serum cholesterol and LDL cholesterol might result in part from a greater inhibitory action of simvastatin on cholesterol synthesis compared with that of pravastatin.

[Very-low-calorie-diets: is there a place for them in the management of the obese diabetic?]. / Les "very-low-calorie diets" ont-elles une place dans la prise en charge du diabétique obèse?

It is well-recognized that standard caloric restrictions (1500 kcal/day) are usually poorly effective in achieving weight losses in overweight type 2 diabetic patients. For that reason very-low-calorie-diets (VLCDs) were developed as a mean for initiating or accelerating weight reduction. Short-term studies indicate that VLCDs result generally in weight losses that are three times greater than those obtained with standard low-calorie-diets. Fasting blood glucose values are improving in parallel to weight losses and in many patients the improvement in glycemic control is better than that expected from the magnitude of weight losses. However the results are rather disappointing after several months or years of follow-up. For example it has been demonstrated that weight regain can be observed as soon as the patient is shifted to a refeeding or maintenance dietary program at the end of the VLCD period. Long-term results on glycemic control and body weight reduction are generally similar with standard low-calorie-diets and with VLCDs, the final results depending on the magnitude of weight loss whatever the prescribed diet. At short-term the VLCDs can be helpful first for initiating weight losses and second for sensitizing the patient to the potential benefits of complying to dietary measures.

[Changes in dietary management of diabetic patients]. / Le changement dans la prise en charge diététique du diabétique.

In the late 1990s, diet remains the cornerstone of diabetes therapy. Dietary and nutritional recommendations should seek to reduce the hyperglycaemic state which is the main risk factor for microangiopathy. Furthermore, the prevention of macrovascular complications should lead to dietary prescriptions that combine such properties as antiatherosclerotic, antithrombotic, and antihypertensive measures and such advantages as reducing oxidative stress. The means for achieving such objectives are, first, weight-loss interventions in obese patients and, secondly, the choice of a judicious balance between carbohydrates and monounsaturated fats in all individuals. Dietary measures must achieve a compromise between their acceptability by the patient and medical requirements. For that reason, caloric restriction should be moderate, leading to progressive weight loss (-3 kg monthly), with reasonable weight targets at the end of the weight-reduction period. Compliance with dietary advice usually results in significant savings in medical costs. However, long-term maintenance of dietary measures is difficult to achieve in most individuals, except those enrolled in well-structured training programmes.

[Dietary assessment in current clinical practice: how to conciliate rapidity, simplicity and reliability?]. / Evaluation alimentaire en pratique courante: comment concilier rapidité, simplicité et fiabilité?

Dietary interviews and food diaries are traditionally used for nutritional assessments. In clinical practice, these methods are time consuming, require high training, and thus remain poorly used. Furthermore, the results are frequently impaired by the underreporting phenomenon which can be due either to underrecording (failure to record what is eaten) or to undereating (volontary food restriction during the assessment period). These difficulties can be overcome by using rapid questionnaires based on 2 principles: 1) underreporting is less for proteins than for other macronutrients; 2) in developed countries, calories from proteins are relatively stable and contribute approximately to one sixth of the total daily energy intake. Estimations given by the rapid questionnaire lead to less misleading results than those provided by 7 day-food records. On the other hand, the rapid questionnaire gives an estimate of specific dietary behaviors such as nibbling, festive meals and consumption of salted entrées, sweet desserts and caloric beverages. In conclusion, helpful and simple recommendations for correcting main nutritional errors can be drawn from estimation of the above mentioned specific behaviors that correspond to a daily average of 500 kcalories.

Effects of moderate changes in protein intake on urinary albumin excretion in type I diabetic patients.

We investigated the short-term effects of moderate increments or decrements of protein intake on albumin excretion rates of type I diabetic patients. Ten normotensive patients with either normal albumin excretion rates (< 20 micrograms/min, group I, n = 5) or persistent mu-albuminuria (20-200 micrograms/min, group II, n = 5) were fed successively three test diets providing different protein intakes. Each patient was randomly allocated to 3-wk sequences of the following diets: low-protein diet (LPD; median 0.84, range 0.76-0.94 g.kg-1.day-1), medium-protein diet (MPD; median 1.33, range 0.98-2.00 g.kg-1.day-1), and high-protein diet (HPD; median 2.05, range 1.54-2.61 g.kg-1.day-1). The three diets were isoenergetic and isoglucidic. In group I patients, no consistent change was found in mu-albuminuria. In group II patients, LPD resulted in a reduction in mu-albuminuria compared with MPD and HPD. Changes in albumin excretion rates were positively correlated to relative changes in protein intake. This suggests that moderately protein-restricted diets can reduce mu-albuminuria in diabetic patients suffering from incipient nephropathy, the degree of reduction depending on the degree of restriction. Because of poor patient compliance with protein intakes < 0.8 g.kg-1.day-1, we conclude that moderately rather than severely protein-restricted diets should be recommended for long-term prescriptions.

[Incidence of endemic goiter on Reunion Island. A search for etiological factors]. / Incidence du goitre endémique à l'île de la Réunion. Recherche des facteurs étiologiques.

In an epidemiological study carried out in Reunion Island, 1,686 randomized school children aged from 11 to 15 years were examined for goitre by cervical palpation. A detailed questionnaire was fully completed by each child and his parents. The iodine level was measured in 168 urinary samples and in the salt and water consumed in the various places investigated. The overall incidence of goitre was 8.2 percent, rising up to 19.7 percent in the mountainous part of the island. The mean urinary iodine level was 40.2 +/- 2.7 micrograms I/g creatinine (m +/- SEM) and fell to 20.0 +/- 3.7 in the highlands. Water and salt contained little iodine. A significant relationship was noted between the presence of goitre on the one hand and sex, familial incidence of goitre, cassava consumption and distance from the coast on the other hand. This study demonstrates that endemic goitre and iodine deficiency are present in a limited area of Reunion Island.

[Insulin, diabetes and cholesterol metabolism]. / Insuline, diabète et métabolisme du cholestérol.

Cholesterol metabolism is altered in diabetic states. Three main mechanisms seem to be involved in these alterations: a) an increased glycation of cholesterol-rich lipoproteins, b) an insulin-resistant state which is mainly present in overweight type 2 diabetic patients, and c) changes in insulin secretion which depends on the clinical type of diabetes. Insulin per se exerts beneficial effects on the metabolism of cholesterol binding lipoproteins. Despite insulin has a stimulatory influence on the endogenous cholesterol synthesis from Acetyl-CoA, this hormone tends to decrease the LDL cholesterol concentrations through two additional effects: a diminution in the ApoB VLDL synthesis and an increase in the LDL catabolism. In well controlled diabetic patients, plasma concentrations of cholesterol binding lipoproteins are generally found within the normal range. These patients exhibit usually a normal sensitivity to insulin in the liver and peripheral tissues. In this case, the VLDL production is generally decreased, the LDL catabolism is either increased or normal, and therefore the endogenous cholesterol synthesis from Acetyl-CoA remains setted at a normal level. In poorly controlled and/or in insulin resistant diabetic patients, both VLDL cholesterol production and cholesterogenesis are increased, mainly as a consequence of the insulin-resistant state. The excessive glycation of LDL results in a diminution of their catabolism and therefore in an increase of their plasma concentrations. The reverse cholesterol transport pathway is also altered, the modifications being characterized by a diminution in HDL cholesterol concentrations, especially in the HDL2 subfraction. All these changes are certainly involved in the accelerated development of cardio-vascular complications encountered in diabetic patients.

The management of differentiated thyroid cancer in Europe in 1988. Results of an international survey.

In order to know how thyroid nodules and differentiated thyroid cancers are investigated and treated in 1988, an international inquiry was performed by mean of a questionnaire based on a well-defined case report of a 35-year-old female with a solitary small thyroid nodule. Clinicians were asked to indicate their diagnostic and therapeutic approaches to the reported case and to some variations. Analysis of the 157 responses from thyroid experts showed that three in vitro tests (sensitive-TSH, free T4 and total T4) and three in vivo tests (99mTc or radioiodide scintiscan, fine needle aspiration and ultrasonography) were performed most frequently. In the case of a solid and cold nodule and in the absence of fine needle aspiration results, 19% of respondents advocated suppressive therapy and 81% surgery. In the same clinical case, but whom fine needle aspiration had been performed and cytology was benign, surgery was advocated by 24%, suppressive therapy by 48% and a regular follow-up without treatment by 28% of respondents. When surgery was performed and the diagnosis was a differentiated thyroid cancer, (near) total thyroidectomy was more frequently chosen than partial thyroidectomy in both papillary (60 and 40%, respectively, of respondents) and follicular (74 and 26%, respectively, of respondents) cancers; 80% of clinicians did not change their surgical technique in relation to histological type of the tumour. Total thyroidectomy was more often recommended in most of the clinical or anatomical variations compared with the basic case report. Pre- or postoperative hormonal therapy was initiated with L-T4 and TSH suppression was controlled by sensitive-TSH and thyroglobulin determinations. After total thyroidectomy, 131I was used with similar modalities for papillary and follicular cancers to ablate a thyroid remnant.

Renal handling of calcium in hypercalciuric calcium oxalate nephrolithiasis.

In order to gain further insight into the mechanisms of calcium (Ca) homeostasis in hypercalciuria, we studied 32 lithiasic patients who were divided into three groups: normocalciuric patients (NC; n = 11), patients with absorptive hypercalciuria (AH; n = 12) and patients with renal hypercalciuria (RH; n = 9). The patients were investigated on 3 occasions: during a random diet, after a Ca-restricted diet and during a Ca tolerance test. The following determinations were made: Ca intake, Ca tubular reabsorption (Ca TR), plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) levels, natriuresis and urinary protein-bound Gla. The latter was measured as a marker of urinary nephrocalcin excretion. Ca TR was decreased in hypercalciuric patients (HC). AH but not RH patients normalized their Ca TR during fasting. Plasma PTH and 1,25(OH)2D levels were similar in all the groups on the 3 occasions. Natriuresis was elevated in RH during the fasting period (p < 0.02 vs. AH). Compared with NC, protein-bound Gla urinary excretion rates (UER) were enhanced in AH after the Ca-restricted period (p < 0.02) and in RH during fasting (p < 0.02). In AH, a strong positive correlation was found between Ca TR and protein-bound Gla UER (r = 0.79, p = 0.002) following a Ca-restricted diet. In the HC group as a whole, fasting protein-bound Gla UER were correlated to plasma 1,25(OH)2D levels (r = 0.68, p < 0.001). In conclusion, the results suggest that PTH directly or indirectly through 1,25(OH)2D increases nephrocalcin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between insulin sensitivity, obesity, body fat distribution and beta-endorphinaemia in obese women.

OBJECTIVE: To study the associations of obesity (as body mass index (BMI)), of body fat distribution (as waist to hip ratio (WHR)) and of beta-endorphinaemia (beta-EP-aemia) with fasting insulin and glucose concentrations, with insulin secretion (as first phase insulin response (FPIR)) and with insulin sensitivity (SI) in obese women. DESIGN: a cross-sectional study of insulin sensitivity in obese women. SUBJECTS: 45 obese women (age: 20-70 y, BMI: 27-50). MEASUREMENTS: Frequently sampled intravenous glucose tolerance test (FSIGTT), FPIR, fasting glucose, fasting insulin, BMI, body fat topography (WHR), beta-EP-aemia, plasma ACTH. RESULTS: In univariate analysis the following positive associations were observed: fasting glucose with age and WHR, fasting insulin with BMI and WHR, beta-EP plasma concentration with WHR; SI was negatively associated with BMI, WHR and beta-EP plasma concentrations. This pattern of associations remained unaltered in multivariate analysis including age, BMI and WHR as independent variables. The contribution of beta-EP plasma concentrations to SI variability was corroborated by a stepwise multiple regression analysis: 53.8% of SI variation could be explained by BMI (30.7%), by beta-EP plasma concentrations (17.2%) and by WHR (5.9%). Finally, women were divided into two groups according to whether they had a peripheral (P-BFD, WHR < or = 0.80, n = 24) or an abdominal (A-BFD, WHR > or = 0.85, n = 16) body fat distribution. After adjustment for age and BMI, SI values were lower while beta-EP and ACTH plasma concentrations were higher in the A-BFD compared to the P-BFD group. In this latter group, 54.8% of SI variation was explained by the same variables as in the whole group. In the A-BFD group, higher WHR was associated with lower FPIR. CONCLUSIONS: 1) The major finding of this study is that, in non-diabetic obese women (especially those with a P-BFD), higher beta-EP plasma concentrations are associated with lower insulin sensitivity. This association is independent of both the magnitude of obesity and the pattern of fat distribution, although these two parameters are strong predictors of SI. 2) The major reduction in SI observed in women with A-BFD probably results from the additive effects of obesity, of elevated beta-EP plasma concentrations and of metabolic and endocrine alterations in relation with the central pattern of fat distribution.

Recurrent mutation at aa 792 in the LDL receptor gene in a French patient.

Many mutations in the low density lipoprotein receptor gene (LDLR) have been characterized at the molecular level in individuals with familial hypercholesterolemia. Most of the mutations that have been reported are large deletions or insertions in the gene, it being much more difficult to identify point mutations. In this study, 139 unrelated French familial hypercholesterolemia subjects were screened for the presence of three different previously described LDLR point mutations, employing the polymerase chain reaction and allele-specific oligonucleotide hybridization. Only one subject carried a point mutation at amino acid position 792, which substituted a Trp codon for a Stop codon. The same mutation has previously been described in a subject originating from Saudi Arabia. Haplotype analysis of LDLR associated with each mutation was performed. The haplotypes were totally different, suggesting that this mutation has occurred more than once.

Exchanging carbohydrates for monounsaturated fats in energy-restricted diets: effects on metabolic profile and other cardiovascular risk factors.

OBJECTIVE: To investigate whether improvements in cardiovascular risk factors, as observed in energy-balance conditions after exchanging carbohydrates (CHO) for monounsaturated (MUFA) fats, are also observed in energy-restricted conditions. DESIGN: Longitudinal, clinical intervention study using two types of energy-restricted diets (-30% of initial energy intake) with similar levels of saturated and polyunsaturated fats: a high CHO diet (55% of energy from CHOs, 10% from MUFAs) and a high MUFA diet (40% of energy from CHOs, 25% from MUFAs). SUBJECTS: A total of 32 overweight subjects (nine males, 23 females, BMI: 26-45 kg/m(2)). MEASUREMENTS: Body weight, serum lipids, fasting plasma insulin and phospholipid fatty acid composition of red blood cells were measured at baseline and after 8 weeks. Various oxidative status parameters (plasma lipid hydroperoxides, total plasma antioxidant capacity, plasma uric acid and vitamin E) and serum-induced smooth muscular cell (SMC) proliferation were also measured at these time points. RESULTS: Weight loss (1.1 kg/week over the first 4 weeks and 6.7 kg at week 8) was not significantly affected by the diet composition. Both diets reduced significantly total serum cholesterol, but the MUFA-rich diet showed better effects on fasting serum triacylglycerol (TG) than the CHO-rich diet: 1.18 vs 1.51 mmol/l for the MUFA-rich diet (after vs before, P<0.05) and 1.42 vs 1.62 for the CHO-rich diet. After 8 weeks, plasma vitamin E concentrations were positively associated with the oleic acid level of red blood cell phospholipids and showed opposite variations in both diets (increase with the MUFA-rich diet and decrease with the CHO-rich diet). Relative changes in SMC proliferation induced by sera were negatively associated with the ratio oleic:linoleic acid of red blood cell phospholipids and were significantly higher with the CHO-rich diet. CONCLUSIONS: The MUFA-rich diet showed better effects on serum TG than the CHO-rich diet, even with energy restriction and weight loss. The results suggest also a protective effect of oleic acid on oxidative stress and SMC proliferation, two other important cardiovascular risk factors.

Is glucose self-monitoring beneficial in non-insulin-treated diabetic patients? Results of a randomized comparative trial.

To study if self-monitoring of glucose, urinary or capillary, could help them to improve their metabolic control through better compliance to diet and/or hypoglycaemic agents, 208 non-insulin-treated poorly controlled diabetic patients were randomized to: group A--regular HbA1c determinations but no self-monitoring, group B--self-urine glucose monitoring, twice every other day, group C--self blood glucose monitoring, twice every other day, and followed six months. At the end of the study period, the decrease of HbA1c over six months--main endpoint--was not significantly different between the three groups (mean +/- SEM; group A: -0.5 +/- 0.2%; group B: -0.1 +/- 0.3%; group C: -0.4 +/- 0.3%). However, the degree of compliance to blood glucose self-monitoring in group C appeared to relate to the outcome: a significant correlation was found between the number of blood glucose strips used and the decrease of HbA1c (r = .36, p less than .02). We conclude that regular self-monitoring has no definite advantage over the usual management for improving metabolic control in non-insulin-treated diabetic patients, though it may possibly help patients ready to comply with its use.