[How I treat and manage a patient with massive obesity].
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Humans↗
Biomedical subjects
A Basdevant
Publications and source records attributed to A Basdevant.
[Pharmacology of estrogens used in the treatment of menopause].
Numerous compounds with estrogenic activity are available to treat menopause. The main ones are oestradiol, administered by various routes, and equine estrogens which are taken orally. These compounds differ from each other by their chemical structure, metabolism and kinetics; the metabolic impact of these drugs especially on the liver depends on these parameters. All estrogens are potent, active, and capable of treating effectively the short and long term manifestations of menopause. Their metabolic safety according to the route of administration remains opened to discussion.
Estradiol↗
[Treatments of massive obesity].
Treatment of massive obesity aims at somatic, psychological and social targets and therefore requires a multidisciplinary team co-ordinated by a physician. Treatment usually begins by taking care of the most worrying somatic and metabolic problems (cardio-respiratory and metabolic disorders) and by correcting the diet. It is then enhanced by a psychological assistance provided by the treating team and, in certain cases, by a psychotherapist. Massive obesity is a chronic, recurrent and severe disease. Its treatment is prolonged and implies numerous constraints (diet, drugs, treatment of a possible sleep apnoea syndrome) which are difficult to tolerate in the long term. This type of management resembles that of other chronic diseases, such as complicated diabetes. From dietetics to the most technical medicine, from the doctor-patient relationship to psychotherapy, the therapeutic methods are numerous, and the burden of using them in a coherent manner falls on the physician.
Humans↗
Snacking patterns in obese French women.
Snacking patterns were studied in 273 obese women by dietary history. Snacking was observed in 60% of the sample and occurred mainly during the afternoon. Total daily energy intake was higher in snackers than in non-snackers because of greater consumption of food at meals and between meals. A variety of foods were consumed as snacks (mean macronutrient content of snacks: 52% carbohydrate (CHO), 37% lipid and 12% proteins). CHO-rich protein-free snacks were a minority (20%). Only 7% of subjects were CHO-rich protein-free snackers. The eating pattern described by Wurtman in "carbohydrate cravers" was reported by less than 10% of these women. We conclude that, in Paris, snacking plays an important role in increasing energy consumption in obese women but macronutrient-specific snacking is not frequent.
Adolescent↗
Hemostatic and metabolic effects of lowering the ethinyl-estradiol dose from 30 mcg to 20 mcg in oral contraceptives containing desogestrel.
The metabolic and hemostatic effects of two oral contraceptives containing 150 mcg desogestrel and 20 mcg ethinyl-estradiol (EE) (MERCILON) or 30 mcg EE (MARVELON) were compared in order to examine the effect of reducing the EE dose in contraceptive pills. Forty-nine women participated in this randomized study during 6 cycles. In both groups, there was a significant increase in triglycerides, HDL-cholesterol and apoprotein A1; the same increase was observed for SBP and CBG. Slight and transient variations of fasting blood glucose levels were seen in the 30 mcg EE group and in the two groups for fasting insulin levels. The increase in renin substrate was significantly higher with the 30 mcg EE than with the 20 mcg EE pill. In both groups, plasminogen increased significantly, but antithrombin III, total and free protein S and fibrinogen decreased significantly only in women taking the 30 mcg EE pill, whereas there was no significant change in the 20 mcg EE group. Reducing the dose of EE in oral contraceptives from 30 mcg to 20 mcg minimizes their impact on renin substrate and hemostatic parameters.
Apolipoprotein A-I↗
[Arterial hypertension and obesity].
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Diabetes Mellitus↗
Missense mutations in exon 5 of the human lipoprotein lipase gene. Inactivation correlates with loss of dimerization.
Most missense mutations of the lipoprotein lipase (LPL) gene identified among LPL-deficient subjects cluster in a segment of the sequence that encodes the catalytic triad as well as functional elements involved in the activation of the lipase at lipid-water interfaces. Consequently, loss of activity may result either from direct alterations of such functional elements or from less specific effects on protein folding and stability. This issue was addressed by examining biochemical properties of four such variants (A176T, G188E, G195E, and S244T) in a heterologous expression system (COS-1 cells). Variant G195E (GGA----GAA) was previously unreported. In all instances, inactive enzyme was recovered in medium, albeit at reduced levels. Cellular synthesis and extracellular degradation were similar to those for wild type, suggesting that reduced secretion resulted from increased intracellular degradation. When cell extracts were subjected to heparin-Superose affinity chromatography followed by elution on a linear salt gradient, all variants exhibited a single, inactive, low affinity immunoreactive peak. By contrast, wild-type enzyme presented an additional, high affinity, active species, which we interpret as homodimeric enzyme. Substitution of the active-site serine (S132A) led to loss of activity but maintenance of the high affinity species. When large amounts of the G188E variant were applied to the column, small but significant amounts of high affinity, active enzyme were recovered. Systematic substitutions at residue 188 showed that only glycine could accommodate structural constraints at this position. We conclude that the mutations examined did not impart lipase deficiency by affecting specific functional elements of the enzyme. Rather, they appear to affect protein folding and stability, and thereby formation and maintenance of subunit assembly.
Adult↗
Effects of bombesin, of a new bombesin agonist (BIM187) and a new antagonist (BIM189) on food intake in rats, in relation to cholecystokinin.
To study the mechanism by which bombesin induces satiety, we studied the effect of two new peptides, BIM187, a bombesin agonist, and BIM189, a bombesin antagonist, on food intake in rats fed 6 h a day. BIM187 at 4 micrograms/kg, significantly reduced food intake at 30 min, but did not change the total 6-h food intake. BIM189 (10 mg/kg), had no effect on food intake when administered alone, even at high doses (20 mg/kg). BIM189 selectively reduced bombesin-induced satiety but had no effect on satiety induced by BIM187. To examine the extent to which the satiety effect of bombesin or related peptides depends on the release of cholecystokinin (CCK), we studied the ability of CCK antagonists, BIM18216 and L364718, to reduce satiety induced by bombesin and BIM187. Neither BIM18216 nor L364718 alone had an effect on the 30-min food intake. They were not able to reverse the effect of bombesin on food intake. In our model, bombesin seems to act on satiety by a mechanism independent of CCK.
Animals↗
Microalbuminuria in obese subjects.
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Adult↗
Steroids and lipid metabolism: mechanism of action.
The effects of steroids on hepatic metabolism depend on the preexisting metabolic status of the individual and the structure, dosage, and, to a certain extent, the route of administration of the steroid compound. Oral administration of synthetic estrogen causes an increase in hepatic production of very-low-density lipoprotein (causing in turn an increase in triglyceride levels), an increase in coagulation factors, and an increase in high-density-lipoprotein cholesterol, which is related to a decrease in hepatic lipase activity. Parenteral administration of estrogen does not appear to cause any such modification. The effects of progestogen on hepatic metabolism are dependent on the androgenic activity of the specific progestogen administered. A progestogen with greater androgenic activity causes a decrease in high-density-lipoprotein cholesterol, which is related to an increase in hepatic lipase activity. This article reviews the effects of steroids (both estrogens and progestogens) on the mechanisms of action in lipid metabolism.
Estrogens↗
[Clinical analysis of eating disorders: therapeutic implications].
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Clinical Protocols↗
Effects of nomegestrol acetate (5 mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women.
The effects of nomegestrol acetate on circulating hormone levels, metabolic and hemostatic parameters and blood pressure were studied in 36 premenopausal women. The progestogen was administered from day 7 to 25 of the cycle during six cycles at a dosage (5 mg/d) known to inhibit ovulation. Analysis were performed before and in the third and sixth cycles. Estradiol and progesterone levels decreased significantly (p less than 0.001) during treatment. Body weight, fasting blood glucose and insulin, total HDL and LDL cholesterol, apolipoprotein B, fibrinogen and plasminogen did not change significantly. Triglycerides in the third cycle (p less than 0.05) and apolipoprotein A1 levels (p less than 0.01) in both periods of sampling decreased significantly. There was a significant increase in antithrombin III (p less than 0.01). These results indicate that nomegestrol acetate has no deleterious effect on blood glucose and lipids. The decrease in apolipoprotein A1 and increase in antithrombin III may be related either to the decrease in estradiol levels induced by the treatment or to the effect of the progestogen itself.
Adolescent↗
Hepatic lipase activity during oral and parenteral 17 beta-estradiol replacement therapy: high-density lipoprotein increase may not be antiatherogenic.
OBJECTIVE: Hepatic lipase activity is involved in the removal of cholesterol and phospholipid from plasma high-density lipoprotein (HDL) to the liver. Changes in hepatic lipase are responsible for some lipoprotein modifications observed during estrogen administration (i.e., increased HDL levels). The aim of this study was to compare the effects of alternative routes of administration of estrogen on hepatic lipase activity and lipoprotein metabolism. DESIGN, PATIENTS: The effects of oral and parenteral estradiol (E2) replacement therapy on post-heparin hepatic lipase were studied in the short-term (6 weeks) in postmenopausal women. INTERVENTIONS: Ten patients received 2 mg/d or oral micronized E2 and 10 patients 3 mg/d of percutaneous E2. RESULTS: Both treatments significantly increased plasma E2 levels. Hepatic lipase decreased (-33%) significantly (P less than 0.05), and the phospholipids and free cholesterol content of HDL and HDL3 increased significantly (P less than 0.05) during oral but not during parenteral treatment. CONCLUSIONS: The short-term pharmacological effect of E2 on hepatic lipase depends on the route of administration. The inhibition of this enzyme may reduce the removal of HDL-cholesterol by the liver. The expected vascular benefits of such a pharmacological increase in HDL are questionable.
Administration, Cutaneous↗
Effect of BIM-18216, a novel cholecystokinin receptor antagonist, on food intake reduction induced by cholecystokinin.
The role of cholecystokinin (CCK) in food intake was investigated in rats by using BIM-18216, a novel CCK receptor antagonist. In rats fed 6 hr/day, BIM-18216 antagonized the reduction of food intake induced by exogenous CCK octapeptide (CCK-8; 4 micrograms/kg) in a dose-dependent manner and had a maximum effect at 1 mg/kg. BIM-18216 did not antagonize the effect of bombesin on food intake and showed some degree of specificity. BIM-18216 was not able to prevent the effect of endogenous CCK at the beginning of the feeding period. These data demonstrate that BIM-18216 is a potent CCK-specific antagonist. These results also suggest that endogenous and exogenous CCK could act by different regulating pathways.
Animals↗
Compound heterozygote for lipoprotein lipase deficiency: Ser----Thr244 and transition in 3' splice site of intron 2 (AG----AA) in the lipoprotein lipase gene.
Cloning and sequencing of translated exons and intron-exon boundaries of the lipoprotein lipase gene in a patient of French descent who has the chylomicronemia syndrome revealed that he was a compound heterozygote for two nucleotide substitutions. One (TCC----ACC) leads to an amino acid substitution (Ser----Thr244), while the other alters the 3' splice site of intron 2 (AG----AA). The functional significance of the Thr244 amino acid substitution was established by in vitro expression in cultured mammalian cells.
Amino Acid Sequence↗
[Contraception in the diabetic woman].
The metabolic and vascular effect of oestroprogestative treatments make the choice of a contraception difficult for the diabetic women. More than the action on blood glucose it is the effect of Ethynyl-oestradiol on blood pressure, blood lipids and hemostasis which makes problem in case of diabetes. Local contraceptive methods are generally preferred owing to the absence of systemic effect and their good tolerance in a diabetic women. The choice of a method must take into consideration not only the type of diabetes but also the existence or absence of micro and macro-angiopathy.
Blood Glucose↗
[Drugs acting on feeding behavior].
The pharmacology of food intake has made considerable progress due to recent developments in neurobiology and to advances in the final analysis of eating behaviour. In this way, the pharmacology of food intake has risen to the rank of a more global pharmacology of eating behaviour. It is now possible to evaluate the points of impact of catecholaminergic, serotoninergic and opioid agents in terms of central or peripheral mode of action and also in terms of behavioral sequence. Some serotoninergic and opioid agents currently under development are opening new therapeutic vistas.
Amphetamines↗