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Biomedical subjects

J Ybarra

Publications and source records attributed to J Ybarra.

At least 19 recordsLinked to original sources

Link between obesity and type 2 diabetes.

The relationship between obesity and diabetes is of such interdependence that the term 'diabesity' has been coined. The passage from obesity to diabetes is made by a progressive defect in insulin secretion coupled with a progressive rise in insulin resistance. Both insulin resistance and defective insulin secretion appear very prematurely in obese patients, and both worsen similarly towards diabetes. Thus, the classic 'hyperbolic relationship' between insulin resistance and insulin secretion and the 'glucose allostasis concept' remain prevailing concepts in this particular field of knowledge. An increase in overall fatness, preferentially of visceral as well as ectopic fat depots, is specifically associated with insulin resistance. The accumulation of intramyocellular lipids may be due to reduced lipid oxidation capacity. The ability to lose weight is related to the capacity to oxidize fat. Thus, a relative defect in fat oxidation capacity is responsible for energy economy and hampered weight loss.

Diabetes Mellitus, Type 2↗

New interdisciplinary cognitive-behavioural-nutritional approach to obesity treatment: a 5-year follow-up study.

OBJECTIVE: The aim of this prospective case-control study was to assess the long-term effectiveness of interdisciplinary cognitive-behavioural-nutritional therapy, combined with daily physical exercise and relaxation sessions, on weight and psychosocial issues during a 6-week in-hospital stay. SETTING: Five years (60 +/- 1 months) later, the patients were readmitted for a one-day medical evaluation including a physical examination and laboratory work-up, and the completion of a detailed questionnaire focusing on dietary and psychosocial factors that may affect weight loss/regain. SUBJECTS: The follow-up population consisted of 55 morbidly obese subjects aged 49.5 +/- 2 years (45 females and 10 males; BMI: 40 +/- 0.7 kg/m2). During their initial 6-week in-hospital stay, they lost an average of 7.6 +/- 0.4 kg. RESULTS: Five years later, 25.5% of the patients had lost a further 11.9 +/- 1.8 kg, 20% maintained their initial weight loss (0.6 +/- 0.4 kg), and 54.5% regained weight (10.4 +/- 1 kg). The weight changes significant correlated with the degree of psychosocial difficulties (p < 0.001), eating behaviour problems (p < 0.001), dietary fat intake (p < 0.005) and total energy intake (p < 0.05). Fasting plasma insulin and blood glucose concentrations were significantly higher in the patients who regained weight after five years, and significantly lower in those who had lost more weight. CONCLUSION: As a whole, these results show the efficacy of an interdisciplinary approach to the long-term treatment of morbidly obese patients. It is likely that an outpatient psychological follow-up would have improved this therapeutic success.

Body Mass Index↗

A new table for prevention of hypoglycaemia during physical activity in type 1 diabetic patients.

OBJECTIVE: The ability to adjust both insulin and nutrition to allow safe participation in physical activity and high performance has recently been recognized as an important management strategy in these patients. In particular, the important role played by the patient in self-monitoring blood glucose during physical activity and then using these data to improve performance and decrease hypoglycaemias is now fully accepted. The primary objective of this study is to compare different therapeutic options in exercising Type 1 diabetic patients (n=67) with or without CHO compensation and/or with or without insulin dosage reduction in order to prevent hypoglycaemias during and after exercise. METHODS: Sixty-seven type 1 diabetic patients were aggregated into four treatment categories according to four strategies to prevent hypoglycaemia episodes, with or without carbohydrate compensation and/or with or without insulin dosage reduction. The protocol included 7 different disciplines and 9 subgroups according to 3 different durations (<20 min., 20-60 min., > 60 min.) and 3 intensity degrees (<60% of Maximal Heart Rate, 60-75% and > 75%). RESULTS: Our study shows that by replacing adequately the carbohydrates during the practice of physical exercise it is possible to prevent almost all hypoglycaemia episodes, independently of the insulin dosage adjustments. Furthermore, the amount of extra-carbohydrates correlates well with the number of hypoglycaemia while the decrease in insulin dosage does not. CONCLUSION: Adequate carbohydrate replacement during and after exercise seems to be the most important measure to prevent hypoglycaemia. However, the insulin dosage adjustment does not play such an important role. A decrease from 20 to 30% seems reasonable only for a long duration exercise (> 60 min.). Finally, a new user-friendly table for prevention of hypoglycaemia is proposed for physical activity of different intensity and duration.

Adult↗

Renal transplantation in a C-ANCA(+) patient with Behcet disease and rapidly progressive glomerulonephritis.

Behcet's disease (BD) is a chronic, relapsing, inflammatory disorder, and the underlying histophatological lesion is vasculitis of unknown cause. Some case reports of BD with positive C-ANCA titers have been reported, but only 2 case reports have documented the association of ANCA-associated glomerulonephritis (GN) and BD, and no renal transplantation cases have been described. We report such a case. A 27-year-old male was referred for consultation due to acute renal failure. Seven years before, BD was diagnosed. At the time of consultation he suffered from uveitis and generalized arthralgias. The serum creatinine was 14 mg/dl and urinalysis showed 4+ protein and microscopic hematuria. Results of serological tests were normal. The ANCA PR 3 titer was 1:100 of cytoplasmic pattern. A renal biopsy showed a rapidly progressive type III glomerulonephritis. In spite of immunosuppressive therapy with cyclophosphamide and high steroid doses, renal function did not recover and hemodialysis therapy was initiated. One year later, the patient underwent a renal transplantation. Follow-up was absolutely normal, and 5 years after transplantation, renal function persisted to be normal, without urinary abnormalities and signs of reactivation of original disease, except for occasional arthralgias. C-ANCA titer was decreased and remained stable (<1:30). He is now receiving maintenance immunosupression with cyclosporin and prednisone. This report shows the long-term successful renal transplantation in a patient with ANCA-associated glomerulonephritis and BD. The success of renal transplant in BD with renal involvement is encouraging and should be pursued.

Adult↗

Reflex sympathetic dystrophy syndrome in renal transplanted patients under immunosuppression with tacrolimus.

Reflex sympathetic dystrophy syndrome (RSDS), which probably has a multifactorial etiology, may appear after kidney transplantation. Its clinical manifestations include severe periarticular pain with inflammatory signs, especially in knees and ankles, causing functional disability. Symptoms develop during the first 3 months after transplantation and usually disappear 3 to 6 months later without sequelae. In renal transplant recipients it has previously been related to immunosuppressive treatment with cyclosporine. Therefore we had suggested that introducing tacrolimus could be a therapeutic option. We now present four cases of RSDS in kidney transplant recipients treated with tacrolimus. All but one patient were receiving tacrolimus monotherapy, excluding other drugs that might have been involved to cause the syndrome. It is also interesting that one of our cases develop RSDS long after transplantation when immunosuppressive treatment was changed. Symptoms correlated with an increase in alkaline phosphatase and with bone scintigraphy findings. All patients recovered without sequels 3 to 6 months afterward. In conclusion, RSDS is a relevant osteoarticular complication in patients receiving either anticalcineurinic drug (CyA or tacrolimus), even under monotherapy or with a low steroid dose.

Adult↗

Interest of pronostic score for optimal clinical management of obese patients.

OBJECTIVE: The aim of this retrospective study was to identify key factors favoring weight regain. METHODS: Therefore, prognostic factors for weight loss and regain have been retrieved and identified among 186 obese patients (40 +/- 2 y and 34 +/- 0.3 kg/m(2)) through the use of a simple questionnaire which considered psychological issues such as depression, anxiety and the patient's individual capacity to follow a diet. All patients have been prescribed a low-calorie diet (1200 kcal/day) being either balanced, food-combining or low-CHO. Follow-up averaged 6.4 +/- 0.3 months of which weight loss accounted for 4.4 +/- 0.1 months. RESULTS: Weight loss was similar in all 3 groups and averaged 6.0 +/- 0.2 kg. The final weight loss and weight regain results have been identical for the 3 groups. A high/bad prognostic score rating is associated with weight regain (P<0.02). Weight regain is significantly influenced by the initial weight loss speed (P<0.0001). CONCLUSIONS: The proposed prognostic score is likely to be helpful for clinicians better to profile the therapeutic approach to individualized obesity management and follow-up. Diet composition does not influence either weight loss or weight regain.

Adaptation, Psychological↗

Double-phase parathyroid 99mTc-Sestamibi scintigraphy in chronic haemodialysis patients: correlation with biochemical markers of parathyroid function.

99mTc-Sestamibi identifies the presence of hyperfunctioning autonomous parathyroid glands in patients with secondary hyperparathyroidism (SHP). The objectives of this study were: (i) to evaluate the interdependence between biochemical markers of SHP and 99mTc-Sestamibi uptake; and (ii) to determine whether 99mTc-Sestamibi uptake could be efficiently predicted by any combination of the former variables. Double-phase parathyroid 99mTc-Sestamibi uptake and total serum calcium, phosphorus, intact parathormone, 25-OH vitamin D and 1,25(OH) vitamin D determinations were performed simultaneously in 74 patients (36 female, 38 male) with SHP. Planar images of the neck and upper thorax were obtained in anterior view, 15 min (early phase) and 120 min (delayed phase) after the injection of 740 MBq of 99mTc-Sestamibi. In each patient, a final parathyroid/thyroid (P/T) activity index was obtained by adding the results of the P/T index of all parathyroid lesions. There was a significant correlation between intact parathormone levels and delayed 99mTc-Sestamibi uptake ( r=0.656; P<0.01). Of all the variables, intact parathormone was the only significant predictor of delayed 99Tc-Sestamibi uptake ( r=0.487; P<0.001). Calcium, phosphorus, vitamin D metabolites, age, gender, time spent on haemodialysis and cause of chronic renal failure displayed no significant correlation with 99mTc-Sestamibi uptake. It can be concluded that 99mTc-Sestamibi uptake is a potential predictor of parathyroid function in SHP patients. Hence, 99mTc-Sestamibi scintigraphy could be useful to assess parathyroid function and in the clinical follow-up of these patients.

Age Factors↗

Acarbose improves indirectly both insulin resistance and secretion in obese type 2 diabetic patients.

BACKGROUND: Acarbose is an oral antidiabetic mainly acting on postprandial blood glucose, inhibiting alphaglucosidase. Through this mechanism, it could improve the peripheral insulin sensitivity and/or increase the insulin secretion. The aim of the present study is to assess the therapeutic efficacy of Acarbose in obese type 2 diabetic patients on both insulin resistance and insulin secretion. METHODS: 17 obese non insulin-dependent diabetic patients, well controlled with diet alone were randomized into 2 groups: acarbose (2 x 50 mg) or placebo during 16 weeks. A glucagon test allowed to evaluate insulin secretion before and after treatment as well as a triple test (glucose-insulin-somatostatin) with indirect calorimetry allowed to evaluate insulin sensitivity. RESULTS: A significant improvement in post-prandial plasma glucose was detected only in the Acarbose group (8.0 +/- 0.5 mmol/l before vs 6.5 0.5 mmol/l after, p<0.05). Basal C-peptide secretion was similar between groups and remained unchanged after treatment. However, stimulated insulin secretion was significantly increased by 30%, p<0.05, in the Acarbose group while no change was detected in the placebo group. Interestingly, the group receiving Acarbose disclosed a 15% reduction in insulin resistance (15.0 +/- 1.8 mmol/l before vs 12.8 +/- 1.4 mmol/l after). CONCLUSIONS: Our results show that a treatment with Acarbose is efficient even in diabetic patients presenting a good glucose control without any other associated treatment. By decreasing post-prandial blood glucose, acarbose improves both insulin sensitivity and secretion.

Acarbose↗

Evaluation of a psycho-educational nutritional program in diabetic patients.

In this study, we have retrospectively (2 years) assessed the efficacy of the nutritional education (NE) program provided to 83 diabetic patients during an in-hospital training week. Two years after NE, type 1 diabetic patients have decreased significantly their total caloric intake, protein (P<0.05) and fat consumption. Type 2a diabetic patients disclosed a significant increase in CHO consumption while type 2b diabetic patients decreased their fat consumption, SFA consumption and total caloric intake. The percentage of patients following the European Association Study for Diabetes (EASD) nutritional recommendations regarding fat intake has increased significantly in all three diabetic groups and in type 2a diabetic patients regarding CHO consumption. In conclusion, a psycho-educational nutritional education program of 1 week allows a significant improvement of the alimentary behavior 2 years thereafter with 45% of the diabetic patients following the current EASD dietary recommendations.

Adult↗

Effects of short-term modest weight loss on fasting and post-prandial lipoprotein sub-fractions in type 2 diabetes mellitus patients.

OBJECTIVE: We assessed the efficacy of a modest weight loss (1.5 +/- 0.3 kg) and simultaneous rapid improvement in glycemic control on fasting an post-prandial lipoprotein sub-fractions in nine overweight (BMI=28 +/- 1.7 kg/m(2)) well controlled Type 2 diabetic patients (HbA(1c)=7.3 +/- 0.1%). MATERIAL AND METHODS: They followed a non-drastical hypocaloric balanced diet (1 561 +/- 39 kcal/day) over ten days in hospital. The fat content of the diet was significantly lowered from 96 +/- 12 g/day to 62 +/- 4 g/day (p<0.03). Plasma lipid and lipoprotein levels were measured in fasting and four hours after standard breakfast and four hours after standard lunch twice before and after ten days of hospitalization. The sub-fractions of very low density and low density lipoprotein were obtained by cumulative flotation ultracentrifugation. RESULTS: This weight loss reduced two well known independent cardiovascular risk factors such as the post-prandial glycemic excursions (p<0.05) and the post-prandial lipemia (p<0.05). Multiple linear regression analyses identified weight loss as an independent variable accounting for the ability to predict post-prandial capillary triglyceride clearance (p<0.05). Improvements in post-prandial glycemic excursions which was also entered as a parameter did not appear as a variable being able to predict these changes (p=0.4). In addition to the 23% improvement in post-prandial capillary triglyceride clearance (p<0.02), a decrement in post-prandial VLDL-2 triglyceride enrichment was found (p<0.05). Finally, fasting and post-prandial LDL-3 cholesterol levels were diminished (p<0.05) and the LDL-2/LDL-3 mass ratio post-prandial kinetics were improved (p<0.05). CONCLUSIONS: Even a modest weight loss in overweight, average controlled type 2 diabetic patients can achieve a significant improvement in two cardiovascular risk factors, namely post-prandial triglyceride excursions and the LDL-2/LDL-3 mass ratio kinetics independently from glycemic control improvements.

Adult↗

High hydrostatic pressure can probe the effects of functionally related ligands on the quaternary structures of the chaperonins GroEL and GroES.

We investigated the effects of high hydrostatic pressure in the range of 1--3 kilobars on tetradecameric GroEL, heptameric GroES, and the GroEL-GroES complex. Unlike GroEL monomers formed by urea dissociation, which can be reassembled back to the tetradecamer, the pressure-dissociated monomers do not reassemble readily. This indicates an alteration of their native structures, an example of conformational drift. Pressure versus time profiles and kinetics of the dissociation of both GroEL and GroES at fixed pressures were monitored by light scattering. Unlike GroEL, GroES monomers do reassociate readily. Reaction conditions were varied by adding ATP, Mg(2+), ADP, AMP-PNP, and KCl. At any individual pressure, the dissociation process is governed by both thermodynamics and kinetics. This leads to the decrease in the yield of monomers at lower pressures. In the presence of Mg(2+) and KCl, GroEL is stable up to 3 kilobars. The presence of either ATP or ADP but not AMP-PNP leads to GroEL dissociation at lower pressures. Interestingly, the GroEL-GroES complex is very stable in the range of 1--2.5 kilobars. However, the addition of ADP destabilizes the complex, which dissociates completely at 1.5 kilobars. The results are rationalized in terms of different degrees of cooperativity between individual monomers and heptameric rings in the GroEL tetradecamer. Such allosteric interactions leading to the alteration of quaternary structure of GroEL in the absence of chemical denaturants are important in understanding the mechanism of chaperonin-assisted protein folding by the GroEL-GroES system.

Adenosine Triphosphate↗

Similar weight loss with low-energy food combining or balanced diets.

OBJECTIVE: The goal of this study was to evaluate the effect of two diets ('food combining' or dissociated vs balanced) on body weight and metabolic parameters during a 6-week period in an in-hospital setting. SUBJECTS AND DESIGN: 54 obese patients were randomly assigned to receive diets containing 4.5 MJ/day (1100 kcal/day) composed of either 25% protein, 47% carbohydrates and 25% lipids (dissociated diet) or 25% protein, 42% carbohydrates and 31% lipids (balanced diet). Consequently, the two diets were equally low in energy and substrate content (protein, fat and carbohydrate) but widely differed in substrate distribution throughout the day. RESULTS: There was no significant difference in the amount of weight loss in response to dissociated (6.2 +/- 0.6 kg) or balanced (7.5 +/- 0.4 kg) diets. Furthermore, significant decreases in total body fat and waist-to-hip circumference ratio were seen in both groups, and the magnitude of the changes did not vary as a function of the diet composition. Fasting plasma glucose, insulin, total cholesterol and triacylglycerol concentrations decreased significantly and similarly in patients receiving both diets. Both systolic and diastolic blood pressure values decreased significantly in patients eating balanced diets. The results of this study show that both diets achieved similar weight loss. Total fat weight loss was higher in balanced diets, although differences did not reach statistical significance. Total lean body mass was identically spared in both groups. CONCLUSION: In summary at identical energy intake and similar substrate composition, the dissociated (or 'food combining') diet did not bring any additional loss in weight and body fat.

Adult↗

The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas.

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. Recent data suggested that the hypopituitarism and mild hyperprolactinemia in this setting are largely due to compression of pituitary stalk and portal vessels. Headaches (HAs) are frequently seen in patients with large adenomas and at times in those with microadenomas. Because the walls of the sella turcica are relatively rigid, we postulate that tumor growth within the sella increases intrasellar pressure (ISP), which in turn impairs portal blood flow, resulting in mild hyperprolactinemia and hypopituitarism. We also postulate that increased mean ISP (MISP) contributes to the development of HAs. Normal MISP is not known but is unlikely to exceed normal intracranial pressure of less than 10-15 mm Hg. We determined MISP in 49 patients who had transsphenoidal surgery for pituitary adenomas. MISP was measured using a commonly available intracranial monitoring kit where a fiberoptic transducer was inserted through a 2-mm dural incision at the time of adenomectomy. Patients with deficient FSH, LH, ACTH, or TSH secretion were considered hypopituitary. Data on serum PRL levels were included for analysis only in patients whose adenomas had negative immunostaining for the hormone. MISP measurements ranged from 7-56 mm Hg, with a mean (+/-SD) of 28.8 +/- 13.5 and a median of 26 mm Hg. The pressure measurements were higher in patients with hypopituitarism than in those with normal pituitary function (P = 4.6013 x 10(-6)). Patients presenting with HAs had higher MISP than those who did not (P = 5.44 x 10(-7)), regardless of their pituitary function or tumor sizes. PRL levels correlated positively with MISP values (r = 0.715, P < 0.0001). Tumor size did not correlate with MISP or PRL levels. The findings of increased MISP in hypopituitary patients and the documented correlation with PRL levels, suggest that ISP is a major mechanism involved in the pathogenesis of hypopituitarism and hyperprolactinemia. Similarly, the increased MISP in patients with HAs, irrespective of tumor size or pituitary function, suggest that increased ISP is a major mechanism involved in the pathogenesis of this symptom. The data support the hypothesis that in patients with pituitary adenomas increased ISP is a major mechanism contributing to the development of hyperprolactinemia, hypopituitarism, and HAs. Increased ISP in these patients leads to compression of the portal vessels and the associated interruption of the delivery of hypothalamic hormones to the anterior pituitary. This would explain the reversibility of pituitary function observed in most patients after adenomectomy. However, increased ISP may also lead to decreased blood supply, resulting in ischemic necrosis in some regions of the pituitary. The latter could limit potential recovery of pituitary function after adenomectomy.

Adenoma↗

GroES in the asymmetric GroEL14-GroES7 complex exchanges via an associative mechanism.

The interaction of the chaperonin GroEL14 with its cochaperonin GroES7 is dynamic, involving stable, asymmetric 1:1 complexes (GroES7.GroEL7-GroEL7) and transient, metastable symmetric 2:1 complexes [GroES7.GroEL7-GroEL7.GroES7]. The transient formation of a 2:1 complex permits exchange of free GroES7 for GroES7 bound in the stable 1:1 complex. Electrophoresis in the presence of ADP was used to resolve free GroEL14 from the GroES7-GroEL14 complex. Titration of GroEL14 with radiolabeled GroES7 to molar ratios of 32:1 demonstrated a 1:1 limiting stoichiometry in a stable complex. No stable 2:1 complex was detected. Preincubation of the asymmetric GroES7.GroEL7-GroEL7 complex with excess unlabeled GroES7 in the presence of ADP demonstrated GroES7 exchange. The rates of GroES7 exchange were proportional to the concentration of unlabeled free GroES7. This concentration dependence points to an associative mechanism in which exchange of GroES7 occurs by way of a transient 2:1 complex and excludes a dissociative mechanism in which exchange occurs by way of free GroEL14. Exchange of radiolabeled ADP from 1:1 complexes was much slower than the exchange of GroES7. In agreement with recent structural studies, this indicates that conformational changes in GroEL14 following the dissociation of GroES7 must precede ADP release. These results explain how the GroEL14 cavity can become reversibly accessible to proteins under in vivo conditions that favor 2:1 complexes.

Chaperonin 10↗

Divalent cations can induce the exposure of GroEL hydrophobic surfaces and strengthen GroEL hydrophobic binding interactions. Novel effects of Zn2+ GroEL interactions.

Fluorescent and non-fluorescent probes have been used to show that divalent cations (Ca2+, Mg2+, Mn2+, and Zn2+) significantly increase hydrophobic exposure on GroEL, whereas monovalent cations (K+ and Na+) have little effect. Zn2+ always induced the largest amount of hydrophobic exposure on GroEL. By using a new method based on interactions of GroEL with octyl-Sepharose, it was demonstrated that Zn2+ binding strengthens GroEL hydrophobic binding interactions and increases the efficiency of substrate release upon the addition of MgATP and GroES. The binding of 4, 4'-bis(1-anilino-8-naphthalenesulfonic acid) to GroEL in the presence of Zn2+ has a Kd congruent with 1 microM, which is similar to that observed previously for the GroEL 4, 4'-bis(1-anilino-8-naphthalenesulfonic acid) complex. Urea denaturation, sedimentation velocity ultracentrifugation, and electron microscopy revealed that the quaternary structure of GroEL in the presence of Zn2+ had a stability and morphology equivalent to unliganded GroEL. In contrast, circular dichroism suggested some loss in both alpha-helical and beta-sheet secondary structure in the presence of Zn2+. These data suggest that divalent cations can modulate the amount of hydrophobic surface presented by GroEL. Furthermore, the influence of Zn2+ on GroEL hydrophobic surface exposure as well as substrate binding and release appears to be distinct from the stabilizing effects of Mg2+ on GroEL quaternary structure.

Adenosine Triphosphate↗