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Biomedical subjects

R Rabasa-Lhoret

Publications and source records attributed to R Rabasa-Lhoret.

At least 19 recordsLinked to original sources
PubMed2006

Apolipoprotein B: a predictor of inflammatory status in postmenopausal overweight and obese women.

AIMS/HYPOTHESIS: Inflammation is implicated in the development of type 2 diabetes and CHD, but the trigger of inflammation is unclear. Although in vitro and animal studies support a role of elevated levels of atherosclerotic lipoproteins in the activation of inflammation, plasma cholesterol cannot predict inflammatory markers in humans. Moreover, the association between inflammatory markers and other traditional risk factors of diabetes and CHD is unclear. To increase our knowledge of in vivo regulation of inflammation, we examined the association between several traditional risk factors and inflammatory markers. We hypothesised that because apolipoprotein B (ApoB) reflects atherogenic particle number, it is the primary predictor of inflammatory status. SUBJECTS, MATERIALS AND METHODS: We examined the association between several traditional risk factors and plasma high-sensitivity (hs) C-reactive protein (CRP), hsTNF-alpha, soluble TNF receptor 1, IL-6, orosomucoid, haptoglobin and alpha(1)-antitrypsin in 77 non-diabetic overweight and obese postmenopausal women. RESULTS: The inflammatory markers correlated positively with total and abdominal adiposity, blood pressure, 2-h OGTT glucose, insulin resistance, triglyceride, total/HDL cholesterol, ApoB, ApoB:apolipoprotein A1 (ApoA1) ratio and Framingham CHD risk points. They correlated negatively with ApoA1, and total, LDL and HDL cholesterol. ApoB was an independent predictor of the interindividual variation in IL-6, hsCRP, orosomucoid, haptoglobin and alpha(1)-antitrypsin (R (2) range 8-40%); other risk factors were less predictive. Compared with BMI-matched control subjects, women with hyperapobetalipoproteinaemia (hyperapoB) had higher hsTNF-alpha, IL-6, hsCRP and orosomucoid (increase 17-104%). CONCLUSIONS/INTERPRETATION: ApoB is the primary predictor of inflammatory markers in postmenopausal overweight and obese women. Given elevated levels of inflammatory markers in hyperapoB women, we hypothesise that hyperapoB women may have an increased risk of developing both CHD and diabetes.

Aged↗
PubMed2006

Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of liver X receptor (LXR) activation on lipid metabolism and insulin action in human skeletal muscle cells prepared from control subjects and from patients with type 2 diabetes. SUBJECTS AND METHODS: Cultured myotubes were obtained from muscle biopsies of 11 lean, healthy control subjects and ten patients with type 2 diabetes. The mRNA levels of LXR isoforms and lipogenic genes were estimated by RT-quantitative PCR, and the effects of LXR agonists on insulin action were evaluated by assays of protein kinase B serine 473 phosphorylation and glycogen synthesis. RESULTS: Both LXRalpha and LXRbeta were expressed in human skeletal muscle and adipose tissue and there was no difference in their mRNA abundance in tissues from patients with type 2 diabetes compared with control subjects. In cultured muscle cells, LXR activation by T0901317 strongly increased expression of the genes encoding lipogenic enzymes, including sterol regulatory element binding protein 1c, fatty acid synthase and stearoyl-CoA desaturase 1, and also promoted triglyceride accumulation in the presence of a high glucose concentration. Importantly, these effects on lipid metabolism did not affect protein kinase B activation by insulin. Furthermore, LXR agonists did not modify insulin action in muscle cells from patients with type 2 diabetes. CONCLUSIONS/INTERPRETATION: These data suggest that LXR agonists may lead to increased utilisation of lipids and glucose in muscle cells without affecting the mechanism of action of insulin. However, the long-term consequences of triglyceride accumulation in muscle should be evaluated before the development of effective LXR-based therapeutic agents.

Adult↗
PubMed2006

Postprandial hyperglycaemia: to treat or not to treat?

Accumulating evidence suggests that the postprandial or the post-75 g glucose load rise in plasma glucose are a contributing factor to the development of atherosclerosis. Many epidemiological studies have shown that post-load hyperglycaemia is a strong and independent risk factor for cardiovascular disease. The few interventional studies available also support a role for postprandial or post-load hyperglycaemia on cardiovascular disease or mortality or on validated surrogates of atherosclerosis. The mechanism through which acute hyperglycaemia could exert its deleterious effects on the vessel wall is very likely multifactorial, but the overproduction of free radicals is probably involved. There is growing evidence that treating postprandial hyperglycaemia should probably be part of the strategies for the prevention and management of cardiovascular diseases in pre-diabetes as well as in diabetes.

Blood Glucose↗
PubMed2006

Lifestyle behaviours and components of energy balance as independent predictors of ghrelin and adiponectin in young non-obese women.

AIM: Dysregulation of the normal levels of ghrelin, leptin and adiponectin in young non-obese subjects could promote food intake, diabetes and cardiovascular disease in later stages of life. Little information is available on how plasmatic concentrations of these hormones may be influenced by eating habits and/or components of energy balance in a young population, which if known, could facilitate their voluntary regulation. METHODS: In this cross-sectional study we examined the predictors of fasting plasma ghrelin, adiponectin and leptin in a population of well-characterized young non-obese women (N = 63). Energy intake was assessed by 24-hour dietary recall, resting metabolic rate (RMR) by indirect calorimetry, physical activity energy expenditure (PAEE) by tri-axial accelerometer, physical fitness by VO(2 peak), and eating behaviors by self administrated questionnaire. RESULTS: Lower RMR and higher HDL-cholesterol were independent predictors of higher plasma ghrelin explaining 17.6% of its variation even after correcting for BMI. Higher total or central fat mass was the only predictor of higher plasma leptin, and no other variable added any power to the prediction equation. Finally, higher energy intake and waist circumference and lower PAEE predicted lower plasma adiponectin in young non-obese women, explaining 43% of the variation in its concentrations even after correcting for total or central fat mass. CONCLUSION: Components of the energy balance (ie: energy intake and/or expenditure) influence adiponectin and ghrelin circulating levels. That is, higher energy intake and lower physical activity independently predict lower adiponectin concentrations, whereas lower resting metabolic rate independently predicts higher ghrelin levels in young non-obese women. Prospective studies are needed to examine whether circulating concentrations of ghrelin and adiponectin can be voluntarily regulated by lifestyle interventions.

Adiponectin↗
PubMed2006

Surrogate indexes vs. euglycaemic-hyperinsulinemic clamp as an indicator of insulin resistance and cardiovascular risk factors in overweight and obese postmenopausal women.

BACKGROUND: There is considerable interest in validating the most convenient method to estimate insulin sensitivity in clinical research protocols that could best indicate cardiovascular risk factors. To address this issue we examined the interrelationships of several cardiovascular risk factors with surrogate indexes such as fasting insulin, the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI) and the revised QUICKI vs the euglycaemic-hyperinsulinemic (EH) clamp in a non-diabetic overweight or obese postmenopausal female population. DESIGN: Cross-sectional study involving 88 obese postmenopausal women (age: 57.5+/-5.0 yrs; body mass index: 32.52+/-4.4 kg/m2; percent body fat: 46.35+/-4.9%). METHODS: Insulin sensitivity was determined by the EH clamp technique as well as by surrogate indexes such as fasting insulin, HOMA, log HOMA, QUICKI and revised QUICKI. Body composition and body fat distribution were measured using dual energy x-ray absorptiometry and computed tomography, respectively. RESULTS: Correlations between insulin resistance indexes (fasting insulin, revised QUICKI, QUICKI, log HOMA, HOMA) vs glucose disposal were similar (range of r's=0.40 to 0.49), suggesting that no index was superior to another with respect to its relationship with the EH clamp. Correlations between the insulin resistance indexes with plasma lipids were comparable among all indexes, however, systolic blood pressure, visceral fat and C-reactive protein were moderately superior with index vs the EH clamp. CONCLUSION: Surrogate measures of insulin resistance, in particular fasting insulin, are simple tools appropriate for epidemiological studies that can be used as substitutes for the EH clamp to estimate glucose disposal and cardiovascular risk factors in overweight and obese postmenopausal women.

Adipose Tissue↗
PubMed2006

Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal women.

AIM: We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross-sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes. METHODS: Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3 +/- 5.3 years; BMI: 32.8 +/- 4.5 kg/m2) by using both the hyperinsulinaemic-euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the metabolic syndrome included visceral fat (>130 cm2), HDL-cholesterol (<1.29 mmol/l), fasting triglycerides (> or =1.7 mmol/l), blood pressure (> or =130/> or =85 mmHg) and fasting glucose (> or =6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0-1 vs. 2 vs. > or =3 features of the metabolic syndrome. RESULTS: We found that insulin sensitivity decreased in a graded fashion (12.19 +/- 3.2 vs. 11.80 +/- 2.3 vs. 9.29 +/- 2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95 +/- 1.1 vs. 3.28 +/- 1.3 vs. 4.65 +/- 2.2), as the number of features of the metabolic syndrome increased from 0-1 to > or =3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished. CONCLUSIONS: These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship.

Adipose Tissue↗
PubMed2005

Diabetes: a major co-morbidity of cystic fibrosis.

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis, its prevalence increases with age of patient and is close to 30% at the age of 30 years. As life expectancy greatly increases, the number of cystic fibrosis patients developing diabetes will increase too. CFRD shares some features with type 1 and type 2 diabetes, initial phase is characterised by postprandial hyperglycaemia followed by a progression toward insulin deficiency. Insulin deficiency is an essential factor in the development of diabetes with an additional contribution of insulin resistance. Systematic screening with an oral glucose tolerance test is recommended from the age of 14 years because clinical signs of CFRD are often confused with signs of pulmonary infection and CFRD occurrence is associated with weight and pulmonary function deterioration. In observational studies CFRD diagnosis is associated with a significant increase in mortality, while treatment allow correction of weight and lung deterioration suggesting that CFRD has a significant impact on CF evolution. Microvascular complications are recognised, although paucity of data does not permit a clear description of their natural history. Annual screening for microvascular complication is recommended. There is no evidence by now that CF patients develop macrovascular complications. The only recommended pharmacological treatment is insulin therapy.

Comorbidity↗
PubMed2005

The prevention of type 2 diabetes: what is the evidence?

The prevalence of diabetes is increasing in epidemic proportion worldwide. Because of the morbidity and mortality associated with the disease, it is becoming a major burden for the health care system. With a better understanding of the pathogenesis of type 2 diabetes, the concept of primary prevention has emerged. A number of studies demonstrated that both lifestyle modification program and pharmacological interventions in subjects with impaired glucose tolerance (IGT) can prevent or delay the progression to diabetes. The Diabetes Prevention Study (DPS) and the Diabetes Prevention Program (DPP) convincingly showed that an intensive lifestyle modification program is highly effective in decreasing the risk of diabetes in a high risk population (risk reduction of 58%). Four other smaller studies have made similar observations. The DPP study showed that metformin can reduced the risk of diabetes by 31% in subjects with IGT. The STOP-NIDDM trial confirmed the efficacy of acarbose in decreasing the risk of diabetes by 36% in similar high risk population. The TRIPOD study showed that troglitazone can reduce the incidence of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that in very obese population on intensive lifestyle modification program, xenical treatment was associated with a 37% reduced incidence of diabetes compared to placebo. Three studies suggested that bariatric surgery in morbidly obese subjects with or without IGT can reduce the incidence of diabetes to near zero. Eight of 10 studies showed that treatment with inhibitors of the renin-angiotensin aldosterone system in high risk population for cardiovascular disease (CVD) were associated with a significant reduction in the subsequent development of diabetes as a secondary outcome. The WOSCOPS study and the HERS study examined the effect of pravastatin and estrogen/progestin respectively on cardiovascular events and observed that these pharmacological interventions were associated with a 30% and 35% reduction in the incidence of diabetes as secondary outcome. There are 3 major trials currently in progress examining the effect of rosiglitazone/ramipril (the DREAM study), nateglinide/valsartan (the NAVIGATOR study) and pioglitazone (the ACT NOW study) on the development of diabetes in IGT subjects as a primary outcome. We also have 3 studies studying the prevention of diabetes as secondary outcomes: the ONTARGET-TRANSCEND study examining telmisartan with or without ramipril, and the ORIGIN study testing glargine insulin/omega 3. The evidence is overwelming-diabetes can be prevented or delayed in high risk population through lifestyle modification or pharmacological interventions. This new information now has to be translated in the real world into well defined strategies for screening and treating high risk population. Prevention of the disease is our only chance to alleviate the ever growing burden of diabetes mellitus in the world.

Diabetes Mellitus, Type 2↗
PubMed2004

Can we identify metabolically healthy but obese individuals (MHO)?

OBJECTIVES: A unique subset of obese individuals termed, Metabolically Healthy but Obese (MHO), has been described in the literature. However, there is no agreed upon method to identify MHO individuals for research protocols or in clinical practice. Therefore, we examined a large cohort of obese older women to attempt to develop a first set of clinical markers that may identify MHO individuals. METHODS: We studied 154 obese postmenopausal women (age: 57.0 +/- 5.3 years and BMI: 34.3 +/- 5.5 kg/m2). Selection criteria for MHO individuals were partially based on the National Cholesterol Education Program's Adult Treatment Panel III report (ATP III) for lipid profiles (triglycerides: < or =1.7 mmol/l, total cholesterol: < or =5.2 mmol/l, HDL-cholesterol: > or =1.3 mmol/l and LDL-cholesterol: < or =2.6 mmol/l) and from the study of Brochu et al. (2001) for insulin sensitivity (HOMA<=1.95). When 4 out of 5 criteria are met, we suggest that a diagnosis of the MHO individual could be made. RESULTS: Based on the proposed criteria, 19 out of 154 (12.3%) postmenopausal women subjects were identified as MHO. By design, MHO individuals showed a favourable lipid profile and higher insulin sensitivity values. CONCLUSION: We suggest a potential new set of clinical markers to identify MHO individuals. Identifying MHO individuals could have important implications for therapeutic medical decision making, subject characterization in research protocols and in medical education.

Blood Pressure↗
PubMed2003

Acarbose in the treatment of elderly patients with type 2 diabetes.

AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.

Acarbose↗
PubMed2003

What kind of simple fasting index should be used to estimate insulin sensitivity in humans?

The hyperinsulinemic euglycemic glucose clamp method is the gold standard for measuring insulin resistance. However it is complex, and simple indexes have been developed. Some of them are based on formulae that calculate the product or the addition of fasting plasma insulin and glucose values whereas others are based on their ratios. We calculated several simple indexes of insulin resistance and compared them to hyperinsulinemic euglycemic clamp data in 111 subjects with a wide range of insulin resistance. We showed that indexes using insulin and glucose ratios in their formulae are poorly correlated with clamp measurements and give false evaluations, particularly in glucose-intolerant and type 2 diabetic subjects. Thus, whatever the glucose profile of study subjects, we suggest the use of a simple index based on the product or the addition of fasting plasma insulin and glucose values instead of their ratios to obtain insulin resistance evaluations close to the hyperinsulinemic euglycemic clamp technique.

Blood Glucose↗
PubMed2003

The use of information technology for the management of intensive insulin therapy in type 1 diabetes mellitus.

OBJECTIVE: The purpose of the study was to evaluate the safety of a computer program used by the patient for the adjustment of insulin doses to achieve tight glycemic control in type 1 diabetic subjects on intensive insulin therapy. METHODS: Ten type 1 diabetic patients participated in the study. Using the basal-bolus (UL-Humalog) insulin regimen, they were randomized in a crossover design to 2 intensive treatment periods of 8 weeks each, one with and the other without the assistance of a computer program via the Internet. They measured their capillary blood glucose regularly, and the results were entered on a daily basis into their log-book or in the computer. During intensive treatment with the computer, the software would provide recommendation for insulin dose adjustment according to specific algorithms. When on intensive treatment without computer assistance, they would adjust their own insulin dose according to the same algorithms. RESULTS: The study subjects followed 89% of the recommendations made by the computer. With the computer, subjects made more insulin dose adjustments (98 versus 50) than without. Intensive treatments with and without computer assistance resulted in a similar improvement of pre-meal/post-prandial capillary blood glucose from 7.6 +/- 2.7/9.5 +/- 2.5 to 6.7 +/- 2.3/8.8 +/- 2.5 and 6.7 +/- 2.6/9.0 +/- 2.6 mmol/L, respectively. Glygated hemoglobin also improved from 7.7 +/- 0.9% to 7.2 +/- 0.7 and 7.3 +/- 0.8%, respectively. The incidence of minor hypoglycemia was similar under both intensive treatments (7.9 +/- 4.0 and 7.1 +/- 5.0/patient/28 days, respectively). Both treatments increased patient behavior while patient knowledge of their disease was improved only during computer assistance. There was no effect on quality of life. The study subjects greatly appreciated the software and wanted to continue using it. CONCLUSIONS: The study demonstrated that the use of computer software by the patient to adjust insulin doses for intensive insulin therapy is feasible and is not associated with increased adverse events.

Algorithms↗
PubMed2001

Use of an alpha-glucosidase inhibitor to maintain glucose homoeostasis during postprandial exercise in intensively treated Type 1 diabetic subjects.

AIM: We evaluated the effects of an alpha-glucosidase inhibitor, acarbose, on glucose homoeostasis during postprandial exercise in Type 1 diabetic subjects. METHODS: Seven Type 1 diabetic subjects with good glycaemic control on ultralente-regular insulin were randomized in a single blind cross-over study to acarbose 100 mg or placebo taken with a mixed meal (600 kcal, 75 g carbohydrates), followed 90 min later by 30 min of exercise at 50% maximum aerobic capacity. Glucose turnover was measured by tracer (d-[6,6,2H2]glucose) methodology, and intestinal glucose absorption was quantified using carbohydrate polymers labelled with [13C]glucose. RESULTS: Acarbose resulted in a significant decrease in the postprandial glycaemic rise (mean +/- SEM 2.9 +/- 0.6 vs. 5.0 +/- 0.7 mmol/l; P < 0.005) and in the glycaemic nadir during exercise (- 0.8 +/- 0.6 vs. 0.9 +/- 1.3 mmol/l below baseline; P < 0.05). Total glucose appearance increased similarly under the two treatments during the postprandial (27.0 vs. 27.9 micromol per kg per min) and exercise (33.9 vs. 33.5 micromol per kg per min) periods. Mean glucose absorption was significantly delayed by acarbose (7.8 vs. 10.2 micromol per kg per min; P < 0.02), but was compensated by the lack of postprandial suppression of hepatic glucose production (106% of basal hepatic glucose production vs. 81%; P < 0.006). Episodes of hypoglycaemia were no different (three vs. six). CONCLUSION: These results indicate that, in Type 1 diabetic subjects, acarbose results in a better glycaemic profile during postprandial exercise and suggest that it could lead to a lower risk of exercise-induced hypoglycaemia due to delayed glucose absorption and less suppression of hepatic glucose production.

Acarbose↗