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Biomedical subjects

B Guerci

Publications and source records attributed to B Guerci.

At least 37 records · Page 2Linked to original sources
PubMed2001

Endothelial dysfunction and type 2 diabetes. Part 1: physiology and methods for exploring the endothelial function.

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.

Diabetes Mellitus↗
PubMed2001

Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus.

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.

Animals↗
PubMed2001

Analysis of the postprandial lipid metabolism: use of a 3-point test.

OBJECTIVES: The oral fat load tests used to study postprandial lipemia are complex and costly and time consuming. A simplified fat load test could be more convenient and more appropriate in routine clinical practice because of the number of lipid determinations required. RESEARCH DESIGN AND METHODS: We evaluated the capacity of a postprandial test model that reduced the number of blood samples taken in thirty three normal weight controls and 17 normotriglyceridemic obese patients (study 1), 10 normolipidemic type 2 diabetic patients and 7 healthy controls (study 2), and 10 hyperlipidemic type 2 diabetic patients studied before and after hypolipidemic therapy (study 3). Blood samples were taken before and up to 8 hours after giving the oral fat load containing retinol. Triglyceride (TG) and retinyl palmitate (RP) concentrations in the plasma, chylomicrons (CM) and non-chylomicron (nCM) fractions were measured. Postprandial lipid responses using conventional area under the curves (AUCc using 5 to 7 lipid determinations) were compared to a 3-point test that uses only three sample points to predict the area under the curve (AUCp: triglycerides at T0, triglycerides at average peak-time (T4), and triglycerides at T8). RESULTS: The AUCc and AUCp for triglycerides and retinyl palmitate were highly correlated in each of the groups and whatever the lipid subfraction (r=0.664 - 0.995, p<0.0001). When incremental AUC (iAUC) were used, the coefficients of correlation for triglycerides remained highly significant between iAUCc and iAUCp (r=0.718 - 0.979, p<0.01 - 0.0001). The same trend of differences was found between cases and controls when AUCp was used instead of AUCc. The means of differences between AUCc and AUCp for triglyceride values were small (0.34 - 0.74 mmol/L.h), and the confidence intervals were acceptable considering the range of the AUCs values (5.60 to 79.8 mmol/L.h for plasma triglycerides). CONCLUSIONS: We found that data obtained with a simplified model of AUC using only 3 points to analyse postprandial lipemia are well correlated with those obtained by conventional AUC, and that the AUCp allows to the same conclusions as AUCc when healthy subjects were compared to patients with altered postprandial metabolism. Thus AUCp may be a good evaluation of the AUCc, and the simplified 3-point protocol may well be used and suitable for studies on large groups of subjects who are eligible for an oral fat load test.

Area Under Curve↗
PubMed2001

Increased plasma apoA-IV level is a marker of abnormal postprandial lipemia: a study in normoponderal and obese subjects.

Plasma apolipoprotein A-IV (apoA-IV) levels are found elevated in hypertriglyceridemic patients. However, the relationship between plasma apoA-IV level and postprandial lipemia is not well known and remains to be elucidated. Thus, our objective was to study the relationship between plasma apoA-IV and postprandial TG after an oral fat load test (OFLT). Plasma apoA-IV was measured at fast and during an OFLT in 16 normotriglyceridemic, normoglucose-tolerant android obese subjects (BMI = 34.6 +/- 2.9 kg/m(2)) and 30 normal weight controls (BMI = 22.2 +/- 2.3 kg/m(2)). In spite of not statistically different fasting plasma TG levels in controls and obese patients, the former group showed an altered TG response after OFLT, featuring increased nonchylomicron TG area under the curve (AUC) compared with controls (516 +/- 138 vs. 426 +/- 119 mmol/l x min, P < 0.05). As compared to controls, obese patients showed increased apoA-IV levels both at fast (138.5 +/- 22.4 vs. 124.0 +/- 22.8 mg/l, P < 0.05) and during the OFLT (apoA-IV AUC: 79,833 +/- 14,281 vs. 68,176 +/- 17,463 mg/l x min, P < 0.05). Among the whole population studied, as among the control and obese subgroups, fasting plasma apoA-IV correlated significantly with AUC of plasma TG (r = 0.60, P < 0.001), AUC of chymomicron TG (r = 0.45, P < 0.01), and AUC of nonchylomicron TG (r = 0.62, P < 0.001). In the multivariate analysis, fasting apoA-IV level constituted an independent and highly significant determinant of AUC of plasma TG, AUC of chymomicron TG, AUC of nonchylomicron TG, and incremental AUC of plasma TG. In conclusion, we show a strong link between fasting apoA-IV and postprandial TG metabolism. Plasma fasting apoA-IV is shown to be a good marker of TG response after an OFLT, providing additional information on post-load TG response in conjunction with other known factors such as fasting TGs.

Adult↗
PubMed2000

Relationship between altered postprandial lipemia and insulin resistance in normolipidemic and normoglucose tolerant obese patients.

OBJECTIVE: Although there are changes in the postprandial lipid responses of obese patients, these are closely associated with high fasting triglycerides (TG). This study of 17 normotriglyceridemic, normoglucose-tolerant android obese subjects (body mass index, BMI = 34.3 +/- 3.1 kg/m2) and 33 normal-weight controls (BMI = 21.8 +/- 1.6 kg/m2) was done to examine their postprandial responses to an oral fat loading test containing retinol (890 calories, 85% fat) and to evaluate the possible association between clinical and biological features of obesity and/or insulin resistance and postprandial lipemia. SUBJECTS AND MEASUREMENTS: Blood samples were taken before giving the fat load and at 2,3,4,5,6 and 8 h after it. Insulin sensitivity was assessed using HOMA, and TG and retinyl palmitate (RP) in the plasma, chylomicrons and non-chylomicron fractions were measured each time. RESULTS: The areas under the curves (AUC) of chylomicron TG for the obese and controls were not different, indicating adequate lipolytic activity. By contrast, the AUC for non-chylomicron TG was significantly greater in the obese than in the controls (512 +/- 135 vs 429 +/- 141 mmol/lmin, P < 0.01). In addition, the AUC for RP in this same fraction was significantly lower in the obese than in the controls (103 +/- 55 vs 157 +/- 88 mg/l min, P < 0.05), suggesting that the TG from endogenous lipoproteins accounted for most of the increase in TG in the non chylomicron fraction. Parameters related to obesity showed no relationship with these postprandial abnormalities, whereas HOMA, which discriminated between the groups, partly explained (r2= 23%, P < 0.01) the significant increase in non-chylomicron TG. CONCLUSIONS: Android obese patients with a fasting TG in the normal range and not different from the fasting TG of lean controls had an abnormal postprandial lipemia response, indicated by a significantly greater TG in the non-chylomicron subfraction than in controls. These alterations may be partly due to postprandial changes in endogenous lipoproteins as a consequence of insulin resistance.

Adult↗
PubMed2000

A new missense mutation in the calcium-sensing receptor in familial benign hypercalcaemia associated with partial lipoatrophy and insulin resistant diabetes.

We studied two patients (a 54-year-old woman and her 16-year-old son) with familial benign hypocalciuric hypercalcaemia (FBHH) associated with severe insulin resistant diabetes in the context of a partial lipodystrophic syndrome. Sequencing of the entire coding sequence of the calcium-sensing receptor (CaR) gene revealed a novel heterozygous mutation at codon 395, leading to the substitution of a cysteine by an arginine residue (Cys395Arg) in the extracellular ligand-binding domain. This mutation was absent in two normocalcaemic relatives and in 54 control subjects. It was recently shown, in transfection studies, that the substitution of this amino acid results in incomplete receptor processing, a severe decrease in cell surface expression and altered signal transduction (Fan et al., 1998). This mutation is therefore likely to be responsible of the FBHH phenotype. A pathophysiological link between this mutation and insulin resistance remains unclear.

Adolescent↗
PubMed2000

No acute response of leptin to an oral fat load in obese patients and during circadian rhythm in healthy controls.

This study was done to elucidate the relationship between postprandial leptin and obesity, and the possible influence of the circadian rhythm on the dynamic leptin response to an oral fat load (OFLT). In experiment 1, we measured the leptin and insulin responses to an oral fat load in 16 non-diabetic obese subjects and in 16 healthy controls, matched for age and gender. In experiment 2, we measured the leptin and insulin responses to an OFLT according to the time of fat load ingestion: 0700 h (diurnal (D) test) or 2200 h (nocturnal (N) test) in nine normal-weight healthy males. Baseline leptin concentration was correlated with the body mass index, body fat mass and percentage of body fat mass in both experiments. The leptin concentrations were higher in women than in men (P<0.001). In experiment 1, the leptin concentrations were higher in obese subjects than in controls, but did not change over time in either group. The plasma insulin concentrations at baseline and during the postprandial state, as well as the area under the curve (AUC) of insulin, were higher in obese subjects than in controls (P<0.05-0. 0001). There was no correlation between postprandial insulin responses and postprandial leptin responses in either obese or control groups. In experiment 2, leptin (D vs N, 2.9+/-1.4 vs 2. 9+/-1.0 ng/ml) and insulin (D vs N, 41+/-18 vs 25+/-9 pmol/l) concentrations were similar at the beginning of the D and N tests after a 10 h fast. The leptin concentrations did not change after D or N tests and were not statistically different for D and N tests. Our results indicate that the leptin concentration in healthy controls and in obese patients is not acutely influenced by a high fat load.

Adult↗
PubMed2000

Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy.

Missense mutations of the lamin A/C gene, LMNA, have been recently identified in Dunnigan-type familial partial lipodystrophy (FPLD), which belongs to a heterogeneous group of rare disorders affecting adipose tissue distribution and metabolism. In this study, we sequenced the LMNA coding region from patients presenting with FPLD or other forms of lipodystrophy. We identified two heterozygous mutations in exon 8, R482W and R482Q, in FPLD patients (six families and one individual) with various clinical presentations. In addition, we found a novel heterozygous mutation (R584H) in exon 11, encoding specifically the lamin A isoform, in a patient with typical FPLD. Clinical and biochemical investigations in FPLD patients revealed that the expression and the severity of the phenotype were markedly dependent on sex, with female patients being more markedly affected. In subjects with generalized lipoatrophy, either congenital (13 case subjects) or acquired (14 case subjects), or Barraquer-Simon syndrome (2 case subjects), the entire LMNA coding sequence was normal. Although FPLD mutations are predominantly localized in exon 8 of LMNA, the finding of a novel mutation at codon 584, together with the R582H heterozygous substitution recently described, confirms that the C-terminal region specific to the lamin A isoform is a second susceptibility region for mutations in FPLD.

Adipose Tissue↗
PubMed2000

[Physiopathology of obesity. Dietary factors, and regulation of the energy balance].

Energy balance and macronutrient balance are the cornerstones upon which any theories of obesity must be built. Obesity can only occur when energy intake remains higher than energy expenditure for an extended period of time. However the macronutrient composition of the diet can also affect energy balance. Fat is a key nutrient because it is poorly regulated at both the level of consumption and oxidation. Psychological and behavioural profiles of obese subjects are clearly important because they can affect food choice and eating patterns. The role of eating frequency and circadian distribution of food is still debated. Eating disorders could be implicated in the development of obesity, but it is uncertain whether obesity is a direct result or a cause of the eating disorder. There are strong evidence to suggest that dietary restraint is associated with loss of dietary control and excessive eating. Early stages of fat storage involve expansion of existing adipocytes (hypertrophy) and later stages involve the recruitment of new adipocytes (hyperplasia). The mechanisms controlling the transformation of preadipocyte could also involve specific dietary components such as polyunsaturated fatty acids or proteins. The age of adiposity rebound, that is a risk factor for later obesity has been found significantly younger in children consuming a high protein diet. These factors could be involved during early infancy or even in utero, according to the hypothesis of fetal programming of adult diseases. There is a need for more longitudinal studies on the role of macronutrient composition, food choice or eating disorders, especially among children, teenagers and young adults.

Adipose Tissue↗
PubMed2000

[How should we use the short-acting insulin analog Lys-Pro in external continuous subcutaneous pumps?].

External pump treatment improves glycemic control, particularly thanks to the continuous basal rate. The pharmacokinetics of the short-acting insulin analog lispro allow a better control of post-prandial hyperglycemia than regular insulin. The use of the short-acting insulin analog in the pump improves HbA1c and blood glucose stability, without increasing the risk of hypoglycemia. Frequent blood glucose self-monitoring is required in order to optimize insulin adjustments, using the retro-active method. Systematic monitoring of urine ketones is also required, for an early detection of any interruption in insulin delivery. Under these conditions, this modality of intensified treatment seems very efficient.

Blood Glucose↗
PubMed1999

[Insulin in the treatment of type 2 diabetes].

Insulin use in NIDDM is a frequent situation. Many acute clinical circumstances justify a transient insulin therapy including ketoacidosis decompensation or hyperosmolar state and severe intercurrent diseases. The problem is more complex when glycemic control is no longer obtained despite maximal doses of oral treatment. Type 2 diabetes is then defined as an insulin-requiring diabetes. There is actually no consensus, but lots of arguments advocate an intensive insulin therapy based on multiple daily injections in this clinical state. However, when patient's overweight is important or if the clinical context is unfavourable, conventional insulin therapy or combined treatment using bedtime insulin and daytime oral agents may be tried.

Blood Glucose↗
PubMed1999

Delayed changes in postprandial lipid in young normolipidemic men after a nocturnal vitamin A oral fat load test.

The oral fat load tests (OFLT) used to study postprandial lipemia are generally conducted during the day. A nocturnal fat load test could be convenient and physiologically more appropriate. We have therefore compared the lipemic responses of 9 normolipidemic young men to OFLT given at 2200 h (nocturnal) and at 0700 h (diurnal). Triglyceride and retinyl palmitate concentrations were measured for 10 h. Peak plasma concentrations or areas under curves (AUC) for triglyceride after the diurnal and nocturnal tests were not significantly different [2.17 +/- 0.78 (diurnal) vs. 2.04 +/- 0.87 mmol/L (nocturnal) and 13.12 +/- 4.45 (diurnal) vs. 13.74 +/- 5.79 mmol/(L. h) (nocturnal)]. Peak plasma concentrations and AUC retinyl palmitate for the two tests were not different [1.71 +/- 0.69 (diurnal) vs. 1.42 +/- 0.66 mg/L (nocturnal) and 7.17 +/- 3.98 (diurnal) vs. 6.63 +/- 4.23 mg/(L. h) (nocturnal)]. The diurnal triglyceride peak occurred significantly earlier (4.3 +/- 1.2 h) than the nocturnal peak (5.8 +/- 1.7 h, P < 0.05). We have developed a model using only three sample time points to predict AUC [triglyceride at 0 h, triglyceride at average peak-time (4 h for diurnal and 6 h for nocturnal tests), and triglyceride at 10 h], thus reducing the number of blood samples. The predicted AUC was well correlated with the total AUC after nocturnal OFLT (r = 0.98, P < 0.0001). The nocturnal test appeared to be well tolerated by the subjects. The three-point simplified protocol may well be suitable for studies on large groups of subjects.

Adult↗
PubMed1999

Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients.

An interruption of continuous sc insulin infusion (CSII) of the insulin analog lispro should result in a more rapid metabolic deterioration of type 1 diabetic patients because of its pharmacokinetic characteristics. We analyzed the metabolic changes occurring during a 5-h interruption of CSII and the 5 h after restarting the pump in 10 type 1 diabetic patients. The study was a randomized, cross-over, open label design comparing insulin analog [Lispro (LP)] and regular insulin [Velosuline (VE)]. Plasma glucose, free insulin, glucagon, betahydroxybutyrate (beta-OHB), and nonesterified fatty acids (NEFA) were measured every hour from 0700 h (time zero) to 1700 h (600 min). After stopping CSII, the plasma glucose level was significantly higher in the LP group than in the VE group (P < 0.05-0.01). The plasma free insulin level decreased significantly with the two treatments, but was significantly lower with LP than with VE (P < 0.05-0.01). Plasma NEFA increased more rapidly and was significantly higher in the LP group than in the VE group (P < 0.01-0.05). Plasma beta-OHB increased earlier with LP, but was not statistically different between the treatments. After restarting the pump, plasma glucose decreased with LP, but continued to increase with VE, and the plasma free insulin peak occurred earlier and was greater with LP than with VE (P < 0.05). Plasma NEFA and beta-OHB levels decreased significantly with the two treatments, but more dramatically with LP treatment. Thus, a short interruption of Lispro in CSII is associated with an earlier, greater metabolic deterioration, but Lispro corrected this metabolic deterioration more effectively.

3-Hydroxybutyric Acid↗
PubMed1999

Increased ability of LDL from normolipidemic type 2 diabetic women to generate peroxides.

BACKGROUND: We assessed the ability of LDL from 30 type 1 diabetic patients (18 men, 12 women), 65 type 2 diabetic patients (35 men, 30 women), and 35 controls (19 men, 16 women) to generate peroxides. The men and women in the diabetic groups were studied separately and matched for age, body mass index, duration of diabetes, glycohemoglobin, and conventional lipid characteristics according to the presence or absence of hyperlipidemia. METHODS: The ability of LDL to form peroxides was assessed by measuring the thiobarbituric acid-reactive substances corrected for LDL-cholesterol [ratio of malondialdehyde (MDA) to LDL-cholesterol]. LDL particle size was expressed as the ratio of LDL-cholesterol to apolipoprotein B (LDL-cholesterol/apoB). RESULTS: The MDA/LDL-cholesterol ratio was higher in type 1 and type 2 diabetic patients with hyperlipidemia than in controls. The MDA/LDL-cholesterol ratio was also higher in type 2 normolipidemic women than in controls (P <0.01). The LDL-cholesterol/apoB ratio was lower in type 2 diabetic women than in type 2 diabetic men (P <0.05). The MDA/LDL-cholesterol ratio was negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.78, P <0.001) in hyperlipidemic type 1 (not type 2) diabetic patients. In normolipidemic type 2 diabetic patients, the MDA/LDL-cholesterol ratio was also negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.75, P <0.001) because of the highly significant negative correlation in type 2 diabetic women (r = -0.89, P <0.01). CONCLUSIONS: LDL from well-controlled type 2 diabetic women is smaller and more prone to form peroxides. This could explain why diabetic women are at greater risk of cardiovascular disease.

Adult↗
PubMed1999

Severity of diabetic retinopathy is linked to lipoprotein (a) in type 1 diabetic patients.

To determine the relationship between plasma Lp(a) concentration and the risk of developing diabetic retinopathy, 341 Type 1 diabetic patients underwent an annual retinal fluorescein angiography and were assigned to one of 3 groups according to the stage of their diabetic retinopathy: no retinopathy (NR), non-proliferative diabetic retinopathy (N-PDR), or proliferative diabetic retinopathy (PDR). One hundred and twenty-three Type 1 diabetic patients had no retinopathy, 188 had N-PDR and 30 had PDR. The ages of the three groups and the duration of diabetes were significantly different. Hypertension, microalbuminuria and diabetic nephropathy were more frequent in PDR than in NR or N-PDR (p < 0.0001). Plasma HbA1c was higher in PDR than in NR or N-PDR (p < 0.01). Type 1 patients who had been diabetic for at least 20 years included 30 NR, 108 N-PDR and 24 PDR. Type 1 diabetic patients with PDR had microalbuminuria and macroproteinuria more frequently than other patients (p < 0.0001 and 0.01, respectively). Type 1 diabetic patients with PDR had the highest median plasma Lp(a) and the highest frequency of Lp(a) above 30 mg/dl (p < 0.05). Multivariate analysis carried out in Type 1 diabetic patients with a duration of diabetes of at least 20 years showed that microproteinuria, HbA1c and Lp(a) accounted significantly for 21% of variance in retinal status. Lp(a) above 30 mg/dl was related to the risk of developing PDR (OR = 8.40, p < 0.05). Lipoprotein(a) appears to be associated with the severity of diabetic retinopathy in Type 1 diabetic patients, and particular attention should be paid to those with Lp(a) above 30 mg/dl and pre-proliferative retinopathy.

Adult↗
PubMed1998

Blood glucose control on Sunday in IDDM patients: intensified conventional insulin therapy versus continuous subcutaneous insulin infusion.

We have assessed the capacity of continuous subcutaneous insulin infusion (CSII) to maintain good blood glucose metabolic control on Sundays, when waking is delayed, with reference to intensified conventional insulin therapy by multiple daily injections (MDI). The study lasted 3 weeks, including 3 week-ends. A total of 20 IDDM patients were selected for metabolic control: ten were treated by CSII and ten by MDI. Blood glucose was determined at least three times a day (fasting on waking, pre-lunch and pre-dinner). The times of blood glucose determinations and their values were recorded in a memory reflectance meter. Waking, the first blood glucose measurement and the first insulin injection (MDI) or bolus (CSII) were about 1 h later on Sundays than on a weekday (44 +/- 4 min in MDI group, P < 0.04; and 59 +/- 7 min in CSII group, P < 0.02). The times of the pre-lunch and pre-dinner blood glucose determinations were not significantly different. The mean waking and pre-lunch blood glucose values of the MDI group were higher on Sundays (11.5 +/- 3.8 and 9.7 +/- 4.5 mmol/l) than on weekdays (8.7 +/- 2.3 and 7.1 +/- 2.5 mmol/1)(P < 0.01). The pre-prandial blood glucose levels of the CSII group on Sundays and weekdays were not statistically different at any time. Changes in the waking time and the subsequent delay in the first insulin bolus on Sunday may alter blood glucose control in patients on MDI, but CSII allows such changes without any glycemic side effects.

Adult↗