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Biomedical subjects

E Bertin

Publications and source records attributed to E Bertin.

At least 19 recordsLinked to original sources

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Adult↗

Maternally inherited diabetes and deafness: a multicenter study.

BACKGROUND: Maternally inherited diabetes and deafness (MIDD), which is seen in 0.5% to 2.8% of patients with type 2 diabetes mellitus, is related to a point mutation at position 3243 of mitochondrial (mt) DNA. Its clinical description is incomplete. OBJECTIVE: To study the clinical presentation and complications of diabetes in patients with MIDD and to identify clinical characteristics that may help select diabetic patients for mtDNA mutation screening. DESIGN: Multicenter prospective descriptive study. SETTING: 16 French departments of internal medicine, diabetes and metabolic diseases, or both. PATIENTS: 54 patients with type 2 diabetes mellitus and the mtDNA 3243 mutation. MEASUREMENTS: Characteristics of diabetes, metabolic control (glycosylated hemoglobin level), complications of diabetes, and involvement of other organs. RESULTS: On average, patients with MIDD were young at diabetes onset and presented with a normal or low body mass index. None were obese. Seventy-three percent of probands had a maternal family history of diabetes. Diabetes was non-insulin-dependent at onset in 87% of patients; however, 46% of patients had non-insulin-dependent disease at onset but progressed to insulin therapy after a mean duration of approximately 10 years. Neurosensory hearing loss was present in almost all patients. Eighty-six percent of patients who received an ophthalmologic examination had macular pattern dystrophy (a specific retinal lesion). Forty-three percent of patients had myopathy, 15% had cardiomyopathy, and 18% (9 of 51) had neuropsychiatric symptoms. Although the prevalence of diabetic retinopathy was 8% among patients who received an ophthalmologic examination, lower than expected after a mean 12-year duration of diabetes, prevalence of kidney disease was 28%. This suggests that a specific renal involvement was the result of mitochondrial disease. CONCLUSIONS: Maternally inherited diabetes and deafness has a specific clinical profile that may help identify diabetic patients for mtDNA testing.

Adolescent↗

Dissociations between featural versus conjunction-based texture processing in infancy: analyses of three potential contributing factors.

Many models of object perception posit that adults encode individual features in visual scenes before processing the conjunction relations among these features to generate holistic representations. Prior research suggests that infants detect textural discrepancies based on individual features more readily than those based on feature conjunctions. While these results suggest adult-like qualitative differences in infants' processing of features versus conjunctions, there are potential alternative explanations. We examined three such explanations: (1) failure to process one of the features that constitute the conjunction, (2) failure to encode and remember conjunction information that is necessary to detect conjunction-based textural discrepancies, and (3) the fact that conjunction-based discrepancies involve stimuli that are more similar to original stimuli than those involving feature-based discrepancies. None of these factors could explain 5.5-month-olds' superior processing of featural than conjunction-based textural discrepancies. Thus, in infancy, as in adulthood, features and conjunction relations appear to be processed by qualitatively different mechanisms.

Child Development↗

Pictorial cues and three-dimensional information processing in early infancy.

Adults derive 3-D information from 2-D images by initially processing local line junction cues and then combining information from many junctions. Prior research indicates that 3-month-olds are sensitive to 3-D cues in individual line junctions. In Experiment 1, we examined whether infants are sensitive to holistic combinations of line junctions that adults use to derive overall 3-D structure. Infants detected a misoriented shape in an array depicting 3-D blocks but not in 2-D patterns that contained all of the trilinear junctions of the 3-D shapes but without the connecting lines. Thus, like adults, infants exhibited sensitivity to holistic combinations of line junctions rather than to individual junctions. In Experiment 2, when confronted with two test patterns, one containing an individual novel element among 15 familiar elements and the other containing a single familiar element among 15 novel elements, infants preferred to look at the former pattern in the 3-D condition but at the latter pattern in the 2-D condition. Thus, akin to pop-out in adults, discrepancies in 3-D cues selectively engaged infants' attention. These results suggest that 3-month-olds are not only sensitive to holistic combinations of line junctions that adults use to derive 3-D information but also selectively attend to these 3-D cues in static images.

Analysis of Variance↗

Action of glucagon and glucagon-like peptide-1-(7-36) amide on lipolysis in human subcutaneous adipose tissue and skeletal muscle in vivo.

In vitro and animal studies have shown that glucagon and glucagon-like peptide-1 (GLP-1)-(7-36) amide may participate in the regulation of lipolysis. However, results on human subjects in vivo are inconclusive. To avoid confounding effects, such as changes in insulin secretion when perfusing hormones iv, we used the in situ microdialysis to analyze the impact of human glucagon and GLP-1 on lipolysis rates and local blood flow. Nine healthy volunteers were given an 80-min local perfusion of each hormone (10(-6) mol/L), both in skeletal muscle (gastrocnemius) and in sc abdominal adipose tissue, after a basal period with perfusion of Ringer's solution. Variations in the lipolysis rate and blood flow, respectively, were assessed by measuring of the dialysate glycerol content and the ethanol ratio (outgoing-to-ingoing ethanol concentration). The in vitro relative recovery of the microdialysis probes was 5.2 +/- 1.2%. No significant effects of either GLP-1 or glucagon on either lipolysis rate or blood flow were detected in muscle or adipose tissue. Isoprenaline (10(-6) mol/L), which was perfused after glucagon or GLP-1 in the same catheters, significantly increased the lipolysis rate (a 249% increase of dialysate glycerol in adipose tissue and a 72% increase in skeletal muscle). Furthermore, isoprenaline, but not glucagon or GLP-1, stimulated lipolysis in vitro in isolated human sc adipose tissue. We conclude that neither glucagon nor GLP-1 affect the lipolysis rate of human sc adipose tissue or skeletal muscle.

Adipose Tissue↗

Gastric emptying is accelerated in obese type 2 diabetic patients without autonomic neuropathy.

OBJECTIVE: To clarify the impact of type 2 diabetes mellitus on the gastric emptying rate. MATERIAL AND METHODS: Using a double-isotope scintigraphic technique, we assessed the gastric emptying of a standard liquid-solid meal in 13 obese type 2 diabetic patients without autonomic neuropathy (age: 47.4 +/- 8.6 yr, body mass index: 33.9 +/- 4.8 kg/m(2), glycaemia: 9.1 +/- 2.6 mmol/l) and in 7 controls with similar sex ratio, age, BMI and body fat distribution. RESULTS: The half gastric emptying time for the liquid phase was not significantly different between diabetic patients and controls (respectively: 52.7 +/- 14.5 min and 63.1 +/- 15.2 min). However, the half gastric emptying time for the solid phase was significantly shortened in diabetic patients versus controls (respectively 88.8 +/- 23.2 min in diabetic patients and 113.6 +/- 26.9 min in controls; p<0.04). Furthermore, a negative relationship was highlighted between the half gastric emptying time for the solid phase and basal glycaemia (r=-0.65, p<0.02) in diabetic patients. No significant relationship was found between gastric emptying parameters and cardiac autonomic nerve function, insulin or gastrin levels. CONCLUSION: Solid gastric emptying is accelerated in obese type 2 diabetic patients without patent autonomic neuropathy when compared to obese non diabetic patients.

Adult↗

Measurement of visceral adipose tissue by DXA combined with anthropometry in obese humans.

OBJECTIVE: To get accurate measurements of visceral adipose tissue (VAT) using dual energy X-ray absorptiometry (DXA). DESIGN: DXA and anthropometric data and their combinations were compared to the VAT area calculated from a computed tomography (CT) single scan. SUBJECTS: 71 overweight subjects (44 women, 27 men), age: 16-70 y, BMI: 27-52 kg/m2. MEASUREMENTS: Total body and segmental tissue composition, and new parameters obtained from DXA, in addition to waist and hip circumferences and abdominal sagittal diameter measurements. RESULTS: The ratio measured at the umbilical level (sagittal diameter - subcutaneous fat width) x (transverse internal diameter)/(height) was closely related to VAT (r=0.94 for women and 0.88 for men). It gave the most predictive equation for VAT: y = 79.6x (s.e. 3.9) - 149 cm2 for the whole population (r2=0.86, P<0.0001, root mean square error=38.2 cm2. An independent relationship between lean mass or its index (r=0.52 and 0.72, P<0.001) and VAT was also found in women. CONCLUSION: This study demonstrates the potential usefulness of DXA to supply accurate measurements of VAT in addition to total body composition determination in obese subjects.

Absorptiometry, Photon↗

Effect of early dietary restriction on insulin action and secretion in the GK rat, a spontaneous model of NIDDM.

The availability of the Goto-Kakisaki (GK) rat model of non-insulin-dependent diabetes mellitus prompted us to test the effect of a limited period of undernutrition in previously diabetic young rats on their insulin secretion and insulin action during adult age. Four-week-old female GK rats were either food restricted (35% restriction, 15% protein diet) or protein and energy restricted (35% restriction, 5% protein diet) for 4 wk. Food restriction in the young GK rat lowered weight gain but did not aggravate basal hyperglycemia or glucose intolerance, despite a decrease in basal plasma insulin level. Furthermore, the insulin-mediated glucose uptake by peripheral tissues in the GK rat was clearly improved. We also found that food restriction, when it is coupled to overt protein deficiency in the young GK rat, altered weight gain more severely and slightly decreased basal hyperglycemia but conversely aggravated glucose tolerance. Improvement of basal hyperglycemia was related to repression of basal hepatic glucose hyperproduction, despite profound attenuation of basal plasma insulin level. Deterioration of tolerance to glucose was related to severe blunting of the residual glucose-induced insulin secretion. It is, however, likely that the important enhancement of the insulin-mediated glucose uptake helped to limit the deterioration of glucose tolerance.

Aging↗

Plasma levels of tumor necrosis factor-alpha (TNF-alpha) are essentially dependent on visceral fat amount in type 2 diabetic patients.

TNF-alpha is considered as one of the potential determinants of insulin resistance. However several data suggest that TNF-alpha expression itself, could be modulated by the degree of adiposity and/or plasma insulin levels. To clarify the determinants of plasma TNF-alpha levels in type 2 diabetes mellitus, we studied the impact of intensive insulin treatment on plasma TNF-alpha levels in 16 type 2 diabetic subjects with failure to oral antidiabetic medication (HbA1c: 10.8 +/- 1.2 %). Furthermore, we analyzed the relationship between plasma TNF-alpha levels and total or regional body fat measurements using anthropometry, bienergetic absorptiometry and computed tomography in a cohort of 33 caucasian obese type 2 diabetic subjects (BMI: 32.2 +/- 4.4 kg/m(2) ). The plasma TNF-alpha level was neither affected by plasma glucose level variations nor intensive insulin treatment despite a 37 % decrease in daily insulin needs at the end of insulin therapy (total duration: 11.5 +/- 2.0 days). The plasma TNF-alpha level was similar in men and women and unrelated to age, fasting glycemia or HbA1c. A relationship was highlighted with BMI (r =0.39, p <0.02), but not with total fat mass. This relationship was only dependent on the intra-abdominal fat mass amount as assessed by the waist-to-hip circumference ratio (r =0.52, p <0.01) and the visceral adipose tissue area (r =0.56, p <0. 01). These results show that plasma TNF-alpha levels are essentially dependent on visceral fat amount, thus suggesting that TNF-alpha could be one of the factors mediating insulin resistance and cardiovascular risk in obese type 2 diabetic patients.

Absorptiometry, Photon↗

Glucose metabolism and beta-cell mass in adult offspring of rats protein and/or energy restricted during the last week of pregnancy.

An association between low birth weight and later impaired glucose tolerance was recently demonstrated in several human populations. Although fetal malnutrition is probably involved, the biological bases of such a relationship are not yet clear, and animal studies on the matter are scarce. The present study was aimed to identify, in adult (8-wk) female offspring, the effects of reduced protein and/or energy intake strictly limited to the last week of pregnancy. Thus we have tested three protocols of gestational malnutrition: a low-protein isocaloric diet (5 instead of 15%), with pair feeding to the mothers receiving the control diet; a restricted diet (50% of the control diet); and a low-protein restricted diet (50% of low-protein diet). Only the low-protein diet protocols, independent of total energy intake, led to a lower birth weight. The adult offspring female rats in the three deprived groups exhibited no decrease in body weight and no major impairment in glucose tolerance, glucose utilization, or glucose production (basal state and hyperinsulinemic clamp studies). However, pancreatic insulin content and beta-cell mass were significantly decreased in the low-protein isocaloric diet group compared with the two energy-restricted groups. Such impairment of beta-cell mass development induced by protein deficiency limited to the last part of intrauterine life could represent a situation predisposing to impaired glucose tolerance.

Aging↗

[Measurement of monocyte activation: perspectives in clinical application in the investigation of the diabetic patient].

Monocytes play a pivotal role in the complex processes of inflammation, immunologic responses and atherothrombosis. Clinical studies essentially reported an increased procoagulant activity in diabetes and coronary disease, suggesting an overexpression of tissue factor. This was further confirmed by the direct measurement of tissue factor on monocyte membrane by flow cytometry. Many receptors can be measured on monocytes by flow cytometry: beta 2 integrins (CD 11 a-b-c/CD 18) involved in adhesion, EPR-1 receptor, receptors for advanced glycation products, urokinase receptor U-PAR. Flow cytometry allows a cell analysis in whole blood. Modern methods allow a standardization of the procedures and a quantification of the number of sites expressed by the cell. However, the respect of preanalytical and analytical conditions is mandatory to obtain reliable data. Besides, clinical studies in diabetes should carefully define the subgroups of patients: type of diabetes, metabolic abnormalities, risk factors, infective complications.

Diabetes Mellitus↗

Major histocompatibility class II genes polymorphism in insulin dependent diabetes mellitus with or without associated thyroid autoimmunity.

Insulin dependent diabetes mellitus (IDDM) is sometimes associated with extrapancreatic organ-specific autoimmune diseases, but whether this phenotype results from a peculiar genetic profile is still unclear. The allelic distribution of the major histocompatibility complex (MHC) class II genes (HLA-DRB1, DQA1, DQB1 and TAP) was analysed in 143 patients with IDDM alone by comparison with 82 IDDM patients with autoimmune thyroid disease (IDDM/AITD). The frequency of the DQB1*0301 IDDM-protective phenotype seemed to be lower in IDDM than in IDDM/AITD patients (16.8% vs 30.5% respectively, p = 0.02). By contrast, the frequency of the DRB1*04-DQB1*0302 IDDM-predisposing phenotype was higher in IDDM than in IDDM/AITD patients (91.3% vs 76.1% of DR4-positive patients respectively, p = 0.007), but these differences were not significant after correcting the p values, except in the case of the DRB1*0405-DQB1*0302 combination (21.3% vs 2.4% of DR4-positive patients, Pc = 0.05). Furthermore, all differences disappeared when patients were matched for age at IDDM-onset. Our data do not long give support for a particular role of MHC class II genes in favouring the occurrence of thyroid autoimmunity in IDDM patients, but rather suggest that some class II alleles or residues might determine the rapidity of progression to IDDM in genetically susceptible individuals. The involvement of non-MHC genes and/or environmental factors remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evaluation of dual-energy X-Ray absorptiometry for body-composition assessment in rats.

Recent developments in dual-energy X-ray absorptiometry (DXA) have rendered feasible the determination of whole-body composition in small laboratory animals by directly measuring fat, fat-free and mineral bone masses. Our aim was to evaluate this technique by cross-calibrating the DXA method with the carcass chemical analysis in a heterogeneous population of nondiabetic Wistar and diabetic GK rats (21 animals were used for precision error and reproducibility determinations and 26 were used for accuracy studies). We report that this technique is optimized for weights >200 g. The respective CV for lean mass, fat mass and percentage of fat mass determined in short-term or transversal studies was 1.1 +/- 0.1, 3.0 +/- 1.3 and 3. 1 +/- 0.4% (mean +/- SD) respectively. Further, this technique is valid for rats weighing from 130 to 200 g by using three successive scans. In longitudinal studies, daily calibrations significantly increased the percentage of fat mass CV to 6.6 +/- 3.3%, but it was significantly decreased to 3.0 +/- 2.7% by the use of triplicate scans. The accuracy for DXA was excellent in reference to the chemical extraction technique (r2 = 0.95 for percentage of fat mass, P < 0.0001), using an adjustment factor of 0.75 (limits of agreement between the two methods for percentage of fat mass = -1.7-2.3%). Mimicry of longitudinal changes in body composition with intraperitoneal injections of saline solution demonstrated a satisfactory detection of body component changes (</=2% of error for each final component analyzed, when increasing total lean mass by 11. 8%). We conclude that DXA is appropriate for rat whole-body composition determination, allowing reliable long-term follow-up of individual animals for the first time.

Absorptiometry, Photon↗

Influence of endogenous and environmental factors on variations of serum lipoprotein (a) concentrations in a large population of insulin-treated diabetic patients.

Variations of serum Lp(a) concentrations were studied in a large population of insulin-treated diabetic patients in relation to the type of diabetes, insulin treatment and long-term complications. Lp(a) concentrations were measured by immunonephelometry in 740 diabetic patients [493 insulin-dependent diabetic (IDDM) patients and 247 insulin-treated Type 2 diabetic (ITD) patients]. Concentrations and distributions were compared with those of 128 non-diabetic controls. Correlations were investigated with lipidic and glycaemic parameters, daily lipid intake, body mass index (BMI), macrovascular and nephropathic complications, and insulin therapy. Both groups of insulin-treated patients (IDDM and ITD) displayed significantly higher Lp(a) concentrations when compared to controls. No relationship was found with macrovascular complications and nephropathy, except in IDDM patients in whom Lp(a) was elevated when creatinine concentration was above 120 mumol/L. Mean variations of Lp(a) were correlated with BMI and triglyceride variations in IDDM patients and only with triglycerides in ITD patients. These results suggest a direct and/or indirect (via serum triglycerides) potential role of exogenous insulin in the modulation of serum Lp(a) concentrations. BMI and lipid daily fat intake could be considered as additional modulating factors of Lp(a) serum concentrations in ITD patients.

Adult↗

Insulin and body fat distribution have no direct effect on plasma leptin levels in obese Caucasian women with and without type 2 diabetes mellitus.

Leptin, a hormone produced by adipose tissue, is potentially involved in the regulation of adiposity. The effects of insulin and body fat distribution on human plasma leptin have not yet been clearly defined. The present study investigated the relationships between plasma leptin and total and regional body fat parameters measured by anthropometry and bienergetic absorptiometry associated or not with computed tomography, taking glucose metabolism into account. A cohort of 51 obese Caucasian women (23 with normal glucose tolerance, 11 with impaired glucose tolerance, and 17 with Type 2 diabetes) was analysed. All non-diabetic subjects had an oral glucose tolerance test together with plasma glucose and insulin measurements. Moreover, a subgroup of 7 diabetic subjects with failure to oral antidiabetic treatment was submitted to about 12 days of intensive subcutaneous insulin therapy. Plasma leptin was essentially dependent on total body fat mass (r = 0.83, p < 0.0001, for the whole population), but not related to adipose tissue distribution. An independent correlation between leptin adjusted on body fat mass and fasting insulinaemia (R = 0.72, p < 0.02) or C-peptide (R = 0.62, p < 0.03) was found significant only in the diabetic group. Insulin treatment was associated with a moderate and transient increase of plasma leptin. The relative variations of plasma leptin levels were strongly negatively correlated with those of free fatty acids. The present data confirm that plasma leptin is not dependent on body fat distribution and suggest an indirect effect of insulin on leptin secretion in clinical conditions.

Adipose Tissue↗

Evaluation of serum glycated lipoprotein(a) levels in noninsulin-dependent diabetic patients.

OBJECTIVE: Serum Lp(a) levels are generally considered unaffected by non-insulin-dependent diabetes mellitus (NIDDM). However, high Lp(a) concentrations as well as an increased rate of nonenzymatic glycation of proteins may be involved in degenerative diabetic complications. DESIGN AND METHODS: We measured serum glycated Lp(a) levels in 17 NIDDM patients, as compared to 14 normoglycaemic controls. Glycated proteins were separated from nonglycated ones by boronate affinity chromatography, and specific proteins assayed by immunonephelometric methods in both fractions. RESULTS: The percentage of glycated Lp(a) was 1.5 +/- 0.4% (mean +/- SD) in the control group, and was significantly higher in NIDDM patients: 4.3 +/- 1.5% (p < 0.01). The basal level of Lp(a) glycation was lower than that of other proteins, particularly apo B (4.0 +/- 0.7%). By contrast, the variations of glycated Lp(a) levels were of greater amplitude (+ 187%) than those of glycated apo B (+ 67%). Glycated Lp(a) values were significantly elevated in patients with micro and macrovascular complications in comparison with uncomplicated patients. CONCLUSIONS: These results suggest that glycated Lp(a) may be considered a potentially interesting parameter in the pathophysiology of diabetic vascular complications.

Adult↗