A diagnostic score for anti-myelin-associated-glycoprotein neuropathy or chronic inflammatory demyelinating polyradiculoneuropathy in patients with anti-myelin-associated-glycoprotein antibody.

BACKGROUND AND PURPOSE: A diagnostic score was developed to discriminate anti-myelin-associated-glycoprotein (MAG) neuropathy from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and applied it to patients with atypical anti-MAG neuropathy. METHODS: The clinical and electrophysiological features of patients with a diagnosis of typical anti-MAG neuropathy were compared to those of patients with a diagnosis of CIDP. The association of each feature with the diagnosis was assessed in the two groups. Features showing a significant association with the diagnosis were included in a multivariable logistic regression model and adjusted odds ratios were estimated for each feature. A score ranging from 1 to 3 was applied to each feature based on the magnitude of the estimated odds ratios. The score was then applied to patients with a clinical diagnosis of CIDP who also had high anti-MAG antibody titers (CIDP-MAG). RESULTS: Thirty-one anti-MAG neuropathy patients, 45 typical CIDP patients and 16 CIDP-MAG patients were included. Scores in anti-MAG antibody patients ranged from 1 to 5 and in CIDP patients from -7 to -1. Using the score, 4/16 CIDP-MAG patients were diagnosed to have anti-MAG neuropathy and 12/16 patients to have CIDP. Response to intravenous immunoglobulin in the CIDP-MAG patients classified as CIDP was similar to that of definite CIDP patients and higher than that of anti-MAG neuropathy patients. CONCLUSIONS: Our score allowed an accurate discrimination to be made, amongst patients with anti-MAG antibodies, of those affected by CIDP and the patients with anti-MAG neuropathy. This score may help proper treatment to be chosen for patients with anti-MAG antibodies with a CIDP-like presentation.

Predictors of the early impairment of renal disease in human obesity.

OBJECTIVE: The mechanisms underlying the association of the increased albumin excretion rate (AER) with adiposity have yet to be clarified. We therefore investigated (1) the predictors of AER after 3 months of lifestyle intervention in a large cohort of nondiabetic obese women and (2) the relationships between AER and the adipose tissue gene expression of adipokines linked to inflammation and insulin resistance. SUBJECTS: A total of 269 obese nondiabetic women (age 49.9+/-13.1 years, body mass index (BMI) 36.8+/-4.6 kg m(-2)) participated in this program. Measurements used were anthropometrics parameters, blood pressure, oral glucose tolerance test, lipids, creatinine, AER, homeostasis model assessment of insulin resistance (HOMA-IR) and glomerular filtration rate at baseline and after 3 months of lifestyle intervention. At baseline, in a subgroup of 34 women, subcutaneous adipose tissue biopsy was carried out for the analysis of mRNA expression levels of adiponectin, suppressor of cytokine signaling 3 (SOCS-3), tumor necrosis factor alpha (TNF-alpha), pentraxine 3 (PTX-3), angiotensinogen and angiotensin-converting enzyme, and a blood sample was also taken from this group for the measurement of circulating adiponectin, interleukin-6, TNF-alpha and PTX-3. Microalbuminuria was defined as albumin/creatinine ratio >or=3.5 mg mmol(-1). Real-time PCR was used to quantify mRNA. RESULTS: Six percent of obese women had microalbuminuria. When dividing the whole cohort into three groups according to AER changes (decrease, stability and increase), we noted that 2 h glucose, insulin and HOMA-IR significantly decreased (P<0.05 for all) only in women who had a decrease in AER, whereas BMI and waist circumference significantly decreased in all the three groups (P<0.05). At baseline, higher AER was associated to significantly higher adipose tissue mRNA expression levels of SOCS-3 and PTX-3 (P<0.05) and to higher TNF-alpha and angiotensinogen expression. CONCLUSIONS: In obese women, weight loss alone is not sufficient to induce the AER decrease that occurs only with a concomitant improvement in glucose homeostasis. The adipose tissue gene expression profile seems to favor the early renal impairment often seen in obese subjects.

Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in obese subjects.

OBJECTIVE: The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor alpha (TNFalpha) and two glucocorticoid-regulated adipokines able to influence the metabolic control. DESIGN AND SUBJECTS: Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1+/-5.3 kg/m(2)). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9+/-5.1 kg/m(2)). MEASUREMENTS: Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFalpha and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11beta-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFalpha. Western blot analysis to evaluate 11beta-HSD1 protein expression. RESULTS: In the majority of the obese subjects, VAT expresses more 11beta-HSD1 than SAT. VAT 11beta-HSD1 expression was not associated with metabolic disorders. SAT 11beta-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11beta-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11beta-HSD1 was associated with increased adiponectin and TNFalpha expression and decreased serum adiponectin levels (all P's <0.05). CONCLUSIONS: In obese subjects, increased 11beta-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release.

Adiponectin receptors gene expression in lymphocytes of obese and anorexic patients.

AIM: Two adiponectin receptors (ADIPORs), ADIPOR1 and ADIPOR2, are widely expressed in tissues. Whether changes in the expression of ADIPORs are associated with obesity and insulin resistance in humans is still unclear. The aim of this study was to explore whether lymphocyte ADIPOR1 and ADIPOR2 mRNA expression is associated with obesity, insulin resistance, first-phase insulin secretion and serum adiponectin levels. METHODS: Using reverse transcription-polymerase chain reaction, we measured ADIPOR1 and ADIPOR2 mRNA levels in the lymphocytes of 59 obese patients, of whom 39 had normal glucose tolerance, 8 had impaired glucose tolerance or impaired fasting glucose, and 12 had type 2 diabetes, and of 21 women with restrictive anorexia nervosa. RESULTS: In all subjects, ADIPOR1 expression was 2.2-fold higher than that of ADIPOR2 (p < 0.0001). The mRNA expression level of both receptors correlated with each other (p < 0.0001). After adjustment for age and sex, lymphocyte ADIPORs mRNA expression (ADIPOR1, p < 0.005; ADIPOR2, p < 0.05) and serum adiponectin (p < 0.0001) were significantly lower in obese patients than in anorexic subjects. In a multivariate analysis with ADIPOR1 as the dependent variable and body mass index (BMI), blood pressure and adiponectin as the independent variables, only serum adiponectin remained positively and independently correlated with ADIPOR1 (p < 0.05). Adiponectin was independently and negatively related to BMI and sex. CONCLUSIONS: We have demonstrated in this study that lymphocytes express ADIPORs and that, similar to serum adiponectin, ADIPORs expression is markedly reduced in obese subjects. ADIPORs expression is not independently related to BMI, insulin resistance and beta-cell function.

Metabolic syndrome in obese Caucasian children: prevalence using WHO-derived criteria and association with nontraditional cardiovascular risk factors.

OBJECTIVE: Studies on the prevalence of metabolic syndrome (MS) in European obese children using child-based criteria are scanty. Moreover, it is unknown if nontraditional cardiovascular disease (CVD) risk factors are associated with the MS at this early age in these subjects. DESIGN AND SUBJECTS: We studied the prevalence of the MS in 588 Caucasian obese children and adolescents by devising a World Health Organization derived definition and child-specific criteria, whose deviation from normalcy was based on an age, sex, and ethnically comparable control group of 1363 subjects. In a subgroup of 206 obese children, we investigated the association of the MS with nontraditional CVD risk factors. MEASUREMENTS: Fasting blood samples for glucose and lipids measurements were taken in both control and obese children. In addition, the obese children underwent an oral glucose tolerance test. In the subgroup of 206 obese children, albumin excretion rate , plasma uric acid, fibrinogen, plasminogen activator inhibitor type 1(PAI-1), C-reactive protein, interleukin 6 and white blood cells were also measured. RESULTS: The prevalence of MS was 23.3%. A similar prevalence of 23% of MS was recorded in the subgroup of 206 obese children in whom measurements of nontraditional CVD risk factors were available. After adjustment for the degree of obesity, subjects with MS had significantly higher uric acid (6.6+/-0.23 vs 6.1+/-0.12 mg/dl, P<0.0001) and PAI-1 plasma concentrations (231.4+/-25.50 vs 214.3+/-12.96 ng/ml, P<0.05) and a higher frequency of microalbuminuria (37 vs 20%, P<0.05) than those without MS. Microalbuminuria, uric acid and PAI-1 explained 10.6% of the variance of MS. CONCLUSION: Approximately, a quarter of Caucasian obese children have the MS. The association of MS with several nontraditional risk factors for CVD early in life suggests a heightened CVD risk in these individuals.

Left ventricular hypertrophy and QT interval in obesity and in hypertension: effects of weight loss and of normalisation of blood pressure.

BACKGROUND: Left ventricular hypertrophy (LVH) and prolonged QT interval at ECG (QTc) are common in both obesity and arterial hypertension (AH), and are risk factors for cardiovascular disease and sudden death. METHODS: We compared the frequencies of LVH (ECG criteria) and QTc in obese-AH (n=41), in normotensive obese (n=75), in lean-AH (n=30), and in lean controls (n=68) comparable for age and sex; in obese patients, LVH and QTc were evaluated under basal conditions and 1 y later, that is, after a significant weight loss induced by bariatric surgery. RESULTS: LVH was more frequent, and QTc was longer, in obese-AH, in normotensive obese, and in lean-AH than in lean controls; after weight loss, frequency of LVH decreased in obese subjects becoming normotensive (n=87), not in obese subjects remaining hypertensive (n=29), while QTc decreased in all obese subjects. CONCLUSION: Weight loss can effectively reduce QTc; when concomitant AH disappears, weight loss can also reduce the prevalence of LVH. In obese patients remaining hypertensive, aggressive pharmacological treatment is therefore indicated to correct LVH.

QT dispersion in uncomplicated human obesity.

OBJECTIVE: Because obese patients generally may be prone to ventricular arrhythmias, this study was designed to measure the interval between Q- and T-waves of the electrocardiogram (QT) interval dispersion (QTD) in uncomplicated overweight and obese patients. QTD is an electrocardiographic parameter whose prolongation is thought to be predictive of the possibility of sudden death caused by ventricular arrhythmias. To better evaluate the association between obesity per se and QTD, the study population was intentionally selected because they were free of complications. RESEARCH METHODS AND PROCEDURES: QTD (defined as the difference between the maximum and the minimum QT corrected interval [QTc] across the 12-lead electrocardiogram) was measured manually in 54 obese patients (Group A: mean body mass index [BMI] of 38.1 +/- 0.9 kg/m2 [SEM], 15 males and 39 females), 35 overweight patients (Group B: mean BMI of 27.3 +/- 0.2 kg/m2, 10 males and 25 females), and 57 normal weight healthy control subjects (Group C: mean BMI of 21.9 +/- 0.2 kg/m2, 17 males and 40 females). The obese and overweight patients had no heart disease, hypertension, diabetes, or impaired glucose tolerance and did not have any hormonal, hepatic, renal or electrolyte disorders. The study subjects were matched in terms of age (mean age 38.4 +/- 1.2 years) and sex. RESULTS: The QTDs were comparable among the three groups: Group A, 56.4 +/- 2.6 ms; Group B, 56.7 +/- 2.1 ms; and Group C, 59.4 +/- 2.1 ms; not significant. The QTc intervals of Group A and Group B were similar to that of Group C (411.8 +/- 3.3, 407.2 +/- 3.9, and 410.3 +/- 3.9 ms, respectively [not significant]) and did not correlate with BMI. An association was found between QTD and QTc (r = 0.24, p < 0.005). Using multivariate stepwise regression analysis of the study population, QTD did not correlate with age, BMI, waist circumference, or abdominal sagittal diameter. DISCUSSION: These data suggest that QTD in uncomplicated obese or overweight subjects is comparable with that in age- and sex-matched normal weight healthy controls. In this study population, no association was found between QTD and anthropometric parameters reflecting body fat distribution.