Association of Apelin Levels in Overweight-obese Children with Pubertal Development, but Not with Insulin Sensitivity: 6.5 Years Follow up Evaluation.

BACKGROUND: Obesity in youth is associated with increased risk of metabolic disorders. Adipose tissue hormones are involved in body-weight regulation. Among these, apelin is recognized as an insulin-sensitizer adipokine. Data on apelin levels in obese children and its relation to insulin-sensitivity are limited. OBJECTIVE: We aimed to evaluate apelin levels in relation to obesity and insulin sensitivity in a large cohort of overweight/obese children and adolescents. Furthermore, these youths were reevaluated after a median 6.5 years of follow-up, thus allowing assessing changes in apelin levels in relation to increasing age and weight changes. METHODS: Clinical data in 909 children and adolescents were collected between 2007 and 2010. Two hundred and one were reexamined at a median 6.5 years of follow-up. All subjects at baseline and at follow-up underwent an OGTT. Apelin levels were measured on sera by ELISA method. RESULTS: At baseline, lower apelin levels were associated with increasing age and puberty (Tanner ≥II 0.67 ± 0.96 ng/mL vs. Tanner I 0.89 ± 1.13 ng/mL, p < .002), but not with body-weight. At follow-up, apelin levels in the 201 subjects reexamined were significantly lower than at baseline (0.45 ± 0.77 ng/mL at follow-up, 0.68 ± 0.95 ng/mL baseline, p < .001), confirming the effects of age and puberty. Body-weight did not affect apelin levels. Multiple regression analysis confirmed that sex and puberty were associated with lower apelin levels, independently from age and insulin-sensitivity. CONCLUSIONS: Apelin levels decrease significantly with pubertal development, whilst body-weight in children and adolescents did not determine changes in apelin. Reduced levels of apelin in children and adolescents may therefore represent a necessary response to maintain the "physiological" insulin resistance of puberty. Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; G: glucose; BMI: Body mass index; DBP: Diastolic blood pressure; ELISA: enzyme-linked immunosorbent assay; HDL-C: High-density lipoprotein-cholesterol; HOMA-B: Homeostatic model assessment for beta-cell function; HOMA-IR: Homeostatic model assessment of insulin-resistance; INS: Insulin; ISI: insulin-sensitivity index; LDL-C: Low-density lipoprotein cholesterol; NW: normal weight; OB: obese; OGTT: oral glucose tolerance test; OW: overweight; SBP: Systolic blood pressure; TC: Total cholesterol; TGs: Triglycerides.

AN ITALIAN SURVEY OF COMPLIANCE WITH MAJOR GUIDELINES FOR L-THYROXINE OF PRIMARY HYPOTHYROIDISM.

OBJECTIVE: The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment. METHODS: This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology. RESULTS: The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers. CONCLUSION: Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography.

The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects.

BACKGROUND: Perilipin 2 (PLIN2), a member of the family of perilipin lipid droplets coating proteins, is very widely expressed. The Ser251Pro (rs35568725) missense mutation in exon 6 of PLIN2 gene was previously associated with increased lipid accumulation, decreased lipolysis and increased number of small lipid droplets per cell. Furthermore, the Pro251 mutation was associated with decreased plasma triglyceride and very low density lipoprotein concentrations in population studies. The aim of this study was to evaluate the effect of the Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to obesity-associated metabolic alterations, such as insulin resistance, decreased insulin-secretion, hyperglycaemia, and dyslipidaemia. METHODS: A large cohort (N = 1692) of Italian obese subjects (mean body mass index = 41 kg/m(2) ) was genotyped for the Ser251Pro mutation. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance and of insulin secretion were also calculated. Clinical and biochemical parameters were collected for all participants. RESULTS: We observed that insulin concentration was significantly reduced at 120 min after the administration of glucose in Pro251 allele carriers, whereas glucose levels were similar in Pro251 allele carriers and non-carriers throughout the OGTT. Furthermore, the CIR120 index of insulin secretion was significantly lower (P < 0.035) and the ISI index of insulin-sensitivity was significantly higher (P < 0.031) in carriers of the Pro251 allele. When we analysed men and women separately to test for gender-specific associations, we observed that in women insulin levels were significantly lower in Pro251 allele carriers compared with wild-type subjects throughout the whole OGTT. In men, we confirmed a significant reduction in insulin concentration only at 120 min after the OGTT. No significant differences between genotype groups regarding triglyceride levels and anyother clinical and metabolic parameters were observed. CONCLUSION: We observed a strong significant association between the PLIN2 Pro251 mutation and lower insulin secretion associated with an increased insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.

Glycated hemoglobin for the diagnosis of diabetes and prediabetes: Diagnostic impact on obese and lean subjects, and phenotypic characterization.

AIMS/INTRODUCTION: Measurement of glycated hemoglobin (HbA1c) has been recommended for the diagnosis of diabetes and prediabetes. However, epidemiological studies have shown significant discordance between HbA1c and glucose-based tests. Of the factors that could influence agreement between HbA1c and the oral glucose tolerance test (OGTT), bodyweight has not been fully evaluated. The aims of the present study were to evaluate the impact of HbA1c criteria to diagnose diabetes and prediabetes compared with OGTT, and to examine HbA1c in relation to body mass index. MATERIALS AND METHODS: Two cohorts were studied, one from an obesity clinic (n = 592) and one from subjects undergoing screening for diabetes (n = 462). All underwent OGTT and HbA1c measurement. RESULTS: In the obese cohort, HbA1c ≥6.5% (≥48 mmol/mol) showed a sensitivity of 69.3% for diabetes, whereas HbA1c 5.7-6.4% (39-46 mmol/mol) did not identify prediabetes well (sensitivity 39.1%). In the diabetes screening cohort, HbA1c had low sensitivities for both diabetes (39.2%) and prediabetes (53.3%). When participants were stratified according to body mass index class I-III, HbA1c agreement with the OGTT for diabetes was much higher (80%, P < 0.005) in class I obesity compared with class II-III obesity; whereas for prediabetes, HbA1c had a low sensitivity in all obesity classes. CONCLUSIONS: The agreement between HbA1c, fasting plasma glucose and 2-h glucose post-OGTT for the diagnosis of prediabetes was poor in our Italian population; whereas HbA1c ≥6.5% showed a relatively good agreement with OGTT for the diagnosis of diabetes. For the first time, we have shown that obesity class influences the diagnostic performance of HbA1c.