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Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants.We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits.Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits.Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.

We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet (OPOD) in morbidly obese patients with and without type 2 diabetes mellitus (T2DM) scheduled for laparoscopic bariatric surgery. Fifty patients (body mass index 53.5 ± 8.4 kg/m2) scheduled for bariatric surgery, including 14 with T2DM, were prospectively enrolled and followed the OPOD regimen: a very low-calorie ketogenic diet for 10 days, followed by a very low-calorie diet for 10 days, and then a low-calorie diet for 10 days. Patients were evaluated at baseline (T0) and after 10 days (T1), 20 days (T2), and 30 days (T3). Body weight, body mass index, waist circumference, and neck circumference were significantly lower at T1, T2, and T3 than at T0 in the 48 patients who completed the OPOD. Two patients discontinued the OPOD after 4–7 days. In patients with T2DM, fasting plasma glucose levels decreased significantly, enabling reduction of diabetic medications. Plasma and urine ketone levels increased at T1 but were all

The study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient to better clarify the remission of diabetes. In this study, we found that the diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even if they showed a normal fasting glycemia and A1c, patients spent a lot of time in hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia, even if they showed a normal glycemia (

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available onFTOin the Italian population. Aims of our study are to investigate: (1) the association ofFTOgene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n=752) of Italian obese subjects; (2) the association between the twoFTOSNPs and age of onset of obesity. Our results demonstrate a strong association betweenFTOSNPs rs9939609 (P<0.043) and rs9930506 (P<0.029) with BMI in the Italian population.FTOrs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI+1.4 kg/m2per G allele). We also observed that the association with BMI of the twoFTOvariants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability inFTOon BMI in a large Italian population.

Background Type 2 diabetes mellitus (T2DM) and obesity are diseases of epidemic proportions. Long-term realistic weight loss by nonsurgical methods has a variable effect on glycemic control, and only a proportion of patients with T2DM have a worthwhile response. Laparoscopic sleeve gastrectomy (LSG) has been proposed as an advantageous bariatric procedure for patients with a lower body mass index (BMI). Our objective was to compare the effects of LSG and medical therapy on patients with T2DM and a BMI of 2 . Methods A total of 18 nonmorbidly obese patients with T2DM, diagnosed according to the American Diabetes Association guidelines, were consecutively enrolled. Of these patients, 9 underwent LSG (group A) and 9 underwent conventional medical therapy (group B). The 2 groups were matched for BMI, glycated hemoglobin (HbA1c) and C-peptide levels, pretrial therapy type, and number of patients with a T2DM duration of >10 years. Results In group A, T2DM resolution was achieved in 8 (88.8%) of the 9 patients (T2DM duration 5.2 yr). Hypertension was controlled in all 8 of 9 patients. Dyslipidemia was corrected. In 1 patient, obstructive sleep apnea syndrome improved. In group B, all 9 patients continued to have T2DM and required hypertensive and hypolipemic therapies throughout the observation period. At baseline, 3 patients were affected by obstructive sleep apnea syndrome and remained affected 1 year later. Conclusion The results of the present study have confirmed the efficacy of LSG in the treatment of nonmorbidly obese T2DM patients, with a remission rate of 88.8% without undesirable excessive weight loss. The results in this group of patients add to those obtained by us in patients with a BMI >35 kg/m 2 .