Serum leptin level and microvascular complications in type 2 diabetes

Background. Type 2 diabetes (T2DM) and its complications are highly prevalent in Egypt and are considered a major health problem. Insulin resistance arising from visceral obesity is the main pathological mechanism of T2DM. Leptin is an adipokine secreted from visceral adipose tissue and its level is proved to be higher in patients with T2DM, but its association with microvascular complications is not yet well-established, for this aim the present study was conducted. Methods. This cross-sectional study was conducted among 120 participants with T2DM recruited from the diabetes outpatient clinic of Alexandria Main Uni­versity Hospital, Alexandria, Egypt. Each participant was subjected to full history taking, complete physical examination and laboratory investigations. Results. Serum leptin level was significantly positively correlated with diabetes duration, BMI, WC, systolic and diastolic blood pressure, FPG, HbA1c, serum insu­lin level, HOMA-IR, total cholesterol, triglycerides and LDL-C. Regarding microvascular complications, serum leptin level was highly significantly positively correlated with UACR, peripheral neuropathy and retinopathy (P < 0.001) and significantly negatively correlated with e-GFR (P = 0.003). Conclusions. Serum leptin level is significantly correlated with microvascular complications in patients with T2DM in Alexandria, Egypt

Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease

Extreme obesity (EO, BMI>50) is frequently associated with neuropsychiatric disease (NPD). As both EO and NPD are heritable central nervous system disorders, we assessed the prevalence of protein truncating (PTV) and copy number variants (CNV) in genes/regions previously implicated in NPD, in adults with EO (n=149) referred for weight loss/bariatric surgery. We also assessed the prevalence of CNVs in patients referred to University College London Hospital (UCLH) with EO (n=218) and obesity (O, BMI 35-50, n=374) and a Swedish cohort of participants from the community with predominantly O (n=161). The prevalence of variants was compared to controls in ExAC/gnomAd database. In the discovery cohort (high NPD prevalence: 77%), the cumulative PTV/CNV allele frequency (AF) was 7.7 % vs 2.6% in controls (Odds Ratio (OR) 3.1, (95% CI 2-4.1, p<0.0001). In the UCLH EO cohort (intermediate NPD prevalence: 47%), CNV AF (1.8% vs 0.9% in controls, OR 1.95, 95% CI 0.96-3.93, p=0.06) was lower than the discovery cohort. CNV AF was not increased in the UCLH O cohort (0.8%). No CNVs were identified in the Swedish cohort with no NPD. These findings suggest PTV/CNVs, in genes/regions previously associated with NPD, may contribute to NPD in patients with EO

Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery

The prevalence of severe obesity, defined as body mass index (BMI) ≥35.0 kg/m2, is rising rapidly. Given the disproportionately high health burden and healthcare costs associated with this condition, understanding the underlying aetiology, including predisposing genetic factors, is a biomedical research priority. Previous studies have suggested that severe obesity represents an extreme tail of the population BMI variation, reflecting shared genetic factors operating across the spectrum. Here, we sought to determine whether a panel of 32 known common obesity-susceptibility variants contribute to severe obesity in patients (n = 1,003, mean BMI 48.4±8.1 kg/m2) attending bariatric surgery clinics in two European centres. We examined the effects of these 32 common variants on obesity risk and BMI, both as individual markers and in combination as a genetic risk score, in a comparison with normal-weight controls (n = 1,809, BMI 18.0–24.9 kg/m2); an approach which, to our knowledge, has not been previously undertaken in the setting of a bariatric clinic. We found strong associations with severe obesity for SNP rs9939609 within the FTO gene (P = 9.3×10−8) and SNP rs2815752 near the NEGR1 gene (P = 3.6×10−4), and directionally consistent nominal associations (P&lt;0.05) for 12 other SNPs. The genetic risk score associated with severe obesity (P = 8.3×10−11) but, within the bariatric cohort, this score did not associate with BMI itself (P = 0.264). Our results show significant effects of individual BMI-associated common variants within a relatively small sample size of bariatric patients. Furthermore, the burden of such low-penetrant risk alleles contributes to severe obesity in this population. Our findings support that severe obesity observed in bariatric patients represents an extreme tail of the population BMI variation. Moreover, future genetic studies focused on bariatric patients may provide valuable insights into the pathogenesis of obesity at a population level