The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects

We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35–2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13–2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14–3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10–6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10–5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.

Appropriate Timing of Gestational Diabetes Mellitus Diagnosis in Medium- and Low-Risk Women: Effectiveness of the Italian NHS Recommendations in Preventing Fetal Macrosomia

Background. Screening strategies for gestational diabetes mellitus (GDM) earlier than 24-28 weeks of gestation should be considered to prevent adverse pregnancy outcomes. Nonetheless, there is uncertainty about which women would benefit most from early screening and which screening strategies should be offered to women with GDM. The Italian National Healthcare Service (NHS) recommendations on selective screening for GDM at 16-18 weeks of gestation are effective in preventing fetal macrosomia in high-risk (HR) women, but the appropriateness of timing and effectiveness of these recommendations in medium- (MR) and low-risk (LR) women are still controversial. Patients and Methods. We retrospectively enrolled 769 consecutive singleton pregnant women who underwent both anomaly scan at 19-21 weeks of gestation and screening for GDM at 16-18 and/or 24-28 weeks of gestation, in agreement with the NHS recommendations and risk stratification criteria. Comparison of maternal characteristics, fetal biometric parameters at anomaly scan (head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW)), and neonatal birth weight (BW) percentile among risk groups was examined. Results. 219 (28.5%) women were diagnosed with GDM, while 550 (71.5%) were normal glucose-tolerant women. Out of 164 HR women, only 62 (37.8%) underwent the recommended early screening for GDM at 16-18 weeks of gestation. AC and EFW percentiles, as well as neonates’ BW percentiles, were significantly higher in HR women diagnosed with GDM at 24-28 weeks of gestation with respect to normal glucose-tolerant women, as well as MR and LR women who tested positive for GDM. Comparative analysis between MR and LR women with GDM and women with normal glucose tolerance revealed significant differences in both AC and EFW percentiles (P<0.05), while there was no significant difference in neonatal BW percentiles. Conclusion. In MR and LR women with GDM, a mild acceleration of fetal growth can be detected at the time of anomaly scan. However, in these at-risk categories, the NHS recommendations for screening and treatment of GDM at 24-28 weeks of gestation are still effective in normalizing BW and preventing fetal macrosomia, thus supporting a risk factor-based selective screening program for GDM.

Influence of Age, Sex and Body Mass Index on the Levels of Glycosylated Haemoglobin among Non-Diabetic Nigerian Population

The influence of age and sex on the levels of glycosylated haemoglobin among non-diabetic Nigerian population were investigated in this study. Seventy-nine non-diabetic individuals volunteered for the study and were grouped into male and female and then into four groups according to age: ≤ 20 years, 21 - 40 years, 41 - 60 years and ≥ 61 years. Fasting blood glucose, 2-hour post-load glucose, packed cell volume and genotype analyses of subjects were initially determined to ensure that subjects were non-diabetic and had no glucose metabolic impairment. Subsequently, glycosylated haemoglobin and body mass index were measured. Student’s t-test, Pearson correlation and one-way analysis of variance were used to compare the data which were presented as a mean ± standard deviation. Statistical significance was accepted at p ˂ 0.05. The results obtained showed that: (1) glycosylated haemoglobin (HbA1c) significantly increased with age, (2) there is no correlation between HbA1c with sex and (3) there was a positive association between Hba1c and body mass index in normal glucose tolerant subjects. Based on the result of this study, the contributions of age and BMI to HbA1c levels should be taking into account when making diagnostic and therapeutic decisions with regard to diabetes care using HbA1c. The hba1c range of (4.0 - 5.2) % could be considered as the normal range for individuals below sixty-one years while the HbA1c level of ≤ 5.27% is suggested for individuals above sixty years. However, further studies are required especially to investigate the non-glycaemic factors affecting HbA1c levels in normal glucose tolerant populations so as to really understand the actual role glycosylated haemoglobin values play in diabetes management and diagnosis.