RESUMEN
BACKGROUND: Obesity is a potential risk factor for development of type 2 diabetes mellitus (T2DM). To achieve long-term weight reduction in patients with T2DM and obesity using comprehensive lifestyle management program (LMP). MATERIALS AND METHODS: This 48-week interventional, multicenter, parallel-group, open-label study included patients aged ≥18 years with T2DM and a body mass index (BMI) of 27-40 kg/m2. The primary objective was to demonstrate a clinically significant weight reduction (≥5%) from baseline in intensive lifestyle modification (ILM) and standard treatment (ST) groups. RESULTS: The ILM group (N = 100) received recommendations for dietary and physical activity, and behavioral counseling. The ST group (N = 30) was managed in accordance with routine T2DM clinical practice. The patients in ST group were older (60.6 ± 8.9 vs. 54.6 ± 10.2 years in ILM group); overall more than 60% were women. At Week 48, the mean reduction in body weight was 5.8% (95% confidence interval [CI]: -6.9, -4.6) and 1.2% (95% CI: -2.6, 0.2) (p < 0.001) in the ILM and ST group, respectively. At Week 48, a weight loss of ≥5% was achieved by 50% of patients in the ILM group versus 13.3% in the ST group (p = 0.002). The decreases in BMI, waist-to-hip ratio and glycated hemoglobin (HbA1c) was significantly greater in the ILM versus ST group with between-group differences of -1.63 (p ≤ 0.001), -0.03 (Ñ ≤ 0.001) and -0.69% (p = 0.002), respectively. CONCLUSION: A clinically significant weight reduction (≥5%) was demonstrated in patients with obesity and T2DM with use of a comprehensive LMP, along with improvements in BMI, waist-to-hip ratio, and HbA1c.
RESUMEN
Supplementation of micronutrients like folate is a double-edged sword in terms of their ambivalent role in cell metabolism. Although several epidemiological studies support a protective role of folate in carcinogenesis, there are also data arguing for an opposite effect. To address this issue in the context of human papillomavirus (HPV)-induced transformation, the molecular events of different folate availability on human keratinocytes immortalized by HPV16 E6 and E7 oncoproteins were examined. Several sublines were established: Control (4.5 µM folate), folate deficient (0.002 µM folate), and repleted cells (4.5 µM folate). Cells were analyzed in terms of oncogene expression, DNA damage and repair, karyotype changes, whole-genome sequencing, and transcriptomics. Here we show that folate depletion irreversibly induces DNA damage, impairment of DNA repair fidelity, and unique chromosomal alterations. Repleted cells additionally underwent growth advantage and enhanced clonogenicity, while the above mentioned impaired molecular properties became even more pronounced. Overall, it appears that a period of folate deficiency followed by repletion can shape immortalized cells toward an anomalous phenotype, thereby potentially contributing to carcinogenesis. These observations should elicit questions and inquiries for broader additional studies regarding folate fortification programs, especially in developing countries with micronutrient deficiencies and high HPV prevalence.
