A haplotype in the dipeptidyl peptidase 4 gene impacts glycemic-related traits of Brazilian older adults.

Dipeptidyl peptidase 4 (DPP4) regulates various physiological pathways and has a pivotal role in glucose homeostasis. The objective of this study was to verify the association of a haplotype constituted by two single nucleotide polymorphisms (rs2268894 and rs6741949) in the DPP4 gene with type 2 diabetes mellitus (T2DM) and fasting glycemia-related variables in a sample of Brazilian older adults, taking serum levels and enzymatic activity of DPP4 into account. Clinical, biochemical, and anthropometric characteristics as well as DPP4 serum levels and enzymatic activity were determined in 800 elderly (≥60 years old) individuals. Assessment of polymorphic sites was performed by real-time PCR whereas haplotypes were inferred from genotypic frequencies. Statistical analyses compared measures and proportions according to T2DM diagnosis and DPP4 haplotypic groups. The most common haplotype consisted of the T-rs2268894/G-rs6741949 string, which was 20% more frequent among non-diabetics. Considering non-diabetic patients alone, carriers of the T/G haplotype had significantly lower levels of blood glucose, insulin, HOMA-IR index, and DPP4 activity. Among diabetic patients, the T/G haplotype was associated with lower DPP4 levels whereas glycemic scores were not affected by allelic variants. Our results suggested that the genetic architecture of DPP4 affects the glycemic profile and DPP4 serum levels and activity among elderly individuals according to the presence or absence of T2DM, with a possible implication of the T/G haplotype to the risk of T2DM onset.

A haplotype in the dipeptidyl peptidase 4 gene impacts glycemic-related traits of Brazilian older adults

Dipeptidyl peptidase 4 (DPP4) regulates various physiological pathways and has a pivotal role in glucose homeostasis. The objective of this study was to verify the association of a haplotype constituted by two single nucleotide polymorphisms (rs2268894 and rs6741949) in the DPP4 gene with type 2 diabetes mellitus (T2DM) and fasting glycemia-related variables in a sample of Brazilian older adults, taking serum levels and enzymatic activity of DPP4 into account. Clinical, biochemical, and anthropometric characteristics as well as DPP4 serum levels and enzymatic activity were determined in 800 elderly (≥60 years old) individuals. Assessment of polymorphic sites was performed by real-time PCR whereas haplotypes were inferred from genotypic frequencies. Statistical analyses compared measures and proportions according to T2DM diagnosis and DPP4 haplotypic groups. The most common haplotype consisted of the T-rs2268894/G-rs6741949 string, which was 20% more frequent among non-diabetics. Considering non-diabetic patients alone, carriers of the T/G haplotype had significantly lower levels of blood glucose, insulin, HOMA-IR index, and DPP4 activity. Among diabetic patients, the T/G haplotype was associated with lower DPP4 levels whereas glycemic scores were not affected by allelic variants. Our results suggested that the genetic architecture of DPP4 affects the glycemic profile and DPP4 serum levels and activity among elderly individuals according to the presence or absence of T2DM, with a possible implication of the T/G haplotype to the risk of T2DM onset.

Muscle Quality Is Associated with History of Falls in Octogenarians.

OBJECTIVES: The aim of this study was to compare muscle quality (MQ) between octogenarians classified as non-fallers, fallers and recurrent fallers and identify confounding intrinsic and extrensic factors that impact likelihood for falls. DESIGN: This observational, descriptive, cross-sectional study included older adults (N=220) aged 80 years or older. MEASUREMENTS: The Short Physical Performance Battery (SPPB) was used to evaluate physical function and MQ was calculated using the ratio of grip strength to arm muscle mass (in kilograms) quantified by DXA. Variables related to sociodemographic, clinical, cognitive function, and falls were evaluated using a questionnaire and symptoms of depression were evaluated by the Geriatric Depression Scale (GDS). A Kruskal-Wallis H test was used to verify differences between groups. Binomial logistic regression was performed to determine the impact of age, depression, polypharmacy, balance, MQ, and sex on participants having more than four falls in their history. RESULTS: Increasing MQ was associated with reduced likelihood of more than four falls in their history. Non-fallers were statistically younger (p = 0.012) and took more medications (p = 0.023) than recurrent fallers. Recurrent fallers had lower MQ when compared with fallers (p = 0.007) and non-fallers (p = 0.001) and had a lower GDS score when compared with fallers (p = 0.022). Finally, fallers presented lower scores for balance when compared to non-fallers (p = 0.013). CONCLUSION: A higher MQ is associated with a reduction in the likelihood falls in octogenarians. Therefore, it may be advantageous for clinicians to evaluate MQ when the screening of the risk of falls in older adults.

Cytotoxic Effect of Prodigiosin, Natural Red Pigment, Isolated from Serratia marcescens UFPEDA 398.

Prodigiosin is a secondary metabolite, with red pigmentation, produced by Serratia marcescens. Red pigment is a natural alkaloid whose chemical structure has three pyrrole rings. Prodigiosin has been described for several biological activities, including antitumor, inducing apotosis in T and B lymphocytes. This work aimed to evaluate the cytotoxic activity of prodigiosin in NCHI-292, HEp-2, MCF-7 and HL-60 tumor cell lines. The red pigment was isolated from Serratia marcescens UFPEDA 398 biomass whose fractions were previously separated by column chromatography, purified, identified and further characterized by GC-MS and compared with the computerized library of m/z values. The pigment corresponded to prodigiosin with maximum absorption at 534 nm, molecular weight 323 and structural formula C20H25N3O. During the prodigiosin purification process a purple absorbance fraction at 272.65 nm was also observed. Significant cytotoxic effects of prodigiosin were evidenced for NCHI-292, Hep-2, MCF-7 and HL-60 tumor cell lines. The isolated purple fraction had no cytotoxic effect (IC50 11.3 µg/mL) when compared to prodigiosin (IC50 3.4 µg/mL) for the tumor cell lines studied. The MCF-7 strain was slightly more pigment resistant (IC50 5.1 µg/mL). Therefore, further studies will be needed to elucidate the antitumor mechanisms of prodigiosin action against tumor strains from flow cytometry tests. However, although these data are preliminary, it was evidenced that prodigiosin showed cytotoxic activity in tumor cell lines suggesting promising antitumor properties. In this sense, future studies on the cytotoxic and genotoxic effects of prodigiosin produced by S. marcecsens UFPEDA 398 are suggested.