RESUMO
Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic ß-cell function (Pßf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes. These treatments increased the abundance of GM SCFA-producing bacteria M (Fusicatenibacter and Blautia) and LM (Roseburia, Bifidobacterium, and [Eubacterium] hallii group). We performed a mediation analysis with structural equation models (SEM). In conclusion, M and LM therapies improve insulin sensitivity and Pßf in prediabetics. GM is partially associated with these improvements since the SEM models suggest a weak association between specific bacterial genera and improvements in IS and Pßf.
Assuntos
Microbioma Gastrointestinal , Linagliptina , Metformina , Estado Pré-Diabético , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Linagliptina/uso terapêutico , Linagliptina/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Adulto , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , IdosoRESUMO
Objective: To assess insulin sensitivity and pancreatic ß-cell function in an adult population of Ecuadorian individuals with Turner syndrome (TS). Design and Methods: This was a cross-sectional correlational study conducted in TS subjects (>20 years old; n = 38). A standard 2-h oral glucose tolerance test was performed in both women with TS and the reference group. Glucose, lipids, insulin, and C-peptide concentrations were measured. Homeostasis Model Assessment (HOMA) of Insulin Resistance, Quantitative Insulin Sensitivity Check Index, McAuley, Matsuda, and Belfiore indices were calculated to evaluate the degree of insulin resistance (IR). The pancreatic ß-cell function was assessed using HOMA-ß, basal C-Peptide Index (CPI), and CPII at 120'. Results: A higher prevalence of impaired glucose tolerance was found in TS subjects compared with the reference group. Although significant differences were found for glucose concentrations at 60' and 120' (but not at 0'), only the baseline insulin concentrations differed significantly between the two groups. The values of the IR indices were statistically different between study and reference groups. A significant number of TS subjects diagnosed with IR were differently classified according to the index applied. The concentrations of C-peptide at 0' and 120' of TS subjects were similar to those of the control group. In contrast, the CPI and CPII values in the study group were significantly lower than those in the control group. Conclusion: It is impossible to select the best surrogate method for the assessment of IR in women with TS. The CPI and CPII values could be preferable to other indices to assess the pancreatic ß-cell function in TS subjects. Our findings suggest that IR and pancreatic ß-cell dysfunction could be independent events in women with TS, and both conditions seem to be caused by the disease per se. Our results imply that early screening and intervention for TS would be therapeutic for TS women.
Assuntos
Índice de Massa Corporal , Intolerância à Glucose/epidemiologia , Resistência à Insulina , Células Secretoras de Insulina/patologia , Síndrome de Turner/fisiopatologia , Adulto , Estudos Transversais , Equador/epidemiologia , Feminino , HumanosRESUMO
OBJECTIVES: Reduced gene expression of PPARGC1A in subjects with insulin resistance (IR) has been reported. Insulin resistance occurs early on the course of Turner syndrome (TS). The main objective of this study was to evaluate the relationship between PPARGC1A promoter DNA methylation status in lymphocytes and insulin sensitivity and secretion in Ecuadorian females with TS. METHODS: We examined a cohort of 34 Ecuadorian patients with TS along with a sex-, age- and BMI-matched reference group. All subjects received a standard 75 g oral glucose tolerance test. Insulin resistance and secretion indices were calculated. The PPARGC1A methylated DNA/unmethylated DNA ratio and mitochondrial content (mtDNA/nDNA ratio) were further determined. RESULTS: Notably, the PPARGC1A DNA methylation level was significantly higher in TS subjects than the reference group and correlated with IR indices. Conversely, mitochondrial content was significantly lower in the study group than healthy controls and negatively correlated with the PPARGC1A methylated DNA/unmethylated DNA ratio in TS individuals. PPARGC1A promoter DNA methylation status contributed to 20% of the total variability in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) independently of BMI or age in TS subjects. CONCLUSIONS: Our collective findings suggest that expression of PPARGC1A and lower mitochondrial number affect the metabolic phenotype in TS subjects.