New insights from continuous glucose monitoring into the route to diabetes.

AIM: Type 2 diabetes mellitus (T2DM) is preceded by a period of impaired glucoregulation. We investigated if continuous glucose monitoring system (CGMS) (1) could improve our capacity to predict the development of T2DM in subjects at risk. (2) Find out if impaired fasting glucose/impaired glucose tolerance differentiation through CGMS would also elucidate differences in clinical phenotypes. MATERIAL AND METHODS: Observational study of 209 hypertensive patients, aged 18 to 85 years who wore at entry a CGMS. Two CGMS metrics, percent of time under the 100 mg/dL glycaemic threshold (TU100) (impaired fasting glucose surrogate phenotype) and area above the 140 mg/dL glycemic threshold (AO140) (impaired glucose tolerance surrogate phenotype) were measured. The median follow-up was 32 months (6-72 mo), and there were 17 new cases of T2DM. RESULTS: In a multivariate Cox proportional hazard survival analysis including the conventional prediabetes-defining criteria and the 2 CGMS-derived variables, only TU100 and HbA1c were significant and independent variables in predicting T2DM development. An increase in 0.1 in TU100 resulted in a 0.69 (95% CI, 0.54-0.88; P < .01) odds ratio of developing T2DM. With cut-off points of 0.5 for TU100 and 5.7% for HbA1c , the test "TU < 0.5 and HbA1c  > 5.7%" had a sensitivity of 0.81 (SD, 0.10), a specificity of 0.83 (SD, 0.03), and a likelihood ratio of 4.82 (SD, 1.03) for T2DM development. CONCLUSIONS: Continuous glucose monitoring system allows for a better T2DM risk-development categorization than fasting glucose and HbA1c in a high-risk population. Continuous glucose monitoring system-derived phenotyping reveals clinical differences, not disclosed by conventional fasting plasma glucose/HbA1c categorization. These differences may correlate with distinct pathophysiological mechanisms.

Glucose time series complexity as a predictor of type 2 diabetes.

BACKGROUND: Complexity analysis of glucose profile may provide valuable information about the gluco-regulatory system. We hypothesized that a complexity metric (detrended fluctuation analysis, DFA) may have a prognostic value for the development of type 2 diabetes in patients at risk. METHODS: A total of 206 patients with any of the following risk factors (1) essential hypertension, (2) obesity or (3) a first-degree relative with a diagnosis of diabetes were included in a survival analysis study for a diagnosis of new onset type 2 diabetes. At inclusion, a glucometry by means of a Continuous Glucose Monitoring System was performed, and DFA was calculated for a 24-h glucose time series. Patients were then followed up every 6 months, controlling for the development of diabetes. RESULTS: In a median follow-up of 18 months, there were 18 new cases of diabetes (58.5 cases/1000 patient-years). DFA was a significant predictor for the development of diabetes, with ten events in the highest quartile versus one in the lowest (log-rank test chi2 = 9, df = 1, p = 0.003), even after adjusting for other relevant clinical and biochemical variables. In a Cox model, the risk of diabetes development increased 2.8 times for every 0.1 DFA units. In a multivariate analysis, only fasting glucose, HbA1c and DFA emerged as significant factors. CONCLUSIONS: Detrended fluctuation analysis significantly performed as a harbinger of type 2 diabetes development in a high-risk population. Complexity analysis may help in targeting patients who could be candidates for intensified treatment. Copyright © 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

Acetaldehyde content and oxidative stress in the deleterious effects of alcohol drinking on rat uterine horn.

After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a severe atrophy in the rat uteirne horn was observed, accompanied by significant alterations in its epithelial cells. Microsomal pathway of acetaldehyde production was slightly increased. Hydroxyl radicals were detected in the cytosolic fraction, and this was attributed to participation of xanthine oxidoreductase. They were also observed in the microsomal fraction in the presence of NADPH generating system. No generation of 1-hydroxyethyl was evidenced. The t-butylhydroperoxide-induced chemiluminescence analysis of uterine horn homogenates revealed a significant increase in the chemiluminiscence emission due to ethanol exposure. In the animals repeatedly exposed to alcohol, sulfhydryl content from uterine horn proteins was decreased, but no significant changes were observed in the protein carbonyl content from the same samples. Minor but significant decreasing changes were observed in the GSH content accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant finding was the diminished activity content of glutathione peroxidase. Results suggest that acetaldehyde accumulation plus the oxidative stress may play an additional effect to the alcohol-promoted hormonal changes in the uterus reported by others after chronic exposure to alcohol.

Metabolism of ethanol to acetaldehyde and increased susceptibility to oxidative stress could play a role in the ovarian tissue cell injury promoted by alcohol drinking.

It is known that drinking alcohol can lead to reproductive problems in women. In this study, we analyzed the possibility that part of those effects were mediated through alterations of ovarian function related to ethanol oxidation to acetaldehyde occurring in situ. Biotransformation in the rat ovary cytosolic fraction was partially inhibited by allopurinol, suggesting the participation of xanthine oxidoreductase in the process. Microsomal pathway was of enzymatic nature, requiring nicotinamide adenine dinucleotide phosphate-oxidase (NADPH), sensitive to oxygen and significantly inhibited by sodium diethyldithiocarbamate, 4-methylpyrazole and diphenyleneiodonium. Aldehyde dehydrogenase activity was detected by histochemistry in the ovarian tissue, in the strome surrounding the follicle while no alcohol dehydrogenase was detected. However, biochemical determination of alcohol dehydrogenase and aldehyde dehydrogenase activities in rat ovarian tissue revealed the presence of some activity of both enzymes but significantly lower than those found in the liver. By repetitive exposure of animals to ethanol, the microsomal metabolism to acetaldehyde was increased but not in the case of the cytosolic fraction. In these animals, t-butylhydroperoxyde-promoted chemiluminiscence was increased in comparison to control, revealing an increased susceptibility to oxidative stress due to alcohol drinking. Ultrastructure of ovarian tissue from rats exposed chronically to alcohol revealed alterations at the level of the granulosa; theca interna and pellucida zones. In the secondary follicle, alterations consisted of marked condensation of chromatin attached to the nuclear inner membrane. Intense dilatation of the outer perinuclear space could be observed. There was a marked dilatation of the rough endoplasmic reticulum accompanied of significant detachment of ribosomes from their membranes. Mitochondria appeared swollen. In the zona pellucida, most of the cell processes from oocyte and corona radiata cells were absent or broken totally or in part. Results suggest that in the rat ovary, metabolism of ethanol to acetaldehyde may play a role in alcohol effects on female reproductive function.

Aplicación de la telemedicina al control de enfermedades crónicas: telecontrol de pacientes con enfermedad pulmonar obstructiva crónica / Usefulness of telemedicine in chronic diseases: home tele-care of patient with chronic obstructive pulmonary disease

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