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Byskov Gordon opublikował 1 rok, 3 miesiące temu
Treatment of adults with empagliflozin within 100 days of T1D diagnosis appeared safe and was associated with improved clinical outcomes. These findings justify a definitive trial to determine if SGLT inhibitors simplify treatment regimens and improve clinical outcomes in recent-onset T1D.
ACTRN12617000016336.
ACTRN12617000016336.
Beyond the immediate toll of injuries and deaths, major disasters are often associated with long-term increased risks of chronic disease. We sought to investigate the incidence of metabolic syndrome (MetS) among survivors of the 2011 Great East Japan Earthquake and tsunami.
Subjects aged ≥18 years from the tsunami-stricken area participated in a prospective cohort study of disaster survivors (the RIAS Study) from 2011 to 2015. After excluding subjects who were previously diagnosed with MetS, we observed the cumulative incidence of MetS across four annual examinations among 7318 subjects (mean age, 59.8 years; 43.5% men). We defined MetS using the International Diabetes Foundation criteria.
The 4-year cumulative incidence of MetS was 18.0% in the overall sample. The incidence was significantly higher among older women survivors relocated to prefabricated temporary housing (40.9%, 95% confidence interval, 36.4-44.6), and other types of housing (36.2%, 95% CI 32.3-40.6) compared to those who were not relocated (34.1%, 95% CI 30.9-37.4). An increase in incidence of MetS was not observed for older men, or younger survivors aged ≤64 years.
Relocation to prefabricated temporary housing was a risk factor for increased incidence of MetS in older women.
Relocation to prefabricated temporary housing was a risk factor for increased incidence of MetS in older women.
To assess whether meeting both fasting plasma glucose (FPG) and HbA1c criteria for prediabetes in people at high risk indicates with near certainty the presence of dysglycemia on repeat testing.
Observational study using data from Vitamin D and Type 2 Diabetes (D2d) study. HbA1c, FPG were measured at screening visit 1; FPG, HbA1c and 2 h plasma glucose (2hPG) measured at screening visit 2 (a median of 21 days later); participants classified as having normal glucose regulation (all 3 tests in normal range), prediabetes or diabetes (at least 1 of 3 tests in diabetes range). A predictive model was developed to estimate the probability of confirming dysglycemia and for detecting diabetes at screening visit 2 based on values of FPG and HbA1c at screening visit 1.
Of 1271 participants who met both FPG and HbA1c criteria for prediabetes at screening visit 1, 98.6% exhibited dysglycemia (defined as prediabetes or diabetes) on repeat testing (84.5% were classified as having prediabetes, 14.1% were reclassified as having diabetes). Of those with diabetes, 62.6% were identified by 2hPG alone.
Combined measurement of FPG and HbA1c is a reliable and reproducible measure to identify presence of dysglycemia among people at high risk. A prediction model is provided to help clinicians decide whether an oral glucose tolerance test will provide value in detecting diabetes based on the 2hPG criterion.
Combined measurement of FPG and HbA1c is a reliable and reproducible measure to identify presence of dysglycemia among people at high risk. A prediction model is provided to help clinicians decide whether an oral glucose tolerance test will provide value in detecting diabetes based on the 2hPG criterion.Stimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achieve this, 3T3-L1 adipocytes were exposed to 0.75 mM palmitate for 24 h, to induce insulin resistance, before treatment with 10 μM isoorientin or the comparative controls such as CL-316,243 (10 μM), pioglitazone (10 μM) and compound C (1 μM) for 4 h. Relevant bioassays and Western blot analysis were conducted on these insulin resistant cells. Our results showed that palmitate exposure could induce insulin resistance and mitochondrial dysfunction as measured by reduction in glucose uptake and impaired mitochondrial bioenergetics parameters. However, treatment with isoorientin reversed these effects by improving glucose uptake, blocking lipid accumulation, and modulating the process of mitochondrial respiration. Mechanistically, isoorientin could mediate lipid metabolism by activating 5′ AMP-activated protein kinase (AMPK), while also effectively modulating the expression of genes involved in fat browning such as peroxisome proliferator-activated receptor gamma (PPAR)γ/α and uncoupling protein 1 (UCP1). In conclusion, isoorientin impacts insulin resistance in vitro by improving glucose uptake and mitochondrial function, consistent to modulating the expression of genes involved in energy metabolism and fat browning.Sympathomimetics are effective, centrally acting drugs that induce weight loss through their potent anorexic and locomotor properties. We reported that sympathomimetics antagonize catecholamine-dependent, alpha-2 adrenergic receptor-dependent signal transduction mediated by chloride/bicarbonate transport. We posit that other drugs that target cellular chloride/bicarbonate antiport would similarly demonstrate anorectic properties, induce locomotion, and diminish weight gain. Male and female inbred mice were housed in groups or stressed by prolonged social isolation. Mice consumed either normal chow or a high fat, high fructose corn syrup, (i.e. „Western”) diet. To inhibit chloride/bicarbonate transport, acetazolamide (ACT, 3 mM) was added to the drinking water. Rodents underwent evaluations of exploratory locomotion and learning with the object recognition test. Mice consuming a „Western” diet gain more weight compared to mice given a normal diet. When placed on a „Western” diet, stressed mice gained weight moe DR ratio of the stressed mice. Decreased food consumption and greater locomotor activity induced by ACT may contribute to acute weight loss; this effect is diminished when rodents were maintained on an unhealthful Western diet. Inhibition of chloride/bicarbonate transport through agents such as acetazolamide could offer a safe, new approach to achieving weight loss.
-Maintenance of tight controls on circulating blood metabolites is crucial to normal, healthy tissue and organismal function. A number of single nucleotide polymorphisms (SNPs) have been associated with changes in the levels of blood metabolites. However, the impacts of the metabolite-associated SNPs are largely unknown because they fall within non-coding regions of the genome.
-We aimed to identify genes and tissues that are linked to changes in circulating blood metabolites by characterizing genome-wide spatial regulatory interactions involving blood metabolite-associated SNPs.
-We systematically integrated chromatin interaction (Hi-C), expression quantitative trait loci (eQTL), gene ontology, drug interaction, and literature-supported connections to deconvolute the genetic regulatory influences of 145 blood metabolite-associated SNPs.
-We identified 577 genes that are regulated by 130 distal and proximal metabolite-associated SNPs across 48 different human tissues. The affected genes are enriched in categories that include metabolism, enzymes, plasma proteins, disease development, and potential drug targets. Our results suggest that regulatory interactions in other tissues contribute to the modulation of blood metabolites.
-The spatial SNP-gene-metabolite associations identified in this study expand on the list of genes and tissues that are influenced by metabolic-associated SNPs and improves our understanding of the molecular mechanisms underlying pathologic blood metabolite levels.
-The spatial SNP-gene-metabolite associations identified in this study expand on the list of genes and tissues that are influenced by metabolic-associated SNPs and improves our understanding of the molecular mechanisms underlying pathologic blood metabolite levels.
To evaluate the effect of hyperinsulinemia on cancer death, we clarified the association between hyperinsulinemia and cancer mortality among Japanese individuals.
All the participants (5586 men and 6652 women) lived in Hiroshima City, underwent a 75g oral glucose tolerance test between 1994 and 2012, and were followed for mortality until August 2013. A systematic review of death certificates was used to confirm the cause of death.
During the follow-up period (median, 10.0 years), 587 participants died of cancer. Lung cancer was the most common cause of organ-specific death. We divided the participants into 3 groups according to the tertiles of fasting immunoreactive insulin (FIRI) levels (low, middle, and high groups). The high group had the highest mortality rate (5.5 per 1000 person-years). The hazard ratio (HR) for cancer mortality of the high group after adjustment for possible confounders, such as age, sex, body mass index, smoking status, alcohol intake, and radiation effects (model 1), was significantly higher than that of the low group (HR, 1.55; 95% confidence interval (CI), 1.23-1.95). In model 2 (model 1 plus fasting plasma glucose) and model 3 (model 1 plus HbA1c), the multivariate HRs for cancer mortality were 1.46 (95% CI, 1.15-1.85) and 1.48 (95% CI, 1.17-1.87), respectively.The HR for cancer death at high FIRI levels (per 1 μU/mL) was 1.04 (95% CI, 1.02-1.05) in all participants after adjusting for fasting plasma glucose level and other confounders. In the subgroup analysis, the HRs were 1.03 (95% CI, 0.98-1.09), 1.05 (95% CI, 1.02-1.08), and 1.04 (95% CI, 1.02-1.06) in the normal, prediabetes, and diabetes group, respectively.
Hyperinsulinemia was associated with a high risk of cancer mortality and may be an important link between cancer mortality and diabetes or prediabetes.
Hyperinsulinemia was associated with a high risk of cancer mortality and may be an important link between cancer mortality and diabetes or prediabetes.Albumin has an oxidized form, known as non-mercaptalbumin (HNA), which reflects systemic oxidative stress. The association between serum HNA levels and diabetic complications are yet to be reported. In this cross-sectional study, we investigated 164 diabetic subjects to assess the correlation between HNA% (the proportion in the total albumin) and various clinical parameters. HNA% was significantly associated with the severity of multiple complications including neuropathy (23.3 ± 4.1% vs 26.2 ± 5.1%) and nephropathy (24.1 ± 3.9%, 24.6 ± 4.2%, 28.5 ± 6.1%, 31.3 ± 5.7%, 37.8 ± 2.9%, stage 1/2/3/4/5, respectively). These findings highlight the universal importance of oxidative stress, indicating HNA% potential as a versatile marker of the severity of diabetic complications.The emerging SARS-CoV-2, a novel human coronavirus, caused the COVID-19 pandemic, with more than 9.5 million cases and 484 000 known fatalities to date (June 24th, 2020). In several regions, healthcare systems have collapsed whereas interventions applied to slow the viral spreading have had major social and economic impacts. After China, Europe, and the United States, Latin America has emerged as the new epicenter of the pandemic. By late-June, the region accounted for roughly 50% of global daily deaths (Gardner, 2020). The evolution of the COVID-19 pandemic in the region has been heterogenous as several countries are currently experiencing exponential growth of their daily cases and fatalities, while others have successfully controlled their corresponding outbreaks. Cuba confi rmed its fi rst COVID-19 cases in mid-March. After a three-month outbreak, the country recently began to move to a post-epidemic phase. This dispatch details some relevant aspects of the strategy deployed in Cuba to face the COVID-19 pandemic and to decrease the impact of this emerging disease in the country.


