In DBLG1 System, multiple parameters can be customized. This study aims at analyzing the impact of a change of the normoglycemia aggressiveness (NA), the hyperglycemia aggressiveness (HA) and the ...glucose target (GT) on the glycemic control of T1D patients. Data is collected from 5977 adult patients who gave their consent (3/2021 to 11/2022). Periods of 14 days before and after a single parameter change are collected. Conditions of 70% of data availability and of 75% of time spent in closed loop are requested for each period. The time in range 70-180 mg/dL (TIR), the time below range 70 mg/dL (TBR), the mean sensor glucose (MG), the coefficient of variation (CV) and the mean daily insulin dose (MDI) of the two periods are compared for each parameter using a Wilcoxon Signed-Rank test. Control for the multiple tests is done using the Benjamini-Hochberg procedure. The size effect is inferred using Cohen’s d. The results are summarized in the table below. On average, an increase of HA or NA improves the TIR and reduces the MG. The TBR appears to increase when the HA is increased and to decrease when HA or NA are reduced. A decrease of the GT increases TIR, TBR and CV, and decreases MG, conversely an increase of the GT decreases TIR, TBR and CV, and increases MG. The size effect is small. The impact on MDI is small or not significant. The most impactful parameter seems to be the GT which affects the MG proportionally. HA and NA had a lower than expected impact.
Disclosure
A.Adenis: Employee; Diabeloop SA. A.Vesin: Employee; Diabeloop SA. H.M.Romero-ugalde: Employee; Diabeloop SA. M.Louis: Employee; Diabeloop SA. C.V.Huber: Employee; Diabeloop SA. L.Pou: None. Y.Tourki: Employee; Diabeloop SA. E.Huneker: Employee; Diabeloop SA. P.Y.Benhamou: Advisory Panel; Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Consultant; Dexcom, Inc., Employee; Diabeloop SA.
Background: During prolonged fasting, glucocorticoids main-tain blood glucose by increasing gluconeogenesis and lipolysis. Glucocorticoids also have anti-i nflammatory effects and are prescribed to ...treat a variety of conditions; however, chronic use leads to many adverse consequences, including altered body composition and hyperglycemia. Little is known about the physiological link between glucocorticoid-induced lipolysis and hyperglycemia. The purpose of this study was to use a pharmacological ATGL inhibitor to limit excess lipolysis and assess outcomes that are adversely affected by glucocorticoid administration, including adiposity and glycemia. It was hypothesized that limiting lipolysis would prevent excess adiposity, excess ectopic lipid within tissues, and hyperglycemia. Methods: C57BL/6J mice were given 100 pg/mL corticosterone (Cort) in the drinking water for two weeks and were either fed a normal chow diet (TekLad 8640) or the same diet supplemented with an ATGL inhibitor, Atglistatin (ATGLi; 2 g/kg diet). Results: Cort-i nduced lipolysis (free glycerol release into blood) was negated by ATGLi. While ~75% of the mice receiving Cort became diabetic (glucose > 250 mg/dL) within two weeks, ATGLi prevented the onset of diabetes. Mice receiving ATGLi were also partially protected against Cort-induced hyperinsulinemia, hypertriglyceridemia, and increases in fat mass but were not protected from Cort-i nduced loss of lean mass. While Cort induced an increase in tissue triglyceride that was ~2.7-3.5 times higher than the control group within the skeletal muscle and liver, respectively (p < 0.0.001), this ectopic lipid deposition was prevented with ATGLi. Conclusions: These data support the idea that preventing excess lipolysis can improve clinical outcomes during a glucocorticoid regimen by mitigating several adverse metabolic outcomes that occur during drug therapy, including hyperglycemia.
Uric acid is associated with cardiovascular disease (CVD) and its risk factors. Here, we examined the association between the serum uric acid level and incident metabolic syndrome in a Japanese ...general population. This retrospective, observational study was based on data obtained from an annual health checkup program in Gunma Prefecture, Japan. We evaluated 14,793 participants who did not use antihypertensive or antidiabetic medications and did not present with CVD or metabolic syndrome at the study baseline in 2009. Metabolic syndrome was defined as per the Japanese diagnostic criteria. A discrete proportional hazards regression model was used to evaluate the association between the serum uric acid level at baseline and the incident metabolic syndrome through 2012 and was adjusted for age, gender, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, high-density lipoprotein cholesterol, and triglyceride. At baseline, the average age of the participants was 48.9 years, who were comprised of 40% women. The mean serum uric acid level at baseline was 5.3 ± 1.4 mg/dL. During the three-year follow-up, 7% of the cohort (n = 1,031) developed metabolic syndrome. The uric acid level was strongly associated with incident metabolic syndrome in the multivariable model (adjusted hazard ratio: 1.10; 95% confidence interval, 1.04-1.17; P < 0.01 per 1 mg/dL increase for uric acid). Higher uric acid levels were independently associated with a greater risk of incident metabolic syndrome in a Japanese general population.
Aim
To evaluate the association between different degrees of hyperglycaemia and the risk of all‐cause mortality among hospitalized patients with COVID‐19.
Materials and Methods
In a retrospective ...study conducted from 22 January to 17 March 2020, 453 patients were admitted to Union Hospital in Wuhan, China, with laboratory‐confirmed severe acute respiratory syndrome coronavirus 2 infection. Patients were classified into four categories: normal glucose, hyperglycaemia (fasting glucose 5.6‐6.9 mmol/L and/or HbA1c 5.7%‐6.4%), newly diagnosed diabetes (fasting glucose ≥7 mmol/L and/or HbA1c ≥6.5%) and known diabetes. The major outcomes included in‐hospital mortality, intensive care unit (ICU) admission and invasive mechanical ventilation (IMV).
Results
Patients with newly diagnosed diabetes constituted the highest percentage to be admitted to the ICU (11.7%) and require IMV (11.7%), followed by patients with known diabetes (4.1%; 9.2%) and patients with hyperglycaemia (6.2%; 4.7%), compared with patients with normal glucose (1.5%; 2.3%), respectively. The multivariable‐adjusted hazard ratios of mortality among COVID‐19 patients with normal glucose, hyperglycaemia, newly diagnosed diabetes and known diabetes were 1.00, 3.29 (95% confidence interval CI 0.65‐16.6), 9.42 (95% CI 2.18‐40.7) and 4.63 (95% CI 1.02‐21.0), respectively.
Conclusion
We showed that COVID‐19 patients with newly diagnosed diabetes had the highest risk of all‐cause mortality compared with COVID‐19 patients with known diabetes, hyperglycaemia and normal glucose. Patients with COVID‐19 need to be kept under surveillance for blood glucose screening.
The anti-hyperglycemic effect of metformin is believed to be caused by its direct action on signaling processes in hepatocytes, leading to lower hepatic gluconeogenesis. Recently, metformin was ...reported to alter the gut microbiota community in humans, suggesting that the hyperglycemia-lowering action of the drug could be the result of modulating the population of gut microbiota. However, the critical microbial signaling metabolites and the host targets associated with the metabolic benefits of metformin remained elusive. Here, we performed metagenomic and metabolomic analysis of samples from individuals with newly diagnosed type 2 diabetes (T2D) naively treated with metformin for 3 d, which revealed that Bacteroides fragilis was decreased and the bile acid glycoursodeoxycholic acid (GUDCA) was increased in the gut. These changes were accompanied by inhibition of intestinal farnesoid X receptor (FXR) signaling. We further found that high-fat-diet (HFD)-fed mice colonized with B. fragilis were predisposed to more severe glucose intolerance, and the metabolic benefits of metformin treatment on glucose intolerance were abrogated. GUDCA was further identified as an intestinal FXR antagonist that improved various metabolic endpoints in mice with established obesity. Thus, we conclude that metformin acts in part through a B. fragilis-GUDCA-intestinal FXR axis to improve metabolic dysfunction, including hyperglycemia.
Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds ...for identifying women at risk of perinatal outcomes can be identified.Design Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials.Data sources Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts.Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools.Results 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses.Conclusions This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes.Systematic review registration PROSPERO CRD42013004608
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of ...type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.
The prevalence of diabetes is growing worldwide with an increasing morbidity and mortality associated with the development of diabetes complications. Free radical production is a normal biological ...process that is strictly controlled and has been shown to be important in normal cellular homeostasis, and in the bodies response to pathogens. However, there are several mechanisms leading to excessive free radical production that overcome the normal protective quenching mechanisms. Studies have shown that many of the diabetes complications result from excessive free radical generation and oxidative stress, and it has been shown that chronic hyperglycemia is a potent inducer for free radical production, generated through several pathways and triggering multiple molecular mechanisms. An understanding of these processes may help us to improving our preventive or therapeutic strategies. In this review, the major molecular pathways involved in free radical generation induced by hyperglycemia are described.
Studies have shown that many of the diabetes complications result from excessive free radical generation and oxidative stress, and it has been shown that chronic hyperglycemia is a potent inducer for free radical production, generated through several pathways and triggering multiple molecular mechanisms. An understanding of these processes may help us to improving our preventive or therapeutic strategies. In this review, the major molecular pathways involved in free radical generation induced by hyperglycemia are described.
PDF
