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PURPOSE: To explore physical activity level (PAL) and to describe variation in glycemia values in people with type 1 diabetes (PWT1D) before and during quarantine imposed by Italian Government due to Sars-Cov-2 pandemic. METHODS: An online survey investigating medical factors and the perceived and PAL in pre- established period before and after the introduction of quarantine was developed. Comparison between pre and post quarantine was assessed by Wilcoxon Signed Ranks test for continuous variables. RESULTS: A total of 154 subjects satisfied the eligibility criteria (54.5% males, 44.8±12.5 years). We found a decrease of PAL (Godin Scale Score 25±1.7vs38.6±1.7 points), steps number and minutes of exercise (respectively 12.606±5026vs4.760±3.145 and 66±4vs38±3) and an increase of glycemia values (142.1± 25.4 mg/dLvs150.8±29.4 mg/dL) CONCLUSIONS: PWT1D reported a decrease in exercise and worst glycemia. Although PWT1D tried to remain active, their PAL was inadequate to prevent glycemia rising. The difficult to maintain a glycemic control could expose patients to diabetes complications and to an higher risk to counteract infections. [ABSTRACT FROM AUTHOR]

Aims: Coronavirus disease (Covid-19) could lead persons with pre-existing medical conditions to severe respiratory infections. The Italian Government introduced quarantine to limit viral transmission. This measure could lead people with type 1 diabetes (PWT1D) to disrupt daily care routine including PA practice with difficulties in glycemia management. This study aims to explore PA level in PWT1D before and during quarantine and to describe variation in glycemia values.Methods: An online survey investigating medical factors and the perceived and PA level in pre-established period before and after the introduction of quarantine was developed. Comparison between pre and post quarantine was assessed by Wilcoxon Signed Ranks test for continuous variables.Results: A total of 154 subjects satisfied the eligibility criteria (54.5% males, 44.8 ± 12.5 years). We found a decrease of PA level (Godin Scale Score 25 ± 1.7vs38.6 ± 1.7 points), steps number and minutes of exercise (respectively 12.606 ± 5026vs4.760 ± 3.145 and 66±4 vs 38±3) and an increase of glycemia values (142.1 ± 25.4 mg/dLvs150.8 ± 29.4 mg/dL).Conclusions: PWT1D reported a decrease in exercise and worst glycemia. Although PWT1D tried to remain active, their PA level was inadequate to prevent glycemia rising. The difficult to maintain a glycemic control could expose patients to diabetes complications and to an higher risk to counteract infections. [ABSTRACT FROM AUTHOR]

Wider access to continuous glucose monitoring systems, including flash glucose monitoring, has enabled people with diabetes to achieve lower HbA1c levels and reduce the amount of time they spend in hypoglycaemia or hyperglycaemia, and has improved their quality of life. An International Consensus Panel proposed different target glucose ranges and recommendations according to different ages and situations (adults, young people and children with type 1 or type 2 diabetes, as well as elderly people who are at higher risk of hypoglycaemia, and women with diabetes during pregnancy). In this expert opinion, we interpret the international recommendations in the context of established clinical practice for diabetes care, and propose three different step-by-step algorithms to help the healthcare professionals use the most innovative glucose metrics, including time in glucose ranges, glucose management indicator, coefficient of variation, and ambulatory glucose profile. In detail, we focus on glucose metrics as measured by the FreeStyle Libre system and as visualized on the LibreView digital diabetes platform to support appropriate interpretation of flash glucose monitoring data. This is specifically structured for healthcare professionals and general practitioners who may have a low level of confidence with diabetes technology, with the aim of optimizing diabetes management, ensuring effective use of healthcare resources and to maximise outcomes for people with diabetes. [ABSTRACT FROM AUTHOR]

Abstract: In this study the effects of stable and intermittent high glucose concentrations on ICAM-1, VCAM-1 and E-selectin production, PKC activity and PKCβI, βII and δ isoforms expression in cultured HUVEC have been examined. In stable high glucose ICAM-1, VCAM-1 and E-selectin concentration and mRNA expression increased, and this effect was even more evident in intermittent high glucose. PKC activity increased in fluctuating glucose compared to stable high glucose, due to an over-expression of βI, βII and δ isoforms. ICAM-1, VCAM-1 and E-selectin, after the adding of total PKC inhibitor bisindolylmaleimide-I (BIMI-I) and LY379196, a specific inhibitor of PKCβ, were equally reduced. 8-Hydroxydeoxyguanosine (8-OHdG), a sensitive indicator of oxidative damage to DNA, increased in stable and even more in intermittent high glucose and was reduced by both BIMI-I and LY379196. However, when thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial complex II and the SOD mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) were added, all adhesion molecules, any PKC isoforms expression and 8-hydroxydeoxyguanosine were normalized in both constant and oscillating glucose. In conclusion intermittent high glucose induces a greater expression of the adhesion molecules than stable high glucose; this effect seems to be related to an activation of PKCβ, but completely dependent from mitochondrial free radicals over-production. [Copyright &y& Elsevier]

The effects of intermittent and constant high glucose in the formation of nitrotyrosine and 8-hydroxydeoxyguanosine (markers of oxidative stress), as well as the possible linkage between oxidative stress and apoptosis in endothelial cells, have been evaluated. Stable high glucose increased nitrotyrosine, 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis levels. However, these effects were more pronounced in intermittent high glucose. Protein kinase C (PKC) was elevated in both such conditions, particularly in intermittent glucose. The adding of the PKC inhibitors bisindolylmaleimide-I and LY379196, a specific inhibitor of PKC-β isoforms, normalized nitrotyrosine and reduced 8-OHdG concentration and cell apoptosis in both stable and intermittent high glucose. Similar results were obtained with the MnSOD mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin chloride that normalized nitrotyrosine, 8-OHdG, and apoptosis and inhibited PKC activation. NAD(P)H oxidase was also measured. NAD(P)H oxidase components p47phox, p67phox, and p22phox was overexpressed during both stable and intermittent high glucose. PKC inhibition and MnSOD mimetic normalized this phenomenon. In conclusion, our study shows that the exposure of endothelial cells to both stable and intermittent high glucose stimulates reactive oxygen species overproduction also through PKC-dependent activation of NAD(P)H oxidase, leading to increased cellular apoptosis. Our data suggest that glucose fluctuations may also be involved in the development of vascular injury in diabetes. [ABSTRACT FROM AUTHOR]

Aims: This real‐world study evaluated the changes in glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics associated with use of the implantable 180‐day Eversense CGM System (Eversense) in patients with type 1 diabetes. Materials and methods: This was a prospective, multicentre, observational study among adult participants aged ≥18 years with type 1 diabetes across seven diabetes‐care centres in Italy who had Eversense inserted for the first time. HbA1c was measured at baseline and at 180 days. Changes in time in range [TIR (glucose 70–180 mg/dL)], time above range [TAR (glucose >180 mg/dL)], time below range [TBR (glucose <70 mg/dL)] and glycaemic variability were also assessed. Data were also analysed by previous CGM use and by mode of insulin delivery. Results: One‐hundred patients were enrolled (mean age 36 ± 12 years, mean baseline HbA1c 7.4 ± 0.92% [57 ± 10 mmol/mol]). Fifty‐six per cent of patients were users of the continuous subcutaneous insulin infusion pump and 45% were previous users of CGM. HbA1c significantly decreased in patients after 180 days of sensor wear (−0.43% ± 0.69%, 5 ± 8 mmol/mol, P < 0.0001). As expected, CGM‐naïve patients achieved the greatest reduction in HbA1c (−0.74% ± 0.48%, 8 ± 5 mmol/mol). TIR significantly increased and TAR and mean daily sensor glucose significantly decreased while TBR did not change after 180 days of sensor wear. Conclusions: Real‐world clinical use of the Eversense CGM System for 180 days was associated with significant improvements in HbA1c and CGM metrics among adults with type 1 diabetes. The study is registered on clinicaltrials.gov (NCT04160156). [ABSTRACT FROM AUTHOR]

Abstract: In diabetes the exposure of the vascular endothelium to high glucose levels results in increased oxidative insult and in vascular dysfunction. We have investigated the effects of rosuvastatin on oxidative stress and apoptosis induced in human umbilical vein endothelial cells (HUVECs) by constant and intermittent high glucose levels. HUVECs were incubated for 14 days in either low (5 mM) or high (20 mM) glucose concentrations, or intermittent high and low glucose on a daily basis. Constant high glucose levels increased p47-phox, p67-phox, and p22-phox expression [components of the Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase complex]; endothelial nitric oxide synthase, nitric oxide, and O2 − production; nitrotyrosine, 8-hydroxy-2′-deoxyguanosine, and caspase-3 expression; and reduced Bcl-2 expression. These effects were significantly greater under intermittent compared to constant high/low glucose conditions. The effect of rosuvastatin (1 μM) in the presence or absence of mevalonate (200 μM) was evaluated in the cells under both constant and intermittent glucose conditions. Rosuvastatin almost normalized all these parameters. These effects of rosuvastatin were prevented when mevalonate was also added, demonstrating the link to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. These data suggest that rosuvastatin has the potential to prevent damage to and apoptosis of HUVECs induced by high glucose exposure, by reducing oxidative stress. The action of rosuvastatin on antioxidant pathways is related to the inhibition of the overexpression of components of NAD(P)H oxidase induced by the two conditions of high glucose. [Copyright &y& Elsevier]

OBJECTIVE -- The aim of this study was to assess the effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. RESEARCH DESIGN AND METHODS -- This was a randomized, double-blind, controlled clinical trial. One hundred subjects (54 men and 46 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III, were followed for 12 months after random assignment to rosiglitazone (4 mg/day) or placebo. Primary end points were flow-mediated dilation and high-sensitivity C-reactive protein (hs-CRP) levels; secondary end points were lipid and glucose parameters, homeostasis model assessment (HOMA) of insulin sensitivity, endothelial function score, and circulating levels of interleukin (IL)-6, IL-18, and adiponectin. RESULTS -- Compared with 60 control subjects matched for age and sex, patients with the metabolic syndrome had decreased endothelial function, raised concentrations of inflammatory markers, and reduced insulin sensitivity. After 12 months, subjects with the metabolic syndrome receiving rosiglitazone showed improved flow-mediated vasodilation (4.2%, P < 0.001) and reduced hs-CRP levels (-0.7 mg/dl, P = 0.04), compared with the placebo group. Moreover, HOMA (-0.8, P = 0.01) and serum concentrations of IL-6 (-0.5 pg/ml, P = 0.045) and IL-18 (-31 pg/ml, P = 0.036) were significantly reduced in subjects receiving rosiglitazone, whereas adiponectin levels showed a significant increment (2.3 µg/ml, P = 0.02). High-density lipoprotein-cholesterol levels increased more and triglyceride levels decreased more in the rosiglitazone group compared with the placebo group. At 1 year of follow-up, 30 subjects receiving rosiglitazone still had features of the metabolic syndrome, compared with 45 subjects receiving placebo (P < 0.001). CONCLUSIONS -- Rosiglitazone might be effective in reducing the prevalence of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Adhesion molecules, particularly intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin, have been associated with cardiovascular disease. Elevated levels of these molecules have been reported in diabetic patients. Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease, and evidence suggests that postprandial hypertriglyceridemia and hyperglycemia may induce an increase in circulating adhesion molecules. However, the distinct role of these two factors is a matter of debate. Thirty type 2 diabetic patients and 20 normal subjects ate three different meals: a high-fat meal, 75 g of glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, plasma nitrotyrosine, ICAM-1, VCAM-1, and E-selectin were assayed during the tests. Subsequently, diabetic subjects took simvastatin 40 mg/day or placebo for 12 weeks. The three tests were performed again at baseline, between 3 and 6 days after starting the study, and at the end of each study. High-fat load and glucose alone produced an increase of nitrotyrosine, ICAM-1, VCAM-1, and E-selectin plasma levels in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters, but reduced the effect on adhesion molecules and nitrotyrosine, which was observed during every different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations in ICAM-1, VCAM-1, E-selectin, and nitrotyrosine during the tests. This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on ICAM-1, VCAM-1, and E-selectin plasma levels, suggesting oxidative stress as a common mediator of such effects. Simvastatin shows a beneficial effect on oxidative stress and the plasma levels of adhesion molecules, which may be ascribed to a direct effect in addition to the lipid-lowering action of the drug. [ABSTRACT FROM AUTHOR]