The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes
. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology ...of type 2 diabetes nor is predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI-measured body fat distribution, liver fat content and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes
to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have imminent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs
. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes.
Microplastics are anthropogenic contaminants which have been found in oceans, lakes and rivers. Investigations focusing on drinking water are rare and studies have mainly been using micro-Fourier ...Transform Infrared Spectroscopy (μ-FT-IR). A major limitation of this technique is its inability to detect particles smaller than 20 μm. However, micro-Raman spectroscopy is capable of detecting even smaller particle sizes. Therefore, we show that this technique, which was used in this study, is particularly useful in detecting microplastics in drinking water where particle sizes are in the low micrometer range. In our study, we compared the results from drinking water distributed in plastic bottles, glass bottles and beverage cartons.
We tested the microplastic content of water from 22 different returnable and single-use plastic bottles, 3 beverage cartons and 9 glass bottles obtained from grocery stores in Germany. Small (–50-500 μm) and very small (1–50 μm) microplastic fragments were found in every type of water. Interestingly, almost 80% of all microplastic particles found had a particle size between 5 and 20 μm and were therefore not detectable by the analytical techniques used in previous studies. The average microplastics content was 118 ± 88 particles/l in returnable, but only 14 ± 14 particles/l in single-use plastic bottles. The microplastics content in the beverage cartons was only 11 ± 8 particles/l. Contrary to our assumptions we found high amounts of plastic particles in some of the glass bottled waters (range 0–253 particles/l, mean 50 ± 52 particles/l). A statistically significant difference from the blank value (14 ± 13) to the investigated packaging types could only be shown comparing to the returnable bottles (p < 0.05).
Most of the particles in water from returnable plastic bottles were identified as consisting of polyester (primary polyethylene terephthalate PET, 84%) and polypropylene (PP; 7%). This is not surprising since the bottles are made of PET and the caps are made of PP. In water from single-use plastic bottles only a few micro-PET-particles have been found. In the water from beverage cartons and also from glass bottles, microplastic particles other than PET were found, for example polyethylene or polyolefins. This can be explained by the fact that beverage cartons are coated with polyethylene foils and caps are treated with lubricants. Therefore, these findings indicate that the packaging itself may release microparticles. The main fraction of the microplastic particles identified are of very small size with dimensions less than 20 μm, which is not detectable with the μ-FT-IR technique used in previous studies.
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•38 mineral waters were analyzed for microplastics by means of μ-Raman spectroscopy.•Microplastics were found in every type of water, almost 80% are sized between 5 and 20 μm.•Statistically significant difference from blank value could only be proven towards returnable bottles.•The found particles correlated with the materials the bottles/cartons were made of.•This indicates that plastic packaging emit microparticles, ingested directly by consumers.
Safety of intranasal human insulin: A review Schmid, Vera; Kullmann, Stephanie; Gfrörer, Wieland ...
Diabetes, obesity & metabolism,
July 2018, Letnik:
20, Številka:
7
Journal Article
Aims
To conduct a review in order to assess the safety of intranasal human insulin in clinical studies as well as the temporal stability of nasal insulin sprays.
Material and methods
An electronic ...search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were extracted.
Results
A total of 38 studies in 1092 individuals receiving acute human intranasal insulin treatment and 18 studies in 832 individuals receiving human intranasal insulin treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycaemia or severe adverse events (AEs) were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other AEs were less commonly reported. There were no reports of participants being excluded as a result of AEs. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks showed that it had a chemical stability of up to 57 days.
Conclusions
Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns; however, there were insufficient data to ensure the long‐term safety of this method of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment.
Metabolomics is a powerful tool that is increasingly used in clinical research. Although excellent sample quality is essential, it can easily be compromised by undetected preanalytical errors. We set ...out to identify critical preanalytical steps and biomarkers that reflect preanalytical inaccuracies.
We systematically investigated the effects of preanalytical variables (blood collection tubes, hemolysis, temperature and time before further processing, and number of freeze-thaw cycles) on metabolomics studies of clinical blood and plasma samples using a nontargeted LC-MS approach.
Serum and heparinate blood collection tubes led to chemical noise in the mass spectra. Distinct, significant changes of 64 features in the EDTA-plasma metabolome were detected when blood was exposed to room temperature for 2, 4, 8, and 24 h. The resulting pattern was characterized by increases in hypoxanthine and sphingosine 1-phosphate (800% and 380%, respectively, at 2 h). In contrast, the plasma metabolome was stable for up to 4 h when EDTA blood samples were immediately placed in iced water. Hemolysis also caused numerous changes in the metabolic profile. Unexpectedly, up to 4 freeze-thaw cycles only slightly changed the EDTA-plasma metabolome, but increased the individual variability.
Nontargeted metabolomics investigations led to the following recommendations for the preanalytical phase: test the blood collection tubes, avoid hemolysis, place whole blood immediately in ice water, use EDTA plasma, and preferably use nonrefrozen biobank samples. To exclude outliers due to preanalytical errors, inspect the biomarker signal intensities reflecting systematic as well as accidental and preanalytical inaccuracies before processing the bioinformatics data.
SGLT2-inhibitors are potent antihyperglycemic drugs for patients with type 2 diabetes and have been shown to reduce body weight. However, it is unclear which body compartments are reduced and to what ...extent.
In this longitudinal observational study, we analyzed the body composition of 27 outpatients with type 2 diabetes mellitus during the first week and up to 6 months after initiation of treatment with SGLT2-inhibitors (n = 18 empagliflozin, n = 9 dapagliflozin) using bioimpedance spectroscopy (BCM, Fresenius). Fluid status of hypertensive patients taking medication with hydrochlorothiazide (n = 14) and healthy persons (n = 16) were analyzed for comparison.
At 6 months, HbA1c decreased by 0.8% (IQR 2.3; 0.4), body weight and BMI by 2.6 kg (1.5; 9.3) and 0.9 kg/m
(0.4; 3.3), respectively. Bioimpedance spectroscopy revealed significant decrease in adipose tissue mass and fat tissue index while lean tissue parameters remained stable. Overhydration (OH) and extracellular water (ECW) decreased by - 0.5 L/1.73 m
(- 0.1; - 0.9) and - 0.4 L/1.73 m
(- 0.1; - 0.8) at day 3, respectively, and returned to the initial value after 3 and 6 months. Plasma renin activity increased by 2.1-fold (0.5; 3.6) at 1 month and returned to the initial level at month 3 and 6. Fluid status of patients with SGLT2 inhibitors after 6 months showed no difference from that of hypertensive patients taking hydrochlorothiazide or healthy persons.
Body weight reduction under the treatment with SGLT2-inhibitors is caused by reduction of adipose tissue mass and transient loss of extracellular fluid, which is accompanied by upregulation of renin-angiotensin-aldosterone system (RAAS). Permanent loss of extracellular water does not occur under SGLT2 inhibition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Context
Pancreatic steatosis leading to beta-cell failure might be involved in type 2 diabetes (T2D) pathogenesis.
Objective
We hypothesized that the genetic background modulates the effect ...of pancreatic fat on beta-cell function and investigated genotype × pancreatic fat interactions on insulin secretion.
Design
Two observational studies.
Setting
University hospital.
Patients or participants
A total of 360 nondiabetic individuals with elevated risk for T2D (Tuebingen Family Study TUEF), and 64 patients undergoing pancreatectomy (Pancreas Biobank PB, HbA1c <9%, no insulin therapy).
Main Outcome Measures
Insulin secretion calculated from 5-point oral glucose tolerance test (TUEF) and fasting blood collection before surgery (PB). A genome-wide polygenic score for T2D was computed from 484,788 genotyped variants. The interaction of magnetic resonance imaging-measured and histologically quantified pancreatic fat with the polygenic score was investigated. Partitioned risk scores using genome-wide significant variants were also computed to gain insight into potential mechanisms.
Results
Pancreatic steatosis interacted with genome-wide polygenic score on insulin secretion (P = 0.003), which was similar in the replication cohort with histological measurements (P = 0.03). There was a negative association between pancreatic fat and insulin secretion in participants with high genetic risk, whereas individuals with low genetic risk showed a positive correlation between pancreatic fat and insulin secretion. Consistent interactions were found with insulin resistance-specific and a liver/lipid-specific polygenic scores.
Conclusions
The associations suggest that pancreatic steatosis only impairs beta-cell function in subjects at high genetic risk for diabetes. Genetically determined insulin resistance specifically renders pancreatic fat deleterious for insulin secretion.
We performed the largest randomized, placebo‐controlled clinical trial to date (N = 112, 12‐week intervention) to investigate the effects and safety of resveratrol supplementation on liver fat ...content and cardiometabolic risk parameters in overweight and obese and insulin‐resistant subjects. At baseline the variability in liver fat content was very large, ranging from 0.09% to 37.55% (median, 7.12%; interquartile range, 3.85%‐12.94%). Mean (SD) liver fat content was 9.22 (6.85) % in the placebo group and 9.91 (7.76) % in the resveratrol group. During the study liver fat content decreased in the placebo group (−0.7%) but not in the resveratrol group (−0.03%) (differences between groups: P = .018 for the intention‐to‐treat ITT population; N = 54, resveratrol, N = 54, placebo and P = .0077 for the per protocol PP population). No effects of resveratrol supplementation on cardiometabolic risk parameters were observed. Resveratrol supplementation was well tolerated and safe.
In conclusion, these data suggest that resveratrol supplementation is safe and that it does not considerably impact liver fat content or cardiometabolic risk parameters in humans.
Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent ...two hyperinsulinemic-euglycemic clamps with d-6,6-
H
glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis.
With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health ...care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.
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