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OBJECTIVES: Aronia melanocarpa (Aronia) is a shrub with small berries, chokeberries. Chokeberries are claimed to possess health benefits due to a high content of polyphenols. Aronia is known to be extremely antioxidant; however, evidence for its health benefits is not established. This review gives an overview of the impact of Aronia on cardiometabolic risk factors and diseases. METHODS: Seventeen studies on cardiometabolic risk factors and diseases were identified through a systematic search on PubMed, Embase, and Cochrane. Inclusion criteria were studies with Aronia as intervention, performed in individuals with cardiometabolic disease or risk factors, e. g., type 2 diabetes (T2D), cardiovascular disease, hypertension, dyslipidaemia, impaired glucose tolerance, overweight, central obesity and smoking. Four of these studies were applicable for a quantitative analysis. RESULTS: Aronia did not influence body weight, circulating triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, or blood pressure. The quantitative analysis revealed a mean reduction in blood glucose of 0.44 mmol/l (P=0.0001) in the treatment group compared with the control group suggesting that Aronia treatment may have a beneficial impact on blood glucose. In addition, treatment durations of 6 weeks to 3 months tended to decrease low-density lipoprotein (LDL) cholesterol, while shorter treatment durations had no effect on LDL cholesterol. The quantitative analysis did not provide data on long-term effects of Aronia on lipids. CONCLUSIONS: More long-term high-quality randomized controlled studies are needed to clarify if dietary supplementation with Aronia has beneficial effects on cardiometabolic diseases.

Background: Chokeberries (Aronia spp.) are known to exhibit both direct and indirect antioxidant properties and have been associated with beneficial effects on human health, including cardiovascular risk factors (inflammation, serum lipids, sugars, blood pressure), oxidative stress, and semen quality. This prospective, double-blinded, randomized, crossover clinical trial was conducted to elucidate the effects of Aronia supplementation on these health targets in mildly hypercholesterolemic men. Methods: The standardized Aronia supplementation comprised three wild Aronia spp. (A. arbutifolia, A prunifolia and A. melanocarpa) and the Aronia hybrid × Sorbaronia mitschurinii (standardized to 150 mg anthocyanins daily). Participants (n = 109) were healthy men with respect to all outcome targets except for the total cholesterol level (5.0–7.0 mM). Participants were randomized to supplementation with either Aronia or placebo for 90 days, followed by a wash-out period and lastly the complementary supplementation. Effects on the health parameters were compared among both the whole group of men and in subgroups according to age, body mass index (BMI), lifestyle, dietary habits, and serum glutathione levels at baseline. The study is registered in ClinicalTrials.gov.: NCT03405753. Results: Glutathione levels were significantly improved after 90 days intake of Aronia supplementation compared to placebo in the subgroup of men with a low level of glutathione at baseline (p = 0.038) and a high coffee intake (p = 0.045). A significant decrease in levels of sperm DNA fragmentation and an increase in the percentage of motile sperm were observed in men aged >40 and in men with BMI > 25. Further, these parameters were significantly improved in the dietary subgroup defined by a high level of coffee intake. Total cholesterol and low-density lipoprotein-cholesterol levels decreased significantly in men 40 years of age and BMI > 25 but did not demonstrate a significant effect in the overall analysis. The observed concurrent increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in subgroups of men, suggests that the endogenous phase II antioxidant glutathione is involved in the modulation of the observed cytoprotective effects. This study is a good foundation for further investigation of these cytoprotective effects in groups with oxidative stress in a dose–response study.

Chokeberries (The standardized Aronia supplementation comprised three wildGlutathione levels were significantly improved after 90 days intake of Aronia supplementation compared to placebo in the subgroup of men with a low level of glutathione at baseline (This study demonstrated a significant increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in specific subgroups of mengt;40 years of age and BMIgt; 25 but did not demonstrate a significant effect in the overall analysis. The observed concurrent increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in subgroups of men, suggests that the endogenous phase II antioxidant glutathione is involved in the modulation of the observed cytoprotective effects. This study is a good foundation for further investigation of these cytoprotective effects in groups with oxidative stress in a dose-response study.

Purpose of Review: Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic review was to examine the effects of different classes of glucose-lowering drugs on fracture risk in patients with type 2 DM. The heterogeneity of the included studies did not allow formal statistical analyses. Recent Findings: Sixty studies were included in the review. Metformin, dipeptidylpeptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium–glucose cotransporter 2-inhibitors do not appear to increase fracture risk. Results for insulin and sulphonylureas were more disparate, although there may be an increased fracture risk related to hypoglycemia and falls with these treatments. Glitazones were consistently associated with increased fracture risk in women, although the evidence was sparser in men. Summary: New glucose-lowering drugs are continuously being developed and better understanding of these is leading to changes in prescription patterns. Our findings warrant continued research on the effects of glucose-lowering drugs on fracture risk, elucidating the class-specific effects of these drugs.

The outset of realistic rendering is a desire to reproduce the appearance of the real world. Rendering techniques therefore operate at a scale corresponding to the size of objects that we observe with our naked eyes. At the same time, rendering techniques must be able to deal with objects of nearly arbitrary shapes and materials. These requirements lead to techniques that oftentimes leave the task of setting the optical properties of the materials to the user. Matching the appearance of real objects by manual adjustment of optical properties is however nearly impossible. We can render objects with a plausible appearance in this way but cannot compare the appearance of a manufactured item to that of its digital twin. This is especially true in the case of translucent objects, where we need more than a goniometric measurement of the optical properties. In this survey, we provide an overview of forward and inverse models for acquiring the optical properties of translucent materials. We map out the efforts in graphics research in this area and describe techniques available in related fields. Our objective is to provide a better understanding of the tools currently available for appearance specification when it comes to digital representations of real translucent objects.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the effects of progressive resistance training (PRT) on muscle strength, intraepidermal nerve fibre density (IENFD) and motor function in individuals with type 2 diabetic polyneuropathy (DPN) and to compare potential adaptations to those of individuals with type 2 diabetes without DPN and healthy controls.METHODS: This was an assessor-blinded trial conducted at the Neurology department, Aarhus University Hospital. Adults with type 2 diabetes, with and without DPN and healthy control participants were randomised to either supervised PRT or non-PRT for 12 weeks. Allocation was concealed by a central office unrelated to the study. The co-primary outcomes were muscle strength in terms of the peak torque of the knee and ankle extensors and flexors, and IENFD. Secondary outcome measures included the 6 min walk test (6MWT), five-time sit-to-stand test (FTSST) and postural stability index obtained by static posturography.RESULTS: A total of 109 individuals were enrolled in three groups (type 2 diabetes with DPN [n = 42], type 2 diabetes without DPN [n = 32] and healthy control [n = 35]). PRT resulted in muscle strength gains of the knee extensors and flexors in all three groups using comparative analysis (DPN group, PRT 10.3 ± 9.6 Nm vs non-PRT -0.4 ± 8.2 Nm; non-DPN group, PRT 7.5 ± 5.8 Nm vs non-PRT 0.6 ± 8.8 Nm; healthy control group, PRT 6.3 ± 9.0 Nm vs non-PRT -0.4 ± 8.4 Nm; pCONCLUSIONS/INTERPRETATION: PRT improved muscle strength of the knee extensors and flexors and motor function in individuals with type 2 diabetic polyneuropathy at levels comparable with those seen in individuals with diabetes without DPN and healthy control individuals, while no effects were observed in IENFD.TRIAL REGISTRATION: ClinicalTrials.gov NCT03252132 FUNDING: Research reported in this paper is part of the International Diabetic Neuropathy Consortium (IDNC) research programme, supported by a Novo Nordisk Foundation Challenge Program grant (grant no. NNF14OC0011633) and Aarhus University.

This chapter investigates the Fennoscandian uplift area since the latest Ice Age and addresses the question if glacial isostatic adjustment may influence current seismicity. The region is in an intraplate area, with stresses caused by the lithospheric relative plate motions. Discussions on whether uplift and plate tectonics are the only causes of stress have been going on for many years in the scientific community. This review considers the improved sensitivity of the seismograph networks, and at the same time attempts to omit man-made explosions and mining events in the pattern, to present the best possible earthquake pattern. Stress orientations and their connection to the uplift pattern and known tectonics are evaluated. Besides plate motion and uplift, one finds that some regions are affected stress-wise by differences in geographical sediment loading as well as by topography variations. The stress release in the present-day earthquakes shows a pattern that deviates from that of the time right after the Ice Age. This chapter treats the stress pattern generalized for Fennoscandia and guides the interested reader to more details in the national chapters.

While osteoporosis is characterized by skeletal fragility due to increased bone turnover and low bone mineral density (BMD), subjects with abdominal obesity and type-2 diabetes have increased risk of bone fractures despite low bone turnover and increased BMD. Diets with increased protein content are reported to increase bone turnover in healthy adults and may be a point of interest in preserving bone strength in subjects with abdominal obesity and/or type-2 diabetes.We examined the effect of 12-weeks dietary intervention on bone turnover in 64 adults with abdominal obesity using data from the MERITS trial. The trial was a randomized, controlled, double blinded study in which participants were allocated to receive either 60 g/d of whey protein hydrolysate or maltodextrin in combination with either high (30 g/d) or low dietary fiber intake (10 g/d). Primarily, we assessed changes in plasma markers of bone turnover Procollagen type 1 N-terminal propeptide (p1NP), C-terminal telopeptide type-1 collagen (CTX), and parathyroid hormone (PTH) within the four intervention groups. In addition, we measured u-calcium and u-carbamide excretion, 25(OH)D, and BMD by whole body DXA scans. Finally, we compared changes in insulin resistance (Homeostasis-model assessment of insulin resistance, HOMA-IR) with changes in bone turnover markers.The trial was registered at www.clinicaltrials.gov as NCT02931630.Sixty-four subjects were included in the study. We did not find any effect of twelve weeks of high protein or high fiber intake on plasma levels of P1NP or CTX. There was a nonsignificant positive association between protein intake and PTH levels (p=0.06). U-calcium and u-carbamide increased in both protein groups. There was a positive association between change in HOMA-IR and PTH (p=0.042), while changes in P1NP and CTX did not associate to changes in HOMA-IR.Twelve weeks of increased whey protein intake in subjects with abdominal obesity did not affect markers of bone turnover significantly, although tended to increase PTH levels. Dietary fiber intake did not affect bone turnover. We report a positive association between change in HOMA-IR and PTH supporting a hypothesis of insulin resistance as a potential key factor in the expanding field of bone fragility in T2D subjects.

Purpose of Review: Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Weight loss in T2DM management may result in lowering of bone mass. In this systematic literature review, we aimed to investigate how exercise affects bone health in people with T2DM. Furthermore, we examined the types of exercise with the potential to prevent and treat bone fragility in people with T2DM. Recent Findings: Exercise differs in type, mechanical load, and intensity, as does the osteogenic response to exercise. Aerobic exercise improves metabolic health in people with T2DM. However, the weight-bearing component of exercise is essential to bone health. Weight loss interventions in T2DM induce a loss of bone mass that may be attenuated if accompanied by resistance or weight-bearing exercise. Summary: Combination of weight-bearing aerobic and resistance exercise seems to be preventive against excessive bone loss in people with T2DM. However, evidence is sparse and clinical trials investigating the effects of exercise on bone health in people with T2DM are warranted.

OBJECTIVE: Abdominal obesity and type 2 diabetes are associated with insulin resistance and low bone turnover along with an increased fracture risk. The mode of action is poorly understood. The bone resorption marker, C-terminal telopeptide type 1 collagen (CTX), and to a lesser extent, the bone formation marker, Procollagen type 1 N-terminal propeptide (P1NP) appear to be inhibited by food consumption. The link between food consumption, insulin resistance and bone turnover remains to be clarified. Primarily we aimed to compare the postprandial CTX, P1NP and PTH responses by two frequently applied methods in assessing metabolic health; oral glucose tolerance test (OGTT) and mixed meal tolerance test. Secondly, we explored the effect of insulin resistance on bone marker responses.METHODS: We enrolled 64 subjects with abdominal obesity. Following 10 h of fasting, subjects initially underwent a standard OGTT (300 kcal) and approximately one week later a mixed meal tolerance test (1130 kcal). Circulating CTX, P1NP and PTH were assessed on both days at time = 0, after 30 min and after 90 min for comparison of the two interventions. We analyzed glucose and insulin levels for the assessment of insulin resistance. Additionally, we measured plasma calcium levels along with the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 2 (GLP-2) in an attempt to identify possible mediators of the postprandial bone response.RESULTS: CTX, P1NP and PTH were suppressed by OGTT and the mixed meal; the latter induced a more pronounced suppression after 90 min. Calcium levels were similar between OGTT and meal. GIP and GLP-2 levels increased after both interventions, although only the meal induced a sustained increase after 90 min. Fasting P1NP was inversely associated with insulin resistance. The meal-induced suppression of P1NP (but not CTX or PTH) was inversely associated with level of insulin resistance.CONCLUSION: The acute postprandial suppression of bone turnover markers is extended after ingestion of a mixed meal compared to an OGTT. The response appears to be independent of gender and prompted by a reduction in PTH. The study additionally indicates a possible link between the development of insulin resistance and low bone turnover - which may be of key essence in the development of the fragile bone structure and increased fracture risk demonstrated in subjects with abdominal obesity and T2D.

Daily coffee consumption is inversely associated with risk of type-2 diabetes (T2D). Cafestol, a bioactive substance in coffee, increases glucose-stimulated insulin secretion in vitro and increases glucose uptake in human skeletal muscle cells. We hypothesized that cafestol can postpone development of T2D in KKAy mice. Forty-seven male KKAy mice were randomized to consume chow supplemented daily with either 1.1 (high), 0.4 (low), or 0 (control) mg of cafestol for 10 weeks. We collected blood samples for fasting glucose, glucagon, and insulin as well as liver, muscle, and fat tissues for gene expression analysis. We isolated islets of Langerhans and measured insulin secretory capacity. After 10 weeks of intervention, fasting plasma glucose was 28−30% lower in cafestol groups compared with the control group (p < 0.01). Fasting glucagon was 20% lower and insulin sensitivity improved by 42% in the high-cafestol group (p < 0.05). Cafestol increased insulin secretion from isolated islets by 75−87% compared to the control group (p < 0.001). Our results show that cafestol possesses antidiabetic properties in KKAy mice. Consequently, cafestol may contribute to the reduced risk of developing T2D in coffee consumers and has a potential role as an antidiabetic drug.

Background Patients with type-1 (T1D) and type-2 diabetes mellitus (T2D) have an increased risk of hip fracture. The underlying mechanisms may involve disturbances in the incretin hormones. Our aim was to clarify if glucose administration i.e. orally or intravenously differentially affects bone turnover markers in healthy males. Methods 12 healthy males were included in a cross-over study consisting of three tests following an 8 hour fast. First, an oral glucose tolerance test (OGTT) was performed. Subsequently, we carried out an isoglycemic intravenous glucose infusion (IIGI) that closely mimicked the glucose response curve to the oral glucose load. We analyzed blood samples for the bone turnover markers serum C-terminal telopeptide of type I collagen (s-CTX) and serum procollagen type I N propeptide (s-P1NP), as well as insulin, glucose, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). Finally, eight of the twelve participants underwent a control experiment where they fasted for 3 h (Control). Results While OGTT induced a 50% reduction in s-CTX, only a ~ 30% reduction was seen during the IIGI and the Control. Neither intervention influenced s-P1NP. The concentration of insulin was highest during the OGTT. However, insulin was also increased significantly during the IIGI compared to the Control. Plasma concentrations of GIP, GLP-1 and GLP-2 were higher under the OGTT than during the IIGI and Control. A linear regression indicated that peak p-GIP significantly predicts nadir s-CTX (p = 0.03), and that peak p-GIP could explain 34% of the variability in nadir s-CTX (adjusted R 2 = 0.34). Conclusion This study indicates that glucose per se does not acutely affect bone turnover markers. However, gastrointestinal hormones, especially GIP, possibly in combination with hyperglycemia, may have an acute, uncoupling effect on bone turnover leading to a decrease in bone resorption but no change in bone formation.

Background: Recently, we demonstrated that whey protein (WP) combined with low dietary fiber improved lipemia, a risk factor for cardiovascular disease in subjects with abdominal obesity. In the present study, we investigated the effects of intake of WP and dietary fiber from enzyme-treated wheat bran on other metabolic parameters of the metabolic syndrome. Methods: The study was a 12-week, double-blind, randomized, controlled, parallel intervention study. We randomized 73 subjects with abdominal obesity to 1 of 4 iso-energetic dietary interventions: 60 g per day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber (HiFi; 30 g dietary fiber/day) or low-fiber (LoFi; 10 g dietary fiber/day) cereal products. We assessed changes in insulin sensitivity, gut hormones (GLP-1, GLP-2, GIP, and peptide YY), body composition, 24-h BP, resting energy expenditure and respiratory exchange ratio (RER), and appetite. Results: Sixty-five subjects completed the trial. Subjective hunger ratings were lower after 12 weeks of WP compared with MD, independent of fiber content (P = 0.02). We found no effects on ratings of satiety, fullness or prospective food consumption for either of the interventions. Intake of WP combined with LoFi increased the postprandial peptide YY response. There were no effects of WP or fiber on insulin sensitivity, body composition, energy expenditure, incretins, or 24-h BP. Conclusions: WP consumption for 12 weeks reduced subjective ratings of hunger in subjects with abdominal obesity. Neither WP nor dietary fiber from wheat bran affected insulin sensitivity, 24-h BP, gut hormone responses, body composition, or energy expenditure compared with MD and low dietary fiber.

In this work, the interaction between 3D optical scanners and objects realized with different materials and colours was investigated. The interaction is mainly related to the translucency of some materials, such as polymers, which is a category of materials in ever-increasing demand by industry. At the same time, the increase of the geometrical complexity of manufactured parts raises the need for the use of 3D optical scanners thanks to their rapidity and effectiveness. Translucency causes a subsurface scattering effect that has been modelled for certain cases and affects the dimensional accuracy of measurements, as well as the quality of reconstruction. Recently, an investigation considered its effect in dimensional verification using a structured light scanner with fringe projection. In this work, the investigation is extended to other 3D optical scanners exploiting different measuring principles: laser, structured light based on phase shifting and gray code, and photogrammetry. This was done in order to study how the subsurface scattering effect can vary with the materials, colours, and also the measuring principle used. To this end, five miniature step gauges made of different polymers and colours were used, and the effects due to their different optical properties investigated. The analysis focused on dimensional verification of bidirectional lengths, first calibrated with a traceable coordinate measuring machine. The quality of the reconstruction was also evaluated through the flatness values. According to the results obtained, translucency of materials has a dual and significant effect: a measurement bias and an increase of the uncertainty due to the different quality of reconstruction retrieved. Thus, it has to be considered properly for each case.

Abdominal obesity is associated with elevated postprandial triglycerides (TG), an independent risk factor for cardiovascular diseases. Previous studies show that whey protein (WP) and dietary fiber may separately reduce postprandial TG. However, few studies have investigated the long-term effects of WP and dietary fiber on postprandial TG. We aimed to investigate the separate and combined long-term effects of WP and dietary fiber from wheat bran on postprandial TG and markers of lipid metabolism in subjects with abdominal obesity. We conducted a 12-week, double-blind, randomized, controlled, parallel intervention study. In a 2 &times, 2 factorial design, 73 adults were randomized to receive 60 g/day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber wheat bran products (HiFi, 30 g dietary fiber/day) or low-fiber refined wheat products (LoFi, 10 g dietary fiber/day). A high-fat meal test was conducted before and after the intervention. Sixty-five subjects were included in the final analyses. There were no differences between intervention groups in postprandial TG assessed as incremental area under the curve (iAUC). WP-LoFi had reduced postprandial TG assessed as total area under the curve (tAUC) and reduced fasting TG compared with all other groups, and reduced fasting apolipoprotein B-48 compared with MD-LoFi. There were no changes in lipoprotein lipase activity. Total cholesterol and apolipoprotein B-100 were reduced after WP intake compared with MD. Total cholesterol was increased after HiFi intake compared with LoFi. In conclusion, intake of WP in combination with low-fiber cereal products for 12 weeks had beneficial effects on postprandial TG tAUC and fasting TG, but not on postprandial TG iAUC in subjects with abdominal obesity. Combining WP with high-fiber wheat bran products did not improve lipid profile.

The effects of chronic coffee exposure in models of type 2 diabetes mellitus (T2D) models is scarcely studied, and the efficacy of the main coffee species has never been compared. We tested the hypothesis that long-term consumption of arabica and robusta coffee may differentially delay and affect T2D development in Zucker diabetic fatty rats. Three study groups received either chow mixed with arabica or robusta instant coffee (1.8% w/w) or unsupplemented chow food for 10 weeks. Both coffee species reduced liver triglyceride content and area under the curve of fasting and postprandial insulin. At study end, plasma adiponectin, total cholesterol and high density lipoprotein levels were higher in the robust group compared with both arabica and control groups. The liver gene expression of Glucose-6-phosphatase, catalytic subunit (G6pc) and Mechanistic target of rapamycin (mTOR) in robusta and Cpt1a in both coffee groups was downregulated. In conclusion, long-term consumption of both coffee species reduced weight gain and liver steatosis and improved insulin sensitivity in a rat model of T2D. Robusta coffee was seemingly superior to arabica coffee with respect to effects on lipid profile, adiponectin level and hepatic gene expression.

Overnight fasting of varying length is common practice when studying glucose and lipid metabolism in rats. However, prolonged fasting may influence insulin sensitivity, and it is unknown to which extent different fasting durations affect postprandial metabolism in rats. The purpose of this study was to investigate the effect of different fasting durations (6-, 12-, or 18-h) on fat tolerance and glucose tolerance in male Sprague Dawley rats. We also aimed to examine the effect of two test fats with different fatty acid composition on postprandial triglycerides. We conducted a fat tolerance test, where butterfat or rapeseed oil was administered in a crossover design (experiment 1), and an oral glucose tolerance test (experiment 2). Regarding the fat tolerance test, we found no effects of fasting duration on triglycerides or free fatty acids, whereas the 18-h fast resulted in reduced glucose and insulin area under the curves. We did not find differential effects of butterfat and rapeseed oil on the outcomes. We found decreased fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR), and increased beta-hydroxybutyric acid concentrations after 18-h fast compared with shorter fasting durations. Regarding the oral glucose tolerance test, both 12-h and 18-h fast resulted in greater peak insulin concentrations than 6-h fast, and peak glucose concentrations were higher after 18-h than 12-h fast. We found no effects of fasting on the insulin sensitivity index. In conclusion, extending the fasting duration had an impact on glucose metabolism in rats, but did not appear to influence fat tolerance.

Background: The global epidemic of type 2 diabetes (T2D) is a challenging health problem. Lifestyle changes, including nutrition therapy, areimportant for the prevention and management of T2D. Seaweeds contain several bioactive substances with potential health properties and may be a low-cost alternative functional food in the prevention of T2D. Objective: The aim of this study was to explore the preventive effects of dried Nordic seaweed species on diabetes in an animal model of T2D. Method: Fiftymale KK-Ay mice were randomly assigned to one of four diets: control diet (chow) or diets supplemented with Alaria esculenta (AE), Saccharina latissima (SL), or Palmaria palmata (PP). The effect of the interventions on the progression of T2D was monitored over 10 weeks and evaluated by circulating glucose, glycated hemoglobin (HbA1c), insulin, glucagon, and lipid levels. Results: The SL group had significantly lower bodyweight, lower HbA1c and insulin levels, as well as higher high density lipoprotein (HDL) cholesterol levels after the 10-week intervention than the control group. At the end of the study, the control group had significantly higher HbA1c (p &lt, 0.001) than all of the seaweed groups. Conclusion: All seaweed groups improved HbA1C compared to control and Saccharinalatissima seaweed had concomitantly beneficial effects on glycemic control and lipid levels in KK-Ay diabetic mice.

Interactions between endocrine α and β cells are critical to their secretory function in vivo. The interactions are highly regulated, although yet to be fully understood. In this study, we aim to assess the impact of α and β cell co-culture on hormone secretion. Mouse clonal cell lines α-TC6-1 (α cell line) and MIN-6 (β cell line) were cultured independently or in combination in a medium containing 5.5, 11.1, or 25 mM glucose, respectively. After 72 h, hormone release was measured using insulin and glucagon secretion assays, the cell distribution was visualized by inverted microscopy and an immunocytochemistry assay, and changes in gene expressions were assessed using the RT-PCR technique. The co-culture of the two cell lines caused a decrease in glucagon secretion from α-TC1-6 cells, while no effect on insulin secretion from MIN-6 cells was revealed. Both types of cells were randomly scattered throughout the culture flask, unlike in mice islets in vivo where β cells cluster in the core and α cells are localized at the periphery. During the α–β cell co-culture, the gene expression of glucagon (Gcg) decreased significantly. We conclude that islet β cells suppress glucagon secretion from α cells, apparently via direct cell-to-cell contact, of which the molecular mechanism needs further verification.

Purpose: Low intake of dietary fibre is associated with the development of type 2 diabetes. Dyslipidaemia plays a key role in the pathogenesis of type 2 diabetes. Knowledge of the impact of dietary fibres on postprandial lipaemia is, however, sparse. This study aimed in subjects with metabolic syndrome to assess the impact on postprandial lipaemia and features of the metabolic syndrome of a healthy carbohydrate diet (HCD) rich in cereal fibre, arabinoxylan and resistant starch compared to a refined-carbohydrate western-style diet (WSD). Methods: Nineteen subjects completed the randomised, crossover study with HCD and WCD for 4-week. Postprandial metabolism was evaluated by a meal-challenge test and insulin sensitivity was assessed by HOMA-IR and Matsuda index. Furthermore, fasting cholesterols, serum-fructosamine, circulating inflammatory markers, ambulatory blood pressure and intrahepatic lipid content were measured. Results: We found no diet effects on postprandial lipaemia. However, there was a significant diet × statin interaction on total cholesterol (P = 0.02) and LDL cholesterol (P = 0.002). HCD decreased total cholesterol (−0.72 mmol/l, 95% CI (−1.29; −0.14) P = 0.03) and LDL cholesterol (−0.61 mmol/l, 95% CI (−0.86; −0.36) P = 0.002) compared with WSD in subjects on but not without statin treatment. We detected no other significant diet effects. Conclusions: In subjects with metabolic syndrome on statins a 4-week diet rich in arabinoxylan and resistant starch improved fasting LDL and total cholesterol compared to subjects not being on statins. However, we observed no diet related impact on postprandial lipaemia or features of the metabolic syndrome. The dietary fibre x statin interaction deserves further elucidation.

Context: Type 1 and type 2 diabetes mellitus are associated with an increased risk of fracture. Objective: The objective of the study was to compare the bone structure and density between type 1 and type 2 diabetes patients and to investigate fracture associations. Design: This was a cross-sectional study. Setting and Patients: Physician-diagnosed type 1 and type 2 diabetes patients were included from the outpatient clinics at two university hospitals participated in the study. Main Outcome Measures: Bone density and structure were assessed by dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Blood samples were collected for bone turnover markers. Prevalent vertebral fractures were assessed by vertebral fracture assessment and x-ray, and incident fractures were collected from The Danish National Hospital Discharge Register. Results: Bone mineral density (BMD) was higher in type 2 than type 1 diabetes patients at the hip, femur, and spine; however, only the hip differed in multivariate-adjusted models. Bone tissue stiffness at the tibia was increased in type 2 diabetes patients also in adjusted models. Sclerostin levels were inversely associated with fracture in type 1 diabetes patients. The patients with the highest tertile of sclerostin had an 81% decreased risk of a fracture compared with the lowest tertile. Conclusions: Type 1 and type 2 diabetes patients differ in BMD of the hip and tissue stiffness at the tibia. Sclerostin may be a marker independent of BMD to predict fractures in type 1 diabetes patients and thus potentially of clinical importance. Studies with longer follow-up are needed.

We propose a method for direct comparison of rendered images with a corresponding photograph in order to analyze the optical properties of physical objects and test the appropriateness of appearance models. To this end, we provide a practical method for aligning a known object and a point-like light source with the configuration observed in a photograph. Our method is based on projective transformation of object edges and silhouette matching in the image plane. To improve the similarity between rendered and photographed objects, we introduce models for spatially varying roughness and a model where the distribution of light transmitted by a rough surface influences direction-dependent subsurface scattering. Our goal is to support development toward progressive refinement of appearance models through quantitative validation.

BACKGROUND: Abdominal obesity is characterized by low-grade inflammation and plays a central role in the development of type 2 diabetes and cardiovascular diseases. Dietary factors can influence low-grade inflammation and affect adipose tissue function. AIM: To investigate the separate and combined effects of whey protein and cereal fiber on inflammatory markers and adipose tissue gene expression in abdominal obesity. METHODS: We performed a 12-week, double-blind, randomized controlled dietary intervention in 65 adults with abdominal obesity. The participants were randomized to 4 groups using a 2 × 2 factorial design; they received either 60 g/day of whey protein or maltodextrin in combination with high-fiber wheat bran products (30 g fiber/day) or low-fiber refined wheat products (10 g fiber/day). Plasma concentrations of tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), interleukin 1 receptor antagonist (IL-1Ra), and adiponectin were measured before and after intervention. Changes in gene expression related to inflammation, insulin signaling, and lipid metabolism were measured in abdominal subcutaneous adipose tissue. RESULTS: After intervention, TNF-α was reduced for both high-fiber groups compared with baseline, but did not significantly differ from the low-fiber groups. There were no differences in fasting or postprandial inflammatory markers between the groups. The relative gene expression of ribosomal protein S6 kinase B1 (S6K1) was increased after whey protein compared with maltodextrin consumption. CONCLUSION: Intake of whey protein in combination with high cereal fiber content did not differentially affect low-grade inflammation or adipose tissue gene expression compared with maltodextrin and low fiber content in individuals with abdominal obesity.

INTRODUCTION: Type 2 diabetes is associated with an increased risk of bone fractures. Bone mineral density (BMD) is increased and bone turnover is low in type 2 diabetes and the increased BMD does not explain the increased fracture risk. However, the low bone turnover may lead to insufficient bone renewal with unrepaired micro-cracks and thus increase fracture risk. Ingestion of food acutely decreases bone resorption markers and the macronutrient composition of meals and meal frequency may influence bone metabolism adversely in subjects with unhealthy eating patterns, e.g., patients with type 2 diabetes. Areas covered: The treatment strategy of bone disease in type 2 diabetics is covered in this review. The current management of diabetic bone disease consists of anti-osteoporotic treatment. However, anti-resorptives may further reduce an already low bone turnover with uncertain effects. Furthermore, the acute and long-term effects of meal ingestion, weight loss alone and in combination with exercise as well as the possible underlying mechanisms are covered in this systematic review. Expert Commentary: Current management of diabetic bone disease is based on principles of anti-osteoporotic treatment in non-diabetic subjects. However, studies are urged to investigate whether anti-resorptives are equally beneficial in type 2 diabetes as in non-diabetic individuals.

Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome. 52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts. miRNA discovery profiling was performed, using array technology, on plasma RNA. Validation was performed by quantitative polymerase chain reaction. The functional effect of miR-758-3p on its predicted target, cholesterol efflux regulatory protein/ATP-binding cassette transporter, was investigated using HepG2 liver cells. Custom miRNA profiling of 25 miRNAs in the discovery cohort found miR-758-3p to be detected in the obese cohort but undetected in the metabolic syndrome cohort. miR-758-3p was subsequently validated as a potential biomarker for metabolic syndrome by quantitative polymerase chain reaction. Bioinformatics analysis identified cholesterol efflux regulatory protein/ATP-binding cassette transporter as miR-758-3p's predicted target. Specifically, mimicking miR-758-3p in HepG2 cells suppressed cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression; conversely, inhibiting miR-758-3p increased cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression. miR-758-3p holds potential as a blood-based biomarker for distinguishing progression from obesity to metabolic syndrome and as a driver in controlling cholesterol efflux regulatory protein/ATP-binding cassette transporter expression, indicating it potential role in cholesterol control in metabolic syndrome.

The earthquake map of Denmark is constantly being improved. Together with data from western Sweden and southern Norway it shows more and more convincingly a gradual, scattered earthquake activity across the Kattegat region from low activity in the Precambrian basement of Scandinavia to lack of earthquakes in south-western Denmark and northern Germany. The activity is only partly connected with mapped geological features.

Anisotropic electronic transport is a possible route towards nanoscale circuitry design, particularly in two-dimensional materials. Proposals to introduce such a feature in patterned graphene have to date relied on large-scale structural inhomogeneities. Here we theoretically explore how a random, yet homogeneous, distribution of zigzag-edged triangular perforations can generate spatial anisotropies in both charge and spin transport. Anisotropic electronic transport is found to persist under considerable disordering of the perforation edges, suggesting its viability under realistic experimental conditions. Furthermore, controlling the relative orientation of perforations enables spin filtering of the transmitted electrons, resulting in a half-metallic anisotropic transport regime. Our findings point towards a co-integration of charge and spin control in a two-dimensional platform of relevance for nanocircuit design. We further highlight how geometrical effects allow finite samples to display finite transverse resistances, reminiscent of Spin Hall effects, in the absence of any bulk fingerprints of such mechanisms, and explore the underlying symmetries behind this behaviour., Comment: 11 pages, 6 figures

cope We aimed to investigate whether changes in the metabolome could explain observed changes in body composition in overweight adults after consumption of butter with high level of medium-chain fatty acids (MCFAs) in combination with casein or whey. Methods and results With GC-ToF and LC-Q/MS, we analyzed metabolites in plasma and urine from a 12-weeks randomized double-blinded human intervention including 52-abdominally overweight adults. The participants consumed 63 g/day of milk fat (high or low in MCFAs) and 60 g/day of protein (whey or casein). Urinary loss of the tricarboxylic acid cycle metabolites and a concomitantly increase of glycerol in blood were observed in the whey + high-MCFAs group, indicating potential lower anabolic processes, such as lipogenesis, by draining substrates. High intake of MCFAs resulted in elevated level of urinary adipic (independently of protein type) and plasma sebacic acid (with whey), indicating a potential increase in oxidation of MCFAs, which might lead to energy loss. Conclusion The type of protein showed highest effect on the overall metabolic profiles, but ω-oxidation of MCFAs in the liver seemed to be the main reason for the observed reduction in body fat mass after consumption of high MCFAs, independent of type of protein. This article is protected by copyright. All rights reserved

Since coffee may help to prevent the development of metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044) and homeostatic model assessment-insulin resistance (HOMA-IR) (mean difference = 15.29, p = 0.033), and plasma adiponectin levels (mean difference = -0.99 µg/mL, p = 0.048). The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating (mean difference = 4.75 U/L, p = 0.014) and intrahepatocellular alanine transaminase activity was assessed by hyperpolarized-13C nuclear magnetic resonance NMR spectroscopy and found to be reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

Background To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role in this compartment remains unclear. Objective The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge. Design Twelve healthy males were recruited for an acute crossover study that consisted of two tests each following an 8-hour fasting period. An oral glucose tolerance test (OGTT) was performed, and blood samples were collected over a 3-hour period. Following a period of at least 1 week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood-collection protocol. Results The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected, systemic insulin levels were lower during the IIGI compared with the OGTT (P < 0.05). miR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide (GLP)-1, GLP-2, and glucose-dependent insulinotropic polypeptide. Conclusions The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.

Background:Dietary medium-chain saturated fatty acids (MC-SFAs) have been shown to reduce total body fat. Previously, we showed that MC-SFAs prevent body fat accumulation, despite weight gain. Here, we aim to explore potential molecular mechanisms underlying the protective effect of MC-SFAs on body fat gain.Methods:The DairyHealth study examined the long-Term effects of milk protein and milk fat with a low or high content of MC-SFA. In this 12 week, randomized, double-blind, diet intervention study, participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (high MC-SFA or low MC-SFA) daily in a two by two factorial design. We used microarrays to measure whole genome gene expression changes in subcutaneous adipose tissue in a subpopulation of 12 participants, 6 in the low MC-SFA+casein group and 6 in the high MC-SFA+casein group. Gene expression of several genes that were found to be changed by MC-SFAs was confirmed in the full study population using qPCR.Results:High MC-SFA resulted in an upregulation of gene expression related to citric acid cycle and oxidative phosphorylation, and a downregulation of gene expression related to complement system and inflammation.Conclusions:We hypothesize that the beneficial effects of MC-SFAs on prevention of fat accumulation are mediated via increased gene expression related to energy metabolism in the adipose tissue. Decreases in inflammation-related gene expression may have beneficial effects in relation to cardiometabolic diseases. © 2017 Macmillan Publishers Limited, part of Springer Nature.

Roughness in graphene is known to contribute to scattering effects which lower carrier mobility. Encapsulating graphene in hexagonal boron nitride (hBN) leads to a significant reduction in roughness and has become the de facto standard method for producing high-quality graphene devices. We have fabricated graphene samples encapsulated by hBN that are suspended over apertures in a substrate and used noncontact electron diffraction measurements in a transmission electron microscope to measure the roughness of encapsulated graphene inside such structures. We furthermore compare the roughness of these samples to suspended bare graphene and suspended graphene on hBN. The suspended heterostructures display a root mean square (rms) roughness down to 12 pm, considerably less than that previously reported for both suspended graphene and graphene on any substrate and identical within experimental error to the rms vibrational amplitudes of carbon atoms in bulk graphite. Our first-principles calculations of the phonon bands in graphene/hBN heterostructures show that the flexural acoustic phonon mode is localized predominantly in the hBN layer. Consequently, the flexural displacement of the atoms in the graphene layer is strongly suppressed when it is supported by hBN, and this effect increases when graphene is fully encapsulated.

Zigzag edges of the honeycomb structure of graphene exhibit magnetic polarization making them attractive as building blocks for spintronic devices. Here, we show that devices with zigzag edged triangular antidots perform essential spintronic functionalities, such as spatial spin-splitting or spin filtering of unpolarized incoming currents. Near-perfect performance can be obtained with optimized structures. The device performance is robust against substantial disorder. The gate-voltage dependence of transverse resistance is qualitatively different for spin-polarized and spin-unpolarized devices, and can be used as a diagnostic tool. Importantly, the suggested devices are feasible within current technologies., Comment: 6 pages, 5 figures, published

BACKGROUND: Low-grade inflammation is involved in the development of diabetes and cardiovascular disease (CVD). Inflammation can be modulated by dietary factors. Dairy products are rich in saturated fatty acids (SFA), which are known to possess pro-inflammatory properties. However, different fatty acid compositions may exert different effects. Other components such as milk proteins may exert anti-inflammatory properties which may compensate for the potential negative effects of SFAs. Generally, the available data suggest a neutral role of dairy product consumption on inflammation.AIM: To investigate the effects of, and potential interaction between, a dietary supplementation with whey protein and milk fat, naturally enriched in medium-chain SFA (MC-SFA), on inflammatory markers in abdominal obese adults.METHODS: The study was a 12-week, randomized, double-blinded, intervention study. Sixty-three adults were equally allocated to one of four groups which received a supplement of either 60 g/day whey or 60 g/day casein plus 63 g/day milk fat either high or low in MC-SFA content. Fifty-two subjects completed the study. Before and after the intervention, changes in plasma interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA), high-sensitive C-reactive protein (hsCRP), adiponectin, and monocyte chemoattractant protein-1 (MCP-1) were measured. Changes in inflammatory genes in the subcutaneous adipose tissue were also documented.RESULTS: There were no differences in circulating inflammatory markers between protein types or fatty acid compositions in abdominally obese subjects, with the exception of an increase in adiponectin in response to high compared to low MC-SFA consumption in women. We found that combined dairy proteins and MC-SFAs influenced inflammatory gene expression in adipose tissue, while no effect was detected by dairy proteins or MC-SFA per se.CONCLUSION: Whey protein compared with casein and MC-SFA-enriched milk fat did not alter circulating markers of low-grade inflammation in abdominally obese subjects, except for an increase in circulating adiponectin in response to high MC-SFA in abdominally obese women.

AIMS/HYPOTHESIS: Heterozygous mutations in the insulin gene that affect proinsulin biosynthesis and folding are associated with a spectrum of diabetes phenotypes, from permanent neonatal diabetes to MODY. In vivo studies of these mutations may lead to a better understanding of insulin mutation-associated diabetes and point to the best treatment strategy. We studied an 18-year-old woman with MODY heterozygous for the insulin mutation p.R46Q (GlnB22-insulin), measuring the secretion of mutant and wild-type insulin by LC-MS. The clinical study was combined with in vitro studies of the synthesis and secretion of p.R46Q-insulin in rat INS-1 insulinoma cells.METHODS: We performed a standard 75 g OGTT in the 18-year-old woman and measured plasma glucose and serum insulin (wild-type insulin and GlnB22-insulin), C-peptide, proinsulin, glucagon and amylin. The affinity of GlnB22-insulin was tested on human insulin receptors expressed in baby hamster kidney (BHK) cells. We also examined the subcellular localisation, secretion and impact on cellular stress markers of p.R46Q-insulin in INS-1 cells.RESULTS: Plasma GlnB22-insulin concentrations were 1.5 times higher than wild-type insulin at all time points during the OGTT. The insulin-receptor affinity of GlnB22-insulin was 57% of that of wild-type insulin. Expression of p.R46Q-insulin in INS-1 cells was associated with decreased insulin secretion, but not induction of endoplasmic reticulum stress.CONCLUSIONS/INTERPRETATION: The results show that beta cells can process and secrete GlnB22-insulin both in vivo and in vitro. Our combined approach of immunoprecipitation and LC-MS to measure mutant and wild-type insulin may be useful for the study of other mutant insulin proteins. The ability to process and secrete a mutant protein may predict a more benign course of insulin mutation-related diabetes. Diabetes develops when the beta cell is stressed because of increased demand for insulin, as observed in individuals with other insulin mutations that affect the processing of proinsulin to insulin or mutations that reduce the affinity for the insulin receptor.

BACKGROUND: Vagal signaling is involved in gastric emptying and the secretion and effect of a number of hormones regulating gluco-metabolic processes and, thus, crucial for metabolic homeostasis.PURPOSE: We hypothesized that vagotomy would increase the risk of developing type 2 diabetes and examined the association between vagotomy and subsequent development of diabetes.METHODS: A nested case-control study was conducted with information on cases and controls from the Danish National Patient Registry. Cases included individuals with a diabetes diagnosis subsequent (>12months) to the first registration of vagotomy and/or upper gastrointestinal disease in the period 1977-2011. Controls had no subsequent diagnosis of diabetes and were matched by incidence density sampling, age and gender. Logistic regression analyses were conducted.RESULTS: 501,724 diabetes patients and 1,375,567 matched controls were included in the analysis. Vagotomy was performed on 2772 individuals and 148,489 individuals had an upper gastrointestinal diagnosis. In this combined population, 30,902 were diagnosed with diabetes. The mean follow-up was 16years. The unadjusted odds ratio for developing diabetes following vagotomy was 0.64 (95% confidence interval (CI): 0.58-0.71) and did not change in an adjusted analysis (0.64, 95% CI: 0.58-0.70). When restricting the multivariate-adjusted analysis to patients with type 2 diabetes and type 1 diabetes, respectively, the multivariate odds ratios were 0.79 (95% CI: 0.70-0.89) and 0.75 (95% CI 0.53-1.08), respectively.CONCLUSION: Vagotomy was associated with a significantly decreased risk of developing type 2 diabetes in a population of patients with upper gastrointestinal disease.

Metabolic syndrome (MetS) is a constellation of factors increasing the risk of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and cancer. MetS diagnosis is cumbersome and the precise diagnosis differs throughout the world. Efforts are underway to find MetS biomarkers that could all be analysed in a single blood sample. Here we review recent advances, including progress on circulating exosomes and microvesicles and their molecular contents, as well as DNA, RNAs, and proteins taken directly from blood samples. While additional research is now warranted to advance upon these findings, there is reason for optimising that such blood-based entities will be beneficial for MetS diagnosis and will help reduce risk of T2DM, CVD, and cancers, contributing both societal and economic benefit.