Nondiabetic Research Articles

Single-cell transcriptomes identify human islet cell signatures and reveal cell-type-specific expression changes in type 2 diabetes.

Blood glucose levels are tightly controlled by the coordinated action of at least four cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 (T2D) diabetes. Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet (dys)function, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single-cell transcriptomes for 638 cells from nondiabetic (ND) and T2D human islet samples. Analyses of ND single-cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single-cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell-type–specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis.

Impairment of neurovascular coupling in Type 1 Diabetes Mellitus in rats is prevented by pancreatic islet transplantation and reversed by a semi-selective PKC inhibitor

Streptozotocin (STZ)-induced chronic hyperglycemia has a detrimental effect on neurovascular coupling, linked to increased PKC-mediated phosphorylation and PKC isoform expression changes. Here, we sought to determine whether: 1) selective PKC-α/β/γ inhibitor, GF109203X, could reverse the effects of chronic hyperglycemia on cerebrovascular reactivity; 2) pancreatic islet transplantation could prevent the development of cerebrovascular impairment seen in a rat model of Type 1 Diabetes.We studied the effect of GF109203X in diabetic (DM), non-diabetic (ND), and transplanted (TR) Lewis rats during either sciatic nerve stimulation (SNS) or the topical applications of the large-conductance Ca2+-operated K+(BKCa) channel opener, NS1619, or the K+ inward rectifier (Kir) channel agonist, KCl. Pial arteriole diameter changes were monitored using a closed cranial window in vivo microscopy technique.The pial arteriole dilatory response associated with SNS was decreased by ~45%, when comparing DM vs either ND or TR rats. Also, pial arteriolar dilations to topical KCl and NS1619 were largely attenuated in DM rats, but not in ND or TR animals. These responses were completely restored by the acute application of GF109203X to the brain surface. The PKC inhibitor had no effect on vascular responses in normoglycemic and TR animals.In conclusion, DM-associated chronic impairment of neurovascular coupling may be readily reversed by a PKC-α/β/γ inhibitor or prevented via pancreatic islet transplantation. We believe that specific PCK isoforms (α/β/γ) are mechanistically linked to the neurovascular uncoupling seen with hyperglycemia.

Is β-cell aging involved in the pathogenesis of diabetes?

β-Cells at different stages have different functions and capacity for proliferation, regenerative and apoptosis. The aim of the present study was to investigate whether there are changes in β-cell phonotype in the development of diabetes to identify potential β-cell targets to prevent the progression of diabetes. A cross-sectional study was performed on pancreatic tissues obtained from 80 patients classified into three groups: 25 with type 2 diabetes (T2D), 25 with impaired fasting glucose (IFG), and 30 non-diabetics (ND). The ratio of the insulin-positive area to pancreatic area was used as an indirect marker of β-cell mass. Insulin-positive duct cells and scattered β-cells were defined as newly generated β-cells, whereas insulin/neurogenin 3 (Ngn3), insulin/v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) and insulin/P16 double-positive cells were defined as immature, mature, and senescent β-cells, respectively; Ki67 was used as a marker of cell proliferation, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) was used as a marker of cell apoptosis. Data were analyzed using the Kruskal-Wallis test. There were no significant differences in β-cell mass, the prevalence of insulin-positive duct cells, scattered β-cells, or insulin/Ngn3, insulin/MafA, and Insulin/Ki67 double-positive cells among groups. The incidence of insulin/P16 double-positive cells was significantly higher in T2D than ND. β-Cell apoptosis was significantly higher in T2D and IFG than ND. The senescence and apoptosis of β-cells may be involved in the course of diabetes.

Retrospective Analysis of Diabetics with Regard to Treatment Duration and Costs

Background: The increasing incidence of diabetes mellitus is also reflected in the patient population of a trauma and orthopaedic centre. Diabetics also exhibit more comorbidities than non-diabetics. In addition to surgical problems in these patients, hospitalisation is often accompanied by complications, which can prolong treatment and increase costs. The aim of this retrospective study is to analyse hospitalisation of diabetics compared to non-diabetics, as well as differences in treatment costs, depending on associated age and comorbidities. Patients/Material and Methods: 17,185 patients were treated at a transregional trauma and orthopaedic centre and were included in this retrospective analysis between 2012 and 2015. Comorbidities and hospitalisation of diabetics and non-diabetics were recorded. All costs charged by DRG were evaluated to calculate the cost per day and per patient, on the basis of the specific case rate. In this calculation, patient-related case rates were divided by the average residence time and the means of the calculated daily rates were calculated. Inclusion criteria were treatment within the various departments and a minimum hospitalisation of one day. Statistical analysis was performed with the SPSS program (version 22.0, SPSS Inc., Chicago, USA). Results: In comparison to non-diabetics (ND), diabetics (D) exhibited significantly more comorbidities, including: obesity, arterial hypertension, coronary heart disease, myocardial infarction (in the history), peripheral arterial disease, chronic kidney disease and hyperlipidaemia. Pneumonia in hospital was considerably commoner in diabetics (2.45 % [D] vs. 1.02 % [ND], p < 0.001). Time in hospital was significantly longer in diabetics (endoprosthetics 13.52 days [D] vs. 12.54 days [ND], p < 0.001; septic surgery 18.62 days [D] vs. 16.31 days [ND], p = 0.007; traumatology 9.82 days [D] vs. 7.07 days [ND], p < 0.001). For patients aged under 60 years, time in hospital was significantly longer for diabetics than for non-diabetics (9.98 days [D] vs. 6.43 days [ND] p < 0.001). Because of the longer time in hospital, treatment costs were higher by € 1,932,929.42 during the investigated time period. Conclusion: Because of their comorbidities, diabetics need to be categorised at an early stage as high-risk patients in traumatological and orthopaedic departments. Hospitalisation and the associated increased treatment costs, as well as postoperative complications, could be minimised in patients with diabetes by implementing an interdisciplinary treatment concept.

P11 Role of MIR-145 as a mediator of DNA damage and senescence in vascular smooth muscle cells from type 2 diabetes patients

Introduction Type 2 diabetes (T2DM) confers a significant risk of premature coronary heart disease and poor outcomes after saphenous vein (SV) bypass grafting. We previously reported an aberrant phenotype in smooth muscle cells (SMC) cultured from T2DM patients, and elevated expression levels of a small non-coding RNA, microRNA (miR)-145. Here we explored the ?relationship between miR-145 overexpression and the senescence- associated secretory phenotype (SASP). Methods Cultured SMC from non-diabetic (ND) and T2DM patients were investigated for markers of senescence (SA β-gal), DNA damage (γH2AX immunofluorescence) and expression of SASP molecules (real time RT-PCR). In some experiments, ND-SMC were exposed to a DNA damaging stimulus, (etoposide 5?µM) and in others, miR-145 expression was manipulated via transfection of pre-miR- or anti-miR-145, as appropriate. Results Native T2DM-SMC displayed increased levels of senescence (n = 7, p Conclusion T2DM SV-SMC are aberrant in terms of senescence, DNA damage and expression of miR-145. Overexpression of miR-145 in ND-SMC increases senescence, DNA damage and secretion of SASP molecules, particularly MCP-1. Delineation of the role of miR-145 as a cause or effect of DNA damage is an important aim.

Appendicitis in Diabetics: Predictors of Complications and Their Incidence

Appendicitis is the most common surgical emergency encountered by the general surgeon. Literature has demonstrated that diabetics may manifest atypical signs of infection, often clouding the diagnostic picture. We conducted a 3-year retrospective analysis of adults with appendicitis to determine differences in presentation, diagnosis, treatment, and outcomes for diabetic versus nondiabetic patients. Demographics, symptoms, imaging, procedure(s), complications, and length of stay (LOS) were obtained via chart review. Factors were compared between patients with and without diabetes using chi-squared test, t test, or Mann-Whitney U test (significance at P ≤ 0.05). Multivariate regression analysis identified variables predicting longer LOS or perforation at diagnosis. Overall, 339 patients met inclusion criteria [303 were nondiabetic (ND), 36 were diabetic (D)]. On univariate analysis, diabetics were more likely to have other comorbid illnesses: obesity (P < 0.001), chronic kidney disease (P = 0.003), hypertension (P < 0.001), coronary artery disease (P < 0.001), peripheral vascular disease (PVD, P = 0.31), and chronic obstructive pulmonary disease (P = 0.002). Diabetics presented with lower white blood cell counts (mean 14.2 ND, 11.9 D, P = 0.02), and were more likely to present with perforation (18.5% ND, 38.9% D, P = 0.008). LOS was longer in diabetics (1.0 day for ND, 3.0 day for D, P < 0.001). Complications were more frequent in diabetics (19.4% D vs 8.6% ND), which trended toward but failed to reach significance (P = 0.066). On multivariate analysis, however, old age was the only characteristic associated with perforation [odds ratio: 1.05 (1.02-1.06), P < 0.001], whereas diabetes, chronic obstructive pulmonary disease, and older age predicted longer LOS (P ≤ 0.001). Diabetics present a more complicated clinical picture having significantly more comorbidities and a trend toward postoperative complications necessitating a higher index of suspicion to detection complications. Further study is needed to evaluate the optimal diagnostic and management approach in this challenging population.

Altered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes.

Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes. T2D and ND hSMC secreted similar levels of IL1ß and vascular endothelial growth factor (VEGF). Treatment with the inflammatory agents lipopolysaccharide (LPS) or palmitate augmented the secretion of many myokines including: GROa, IL6, IL8, IL15, and TNFa, but did not consistently alter the protein content and/or phosphorylation of IkBa, p44/42 MAPK, p38 MAPK, c-Jun N-terminal kinase (JNK) and NF-kB, nor lead to consistent changes in basal and insulin-stimulated glucose uptake or free fatty acid oxidation. Conversely, treatment with pioglitazone or oleate resulted in modest reductions in the secretion of several myokines. Our results demonstrate that altered secretion of a number of myokines is an intrinsic property of skeletal muscle in T2D, suggesting a putative role of myokines in the response of skeletal muscle to T2D.

The effect of taurine and enriched environment on behaviour, memory and hippocampus of diabetic rats

Diabetes mellitus (DM) has been studied recently as a major cause of cognitive deficits, memory and neurodegenerative damage. Taurine and enriched environment have stood out for presenting neuroprotective and stimulating effects that deserve further study. In this paper, we examined the effects of taurine and enriched environment in the context of diabetes, evaluating effects on behaviour, memory, death and cellular activity. Eighty-eight Wistar rats were divided into 2 groups (E=enriched environment; C=standard housing). Some animals (24/group) underwent induction of diabetes, and within each group, some animals (half of diabetics (D) and half of non-diabetics (ND)/group) were treated for 30days with taurine (T). Untreated animals received saline (S). In total, there were eight subgroups: DTC, DSC, NDTC, NDSC, DTE, DSE, NDTE and NDSE. During the experiment, short-term memory was evaluated. After 30th day of experiment, the animals were euthanized and was made removal of brains used to immunohistochemistry procedures for GFAP and cleaved caspase-3. As a result, we observed that animals treated with taurine showed better performance in behavioural and memory tasks, and the enriched environment had positive effects, especially in non-diabetic animals. Furthermore, taurine and enriched environment seemed to be able to interfere with neuronal apoptosis and loss of glial cells, and in some instances, these two factors seemed to have synergistic effects. From these data, taurine and enriched environment may have important neurostimulant and neuroprotective effects.

Toll-like receptor 7 involves the injury in acute kidney ischemia/reperfusion of STZ-induced diabetic rats.

To determine whether Toll-like receptor 7 (TLR7) is the potential targets of prevention or progression in the renal ischemia/reperfusion (I/R) injury of STZ-induced diabetic rats. Thirty six Sprague-Dawley rats were randomly arranged to the nondiabetic (ND) or diabetic group (DM), with each group further divided into sham (no I/R injury), I/R (ischemia-reperfusion) and CD (given by Chloroquine) group. Preoperatively, Chloroquine (40 mg/kg, intraperitoneal injection.) was administrated 6 days for treatment group. I/R animals were subjected to 25 min of bilateral renal ischemia. Renal function, histology, apoptosis, cytokines, expression of TLR7, MyD88 and NF-κB were detected. The serum levels of blood urea nitrogen, creatinine, IL-6 and TNF-α, apoptotic tubular epithelial cells, expression of TLR7, MyD88 and NF-κB were significantly increased in DM+I/R group, compared with ND+I/R group (p<0.05). All these changes were further improved by TLR7 inhibition Chloroquine except Paller scores (p<0.05). Toll-like receptor 7 inhibition attenuates the acute renal ischemia/reperfusion injury of STZ-induced diabetic in SD rats.

COGNITIVE FUNCTION-A COMPARISON BETWEEN ELDERLY NON DIABETIC AND DIABETIC SUBJECTS.

30Jun 2016 COGNITIVE FUNCTION-A COMPARISON BETWEEN ELDERLY NON DIABETIC AND DIABETIC SUBJECTS. C.Anitha Mohan and P.Kannan. Assistant Professor, Institute of Physiology, Madurai Medical College, Madurai. Senoir Assistant Professor, Institute of Child Health and Research Centre, Government Rajaji Hospital, Madurai.

Resveratrol improves glycemic control in insulin-treated diabetic rats: participation of the hepatic territory.

BackgroundResveratrol is a natural polyphenol that has been proposed to improve glycemic control in diabetes, by mechanisms that involve improvement in insulin secretion and activity. In type 1 diabetes (T1D), in which insulin therapy is obligatory, resveratrol treatment has never been investigated. The present study aimed to evaluate resveratrol as an adjunctive agent to insulin therapy in a T1D-like experimental model.MethodsRats were rendered diabetic by streptozotocin (STZ) treatment. Twenty days later, four groups of animals were studied: non-diabetic (ND); diabetic treated with placebo (DP); diabetic treated with insulin (DI) and diabetic treated with insulin plus resveratrol (DIR). After 30 days of treatment, 24-hour urine was collected; then, blood, soleus muscle, proximal small intestine, renal cortex and liver were sampled. Specific glucose transporter proteins were analyzed (Western blotting) in each territory of interest. Solute carrier family 2 member 2 (Slc2a2), phosphoenolpyruvate carboxykinase (Pck1) and glucose-6-phosphatase catalytic subunit (G6pc) mRNAs (qPCR), glycogen storage and sirtuin 1 (SIRT1) activity were analyzed in liver.ResultsDiabetes induction increased blood glucose, plasma fructosamine concentrations, and glycosuria. Insulin therapy partially recovered the glycemic control; however, resveratrol as adjunctive therapy additionally improved glycemic control and restored plasma fructosamine concentration to values of non-diabetic rats. Resveratrol did not alter the expression of the glucose transporters GLUT2 and SGLT1 in the intestine, GLUT2 and SGLT2 in kidney and GLUT4 in soleus, suggesting that fluxes of glucose in these territories were unaltered. Differently, in liver, resveratrol promoted a reduction in Slc2a2, Pck1, and G6pc mRNAs, as well as in GLUT2 protein (P < 0.05, DIR vs. DI); besides, it increased (P < 0.01, DIR vs. DI) the hepatic glycogen content, and SIRT1 protein.ConclusionsResveratrol is able to improve glycemic control in insulin-treated T1D-like rats. This effect seems not to involve changes in glucose fluxes in the small intestine, renal proximal tubule, and soleus skeletal muscle; but to be related to several changes in the liver, where downregulation of Slc2a2/GLUT2, Pck1, and G6pc expression was observed, favoring reduction of glucose production and efflux. Besides, resveratrol increased SIRT1 nuclear protein content in liver, which may be related to the observed gene expression regulations.

The Effect of Aerobic Exercise Training on Plasma Apelin Levels and Pain Threshold in T1DM Rats.

BackgroundDiabetes mellitus (types 1 and 2) leads to secondary complications such as neuropathy, which reduce a patient’s quality of life. Apelin and its receptor, APJ, have been shown to have antinociceptive effects and to decrease blood glucose levels.ObjectivesThe present experimental study was conducted in Iran and investigated the role of apelin, which is used to manage type 1 diabetes mellitus, during exercise training.Materials and MethodsMale Wistar rats (n = 36) were assigned by simple random allocation to six groups (n = 6): non-diabetic (ND), diabetic (D), sedentary non-diabetic (SND), sedentary diabetic (SD), exercise non-diabetic (END), and exercise diabetic (ED). Diabetes was induced by a single subcutaneous injection of streptozotocin (50 mg/kg). Exercise training consisted of treadmill running 60 minutes/day × 5 days/week for 10 weeks. The tail-flick test was used to assess the thermal pain threshold, and an apelin enzyme immunoassay kit was utilized to assess plasma apelin levels.ResultsPlasma apelin level was higher (0.3 vs. 0.1, P < 0.0001) and the tail-flick latency was lower (2.2 vs. 3.8, P < 0.0001) in the D group than in the ND group. After the training program, plasma apelin levels decreased in the exercise groups, and the tail-flick latency increased in the ED group. No correlation was found between apelin blood concentrations and tail-flick latency following the training program in the ED group.ConclusionsThese findings suggest that apelin does not play any significant role in regulating the pain threshold in type 1 diabetes mellitus during exercise training.

Premature loss of muscle mass and function in type 2 diabetes

IntroductionMuscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. AimTo study whether adult DM2 patients up to 60years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. MethodologyAppendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. ResultsApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but did not correlate with ApFFM. ConclusionsWe found a clear deterioration of lean mass and muscle functions among adult DM2 patients of up to 60years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.

CRT-200.80 Primary Percutaneous Coronary Intervention in Diabetic Patients. Independents Predicitors of Survival and Event-free Survival

Some studies showed that diabetic patients (D) group (DG) had a worse outcome when compared to nondiabetic (ND) patients group (NDG), after primary percutaneous coronary intervention (PCI). The objectives were to compare mortality and major coronary events (MACE) at 30 days and 1 year of DG and NDG

The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study.

Background. The aim of this study was to validate the impact of type 2 diabetes (T2D) on the platelet reactivity in patients with acute ST elevation myocardial infarction (STEMI) treated with adenosine diphosphate (ADP) receptor blockers. Methods. A pilot prospective study was performed. Totally 67 patients were enrolled. 21 patients had T2D. Among all study population, 33 patients received clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor blocker therapy had been tested in two time intervals using light transmission aggregometry with specific inducer and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Results. There were no significant differences in platelet aggregability among T2D and nondiabetic (ND) group. The platelet reactivity index of VASP-P did not differ significantly between T2D and ND group (59.4 ± 30.9% versus 60.0 ± 25.2% and 33.9 ± 25.3% versus 38.6 ± 29.3% in second testing). The number of ADP receptor blocker nonresponders did not differ significantly between T2D and ND patients. The time interval from ADP receptor blocker loading dosing to the blood sampling was similar in T2D and ND patients in both examinations. Conclusion. This prospective study did not confirm the higher platelet reactivity and higher prevalence of ADP receptor blocker nonresponders in T2D acute STEMI patients.

Double product break point estimates ventilatory threshold in individuals with type 2 diabetes.

[Purpose] To verify the identification of the anaerobic threshold through the double product breakpoint (DPBP) method for individuals with type 2 diabetes. [Subjects and Methods] Nine individuals with T2D (7 females; age=63.2 ± 8.9 y) and 10 non-diabetic (ND) (7 females; age=58.3 ± 7.8 y) performed an incremental exercise test on a cycle ergometer. Heart rate (HR), blood pressure (BP) and expired gas were measured at the end of each stage. The ventilatory threshold (VT) and DPBP were considered as the exercise intensities above which an over proportional increases in VE and DP were observed in relation to increasing workload. [Results] No differences were observed between the workloads, HR and VO2 corresponding to the AT identified respectively by VT and DPBP. For the T2D, strong correlations between VT and DBPB workloads (r=0.853), HR (r=0.714), and VO2 (r=0.863) were found. These relationships were similar to those found for the control group (r=0.923; r=0.881; and r=0.863, respectively). [Conclusion] These results demonstrate that the DPBP enables for the prediction of AT and correlated well the VT in both the T2D and ND participants.

Both vascular endothelial growth factor and soluble Flt-1 are increased in type 2 diabetes but not in impaired fasting glucose.

Inadequate vascular remodeling is contributory to increased cardiovascular events in people with type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG). Vascular endothelial growth factor (VEGF) and its regulatory molecule soluble Flt-1(sFlt-1) play important roles in atherogenesis. We measured fasting plasma concentrations of VEGF and sFlt-1 in 11 nondiabetic (ND) (aged 46.1 +/- 2.1 years; body mass index [BMI], 26.1 +/- 0.9 kg/m; glucose, 5.0 +/- 0.1 mM), 15 IFG (aged 52.9 +/- 1.8 years; BMI, 32.7 +/- 1.3 kg/m; glucose, 6.4 +/- 0.1 mM), and 8 DM (aged 55.8 +/- 3.2 years; BMI, 30.0 +/- 1.0 kg/m; glucose, 9.3 +/- 0.5 mM) subjects. Plasma VEGF (42.1 +/- 4.0 vs 24.2 +/- 0.9 vs 29.4 +/- 3.8 pg/mL, respectively) and sFlt-1 (119.4 +/- 4.9 vs 58.9 +/- 3.2 vs 56.7 +/- 1.2 pg/mL, respectively) concentrations were higher (P < 0.04) in DM than IFG and ND subjects. Whereas VEGF concentrations were significantly lower (P < 0.05) in IFG than in ND subjects, sFlt-1 concentrations did not differ between the IFG and ND subjects. Although plasma VEGF concentrations were higher (35%) in DM than in ND subjects, VEGF action on vascular remodeling was likely attenuated by higher sFlt-1 concentrations in DM. In contrast, IFG subjects did not have major perturbations in either VEGF or sFlt-1 levels. Further studies defining the roles of these mediators in DM and IFG are necessary to extend these observations.

Time in blood glucose range 70 to 140 mg/dl >80% is strongly associated with increased survival in non-diabetic critically ill adults.

IntroductionHyperglycemia, hypoglycemia and increased glucose variability are independently associated with increased risk of death in critically ill adults. The relationship between time in targeted blood glucose range (TIR) and mortality is not well described and may be a factor that has confounded the results of the major interventional trials of intensive insulin therapy.MethodsWe conducted a retrospective analysis of prospectively collected data involving 3,297 patients with intensive care unit (ICU) lengths of stay (LOS) of ≥1.0 day who were admitted between 1 January 2009 and 31 December 2013 to a single mixed medical-surgical ICU. We investigated the relationship between TIR 70 to 140 mg/dl with mortality and compared outcomes of non-diabetics (NON) and individuals with diabetes mellitus (DM), including stratifying by TIR above (TIR-hi) and below (TIR-lo) the median value for the NON and DM groups.ResultsThere were 85,799 blood glucose (BG) values for the NON group and 32,651 for the DM group, and we found that 75.5% and 54.8%, respectively, were between 70 and 140 (P <0.0001). The median (interquartile range) TIR (%) values for the NON and DM groups were 80.6% (61.4% to 94.0%) and 55.0% (35.5% to 71.1%), respectively (P <0.0001). For the NON group, mortality was 8.47% and 15.71% for TIR-hi and TIR-lo, respectively (P <0.0001). For the DM group, mortality was 16.09% and 14.44% for TIR-hi and TIR-lo, respectively (P = NS). We observed similar relationships for the NON group when we stratified by ICU LOS or severity of illness, especially in the most severely ill patients. There was a cumulative interaction of indices of hypoglycemia, hyperglycemia or glucose variability with TIR. Multivariable analysis demonstrated, for the NON group, that TIR-hi was independently associated with increased survival (P =0.0019). For the NON group, the observed-to-expected mortality ratios for TIR-hi and TIR-lo, based on Acute Physiology and Chronic Health Evaluation IV methodology, were 0.53 and 0.78, respectively. In contrast, among those in the DM group, there was no clear relationship between TIR 70 to 140 mg/dl and survival.ConclusionsIndependently of ICU LOS and severity of illness, TIR 70 to 140 mg/dl >80% is strongly associated with survival in critically ill patients without diabetes. These findings have implications for the design of clinical protocols for glycemic control in critically ill patients as well for the design of future interventional trials of intensive insulin therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0908-7) contains supplementary material, which is available to authorized users.

Effect of 12 Weeks of Periodized Resistance Training Upon Total Plasma Adiponectin Concentration in Healthy Young Men.

The effects of resistance training on adiponectin have thus far yielded equivocal results. However, the effect of periodized resistance training on plasma adiponectin in offspring of type 2 diabetic and nondiabetic (ND) parents (first-degree family history) has yet to be determined. Untrained healthy young men with and without a first-degree family history of type 2 diabetes were assigned to an exercise intervention group (E) or an active control group (C). The E group performed a 12-week periodized resistance training program, whereas the C group did not participate in any structured exercise program. Fasting plasma samples were obtained pre- and posttraining. Total plasma adiponectin changed significantly in the E group (33.7 ± 14.7%, p = 0.025) but not in the C group (10.8 ± 19.2%). Offspring of type 2 diabetic parents subjects had significantly greater improvements in plasma adiponectin (69.3 ± 34.8%) compared with ND subjects (-3.2 ± 29.9%, p = 0.046). Regular aerobic exercise was significantly correlated with average plasma adiponectin (r = 0.32), whereas first-degree family history of type 2 diabetes (r = -0.58) and decreases in body fat percentage (r = -0.77) were inversely correlated with average plasma adiponectin. Periodized high-intensity resistance training seems to increase plasma adiponectin, particularly in individuals with a first-degree family history of type 2 diabetes or those who experience a significant loss of fat mass. The direct correlation between regular aerobic exercise and adiponectin further suggests that a combination of aerobic and resistance training yields greater improvements in plasma adiponectin compared with resistance training alone.

Influence of menopause and Type 2 diabetes on pulmonary oxygen uptake kinetics and peak exercise performance during cycling.

We investigated if the magnitude of the Type 2 diabetes (T2D)-induced impairments in peak oxygen uptake (V̇O2) and V̇O2 kinetics was affected by menopausal status. Twenty-two women with T2D (8 premenopausal, 14 postmenopausal), and 22 nondiabetic (ND) women (11 premenopausal, 11 postmenopausal) matched by age (range = 30-59 yr) were recruited. Participants completed four bouts of constant-load cycling at 80% of their ventilatory threshold for the determination of V̇O2 kinetics. Cardiac output (CO) (inert gas rebreathing) was recorded at rest and at 30 s and 240 s during two additional bouts. Peak V̇O2 was significantly (P < 0.05) reduced in both groups with T2D compared with ND counterparts (premenopausal, 1.79 ± 0.16 vs. 1.55 ± 0.32 l/min; postmenopausal, 1.60 ± 0.30 vs. 1.45 ± 0.24 l/min). The time constant of phase II of the V̇O2 response was slowed (P < 0.05) in both groups with T2D compared with healthy counterparts (premenopausal, 29.1 ± 11.2 vs. 43.0 ± 12.2 s; postmenopausal, 33.0 ± 9.1 vs. 41.8 ± 17.7 s). At rest and during submaximal exercise absolute CO responses were lower, but the "gains" in CO larger (both P < 0.05) in both groups with T2D. Our results suggest that the magnitude of T2D-induced impairments in peak V̇O2 and V̇O2 kinetics is not affected by menopausal status in participants younger than 60 yr of age.