Effect Of Type 2 Diabetes Mellitus Research Articles

P6309Impaired secretion of clusterin in pericardial fluid of diabetics, a deleterious outcome for the cardiac micro-vasculature

Abstract Background Extracellular vesicles are vital mediators of cell-to-cell communications. We previously demonstrated that in the adult heart, exosomes released in the pericardial fluid (PF) have the functional capability to induce cell survival and angiogenesis in recipient endothelial cells. It has previously been shown that PF exosomes from patients with an existing myocardial infarction (MI) contain clusterin (CLU). Remarkably, secreted CLU is cardio-protective as evidenced by enhanced arteriogenesis and reduced apoptosis in animal models of MI. We hypothesize that type 2 Diabetes Mellitus (T2DM) along with ischemic heart disease (IHD) alters PF EV content impairing its reparative angiogenic potential. Aim To investigate the role of T2DM in modulating human PF exosomal content and its vascular action. Methods and results PF samples were collected from 3 different groups of patients (N=3): 1) Ischemic heart disease (IHD) with or 2) without T2DM, and 3) non-ischaemic, non-diabetic controls operated for mitral valve repair. The impact of PF exosomes on human coronary microvascular ECs (HCMECs) was evaluated by cell based functional assays for measuring apoptosis, proliferation and angiogenesis. Interestingly, unlike PF exosomes from control patients, PF exosomes from DM patients with IHD promoted EC apoptosis and impaired angiogenesis. To investigate the effect of T2DM on PF content, we performed high throughput proteomic and metabolomic analysis of whole PF and PF EVs. We identified proteins and metabolites that were differentially expressed under T2DM condition by using the R package Limma. Employing a network approach, protein and metabolic data were integrated by using our newly developed inhouse R package Metabosignal. This networks approach revealed an interesting interaction circuit involving protein CLU. The T2DM-associated reduction of CLU level in the PF, identified from the “omics” analyses was confirmed by ELISA (n=8 patients per group). To examine the effects of DM and ischemia on CLU intracellular expression and secretion, HCMECs were exposed to high D-glucose (HG, 25 mM) and hypoxia (1%O2). In line with our PF data, HCMECs exposed to HG and hypoxia showed lower levels of both CLU mRNA and secreted CLU (ELISA). Importantly, recombinant CLU (rCLU) treatment on HCMECs rescued their angiogenic potential, induced cell proliferation and protected them from apoptosis under both HG and hypoxia conditions. In addition, silencing of endogenous levels of CLU in HCMECs impaired angiogenesis, suggesting that CLU might be an inherent component of the angiogenesis machinery in ECs. Conclusions This study suggests that DM reduces the level of secreted CLU in the PF, depriving myocardial micro-vessels of this protective and regenerative mediator. Restoring diminished CLU levels in the diabetic heart could be a possible therapeutic approach for contrasting diabetic micro-angiopathy. Acknowledgement/Funding British Heart Foundation Program Grant

Microbiome, diabetes and heart: anovel link?

Patients with type2 diabetes suffer from a high cardiovascular risk. The underlying pathomechanisms are not fully understood and treatment options are correspondingly limited. The gut microbiome could be anew important player in cardiometabolic diseases. Dysbiosis of the intestinal flora has been associated with insulin resistance, diabetes mellitus and cardiovascular diseases, such as atherosclerosis and heart failure. The negative cardiovascular effects of type2 diabetes mellitus could therefore partly be mediated by gut microbiota. This review article discusses specific gut microbiome-associated mechanisms, which are modulated in both type2 diabetes and cardiovascular diseases. It is presented how intestinal bacteria may contribute to systemic low-grade inflammation. Furthermore, it is shown how the intestinal microbiome as a complex metabolic organ is able to influence the cardiometabolic phenotype via production of bioactive metabolites. Further studies will have to demonstrate whether these mechanisms contribute to the high cardiovascular risk in type2 diabetes.

Abstract TP130: Transcriptome Analysis of Mononuclear Cell Responses After Ischemic Stroke in Type 2 Diabetic Mice

Introduction: Type 2 diabetes mellitus (T2DM) is a major risk factor of ischemic stroke and is associated with poor outcome after stroke. However, the mechanisms underlying the detrimental effects of diabetes are largely unclear. We used single-cell RNA sequencing (scRNA seq) to determine the transcriptome profiles of blood peripheral mononuclear cells (BPMNs) under diabetic and ischemic conditions using T2DM mouse model. Hypothesis: The altered gene expression under diabetic condition affects the normal differentiation of BPMNs, resulting in the aggravation of ischemic brain injury. Methods: We performed scRNA seq for BPMNs from four groups of mice, consisting of db/db mice with or without stroke and db/+ mice with or without stroke. Stroke was induced by distal middle cerebral artery occlusion. We specified the cell types of BPMNs and compared the transcriptome among the groups of mice. We assessed the biological role of identified differentially expressed genes (DEGs) by enrichment analysis. Results: In the comparison between db/db and db/+ groups, 168 up-regulated and 245 down-regulated DEGs were identified. The db/db group was composed of a larger population of macrophages and a smaller population of lymphocytes compared to db/+ group. The gene Cebpa , known to be associated with myeloid maturation, was significantly down-regulated in monocytes/macrophages, indicating the adverse effect of diabetes on the normal differentiation of myeloid cells. In addition, enrichment analysis revealed that up-regulated DEGs were related to the gene ontology term translation in B cells and innate immune response in monocytes. On the other hand, the down-regulated DEGs were related to antigen processing and presentation in macrophages. In the comparison between stroke and non-stroke groups, 21 up-regulated and 223 down-regulated DEGs were identified, in which down-regulated DEGs were related to cellular oxidant detoxification in T cells. Conclusions: The present study demonstrated altered gene expression profile and molecular network across various cell types in PBMCs in response to diabetic and ischemic conditions by scRNAseq, providing a clue to the underlying mechanism of the adverse effect of T2DM on native immunity and response to stroke.

Menopause and diabetes: EMAS clinical guide

IntroductionWhether menopause increases the risk of type 2 diabetes mellitus (T2DM) independently of ageing has been a matter of debate. Controversy also exists about the benefits and risks of menopausal hormone therapy (MHT) in women with T2DM. AimsTo summarise the evidence on 1) the effect of menopause on metabolic parameters and the risk of T2DM, 2) the effect of T2DM on age at menopause, 3) the effect of MHT on the risk of T2DM, and 4) the management of postmenopausal women with T2DM. Materials and methodsLiterature review and consensus of experts’ opinions. Results and conclusionMetabolic changes during the menopausal transition include an increase in and the central redistribution of adipose tissue, as well as a decrease in energy expenditure. In addition, there is impairment of insulin secretion and insulin sensitivity and an increase in the risk of T2DM. MHT has a favourable effect on glucose metabolism, both in women with and in women without T2DM, while it may delay the onset of T2DM. MHT in women with T2DM should be administered according to their risk of cardiovascular disease (CVD). In women with T2DM and low CVD risk, oral oestrogens may be preferred, while transdermal 17β-oestradiol is preferred for women with T2DM and coexistent CVD risk factors, such as obesity. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as progesterone, dydrogesterone or transdermal norethisterone. Postmenopausal women with T2DM should be managed primarily with lifestyle intervention, including diet and exercise. Most of them will eventually require pharmacological therapy. The selection of antidiabetic medications should be based on the patient’s specific characteristics and comorbidities, as well on the metabolic, cardiovascular and bone effects of the medications.

Study of the Osteoporotic Changes in Postmenopausal Women with Type-2 Diabetes Mellitus

Introduction: Osteoporosis and Diabetes Mellitus (DM) are common medical conditions in the society with an increasing prevalence in elderly people. Osteoporosis is more common in female than male and postmenopausal women are vulnerable to it. Objective: The aim of this study was to verify the effect of type-2 diabetes mellitus on bone mineral density in postmenopausal women and, thereby, to evaluate the risk of osteoporosis in them. Materials and Methods: This cross-sectional study was carried out at National institute of Nuclear Medicine and Allied Sciences (NINMAS), BSMMU campus, Shahbagh, Dhaka, over a period of one year. 175 postmenopausal women were enrolled as study subjects, among them 72 (41.10%) were diabetic and rest 103 (59.90%) were nondiabetic and they were assigned as Group-I and Group-II respectively. The bone mineral density (BMD) was measured by central DEXA device at lumbar spines and left femoral neck of each study subject. Results: The mean (±SD) ages of group-I and group-II were 58.79 (±8.06) and 58.27 (±8.39) respectively with an age range of 45 to 75 years in both cases. A total of 30 (41.66%) patients in diabetic group (group-I) and 40 (38.83%) patients in non-diabetic (group-II) had osteoporosis at lumbar spines. On the other hand, 40 (56.94%) patients in group-I and 58 (56.31%) patients in group-II had osteoporosis at femoral neck. The Odds Ratios of osteoporosis for lumbar spines and femoral. neck were 1.125 and 1.026 respectively. The differences of frequencies of osteoporosis between group-I and group-II were not statistically significant at any anatomical site and the association between osteoporosis and type-2 diabetes mellitus was not significant. According to Odds Ratio type-2 diabetes mellitus was not a risk factor for developing osteoporosis in postmenopausal women. Conclusion: Postmenopausal women are prone to develop osteoporosis and type-2 diabetes mellitus may have adverse influence on osteoporosis, which was supported by few previous studies. This study could not establish any significant effect of type-2 diabetes mellitus on osteoporosis in postmenopausal women.Bangladesh J. Nuclear Med. 18(1): 21-26, January 2015

Cardiac autonomic neuropathy may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus.

Cardiac autonomic neuropathy (CAN) is a frequent and severe complication of type 1 diabetes mellitus (T1DM). CAN diagnosis is associated with increased cardiovascular morbidity and mortality, often due to progressive atherosclerosis. Carotid intima media thickness (CIMT) is a surrogate marker of the atherosclerosis. The aim of our study was to evaluate the relationship between CIMT and CAN in T1DM patients. Total of 49 T1DM patients and 45 healthy controls were examined for CAN presence and CIMT. CAN was diagnosed based on the results of Ewing test battery and spectral analysis of heart rate variability. CIMT was measured by two-dimensional ultrasound. Biochemical, anthropometric and anamnestic risk markers of atherosclerosis were evaluated. We used logistic types of generalized additive models (GAM) for statistical analysis. CAN was detected in 22 out of 49 T1DM patients (45%). All 45 healthy controls had normal cardiovascular autonomic tests results. CIMT was significantly positively associated with T1DM diagnosis (p=0.0251), CAN diagnosis (p=0.007), age (p<0.0001), BMI (p=0.0435) and systolic blood pressure (p=0.0098). CAN effect on CIMT interacted with the effect of T1DM. The combination of both factors significantly increased CIMT more than the sum of the individual T1DM and CAN status. CAN is significantly associated with higher CIMT in T1DM patients. CAN may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus.

Insulin does not rescue cortical and trabecular bone loss in type 2 diabetic Goto-Kakizaki rats.

In type 2 diabetes mellitus (T2DM), the decreased bone strength is often associated with hyperglycemia and bone cell insulin resistance. Since T2DM is increasingly reported in young adults, it is not known whether the effect of T2DM on bone would be different in young adolescents and aging adults. Here, we found shorter femoral and tibial lengths in 7-month, but not 13-month, Goto-Kakizaki (GK) T2DM rats as compared to wild-type rats. Bone µCT analysis showed long-lasting impairment of both cortical and trabecular bones in GK rats. Although insulin treatment effectively improved hyperglycemia, it was not able to rescue trabecular BMD and cortical thickness in young adult GK rats. In conclusion, insulin treatment and alleviation of hyperglycemia did not increase BMD of osteopenic GK rats. It is likely that early prevention of insulin resistance should prevail over treatment of full-blown T2DM-related osteopathy.

Outcome Analysis of Patients with Gallstone Disease Receiving Cholecystectomy: A Population-Based Cohort Study

Background/Aims: Cholecystectomy is generally performed to treat patients with gallstone disease (GSD) in clinical practice. The present study aimed to investigate whether type 2 diabetes mellitus (T2DM) may influence the overall survival of GSD patients. Methods: The National Health Insurance Research Database, a population-based registry data in Taiwan, was used to identify GSD patients from 2001 to 2008. The risk of cancers and effects of T2DM on the overall survival of GSD patients receiving cholecystectomy were estimated by hazards ratios (HRs) and 95% CIs using the Cox proportional hazard model. Results: Among 392,028 eligible GSD patients, 81,971 underwent cholecystectomy, whereas 310,057 did not. After cholecystectomy, the HR for developing cancer was 1.14. The HR for the overall survival was 0.74-fold lower for patients who underwent cholecystectomy than that for patients who did not. GSD patients without T2DM who underwent cholecystectomy (0.78-fold lower risk) had a longer survival, whereas those with T2DM had shorter survival (1.64-fold higher risk without cholecystectomy and 1.13-fold higher risk with cholecystectomy) compared with those without T2DM who did not undergo cholecystectomy. Conclusions: Our major findings suggest that T2DM may worsen the prognosis of GSD patients after cholecystectomy, which provides useful insight into the treatment of T2DM among GSD patients in clinical settings.

Sexual dysfunction in female patients with type 2 diabetes mellitus: a cross-sectional single-centre study among Turkish patients

The aim of the study was to assess the prevalence of female sexual function and related factors in Turkish women with type 2 diabetes mellitus (T2DM). A total of 93 female patients diagnosed with T2DM (age 48.0 ± 7.2 years (Mean ± SD) were included. Data on age, diabetes age, HbA1c level, educational level, diabetes treatment, diabetes-related complications, co-morbid disorders and concomitant medications were recorded, as were the scores obtained using a Female Sexual Function Index (FSFI) questionnaire. Sexual dysfunction was noted in 55.9% of patients including problems related to desire (60.2%), arousal (52.7%), lubrication (55.9%), orgasm (51.6%) and satisfaction (58.1%) as well as pain during sexual intercourse (54.8%). Total scores were correlated negatively to age (r= −0.329, p = 0.001) and duration of diabetes (r= −0.246, p = 0.018), while significantly higher in patients with than without hypertension (19.6 vs. 22.4, p = 0.012) and with than without insulin therapy (20.0 vs. 23.7, p = 0.050). Our findings indicate the adverse effects of T2DM on sexual function in 55.9% of women in all domains of sexual response cycle, although this seems to be associated with older age, longer duration of diabetes, insulin and antidepressant therapy, presence of hypertension as well as end-organ complications of neuropathy and coronary artery disease (CAD).

Hyperglycemia is associated with increased risk of patient delay in pulmonary tuberculosis in rural areas.

Excessive time between the first presentation of symptoms of pulmonary tuberculosis (PTB) and diagnosis contributes to ongoing transmission and increased risk of infection in the community, as well as to increased disease severity and higher mortality. People with type 2 diabetes mellitus (T2DM) have a higher risk of developing PTB. However, the effect of T2DM on delayed diagnosis of PTB is not fully understood. This study investigated the effects of hyperglycemia (diabetes and prediabetes) and other factors on PTB patient delay in a rural area of China. In the present community-based investigation, PTB patients aged ≥16 years newly diagnosed at county tuberculosis dispensaries were recruited consecutively between September 2011 and December 2013. Fasting blood glucose was determined in all subjects, and a structured questionnaire was used to collect basic information. Of the 2280 patients, 605 (26.5%) had hyperglycemia. The median (interquartile range) time to seeking health care was 44 (59) days. Health care seeking was delayed in 1754 subjects, and hyperglycemia was independently associated with an increased probability (odds ratio 2.10; 95% confidence interval 1.49-2.97) of patient delay in subjects aged ≥30 years. Other factors associated with patient delay were cough, night sweats, and lack of knowledge regarding typical tuberculosis symptoms. The onset of hemoptysis was negatively correlated with patient delay. Patient delay appears to be a serious problem in this rural area with a high prevalence of tuberculosis. Hyperglycemia is independently associated with an increased probability of patient delay, which, in turn, may result in more serious clinical manifestations.

Increased Benefit With Vorapaxar Use in Patients With a History of Myocardial Infarction and Diabetes Mellitus: What the Data Show Us.

Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial metabolic disease mainly characterized by hyperglycemia and insulin resistance. Abnormal platelet reactivity associated with an increased risk of cardiovascular disease (CVD) is also a feature characteristic of patients with T2DM. Dual antiplatelet therapy consisting of aspirin and an adenosine diphosphate platelet P2Y12 receptor antagonist, such as clopidogrel, represents the standard antithrombotic regimen for the secondary prevention of CVD risk in T2DM. However, a high proportion of patients with T2DM exhibit high on-treatment platelet reactivity to aspirin and/or clopidogrel, associated with a greater risk of adverse cardiovascular events compared with nondiabetic patients. Consequently, novel antiplatelet therapeutic approaches may be required in order to avoid such events. Vorapaxar is a novel antiplatelet agent that targets the platelet protease-activated receptor 1 and inhibits thrombin-induced platelet activation. Vorapaxar has been studied in 2 phase III clinical trials and has been approved for use in the secondary prevention of atherothrombotic events in patients with a previous myocardial infarction (MI) or peripheral arterial disease. New data from the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial MI cohort demonstrate that the subgroup of patients with T2DM exhibits increased benefit from vorapaxar use compared with non-T2DM patients. The aim of the present work is to critically review the current knowledge concerning vorapaxar use in patients with T2DM as well as to discuss the possible mechanism(s) underlying vorapaxar's beneficial effect in T2DM.

Effect of Type2 Diabetes Mellitus on Sudanese Male Fertility

The main objective of the study was to evaluate the effect of type2 diabetes mellitus on Sudanese male fertility. The second objective was to correlate the presence of hypogonsdism in diabetic subjects with age, glycemic control and duration of diabetes. A cross sectional study conducted on 300 men with type2 diabetes mellitus aged >40 years and 100 healthy men age matched. Total testosterone, follicle stimulating hormone, lutenizing hormone and HbA1c were measured. Data about age and duration of diabetes were collected. Results were computed using SPSS (statistical package for social science) software. Significant proportion of diabetic men showed low levels of serum testosterone (hypogonadal), with (78%) had testosterone level below 300 ng/dl (10.4 nmol/liter) and significant increase levels of FSH and LH in hypogonadal patients (P <0.05). The control group included 10% hypogonadal subjects. Testosterone had inverse linear relationship with age of diabetic subjects and no relationships with duration of diabetes and HbA1c. Serum testosterone levels were significantly low in Sudanese diabetic males, this accompanied with significantly high levels of FSH and LH. Testosterone level inversely correlated with age, but not with HbA1c and duration of diabetes. Keywords: Type-2 Diabetes Mellitus, Testosterone, Follicle Stimulating Hormone, Leutenizing Hormone, HbA1c

Retinal blood flow is increased in type 1 diabetes mellitus patients with advanced stages of retinopathy.

BackgroundDiabetic retinopathy (DRP) is a common microvascular complication seen in patients with type 1 diabetes mellitus (T1DM). The effects of T1DM and concomitant (proliferative) DRP on retinal blood flow are currently unclear. Therefore, we measured retinal vascular blood flow in T1DM patients with and without DRP and non-diabetic controls. We further assessed the acute effects of panretinal photocoagulation on retinal microvascular bloodflow in eight patients with diabetes.MethodsThirty-three T1DM patients with proliferative DRP, previously treated with panretinal photocoagulation (pDRP), 11 T1DM patients with untreated non-proliferative retinopathy (npDRP) and 32 T1DM patients without DRP (nDRP) were compared with 44 non-diabetic gender-matched controls. Using scanning laser Doppler flowmetry (HRF, Heidelberg) blood flow in the retinal microvasculature was measured temporal and nasal of the optic disc and averaged into one flow value per eye. The right eye was used as a default for further analyses. Eight patients with novel proliferative retinopathy (4 T1DM and 4 with type 2 diabetes) were measured before and several months after photocoagulation. Between-group differences in retinal blood flow were assessed using ANOVA corrected for multiple comparisons (Bonferroni).ResultsRetinal blood flow was higher in the treated pDRP compared with the nDRP group and controls (all PBonferroni < 0.01). Furthermore, there was a positive linear trend for blood flow with lowest blood flow in the control group and highest in the pDRP group (P-for-trend < 0.01). In the eight patients with novel proliferative retinopathy, blood flow did not significantly change before and after panretinal photocoagulation (P > 0.05). Using regression analysis, no variables were found as predictors of retinal blood flow.ConclusionsIn comparison with controls and nDRP patients, retinal blood flow significantly increased in the pDRP group, which previously underwent photocoagulation treatment, but not in the npDRP patients. These changes may be a consequence of a failing vascular autoregulation in advanced diabetic retinopathy.

Evaluation of pulmonary functions in patients of type-2 diabetes mellitus

Background: The review of literature revealed conflicting documentation regarding the effect of type-2 DM (diabetes mellitus) on pulmonary functions. Some authors have reported normal pulmonary functions and even concluded that spirometry testing is not at all necessary in diabetic patients. Some studies have shown abnormal pulmonary functions in patients of DM. Moreover, the duration of DM and glycemic control have varied impact on the pulmonary functions. The present study was undertaken to resolve the conflict and also to explore the pulmonary functions in type-2 diabetics of this cross section of population. Methods: The pulmonary function tests FVC, FEV1, FEV3, PEFR and MVV were performed in 50 type-2 diabetics and 50 controls by computerized medspiror using standard laboratory methods. The data was documented statistically analyzed. By giving suitable class intervals, intra-diabetic groups were made to assess the effect of extent duration of diabetics on pulmonary function test. Results: Pulmonary functions FVC, FEV1, FEV3 PEFR and MVV were decreased in type-2 diabetes mellitus. Duration of type 2 DM was significantly associated with decrease in FVC, FEV1%, PEFR and MVV. Conclusions: Longer duration of type 2 diabetes is significantly associated with reduction in pulmonary functions FVC, FEV1%, PEFR and MVV which underlines the respiratory system as one of the target organs of type-2 diabetes mellitus.

Propolis restored adiponectin level in type 2 diabetes through PPARγ activation

Adipose tissue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. Hypoadiponectinemia contributes to the development of obesity and related disorders such as diabetes, hyperlipidemia, and cardiovascular diseases. In this study, we investigated the effects of Brazilian propolis on adiponectin levels in type 2 diabetes mellitus (T2DM), the mechanism of signaling pathway was explored as well. T2DM was induced in male Wistar rats using high fat diet and low dose of streptozotocin (STZ, 35 mg/kg, i.p.). Propolis was administered by oral tubes. Peroxisome proliferator activated receptor gamma (PPARγ) levels in sub abdominal adipose tissue, serum levels of adiponectin, tumor necrosis factor-α (TNF-α) and insulin were detected by Enzyme Linked Immunosorbent Assay (ELISA). Malondialdehyde (MDA) and reduced glutathione (GSH) in sub abdominal adipose tissue, fasting plasma glucose, plasma triglycerides and total cholesterol levels were measured by colorimetric method. Results showed that Brazilian propolis ameliorated hypoadiponectinemia in T2DM rats and relieved high glucose-induced adiponectin decrease. The signaling pathway analysis indicated that PPARγ regulation was involved. In conclusion, Brazilian propolis could have beneficial effect in T2DM by increasing tissue PPARγ levels, restoring serum adiponectin levels, enhancing insulin sensitivity and subsequently, attenuating elevated glucose level.

The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice

Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin–angiotensin–aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II–AT1R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events.

Double trouble: T2DM genetic risk factors play a causal role in CAD.

Double trouble: T2DM genetic risk factors play a causal role in CAD.

Quantitative stress echocardiography in pediatric patients with type-1 diabetes mellitus

s of the 51st Workshop for Pediatric Research 51st Workshop for Pediatric Research Gottingen, Germany 16-17 April 2015 This supplement has not been sponsored. Meeting abstracts Aims Type-1 diabetes mellitus (T1DM) is among the most common chronic diseases in children. Serious long-term complications include both ultra-morphologic and functional cardiac impairment. Whether these pathologic processes already take place in the early phase of T1DM yet has to be determined. Aim of this prospective, blinded, clinical study was to assess the effect of T1DM on left ventricular (LV) myocardial function in pediatric patients using quantitative stress echocardiography. Methods We included 40 patients with T1DM (aged 11.53 ± 3.1 years) and 44 sex-matched healthy controls (11.43 ± 2.9 years; p = 0.91). Conventional and quantitative echocardiography was performed both at rest and during physical exercise on a bicycle. Myocardial strain and strain rate were measured using speckle tracking echocardiography. Results Children with T1DM had increased myocardial contractility both at rest and at all levels of physical stress testing when compared to healthy volunteers. At rest, T1DM patients had significantly higher circumferential strain rate (-2.05 ± 0.35 s -1 ) than healthy controls (-1.86 ± 0.25 s -1 ; p = 0.016). During exercise, diabetic children showed more negative values for longitudinal strain rate (-2.59 ± 0.47 s -1 ) than healthy controls (-2.32 ± 0.41 s -1 ; p = 0.021). Furthermore, in T1DM patients, disease duration inversely correlated with myocardial strain rate and serum HbA1c levels correlated with strain both at rest and during stress testing. Conclusion Long-term impairment of cardiac function in diabetic cardiomyopathy may be preceded by a transient phase of increased myocardial contractility early in the course of T1DM. The extent of hyperglycemia in childhood correlates with the alteration of myocardial contractility.

Impact of type 2 diabetes mellitus on the prognosis of early stage triple-negative breast cancer in People's Republic of China.

BackgroundType 2 diabetes mellitus (T2DM) is one of the most common chronic metabolic diseases. Increased cause-specific mortality and decreased disease-free survival (DFS) have been reported among cancer patients with T2DM compared with patients without T2DM, even after adjustments of other comorbidities. However, less is known about the impact of T2DM and other comorbidities on DFS in Chinese patients with early stage triple-negative breast cancer (TNBC).Patients and methodsWe assessed patients who were newly diagnosed with early stage primary TNBC at the Department of Breast Surgery, Fudan University, from 2003 to 2011. Of the 1,100 TNBC patients, 865 female patients had invasive and early stage TNBC. The association of the variables in the T2DM and non-T2DM groups was compared using the Pearson’s chi-square and independent t-tests. DFS was estimated using the Kaplan–Meier method. The effects of T2DM and other possible risk factors on DFS were assessed by Cox proportional hazards regression using univariate or multivariate analysis.ResultsA total of 865 early stage primary TNBC cases were studied, including 104 (12.02%) subjects with T2DM. Metastatic or recurrent disease was detected in 24 (23.08%) patients in the T2DM group and 35 (4.60%) patients in the non-T2DM group. Patients with T2DM exhibited a significantly lower DFS than patients without T2DM (log-rank P<0.001). Similar results were observed when patients with positive lymph nodes were compared with patients with negative lymph nodes (log-rank P=0.003). T2DM was independently associated with a lower DFS after adjustments of other variables (adjusted hazard ratio, 7.719; 95% confidence interval, 4.304–13.843; P<0.001) and adjustments of lymph node positivity (adjusted hazard ratio, 2.407; 95% confidence interval, 1.391–4.166; P=0.002). The DFS rates at 2 years for the T2DM group and the non-T2DM group were 78% and 97%, respectively. The prognostic influence of T2DM was consistent across the subgroups, including subgroups by age (>50 or ≤50), menopausal status (post- or premenopausal), tumor size (>5 cm or ≤5 cm), lymph node involvement (positive or negative), and adjuvant chemotherapy (received or not) using the Kaplan–Meier method (log-rank P<0.05).ConclusionIn the People’s Republic of China, T2DM is an independent prognostic risk factor that indicates an increased likelihood of recurrence and metastasis in patients with early stage TNBC. The presence of T2DM should be taken into account when evaluating the risk for an early stage TNBC patient. More effective therapeutic regimens are needed for early stage TNBC patients with T2DM.

Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes.

The effect of type 2 diabetes mellitus (T2DM) on bone is controversial. Therefore, the present study investigated whether T2DM causes osteoporosis and explored the underlying mechanisms involved in this process. The effects of T2DM on bone physiology were analyzed in a mouse model of T2DM; KK/Upj‑Ay/J (KK‑Ay) mice develop diabetes after 8 weeks and exhibit stable diabetes symptoms and signs after 10 weeks when fed a KK‑Ay mouse maintenance fodder. Diabetic mice exhibited hyperglycemia, hyperinsulinemia and increased body and fat pad weight in comparison with C57BL/6 non-diabetic mice. Furthermore, diabetic mice demonstrated low bone weight and bone mineral density in the femur, tibia and fifth lumbar vertebra. Using von Kossa and tartrate-resistant acid phosphatase (TRAP) staining, alkaline phosphatase and TRAP activity analyses and gene profiling it was demonstrated that osteoblastogenesis and osteoclastogenesis were impaired in diabetic mice. To evaluate the bone biomechanics, the ultimate load of the bone was analyzed. It was found that the ultimate load of the tibia in diabetic mice was lower than that in the controls. The results from the present study suggest that bone metabolism is impaired in T2DM, resulting in decreased osteoblastogenesis, osteoclastogenesis and bone mass.