Pub Date : 2012-01-01Epub Date: 2012-02-28DOI: 10.1155/2012/921685
Gian Paolo Fadini, Mattia Albiero, Lisa Menegazzo, Elisa Boscaro, Carlo Agostini, Saula Vigili de Kreutzenberg, Marcello Rattazzi, Angelo Avogaro
Diabetes mellitus (DM) alters circulating progenitor cells relevant for the pathophysiology of coronary artery disease (CAD). While endothelial progenitor cells (EPCs) are reduced, there is no data on procalcific polarization of circulating progenitors, which may contribute to vascular calcification in these patients. In a cohort of 107 subjects with and without DM and CAD, we analyzed the pro-calcific versus endothelial differentiation status of circulating CD34+ progenitor cells. Endothelial commitment was determined by expression of VEGFR-2 (KDR) and pro-calcific polarization by expression of osteocalcin (OC) and bone alkaline phosphatase (BAP). We found that DM patients had significantly higher expression of OC and BAP on circulating CD34+ cells than control subjects, especially in the presence of CAD. In patients with DM and CAD, the ratio of OC/KDR, BAP/KDR, and OC+BAP/KDR was about 3-fold increased than in other groups. EPCs cultured from DM patients with CAD occasionally formed structures highly suggestive of calcified nodules, and the expression of osteogenic markers by EPCs from control subjects was significantly increased in response to the toll-like receptor agonist LPS. In conclusion, circulating progenitor cells of diabetic patients show a phenotypic drift toward a pro-calcific phenotype that may be driven by inflammatory signals.
{"title":"Procalcific phenotypic drift of circulating progenitor cells in type 2 diabetes with coronary artery disease.","authors":"Gian Paolo Fadini, Mattia Albiero, Lisa Menegazzo, Elisa Boscaro, Carlo Agostini, Saula Vigili de Kreutzenberg, Marcello Rattazzi, Angelo Avogaro","doi":"10.1155/2012/921685","DOIUrl":"https://doi.org/10.1155/2012/921685","url":null,"abstract":"<p><p>Diabetes mellitus (DM) alters circulating progenitor cells relevant for the pathophysiology of coronary artery disease (CAD). While endothelial progenitor cells (EPCs) are reduced, there is no data on procalcific polarization of circulating progenitors, which may contribute to vascular calcification in these patients. In a cohort of 107 subjects with and without DM and CAD, we analyzed the pro-calcific versus endothelial differentiation status of circulating CD34+ progenitor cells. Endothelial commitment was determined by expression of VEGFR-2 (KDR) and pro-calcific polarization by expression of osteocalcin (OC) and bone alkaline phosphatase (BAP). We found that DM patients had significantly higher expression of OC and BAP on circulating CD34+ cells than control subjects, especially in the presence of CAD. In patients with DM and CAD, the ratio of OC/KDR, BAP/KDR, and OC+BAP/KDR was about 3-fold increased than in other groups. EPCs cultured from DM patients with CAD occasionally formed structures highly suggestive of calcified nodules, and the expression of osteogenic markers by EPCs from control subjects was significantly increased in response to the toll-like receptor agonist LPS. In conclusion, circulating progenitor cells of diabetic patients show a phenotypic drift toward a pro-calcific phenotype that may be driven by inflammatory signals.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/921685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30551531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-06-03DOI: 10.1155/2012/701643
Wen-Ko Chiou, Jawl-Shan Hwang, Kuang-Hung Hsu, Jen-Der Lin
Aims: Hyperinsulinemia in overweight status, obesity, and type 2 diabetes mellitus (DM) is often accompanied by cancer. Gender is important in cancer epidemiology, clinical presentation, and response to therapy in different histological types of malignancy. Insufficient information is available concerning gender differences in DM with organ-specific and nonorgan-specific cancers. This study aimed to analyze gender differences in hospitalized cancer patients with or without type 2 DM.
Methods: We retrospectively reviewed ten years of patients hospitalized in one institution, enrolling 36,457 female and 50,004 male cancer patients of which 5,992 females and 8,345 males were diagnosed as type 2 DM.
Results: Statistically significant increases in incidence of type 2 DM were found in patients of both genders with pancreatic, liver, and urinary tract cancer. Increased incidence of type 2 DM was found in lung and hematologic malignancies in females and prostate cancer in males. Increases in mortality rates of females with type 2 DM (2.98%) were higher than those in males. DM increased mortality rates in gender-specific cancers from 1.91% (uterus, HR: 1.33) to 5.04% (ovary, HR: 1.49).
Conclusion: Type 2 DM increased mortality of cancer patients of both genders, with higher increases in gender-specific than in nongender-specific cancers.
{"title":"Diabetes mellitus increased mortality rates more in gender-specific than in nongender-specific cancer patients: a retrospective study of 149,491 patients.","authors":"Wen-Ko Chiou, Jawl-Shan Hwang, Kuang-Hung Hsu, Jen-Der Lin","doi":"10.1155/2012/701643","DOIUrl":"https://doi.org/10.1155/2012/701643","url":null,"abstract":"<p><strong>Aims: </strong>Hyperinsulinemia in overweight status, obesity, and type 2 diabetes mellitus (DM) is often accompanied by cancer. Gender is important in cancer epidemiology, clinical presentation, and response to therapy in different histological types of malignancy. Insufficient information is available concerning gender differences in DM with organ-specific and nonorgan-specific cancers. This study aimed to analyze gender differences in hospitalized cancer patients with or without type 2 DM.</p><p><strong>Methods: </strong>We retrospectively reviewed ten years of patients hospitalized in one institution, enrolling 36,457 female and 50,004 male cancer patients of which 5,992 females and 8,345 males were diagnosed as type 2 DM.</p><p><strong>Results: </strong>Statistically significant increases in incidence of type 2 DM were found in patients of both genders with pancreatic, liver, and urinary tract cancer. Increased incidence of type 2 DM was found in lung and hematologic malignancies in females and prostate cancer in males. Increases in mortality rates of females with type 2 DM (2.98%) were higher than those in males. DM increased mortality rates in gender-specific cancers from 1.91% (uterus, HR: 1.33) to 5.04% (ovary, HR: 1.49).</p><p><strong>Conclusion: </strong>Type 2 DM increased mortality of cancer patients of both genders, with higher increases in gender-specific than in nongender-specific cancers.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/701643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30693545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-06-14DOI: 10.1155/2012/859395
Karen J Nickelson, Kelly L Stromsdorfer, R Taylor Pickering, Tzu-Wen Liu, Laura C Ortinau, Aileen F Keating, James W Perfield
Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent health benefits remain when body weight is similar. The development of obesity in female mice receiving a high-fat diet was delayed; however, subsequent comparisons of weight-matched obese mice revealed greater adiposity in obese female mice. Despite excess adiposity and enlarged adipocyte size, obese females remained more glucose tolerant than weight-matched male mice, and this benefit was associated with increased expression of adiponectin and reductions in immune cell infiltration and oxidative stress in adipose tissue. Therefore, the protective benefits of estrogen persist in the obese state and appear to improve the metabolic phenotype of adipose tissue and the individual.
{"title":"A comparison of inflammatory and oxidative stress markers in adipose tissue from weight-matched obese male and female mice.","authors":"Karen J Nickelson, Kelly L Stromsdorfer, R Taylor Pickering, Tzu-Wen Liu, Laura C Ortinau, Aileen F Keating, James W Perfield","doi":"10.1155/2012/859395","DOIUrl":"https://doi.org/10.1155/2012/859395","url":null,"abstract":"<p><p>Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent health benefits remain when body weight is similar. The development of obesity in female mice receiving a high-fat diet was delayed; however, subsequent comparisons of weight-matched obese mice revealed greater adiposity in obese female mice. Despite excess adiposity and enlarged adipocyte size, obese females remained more glucose tolerant than weight-matched male mice, and this benefit was associated with increased expression of adiponectin and reductions in immune cell infiltration and oxidative stress in adipose tissue. Therefore, the protective benefits of estrogen persist in the obese state and appear to improve the metabolic phenotype of adipose tissue and the individual.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/859395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2011-12-27DOI: 10.1155/2012/250621
N Wolfson, D Gavish, Z Matas, M Boaz, M Shargorodsky
Objective: Adiponectin has anti-atherogenic and anti-inflammatory properties. We investigated the influence of adiponectin on glucose tolerance status, adiposity and cardiovascular risk factors (CVRFs).
Design and patients: Study consisted of 107 subjects: 55 with normal glucose tolerance (NGT) and 52 with impaired glucose regulation (IGR) who were divided into two groups: 24 subjects with impaired fasting glucose (IFG Group) and 28 patients with type 2 diabetes mellitus (DM Group). In additional analysis, study participants were divided into two groups, according to CVRFs: low and high risk.
Measurements: Patients were evaluated for glucose, HbA1C, insulin, lipids, CRP, HOMA-IR and adiponectin.
Results: Adiponectin was significantly higher in NGT group than in IFG (P = 0.003) and DM (P = 0.01) groups. Adiponectin was significantly, positively associated with HDL and inversely associated with glucose, HbA1c, ALT, AST, TG, HOMA-IR. Patients with higher CVRFs load have lesser adiponectin compared to patients with low cardiovascular risk P < 0.0001). Adiponectin was inversely associated with the number of risk factors (r = -0.430, P = 0.0001).
Conclusions: Circulating adiponectin was significantly lower in subjects with different degree of IGR compared to subjects with normal glucose homeostasis. Adiponectin was significantly lower in high risk group than low risk group and decreased concurrently with increased number of CVRFs.
{"title":"Relation of adiponectin to glucose tolerance status, adiposity, and cardiovascular risk factor load.","authors":"N Wolfson, D Gavish, Z Matas, M Boaz, M Shargorodsky","doi":"10.1155/2012/250621","DOIUrl":"https://doi.org/10.1155/2012/250621","url":null,"abstract":"<p><strong>Objective: </strong>Adiponectin has anti-atherogenic and anti-inflammatory properties. We investigated the influence of adiponectin on glucose tolerance status, adiposity and cardiovascular risk factors (CVRFs).</p><p><strong>Design and patients: </strong>Study consisted of 107 subjects: 55 with normal glucose tolerance (NGT) and 52 with impaired glucose regulation (IGR) who were divided into two groups: 24 subjects with impaired fasting glucose (IFG Group) and 28 patients with type 2 diabetes mellitus (DM Group). In additional analysis, study participants were divided into two groups, according to CVRFs: low and high risk.</p><p><strong>Measurements: </strong>Patients were evaluated for glucose, HbA1C, insulin, lipids, CRP, HOMA-IR and adiponectin.</p><p><strong>Results: </strong>Adiponectin was significantly higher in NGT group than in IFG (P = 0.003) and DM (P = 0.01) groups. Adiponectin was significantly, positively associated with HDL and inversely associated with glucose, HbA1c, ALT, AST, TG, HOMA-IR. Patients with higher CVRFs load have lesser adiponectin compared to patients with low cardiovascular risk P < 0.0001). Adiponectin was inversely associated with the number of risk factors (r = -0.430, P = 0.0001).</p><p><strong>Conclusions: </strong>Circulating adiponectin was significantly lower in subjects with different degree of IGR compared to subjects with normal glucose homeostasis. Adiponectin was significantly lower in high risk group than low risk group and decreased concurrently with increased number of CVRFs.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/250621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30393366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-01-04DOI: 10.1155/2012/851487
Eva Horová, Jiří Mazoch, Jiřina Hiigertová, Jan Kvasnička, Jan Skrha, Jan Soupal, Martin Prázný
Aims: The aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in Type 1 diabetes during hyperinsulinemic clamp.
Patients and methods: Sixteen patients (51 ± 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmol·L(-1)). Insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. Microvascular reactivity (MVR) was measured by laser Doppler flowmetry.
Results: Maximum perfusion and the velocity of perfusion increase during PORH were higher in hyperglycemia compared to baseline (47 ± 16 versus 40 ± 16 PU, P < 0.01, and 10.4 ± 16.5 versus 2.6 ± 1.5 PU·s(-1), P < 0.05, resp.). Time to the maximum perfusion during TH was shorter and velocity of perfusion increase during TH higher at hyperglycemia compared to isoglycemic phase (69 ± 15 versus 77 ± 16 s, P < 0.05, and 1.4 ± 0.8 versus 1.2 ± 0.7 PU·s(-1), P < 0.05, resp.). An inverse relationship was found between insulinemia and the time to maximum perfusion during PORH (r = -0.70, P = 0.007).
Conclusion: Acute glycemia did not impair microvascular reactivity in this clamp study in Type 1 diabetic patients. Our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with Type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.
目的:探讨高胰岛素钳夹术中急性血糖升高对1型糖尿病微血管和内皮的影响。患者与方法:16例患者(51±7岁)在等高血糖钳夹术中(血糖升高5.5 mmol·L(-1))检查无并发症。分析胰岛素、脂质参数、细胞粘附分子及纤维蛋白原。用激光多普勒血流仪测定微血管反应性(MVR)。结果:与基线相比,高血糖时PORH的最大灌注和灌注增加速度更高(47±16比40±16 PU, P < 0.01; 10.4±16.5比2.6±1.5 PU·s(-1), P < 0.05,均有统计学意义)。与等糖期相比,高血糖期TH至最大灌注时间更短,灌注速度更快(69±15 vs 77±16 s, P < 0.05, 1.4±0.8 vs 1.2±0.7 PU·s, P < 0.05,均为P < 0.05)。胰岛素血症与PORH期间达到最大灌注时间呈负相关(r = -0.70, P = 0.007)。结论:在钳形研究中,急性血糖没有损害1型糖尿病患者的微血管反应性。我们的研究结果表明胰岛素可能通过其血管扩张作用在1型糖尿病患者微血管灌注的调节中发挥重要作用,并可以抵消急性血糖波动的影响。
{"title":"Acute hyperglycemia does not impair microvascular reactivity and endothelial function during hyperinsulinemic isoglycemic and hyperglycemic clamp in type 1 diabetic patients.","authors":"Eva Horová, Jiří Mazoch, Jiřina Hiigertová, Jan Kvasnička, Jan Skrha, Jan Soupal, Martin Prázný","doi":"10.1155/2012/851487","DOIUrl":"https://doi.org/10.1155/2012/851487","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in Type 1 diabetes during hyperinsulinemic clamp.</p><p><strong>Patients and methods: </strong>Sixteen patients (51 ± 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmol·L(-1)). Insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. Microvascular reactivity (MVR) was measured by laser Doppler flowmetry.</p><p><strong>Results: </strong>Maximum perfusion and the velocity of perfusion increase during PORH were higher in hyperglycemia compared to baseline (47 ± 16 versus 40 ± 16 PU, P < 0.01, and 10.4 ± 16.5 versus 2.6 ± 1.5 PU·s(-1), P < 0.05, resp.). Time to the maximum perfusion during TH was shorter and velocity of perfusion increase during TH higher at hyperglycemia compared to isoglycemic phase (69 ± 15 versus 77 ± 16 s, P < 0.05, and 1.4 ± 0.8 versus 1.2 ± 0.7 PU·s(-1), P < 0.05, resp.). An inverse relationship was found between insulinemia and the time to maximum perfusion during PORH (r = -0.70, P = 0.007).</p><p><strong>Conclusion: </strong>Acute glycemia did not impair microvascular reactivity in this clamp study in Type 1 diabetic patients. Our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with Type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/851487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30401554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-01-05DOI: 10.1155/2012/859186
Anna Bugge, Bianca El-Naaman, Robert G McMurray, Karsten Froberg, Claus Henrik Nielsen, Klaus Müller, Lars Bo Andersen
The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO(2peak)) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were followed for 4 years. Anthropometrics and VO(2peak) were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR) was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58-8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls.
{"title":"Sex differences in the association between level of childhood interleukin-6 and insulin resistance in adolescence.","authors":"Anna Bugge, Bianca El-Naaman, Robert G McMurray, Karsten Froberg, Claus Henrik Nielsen, Klaus Müller, Lars Bo Andersen","doi":"10.1155/2012/859186","DOIUrl":"https://doi.org/10.1155/2012/859186","url":null,"abstract":"<p><p>The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO(2peak)) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were followed for 4 years. Anthropometrics and VO(2peak) were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR) was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58-8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/859186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30408632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-04-17DOI: 10.1155/2012/635472
Thomas Forst, Matthias M Weber, Andreas Pfützner
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.
{"title":"Cardiovascular benefits of GLP-1-based herapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control.","authors":"Thomas Forst, Matthias M Weber, Andreas Pfützner","doi":"10.1155/2012/635472","DOIUrl":"https://doi.org/10.1155/2012/635472","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/635472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30609744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-05-20DOI: 10.1155/2012/672658
Matteo Monami, Ilaria Dicembrini, Niccolò Marchionni, Carlo M Rotella, Edoardo Mannucci
Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for "exenatide," "liraglutide," "albiglutide," "semaglutide," and "lixisenatide" was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of -1.0 [-1.3; -0.6] kg/m(2). Considering the average BMI at baseline (32.4 kg/m(2)) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction.
{"title":"Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis.","authors":"Matteo Monami, Ilaria Dicembrini, Niccolò Marchionni, Carlo M Rotella, Edoardo Mannucci","doi":"10.1155/2012/672658","DOIUrl":"https://doi.org/10.1155/2012/672658","url":null,"abstract":"<p><p>Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for \"exenatide,\" \"liraglutide,\" \"albiglutide,\" \"semaglutide,\" and \"lixisenatide\" was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of -1.0 [-1.3; -0.6] kg/m(2). Considering the average BMI at baseline (32.4 kg/m(2)) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/672658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30674114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-06-18DOI: 10.1155/2012/829758
Rong-Huai Zhang, Haitao Guo, Machender R Kandadi, Xiao-Ming Wang, Jun Ren
(1) Hyperglycemia leads to cytotoxicity in the heart. Although several theories are postulated for glucose toxicity-induced cardiomyocyte dysfunction, the precise mechanism still remains unclear. (2) This study was designed to evaluate the impact of elevated extracellular Ca(2+) on glucose toxicity-induced cardiac contractile and intracellular Ca(2+) anomalies as well as the mechanism(s) involved with a focus on Ca(2+)/calmodulin (CaM)-dependent kinase. Isolated adult rat cardiomyocytes were maintained in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) media for 6-12 hours. Contractile indices were measured including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-PS (TPS), and time-to-90% relengthening (TR(90)). (3) Cardiomyocytes maintained with HG displayed abnormal mechanical function including reduced PS, ±dL/dt, and prolonged TPS, TR(90) and intracellular Ca(2+) clearance. Expression of intracellular Ca(2+) regulatory proteins including SERCA2a, phospholamban and Na(+)-Ca(2+) exchanger were unaffected whereas SERCA activity was inhibited by HG. Interestingly, the HG-induced mechanical anomalies were abolished by elevated extracellular Ca(2+) (from 1.0 to 2.7 mM). Interestingly, the high extracellular Ca(2+)-induced beneficial effect against HG was abolished by the CaM kinase inhibitor KN93. (4) These data suggest that elevated extracellular Ca(2+) protects against glucose toxicity-induced cardiomyocyte contractile defects through a mechanism associated with CaM kinase.
{"title":"Ca+2/calmodulin-dependent protein kinase mediates glucose toxicity-induced cardiomyocyte contractile dysfunction.","authors":"Rong-Huai Zhang, Haitao Guo, Machender R Kandadi, Xiao-Ming Wang, Jun Ren","doi":"10.1155/2012/829758","DOIUrl":"https://doi.org/10.1155/2012/829758","url":null,"abstract":"<p><p>(1) Hyperglycemia leads to cytotoxicity in the heart. Although several theories are postulated for glucose toxicity-induced cardiomyocyte dysfunction, the precise mechanism still remains unclear. (2) This study was designed to evaluate the impact of elevated extracellular Ca(2+) on glucose toxicity-induced cardiac contractile and intracellular Ca(2+) anomalies as well as the mechanism(s) involved with a focus on Ca(2+)/calmodulin (CaM)-dependent kinase. Isolated adult rat cardiomyocytes were maintained in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) media for 6-12 hours. Contractile indices were measured including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-PS (TPS), and time-to-90% relengthening (TR(90)). (3) Cardiomyocytes maintained with HG displayed abnormal mechanical function including reduced PS, ±dL/dt, and prolonged TPS, TR(90) and intracellular Ca(2+) clearance. Expression of intracellular Ca(2+) regulatory proteins including SERCA2a, phospholamban and Na(+)-Ca(2+) exchanger were unaffected whereas SERCA activity was inhibited by HG. Interestingly, the HG-induced mechanical anomalies were abolished by elevated extracellular Ca(2+) (from 1.0 to 2.7 mM). Interestingly, the high extracellular Ca(2+)-induced beneficial effect against HG was abolished by the CaM kinase inhibitor KN93. (4) These data suggest that elevated extracellular Ca(2+) protects against glucose toxicity-induced cardiomyocyte contractile defects through a mechanism associated with CaM kinase.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/829758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30728107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01Epub Date: 2012-06-26DOI: 10.1155/2012/801610
Noboru Hara
Prostate cancer and the androgen deprivation therapy (ADT) thereof are involved in diabetes in terms of diabetes-associated carcinogenesis and ADT-related metabolic disorder, respectively. The aim of this study is to systematically review relevant literature. About 218,000 men are estimated to be newly diagnosed with prostate cancer every year in the United States. Approximately 10% of them are still found with metastasis, and in addition to them, about 30% of patients with nonmetastatic prostate cancer recently experience ADT. Population-based studies have shown that dissimilar to other malignancies, type 2 diabetes is associated with a lower incidence of prostate cancer, whereas recent large cohort studies have reported the association of diabetes with advanced high-grade prostate cancer. Although the reason for the lower prevalence of prostate cancer among diabetic men remains unknown, the lower serum testosterone and PSA levels in them can account for the increased risk of advanced disease at diagnosis. Meanwhile, insulin resistance already appears in 25-60% of the patients 3 months after the introduction of ADT, and long-term ADT leads to a higher incidence of diabetes (reported hazard ratio of 1.28-1.44). Although the possible relevance of cytokines such as Il-6 and TNF-α to ADT-related diabetes has been suggested, its mechanism is poorly understood.
{"title":"Prostate carcinogenesis with diabetes and androgen-deprivation-therapy-related diabetes: an update.","authors":"Noboru Hara","doi":"10.1155/2012/801610","DOIUrl":"https://doi.org/10.1155/2012/801610","url":null,"abstract":"<p><p>Prostate cancer and the androgen deprivation therapy (ADT) thereof are involved in diabetes in terms of diabetes-associated carcinogenesis and ADT-related metabolic disorder, respectively. The aim of this study is to systematically review relevant literature. About 218,000 men are estimated to be newly diagnosed with prostate cancer every year in the United States. Approximately 10% of them are still found with metastasis, and in addition to them, about 30% of patients with nonmetastatic prostate cancer recently experience ADT. Population-based studies have shown that dissimilar to other malignancies, type 2 diabetes is associated with a lower incidence of prostate cancer, whereas recent large cohort studies have reported the association of diabetes with advanced high-grade prostate cancer. Although the reason for the lower prevalence of prostate cancer among diabetic men remains unknown, the lower serum testosterone and PSA levels in them can account for the increased risk of advanced disease at diagnosis. Meanwhile, insulin resistance already appears in 25-60% of the patients 3 months after the introduction of ADT, and long-term ADT leads to a higher incidence of diabetes (reported hazard ratio of 1.28-1.44). Although the possible relevance of cytokines such as Il-6 and TNF-α to ADT-related diabetes has been suggested, its mechanism is poorly understood.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/801610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30759709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}