| 1. |
- Abu Seman, N, et al.
(author)
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Evaluation of the association of plasma pentraxin 3 levels with type 2 diabetes and diabetic nephropathy in a Malay population
- 2013
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In: Journal of diabetes research. - : Hindawi Limited. - 2314-6745 .- 2314-6753. ; 2013, s. 298019-
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Journal article (peer-reviewed)abstract
- Recent reports have demonstrated that elevated plasma long pentraxin 3 (PTX3) levels are associated with cardiovascular and chronic kidney diseases. In the current study, we investigated the plasma PTX3 levels in 296 Malay subjects including the subjects with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) patients with or without DN by using an enzyme-linked immune-sorbent assay. Results showed that in males, plasma PTX3 levels in T2DM patients without DN were lower than that in the subjects with NGT (2.78 versus 3.98 ng/mL;P=0.021). Plasma PTX3 levels in T2DM patients with DN were decreased compared to the patients without DN (1.63 versus 2.78 ng/mL;P=0.013). In females, however, no significant alteration of plasma PTX3 levels among NGT subjects and T2DM patients with and without DN was detected. Furthermore, an inverse correlation between PTX3 and body mass index was found in male subjects with NGT (P=0.012;r=-0.390), but not in male T2DM patients, neither in all females. The current study provided the first evidence that decreased plasma PTX3 levels are associated with T2DM and DN in Malay men and also suggested that PTX3 may have different effects in DN and chronic kidney diseases.
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| 2. |
- Ahmad Kiadaliri, Aliasghar, et al.
(author)
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Predicting Changes in Cardiovascular Risk Factors in Type 2 Diabetes in the Post-UKPDS Era: Longitudinal Analysis of the Swedish National Diabetes Register
- 2013
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In: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6745 .- 2314-6753. ; 2013
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Journal article (peer-reviewed)abstract
- The aim of the current study was to provide updated time-path equations for risk factors of type-2-diabetes-related cardiovascular complications for application in risk calculators and health economic models. Observational data from the Swedish National Diabetes Register were analysed using Generalized Method of Moments estimation for dynamic panel models ( , aged 25–70 years at diagnosis in 2001–2004). Validation was performed using persons diagnosed in 2005 ( ). Results were compared with the UKPDS outcome model. The value of the risk factor in the previous year was the main predictor of the current value of the risk factor. People with high (low) values of risk factor in the year of diagnosis experienced a decreasing (increasing) trend over time. BMI was associated with elevations in all risk factors, while older age at diagnosis and being female generally corresponded to lower levels of risk factors. Updated time-path equations predicted risk factors more precisely than UKPDS outcome model equations in a Swedish population. Findings indicate new time paths for cardiovascular risk factors in the post-UKPDS era. The validation analysis confirmed the importance of updating the equations as new data become available; otherwise, the results of health economic analyses may be biased.
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| 3. |
- Backe, Marie Balslev, et al.
(author)
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The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis
- 2019
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In: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2019
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Journal article (peer-reviewed)abstract
- Aims: Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase inhibitor GSK-J4 reduces cytokine-induced destruction of beta-cells and improves beta-cell function. Here, we investigate the therapeutic potential of GSK-J4 to prevent diabetes development and examine the importance of H3K4 methylation for islet function. Materials and Methods: We used two mouse models of diabetes to investigate the therapeutic potential of GSK-J4. To clarify the importance of H3K4 methylation, we characterized a mouse strain with knockout (KO) of the H3K4 demethylase KDM5B. Results: GSK-J4 administration failed to prevent the development of experimental diabetes induced by multiple low-dose streptozotocin or adoptive transfer of splenocytes from acutely diabetic NOD to NODscid mice. KDM5B-KO mice were growth retarded with altered body composition, had low IGF-1 levels, and exhibited reduced insulin secretion. Interestingly, despite secreting less insulin, KDM5B-KO mice were able to maintain normoglycemia following oral glucose tolerance test, likely via improved insulin sensitivity, as suggested by insulin tolerance testing and phosphorylation of proteins belonging to the insulin signaling pathway. When challenged with high-fat diet, KDM5B-deficient mice displayed similar weight gain and insulin sensitivity as wild-type mice. Conclusion: Our results show a novel role of KDM5B in metabolism, as KDM5B-KO mice display growth retardation and improved insulin sensitivity.
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| 4. |
- Bravo, Carolina, et al.
(author)
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Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women
- 2017
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In: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; , s. 1-12
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Journal article (peer-reviewed)abstract
- Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m2). LAR was negatively associated with HOMA-S (; ), Matsuda-ISICOMP (; ), and the calculated sensitivity index (CSi) derived from IVGTT (; ). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit () nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regression). The discriminatory capacity of both ratios to classify insulin-resistant versus insulin-sensitive subjects was similar for HOMA-S (), Matsuda-ISICOMP (), or CSi (). In conclusion, LAR showed consistent negative associations with different systemic insulin sensitivity indexes. The use of HMWA to generate leptin/HMWA ratio did not show any advantage over LAR as a biomarker of systemic insulin sensitivity in normoglycemic women
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| 5. |
- Cataldo Buscunan, Rodrigo, et al.
(author)
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Platelet Serotonin Levels Are Associated with Plasma Soluble Leptin Receptor Concentrations in Normoglycemic Women
- 2019
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In: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2019
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Journal article (peer-reviewed)abstract
- Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin, TNFα, and MCP1 were determined by immunoassays. Platelet 5HT levels and NEFAs were measured before and after OGTT. The free leptin index was calculated from leptin and sOb-R measurements. Insulin sensitivity indexes derived from OGTT (HOMA-S and Matsuda ISICOMP) and plasma NEFAs (Adipose-IR, Revised QUICKI) were also calculated. Our data show that among metabolic traits, platelet 5HT levels were associated with plasma sOb-R (, , corrected ). Platelet 5HT levels were reduced in response to OGTT ( vs platelets, ). In conclusion, platelet 5HT levels are positively associated with plasma sOb-R concentrations and reduced in response to glucose intake possibly indicating a role of peripheral 5HT in leptin-mediated appetite regulation.
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| 6. |
- Danielsson, AK, et al.
(author)
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Cannabis Use as Risk or Protection for Type 2 Diabetes: A Longitudinal Study of 18 000 Swedish Men and Women
- 2016
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In: Journal of diabetes research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2016, s. 6278709-
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Journal article (peer-reviewed)abstract
- Aims. Whether or not cannabis use may increase or decrease the risk of type 2 diabetes is not clear. We analyzed the association between cannabis and subsequent type 2 diabetes and if a potential positive or reverse association persisted after controlling for potential confounders.Methods. In this population-based cohort study, 17,967 Swedish men and women (aged 18–84 years), who answered an extensive questionnaire in 2002 (including questions on cannabis use), were followed up for new cases of type 2 diabetes (n=608) by questionnaire (in 2010) and in health registers during 2003–2011. Odds ratios (ORs) with 95% CIs were estimated in a multiple logistic regression analysis. Potential confounders included age, sex, BMI, physical inactivity, smoking, alcohol use, and occupational position.Results. The crude association showed that cannabis users had a reduced risk of type 2 diabetes OR = 0.68 (95% CIs: 0.47–0.99). However, this inverse association attenuated to OR = 0.94 (95% CIs: 0.63–1.39) after adjusting for age.Conclusions. The present study suggests that there is no association between cannabis use and subsequent type 2 diabetes after controlling for age. To make more robust conclusions prospective studies, with longer periods of follow-up and more detailed information about cannabis use, are needed.
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| 7. |
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| 8. |
- Ekberg, NR, et al.
(author)
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Protective Effect of the HIF-1A Pro582Ser Polymorphism on Severe Diabetic Retinopathy
- 2019
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In: Journal of diabetes research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2019, s. 2936962-
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Journal article (peer-reviewed)abstract
- Objective. Hypoxia is central in the pathogenesis of diabetic retinopathy (DR). Hypoxia-inducible factor-1 (HIF-1) is the key mediator in cellular oxygen homeostasis that facilitates the adaptation to hypoxia. HIF-1 is repressed by hyperglycemia contributing by this to the development of complications in diabetes. Recent work has shown that the HIF-1A Pro582Ser polymorphism is more resistant to hyperglycemia-mediated repression, thus protecting against the development of diabetic nephropathy. In this study, we have investigated the effect of the HIF-1A Pro582Ser polymorphism on the development of DR and further dissected the mechanisms by which the polymorphism confers a relative resistance to the repressive effect of hyperglycemia. Research Design and Method. 703 patients with type 1 diabetes mellitus from one endocrine department were included in the study. The degree of retinopathy was correlated to the HIF-1A Pro582Ser polymorphism. The effect of glucose on a stable HIF-1A construct with a Pro582Ser mutation was evaluated in vitro. Results. We identified a protective effect of HIF-1A Pro582Ser against developing severe DR with a risk reduction of 95%, even when adjusting for known risk factors for DR such as diabetes duration, hyperglycemia, and hypertension. The Pro582Ser mutation does not cancel the destabilizing effect of glucose but is followed by an increased transactivation activity even in high glucose concentrations. Conclusion. The HIF-1A genetic polymorphism has a protective effect on the development of severe DR. Moreover, the relative resistance of the HIF-1A Pro582Ser polymorphism to the repressive effect of hyperglycemia is due to the transactivation activity rather than the protein stability of HIF-1α.
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| 9. |
- Eken, SM, et al.
(author)
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Making sense in antisense: therapeutic potential of noncoding RNAs in diabetes-induced vascular dysfunction
- 2013
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In: Journal of diabetes research. - : Hindawi Limited. - 2314-6745 .- 2314-6753. ; 2013, s. 834727-
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Journal article (peer-reviewed)abstract
- The rapid rise of type II diabetes mellitus and its accompanying vascular complications call for novel approaches in unravelling its pathophysiological mechanisms and designing new treatment modalities. Noncoding RNAs represent a class of previously unknown molecular modulators of this disease. The most important features of diabetes-induced vascular disease, which include metabolic deregulation, increased oxidative stress, release of inflammatory mediators like adipokines, and pathologic changes in vascular cells, all are depicted and governed by a certain set of noncoding RNAs. While these mechanisms are being unravelled, new diagnostic and therapeutic opportunities to treat diabetes-induced vascular disease emerge.
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| 10. |
- Gobbo, Marina, et al.
(author)
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Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions.
- 2015
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In: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2015
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Journal article (peer-reviewed)abstract
- The antitumor properties of melatonin (MLT) are known for prostate cancer cells. This study investigated whether MLT affects prostate maturation and interferes with tissue injuries induced by diabetes. MLT was administered to Wistar rats from 5 weeks of age in the drinking water (10 μg/kg b.w.), and diabetes was induced at the 13th week by streptozotocin (4.5 mg/100g b.w., i.p.). The animals were euthanized in the 14th and 21st weeks. MLT reduced the immunostained cells for androgen receptor (AR) by 10% in younger rats. Diabetes decreased cell proliferation and increased apoptosis. MLT treatment impeded apoptosis (p = 0.02) and augmented proliferation (p = 0.0008) and PCNA content in prostate following long-term diabetes due to restoration of testosterone levels and expression of melatonin receptor type 1B. The effect of MLT (500 µM, 5 mM, and 10 mM) on androgen-dependent (22Rv1) and androgen-independent (PC3) cancer cells and human prostate epithelial cells (PNTA1) under normal and hyperglycemic conditions (HG, 450 mg/dL) was analyzed. Contrary to PNTA1 and 22Rv1 cells, MLT improved the proliferation of PC3 cells in hyperglycemic medium. The combined data indicated that MLT had proliferative and antiapoptotic effects in prostate cells subjected to HG levels and it seems to involve specific MLT pathways rather than AR.
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