Experimental Diabetes Research最新文献

Diabetic macular edema (DME) remains an important cause of visual loss in patients with diabetes mellitus. Although photocoagulation and intensive control of systemic metabolic factors have been reported to achieve improved outcomes in large randomized clinical trials (RCTs), some patients with DME continue to lose vision despite treatment. Pharmacotherapies for DME include locally and systemically administered agents. We review several agents that have been studied for the treatment of DME.

LYR motif containing 1 (LYRM1) is a novel gene that is abundantly expressed in the adipose tissue of obese subjects and is involved in insulin resistance. In this study, free fatty acids (FFAs) and tumor necrosis factor-α (TNF-α) are shown to upregulate LYRM1 mRNA expression in 3T3-L1 adipocytes. Conversely, resistin and rosiglitazone exert an inhibitory effect on LYRM1 mRNA expression. These results suggest that the expression of LYRM1 mRNA is affected by a variety of factors that are related to insulin sensitivity. LYRM1 may be an important mediator in the development of obesity-related insulin resistance.

Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR = 0.78 (95%  CI = 0.67-0.92), P = 0.003) and was also associated with 2 h postload plasma glucose (P = 0.04), high-density lipoprotein cholesterol (P = 0.004), and total cholesterol (P = 0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.

The present study investigates the relationship between diabetes metabolic control represented by levels of HbA1c, early glycation products-(fructosamine (FAM)), serum-advanced glycation end products (s-AGEs), lipoperoxidation products (LPO), advanced oxidation protein products (AOPP) and circulating TGF-β in young patients with DM1. The study group consisted of 79 patients with DM1 (8-18 years). 31 healthy children were used as control (1-16 years). Baseline characteristics of patients were compared by Student's t-test and nonparametric Mann-Whitney test (Statdirect), respectively. The correlations between the measured parameters were examined using Pearson correlation coefficient r and Spearman's rank test, respectively. A P value < 0.05 was considered as statistically significant. HbA1c was measured by LPLC, s-AGEs spectrofluorimetrically, LPO and AOPP spectrophotometrically and TGF-β by ELISA. Our results showed that parameters of glycation and oxidation are significantly higher in patients with DM1 than in healthy control. The level of serum TGF-β was significantly higher in diabetics in comparison with control: 7.1(3.6; 12.6) versus 1.6(0.8; 3.9) ng/mL. TGF-β significantly correlated with age and duration of DM1. There was not found any significant relation between TGF-β and parameres of glycation and oxidation. However, these results do not exclude the association between TGF-β and the onset of diabetic complications.

Diabetes mellitus (DM) is a worldwide growing disease and represents a huge social and healthcare problem owing to the burden of its complications. Micro- and macrovascular diabetic complications arise from excess damage through well-known biochemical pathways. Interestingly, microangiopathy hits the bone marrow (BM) microenvironment with features similar to retinopathy, nephropathy and neuropathy. The BM represents a reservoir of progenitor cells for multiple lineages, not limited to the hematopoietic system and including endothelial cells, smooth muscle cells, cardiomyocytes, and osteogenic cells. All these multiple progenitor cell lineages are profoundly altered in the setting of diabetes in humans and animal models. Reduction of endothelial progenitor cells (EPCs) along with excess smooth muscle progenitor (SMP) and osteoprogenitor cells creates an imbalance that promote the development of micro- and macroangiopathy. Finally, an excess generation of BM-derived fusogenic cells has been found to contribute to diabetic complications in animal models. Taken together, a growing amount of literature attributes to circulating progenitor cells a multi-faceted role in the pathophysiology of DM, setting a novel scenario that puts BM and the blood at the centre of the stage.

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.

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.

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.