Treatment of obese diabetics.
ABSTRACT Fat accumulation is a typical phenomenon in the pathogenesis of Type 2 diabetes. Also Type 1 diabetics are getting obese these days living in an environment with typical caloric overfeeding and low physical activity. Weight reduction is an important part of therapy in all obese diabetic patients. Orlistat is the only accessible antiobesity drug today. Weight neutral antidiabetics like metformin and DPP-4 inhibitors can be also used. Incretin analogues (exenatide and liraglutide) are also very important drugs inducing weight loss in diabetic and also in nondiabetic patients. Insulin therapy causes mostly weight gain. Long acting insulin analogues are able to induce small weight loss in Type 1 diabetes or only a small weight increase or weight loss in Type 2 diabetic patients. Procedures of bariatric surgery are very important in the treatment being able to induce remission of Type 2 diabetes. Weight reduction can be supported also using the new class of antiadiabetic drugs- SGLT inhibitors which are blocking glucose absorption in kidneys. The use of new incretine analogues injected at the interval of one to two weeks is the most important strategy for the treatment of obese Type 2 diabetic patients and perhaps also of Type 1 diabetic patients even in combination with insulin.
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ABSTRACT: Obesity markedly increases susceptibility to a range of diseases and simultaneously undermines the viability and fate selection of haematopoietic stem cells (HSCs), and thus the kinetics of leukocyte production that is critical to innate and adaptive immunity. Considering that blood cell production and the differentiation of HSCs and their progeny is orchestrated, in part, by complex interacting signals emanating from the bone marrow microenvironment, it is not surprising that conditions that disturb bone marrow structure inevitably disrupt both the numbers and lineage-fates of these key blood cell progenitors. In addition to the increased adipose burden in visceral and subcutaneous compartments, obesity causes a marked increase in the size and number of adipocytes encroaching into the bone marrow space, almost certainly disturbing HSC interactions with neighbouring cells, which include osteoblasts, osteoclasts, mesenchymal cells and endothelial cells. As the global obesity pandemic grows, the short-term and long-term consequences of increased bone marrow adiposity on HSC lineage selection and immune function remain uncertain. This Review discusses the differentiation and function of haematopoietic cell populations, the principal physicochemical components of the bone marrow niche, and how this environment influences HSCs and haematopoiesis in general. The effect of adipocytes and adiposity on HSC and progenitor cell populations is also discussed, with the goal of understanding how obesity might compromise the core haematopoietic system.Nature Reviews Endocrinology 10/2014; DOI:10.1038/nrendo.2014.169 · 11.03 Impact Factor
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ABSTRACT: Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, (18)F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to (18)F-FDG, other radiopharmaceuticals such as (99m)Tc-sestamibi, (123)I-metaiodobenzylguanidine (MIBG), (18)F-fluorodopa and (18)F-14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity.European Journal of Nuclear Medicine 02/2014; 41(4). DOI:10.1007/s00259-013-2611-8 · 4.53 Impact Factor
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ABSTRACT: Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere-broventricular dose of metformin and compound C, in a broader attempt to investigate the regula-tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par-ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres-sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.Neural Regeneration Research 09/2013; 8(25):2379-88. DOI:10.3969/j.issn.1673-5374.2013.25.009 · 0.23 Impact Factor