User:Neuralia/sandbox/ORMD

Based on published evidence, a hypothesis is proposed for a specific type of microcirculatory déficit -failure of postprandial hyperemic responses affecting abdominal and other tissues- to be primarily responsible for the further development of fat-tissue and systemic inflammation in obesity-related metabolic diseases (ORMD). According to this view, inadequate chemical signaling at the capillary endothelial level, and/or defective vasodilatory responses, postprandially occuring every day in the splanchnic circulation of ORMD-prone individuals would persistently cause scattered hypoxic events in tissues such as abdominal fat which would trigger abnormal macrophage recruitment and local, patchy inflammation, followed by the abnormally high release of pro-inflammatory signals into the circulation. Resulting systemic inflammation has been blamed by many authors for the further development of insulin resistance in target tissues, as well as other manifestations of metabolic disease. This hypothesis may successfully explain clinical evidence of rapid improvement of metabolic disease that occurs as a result of bariatric surgery, exercise training or metformin treatment, and serve as a basis to formulate novel research questions related to the vasodilatory control of capillary function in ORMD and its eventual improvement for prevention or treatment purposes.

How quickly does systemic inflammation subside following bariatric surgery: implications for "diabesity"
Although not altogether conclusive, several explanations have been offered for the perplexing but proven fact*** that bariatric surgery (BS) can "cure" type 2 diabetes (T2D) within a few weeks of its completion.*** Given that -in the long term- BS has already been shown to ameliorate the systemic inflammation known to accompany obesity** (CHECK 27620343,28403936,28990150,29024428,30390093,30724385,31558407,32707229,34108550,34501231), and since inflammation per se has been proven to be diabetogenic,* it seems well justified at this stage to undertake novel research towards finding out just how quickly BS can produce detectable anti-inflammatory effects in treated patients. If systemic and/or tissular inflammation subsides within weeks after BS in obese/T2D patients, then the curative effect of BS on this type of diabetes could in fact be explained by an anti inflammatory effect resulting from the operation. Beyond BS circumstamces, such a hypothetical confirmation would swiftly enlighten our understanding of why obesity very often leads to metabolic disease (and T2D), and further pave the way to assuming that an improvement of abdominal microcirculatory function may play be a major target in the prevention and early treatment of obesity-related metabolic disorders (ORMD). Sections below further elaborate on the logics behind such a tentative conclusion, based on the hypotheis that a specific type of microcirculatory déficit -failure of postprandial hyperemic responses (PPH failure) affecting abdominal and other tissues- is primarily responsible for the development of tissular and systemic inflammation (and insulin resistance) in ORMD.

General background
Obesity-related metabolic disese (ORMD) is a multisymptom clinical entity characterized by abnormally high body mass-index (BMI) plus one or more accompanying, readly testable pathological signs including high inflammation-marker levels (CRP, HSP, etc) in the blood, hypertension, glucose intolerance, insulin-resistance, and dyslipidemia (high TG/low HDL). Moreover, ORMD is casuistically and pathophysiologically associated with a wide number of comorbidities that include type 2 diabetes (T2D), coronary heart disease, stroke, polycystic ovary disease, low fertility, non-alcoholic fatty liver disease, osteoarthritis, sleep apnoea, gout, gallbladder disease, and microvascular pathologies such as retinopathy and nephropathy.

Globally taken, ORMDs constitutes one of the most devastating epidemics of current times. Reexamining available evidence for new insights in the pathophysiology of the entity may hopefully lead to novel and better ways to prevent and treat patients affected.

Functional hyperemia and PPH
All organs and tissues of the body operate at different intensities at different moments, higher intensities generally involving increased energy expenditure per time unit. Increasing tissular blood circulation in the face of increased workload is generally known as functional hyperemia (FH). FH occurs in many organs and tissues (muscle, CNS, fat tissue, etc) at appropriate times, generally operating by an increase in blood flow (BF) during the lapse of high energy demand; with such high BF being generally mediated by the local surge of prevailing vasodilatory signals (prominently nitric oxide (NO), but also adenosine and prostacyclin) at the vascular endothelial level. FH mediating signals trigger vasodilation, capillary recruitment and increased tissular blood flow per weight unit, thus providing more oxygen and metabolic fuels to the tissue performing intense work. Being an adaptative phenomenon, FH typically occurs in muscle during (rythmic) exercise, heart during induced tachicardia , kidney after food ingestion ,  or particular brain regions or pathways during periods of high neuronal firing.

FH occuring after food ingestion has been termed postprandial hyperemia (PPH). PPH of long duration (hours-long) has been described to occur in skeletal muscle, and importantly also in the superior mesenteric (or splanchnic) vascular bed , affecting blood flow in the stomach , intestine ,  kidney , fat tissue ,  and other abdominal organs such as pancreas   and liver following the ingestion of  food in sufficiently large amounts. Topologically accompanying food bolus transit, the intensity and duration of PPH along each gut segment will depend on meal characteristics of amount and composition.

PPH is believed to occur every day in normal life (following each main meal), appearing to be teleologically designed to increase the provision of oxygen and nutrients to tissues and organs involved in the energetically demanding processes of food digestion, absorption and detoxification.

Pancreas inflammation in diabetes
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Gastric mucosa inflammation in obesity
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