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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Weight loss favorably modifies most cardiovascular risk factors, in particular the diagnostic criteria for metabolic syndrome, type 2 diabetes mellitus, and hypertension. Treating the spectrum of diabetes by promoting disease control or resolution invariably improves cardiovascular outcomes. However, in clinical trials and routine medical practice, long-term weight loss has been difficult to achieve due to wavering patient motivation, inadequate resources, ineffective medical treatments, lack of psychosocial support, recidivism, or combinations thereof. The issue is not information but rather methods, motivation, and behavioral changes. This article reviews surgical and nonsurgical methods of weight loss and their impact on cardiovascular risk factors, especially the resolution of type 2 diabetes mellitus, and the implications for cardiovascular event reduction in patients with morbid obesity.
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PMID:Impact of surgical and nonsurgical weight loss on diabetes resolution and cardiovascular risk reduction. 1949 Aug 24

The trafficking of glycerol from adipose and hepatic tissue is mainly mediated by 2 aquaporin channel proteins: AQP7 and AQP9, respectively. In rodents, both aquaporins were found to act in a coordinated manner. The aim was to study the relationship between adipose AQP7 and hepatic AQP9 messenger RNA expression and the presence of glucose abnormalities simultaneously in morbid obesity. Adipose tissue (subcutaneous [SAT] and visceral [VAT]) and liver biopsies from the same patient were obtained during bariatric surgery in 30 (21 male and 9 female) morbidly obese subjects. Real-time quantification of AQP7 in SAT and VAT and hepatic AQP9 gene expression were performed. A 75-g oral glucose tolerance test was performed in all subjects. The homeostasis model assessment of insulin resistance and lipidic profile were also determined. Visceral adipose tissue AQP7 expression levels were significantly higher than SAT AQP7 (P = .009). Subcutaneous adipose tissue AQP7 positively correlated with both VAT AQP7 and hepatic AQP9 messenger RNA expression (r = 0.44, P = .013 and r = 0.45, P = .012, respectively). The correlation between SAT AQP7 and liver AQP9 was stronger in intolerant and type 2 diabetes mellitus subjects (r = 0.602, P = .011). We have found no differences in compartmental AQP7 adipose tissue distribution or AQP9 hepatic gene expression according to glucose tolerance classification. The present study provides, for the first time, evidence of coordinated regulation between adipose aquaglyceroporins, with a greater expression found in visceral fat, and between subcutaneous adipose AQP7 and hepatic AQP9 gene expression within the context of human morbid obesity.
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PMID:Gene expression of paired abdominal adipose AQP7 and liver AQP9 in patients with morbid obesity: relationship with glucose abnormalities. 1961 2

The gut can contribute to the control of glucose homeostasis by its high glycolytic capacity and a recently described function, gluconeogenesis. In addition to its quantitative role in endogenous glucose production, a qualitative role of central signaling was recently described for intestinal gluconeogenesis. Relating to the control of energy homeostasis, intestinal gluconeogenesis, by its detection by a hepatoportal glucose sensor, is able to generate a central signal promoting a decrease in food intake. This mechanism may contribute to the well-known satiety effect initiated by food protein. In relation to the control of glucose homeostasis, intestinal gluconeogenesis has been suggested to be a key factor of the central enhancement of insulin sensitivity for the whole body. It may account for the rapid amelioration of insulin resistance occurring after gastric bypass, a specific type of surgery for morbid obesity. Because these beneficial effects may take place in the context of established physiopathology, they allow one to envision new strategies of prevention or treatment of obesity and type 2 diabetes in humans.
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PMID:A novel function of intestinal gluconeogenesis: central signaling in glucose and energy homeostasis. 1964 21

Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea that FTO itself is involved in obesity. We show that a dominant point mutation in the mouse Fto gene results in reduced fat mass, increased energy expenditure, and unchanged physical activity. Exposure to a high-fat diet enhances lean mass and lowers fat mass relative to control mice. Biochemical studies suggest the mutation occurs in a structurally novel domain and modifies FTO function, possibly by altering its dimerisation state. Gene expression profiling revealed increased expression of some fat and carbohydrate metabolism genes and an improved inflammatory profile in white adipose tissue of mutant mice. These data provide direct functional evidence that FTO is a causal gene underlying obesity. Compared to the reported mouse FTO knockout, our model more accurately reflects the effect of human FTO variants; we observe a heterozygous as well as homozygous phenotype, a smaller difference in weight and adiposity, and our mice do not show perinatal lethality or an age-related reduction in size and length. Our model suggests that a search for human coding mutations in FTO may be informative and that inhibition of FTO activity is a possible target for the treatment of morbid obesity.
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PMID:A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. 1968 May 40

Morbid obesity, a physiological dysfunction in humans associated with environmental, genetic and endocrinological origins, has significantly increased in the past few decades in the USA. Many methods have emerged for treating morbid obesity, such as diets, exercise, behavior modification, liposuction, drugs, and surgery; among these, bariatric surgery reduces weight and appears to have other curative effects. Roux-en-Y gastric bypass is the principal form of bariatric surgery, followed by laparoscopic adjustable gastric banding, gastric sleeve operation, duodenojejunal bypass and biliopancreatic diversion. This weight-loss surgery may also affect comorbidities of morbid obesity, such as type 2 diabetes mellitus (T2D), atherosclerosis, hypertension and steatohepatitis. Weight-loss surgery, for example, is associated with a more than 80% diabetes (data indicates > 80%) remission rate in severely obese persons. Empirical evidence also suggests that the use of bariatric surgery reduces atherosclerosis, and may ameliorate other comorbities. This warrants closer examination.
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PMID:Bariatric Surgery to Correct Morbid Obesity Also Ameliorates Atherosclerosis in Patients with Type 2 Diabetes Mellitus. 1991 85

Surgical treatment of morbid obesity has been shown to be efficient for long-term weight loss and to improve obesity-related complications. The improvement of type 2 diabetes (T2DM) is dependent of the type of surgery, and is more frequent with gastric bypass than with gastric band. Normalization of glucose metabolism is rapid, often occurring before weight loss, and shown to be related to both a decrease in insulin resistance and an increase in insulin secretion. Some factors limiting the efficiency of gastric bypass on T2DM is the duration of diabetes and the residual beta-cell mass. However, a decrease in diabetes-related death has been found in a large series of surgical cases. These data constitute a good argument for proposing surgery in T2DM obese patients as soon as possible. Nevertheless, whether or not this suggests changing the usual indications for bariatric surgery in T2DM patients, such as a body mass index (BMI) score of<35 kg/m(2), remains controversial.
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PMID:Bariatric surgery for diabetes treatment: why should we go rapidly to surgery. 2015 44

Roux-en-Y gastric bypass (RYGB) surgery is the most effective treatment for morbid obesity and remission of associated type 2 diabetes, but the mechanisms involved are poorly understood. The aim of the present study was to develop and validate a rat model for RYGB surgery that allows repeated measurement of meal-induced changes in gut and pancreatic hormones via chronic venous catheters. Male Sprague Dawley rats made obese on a palatable high-fat diet were subjected to RYGB or sham surgery and compared with chow-fed, lean controls. Hormonal responses to a mixed-liquid test meal were examined by frequent blood sampling through chronically implanted jugular catheters in freely behaving rats, 3-4 months after surgery, when RYGB rats had significantly reduced body weight and fat mass compared with sham-operated rats. Hyperleptinemia, basal hyperinsulinemia, and hyperglycemia as well as postprandial glucose intolerance seen in sham-operated, obese rats were completely reversed by RYGB and no longer different from lean controls. Postprandial increases in glucagon-like peptide-1, peptide YY, and amylin as well as suppression of ghrelin levels were all significantly augmented in RYGB rats compared with both sham-operated obese and lean control rats. Thus, our rat model replicates most of the salient hormonal and glycemic changes reported in obese patients after RYGB, with the addition of amylin to the list of potential candidate hormones involved in hypophagia, weight loss, and remission of diabetes. The model will be useful for elucidating the specific peripheral and central mechanisms involved in the suppression of appetite, loss of body weight, and remission of type 2 diabetes.
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PMID:Meal-induced hormone responses in a rat model of Roux-en-Y gastric bypass surgery. 2017 62

Bariatric surgery is known to be the most effective and long lasting treatment for morbid obesity and many related conditions, but now mounting evidence suggests it may be among the most effective forms of treatment for metabolic diseases and conditions including type 2 diabetes, hypertension, high cholesterol levels, non-alcoholic fatty liver disease and obstructive sleep apnea. Surgery for severe obesity goes way beyond weight loss. This surgery results in the complete remission or significant improvement of type 2 diabetes and other life-threatening diseases in most patients. The new name metabolic surgery was created and reflects this expanded and evolving view of surgery. Therefore, metabolic surgery is expected to play an ever increasing role in managing these diseases. New research results indicate that metabolic surgery may improve insulin resistance and secretion by mechanisms independent of weight loss, most likely involving changes in gastrointestinal hormones. Many patients with type 2 diabetes experience complete remission within days of metabolic surgery, long before significant weight is lost. This has led to a new concept that metabolic surgery may also be appropriate for diabetic individuals who are of normal weight or only slightly overweight.
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PMID:[Indications and principles of metabolic surgery]. 2036 70

Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.
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PMID:Metabolic syndrome and chronic kidney disease. 2036 11

Obesity has reached epidemic proportions and is continuing to grow into one of the leading healthcare issues worldwide. With this development, bariatric surgery has emerged as an acceptable treatment for morbid obesity, generally achieving meaningful and sustained weight loss. In a surprising turn of events, bariatric surgery was also found to be the most effective therapy for type 2 diabetes mellitus (T2DM). This observation has sparked a great deal of research that has improved our understanding of T2DM pathophysiology; it has facilitated the development of medical treatment and is expanding the indications for bariatric surgery. It was traditionally accepted that bariatric surgery causes weight loss by restriction of gastric volume, intestinal malabsorption, or a combination of the two. Laparoscopic adjustable gastric banding (LAGB) is considered a purely restrictive procedure that involves the placement of an adjustable band around the cardia of the stomach, creating a 15 ml pouch. Laparoscopic sleeve gastrectomy (LSG) is the resection of the fundus all along the greater curvature of the stomach. LSG was once considered a restrictive procedure, but this presumption has recently come under scrutiny. Bilio-pancreatic diversion (BPD) is an example of a procedure that was considered predominantly malabsorptive. In this operation, the ingested nutrients are diverted from the stomach to the ileum, bypassing a large segment of proximal bowel. Roux-en-Y gastric bypass (RYGB) traditionally combines both mechanisms, partitioning a small pouch from the proximal stomach and diverting the ingested nutrients to the jejunum with a roux-en-Y gastro-jejunostomy. However, recent investigation suggests additional mechanisms of action including hormonal. Today, RYGB is the procedure of choice for morbidly obese patients. The effect of bariatric surgery on T2DM was initially described in 1995 by Pories et al., who reported that there was an overall T2DM resolution after RYGB of 82.9% (1). A resolution rate of approximately 80% has been demonstrated repeatedly (2,3). The initial assumption was that the mechanism causing this effect was through weight loss. It is becoming evident that the anti-diabetic effect is not entirely weight loss as there is a consistent observation that the improvement of glucose and insulin levels occurs within days after RYGB, clearly too soon to be due to the weight loss (1,4). The ensuing body of literature has generated two leading theories attempting to explain this weight-independent anti-diabetic effect after RYGB. The 'hindgut' proposes that rapid delivery of partially digested nutrients to the distal bowel up-regulates the secretion of incretins such as glucagon-like peptide-1 (GLP-1). The result of the increased incretin secretion is an enhanced glucose-dependent insulin secretion, as well as a number of other changes causing improved glucose tolerance (4). In the second theory, 'the foregut hypothesis', the exclusion of the duodenum results in the inhibition of a 'putative' signal that is responsible for insulin resistance (IR) and/or abnormal glycaemic control. In a non-obese diabetic rat model, surgical diversion of the proximal bowel caused rapid improvement of diabetes without reduction of food intake or change in weight (5). Many aspects regarding surgical treatment of T2DM are still questionable and unexplained. Emerging data are starting to clarify the mechanisms participating in the anti-diabetic effect, and also challenging long-held theories.
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PMID:Neuro-modulation and bariatric surgery for type 2 diabetes mellitus. 2037 65


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