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

Nutritional and genetic factors interact in the etiology of type 2 diabetes. Undernutrition followed by overnutrition increases adiposity and the risk of diabetes. The thrifty hypotheses suggest that the nutritional challenges could have happened thousands of year ago (thrifty gene selection) or during one's intrauterine life (thrifty phenotype). Current strategies for the prevention of diabetes are related to avoiding overnutrition.
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PMID:Nutrition, growth, and body size in relation to insulin resistance and type 2 diabetes. 1272 36

Glucose-dependent insulinotropic polypeptide (GIP or gastric inhibitory polypeptide) is a gastrointestinal hormone, which modulates physiological insulin secretion. Due to its insulinotropic activity, there has been a considerable increase of interest in utilising the hormone as a potential therapy for type 2 diabetes. One of the difficulties in attempting to harness the insulinotropic activity of GIP into an effective therapeutic agent is its short biological half-life in the circulation. However, recent years have witnessed the development of a substantial number of designer enzyme-resistant 'super GIP' molecules with potent insulinotropic and anti-diabetic properties. In addition, observations in transgenic GIP receptor deficient mice indicate that GIP directly links overnutrition to obesity, therein playing a crucial role in the development of obesity and related metabolic disorders. The present review aims to highlight the rapidly emerging potential therapeutic applications of GIP, and especially, enzyme-resistant GIP analogues.
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PMID:Glucose-dependent insulinotropic polypeptide (GIP): anti-diabetic and anti-obesity potential? 1460 2

Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.
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PMID:Inflammation: the link between insulin resistance, obesity and diabetes. 1469 76

There is growing support for the hypothesis that obesity is an inflammatory condition leading to chronic activation of the innate immune system, which ultimately causes progressive impairment of glucose tolerance. Experimental studies in animals and evidence from prospective and longitudinal studies in humans are consistent with an etiologic role of subclinical inflammation in the pathogenesis of type 2 diabetes, primarily as a mediator of obesity-induced insulin resistance. However, the exact chain of molecular events linking overnutrition, activation of the innate immune system, and impairment of insulin signaling in peripheral tissues remains incompletely understood. Notwithstanding this limitation, treating the underlying subclinical inflammation may constitute a novel approach to prevention and/or treatment of type 2 diabetes.
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PMID:A burning question: does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? 1579 28

During the past decade, obesity has substantially increased in Korea, and this is leading to dramatic increases in complications such as type 2 diabetes. In this review, we discuss the past and the current situation of obesity in Korea based on the national health and nutrition surveys of 1995, 1998, and 2001. Because Korea is geographically isolated with relatively few migrants and has a low level of genetic heterogeneity, this report demonstrates the impact of environmental factors on the development of obesity beyond epidemiological information about one of the Asian countries. The third national health and nutrition survey reported in 2001 announced that the overall prevalence of obesity [body mass index (BMI) > or = 25.0 kg m(-2)] in Korean adults is 30.6% (32.4% in men and 29.4% in women). The prevalence of obesity in adults and children has increased rapidly from 1990s through the beginning of the new millennium and is steadily increasing in parallel with our rapid socio-economic progress. In particular, special attention should be paid to two groups in hormonal transition: first, middle-aged men and women who experience a great increase in body weight, BMI and waist circumference because of andropause or menopause, and second, adolescents in middle to high school who are preparing for qualification or entrance examinations and are prone to overnutrition or nutritional imbalance and physical inactivity.
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PMID:Prevalence of obesity in Korea. 1583 62

Nonalcoholic steatohepatitis (NASH), the lynchpin between steatosis and cirrhosis in the spectrum of nonalcoholic fatty liver disorders (NAFLD), was barely recognized in 1981. NAFLD is now present in 17% to 33% of Americans, has a worldwide distribution, and parallels the frequency of central adiposity, obesity, insulin resistance, metabolic syndrome and type 2 diabetes. NASH could be present in one third of NAFLD cases. Age, activity of steatohepatitis, and established fibrosis predispose to cirrhosis, which has a 7- to 10-year liver-related mortality of 12% to 25%. Many cases of cryptogenic cirrhosis are likely endstage NASH. While endstage NAFLD currently accounts for 4% to 10% of liver transplants, this may soon rise. Pathogenic concepts for NAFLD/NASH must account for the strong links with overnutrition and underactivity, insulin resistance, and genetic factors. Lipotoxicity, oxidative stress, cytokines, and other proinflammatory mediators may each play a role in transition of steatosis to NASH. The present "gold standard" management of NASH is modest weight reduction, particularly correction of central obesity achieved by combining dietary measures with increased physical activity. Whether achieved by "lifestyle adjustment" or anti-obesity surgery, this improves insulin resistance and reverses steatosis, hepatocellular injury, inflammation, and fibrosis. The same potential for "unwinding" fibrotic NASH is indicated by studies of the peroxisome proliferation activator receptor (PPAR)-gamma agonist "glitazones," but these agents may improve liver disease at the expense of worsening obesity. Future challenges are to approach NAFLD as a preventive public health initiative and to motivate affected persons to adopt a healthier lifestyle.
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PMID:Nonalcoholic fatty liver disease: from steatosis to cirrhosis. 1644 87

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

During the past 10 years, there has been a dramatic increase in the prevalence of obesity in the United States and other developed nations. Recent studies indicate that adipose tissue is an endocrine organ producing numerous proteins, collectively referred to as adipokines, with broad biological activity, that play an important autocrine role in obesity-associated complications. Adipose tissue in general and visceral fat in particular are thought to be key regulators of inflammation. Inflammation is heavily involved in the onset and development of atherothrombotic disease. Moreover, chronic inflammation may also represent a triggering factor in the origin of the metabolic syndrome and type 2 diabetes mellitus. According to a hypothesis, stimuli such as overnutrition, physical inactivity, and aging would result in cytokine hypersecretion and eventually lead to insulin resistance and diabetes in genetically or metabolically predisposed individuals. This article discusses the current understanding of important adipokines thought to be involved in the metabolic and cardiovascular risk associated with obesity. Available evidence linking fat removal by liposuction to modification of cardiovascular risk and vascular inflammatory markers in the obese patient is also presented. Most studies have shown that liposuction produces beneficial effects on insulin resistance and vascular inflammation in the obese patient, reducing its cardiovascular risk. Besides having a significant role in body contouring of the obese patient at the end of the lengthy process of bariatric surgery and massive weight loss, plastic surgery should be incorporated into a multifaceted program of lifestyle changes that allows the obese patient to obtain weight loss and, more importantly, to maintain the reduced weight in the long term.
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PMID:Role of adipokines in the obesity-inflammation relationship: the effect of fat removal. 1757 1

Lipid droplet proteins of the PAT (perilipin, adipophilin, and TIP47) family regulate cellular neutral lipid stores. We have studied a new member of this family, PAT-1, and found that it is expressed in highly oxidative tissues. We refer to this protein as "OXPAT." Physiologic lipid loading of mouse liver by fasting enriches OXPAT in the lipid droplet tissue fraction. OXPAT resides on lipid droplets with the PAT protein adipophilin in primary cardiomyocytes. Ectopic expression of OXPAT promotes fatty acid-induced triacylglycerol accumulation, long-chain fatty acid oxidation, and mRNAs associated with oxidative metabolism. Consistent with these observations, OXPAT is induced in mouse adipose tissue, striated muscle, and liver by physiological (fasting), pathophysiological (insulin deficiency), pharmacological (peroxisome proliferator-activated receptor [PPAR] agonists), and genetic (muscle-specific PPARalpha overexpression) perturbations that increase fatty acid utilization. In humans with impaired glucose tolerance, PPARgamma agonist treatment induces adipose OXPAT mRNA. Further, adipose OXPAT mRNA negatively correlates with BMI in nondiabetic humans. Our collective data in cells, mice, and humans suggest that OXPAT is a marker for PPAR activation and fatty acid oxidation. OXPAT likely contributes to adaptive responses to the fatty acid burden that accompanies fasting, insulin deficiency, and overnutrition, responses that are defective in obesity and type 2 diabetes.
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PMID:OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization. 1713 Apr 88

Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose-induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.
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PMID:Inflammation in metabolic syndrome and type 2 diabetes: Impact of dietary glucose. 1715 Dec 91


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