Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance (IR) is a phenomenon which associates several serious "diseases of civilization" within the framework of Reaven's metabolic syndrome. In the submitted paper the authors describe the so-called "paradox of insulin resistance"--a paradoxical finding of inadequate insulin action under laboratory induced conditions while under "common" conditions the finding is reversed. Diabetes mellitus type 2 (with obesity) is characterized by excessive filling of cells by energetically rich substances. A low energy output, inadequate physical activity in these subjects leads to the development of regulatory mechanisms, which restrict further nutrient (glucose) uptake from blood into cells. During subsequent stages of the disease the excessive glucose uptake by adipose tissue cells and muscle is ensured by the high concentration gradient, hyperglycaemia and hyperinsulinaemia. Induction of "comparable" conditions in clamp studies leads to paradoxical results. During relative hypoglycaemia and hypoinsulinaemia (as compared with normal conditions) the tissues of the diabetic patient, due to regulatory mechanisms, take up a smaller amount of glucose than tissues of non-diabetic subjects (although under normal conditions the glucose uptake is higher). This phenomenon is called "Paradox of insulin resistance". In a major proportion of patients IR can be induced by mere maintenance of hyperinsulinaemia, it can be minimalized by reducing the nutrient intake and by increasing physical exertion. Differentiation of patients where IR is a secondary, regulatory phenomenon is one of the basic tasks of the physician. Only patients who suffer from primary disorders of insulin function, primary IR and true insulin deficiency should be treated by administration of hyperinsulinaemia inducing drugs. It is questionable how suitable it is to administer these drugs to patients who suffer from a life-style disorder and are threatened by complications associated with hyperinsulinism.
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PMID:[The paradox of insulin resistance]. 1095 72

Multiple metabolic syndrome (MMS) implies a frequent coincidence of four basic serious metabolic risk factors for subsequent manifestation of cardiovascular disease. The latter include: central type obesity, arterial hypertension, dyslipoproteinaemia and diabetes mellitus type II (non-insulin-dependent diabetes mellitus--NIDDM). MMS is also described as syndrome X, Reaven's syndrome, insulin resistance syndrome, metabolic syndrome or as the "deadly quartet". NIDDM in humans is conceived as a syndrome the pathogenesis of which is multifactorial and it is not an unequivocal nosological unit. It many epidemiological studies reliable evidence was provided that in the aetiology of NIDDM a marked genetic influence is involved. Its genetic predisposition is conditioned by the interaction of candidate genes and a complex of influences of the external environment. Evidence was provided that MMS phenotypes cumulate only in members of some families. The mode of genetic transmission of NIDDM remains obscure.
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PMID:[Genetic predisposition for multiple metabolic syndrome. Part 1. Diabetes mellitus type 2--incidence and prevalence]. 1095 28

Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine constitutively produced by adipose tissue that may mediate insulin resistance. Studies in Caucasian subjects have suggested that the G-308A transition in the 5' region of the TNF-alpha gene may be associated with insulin resistance and obesity. These factors have been proposed to underlie the clustering of type 2 diabetes, hypertension, and dyslipidemia found in the metabolic syndrome, the prevalence of which is reaching epidemic proportions in Hong Kong Chinese. We investigated the association of this gene polymorphism with the components of the metabolic syndrome including the lipid profile, as well as with the indices of obesity and insulin resistance as measured by the insulin-glucose product, in 440 Chinese subjects (healthy [27.5%] and overlapping groups with type 2 diabetes [54.1%], hypertension [38.8%], dyslipidemia [39.3%], or obesity [39.5%]). The frequency of the mutant A allele was 7.4% in 121 healthy controls and 9.0% in the total population. The mutation was not associated with any component of the metabolic syndrome or with the prevalence of albuminuria and retinopathy in these subjects. Furthermore, there was no difference in anthropometric measures, insulin resistance, or lipid levels between subjects with the GG genotype and those with the mutant allele. In summary, the TNF-alpha gene G-308A polymorphism is unlikely to play an important role in the development of these disorders in this population.
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PMID:Tumor necrosis factor alpha gene G-308A polymorphism in the metabolic syndrome. 1095 20

We studied whether there is an association between the single nucleotide polymorphism c.533A>C (K121Q) in the glycoprotein PC-1 gene and features of the metabolic syndrome in case-control and intrafamily association studies in 922 subjects from Finland and Sweden. No difference was observed in the Q allele frequency between control subjects and type 2 diabetic subjects (12.9 vs. 15.1%). The QK genotype was associated with higher fasting plasma glucose (FPG) concentrations than the KK genotype in type 2 diabetic patients (P <0.001) and their relatives (P <0.05). A permutation test of siblings discordant for the QK and KK genotypes also showed that the nondiabetic siblings with the QK genotype had higher FPG (6.1 +/- 2.0 vs. 5.4 +/- 0.6 mmo/l, P <0.001) and fasting insulin (7.0 +/- 3.6 vs. 4.8 +/- 2.6 mU/l, P <0.05) concentrations than the carriers of the KK genotype. In addition, diabetic siblings with the QK genotype had higher systolic blood pressure (147.0 +/- 18.0 vs. 140.0 +/- 18.7 mmHg, P <0.05) and higher fasting (9.9 +/- 3.0 vs. 8.8 +/- 2.8 mmol/l, P <0.05) and 2-h plasma glucose (17.3 +/- 8.5 vs. 12.9 +/- 4.2 mmol/l, P < 0.05) concentrations than the diabetic carriers of the KK genotype. The present study shows that, although the Q allele of the human glycoprotein PC-1 gene is associated with surrogate measures of insulin resistance, it may not be enough to increase the susceptibility to type 2 diabetes.
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PMID:Association between the human glycoprotein PC-1 gene and elevated glucose and insulin levels in a paired-sibling analysis. 1096 47

Since obesity is a major risk factor for cardiovascular disease (CVD), the increasing prevalence and degree of obesity in all developed countries has the potential to significantly offset the current efforts to decrease CVD burden in our population. Obesity is pathogenetically related to several clinical and sub-clinical abnormalities that contribute to the development of atherosclerotic placks and their complication, leading to the onset of cardiovascular events. Obesity seems to interact with inheritable factors in determining the onset of insulin resistance, a metabolic abnormality that is responsible for altered glucose metabolism and predisposition to type 2 diabetes, but that also has a major role in the development of dyslipidemia, hypertension and many other sub-clinical abnormalities that contribute to the atherosclerotic process and onset of cardiovascular events. Inheritable factors seem to modulate the onset of type 2 diabetes, dyslipidemia, hypertension and various insulin resistance-related sub-clinical abnormalities, often in a clustering pattern that is commonly referred to as the "metabolic syndrome." Inheritable factors also are involved in the onset of CVD in a given population or individuals with various components of the metabolic syndrome. Intense research is currently undergoing to better understand the molecular mechanisms that could explain the relationship between environmental and inheritable factors that lead from obesity to atherosclerosis and cardiovascular event. The elucidation of these mechanisms will provide improved therapeutic strategies to reduce cardiovascular risk in the obese patients. However, effective therapeutic tools that control each of the known pathophysiological steps mediating CVD in obese patients are already available and should be used more aggressively. Patient education and coordinated approach of physicians, nurses and other health care providers in a multidisciplinary treatment of the obese patient is of fundamental importance to reduce CVD burden in our population.
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PMID:Obesity and cardiovascular disease. Pathogenetic role of the metabolic syndrome and therapeutic implications. 1098 24

Japanese Americans have experienced a higher prevalence of type 2 diabetes than in Japan. Research conducted in Seattle suggests that lifestyle factors associated with 'westernization' play a role in bringing out this susceptibility to diabetes. These lifestyle factors include consumption of a diet higher in saturated fat and reduced physical activity. A consequence of this is the development of central (visceral) adiposity, insulin resistance, and other features associated with this insulin resistance metabolic syndrome, such as dyslipidemia (high triglycerides, low HDL-cholesterol, and small and dense LDL particles), hypertension, and coronary heart disease. We have postulated that the superimposition of insulin resistance upon a genetic background of reduced beta-cell reserve results in hyperglycemia and diabetes among Japanese Americans. This article reviews evidence that support this view.
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PMID:Type 2 diabetes and the metabolic syndrome in Japanese Americans. 1102 87

LDL-cholesterol subfractions have a different atherogenity; the most atherogenic are small LDL3 called small dense LDL. A clear relationship was proved between their concentration and early manifestation of ischaemic heart disease. In some instances they were found to act as an independent risk factor of cardiovascular disease. Their concentration depends to a great extent on the triacyglycerol concentration. They are found most frequently in patients with combined hyperlipidaemia, in associated metabolic syndrome and in patients with type 2 diabetes mellitus. Their plasma concentration can be reduced by non-pharmacological methods (restriction of animal fats, reduction of body weight, physical activity) as well as by pharmacological means (in particular fibrates). Micronized phenofibrate reduces significantly the concentration of small LDL3 and thus contributes to normalization of dyslipoproteinaemia and reduction of the risk of cardiovascular complications.
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PMID:[Micronized fenofibrate and LDL-cholesterol subfractions]. 1104 66

Type 2 diabetes mellitus is associated with hypertension. If untreated, hypertension has a major impact on the clinical course of Type 2 diabetes and its vascular complications. In this review, we discuss rationale for the use of ACE inhibitors (ACEI) in hypertensive Type 2 diabetic patients and compare those theoretical assumptions with results of recent major clinical trials. Furthermore, possible directions for future clinical and experimental research are outlined. The RAS and its effector angiotensin II are important players in a number of cardiovascular and renal disorders. Recent evidence suggests that RAS and factors functionally linked to RAS are activated in Type 2 diabetes. Therefore, there is a theoretical basis for the use of ACEI in the treatment of hypertension in diabetic patients. Some recent studies reported superior outcome in patients treated with ACEI-based antihypertensive regimens compared with non-ACEI based treatments in reducing the risk of macrovascular disease (CAPPP, FACET, ABCD) or both micro- and macrovascular complications in Type 2 diabetes (HOPE). However, at least two of the large prospective studies discussed in this review (UKPDS 38, HOT), supported by results from previously published SHEP study, have recently suggested that the degree of reduction of blood pressure, rather than the choice of a particular class of antihypertensive agent, is associated with decreased risk of cardiovascular events. Studies focusing on renal end-points suggest that ACEI have a superior antiproteinuric effect than the other agents. However, whether ACEI are more nephroprotective, as assessed by the rate of decline in renal function, still remains to be elucidated. Despite promising results from recent trials, large numbers of patients progress despite ACEI treatment. Incomplete inhibition of the RAS may underlie this phenomenon. Treatment strategies that could enhance the degree of RAS inhibition represent one possible direction for clinical research in the near future. However, it is unlikely that the course of such a complex syndrome as Type 2 diabetes could be dramatically changed by just one class of antihypertensive agents. This goal is more likely to be achieved by multifactorial intervention, reflecting the complexity of metabolic syndrome. ACEI should be viewed as an important, but not the only, part of this complex approach.
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PMID:Therapeutic potential of ACE inhibitors for the treatment of hypertension in Type 2 diabetes. 1106 Aug 23

Patients with type 2 diabetes (formerly known as non-insulin-resistant diabetes) have a significantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients. By inducing endothelial changes, hyperglycemia contributes directly to atherosclerosis. Type 2 diabetes is also associated with atherogenic dyslipidemias. This form of diabetes, or the precursor state of insulin resistance, commonly occurs as a metabolic syndrome (formerly known as syndrome X) consisting of hypertension, atherogenic dyslipidemia and a procoagulant state, in addition to the disorder of glucose metabolism. All cardiovascular risk factors except smoking are more prevalent in patients with type 2 diabetes. In addition to exercise, weight control, aspirin therapy and blood pressure control, therapy to modify lipid profiles is usually necessary. The choice of agent or combination of statin, bile acid sequestrant, fibric acid derivative and nicotinic acid depends on the lipid profile and characteristics of the individual patient.
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PMID:Attenuating cardiovascular risk factors in patients with type 2 diabetes. 1114 70

The rising prevalence of obesity is accompanied by an increasing number of patients with the metabolic complications of obesity. The major complications come under the heading of the metabolic syndrome. This syndrome is characterized by plasma lipid disorders (atherogenic dyslipidemia), raised blood pressure, elevated plasma glucose, and a prothrombotic state. The clinical consequences of the metabolic syndrome are coronary heart disease and stroke, type 2 diabetes and its complications, fatty liver, cholesterol gallstones, and possibly some forms of cancer. At the heart of the metabolic syndrome is insulin resistance, which represents a generalized derangement in metabolic processes. Obesity is the predominant factor leading to insulin resistance, although other factors play a role. The mechanistic link between insulin resistance and the metabolic syndrome is complex. The relationship is modulated by yet other factors, such as physical activity, body fat distribution, hormones, and a person's genetic polymorphic architecture. A better understanding of the molecular basis of this relationship is needed to suggest new targets for prevention and treatment of the complications of obesity. In addition, understanding at the clinical level will lead to improved management of these complications.
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PMID:Metabolic complications of obesity. 1118 17


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