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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cowden's Syndrome (CS), or multiple hamartoma syndrome, is an autosomal dominant disorder characterized by mucocutaneous lesions, multiple benign tumors of internal organs and an increased risk of breast cancer. Here, we describe and illustrate in detail the benign breast pathology of 59 breast cases from 19 women with CS. Fibrosis is a significant characteristic of the breasts of patients with CS. Fibroadenomas appear to hyalinize at an early age and are frequently complex. The specimens demonstrate a spectrum of dense hyalinization of both the lobule and the stroma, and hyaline nodules appear to be the most characteristic lesion. This hyalinization process shares striking similarities with keloids, as well as the sclerotic nodules seen in the skin of CS individuals. Ductal carcinoma in CS was common, and it appeared to be associated with stromal hyalinization. Other frequently found benign features are adenosis and cysts. Of interest, the features of the benign breast disease in CS show certain similarities with senescent lobules, fibrous mastopathy of diabetes mellitus, and mammary hamartomas. These observations provide a framework for pathologists to identify this underrecognized syndrome.
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PMID:Similarities of cutaneous and breast pathology in Cowden's Syndrome. 985 41

Most people with the Metabolic Syndrome die from thrombotic complications superimposed to degenerative arterial vascular lesions, mostly myocardial infarction. Type-2-Diabetes is a risk factor per se for such complications, but often clusters with dyslipoproteinemia, hypertension and obesity. This is referred to as "Metabolic Syndrome" and often operates on a genetically programmed susceptibility which accelerates the pathogenesis of coronary artery disease in front of a much wider diabetes specific cardiopathy. From a pathophysiological point of view none of these associated risk factors explains the pathogenetic series of events leading to the precipitation of an occlusive thrombus at sites of complicated coronary plaques. In patients with the Metabolic Syndrome the coagulation system is switched towards a prethrombotic state, involving increased plasmatic coagulation, diminished fibrinolysis, decreased endothelial thromboresistance and predominantly platelet hyperreactivity ("diabetic thrombocytopathy"). Some of these factors are associated with an increased coronary risk (e.g. fibrinogen, PAI-1, platelets), but are also directly linked to the pathogenesis of "atherothrombosis". Altered cardiac remodelling together with adhesion and coagulation mechanisms appears suitable to explain decreased functional performance of infarcted organs, decreased success of acute (reduced fibrinolytic response, no reflow phenomenon) and longterm intervention strategies for vessel patency (PTCA, CABG) in Diabetes. Glucose adjustment alone will not adequately neutralize these complex mechanisms, but in the situation of myocardial infarction eumetabolization with parenteral glucose-insulin-potassium infusion appears mandatory similar to non-diabetics. On the longterm a multidimensional interventional repertoire is required particularly in patients with the Metabolic Syndrome including antihypertensive, antidyslipoproteinemic and antithrombotic drugs, customized according to the individual patients needs as assessed by early diagnostic measures ("early secondary prevention").
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PMID:[The heart and metabolic syndrome]. 1035 72

Congenital generalized lipodystrophy (CGL, Berardinelli-Seip Syndrome, OMIM # 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (theta(max) = 0.05). There was evidence for genetic heterogeneity (alpha = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL1 critical region harbors a plausible candidate gene encoding the retinoid X receptor alpha (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue.
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PMID:A gene for congenital generalized lipodystrophy maps to human chromosome 9q34. 1048 16

Insulin resistance describes an impaired biological response to insulin, which underpins the development of type 2 (non-insulin-dependent) diabetes mellitus (T2DM). Initially, insulin resistance causes a compensatory hyperinsulinaemia, which gives way to pancreatic beta-cell failure. Insulin resistance and hyperinsulinaemia conspire together in the development of a diverse collection of risk factors for coronary heart disease, namely obesity, T2DM, dyslipidaemia, hypertension, atherosclerosis, and a pro-coagulant state. This collection of factors is commonly found in T2DM patients, and is recognised as the Insulin Resistance Syndrome or Syndrome X. By targeting insulin resistance as a treatment strategy for T2DM, it should be possible to broaden the potential benefits, so that improved glycaemic control is complemented with improvements to other components of Syndrome X. At present, metformin and thiazolidinediones are the only therapies for T2DM that directly address aspects of insulin resistance. Increasing awareness of the clinical implications of insulin resistance, and increasing knowledge of the cellular basis of insulin resistance, provide the rationale and a means for developing an anti-insulin resistance approach to the treatment of T2DM.
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PMID:Insulin resistance and antidiabetic drugs. 1053 41

Obesity, insulin resistance and disturbed glucose metabolism cluster within the Insulin Resistance Syndrome (IRS). Whether this reflects shared genetic or environmental factors detectable in 'normal' populations (not selected for IRS features) is unknown. This study estimated (i) genetic influences on IRS traits and (ii) shared and specific genetic and environmental factors on the relationships between these traits in healthy female twins. Fasting insulin, glucose, total and central fat were measured in 59 monozygotic (MZ) and 51 dizygotic (DZ) female twin pairs aged (+/- SD) 52 +/- 13 years. Body fat was measured by dual-energy X-ray absorptiometry, insulin resistance and secretion by a modified homeostasis model assessment. Using intraclass correlation coefficients and univariate model-fitting analyses, genetic influences were found in total fat, central fat, insulin resistance, fasting glucose and insulin secretion, with genetic factors explaining 64, 57, 59, 75 and 68% of their variance, respectively, using the latter technique. In matched analysis intra-pair differences in total and central fat related to intra-pair differences in insulin resistance (r2 = 0.19, P < 0.001). Multivariate model-fitting showed a close genetic relationship between total and central fat (r = 0.88). The genetic correlation between IR and central fat (0.41) was significantly greater than that for total fat (0.24), suggesting that central fat is not only a predictor of, but shares considerable genetic influence with, insulin resistance. In Cholesky analysis, these genetic influences were separate from those shared between central and total fat. In conclusion, both shared and specific genetic factors regulate components of the IRS in healthy females. However, there were discrete genetic influences on beta-cell insulin secretion, not shared with other IRS components, suggesting that a separate genetic propensity exists for Type 2 diabetes. These findings suggest we may understand the genetic and environmental influences on IRS from the study of the normal population.
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PMID:Clustering of insulin resistance, total and central abdominal fat: same genes or same environment? 1055 33

We examined the determinants of glycaemic control in a consecutive cohort of 562 newly-referred Chinese type 2 diabetic patients (57% women) during a 12-month period. All patients underwent a structured assessment with documentation of clinical and biochemical characteristics. Pancreatic beta-cell function was assessed by fasting plasma C-peptide concentration. Insulin deficiency was defined as fasting plasma C-peptide <0.2 pmol/ml. Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA) based on a product of fasting plasma glucose and insulin concentrations. Treatment was considered appropriate when insulin-deficient patients were treated with insulin and non-insulin-deficient patients were treated with oral agents or diet. Mean (+/-SD) age was 54.3+/-13.8 years (range 17-87 years) and disease duration was 5.0+/-5.9 years. At the time of referral, 70.5% (n=396) were on drug therapy (9% on insulin and 62.8% on oral agents), 20.6% (n=116) were on diet and 9% (n=50) had not received any form of treatment. The mean HbA(lc) was 8.4+/-2.3%. The geometric mean (x// antilog SD) of IR was 4.62x//2.51 (range 0. 63-162.7) and correlated only with waist : hip ratio (WHR, p=0.008). The geometric mean of plasma C peptide was 0.47x//2.89 nmol/l and correlated with BMI (p<0.001). Glycated haemoglobin was correlated positively with age (p=0.013), disease duration (p<0.001), IR (p<0. 001) and negatively with BMI (p<0.001). Glycated haemoglobin was lower in patients who had seen a dietitian (7.9% vs. 8.7%, p<0.001) or diabetes nurse (7.8% vs. 8.7%, p<0.001) or who performed self blood glucose monitoring (7.9% vs. 8.6%, p=0.001) and higher among smokers (8.9% vs. 8.2%, p=0.003). Compared to insulin-deficient patients (n=118), non-insulin-deficient patients (n=413) had features resembling that of the Metabolic Syndrome with increased WHR (p=0.005), blood pressure (p<0.001), BMI (p=0.001) and were older (p=0.04). Amongst the insulin-deficient patients, 27% were treated with oral agents or diet. Patients receiving appropriate therapy (n=362) had a lower HbA(lc) than those treated inappropriately (n=173) (8.2% vs. 8.7%, p=0.02). On multivariate analysis, short disease duration (p<0.001), low IR (p<0.001), high BMI (p=0.001), diabetes education (p<0.001), lack of smoking (p=0. 014) and choice of appropriate treatment (p=0.009) were the independent determinants of good glycaemic control.
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PMID:Glycaemic control in type 2 diabetes: the impact of body weight, beta-cell function and patient education. 1075 Dec 38

Obesity and Type 2 diabetes are now major public health issues in developed nations and have reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican-Americans, African-Americans, and Australian Aborigines. These groups all show hyperinsulinemia and insulin resistance, which have been demonstrated to be future predictors of Type 2 diabetes and have also been suggested as key factors in the etiology of the Metabolic Syndrome. It is now increasingly recognized that Type 2 diabetes is part of a cluster of cardiovascular disease (CVD) risk factors comprising the Metabolic Syndrome. This group is at very high risk of atherosclerosis because each of the risk factors in the Metabolic Syndrome cluster in its own right is an important CVD risk factor. They also contribute cumulatively to atherosclerosis. A key strategy in reducing macrovascular disease lies in the better understanding of the Metabolic Syndrome--glucose intolerance, hypertension, hyperlipidemia, and central obesity. Although it has been suggested that hyperinsulinemia/insulin resistance is the central etiological factor for the Metabolic Syndrome, epidemiological data do not support the idea that this can account for all of the cluster abnormalities. We have animal and human data suggesting that hyperleptinemia rather than, or synergistically with, hyperinsulinemia may play a central role in the genesis of the CVD risk factor cluster that constitutes the syndrome. Studies in Psammomys obesus (the Israeli sand rat) suggest hyperinsulinemia/insulin resistance is an early metabolic lesion in the development of obesity and Type 2 diabetes. This animal also develops other features of the Metabolic Syndrome, making it an excellent model to investigate etiology. Psammomys, when placed on an ad libitum laboratory diet, develops hyperinsulinemia, insulin resistance, impaired glucose tolerance, diabetes, and dyslipidemia. It also develops hyperleptinemia and leptin insensitivity, and hyperleptinemia is correlated with insulin resistance independent of changes in body weight. It is likely that a similar sequence occurs in the transition from the prediabetic state to Type 2 diabetes in humans. More recently, other potential players in the etiology of the Metabolic Syndrome have been suggested including endothelial dysfunction and acetylation-stimulating protein (ASP). It has been suggested that endothelial dysfunction may be an antecedent for both Type 2 diabetes and the Metabolic Syndrome. In addition, ASP is a serious new candidate for an important role in insulin resistance. The ASP pathway plays a critical role in fatty acid metabolism and storage, and it has been suggested that ineffective storage of fatty acids by adipocytes due to a defect in the ASP pathway may lead to insulin resistance and Type 2 diabetes.
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PMID:Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. 1084 50

Hyperglycemia in Type 2 diabetes represents a steady-state re-regulation of plasma glucose to a higher-than-normal level after an overnight fast. The underlying pathophysiology represents an interaction between impaired beta-cell function and peripheral and hepatic insulin resistance which leads to abnormal hepatic glucose production. Subjects with the Metabolic Syndrome are at an increased risk for Type 2 diabetes and often have one or both of these disorders present even when glucose tolerance is normal. Thus, sophisticated measures of beta-cell function and insulin sensitivity demonstrate a high frequency in populations characterized as having a high prevalence of atherosclerosis, central obesity, hypertension, and dyslipidemia with or without impaired glucose tolerance. Hyperglycemia compensates for the impairment of beta-cell function and therefore, in our view, the beta-cell is the critical factor in its development. Hyperinsulinemia, a curvilinear compensation for insulin resistance that is closely correlated with central adiposity, is another important predictor of hyperglycemia. In a Japanese-American population followed for five years, impaired beta-cell function was present at baseline and preceded the accumulation of intraabdominal fat in those who developed Type 2 diabetes five years later. This interaction between these two pathophysiologic abnormalities in this sequence supports the hypothesis that beta-cell dysfunction contributes to the development of central adiposity by reduced CNS insulin signaling.
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PMID:Mechanisms for hyperglycemia in the metabolic syndrome. The key role of beta-cell dysfunction. 1084 53

High plasminogen activator inhibitor 1 (PAI-1) levels are associated with an increased cardiovascular risk of atherothrombosis. Furthermore, increased plasma PAI-1 levels are associated with dyslipidemia, hyperinsulinemia and hypertension. This association between PAI-1 and metabolic components of the Metabolic Syndrome could explain the predisposition of insulin resistant patients to atherothrombosis. Recent studies have suggested that visceral adipose tissue might be the link between elevated plasma PAI-1 and insulin resistance in the Metabolic Syndrome. Indeed, visceral adipose tissue was proposed as a potentially important source of PAI-1 in humans. However, in light of recent studies, visceral adipose tissue appears to be involved in the increase of plasma PAI-1 via the metabolic disorders usually associated with central obesity, rather than directly. High plasma PAI-1 levels are undoubtedly related to insulin resistance, and the mechanisms which could explain such an increase in the Metabolic Syndrome appear to be multi-factorial and remain to be elucidated. These mechanisms may involve several metabolic disorders such as hyperinsulinemia, dyslipidemia, impaired glucose tolerance and hypertension, which would favor PAI-1 synthesis and release from different cell types.
Diabetes Metab Res Rev
PMID:Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance. 1086 19

Total generalized lipodystrophy (Berardinelli - Seip Syndrome) is a rare hereditary disease characterized by insulin-resistant diabetes mellitus and a small quantity of adipose tissue and is of unknown origin. Common cardiovascular alterations related to this syndrome are cardiac hypertrophy and arterial hypertension. This article reports a case of Berardinelli - Seip syndrome and reviews the literature with special emphasis on the cardiovascular manifestations of this syndrome.
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PMID:Cardiac involvement in total generalized lipodystrophy (Berardinelli- Seip syndrome). 1101 10


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