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

Abdominal obesity, particularly excess intraperitoneal fat, is considered to play a major role in causing insulin resistance and NIDDM. To determine if NIDDM patients accumulate excess intraperitoneal fat, and whether this contributes significantly to their insulin resistance, 31 men with mild NIDDM with a wide range of adiposity were compared with 39 nondiabetic, control subjects for insulin sensitivity (measured using euglycemic-hyperinsulinemic clamp technique with [3-3H]glucose turnover) and total and regional adiposity (assessed by hydrodensitometry and by measuring subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses using magnetic resonance imaging [MRI], and truncal and peripheral skinfold thicknesses using calipers). MRI analysis revealed that intraperitoneal fat was not increased in NIDDM patients compared with control subjects; in both groups it averaged 11% of total body fat. NIDDM patients, however, had increased truncal-to-peripheral skinfolds thickness ratios. In NIDDM patients, as in control subjects, amounts of truncal subcutaneous fat showed a stronger correlation with glucose disposal rate than intraperitoneal or retroperitoneal fat; however, NIDDM patients were more insulin resistant at every level of total or regional adiposity. Further, no particular influence of excess intraperitoneal fat on hepatic insulin sensitivity was noted. We conclude that NIDDM patients do not have excess intraperitoneal fat, but that their fat distribution favors more truncal and less peripheral subcutaneous fat. Moreover, for each level of total and regional adiposity, NIDDM patients have a heightened state of insulin resistance.
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PMID:Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM. 892 52

Abdominal obesity has emerged as a strong and independent predictor for non-insulin dependent diabetes mellitus (NIDDM). Adiposity located centrally in the abdominal region, and particularly visceral as opposed to subcutaneous fat, is also distinctly associated with hyperlipidemia, compared with generalized distributions of body fat. These lipoprotein abnormalities are characterized by elevated very low density lipoprotein (VLDL) and low density lipoprotein (LDL) levels, small dense LDL with elevated apolipoprotein B levels, and decreased high density lipoprotein2b (HDL2b) levels. This is the same pattern seen in both familial combined hyperlipidemia and NIDDM. The pronounced hyperinsulinemia of upper-body obesity supports the overproduction of VLDL and the increased LDL turnover. We have proposed that an increase in the size of the visceral fat depot is a precursor to the increased lipolysis and elevated free fatty acid (FFA) flux and metabolism and to subsequent overexposure of hepatic and extrahepatic tissues to FFA, which then, in part, promotes aberrations in insulin actions and dynamics. The resultant changes in glucose/insulin homeostasis, lipoprotein metabolism, and vascular events then lead to metabolic morbidities such as glucose intolerance, NIDDM, dyslipidemia, and increased risk for coronary heart disease.
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PMID:Intra-abdominal fat: is it a major factor in developing diabetes and coronary artery disease? 896 90

The application of magnetic resonance imaging and computed tomography to obesity research has changed the focus from body mass and skinfold thickness to abdominal fat mass and visceral adiposity. Intra-abdominal fat constitutes less than 20% of total body fat but is a major determinant of fasting and postprandial lipid availability because of its physiological (lipolytic rate and insulin resistance) and anatomical (portal drainage) properties. High levels of serum free fatty acids, as a result of abdominal obesity, cause excessive tissue lipid accumulation and contribute to dyslipidaemia, beta cell dysfunction, and hepatic and peripheral insulin resistance. An individual's risk of non-insulin dependent diabetes mellitus and cardiovascular disease relates closely to the inheritance of central obesity and susceptibility to tissue lipotoxicity.
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PMID:Abdominal obesity. 950 33

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Insulin resistance is characterized by impaired responsiveness to endogenous or exogenous insulin and often results in the insulin resistance syndrome, a clustering of cardiovascular risk factors that includes abdominal obesity, hypertension, dyslipidemia, glucose intolerance, and hyperinsulinemia. Although the mechanism responsible for insulin resistance has not been completely defined, it is likely due to defective insulin receptor signaling and results in decreased use of glucose. Troglitazone, the first in a new class of drugs, directly decreases insulin resistance by improving insulin-mediated glucose disposal and reduces plasma insulin concentrations. Glycemic control achieved with troglitazone monotherapy is equivalent to that with sulfonylurea and metformin, and when combined with these agents offers additional plasma glucose reduction. Studies are necessary to determine the effect of thiazolidinediones on morbidity and mortality of patients with type 2 diabetes and insulin resistance.
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PMID:The role of troglitazone in treating the insulin resistance syndrome. 975 9

The United States is in the midst of an epidemic of obesity involving more than one third of the adult population. The prevalence of obesity increased by 40% between 1980 and 1990. Obesity is a chronic disease with a multifactorial etiology including genetics, environment, metabolism, lifestyle, and behavioral components. A chronic disease treatment model involving both lifestyle interventions and, when appropriate, additional medical therapies delivered by an interdisciplinary team including physicians, dietitians, exercise specialists, and behavior therapists offers the best chance for effective obesity treatment. Lifestyle factors such as proper nutrition, regular physical activity, and changes in eating behaviors should be coordinated by this team. This review addresses the modern epidemic of obesity, the strong association between obesity and comorbidities such as coronary heart disease, type 2 diabetes, hypertension, and dyslipidemia. In addition to obesity, the health risks of abdominal obesity and adult weight gain are discussed. The evidence that supports health benefits from modest weight loss (between 5% and 10% of body weight) is evaluated and the 5 key principles of effective obesity therapy are put forward. Obesity is a therapeutic challenge best met by teams of health care professionals, including dietitians and physicians, working together to deliver optimal treatment.
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PMID:Obesity as a chronic disease: modern medical and lifestyle management. 978 30

Although the health hazards of obesity are well established, obese individuals are not all at equal risk of developing a disease, which reflects the heterogeneity of this condition. The regional distribution of body fat is now recognized as a very important component of the obesity-related health hazards. Epidemiological studies have shown that abdominal obesity, that is, a preponderance of fat in the abdominal area, is a better predictor of both cardiovascular disease and type 2 diabetes than obesity per se. It is now generally accepted that the fat located within the abdominal cavity, the visceral fat, is the best correlate of most of the highly atherogenic metabolic complications seen in individuals with abdominal obesity. These include, among others, insulin resistance and hyperinsulinaemia, hypertriglyceridaemia, reduced plasma high-density lipoprotein (HDL) cholesterol concentrations and an increased number of small, dense low-density lipoprotein (LDL) particles. This review summarizes the evidence that these metabolic complications may account to a large extent for the increased risk of cardiovascular disease associated with abdominal/visceral obesity. Abdominal obesity may be the most prevalent denominator of highly atherogenic dyslipidaemic and hyperinsulinaemic/insulin-resistant states in affluent, sedentary societies. Targeting individuals with this high-risk trait in primary prevention is therefore crucial if we are truly to have an impact on the incidence of cardiovascular disease.
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PMID:Abdominal obesity and its metabolic complications: implications for the risk of ischaemic heart disease. 984 78

The recently described variant of the human beta3-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity to gain weight. We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta3-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta3-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy. The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Arg64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness: 3.48 +/- 0.32 vs. 5.76 +/- 0.36 micromol x 10(5) cells(-1) x 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 micromol x 10(5) cells(-1) x 90 min(-1)). We concluded that the Trp64Arg mutation of the beta3-AR gene is associated with lower lipolytic activities.
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PMID:Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes. 989 31

The problem of obesity is often not recognised. For example, the prevalence of obesity in Sweden is estimated to be 10%, but a study of a county of 414358 inhabitants and the records from 41 primary healthcare centres found that only 949 (3.1%) of patients were registered as obese. This is alarming, since overweight and obesity can be easily identified and the prevention and treatment of obesity is crucial in order to prevent type 2 diabetes. A screening programme in Kisa, a district of southern Sweden, found that 45% of men and 32% of women were overweight (BMI 25-30 kg/m2), while 12% of men and 17% of women were obese (BMI >30 kg/m2). Among people without diagnosed diabetes, a family history of obesity emerged in 1384 subjects; 707 were overweight or obese (BMI >25 kg/m2), with 270 of these having abdominal obesity. Of 212 of these patients who agreed to an oral glucose tolerance test, 16 were found to have type 2 diabetes and 70 impaired glucose tolerance. It is vital that primary healthcare teams become more active in developing co-ordinated programmes of identification, registration and long-term management of overweight and obese people.
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PMID:Steps towards the prevention of obesity and associated complications. 1038 76

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relationship, and ET-1 effects on vascular wall structure are similar to the long-term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their total insulin exposure to see if plasma ET-1 might be a link between insulin exposure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight glycaemic control for 2 years in a cross-sectional design. We measured basal and glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinfold thickness, glomerular filtration rate, albumin excretion rate and standard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Type II diabetes. Patients with an albumin excretion rate >300 microg/min were excluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 normal subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in Type II diabetes (P=0.0001). In all patients with measurable plasma C-peptide, plasma ET-1 was associated with basal plasma C-peptide (r=0.5018, P<0.0001), with stimulated plasma C-peptide (r=0.5379, P<0.0001), and with total daily insulin dose (r=0.2219, P=0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily insulin dose. Our study shows that the plasma concentration of ET-1 is closely associated with insulin secretion and insulin dose in patients with diabetes. Plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Increased insulin exposure in patients with diabetes may have long-term effects on vascular wall structure through its stimulation of ET-1 expression.
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PMID:Plasma endothelin-1 and total insulin exposure in diabetes mellitus. 1040 69


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