Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein tyrosine phosphatases (PTPs) are required for the dephosphorylation of the insulin receptor (IR) and its initial cellular substrates, and it has recently been reported that PTP-1B may play a role in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus (DM). We therefore determined the amount and activity of PTP-1B in abdominal adipose tissue obtained from lean nondiabetic subjects (lean control (LC)), obese nondiabetic subjects (obese control (OC)), and subjects with both type 2 DM (DM2) and obesity (obese diabetic (OD)). PTP-1B protein levels were 3-fold higher in OC than in LC (1444 +/- 195 U vs 500 +/- 146 U (mean +/- SEM), P < .015), while OD exhibited a 5.5-fold increase (2728 +/- 286 U, P < .01). PTP activity was assayed by measuring the dephosphorylating activity toward a phosphorus 32-labeled synthetic dodecapeptide. In contrast to the increased PTP-1B protein levels, PTP-1B activity per unit of PTP-1B protein was markedly reduced, by 71% and 88% in OC and OD, respectively. Non-PTP-1B tyrosine phosphatase activity was comparable in all three groups. Similar results were obtained when PTP-1B activity was measured against intact human IR. A significant correlation was found between body mass index (BMI) and PTP-1B level (r = 0.672, P < .02), whereas BMI and PTP-1B activity per unit of PTP-1B showed a strong inverse correlation (r = -0.801, P < .002). These data suggest that the insulin resistance of obesity and DM2 is characterized by the increased expression of a catalytically impaired PTP-1B in adipose tissue and that impaired PTP-1B activity may be pathogenic for insulin resistance in these conditions.
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PMID:Marked impairment of protein tyrosine phosphatase 1B activity in adipose tissue of obese subjects with and without type 2 diabetes mellitus. 1044 21

Both type 2 diabetes mellitus (DM2) and left ventricular hypertrophy are associated with an increased risk of cardiovascular diseases (CVD). A strong association between hyperinsulinemia, which is the hallmark of DM2 and of insulin resistance syndrome (a cohort of metabolic abnormalities such as DM2, dyslipidemia, hyperuricemia, obesity, hypertension, hyperfibrinogenemia), and left ventricular (LV) hypertrophy was found in several studies. We studied 140 consecutive (both normo- and hypertensive) DM2 patients to determine a possible link between metabolic features and the degree of LV mass, calculated by the ECG method of Cornell voltage. The Cornell voltage value was 12.9+/-0.5 mm in the DM2 population as a whole, and 13.6+/-0.7 vs 11.7+/-0.9 mm (p=NS) in hypertensive and normotensive DM2 subgroups, respectively. Among all the metabolic parameters taken into account, the multivariate analysis shows that the fasting plasma insulin level is the strongest independent predictor of LV mass, both in the whole population (p=0.0005) and in the normo (p=0.0460) and hypertensive DM2 (p=0.0184) subgroups.
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PMID:Left ventricular mass in type 2 diabetes mellitus. A study employing a simple ECG index: the Cornell voltage. 1080 69

The aim of this study was to estimate the prevalence of type 2 diabetes mellitus (DM2), impaired glucose tolerance (IGT), and the frequency of dyslipidemia, obesity, and hypertension in the rural Aymara population from Northern Chile. In this cross-sectional study, 196 Aymara adult subjects were characterized with respect to their reported physical activity, fasting plasma glucose levels, insulin concentrations, blood pressures, body mass indexes, and plasma lipid profiles. The participants also underwent a 2-h oral glucose tolerance test. The diagnostic criteria for DM2 and IGT followed those of the World Health Organization. The overall prevalence of DM2 was estimated as 1.5% (95% confidence interval: 0.3--4.5). Overall prevalence of IGT was calculated as 3.6% (1.5--7.3). The occurrence of obesity and dyslipidemia was relatively high in the Aymara population, although the frequency of sedentary habits, and the prevalence of hypertension were low. In conclusion, the prevalence of DM2 in the rural Aymara population living at high altitudes in Northern Chile, was much lower than that of other Amerindian groups that adopted lifestyles from industrialized Western societies. Despite a relatively high prevalence of a body mass index of at least 30 kg/m(2), especially in women (23.5%), high physical activity levels and low plasma-insulin concentrations may have been responsible in part for the low prevalence of DM2 in the Aymara population.
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PMID:Low prevalence of type 2 diabetes despite a high average body mass index in the Aymara natives from Chile. 1136 69

Elevated plasma angiotensinogen (AGT) levels have been demonstrated in insulin-resistant states such as obesity and type 2 diabetes mellitus (DM2), conditions that are directly correlated to hypertension. We examined whether hyperinsulinemia or hyperglycemia may modulate fat and liver AGT gene expression and whether obesity and insulin resistance are associated with abnormal AGT regulation. In addition, because the hexosamine biosynthetic pathway is considered to function as a biochemical sensor of intracellular nutrient availability, we hypothesized that activation of this pathway would acutely mediate in vivo the induction of AGT gene expression in fat and liver. We studied chronically catheterized lean (approximately 300 g) and obese (approximately 450 g) Sprague-Dawley rats in four clamp studies (n = 3/group), creating physiological hyperinsulinemia (approximately 60 microU/ml, by an insulin clamp), hyperglycemia (approximately 18 mM, by a pancreatic clamp using somatostatin to prevent endogenous insulin secretion), or euglycemia with glucosamine infusion (GlcN; 30 micromol. kg(-1). min(-1)) and equivalent saline infusions (as a control). Although insulin infusion suppressed AGT gene expression in fat and liver of lean rats, the obese rats demonstrated resistance to this effect of insulin. In contrast, hyperglycemia at basal insulin levels activated AGT gene expression in fat and liver by approximately threefold in both lean and obese rats (P < 0.001). Finally, GlcN infusion simulated the effects of hyperglycemia on fat and liver AGT gene expression (2-fold increase, P < 0.001). Our results support the hypothesis that physiological nutrient "pulses" may acutely induce AGT gene expression in both adipose tissue and liver through the activation of the hexosamine biosynthetic pathway. Resistance to the suppressive effect of insulin on AGT expression in obese rats may potentiate the effect of nutrients on AGT gene expression. We propose that increased AGT gene expression and possibly its production may provide another link between obesity/insulin resistance and hypertension.
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PMID:Hyperglycemia modulates angiotensinogen gene expression. 1150 94

Obesity and type 2 diabetes mellitus (DM2) are 2 closely related syndromes, with obesity occurring in 70% to 80% of DM2 patients. Both syndromes are characterized by insulin resistance (IR). However, the metabolic characteristics of lean DM2 patients are not clearly defined, a fact attributed to the heterogeneity of the diabetes syndrome. Our objective was to study glucose metabolism in lean DM2 patients, in terms both of the basal and the insulin-stimulated states, and particularly, to investigate whether 2 subpopulations of diabetic patients are identifiable on the basis of degree of IR. Sixteen nonobese (body mass index [BMI] less than 27 kg. m(-2)) DM2 subjects with light to moderate fasting hyperglycemia were studied. Ten healthy subjects were used as a control group, with no family history of DM2 and matched by age, sex, and BMI in the diabetic group. All participants underwent an intravenous glucose tolerance test with frequent sampling over 180 minutes. Insulin sensitivity (IS) and glucose effectiveness at zero insulin (GEZI) were calculated using Bergman's minimal model. Non-insulin-mediated glucose uptakes (NIMGU) and insulin-mediated glucose uptakes (IMGU) were calculated for the basal (F) and insulin-stimulated states at 11.1 mmol/L of glucose (11.1). The beta-cell function was calculated via the acute insulin response to glucose (AIRg). Clustering techniques were used to identify subpopulations of DM2 patients on the basis of insulin sensitivity. The group of DM2 patients was characterized by both IR (IS index, 6.23 +/- 4.68 v 12.75 +/- 7.74 x 10(-5). min(-1). (pmol. L(-1))(-1), P <.01) and insulin secretion abnormalities (AIRg, 336 +/- 456 v 1,912 +/- 1,293 pmol/L. min, P <.0001), but showed similar values for GEZI (0.011 +/- 0.005 v 0.011 +/- 0.007 min(-1), not significant [NS]) in comparison to the control group. For the basal state, no differences were found between the DM2 patients and control subjects for NIMGU(F) (0.13 +/- 0.07 v 0.08 +/- 0.05 mmol/kg. min, NS) or for IMGU(F) (0.05 +/- 0.04 v 0.05 +/- 0.02 mmol/kg. min, NS). For the insulin-stimulated state, the DM2 patients showed a reduction of approximately 50% in the IMGU(11.1) value (0.20 +/- 0.17 v 0.38 +/- 0.24 mmol/kg. min, P <.05), but no significant differences were found for NIMGU(11.1) (0.19 +/- 0.09 v 0.20 +/- 0.12 mmol/kg. min, NS) in relation to the control group. Using the clustering technique, it was possible to identify 2 subpopulations of DM2 patients, a DM-IS group (n = 6) that was insulin sensitive (IS index, 11.70 +/- 2.40 x 10(-5). min(-1). (pmol. L(-1))(-1)) and a DM-IR group (n = 10) that was insulin resistant (IS index, 3.02 +/- 1.60 x 10(-5). min(-1). (pmol. L(-1))(-1)). The DM-IS group was characterized by an absence of IR, diminished GEZI, and a reduction in AIRg; whereas the DM-IR group was characterized by IR and a reduction in AIRg, but normal GEZI. We conclude that (1) as a group, DM2 patients are characterized by IR and beta-cell dysfunction, but normal NIMGU; (2) two subpopulations of DM2 patients can be identified on the basis of insulin sensitivity, with the DM-IS group further characterized by diminished GEZI; and finally, (3) deterioration in the pancreatic response to glucose stimulus is a sine qua non condition for a profound alteration in glucose metabolism in DM2 patients.
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PMID:Glucose metabolism in lean patients with mild type 2 diabetes mellitus: evidence for insulin-sensitive and insulin-resistant variants. 1214 80

Right classification of diabetes is important clinical issue. The aim of present study was to compare clinical, biochemical and immunological features, to analyze their practical use and to establish new decision tree which make the distinction between diabetes type 1, LADA, diabetes type 2 and MODY. We studied 97 not obese (mean BMI 26.3 +/- 4.9 kg/m2) patients aged 14 to 70 years, mean age 43 +/- 11.7 years, 53 women, 44 men. Mean duration of diabetes--2.3 +/- 4.3 years. We measured basal and stimulated C-peptide (6 minutes after 1 mg i.v. glucagon) (ELISA) and antibodies titers to glutamic acid decarboxylase--antiGAD65, tyrosine phosphatase-like molecule--IA2 and insulin--IAA (RIA). Autoimmune diabetes (LADA, type 1) was diagnosed with presence of one or more islet antigen antibodies. The highest frequencies had anti-GAD antibodies 33/97 (34%). The most complicated was to sort out group of patients with LADA. Comparison between this group and patients with diabetes type 2 have shown that BMI, co-existence of autoimmune disease, autoimmune markers and basal and stimulated C-peptide level measured at entry for the classification were useful in differentiation. Moreover we observed significantly lower C-peptide basal, stimulated and over basal level in group with MODY diabetes in comparison to diabetes type 2 patients. In the studied group were 5 patients with diabetes type 2 and obesity, in relatively young age. At the end there was one case of ADM (atypical diabetes mellitus). Clinical criteria for the classification of diabetes not always correlated with diagnosis. Autoimmune markers, basal and stimulated C-peptide were useful specially in differentiation between LADA and diabetes type 2 or diabetes type 1. Autoimmune diabetes co-existe with autoimmune disease. Proposed diagnostic scheme take for consideration presence of autoantibodies as well as C-peptide criteria.
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PMID:[Clinical, biochemical and immunological characteristic of diabetes type I, LADA, diabetes type II, and MODY patients]. 1268 30

Microalbuminuria is a marker for diabetic nephropathy. It also signifies cardiovascular disease, as well as nephropathy, in type 2 diabetes (DM2). Microalbuminuria may precede DM2, occurring with the insulin resistance syndrome and its components, including obesity and hypertension. Other indicators of cardiovascular risk, such as markers of inflammation, are associated with microalbuminuria in populations of patients with and without diabetes. With the rising prevalence of DM2 in minority youth, especially in Native Americans, a marker for future disease risk would allow earlier prevention strategies to be tested. Before microalbuminuria can be used in a prevention strategy, more needs to be known about the mechanism(s) of the association between elevated excretion, its relationship to glucose intolerance, and its relative contribution to cardiovascular and renal disease. These questions are especially applicable as we begin to observe the long-term complications of diabetes in youth.
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PMID:Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective. 1476 31

As type 2 diabetes mellitus (DM2), obesity and sedentary lifestyles are increasing in developing countries, this observational study investigated the role of physical activity on DM2 in Jamaica. Anthropometry, body composition (by bioelectrical impedance analysis) and glucose tolerance status was assessed in 722 adults in 1993 and 1997. Energy expenditure was estimated in a subset using measured resting energy expenditure in combination with self-reported activity recalls. The rates of impaired glucose tolerance (IGT) were 23.7 and 27.3%, and DM2 were 16.3 and 23.7% among men and women, respectively. After adjusting for body composition, a one-unit increase in physical activity significantly reduced the odds of having diabetes (OR = 0.05; 95% CI: 0.004, 0.66), but not IGT. Hence, decreased physical activity is a significant independent contributor to the high rates of glucose intolerance in Jamaica. Efforts must be directed at minimizing obesity and increasing physical activity in developing countries.
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PMID:Energetic determinants of glucose tolerance status in Jamaican adults. 1516 40

The incidence of obesity and type 2 diabetes mellitus (DM2) in the United States has been increasing dramatically over the past 15 years, and is now at epidemic proportions. DM2 is the clinical manifestation of a long-term metabolic process that is initiated by cells' decreased sensitivity to the actions of insulin. Many outcome studies have identified DM2 as a strong and independent risk factor for the development of cardiovascular complications such as hypertension, arteriosclerosis, and heart failure. The goals of therapy in treating DM2 are to improve the long-term outlook for these patients. However, in selecting a therapeutic regimen for patients, clinicians should be aware that potentially severe adverse events may occur at a rate not previously identified in phase 3 studies. Certain therapies used to treat DM2, by effectively increasing the sensitivity of insulin, have also been reported to cause adverse effects, which can precipitate symptomatic heart failure. The purpose of this column is to discuss the therapeutic options available for treating patients with DM2, the potential pathophysiology of the adverse events of symptomatic heart failure, encouragement of use of the US Food and Drug Administration MedWatch program for reporting adverse events associated with medication therapy, and review of newer treatment guidelines for use of insulin-sensitizing agents in patients with chronic heart failure.
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PMID:Cardiovascular implications of thiazolidinedione therapy. 1524 73

The continuing increase in the incidence of type 2 diabetes mellitus (DM2) and obesity in children and adolescents is attributable to excessive caloric intake. Abnormal lipid metabolism in the postprandial state leads to long exposure of the vasculature to hyperlipidemia. Most children and adolescents with DM2 are obese, and many have fasting hypertriglyceridemia. Clustering of hyperlipidemia, DM2 and obesity increases the risk for cardiovascular disease. We therefore studied lipids, insulin, C-peptide, and glucose in response to an oral fat load simulating the fat content of a high-fat, fast-food meal in 12 type 2 diabetic obese, 15 non-diabetic obese, and 12 non-diabetic non-obese (control) adolescents (aged 10-19 yr; 87% African-Americans). All three groups were age-, sex-, and sexual maturation-matched. Mean body mass indices were similar in the diabetes and obese groups (32.7 +/- 1.1 vs 35.8 +/- 1.6 kg/m2). All patients with DM2 had fasting C-peptide > 0.2 nmol/l (0.7 ng/ml) and negative diabetes-associated autoantibodies. Serum total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, insulin, C-peptide, and plasma glucose levels were measured at 0, 2, 4, and 6 h after the fat load. The area under the curve (AUC) was calculated by trapezoidal estimation. Triglyceride AUC was significantly greater in the diabetes group than in the other two groups (15.7 +/- 2.9 vs 9.2 +/- 0.7 and 7.5 +/- 0.7 mmol x h/l [1389 +/- 258 vs 819 +/- 60 and 663 +/- 62 mg x h/dl]; p < 0.02 and <0.004, respectively), as were insulin, C-peptide, and glucose AUCs. Incremental triglyceride response (delta triglyceride = peak - fasting) in the diabetes group was significantly higher than that in the control group (2.1 +/- 0.7 vs 0.8 +/- 0.1 mmol/l 189.7 +/- 58.4 vs 71.2 +/- 11.1 mg/dl]; p < 0.04). Insulin resistance was estimated using the homeostasis model assessment (HOMA), which was greater in the diabetes group than in the obese and control groups (14.4 +/- 2.8 vs 5.2 +/- 0.8 and 3.2 +/- 0.4; p < 0.001 and < 0.0001, respectively). The diabetes group was divided into subgroups of high and normal fasting triglycerides on the basis of triglyceride levels above and below the 95th percentile. The delta triglyceride in the subgroup with high fasting triglycerides was substantially greater than in the subgroup with normal fasting triglycerides (3.4 +/- 1.1 vs 0.8 +/- 0.2 mmol/l [305.2 +/- 96.8 vs 74.2 +/- 18.0 mg/dl]; p < 0.001). Total cholesterol and triglyceride AUCs were much greater in the high vs normal fasting triglycerides subgroup (33.0 +/- 2.9 vs 24.2 +/- 1.9 and 23.6 +/- 3.5 vs 7.8 +/- 0.6 mmol x h/l [1274 +/- 113 vs 934 +/- 72 and 2085 +/- 309 vs 692 +/- 49 mg x h/dl]; p < 0.02 and <0.0001, respectively), as were insulin and C-peptide AUCs. HOMA was greater in the high vs normal fasting triglycerides subgroup (20.8 +/- 4.0 vs 8.0 +/- 1.6; p < 0.0001). In addition to elevated plasma glucose levels, there were no significant differences in either insulin or lipid parameters among the diabetes subgroup with normal fasting triglycerides, the obese group, and controls. Our data suggest that postprandial hyperlipidemia in response to a fat loading test is present in adolescents with DM2 who already have fasting hypertriglyceridemia. The degree of insulin resistance as an underlying abnormality--not DM per se--determines the degree of postprandial lipemia.
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PMID:Postprandial hyperlipidemia after a fat loading test in minority adolescents with type 2 diabetes mellitus and obesity. 1527 Apr 3


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