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)

1. Pretranslational suppression of glucose transport protein, isozyme 4 (GLUT 4), is a major mechanism of insulin resistance in adipocytes in obesity and non-insulin-dependent diabetes mellitus (NIDDM). 2. Patients with gestational diabetes mellitus (GDM) are heterogeneous; adipocyte GLUT 4 levels are either normal or markedly reduced but all patients exhibit abnormalities in GLUT 4 subcellular distribution and insulin-mediated translocation. 3. Skeletal muscle GLUT 4 expression is normal in obesity, impaired glucose tolerance (IGT), GDM, and NIDDM, indicating that functional activity or translocation of GLUT 4 may be impaired. 4. Adipocyte defects in GDM consistent with abnormalities in GLUT 4-vesicle traffic have implications with respect to potential mechanisms of insulin resistance in human muscle. Given the central role of insulin resistance in NIDDM and Syndrome 'X', elucidating the underlying mechanism in muscle is critical for developing more effective treatment and disease prevention.
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PMID:Glucose transporter proteins and insulin sensitivity in humans. 808 95

Normal pregnancy produces profound metabolic alterations that occur, in large part, by the conclusion of the first trimester. Although necessary to support the metabolic needs of the conceptus, the metabolic and cardiovascular changes of pregnancy are well established weeks before the metabolic needs of the fetus and placenta are fully expressed. The endocrine and metabolic characteristics of gestational diabetes, therefore, can only be understood against the backdrop of the rapidly changing conditions of normal pregnancy. Nondiabetic pregnancy produces an "accelerated starvation" in the fasting state with an earlier and more profound hypoglycemia and an increased fasting insulin. In the fed state, normal pregnancy produces a higher postprandial glycemic response despite an amplified first phase insulin response and higher plasma insulin concentrations. Both the intravenous glucose tolerance test and the steady state euglycemic clamp demonstrate that, by the second trimester, pregnancy produces peripheral and, perhaps, hepatic insulin resistance. The decreased peripheral uptake of glucose and the increased basal production of glucose in the fasting state support an increased flux of glucose to the fetus. Weight-matched obese gestational diabetic gravidae demonstrate a greater fall in fasting glucose and greater increase in ketosis compared with normal control gravidae. Obese GDM patients appear to have increased fasting insulin concentration compared with lean GDM and nondiabetic controls, whereas nonobese GDM patients do not appear to have elevated fasting insulin concentrations. Women with gestational diabetes have a greater rise in SI postpartum than controls, though the SI is the same in normal and gestational diabetic pregnancy in the third trimester.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic changes in gestational diabetes. 822 70

Researchers and care providers must recognize that different centers are not automatically comparable in results because the geographic location, the demographic characteristics of the patient population, and the program strategy will alter the rate of patients assigned to insulin therapy and adverse pregnancy outcome. For example, in San Antonio, Texas, with a chronic health problem of obesity and diabetes, the prevalence of GDM is approximately 11%, whereas the general reported rate is 2% to 3%. Despite the disparity in the prevalence of the disease in different demographic areas, pregnancy outcome should be comparable for all centers when a proper management approach has been used. Utilizing our management approach in a large-scale program resulted in an incidence of macrosomia comparable to that in the general population. As a general rule, because constant evaluation of glycemia in pregnancy is the best gauge of the efficacy of the treatment, the use of verified self-monitoring of blood glucose has become a principal component of management. Appropriate assignment of patients to treatment modality utilizing verified blood glucose determinations and targeting mean blood glucose levels throughout pregnancy to 95 mg/dL (5.3 mmol/L) that is similar to normal nondiabetic blood glucose levels will result in pregnancy outcome comparable to the general population.
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PMID:Management of gestational diabetes. 822 72

The aim of this study was to assess the effect of obesity on the outcome of gestational diabetes (GD). The age of the subject (31 +/- 5 years) and duration of pregnancy (29 +/- 5 weeks) were similar at the time of diagnosis for the 19 obese (34 +/- 6 kg/m2) and 19 non-obese (23.0 +/- 2.1 kg/m2) subjects. Before treatment, the area under the curve of the glucose tolerance test and the mean capillary blood glucose levels were similar in both groups; however, the baseline blood glucose levels of the obese patients (6.0 +/- 0.8 mmol/l) were higher than those of the non-obese patients (5.3 +/- 0.8 mmol/l; P < 0.01). During pregnancy, the total weight gain of the obese patients was less (10.6 +/- 5.0 vs. 15.2 +/- 4.7 kg, P < 0.006). Fifteen of the obese patients required treatment with insulin, while only six of the non-obese women required insulin (P < 0.005). During insulin therapy, the mean capillary blood glucose, glycosylated haemoglobin and fructosamine levels were similar in both groups. In conclusion, our data suggest that GD in obese patients is characterized by lower weight gain and higher baseline glucose with the result that insulin therapy is more frequently instituted.
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PMID:Comparison of obese and non-obese patients with gestational diabetes. 824 30

Mechanisms causing cellular insulin resistance in gestational diabetes mellitus are not known. We, therefore, studied isolated omental adipocytes obtained during elective cesarean sections in nondiabetic (control) and GDM gravidas. Cellular insulin resistance was attributed to impaired stimulation of glucose transport; compared with control subjects, basal and maximally insulin-stimulated transport rates (per surface area) were reduced 38 and 60% in GDM patients, respectively. To determine underlying mechanisms, we assessed the number, subcellular distribution, and translocation of GLUT4, the predominant insulin-responsive glucose transporter isoform. The cellular content of GLUT4 was decreased by 44% in GDM patients as assessed by immunoblot analysis of total postnuclear membranes. However, GDM patients segregated into two subgroups; half expected profound (76%) cellular depletion of GLUT4 and half had GLUT4 levels in the normal range. Cellular GLUT4 was negatively correlated with adipocyte size in the control subjects and GDM patients with normal GLUT4 (r = 0.60), but fell way below this continuum in GDM patients with low GLUT4, indicating that heterogeneity was not caused by differences in obesity. All GDM. distribution. In basal cells, increased amounts of GLUT4 were detected in membranes fractionating with (such that the plasma membrane GLUT4 level in GDM (such that the plasma membrane GLUT4 level in GDM patients was equal to that observed in insulin-stimulated cells from control subjects). Furthermore, insulin stimulation induced translocation of GLUT4 from low-density microsomes to plasma membranes in control subjects but did not alter subcellular distribution in GDM patients. In other experiments, cellular content of GLUT1 was normal in GDM patients, and GLUT1 did not undergo insulin-mediated recruitment to plasma membranes in either control subjects or GDM patients. A faint signal was detected for GLUT3 only in low-density microsomes and only with one of two different antibodies. In GDM, we conclude that insulin resistance in adipocytes involves impaired stimulation of glucose transport and arises from a heterogeneity of defects intrinsic to the glucose transport effector system. GLUT4 content in adipocytes is profoundly depleted in approximately 50% of GDM patients, whereas all patients are found to exhibit a novel abnormality in GLUT4 subcellular distribution. This latter defect is characterized by accumulation of GLUT4 in membranes cofractionating with plasma membranes and high-density microsomes in basal cells and absence of translocation in response to insulin. The data suggest that abnormalities in cellular traffic or targeting relegate GLUT4 to a membrane compartment from which insulin cannot recruit transporters to the cell surface and have important implications regarding skeletal muscle insulin resistance in GDM and NIDDM.
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PMID:Multiple defects in the adipocyte glucose transport system cause cellular insulin resistance in gestational diabetes. Heterogeneity in the number and a novel abnormality in subcellular localization of GLUT4 glucose transporters. 824 23

Increased birth-weight (macrosomia) can complicate the diabetic pregnancy, but many factors other than hyperglycaemia can influence birth-weight, in particular maternal obesity. In a mixed population (European, Maori and Pacific Islander) with a high prevalence of glucose intolerance and obesity we have examined the relative impact of various maternal factors on birth-weight in women with both established and gestational diabetes. Mean birth-weight was significantly greater in women with established or gestational diabetes than in controls (p < 0.0001), but was similar in women with gestational and established diabetes, despite glycaemic control being significantly poorer (p < 0.0001) in the latter. Birth-weight closely paralleled prepregnancy body mass index rather than glycaemic control, but in Maori women it was lower than expected, probably because of their high prevalence of smoking. Daily cigarette consumption was negatively correlated with birth-weight (p < 0.01) despite the smokers having significantly poorer glycaemic control (p < 0.001). The most significant variables influencing birth-weight in the diabetic pregnancy were gestational age at delivery, prepregnancy body mass index, maternal height, estimated weight gain during pregnancy, the presence of hypertension and cigarette smoking (the latter 2 having negative effects on birth-weight). Glycaemic control in the last half of pregnancy was not significant in this analysis. We conclude that within the limits of glycaemic control which we obtained, birth-weight was largely determined by maternal factors other than hyperglycaemia. Birth-weight thus has severe limitations as an outcome measure of the diabetic pregnancy.
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PMID:Determinants of birth-weight in women with established and gestational diabetes. 830 85

Gestational diabetes is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy. Gestational Diabetes generally disappears as soon as the pregnancy is terminated. The prevalence of gestational diabetes is 2% to 13%, depending on the genetic characteristics and environment of the population under study. Classic risk factors identify a population of women at risk of gestational diabetes (obesity, family history of diabetes, or previous poor obstetric history); however, these risk factors identify only 60% of women diagnosed as having gestational diabetes. Therefore, it is necessary to screen all pregnant women, regardless of history, for gestational diabetes. The optimal time to screen for gestational diabetes in pregnancy is between 24 and 28 weeks of gestation. The screening test consist of 50 g of oral glucose followed by a plasma determination at 1 hour. If the plasma glucose 1 hour after the oral load is > or = 140 mg/dl, a glucose tolerance test is indicated. The goal of management (diet, insulin and exercise) of the gestational diabetic women is to maintain normoglycemia, needed to avoid complications for the fetus and mother.
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PMID:[Gestational diabetes: new approaches to an old and growing problem]. 834 20

The diagnosis of gestational diabetes was developed to predict neonatal outcome (particularly perinatal mortality, macrosomia and hypoglycaemia) and future maternal diabetes. A variety of criteria for this diagnosis have evolved over time, assessed predominantly among European women. We describe a Pacific Islands woman with multiple risk factors for future diabetes yet a borderline 100 g glucose tolerance test result, who delivered a stillborn macrosomic baby weighing 6.7 kg at 38 weeks' gestation. Six weeks postpartum, diabetes was diagnosed by 75 g oral glucose tolerance test. This case highlights the need for caution when interpreting the glucose tolerance test in pregnancy and suggests that closer fetal monitoring and involvement of the diabetes team may be necessary among women with a borderline glucose tolerance test in the presence of additional risk factors for future diabetes (eg obesity, ethnic group).
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PMID:Criteria for gestational diabetes: a cautionary tale. 841 81

Of the various types of diabetes mellitus, non-insulin-dependent diabetes (NIDDM) is by far the most common and is increasing rapidly in many populations around the world. It is a heterogeneous disorder, characterized by a genetic predisposition and interaction between insulin resistance and decreased pancreatic beta-cell function. There is a strong association between the presence of obesity and low levels of physical exercise and the development of NIDDM. However, NIDDM may also develop in lean individuals and the incidence increases significantly with increasing age. A diagnosis of impaired glucose tolerance or gestational diabetes is a strong predictor for future development of NIDDM and should signal appropriate interventions to prevent or delay the progression to NIDDM. NIDDM is frequently associated with other conditions such as hypertension, hypertriglyceridemia and decreased high-density lipoprotein which are additional risk factors for atherosclerosis and cardiovascular disease. The 'insulin resistance syndrome', which includes obesity, NIDDM, hypertension, hyperinsulinemia and dyslipidemia is a major and increasing cause of morbidity and mortality in many populations. In addition, people with NIDDM and poor glycemic control may develop severe microvascular complications of diabetes, including retinopathy, nephropathy and neuropathy. Appropriate diet, weight control and increased physical activity will increase insulin sensitivity in insulin resistant patients and are effective treatments for patients with NIDDM or may prevent the development of NIDDM in susceptible individuals. If these measures are unsuccessful, then oral hypoglycemic agents or insulin therapy may be required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NIDDM--the devastating disease. 852 17

The purpose of this study was to determine which patient and pregnancy characteristics in the first pregnancy complicated by gestational diabetes mellitus (GDM) were associated with the diagnosis of GDM before 24 weeks' gestation in a subsequent pregnancy--early recurrent GDM. The case notes of 180 women who previously had GDM diagnosed and who had glucose tolerance tests performed before 24 weeks' gestation in their next ongoing pregnancy were reviewed. Factors examined included severity of GDM, insulin requirement, racial origin, macrosomia, obesity, age, family history of diabetes, preeclampsia, and parity. Multivariate analysis showed that women with early recurrent GDM were more likely, in their first pregnancy with GDM, to have needed insulin (odds ratio [OR] 11.26; 95% confidence interval [CI] 2.02 to 62.65), to be more often of non-Northern European origin (OR, 5.53; 95% CI, 2.46 to 12.44), to have had a macrosomic infant (OR, 4.01; 95% CI, 1.40 to 11.49) or severe GDM (OR, 3.52; 95% CI, 1.60 to 7.76), and were more often 30 years or more of age (OR, 2.27; 95% CI, 1.05 to 4.90). Obesity, family history, fasting plasma glucose levels, and parity were not significant risk factors. However, even without any of the significant risk factors, logistic regression modeling suggested that a woman who has had GDM in a previous pregnancy has a 5.1% (95% CI, 2.2 to 11.6%) chance of having early recurrent GDM. We therefore continue to recommend that all women who have had GDM diagnosed previously should have glucose tolerance testing performed early (before 24 weeks' gestation) in any future pregnancies.
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PMID:Factors predictive of recurrent gestational diabetes diagnosed before 24 weeks' gestation. 854 Sep 42


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