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

Women with impaired glucose tolerance are at high risk of developing noninsulin dependent diabetes mellitus (NIDDM). The Mercy Hospital for Women has a long-term follow-up programme for women with gestational diabetes, which identifies many women with impaired glucose tolerance. Two hundred of these women were entered into a randomized controlled trial of intensive versus routine dietary advice. Seven women were lost to follow-up. The annual incidence rates of diabetes mellitus for the 2 groups were 6.1% (intervention) and 7.3% (control), an incident rate ratio of 0.83, 95% confidence interval 0.47-1.48, p = 0.50. Overall, there was a return to normal glucose tolerance in 44% of patients. Multivariate analysis showed that body mass index, fasting and 2-hour plasma glucose levels at trial entry were significantly associated with an increased risk of diabetes mellitus. Impaired glucose tolerance is an important condition that should be treated with advice about lifestyle modification (diet and/or exercise). We consider that future trials in the management of women with previous gestational diabetes who have impaired glucose tolerance should investigate the effect of pharmacological intervention in addition to diet and/or exercise, the latter providing a therapy that it would be unethical to exclude on the evidence presently available.
 ...
PMID:A trial of simple versus intensified dietary modification for prevention of progression to diabetes mellitus in women with impaired glucose tolerance. 1075 70

The authors have studied the behaviour of plasma glucose, insulinaemia and insulin-glucose ratio in 2 groups of pregnant women with BMI values > or = or <26, respectively. Each group was divided into 3 subgroups on the basis of an oral glucose tolerance test (OGTT) response: GIGT (gestational impaired glucose tolerance), GD (gestational diabetes), and C (normal controls). Data from non-obese pregnant women demonstrate that both basal and OGTT-stimulated glucose levels were significantly different in all subgroups. The total insulin amount in the GIGT and GD subgroups is quite similar to or greater than the controls, but with a significant reduction of the insulin-glucose ratio. In GD also an absolute deficiency of insulin rise at 30 min during the glucose load, as in subjects with Type 2 diabetes mellitus (T2DM), was observed. The behaviour of these parameters in obese pregnant women seems to be similar, even though with some significant differences: in these subjects, there is a less clear-cut differentiation among all subgroups, and the appearance of gestational diabetes is not accompanied by a significant decrease of insulin secretion at 30 min. Our data seem to demonstrate that insulin resistance with an inadequate hyperinsulinaemia is a common factor for the alterations of carbohydrate metabolism during pregnancy. Only in the non-obese patients with gestational diabetes, is there an absolute defect of early insulin response to the glucose load, as it is seen in T2DM.
 ...
PMID:Glucose tolerance and insulin secretion in pregnancy. 1078 52

This article reviews maternal metabolic strategies for accommodating fetal nutrient requirements in normal pregnancy and in gestational diabetes mellitus (GDM). Pregnancy is characterized by a progressive increase in nutrient-stimulated insulin responses despite an only minor deterioration in glucose tolerance, consistent with progressive insulin resistance. The hyperinsulinemic-euglycemic glucose clamp technique and intravenous-glucose-tolerance test have indicated that insulin action in late normal pregnancy is 50-70% lower than in nonpregnant women. Metabolic adaptations do not fully compensate in GDM and glucose intolerance ensues. GDM may reflect a predisposition to type 2 diabetes or may be an extreme manifestation of metabolic alterations that normally occur in pregnancy. In normal pregnant women, basal endogenous hepatic glucose production (R(a)) was shown to increase by 16-30% to meet the increasing needs of the placenta and fetus. Total gluconeogenesis is increased in late gestation, although the fractional contribution of total gluconeogenesis to R(a), quantified from (2)H enrichment on carbon 5 of glucose (65-85%), does not differ in pregnant women after a 16-h fast. Endogenous hepatic glucose production was shown to remain sensitive to increased insulin concentration in normal pregnancy (96% suppression), but is less sensitive in GDM (80%). Commensurate with the increased rate of glucose appearance, an increased contribution of carbohydrate to oxidative metabolism has been observed in late pregnancy compared with pregravid states. The 24-h respiratory quotient is significantly higher in late pregnancy than postpartum. Recent advances in carbohydrate metabolism during pregnancy suggest that preventive measures should be aimed at improving insulin sensitivity in women predisposed to GDM. Further research is needed to elucidate the mechanisms and consequences of alterations in lipid metabolism during pregnancy.
 ...
PMID:Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. 1079 99

The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. The membrane protein plasma cell membrane glycoprotein-1 (PC-1) has been identified as an inhibitor of insulin receptor tyrosine kinase (IRTK) activity. We investigated insulin receptor function and PC-1 levels in muscle from three groups of obese subjects: women with GDM, pregnant women with normal glucose tolerance, and nonpregnant control subjects. Subjects (n = 6 for each group) were similar in age and degree of obesity (body fat >30%). IRTK activity, insulin receptor tyrosine phosphorylation, and protein levels of membrane glycoprotein PC-1 were determined in rectus abdominus muscle biopsies obtained at the time of either elective cesarean section or gynecological surgery. No significant differences were evident in basal insulin receptor tyrosine phosphorylation or IRTK activity in the three groups. After maximal insulin (10(-7) mol/l) stimulation, IRTK activity measured with the artificial substrate poly(Glu,Tyr) increased in all subjects but was lower in women with GDM by 25% (P < 0.05) and 39% (P < 0.001) compared with pregnant and nonpregnant control subjects, respectively. Similarly, insulin receptor tyrosine phosphorylation was significantly decreased in subjects with GDM (P < 0.05) compared with pregnant and nonpregnant control subjects. Treatment of the insulin receptors with alkaline phosphatase to dephosphorylate serine/threonine residues increased insulin-stimulated IRTK activity significantly in pregnant control and GDM subjects (P < 0.05), but these rates were still lower compared with nonpregnant control subjects (P < 0.05). PC-1 content in muscle from GDM subjects was increased by 63% compared with pregnant control subjects (P < 0.05) and by 206% compared with nonpregnant control subjects (P < 0.001). PC-1 content was negatively correlated with insulin receptor phosphorylation (r = -0.55, P < 0.05) and IRTK activity (r = -0.66, P < 0.05). These results indicate that pregnant control and GDM subjects had increased PC-1 content and suggest excessive phosphorylation of serine/threonine residues in muscle insulin receptors and that both may contribute to decreased IRTK activity. These changes worsen in women with GDM when controlling for obesity. These postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life.
 ...
PMID:Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese women with gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM. 1087 Nov 98

The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.
 ...
PMID:Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes. 1090 87

Studies of metabolic processes have been enhanced by our understanding of the relationships among obesity, body fat distribution, insulin sensitivity and islet beta-cell function. Thus, we have learned that although insulin resistance is usually associated with obesity, even lean subjects can be insulin resistant due to the accumulation of visceral fat. Insulin sensitivity and beta-cell function are also intimately linked. The hyperbolic relationship between these two parameters explains why insulin-resistant individuals have markedly enhanced insulin responses, whereas subjects who are insulin sensitive exhibit very low responses. Failure to take into account this relationship will lead to erroneous conclusions. By accounting for this important interaction, it has been clearly demonstrated that subjects at high risk of developing type 2 diabetes (older individuals, women with a history of gestational diabetes or polycystic ovary syndrome, subjects with impaired glucose tolerance and first-degree relatives of individuals with type 2 diabetes) have impaired beta-cell function. Furthermore, the progression from normal glucose tolerance to impaired glucose tolerance and type 2 diabetes is associated with declining insulin secretion.
 ...
PMID:Obesity, body fat distribution, insulin sensitivity and Islet beta-cell function as explanations for metabolic diversity. 1116 May 60

In summary, much controversy exists surrounding the diagnosis, treatment, and even existence of GDM. At present, there is not enough evidence to advocate the Carpenter and Coustan criteria over the NDDG criteria. In univariate analysis, the Toronto Tri-Hospital Study demonstrated an increased incidence of cesarean section, macrosomia, and preeclampsia with increasing carbohydrate intolerance in those who did not meet NDDG criteria for GDM. Multivariate analysis, however, showed that this contribution is small relative to other nonmodifiable risk factors. A shift to the Carpenter and Coustan criteria would identify a larger population of patients with GDM and increase treatment costs. In addition, although treatment of these borderline GDM patients might reduce macrosomia, there is no evidence to indicate that it reduces the cesarean section rate. The precise threshold at which glucose intolerance adversely affects pregnancy outcomes and increases the risk for the development of type 2 diabetes in the mother is unknown. The perinatal risks associated with hyperglycemia seem to increase continuously with increasing maternal hyperglycemia. More randomized intervention trials are needed to define the effects of graded increases in glucose intolerance on maternal and fetal morbidity.
 ...
PMID:Gestational diabetes mellitus. 1132 34

We assessed the safety of insulin lispro in gestational, type 1 and type 2 diabetes mellitus, analysing 635 pregnancies over a period of 7 years. We also evaluated patient satisfaction, sending an internationally-accepted anonymous diabetes treatment satisfaction questionnaire to 22 patients (three type 1, 19 gestational diabetes) who received regular and lispro insulin in successive pregnancies. The success rate of pregnancies in women with gestational diabetes managed with diet alone (n=325) was 99.3%. All 213 pregnancies in women with gestational diabetes requiring insulin were successful. There was no difference in maternal or fetal outcomes whether patients used regular insulin (n=138) or insulin lispro (n=75), but pre-delivery HbA1c was lower with insulin lispro (p<0.05). Pregnancy loss in patients with pre-gestational diabetes (89 pregnancies in type 1 and eight in type 2 diabetes) was 18.6% for insulin and 3.7% for insulin lispro (p=0.10). The incidences of congenital anomalies with regular insulin were 7.9% and 15.8% in gestational and pre-gestational diabetes, respectively; the figures for insulin lispro were 6.6% (p=0.79) and 3.8% ( p=0.16), respectively. Nineteen of the 22 surveyed patients completed the questionnaire. Satisfaction was higher with insulin lispro (26.3+/-2.3 vs. 18+/-8.9, p=0.0005). We found no increase in adverse outcome using lispro insulin in diabetic pregnancies, in either gestational or pre-gestational diabetes. Patient satisfaction favoured insulin lispro. Several patients with type 1 diabetes who used regular insulin during pregnancy, chose lispro after delivery, but all who used lispro in pregnancy preferred to continue.
 ...
PMID:Insulin lispro and regular insulin in pregnancy. 1135 99

Gestational diabetes (GDM) is a carbohydrate intolerance resulting in hyperglycaemia of variable severity with onset or first recognition during pregnancy. The incidence of GDM is between 0.15-15%, which corresponds to the prevalence of type 2 diabetes and IGT in a given country.--The predominant pathogenic factor in GDM could be the inadequate insulin secretion. If GDM is not properly treated the risk of adverse maternal (preeclampsia) and fetal (large-for-gestational-age infant, macrosomia, birth trauma, cesarean section, still-birth) outcome increases. Hypertension is more prevalent in GDM, and GDM is diagnosed more frequently in women with chronic hypertension.--In order to screen for disturbances of carbohydrate metabolism during pregnancy a simple method suitable for all pregnant women would be desirable, however no such method is available at present. According to the latest WHO recommendation the screening for GDM should be performed universally with the standard 75 g oGTT evaluating only the 2-hour blood glucose values or together with the fasting ones. The latter could provide even an exact diagnosis of the carbohydrate metabolic state.--To manage GDM the first step prompt after diagnosis is to educate adequate dietary needs. If the blood sugar values in spite of an adequate diet exceed the desirable target values, insulin treatment has to be initiated.--GDM is a predictor of diabetes (mainly type 2) later in life. The cumulative incidence of type 2 diabetes is about 50% at 5 years. This review of the current literature including our own experience strongly supposes that prior GDM is also a predictor or even an early manifestation of the metabolic (insulin resistance) syndrome. By all means GDM is a cardiovascular risk factor that could be screened to prevent late complications. The previously presented evidence also strongly suggests that yearly check-ups for women with previous GDM are inevitably important.
 ...
PMID:Gestational diabetes: current aspects on pathogenesis and treatment. 1146 May 87

The review of several diabetes epidemiological studies confirms that diabetes is one of the most prevalent non-communicable diseases globally, and it is the fourth or fifth leading cause of death in most developed countries. Diabetes prevalence ranges from nearly 0% in New Guinea to 50% in the Indians of Arizona. No modifiable risk factors have been clearly established in persons with type 1 diabetes, but major environmental determinants have been suggested. Impaired glucose tolerance, gestational diabetes, insulin resistance, obesity and lack of physical activity have been consistently identified as risk factors for type 2 diabetes. The prevalence of diabetes increases with age, but a sex-specific tendency has not been consistent. In addition, the prevalence of diabetes is higher in African-Americans and Hispanics when compared to other ethnic groups. Diabetes affects almost all organs of the body and is the leading cause of blindness and amputations of legs, imposing both clinical and economic costs to patients and society.
 ...
PMID:The public health burden of diabetes: a comprehensive review. 1156 71


<< Previous 1 2 3 4 5 6 7 8 9 10