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

Recent studies have shown that mutations in the glucokinase gene on chromosome 7 can cause an autosomal dominant form of NIDDM with a variable clinical phenotype and onset during childhood. The variable clinical phenotype includes mild fasting hyperglycemia (i.e., a plasma glucose value of > 110 mg/dl, a value that is at least 2-3 SDs above normal), impaired glucose tolerance, gestational diabetes mellitus, as well as overt NIDDM as defined using National Diabetes Data Group or World Health Organization criteria. Because gestational diabetes mellitus was a clinical feature associated with glucokinase mutations, we have screened a group of women with gestational diabetes who also had a first-degree relative with diabetes mellitus for the presence of mutations in this gene. Among 40 subjects, we identified two mutations, suggesting a prevalence of approximately 5% in this group. Extrapolating from this result, the prevalence of glucokinase-deficient NIDDM among Americans may be approximately 1 in 2500.
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PMID:Identification of glucokinase mutations in subjects with gestational diabetes mellitus. 849 17

We determined the prevalence of antibodies to glutamic acid decarboxylase (anti-GAD) in Japanese diabetic patients. Anti-GAD were detected by RIP Anti-GAD Hoechst, which is a new sensitive radioimmunoassay (RIA) kit using purified pig brain GAD as the antigen. One thousand nine hundred Japanese patients were collected by the Study Group for Antibodies to GAD. The prevalence of anti-GAD in the subjects of this study was: 35.4% (326/921) in all patients with IDDM, 50.3% (96/191) in patients with IDDM less than 1-year duration, 4.3% (29/680) in NIDDM, 37.9% (39/103) in slowly progressive IDDM, 10.5% (4/38) in gestational diabetes mellitus, 0% (0/27) in impaired glucose tolerance, 4.8% (6/124) in the school children with glycosuria, 2.1% (1/47) in the relatives of IDDM and 5.0% (1/20) in neurological diseases without diabetes. The prevalence in normal subjects was 2.2% (7/323). Anti-GAD are frequently detected by the RIA kit in patients with IDDM of short duration and this assay may be useful for population screening for IDDM and for better understanding of its pathogenesis.
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PMID:Antibodies to GAD in Japanese diabetic patients: a multicenter study. 852 98

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 development of both type II diabetes and gestational diabetes is probably governed by a complex and variable interaction of genes and environment. Molecular genetics has so far failed to identify discrete gene mutations accounting for metabolic changes in NIDDM. Both beta cell dysfunction and insulin resistance are operative in the manifestation of these disorders. Specific and sensitive immunoradiometric assays found fasting hyperproinsulinemia and first-phase hypoinsulinemia early in the natural history of the disorder. A lack of specificity of early radioimmunoassays for insulin resulted in measuring not only insulin but also proinsulins, leading to overestimation of insulin and misleading conclusions about its role in diabetes. The major causes of insulin resistance are the genetic deficiency of glycogen synthase activation, compounded by additional defects due to metabolic disorders, receptor downregulation, and glucose transporter abnormalities, all contributing to the impairment in muscle glucose uptake. The liver is also resistant to insulin in NIDDM, reflected in persistent hepatic glucose production despite hyperglycemia. Insulin resistance is present in many nondiabetics, but in itself is insufficient to cause type II diabetes. Gestational diabetes is closely related to NIDDM, and the combination of insulin resistance and impaired insulin secretion is of importance in its pathogenesis.
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PMID:The genetics and pathophysiology of type II and gestational diabetes. 856 92

Low molecular weight acid phosphatase encoded by the highly polymorphic locus ACP1 is a member of the protein-tyrosin phosphatase family (PTPases) which plays an essential role in the control of receptor signalling through phosphotyrosine pathways. Recent experiments have shown that purified rat liver ACP, corresponding to human ACP1, is able to hydrolyze a phosphotyrosine-containing synthetic peptide corresponding to the 1146-1158 sequence of the human insulin receptor, and shows a high affinity for it. This prompted us to analyze the degree of glycemic control in relation to ACP1 genetic variability in a sample of 214 diabetic pregnant women including IDDM, NIDDM and gestational diabetes. The ACP1 genotype was also determined in 482 non-diabetic pregnant women. In diabetic women glycemic levels in the last trimester of pregnancy appear to be significantly associated with the ACP1 genotype, and correlate positively with ACP1 enzymatic activity. The data suggest that quantitative variations of ACP1 may influence the clinical manifestations of diabetic disorders, and call for further studies on the role of this enzyme in the modulation of insulin-receptor phosphotyrosine pathways.
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PMID:Phosphotyrosine protein phosphatases and diabetic pregnancy: an association between low molecular weight acid phosphatase and degree of glycemic control. 862 Sep 37

Insulin resistance appears to be central to obesity, NIDDM, hyperlipidemia, and cardiovascular disease. While obese women with abdominal (android) fat distribution are more insulin resistant than those with peripheral (gynecoid) obesity, in nonobese women, the relationship between abdominal fat and insulin resistance is unknown. By measuring regional adiposity with dual-energy X-ray absorptiometry and insulin sensitivity by euglycemic-hyperinsulinemic clamp in 22 healthy women, with a mean +/- SE body BMI of 26.7 +/- 0.9 kg/m2 and differing risk factors for NIDDM, we found a strong negative relationship between central abdominal (intra-abdominal plus abdominal subcutaneous) fat and whole-body insulin sensitivity (r = -0.89, P < 0.0001) and nonoxidative glucose disposal (r = -0.77, P < 0.001), independent of total adiposity, family history of NIDDM, and past gestational diabetes. There was a large variation in insulin sensitivity, with a similar variation in central fat, even in those whose BMI was <25 kg/m2. Abdominal fat had a significantly stronger relationship with insulin sensitivity than peripheral nonabdominal fat (r2 = 0.79 vs. 0.44), and higher levels were associated with increased fasting nonesterified fatty acids, lipid oxidation, and hepatic glucose output. Because 79% of the variance in insulin sensitivity in this heterogeneous population was accounted for by central fat, abdominal adiposity appears to be a strong marker and may be a major determinant of insulin resistance in women.
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PMID:Abdominal fat and insulin resistance in normal and overweight women: Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. 862 Oct 15

Diabetes sometimes appears for the first time during pregnancy. It is important that all cases are detected, so all pregnant woman should be screened for this condition. Screening protocols vary but usually involve urinalysis at all clinic visits plus a blood glucose test, taken after a meal, at 24-28 weeks. Risk factors include increasing maternal age (25 years upwards); obesity; family history of diabetes; and previous unexplained stillbirths or babies with congenital abnormalities. There is an increased frequency of gestational diabetes in Oriental women and those from the Indian subcontinent and the Middle East Once diagnosed, careful monitoring of diabetes is essential during pregnancy to minimise complications to mother and baby Mothers should be taught to monitor their own blood glucose levels. There is no place for urinalysis in the management of gestational diabetes mellitus. Advice from a dietitian is important and there should be easy access to a diabetes specialist nurse. The baby may be born large (macrosomia), with an increased risk of respiratory distress syndrome and hypoglycaemia. Hypocalcaemia and hyper-bilirubinaemia are other complications. Mothers may suffer birth trauma and require an assisted delivery because of the baby's large size. Although most women return to normal blood glucose levels in the puerperium, they are at considerably increased risk of developing non-insulin dependent diabetes mellitus in the following years. General education about recognising the symptoms of diabetes should be given, as well as advice about future pregnancies-including the need to seek preconceptual advice.
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PMID:Gestational diabetes mellitus. 868 Jan 75

There is now strengthening evidence that meticulous control of maternal carbohydrate and fat metabolism before and during pregnancy in women with diabetes mellitus had positive benefits for the offspring, not only by reducing the incidence of congenital malformations, but also by diminishing fetal loss, reducing immediate neonatal complications and, in the long term, reducing unnecessary obesity, improving neuropsychological development and reducing the emergence of diabetes in the offspring at a relatively early age. Women who develop GDM are at a significant risk of developing NIDDM, and prevention of obesity, consumption of a high-fibre diet and possibly prophylactic hypoglycaemic therapy may reduce this otherwise inevitable progression, which will affect at least 50%.
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PMID:Diabetes. 884 51

To study why gestational diabetes (GDM) is more common in some ethnic groups than others, we tested the hypothesis that GDM is more common in people who are temporally closer to developing non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). The prevalence of GDM and the mean age of affected women in each major ethnic group were determined. From our database of NIDDM 6052 patients, the mean age of onset in each ethnic gorup was calculated and the mean difference between age of developing GDM and age of developing NIDDM derived (NIDDM-GDM age gap). This age gap was used to adjust for the susceptibility to GDM of each group. The overall prevalence of GDM was 6.7% (CI 6.0%-7.4%). In Anglo-Celtic women it was 3.0% (CI 2.3%-3.7%). For the other ethnic groups the prevalence and odds ratio (OR) were: Chinese (15.0% CI 11.8%-18.2% OR 5.6), Vietnamese (9.6% CI 6.6%-12.5% OR 3.6), Indian (16.7% CI 9.8%-23.5% OR 6.4), Arabic (7.3% CI 4.6%-10.1% OR 2.5) and Aborigines (10.1% CI 3.8%-16.4% OR 3.7). The OR for susceptibility to GDM did not change after adjustment for BMI and maternal age and it correlated significantly with the NIDDM-GDM age gap (r = -0.85; p = 0.03). However, it fell substantially after adjustment for NIDDM-GDM age gap. For women of different ethnic origins there is a difference in the time gap between their pregnancies and the time at which they would on average be expected to develop diabetes. This difference may be an important factor underlying the higher prevalence of GDM in some ethnic populations.
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PMID:Why does ethnicity affect prevalence of gestational diabetes? The underwater volcano theory. 886 51

We conducted a randomized placebo-controlled study to determine the effects of the thiazolidinedione compound troglitazone on whole-body insulin sensitivity (SI), pancreatic beta-cell function, and glucose tolerance in 42 Latino women with impaired glucose tolerance (IGT) and a history of gestational diabetes mellitus (GDM), characteristics that carry an 80% risk of developing NIDDM within 5 years. After baseline oral (OGTT) and intravenous (IVGTT) glucose tolerance testing, subjects were assigned to take placebo or 200 or 400 mg troglitazone daily for 12 weeks (14 subjects per treatment group). An OGTT and IVGTT were repeated during the 12th week of treatment. Five subjects failed to complete the trial for personal reasons, and medication compliance averaged 90% in the remaining subjects, none of whom experienced a serious adverse event. SI, calculated by minimal model analysis of IVGTT results, changed by only 4 +/- 14% during 12 weeks of placebo administration, but increased 40 +/- 22 and 88 +/- 22% above basal during treatment with 200 and 400 mg troglitazone, respectively (P = 0.01 among groups). Troglitazone administration was also associated with a dose-dependent reduction in the total insulin area during IVGTTs, which was highly significant (P < 0.001), and with a reduction during OGTTs, which approached statistical significance (P = 0.09). Glucose tolerance improved slightly in all groups, but the magnitude of change did not differ significantly among groups, whether it was assessed as the number of subjects who continued to manifest IGT at 12 weeks (P = 0.64 among groups), the change in total glucose area during OGTTs (P = 0.58), or the change in fractional glucose disappearance rates during IVGTTs (P = 0.28). Among the women who received troglitazone, the greatest improvement in SI occurred in the women who had the highest diastolic blood pressures and the best IVGTT insulin responses during baseline testing. Our findings indicate that troglitazone improved whole-body insulin sensitivity and lowered circulating insulin concentrations in women with prior GDM who are at very high risk for NIDDM. The lack of improvement in glucose tolerance despite improved insulin sensitivity may be a manifestation of the beta-cell defect that predisposes the women to NIDDM. The overall pattern of response to troglitazone in our high-risk patients indicates that the drug is an ideal agent with which to test whether the amelioration of insulin resistance can delay or prevent diabetes in women with limited beta-cell reserve.
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PMID:Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM. 886 63


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