Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.
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PMID:Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus. 1189 23

Serum ceruloplasmin was reported to be an independent risk factor for cardiovascular disease. We investigated whether serum ceruloplasmin level is elevated in subjects with metabolic syndrome (MS, insulin resistance syndrome) in a community-based population. A total 883 subjects over 40 years of age were studied among a population of the Chongup district, a rural area of South Korea. Serum ceruloplasmin levels were measured, and oral glucose tolerance tests were performed. Known cardiovascular risk factors, such as serum lipids, fasting insulin level, and urinary albumin excretion rate (UAER), were also measured. Serum ceruloplasmin levels in the subjects with MS (n = 167, 325 +/- 141 mg/L) were significantly higher than in those without MS (278 +/- 93 mg/L, P <.001). The mean ceruloplasmin level also increased as the glucose tolerance worsened (278 +/- 95 mg/L in normal glucose tolerance [NGT], 303 +/- 108 mg/L in impaired glucose regulation, and 328 +/- 148 mg/L in diabetes; P <.001). Serum ceruloplasmin level was positively correlated with age, fasting glucose, postload 2-hour glucose, total cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, and UAER and negatively with high-density lipoprotein (HDL)-cholesterol. In multiple regression analysis, serum ceruloplasmin level was independently associated with age, fasting glucose, triglyceride, HDL-cholesterol, and UAER. In conclusion, serum ceruloplasmin level is elevated in the subjects with MS, as well as in subjects with impaired glucose regulation or diabetes mellitus. In addition, serum ceruloplasmin level is associated with various cardiovascular risk factors. These results suggest that elevated serum ceruloplasmin level can be a marker for metabolic stresses associated with MS.
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PMID:Elevated serum ceruloplasmin levels in subjects with metabolic syndrome: a population-based study. 1207 27

The objective was to evaluate a screening procedure for detecting high-yield candidates for an OGTT, in a population of middle-aged Swedish women. A two-step screening procedure was performed in 6917 subjects. Women with a positive screening outcome, i.e. increased non-fasting capillary blood glucose, serum triglycerides, BMI, WHR, blood pressure or a family history of diabetes, pharmacological treatment of hypertension or hyperlipidaemia at the primary screening underwent a 75-g OGTT. A control group of women with negative screening outcome (n = 221) also underwent an OGTT. In 2923 women with positive screening outcome, 517 (17.7%) had NFG/IGT (normal fasting venous blood glucose <5.6 mmol/l and 2h-glucose 6.7-9.9 mmol/l), 109 (3.7%) IFG/IGT (fasting 5.6-6.0 and 2h 6.7-9.9 mmol/l) and 223 (7.6%) diabetes (fasting > or = 6.1 or 2h > or = 10.0 mmol/l). These figures were three, five and four times higher, respectively, than in the control group with negative screening outcome (p < 0.001 for all); no differences were found for IFG/NGT (fasting 5.6-6.0 and normal 2h < 6.7 mmol/l) (4.6% vs. 7.2%). For predicting impaired glucose metabolism (IFG/NGT, NFG/IGT, IFG/IGT, diabetes), the screening instrument showed an estimated sensitivity of 70%, specificity of 55%, positive predictive value of 34% and negative predictive value of 85%, based on findings in the control sample. The odds ratio for NFG/IGT increased with the numbers of risk factors from 2.8 to 7.7, for IFG/ IGT from 5.7 to 55.0 and for diabetes from 2.5 to 18.1. High B-glucose, WHR and BMI were the three most important factors associated with an increased risk for NFG/IGT, IFG/IGT and diabetes. In subjects with IFG/NGT, none of the screening variables was associated with an increased risk. In summary, the results show a population screening method focused on features of the metabolic syndrome that discloses high-yield candidates for OGTT. A high prevalence of unknown impaired glucose metabolism was found in middle-aged women with a positive screening profile.
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PMID:A screening procedure detecting high-yield candidates for OGTT. The Women's Health in the Lund Area (WHILA) study: a population based study of middle-aged Swedish women. 1218 15

Postprandial hyperglycemia has been shown to increase the risk of cardiovascular disease as much as overt diabetes mellitus does. The aim of this study was to determine whether isolated post-challenge hyperglycemia during an oral glucose tolerance test (OGTT) is related to exaggerated neointimal proliferation after coronary stent implantation. Forty seven coronary lesions treated with stents in 40 patients who had normal fasting glucose levels (<110 mg/dl) were categorized into the following 2 groups according to the results of a 75-g OGTT: 29 lesions in 24 patients with normal glucose tolerance (NGT group) and 18 lesions in 16 patients with abnormal glucose tolerance (AGT group). Although there were no differences in angiographic characteristics before and immediately after stenting between the 2 groups, the minimal lumen diameter was significantly smaller (p=0.04) and the degree of stenosis and late loss were also significantly greater (p=0.01 and p=0.047) in the AGT group than in the NGT group at 6-month follow-up. Multiple regression analysis including the insulin concentrations during an OGTT revealed that the 120-min plasma glucose concentration after glucose load significantly correlated with late loss (p=0.0018) and the degree of stenosis (p=0.0100) at follow-up. It is concluded that isolated post-challenge hyperglycemia exaggerates neointimal hyperplasia after coronary stent implantation.
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PMID:Isolated post-challenge hyperglycemia in patients with normal fasting glucose concentration exaggerates neointimal hyperplasia after coronary stent implantation. 1252 Jan 54

Women with previous gestational diabetes (pGDM) are frequently insulin-resistant, which could relate to intramyocellular lipid content (IMCL). IMCL were measured with (1)H nuclear magnetic resonance spectroscopy in soleus (IMCL-S) and tibialis-anterior muscles (IMCL-T) of 39 pGDM (32 +/- 2 years, waist-to-hip ratio 0.81 +/- 0.01) and 22 women with normal glucose tolerance (NGT; 31 +/- 1 years, 0.76 +/- 0.02) at 4-6 months after delivery. Body fat mass (BFM) was assessed from bioimpedance analysis, insulin sensitivity index (S(I)), and glucose effectiveness (S(G)) from insulin-modified frequently sampled glucose tolerance tests. pGDM exhibited 45% increased BFM, 35% reduced S(I) and S(G) (P < 0.05), and 40% (P < 0.05) and 55% (P < 0.005) higher IMCL-S and IMCL-T, respectively. IMCL related to body fat (BFM P < 0.005, leptin P < 0.03), but only IMCL-T correlated (P < 0.03) with S(I) and glucose tolerance index independent of BMI. Insulin-resistant pGDM (n = 17) had higher IMCL-S (+66%) and IMCL-T (+86%) than NGT and insulin-sensitive pGDM (+28%). IMCL were also higher (P < 0.005, P = 0.05) in insulin-sensitive pGDM requiring insulin treatment during pregnancy and inversely related to the gestational week of GDM diagnosis. Thus, IMCL-T reflects insulin sensitivity, whereas IMCL-S relates to obesity. IMCL could serve as an additional parameter of increased diabetes risk because it identifies insulin-resistant pGDM and those who were diagnosed earlier and/or required insulin during pregnancy.
Diabetes 2003 Feb
PMID:Increased intramyocellular lipid concentration identifies impaired glucose metabolism in women with previous gestational diabetes. 1254 May 93

To clarify whether pancreatic beta-cell function and/or insulin resistance contributes to development of glucose intolerance in Japanese subjects, we investigated 551 subjects who underwent a 75-g oral glucose tolerance test (OGTT). Subjects were divided into 3 groups: normal glucose tolerance (NGT, n = 238), impaired glucose tolerance (IGT, n = 211), and newly diagnosed type 2 diabetes mellitus (n = 102). The diabetics were subdivided into 3 subgroups as follows: diabetes with normal fasting glucose (fasting plasma glucose [FPG] < 110 mg/dL), diabetes with impaired fasting glucose (FPG 110 to 125 mg/dL), and diabetes with diabetic fasting glucose (FPG >or= 126 mg/dL). Insulinogenic index as early-phase insulin secretion, homeostasis model assessment (HOMA-beta and HOMA-resistance), and 4 different formulas of insulin sensitivity index were assessed by plasma glucose and insulin concentrations obtained at fasting or during a 75-g OGTT. Both early-phase insulin secretion and insulin sensitivity were low even in the IGT stage compared with NGT. The transition from IGT to diabetes was accompanied by a progressive deterioration of insulin reserve as well as insulin resistance. During the further progression in diabetes, insulinogenic index decreased additionally, whereas declines in insulin sensitivity were relatively small. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of glucose intolerance in Japanese subjects.
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PMID:Pancreatic beta-cell function and insulin sensitivity in japanese subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes mellitus. 1270 Oct 62

The regulation of hepatic VLDL secretion mainly depends on apolipoprotein (apo) B synthesis, on microsomal triglyceride transfer protein, insulin and the availability of triglycerides, free fatty acids (FFA) and cholesteryl ester. Four sources of fatty acids are used for lipoprotein synthesis: de-novo lipogenesis, cytoplasmic triglyceride stores, fatty acids derived from lipoproteins taken up directly by the liver and plasma FFA. Quantitatively, de-novo lipogenesis plays a minor role in regulating VLDL synthesis, but evidently it is elevated under conditions of high carbohydrate feeding. Cytoplasmic triglyceride stores appear to essentially contribute to VLDL triglycerides. Plasma FFA enter the hepatocytes and are either oxidized or esterified. The relationship between oxidation and esterification appears to be important in regulating the VLDL synthesis. An enhanced esterification is accompanied by increased VLDL secretion. The addition of oleic acid to hepatocytes has been shown to stimulate production of VLDL triglyceride and apoB. In human beings, an acute experimental elevation of plasma FFA stimulates VLDL production. In healthy men strong positive relations were found between the late increases in large triglyceride-rich lipoproteins and plasma FFA concentrations after 6 h following a mixed meal. In contrast, n-3 fatty acids impair VLDL assembly and secretion. Chronic hyperinsulinemia seems to stimulate VLDL production. On the other hand, the short-term addition of insulin has been shown to inhibit VLDL-triglyceride and apoB production in vitro. There is in vivo evidence that acute hyperinsulinemia suppresses VLDL-apoB and VLDL-triglyceride production in insulin-sensitive humans. Part of this action is due to suppression of plasma FFA. In patients with impaired glucose tolerance (IGT), VLDL production was increased when compared with subjects with normal glucose (NGT). When infusing a lipid emulsion, VLDL production could not be further stimulated in IGT patients in contrast to NGT persons. Hypertriglyceridemia in type 2 diabetes mellitus is usually the consequence of a VLDL overproduction. In type 2 diabetic patients, in contrast to normal men, insulin failed to suppress VLDL1 particle release. In normal men, an elevation of blood glucose led to a decrease in fatty acid oxidation and an increase in hepatic triglyceride secretion. Under these conditions, approximately 30% of total VLDL triglycerides coming out of the liver did not originate from plasma FFA. In conclusion, plasma FFA seem to play an important role in stimulating hepatic VLDL production. Other factors such as chronic hyperinsulinemia or nutrition modify this effect.
Exp Clin Endocrinol Diabetes 2003 Aug
PMID:Influence of plasma free fatty acids on lipoprotein synthesis and diabetic dyslipidemia. 1295 28

Hypertension and diabetes are risk factors for arteriosclerosis and have a synergistic effect on the progression of arteriosclerosis. The aim of this study was to determine the correlation between complications of hypertension and diabetes and arteriosclerosis as assessed by pulse wave velocity (PWV) in elderly subjects. The subjects of this study were 186 people aged 60 years or older (mean age: 68.8 +/- 5.8 years) who were scheduled to undergo health examinations. PWV, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting blood sugar (FBS), total cholesterol (TC), triglyceride (TG) and HDL cholesterol (HDL) were measured in each subject. The patients were divided according to the American Diabetes Association (ADA) diagnostic criteria for diabetes based on fasting blood sugar level into the following three groups: a normal (NGT) group (FBS < 110 mg/dl), an impaired fasting glucose (IFG) group (110 < or = FBS < 126 mg/dl) and a diabetes mellitus (DM) group (FBS > or = 126 mg/dl or receiving treatment for diabetes). Based on the JNC-VI and WHO/ISH diagnostic criteria, subjects who had a SBP of 140 mmHg or higher or a DBP of 90 mmHg or higher or who had been taking hypotensive drugs were assigned to the hypertension (HT) group, and the other subjects were assigned to the normotension (NT) group. PWV showed significant positive correlations with SBP and FBS (r = 0.499 and r = 0.300, respectively). The effects of hypertension on PWV were significantly higher in subjects with HT than in subjects with NT in all of the glucose tolerance groups (all p < 0.01). Moreover, in the subjects with HT, PWV started to increase from the IFG stage, and PWV was significantly higher in the DM groups than in the NGT group (p < 0.01). In multiple regression analysis using PWV as an objective variable, SBP and FBS were selected as significant explanatory variables. The results of this study indicate the need for stricter management of elderly people with slight glucose tolerance impairment and hypertension in order to prevent the occurrence of arteriosclerosis.
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PMID:[Relation of hypertension and glucose tolerance impairment in elderly people to the development of arteriosclerosis--investigation using pulse wave velocity]. 1468 53

We evaluated insulin release and insulin sensitivity in women with basal and/or postprandial hyperglycemia but normal oral glucose tolerance test (OGTT) in previous pregnancy (GHG). These women were individually matched with females without previous hyperglycemia (NGT). Both groups consisted of normal glucose-tolerant women at the time of this study. They underwent OGTT (75 g; n=32 pairs) and hyperglycemic clamp experiments (10 mmoll(-1); n=27 pairs) with plasma glucose, insulin, and C-peptide measurements and calculation of insulinogenic index, first- and second-phase insulin release, and insulin sensitivity index (ISI). The GHG group showed higher glycosylated hemoglobin levels (6.2+/-0.6% versus 5.8+/-0.8%; P<0.05); lower insulinogenic index at 30 min (134.03+/-62.69 pmol mmol(-1) versus 181.59+/-70.26 pmol mmoll(-1); P<0.05) and diminished C-peptide response in relation to glucose (4.05+/-0.36 nmol mmol(-1) versus 4.23+/-0.36 nmol mmol(-1); P<0.05) at OGTT. Both groups did not show difference in insulin secretion and ISI by hyperglycemic clamp technique. We concluded that in up to 12 years from index pregnancy, women with previous GHG, presenting normal glucose tolerance and well-matched with their controls, showed beta-cell dysfunction without change in ISI. As women with previous GHG are at risk of type 2 diabetes, beta-cell dysfunction may be its primary defect.
Diabetes Res Clin Pract 2004 Feb
PMID:Pancreatic beta-cell defects in women at risk of type 2 diabetes. 1473 48

Previous studies have established that impaired glucose tolerance (IGT) patients with fasting hyperglycemia (IGT/FH: fasting plasma glucose (FPG) level 6.1-7.0 mmol/l and 2 h PG level of 7.8-11.1 mmol/l) exhibit higher insulin resistance than those with isolated IGT (FPG level <6.1 mmol/l and 2 h PG level of 7.8-11.1 mmol/l), but the association with microalbuminuria has not been determined. Here, we evaluate the prevalence of microalbuminuria in non-diabetic Japanese males 20-70 years of age. The subjects were classified into four groups based on the results of OGTT: normal glucose tolerance (NGT: n=71), impaired fasting glucose (IFG: n=24), isolated IGT (n=36), and IGT/FH (n=23). A urinary albumin-to-creatinine ratio (ACR) from 30 to 300 microg/mg creatinine was counted as microalbuminuria. The prevalence of microalbuminuria was higher in subjects with IGT/FH than in subjects with isolated IGT (26% versus 14%). Logistic regression analysis showed microalbuminuria to be more significantly associated with IGT/FH (OR=3.82, 95% CI 1.09-13.36) than with isolated IGT (OR=1.75, 95% CI 0.50-6.17). While insulin resistance (HOMA-IR) in isolated IGT was not significantly different from that in NGT, insulin resistance in IGT/FH was significantly higher (P<0.01). Regression analysis of ACR in IGT showed a significant correlation with insulin resistance (P=0.012). Accordingly, microalbuminuria is more strongly associated with IGT/FH than with isolated IGT, most likely due to the higher insulin resistance.
Diabetes Res Clin Pract 2004 Jun
PMID:IGT with fasting hyperglycemia is more strongly associated with microalbuminuria than IGT without fasting hyperglycemia. 1512 10


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