Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.
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PMID:Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis. 1155 32

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

We examined whether plasma fibrinogen levels and the beta-fibrinogen gene G(-455)-->A polymorphism were related to microvascular or macrovascular disease in patients (n = 909) with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC). Univariate regression showed that fibrinogen levels were correlated with BMI (r = 0.15; P < 0.0001), HbA(1c) (r = 0.11; P = 0.0014), total cholesterol (r = 0.17; P < 0.0001), and LDL cholesterol (r = 0.16; P < 0.0001) in all patients. In men, but not women, waist-to-hip ratio (r = 0.20; P < 0.0001) and triglycerides (r = 0.13; P = 0.0047) also became powerful predictors of fibrinogen level; in women, but not men, fibrinogen was correlated with both diastolic (r = 0.16; P = 0.0011) and systolic (r = 0.11; P = 0.0241) blood pressure. Fibrinogen was correlated with urinary albumin excretion rates in men (r = 0.13; P = 0.0033), but not in women. In both sexes, however, the development of proteinuria (albumin excretion >300 mg/24 h) was accompanied by 1.5-fold increment in plasma fibrinogen compared with patients with normal excretion or microalbuminuria. In addition, high fibrinogen levels were associated with a lower average ankle-brachial index in women (r = -0.13; P = 0.0075), but not men. Multiple regression analyses demonstrated that plasma fibrinogen was independently correlated with high albumin excretion rate in men, and with low average ankle-brachial index in women. Fibrinogen was not correlated with the severity of retinopathy. Carotid artery intima-medial thickness was not correlated with fibrinogen, and the G(-455)-->A polymorphism in the 5' promoter region of the beta-fibrinogen gene did not influence circulating fibrinogen levels. However, the presence of the more common G(-455) allele was associated with greater intima-medial thickness in the internal carotid artery (ANCOVA P = 0.045). Last, hyperfibrinogenemia in type 1 diabetes is associated with components of the insulin resistance syndrome trait cluster, and the association is influenced by sex.
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PMID:Fibrinogen is a marker for nephropathy and peripheral vascular disease in type 1 diabetes: studies of plasma fibrinogen and fibrinogen gene polymorphism in the DCCT/EDIC cohort. 1271 2

The aim of the study was to test the hypothesis that in diabetic patients without overt nephropathy there may be a correlation between the activity of natural anticoagulant proteins and glomerular dysfunction. Assays for functional activity of proteins S and C, measurements of urinary albumin excretion, lipid parameters and haemoglobin A1c were performed in 91 patients with type 1 diabetes mellitus and 85 patients with type 2. Patients with type 1 diabetes and microalbuminuria had significantly higher mean age (44.1 +/- 10.9 vs. 37.9 +/- 12.7 years; p<0.05), fibrinogen level (3.75 +/- 1.0 vs. 3.21 +/- 0.8 g/l; p<0.01), protein S activity (92.3 +/- 17.6 vs. 84.5 +/- 15.5%; p<0.05) and higher prevalence of retinopathy (p<0.01) and macrovascular disease (p<0.01) than those with normoalbuminuria. Albumin excretion was significantly correlated to age (r=0.25, p<0.05), fibrinogen level (r=0.39, p<0.01), protein S activity (r=0.27; p<0.05), total cholesterol (r=0.23; p<0.05), apoprotein B (r=0.22; p<0.05), retinopathy (r=0.33; p<0.01) and macrovascular disease (r=0.33; p<0.01). Patients with type 2 diabetes mellitus and microalbuminuria had significantly higher apoprotein B levels (1.17 +/- 0.3 vs. 1.06 +/- 1.2 mg/dl; p<0.05) than those with normoalbuminuria, and apoprotein B was significantly correlated to albumin excretion (r=0.22; p<0.05). In a multivariate model of type 1 diabetes mellitus with fibrinogen, protein S and C activity, cholesterol, triglycerides, haemoglobin A1c, retinopathy, and macrovascular disease as independent parameters (r=0.53; p<0.003), there was significant independent correlation of fibrinogen (beta=0.28; p<0.01), protein S activity (beta=0.27; p<0.05) and retinopathy (beta=0.21; p<0.01) with albumin excretion. We conclude that in type 1 diabetes, relative elevation of fibrinogen level and protein S activity appear in the early stages of development of diabetic nephropathy, and may be related to the pathogenesis of diabetic kidney disease.
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PMID:Urinary albumin excretion is correlated to fibrinogen levels and protein S activity in patients with type 1 diabetes mellitus without overt diabetic nephropathy. 1514 63

BACKGROUND: Latent tissue scurvy in clinical and experimental ascorbic acid (AA) deficiency resembles diabetic microangiopathy as reflected in capillary hyperperfusion and increased transcapillary escape rate (TER), von Willebrand factor (vWf), and capillary fragility (CF). We aimed to investigate the possible clinical impact of the low plasma AA level observed in type 1 diabetes mellitus. METHODS: Twenty normoalbuminuric patients with retinopathy were included in a randomized, double-blinded, placebo-controlled 6-month study with AA (6 g/day; n=10, mean age+/-S.D. 35.3+/-8.5 years, diabetes duration 17.2+/-3.3 years) or placebo (n=10; mean age 37.8+/-6.6 years, diabetes duration 18.4+/-1.7 years). RESULTS: An inverse correlation between log plasma AA (HPLC method) and TER of (125)I-labelled albumin was found (r=-0.66, p=0.002). TER decreased in the AA-treated group from 6.8+/-1.0 to 5.4+/-1.5%/h compared to the unchanged placebo group (from 5.6+/-1.5 to 5.9+/-1.1%/h; p=0.031). The CF (capillary resistance test) decreased in the AA group compared to the placebo group (p=0.028), while vWf, fibrinogen and fibronectin levels, and glomerular filtration rate (clearance of (125)I-iothalamate) remained unchanged. CONCLUSIONS: The results suggest that a low plasma AA level might be associated (pathogenetic?) with development of microangiopathy in type 1 diabetes mellitus and points to a possible treatment modality.
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PMID:Vitamin C treatment reduces transcapillary escape rate of albumin in type 1 diabetes. 1558 46

To evaluate markers of inflammation, we studied 48 patients with type 1 diabetes [DM1, 23F:25M, 19.9+/-9.8 years and duration of DM of 5 (1-21) years& and 66 non-DM subjects, matched for sex, age, and stages of puberty according to Tanner. C-reactive protein (CRP), alpha1-acid glycoprotein (AGP) and fibrinogen were measured by turbidimetric immunoassay and urinary albumin excretion rate (AER) was determined in timed overnight urine samples by RIA. Microalbuminuria was defined when two out of three urine samples had AER ranging 20-200 microg/min. Retinopathy was evaluated by indirect ophthalmoscopic in DM patients. The CRP and AGP levels were higher in DM1 patients as compared to controls, respectively [0.23 (0.01-2.90) vs. 0.14 (0.01-2.41) mg/dl, p= 0.0172& and [53.5 (37-115) vs. 40 (19-78) mg/dl, p< 0.0001]. Fibrinogen levels were not different between both groups. Stepwise multiple regression analysis showed that HbA1c and plasma glucose were the independents predictive variables of AGP, respectively (r2= 0.26; p< 0.05 and r2= 0,29; p< 0,05); CRP and fibrinogen did not correlate significantly with the independents variables. PCR correlate with HbA1c (r= 0.18; p= 0.05) by Pearson's correlation. In conclusion, CRP and AGP were higher in DM1 patients, without microalbuminuria, retinopathy and clinical macrovascular disease. Prospective studies must be addressed to determine the influence of AGP and CRP in the development of chronic complications.
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PMID:[Markers of inflammation in type 1 diabetic patients]. 1564 Aug 80

A potential role for the platelet Fc gammaRIIA immunoreceptor (FcR) in collagen-mediated platelet activation associated with diabetes has recently been described. This study was undertaken to prospectively determine which diabetes patient population (type 1, type 2, or both) was more likely to over express platelet FcR and to determine what clinical or laboratory features characterized this population. One hundred and twenty type 2 diabetes, 135 type 1 diabetes, and 275 control patients participated in this cross-sectional study. Relative FcR expression was assessed by flow cytometry of antibody-labeled platelets. FcR expression was higher in type 2 diabetes than in type 1 diabetes or control subjects [mean+/-S.D.=15.17+/-4.66 versus 10.28+/-3.11 (p<0.05) and versus 10.33+/-2.59 (p<0.05), respectively]. This relationship was independent of sex, BMI, HDL cholesterol, triglycerides, blood pressure, glucose control, fibrinogen, and smoking. An inverse association between platelet FcR expression and plasma LDL cholesterol levels was also observed along with a modest correlation with age. Among type 2 patients there was inverse and no correlation between FcR expression and LDL levels and age respectively. Increased platelet FcR expression in type 2 diabetes may play a role in arterial vasoocclusive complications associated with this population. It is hypothesized decreased FcR expression could potentially represent a form of compensatory biological response to an adverse lipid profile in which sensitivity of platelets to collagen may be relatively down regulated in type 2 diabetes.
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PMID:Increased platelet Fc receptor expression in diabetes is limited to those with type 2 disease and low LDL cholesterol levels. 1600 80

The present study sought to examine the occurrence of subclinical markers of cardiovascular risk and cardiac dysfunction with increasing disease duration in type 1 diabetes mellitus (DM). There are few data on subclinical cardiovascular abnormalities in type 1 DM. The study included 100 patients without any cardiovascular complaints (mean age 46.6 years, range 22 to 63), with a history of type 1 DM ranging from 2 to 36 years, and 75 age-matched controls. Standard 2-dimensional and Doppler echocardiography and pulse-wave tissue Doppler (tD) mapping of systolic (Sm) and diastolic (Em, Am) velocities (12 left ventricular [LV] segments and right-sided cardiac) were performed. An Em/Am ratio of <1 was considered to represent abnormal segmental diastolic function. Flow-mediated dilation (FMD) of the brachial artery, carotid intima media thickness (IMT) measurement, and extensive laboratory analysis were performed. The FMD was reduced, and IMT increased in patients (p < 0.01). Regional tD-derived diastolic and systolic functional abnormalities were observed within the first decade of the disease. Significant correlations were found between FMD and LV segments with tD-derived dysfunction, the duration of DM, and fibrinogen (p < 0.0001 for all). Stepwise regression analysis showed that FMD was the strongest predictor of abnormal segmental function (p < 0.0001). Data further presented as an analysis of tertiles by DM duration show an increasing occurrence of subclinical cardiac dysfunction and cardiovascular risk markers compared with age-matched controls. In conclusion, FMD is associated with abnormal segmental cardiac function in type 1 DM.
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PMID:Flow mediated dilatation and cardiac function in type 1 diabetes mellitus. 1637 88

Diabetes is an emblematic example of a heterogeneous disease. Systemic inflammation has emerged as a prominent factor in the type 2 diabetes pathoetiology, but it remains ill-defined in type 1 diabetes. There is a wide spectrum of associations between inflammatory responses and diabetic syndromes. At one end of this spectrum, there is type 1 diabetes for which there is convincing evidence that chronic inflammation of pancreatic islets is a central aspect of disease pathogenesis. At the opposite end, is type 2 diabetes that is clearly associated with systemic inflammation, which could be either the cause or simply mark the underlying pathology. Accumulating evidence has substantiated that a subgroup of adult patients clinically diagnosed with type 2 diabetes exhibit autoantibody responses to islet autoantigens. The presence of these immunologic abnormalities is associated with a severe insulin secretory defect and the absence of signs of systemic inflammation as documented by plasma C-reactive protein and fibrinogen levels that are comparable with those of control populations. Islet autoantibody evaluation should be part of the diagnostic assessment for clinically diagnosed type 2 diabetes not only because it might predict the rate of progression to insulin requirement in adult populations but also to identify a pathogenically distinct disease phenotype characterized by the absence of systemic inflammation and its related disorders. A more appropriate characterization of this subgroup of clinically diagnosed type 2 diabetes, diabetes of autoimmune pathogenesis, will promote future research into the etiology, natural history, and treatment.
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PMID:The heterogeneity of diabetes: unraveling a dispute: is systemic inflammation related to islet autoimmunity? 1732 78

Present analyses used data from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective study of subjects with childhood type 1 diabetes (T1D), diagnosed between 1950 and 1980. Baseline exams took place 1986-1988 with biennial exams since. The Framingham risk equation was applied to generate the probability of risk for coronary heart disease (CHD) (MI, CHD death, or Q-waves) in 552 CHD free subjects who experienced 42 events over the 10-year follow-up period. Probabilities were split in to deciles. Expected and observed events were compared and demonstrated poor prediction. Risk factors previously found to be associated with CHD in T1D other than those in the Framingham risk function (age, smoking, cholesterol/HDLc, systolic blood pressure) were compared within the highest risk deciles. In men, elevated fibrinogen (p=0.007), white blood cell count (WBC) (p=0.037), albumin excretion rate (AER) (p=0.0001), and lower HDLc (p=0.048) were predictive. In females, higher Beck Depression Inventory (p=0.008), HbA1 (p=0.008), AER (p=0.01), LDLc (p=0.007), fibrinogen (p=0.006), WBC (p=0.005), non-HDLc (p=0.0005), WHR (p=0.003), and estimated glucose disposal rate (p=0.002) were associated. Risk factors not considered by the Framingham risk equation may account for the lack of fit and should be examined further.
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PMID:Cardiovascular disease risk prediction in type 1 diabetes: accounting for the differences. 1746 46


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