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

Previously both specific and nonspecific immune reactions have been reported in patients with type I diabetes mellitus. In this study the effect of various immunosuppressive drugs and insulin was studied on in vitro lymphocyte-mediated cytotoxicity in 20 type I diabetic patients. Twenty sex- and age-matched healthy subjects served as controls. Human pancreas-extract (300 micrograms/ml protein)-coated, 51-Chromium labeled chicken erythrocytes were used as target cells and separated T-lymphocytes as effector cells with and without azathioprine 50 micrograms/50 microliters (Wellcome), Cyclosporine A 5 ng/50 microliters (Sandoz) and MC Actrapid insulin 0.1 IU/50 microliters (Novo). The degree of cytotoxicity was expressed with cytotoxic capacity: the number of maximal killed target cells. Simultaneously islet cell antibodies (ICA) in sera and the number of activated T-lymphocytes were assessed. Significant lymphocyte-mediated cytotoxicity was observed in the majority of type I diabetic patients (18/20), while no cytotoxicity was found in the control cases. The cytotoxicity decreased in all 16 patients using azathioprine or insulin, independently of ICA and HLA-DR positivity. The number of killed target cells was lowered considerably by Cyclosporine A in all 18 patients having cytotoxicity against pancreas-extract. Our observations reveal that Cyclosporine A proved to be the most effective immunosuppressive agent in vitro. It decreases not only the leucocyte migration inhibition as previously observed, but also the lymphocyte-mediated cytotoxicity, which represents the late stage of cellular immune reactions against pancreatic tissue.
 ...
PMID:The effect of azathioprine, cyclosporine A and insulin on the in vitro lymphocyte-mediated cytotoxicity in type I diabetic patients. 130 69

Immunoreactive glucagon responses were measured in 21 normoglycaemic adult offspring of non-insulin dependent (Type 2) diabetic parents, in the fasting state and during an oral glucose tolerance test. In 7 of the 21 offspring, the mean fasting immunoreactive glucagon value was significantly lower than the control value (p < 0.001). In this group, glucose stimulation did not produce inhibition of immunoreactive glucagon secretion. The insulin response in this group was not significantly different from the values in the other study groups. In the other 14 offspring, the pattern of glucagon response to glucose stimulation was similar to controls. It is likely that this non-suppressive effect of glucose on immunoreactive glucagon in some of the "prediabetic" individuals is an early change in the alpha cell function during the natural history of non-insulin dependent diabetes in Asian Indian subjects.
 ...
PMID:Glucagon response to glucose load in offspring of conjugal type 2 diabetic parents in south India. 130 29

Levels of insulin-like growth factor 1 (IGF-1) or somatomedin C were investigated in 12 subjects with only the onset (3-18 mos.) of IDDM. These levels were low as compared to control values (213 + 65 and 450 + 40 ng/ml) and vice versa, growth hormones levels were higher than those in control subjects (14.0 + 8.0 and 7.5 + 1.2 ng/ml). In one month after intensified insulin infusion and three daily injections, the ratio is smoothed (IGF-1 -- 320 + 20 during CSII; 280 + 12 ng/ml during conventional insulin therapy and GH -- 10.0 + 1.2 for CSII and 15.0 + 1.7 ng/ml for CIT). The disturbed GH/IGF-1 ratio correlated with the glycemia level (r = 0.65). A close connection was established between the levels of IGF-1 and C-peptide concentrations in patients with IDDM onset (r = 0.70, p < 0.05), making it possible to influence beta-cell proliferation and to maintain DM remission.
 ...
PMID:[Insulin-like growth factor I in patients with newly detected insulin-dependent diabetes mellitus]. 130 86

To determine the role of insulin clearance in the dawn phenomenon, we studied 10 adolescents with IDDM in comparison to 10 healthy, matched control subjects reported previously. In diabetics, metabolic clearance rate of insulin was calculated during i.v. infusion of insulin from 0100 to 0430 h and from 0430 to 0800 h (0.17 and 0.33 mU/kg/min, respectively), with a Harvard pump, while maintaining nocturnal euglycemia. In controls, metabolic clearance rate of insulin was calculated from the prehepatic insulin secretion rate based on C-peptide levels. In diabetic and control subjects, plasma glucose, free insulin, and glucagon concentrations were similar and did not change during the dawn period. However, metabolic clearance rate of insulin increased during the dawn period in diabetic (9.42 +/- 0.91 to 19.89 +/- 1.52 mL/kg/min, p less than 0.0001) and control subjects (4.87 +/- 1.11 to 9.30 +/- 1.50 mL/kg/min, p = 0.008). Plasma cortisol and adrenocorticotropic hormone levels increased and growth hormone (GH) decreased significantly during the dawn period. Diabetic adolescents had significantly higher plasma GH levels than control subjects throughout the night. We conclude the 1) increased insulin clearance is responsible for the dawn phenomenon in healthy and diabetic adolescents and 2) insulin resistance due to GH is an unlikely cause for the dawn phenomenon because diabetic subjects, despite higher GH levels, maintain plasma glucose levels similar to control subjects without requiring higher plasma free insulin concentrations.
 ...
PMID:The dawn phenomenon: comparison between normal and insulin-dependent diabetic adolescents. 131 57

Points of agreement: (1) In IDDM, hypertension occurs in patients who have already developed nephropathy, probably in the microalbuminuric phase. (2) Hypertension is an important accelerator of the development of diabetic nephropathy. (3) Hypertension, obesity and NIDDM are often associated, and insulin resistance is commonly observed in all three states. (4) Antihypertensive therapy retards the development of diabetic nephropathy in IDDM and reduces proteinuria in NIDDM. (5) The choice of antihypertensive agent in the diabetic patient must be based upon the efficacy of the drug as well as avoidance of side effects including deleterious influence on glucose, insulin and lipid levels and renoprotection. (6) Carefully conducted long-term comparative trials between different classes of antihypertensive drugs in microalbuminuric IDDM and NIDDM patients are essential. Points of major controversy: (1) Detection of IDDM patients prone to the development of diabetic nephropathy can be performed by measuring specific parameters such as erythrocyte Na(+)-Li+ countertransport activity. (2) Insulin resistance is a pathogenic mechanism rather than purely an association with hypertension and obesity. (3) A certain class of antihypertensive agents--ACE inhibitors--confers a specific renoprotective effect in diabetic nephropathy, in addition to its effects upon systemic blood pressure. (4) Reduction of blood pressure should be considered in the normotensive microalbuminuric diabetic patient. (5) Microalbuminuria is a sufficient 'surrogate endpoint' for the progression of renal failure.
 ...
PMID:Meeting report of the International Society of Hypertension Conference on Hypertension and Diabetes. 131 6

Diabetes mellitus (DM) is frequently associated with hypertension for which an independent pathomechanism has been suggested. We studied 26 patients with insulin-dependent (IDDM) and 18 patients with non-insulin-dependent (NIDDM) uncomplicated DM; all patients were in metabolic balance and none of them had hypertension. Exchangeable body sodium (NaE was estimated by isotope dilution, using appr. 1.1 Mbq 24NA. In a subset of 8 IDDM and 8 NIDDM patients atrial natriuretic peptide (ANP) plasma concentration was determined prior to and after the infusion of 2000 ml physiological saline over 2 hr. NaE was significantly increased both in IDDM and NIDDM patients (104.4 +/- 11.4% and 109.9 +/- 8.0% of the normal value for healthy subjects of identical body surface area; p < 0.05 and < 0.001 resp.). Mean blood pressure (MBP) correlated significantly with NaE in both groups (r = 0.364 and r = 0.520; p < 0.05 and < 0.025, resp.) but not in healthy control subjects (r = 0.112; N.S.). Resting ANP levels were not significantly different in IDDM (34.9 +/- 11.3 pg/ml), NIDDM (42.6 +/- 11.7 pg/ml) or control subjects (40.9 +/- 17.2 pg/ml) however the infusion of saline resulted in a significantly greater increase of plasma ANP in the NIDDM patients (to 82.9 +/- 43.2 pg/ml; P < 0.01) than in the controls (55.6 +/- 23.7 pg/ml; P < 0.01) which was associated with a significantly less increase in sodium excretion (UNAV) in the NIDDM patients (+86% vs. 3170%; P < 0.02) indicating down-regulation of ANP receptors in the kidney of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Body sodium, atrial natriuretic peptide and blood pressure in diabetes mellitus. 134 Jun 60

One of the most frequent and important complications of IDDM is hypertension. It begins usually in adulthood and is rare in children. In order to study the behaviour and control of BP in IDDM children and adolescents we analyzed the BP levels of 106 patients (48 males, 58 females; age 1.5-16 yrs) in relation to sex, age, duration of the disease, and different parameters of metabolic control; moreover we studied the modifications of BP levels with years (tracking). BP levels, registered every 3-6 mos, were compared to the standard levels for age of the local population (2000 students between 7 and 16 yrs of age) and expressed as standard deviation scores (SDS) of the means. For each subject a line describing the change of the SDS over time was calculated by the method of least squares: the slope of this line is called trend and represents the tendency of the BP to increase or maintain stable or decrease with time, i.e to develop or not hypertension. All patients, except one 16 y. old girl, had normal BP and no microalbuminuria, but 10 of them presented with mean levels in the upper quartile and a constantly upward BP trend. Two of these patients showed after a 2 year follow-up stable hypertension and microalbuminuria. Moreover, an analytical and statistical study pointed out that BP levels of IDDM children seem to be influenced in addition to age, sex, height, weight, ponderal excess, as the general population, by the duration of the disease the insulin dose and some metabolic parameters (HbA1, HbA1c, glycemia, creatininemia).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Blood pressure tracking in juvenile insulin dependent diabetes mellitus: preliminary data. 134 Jun 64

Although no distinct advantage of Human insulin (HI) over mixed Bovine-Porcine insulin (BPI) including antigenicity has been noted, initiation of therapy with HI in subjects with new onset IDDM as well as changeover from BPI to HI regimen even in subjects with well controlled DM with BPI has recently become a routine clinical practice. In this study, we assessed metabolic control by determination of fasting plasma glucose and HbA1C levels as well as serum cholesterol and triglyceride concentrations in 12 men and 2 women (ages 43-74 yrs) with uncontrolled DM while receiving BPI and again at the end of 6 months following changeover to HI with identical insulin regimen in terms of the type of insulin as well as the dosage. The subjects were divided into two groups according to the presence of antibodies to insulin of both bovine and porcine forms in their sera. Metabolic control improved significantly in 6 subjects, with positive antibody titers to bovine-porcine insulin as reflected by lowering of all metabolic parameters (p < 0.05 of all comparisons). However, the remaining 8 subjects with negative antibody titers failed to show a significant change in any of the parameters. Therefore, this study suggests that a changeover from BPI to HI maybe recommended in subjects with presence of BPI antibodies and not in all DM subjects treated with BPI regimen. Moreover, it may be feasible to initiate therapy with BPI regimen in new onset IDDM and change later to HI on occurrence of BPI antibodies; since if HI regimen is used at onset and antibodies to HI develop; the only option available then, may be the increased dosage of HI.
 ...
PMID:Metabolic control following transfer from mixed bovine-porcine insulin to human insulin in subjects with IDDM: influence of the presence of insulin antibodies. 134 15

Lipoprotein(a) [Lp(a)] has been added to the list of independent risk factors for cardiovascular disease (CVD), whose incidence is greater in obese subjects. There are few data available on the serum Lp(a) concentrations in obese individuals with or without insulin dependent diabetes mellitus (NIDDM). We selected 31 obese men with normal glucose tolerance (NGT) tests, 15 obese diabetic men, 14 non obese diabetic men and 17 healthy men as controls. We measured serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin and Lp(a). The mean Lp(a) levels in NGT obese men were 70.00 +/- 13.40 mg/l, which were similar to those found in normal controls (75.98 +/- 24.70 mg/l); significantly higher mean Lp(a) levels were found in obese diabetic men (168.84 +/- 56.43 mg/l) and in non obese diabetic men (240.85 +/- 63.35 mg/l). No significant correlation between Lp(a) levels and age, body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, insulin, was found; only a significant positive correlation between Lp(a) levels and glucose could be revealed (P < 0.05). Since higher levels of Lp(a) were found in NIDDM subjects with or without obesity, we conclude that hyperglycemia may influence the levels of serum Lp(a) facilitating its glycosylation in the liver with the consequence of a decline in its catabolic rate.
 ...
PMID:Serum lipoprotein Lp(a) in obesity. 134 6

Population studies have suggested an increased frequency of small DNA insertions (class I alleles) 5' to the insulin gene in insulin dependent (type I) diabetes mellitus (IDDM). The present study examined this relationship within families. Forty-one families with at least one diabetic offspring were studied. Analysis of the insulin gene polymorphism was performed by digestion of DNA with Bg1I, SstI, RsaI, or PvuII and hybridisation with an insulin gene probe or polymorphic region specific probes. An increased frequency of class I alleles was found among the parents of diabetics (p = 0.02), as well as a trend towards increased frequency of parents homozygous for class I alleles and matings of two homozygous subjects. This increased homozygosity for class I alleles was present in non-diabetic sibs as well (p = 0.01). These results show that ascertainment through an offspring with IDDM selects for families with high frequencies of homozygosity for the class I allele and thus suggests that the insulin gene polymorphism is indeed providing part of the genetic predisposition to IDDM. When the major portion of genetic predisposition is provided by other genes (estimates are that HLA accounts for 30 to 70% in IDDM), identification of additional susceptibility genes becomes difficult. Even when formal linkage analysis is uninformative, our studies indicate that analysis for aggregation of specific alleles within families is a useful approach to this problem.
 ...
PMID:The aggregation of the 5' insulin gene polymorphism in insulin dependent (type I) diabetes mellitus families. 135 34


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