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)

Alterations in the metabolism of glycosaminoglycans (GAG) may play a role in the pathogenesis of diabetic-associated microangiopathy. Consequently, the relationship between diabetic nephropathy and retinopathy and urinary GAG distribution was assessed in 96 IDDM patients in comparison to 103 healthy controls. GAG concentration in 24h urine samples was determined by precipitation with cetylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (P = 0.0008) in urinary GAG excretion between patients (24.3 +/- 1.5 mg/24 h, mean +/- SEM) and controls (16.2 +/- 0.75 mg/24 h) could be detected. In patients with IDDM of longer duration, GAG excretion was increased (< or = 10 yr: 20.8 +/- 2.1 vs > 10 yr: 27.4 +/- 2.1 mg/24 h; P = 0.03). Furthermore, IDDM patients with class 4 nephropathy and retinopathy exhibited a markedly higher GAG excretion compared to those without nephropathy (33.1 +/- 3.0 vs 22.6 +/- 1.7 mg/24 h, P = 0.005) or retinopathy (29.7 +/- 2.8 vs 21.2 +/- 1.7 mg/24 h, P = 0.009). An increased urinary GAG concentration was detected in IDDM patients with albuminuria (> 300 mg/24 h: 29.9 +/- 3.3 vs < 30 mg/24 h: 23.0 +/- 1.7 mg/24 h; P = 0.048), proteinuria (> 0.5 g/24 h: 30.3 +/- 3.7 vs < 0.05 g/24 h: 22.7 +/- 1.6 mg/24 h) and in patients with augmented serum creatinine in comparison to those with normal values (> 0.12 mg/L: 34.9 +/- 2.3 vs < 0.12 mg/L: 22.4 +/- 1.6 mg/24 h; P = 0.01). The results demonstrate a close relationship renal GAG excretion and the presence of microangiopathy in IDDM patients.
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PMID:Diabetic microangiopathy and urinary glycosaminoglycans. 922 10

In a prospective study we have measured serum levels of sex hormone-binding globulin (SHBG), androgens, oestrogens and gonadotropins in 20 male IDDM patients with the aim of evaluating the effect of improved glycaemic control on these levels and to compare the IDDM patients with an age- and weight-matched healthy non-diabetic control group. The patients were chosen from the male IDDM patients attending the outpatient clinic at the Department of Endocrinology, Odense University Hospital. Glycaemic control was optimized by a trained diabetologist according to the patients' measurements of home blood glucose concentrations and reported hypoglycaemic episodes during a three month period. Prior to regulation the patients, compared to healthy control subjects, had significantly higher serum levels of oestrone (0.29 +/- 0.02 vs 0.16 +/- 0.01 nmol/l (Mean +/- SEM), p < 0.01), 17 beta-oestradiol (0.12 +/- 0.01 vs 0.08 +/- 0.01 nmol/l, p < 0.01), dihydrotestosterone (4.20 +/- 0.18 vs 1.66 +/- 0.09 nmol/l, p < 0.01), total testosterone (20.7 +/- 0.9 vs 17.8 +/- 1.1 nmol/l, p < 0.05) and SHBG (42.3 +/- 2.9 vs 15.5 +/- 3.5 nmol/l, p < 0.05), while the calculated free-testosterone was lower (0.34 +/- 0.02 vs 0.40 +/- 0.02 nmol/l, p = 0.068). After regulation, the patients obtained significantly lower levels of glycosylated haemoglobin (10.4 +/- 0.3 vs 8.9 +/- 0.2%, p < 0.005) and serum fructosamine (1.50 +/- 0.05 vs 1.34 +/- 0.04 nmol/l, p < 0.005) on a higher 24 hour insulin dose (52.7 +/- 4.4 vs 59.2 +/- 4.6 IU/24 h, p < 0.005). Levels of free-testosterone (0.41 +/- 0.04 nmol/l), oestrone (0.33 +/- 0.03 nmol/l), oestradiol (0.14 +/- 0.01 nmol/l), delta 4-androstenedione (4.44 +/- 0.43 vs 3.85 +/- 0.42 nmol/l), and prolactin (249 +/- 24 vs 200 +/- 19 mIU/l) increased compared to values obtained before regulation (all p < 0.05). We conclude that SHBG, testosterone, dihydrotestosterone and oestrogen levels are increased in male IDDM patients. High SHBG levels tend to keep the free fractions of sex hormones within normal limits. During improvement of glycaemic control with insulin, levels of free-testosterone and its bioprecursors and metabolites rise. This may partly be due to the increased daily insulin dose and/or to the improvement in glycaemic control itself.
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PMID:Elevated levels of sex hormones and sex hormone binding globulin in male patients with insulin dependent diabetes mellitus. Effect of improved blood glucose regulation. 940 41

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
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PMID:Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus. 944 Apr 74

The effects of insulin-induced hypoglycaemia on the neutrophil respiratory burst were investigated in six patients with type 1 diabetes and six non-diabetic control subjects. Plasma glucose reached similar nadirs in control subjects (0.9 +/- 0.1 mmol 1(-1); mean +/- SEM) and diabetic patients (1.2 +/- 0.2 mmol 1(-1)) (NS). The resting neutrophil respiratory burst was similar in control subjects (1.26 +/- 0.15 mV) and diabetic patients (1.03 +/- 0.18 mV) (NS). The neutrophil respiratory burst fell following hypoglycaemia in control subjects and diabetic patients to 0.38 +/- 0.05 mV (P < 0.001) and 0.54 +/- 0.09 mV (P < 0.05), respectively. This fall was significantly greater in control subjects (ANOVA; P < 0.001). Resting neutrophil counts were not significantly different in control subjects (3.2 +/- 0.3 x 10(9) 1(-1)) and diabetic patients (6.1 +/- 1.5 x 10(9) 1(-1)). Following hypoglycaemia, neutrophil numbers increased in control subjects and diabetic patients to 11.5 +/- 1.4 x 10(9) 1(-1) (P < 0.01) and 9.7 +/- 1.7 x 10(9) 1(-1) (P < 0.05), respectively. This increase was significantly greater in control subjects (ANOVA; P < 0.001). These results suggest that the neutrophil respiratory burst is suppressed in response to hypoglycaemia and that this phenomenon is more pronounced in non-diabetic subjects.
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PMID:Attenuated neutrophil respiratory burst following acute hypoglycaemia in diabetic patients and normal subjects. 945 68

The Schwabing Insulin Prophylaxis Trial is a randomised, controlled pilot study designed to examine whether insulin therapy can delay or prevent the clinical onset of Type I diabetes in high risk first degree relatives of people with the disease. First degree relatives of patients with Type I diabetes, who were aged 4 years or more, had an islet cell antibody (ICA) value more than 20 Juvenile Diabetes Foundation Units (JDF-U), a reduced first phase insulin response (FPI) to an i.v. glucose tolerance test less than the 5th centile, and a normal oral glucose tolerance test were eligible for the trial. Between January 1989 and October 1995, 1736 relatives of patients with Type I diabetes were screened for ICA. We identified 64 cases (3.7%) with ICA values more than 20 JDF-U. Of ICA positive relatives, 17 (27%) had a low FPI and were eligible for enrolment. Of these 14 agreed to participate, of whom 7 were randomised to the treatment group and 7 to the control group. In the treatment group, human insulin was administered i.v. by continuous infusion for 7 days, followed by daily s. c. injections for 6 months. Intravenous insulin infusions were repeated every 12 months. In the treatment group 3 of the 7 individuals (follow-up from time of eligibility: 2.3 to 7.1 years) and in the control group 6 of the 7 untreated individuals (1.7 to 7.1 years) developed clinical diabetes. Life table analysis showed that clinical onset of Type I diabetes was delayed in insulin-treated subjects compared with control subjects (means+/-SEM diabetes-free survival: 5.0+/-0.9 years vs 2.3+/-0.7 years, p < 0.03). Insulin levels after i.v. glucose increased in the first year of intervention therapy. Titres of ICA, and antibodies to glutamic acid decarboxylase, and tyrosine phosphatase-like protein IA2 remained unchanged. These data suggest that insulin prophylaxis can delay the onset of overt diabetes in high risk relatives. This is encouraging in view of 1) the continuing American Diabetes Prevention Trial, which is currently testing the effect of parenteral insulin in a large nation-wide study and 2) the initiation of pilot trials to determine whether new antigen-specific intervention is more effective in delaying the clinical onset of Type I diabetes.
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PMID:Delay of type I diabetes in high risk, first degree relatives by parenteral antigen administration: the Schwabing Insulin Prophylaxis Pilot Trial. 962 70

To assess the effect of simvastatin on fasting and postprandial triglyceride (TG)-rich lipoproteins in subjects with type 1 diabetes and elevated LDL cholesterol levels, eight patients participated in a simvastatin versus placebo, randomized, crossover study. At the end of each drug period fasting and postprandial lipoprotein studies were undertaken. Fasting plasma total and LDL cholesterol and apolipoprotein B (apo B) were significantly lower on simvastatin compared to placebo. Postprandial studies: simvastatin versus placebo consistently decreased the area under the curve (AUC, mean+/-SEM) of TG in plasma (12.52+/-9.07 versus 18.70+/-10.48 mmol x h/L, p = 0.02). Similarly, TG AUC was lower: in the chylomicron subfraction (Sf > 400) 3.24+/-2.71 versus 5.27+/-4.61 mmol x h/L p = 0.03; and in the [chylomicron remnant + VLDL] subfraction (Sf 20-400) 3.98+/-2.51 versus 7.04+/-3.88 mmol x h/L, p = 0.01. This was due to decreased particle n umber rather than size, as shown by a decrease in the AUC of apo B in Sf 20-400 (600+/-360 versus 980+/-600 mg x h/L, p = 0.02) and the lack of change in the ratio of TG/apo B. Intestinal lipoproteins contributed to the simvastatin effect, as shown by the lower AUC of retinyl esters in both subfractions. Chylomicrons: 627.61+/-363.43 versus 948.19+/-568.34 nmol x h/L, p = 0.02 and remnants: 129.23+/-67.12 versus 208.49+/-92.11 nmol x h/L, p = 0.04. Our data suggest an additional mechanism by which simvastatin can decrease the risk of atherosclerosis in patients with type I diabetes: a decrease of the number of circulating intestinal and hepatic postprandial TG-rich lipoprotein particles.
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PMID:Effects of simvastatin on fasting and postprandial triglyceride-rich lipoproteins in patients with type I diabetes mellitus. 1043 74

Thiamine plays an important role in the regulation of glucose metabolism and pancreatic beta-cell functioning. A role for this vitamin in cellular glucose transport has been indicated in the literature. The aim of this study was to determine whether a lipophilic form of thiamine (benzoyloxymethyl-thiamine, BOM) was able to improve metabolic control in patients with long-standing insulin-dependent diabetes mellitus (type 1). A total of 10 children with type 1 diabetes of long duration (age 11.4 +/- 1.2 years, duration of the disease 4.5 +/- 0.7 years, means +/- SEM) were studied before and after treatment with BOM in a randomized double-blind and placebo-controlled study. Five patients were assigned to the BOM-treated group and five to the placebo-group. In all patients basal and glucagon-stimulated C-peptide secretion was undetectable. Thiamine status was assayed by measuring the plasma content of thiamine and its monophosphate form at entry and after 3 months of treatment. The blood HbA(1C) levels and the daily dose of insulin per kg body weight were assessed in both groups before treatment, after 1 month and 3 months of treatment, then 3 months following its suspension. The plasma content of thiamine + thiamine monophosphate in type 1 diabetic patients (35.3 +/- 3.6 pmol/mL) was significantly lower when compared with that measured in six age-matched normal subjects (53.2 +/- 2.3 pmol/mL, P < 0.05).
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PMID:Lipophilic thiamine treatment in long-standing insulin-dependent diabetes mellitus. 1119 26

The insulin tolerance test (ITT) is regarded the gold standard for assessing growth hormone (GH) release in adult patients with suspected GH deficiency. Some of these patients also have diabetes mellitus. There are contradictory reports regarding the GH response to ITT in type 1 diabetic patients with varying degrees of metabolic control. This is also true for the clonidine test. We studied ten patients with uncomplicated type 1 diabetes mellitus during periods of poor and improved metabolic control and compared them with ten healthy control subjects. The GH secretion was assessed by an ITT with an insulin infusion of 2.5 mU/kg/min and an intravenous clonidine test. The GH response to ITT was similar during poor and improved metabolic control (mean +/- SEM) (AUC 2327 +/- 616 vs. 2649 +/- 508 microg/l x min) and did not differ from the response in control subjects (AUC 2587 +/- 343 microg/1 x min). The clonidine test induced a significantly greater GH response during poor than during improved metabolic control in the diabetic patients (AUC 2598 +/- 492 vs. 1508 +/- 368 microg/l x min, p < 0.05); this response was greater than in the control subjects (670 +/- 226 x microg/l x min, p < 0.005 vs. improved metabolic control). Thus, the GH response to ITT is similar in diabetic patients with varying degrees of metabolic control and healthy subjects, while the GH response to the clonidine test is higher in the type 1 diabetic patients than in healthy controls.
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PMID:Growth hormone response to the insulin tolerance and clonidine tests in type 1 diabetes. 1053 50

Secretion of leptin, the obese gene product, is stimulated by insulin and glucocorticoids and reduced by fasting. In subjects with diabetic ketoacidosis (DKA), severe insulinopenia and prolonged fasting might cause a decrease in serum leptin levels, and subsequent insulin therapy would reverse the decrease. Otherwise, some other confounding factors, neither insulin nor fasting, might affect serum leptin levels in patients with DKA. The present study was undertaken to address these issues. Eleven patients with type 1 diabetes mellitus (seven males and four females, aged 44+/-6 years, mean +/- SEM), admitted to Jichi Medical School Hospital presenting DKA, were studied during the therapeutic period. Thirty-five sex-, age- and body mass index-matched healthy subjects served as controls. Serum leptin levels at the hospitalization were significantly greater than those of the matched control subjects (5.5+/-1.0 vs. 3.2+/-0.3 microg/l, P < 0.01). After the start of therapy with a small dose of short-acting insulin and a large volume of fluid infusion, serum leptin concentrations further increased to 10.6+/-3.6 microg/l at 24 h, and thereafter the concentrations gradually decreased and normalized at the discharge (3.3+/-0.7 microg/l, day 24+/-4). The peak levels at 24 h were significantly higher than the levels at the discharge (P < 0.05), and also +77+/-34% higher than those at the hospitalization (P < 0.005). Serum cortisol levels (1830+/-200 nmol/l) were markedly elevated at hospitalization. These results indicate that serum leptin levels are increased even under insulinopenia and fasting in the patients with DKA. Such a finding may be associated with marked hyperglycemia or enhanced secretion of glucocorticoid hormone, although the exact mechanisms remain to be elucidated. We speculate that leptin may serve as a stress peptide in DKA, but further analysis is necessary to explore a physiological role of leptin in DKA.
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PMID:Serum levels of leptin and changes during the course of recovery from diabetic ketoacidosis. 1058 Jun 17

The objective of the present study was to compare the effects of two diets on the atherogenic potential of two VLDL subfractions harvested from fasting subjects by measuring the number and composition of particles and the amount of esterified cholesterol accumulated in macrophages. A high (25%) monounsaturated fatty acid (Mono) diet and a high (61%) carbohydrate (CHO) diet were provided for 4 wk in a randomized crossover design to 19 normolipidemic, nonobese patients with type 1 diabetes. The two diets were matched for protein, polyunsaturated/saturated fatty acids, cholesterol and fiber content. The number of circulating big VLDL (S:(f) 100-400) particles was greater during the high Mono than during the high CHO diet based on the levels of apolipoprotein B (means +/- SEM): 31.4 +/- 7.4 versus 20.0 +/- 3.8 mg/L (P: < 0.025, paired t test). The following variables did not differ during the diet periods: number of small VLDL (S:(f) 20-100) particles, esterified cholesterol accumulated in THP-1 macrophages incubated with the same number of big and small VLDL particles and particle composition. We conclude that a high CHO diet might be preferable to a high Mono diet, on the basis of the premise that more big VLDL particles could increase the atherosclerotic risk in patients with diabetes.
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PMID:A high carbohydrate versus a high monounsaturated fatty acid diet lowers the atherogenic potential of big VLDL particles in patients with type 1 diabetes. 1101 81


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