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)

Human intoxication with the rodenticide Vacor [N-3-pyridylmethyl-N'-p-nitrophenyl urea or 1-(4-nitrophenyl)-3-(3-pyridylmethyl) urea] induces acute IDDM. We report here that Vacor specifically inhibits the NADH:ubiquinone reductase activity of complex I in mammalian mitochondria. The activity of other respiratory enzymes of mitochondria is unaffected by Vacor at concentrations that completely inhibit the redox and energetic function of complex I. Vacor inhibition of complex I activity quantitatively correlates with the inhibition of insulin release in insulinoma cells and pancreatic islets and is also consistent with the doses reported in cases of human poisoning. These results indicate that the toxic and diabetogenic action of Vacor primarily derives from the inhibition of mitochondrial respiration of NAD-linked substrates in the high-energy demanding cells of the pancreatic islets. This newly identified mechanism of the pathological effects resulting from Vacor intoxication could constitute a paradigm in which to understand environmental or metabolic causes of IDDM.
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PMID:Inhibition of mitochondrial complex I may account for IDDM induced by intoxication with the rodenticide Vacor. 886 57

In Jamaica, malnutrition related diabetes mellitus (MRDM) presents the clinical picture of phasic insulin dependence. This study was undertaken to investigate nephropathic changes associated with this group of patients. Fourteen phasic insulin dependent diabetes mellitus (PIDDM) patients were compared with 10 insulin dependent (IDDM) and 10 non-insulin dependent (NIDDM) diabetes mellitus patients, and 10 normal controls. Each group was matched for age, sex, body mass index (BMI) and, in the case of the diabetic patient controls, duration of diabetes. Urinary microalbumin concentration was significantly (p < 0.05) higher in the PIDDM group (mean +/- SD: 153 +/- 48.3 mg/dl) than in the groups of NIDDM (35.7 +/- 9.6 mg/dl) or IDDM (38.6 +/- 15.8 mg/dl) patients. Serum urea and creatinine concentrations (mean +/- SE 7.6 +/- 1.0 mmol/l and 130.0 +/- 20.3 mumol/l, respectively) were higher in the PIDDM patients than in the NIDDM and IDDM groups. Confounding factors such as hypertension and urinary tract infections were excluded as causes for these differences. We conclude that PIDDM patients have more severe renal dysfunction than NIDDM patients and, since glycosylated haemoglobin concentrations are comparable in these groups, we attribute this to a renal insult due to malnutrition predating the onset of the PIDDM.
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PMID:Kidney function in phasic insulin dependent diabetes mellitus in Jamaica. 914 47

The Kidd blood group locus encodes a urea transporter which is expressed on human red cells and in the kidney. This gene is located on chromosome 18q12, and evidence for linkage and association with type 1 diabetes mellitus has been reported. To investigate this further, the genetic basis for the blood group Jk(a)/Jk(b) polymorphism was first determined by sequencing reverse-transcribed reticulocyte RNAs from Jk(a+b-) and Jk(a-b+) donors. The Jk(a)/Jk(b) polymorphism was caused by a transition (G838A), resulting in a Asp280Asn amino acid substitution and an MnlI restriction fragment length polymorphism (RFLP). Using the MnlI RFLP, we found that the Jk(a)/Jk(b) polymorphism was not in linkage disequilibrium with type 1 diabetes in 228 multiplex UK and US families tested.
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PMID:The molecular basis of the Kidd blood group polymorphism and its lack of association with type 1 diabetes susceptibility. 921 69

We assessed the relationship between erythrocyte Na+/H+ antiport activity and myocardial anatomical-functional parameters (by Doppler echocardiography) in normotensive IDDM patients, with and without microalbuminuria. We studied 33 normotensive IDDM subjects and 14 matched healthy controls (group 4). Based on urinary albumin excretion rate (UAER), 23 diabetics were normoalbuminuric, 10 microalbuminuric (group 3). Normoalbuminurics were divided up for normal (group 1, n = 13) or high (group 2, n = 10) antiport activity. We evaluated fasting glycaemia and 24-h urine glucose output, HbA1c, plasma lipids, urea, creatinine and electrolyte clearances, UAER, erythrocyte Na+/H+ countertransport, M-Mode and 2D echocardiograms with Doppler analysis. Antiport, which was higher in diabetics than controls, was significantly overactive in groups 2 and 3 vs group 4, independently from UAER. Diabetics showed left ventricular volume, cardiac mass and systolic function within the control range. In left ventricular diastolic filling, while peak E was similar in diabetic and healthy people, the late peak transmitral flow velocity (peak A) was significantly higher in diabetics than controls, and this was also true in groups 2 and 3 vs group 4. Antiport activity was positively related to peak A (p < 0.03). These observations suggest that (a) the Na+/H+ antiport may be overactive in diabetes, apart from microalbuminuria; (b) increased Na+/H+ antiport activity, in normotensive IDDM people, may be associated with preclinical diastolic myocardial dysfunction ("incipient diabetic cardiomyopathy"?).
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PMID:Erythrocyte Na+/H+ exchange and preclinical abnormalities of the left ventricular diastolic function in normotensive type 1 (insulin-dependent) diabetic patients. 940 45

Thirty-two patients with diabetes mellitus (22 IDDM and 10 NIDDM, 21 males and 11 females, age 44+/-11.8 years) were followed for 5.2+/-3.8 years after the onset of chronic renal failure, with the aim of evaluating the effect of low protein diets on the rate of decline of the residual renal function. During the 1.8+/-1.6 year follow-up period on free or uncontrolled low protein diet the mean rate of decline of creatinine clearance was 0.9+/-0.6 ml/min/month, significantly greater than that observed during 3.7+/-3.1 years on low or very low protein diets. The reduction of protein intake was followed by a significant decrease in daily urinary protein loss. A better glycaemic control was obtained on the low protein diet, and the daily insulin requirement decreased. The anthropometry, as well as the serum concentrations of rapid turnover proteins, did not change, in spite of the low or very low protein dietary supply for a long duration. The values of mean arterial pressure were quite similar during the follow-up period on free or uncontrolled low protein diet and during the study period on the low protein diet. A good compliance with reduced dietary intake (as demonstrated by the measurement of the daily urea excretion) was obtained in a large number of patients. In conclusion, our study confirms the protective effect on the residual renal function of low protein diets in IDDM and NIDDM patients with chronic renal failure due to diabetic nephropathy, in the absence of any sign of protein malnutrition.
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PMID:Dietary treatment of diabetic nephropathy with chronic renal failure. 987 Apr 26

Insulin-dependent diabetes mellitus (IDDM) is rare in Chinese children. There have been no reports on the prevalence of peripheral neuropathy in Chinese children with IDDM. This study aimed to determine prevalence of subclinical peripheral neuropathy in Chinese children with IDDM. Motor and sensory nerve conduction studies of both median, ulnar, peroneal, and tibial (motor nerves) and median, ulnar, and sural (sensory nerves) were performed in 38 children with IDDM (18 males, 20 females). The age was 4-21 years (mean = 12.7 years; median = 12 years, 6 months). The duration of diabetes was less than 5 years in 15, 5-10 years in 14, and more than 10 years in nine. Neurophysiologic evidence of subclinical peripheral neuropathy was present in 26 patients (68.4%) of which motor, sensory, or motor and sensory involvement was 26 (68.4%), eight (21.1%), and 26 (68.4%), respectively. Twelve (31.6%) and 14 (36.8%) children had mild and moderate degrees of peripheral neuropathy, respectively. Among the 26 children with abnormal nerve-conduction studies, two (7.7%) had symptoms of numbness and pain in the lower limbs. Thus, two children had symptomatic neuropathy and most (n = 24) had asymptomatic peripheral neuropathy. Two children had systemic hypertension, and one (3.8%) had laboratory evidence of early renal complications. Analysis of demographic and laboratory risk factors for the development of subclinical peripheral neuropathy revealed that the age of onset, duration of diabetes, level of hemoglobin A1c, triglyceride, cholesterol, serum creatinine, and urea, microalbumin/creatinine ratio, and urinary microalbumin excretion rate were significantly related to the development of subclinical peripheral neuropathy in specific nerves.
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PMID:Prevalence of peripheral neuropathy with insulin-dependent diabetes mellitus. 1020 29

We assessed clinical and biochemical predictors of death and/or cardiovascular disease in 147 type 1 diabetes mellitus (DM) patients followed-up for 14 years. At follow-up, 28 of patients (19%) had died, and 25 patients (18%) had developed or died of coronary artery disease (CAD). At baseline, those who died had significantly higher serum creatinine (p=0.001) and urine albumin/creatinine ratio (p=0.016), greater prevalence of retinopathy (p=0.006), lower serum apolipoprotein A1 (p=0.046), and lower daily insulin dose (p=0.024) than those who survived. CAD patients had a longer duration of diabetes (p<0.001), were older at the onset of diabetes and at presentation (p=0.001), and had higher prevalences of retinopathy (p=0.005) and neuropathy (p=0.016). The CAD group also had higher baseline serum creatinine (p=0.02), lower HDL cholesterol (p=0.004) and apolipoprotein A1 (p=0.007) and higher LDL cholesterol (p=0.028) and apolipoprotein B concentrations (p=0.027). Under logistic regression analysis (adjusted for age and sex), baseline urine albumin/creatinine ratio (p=0.003), presence of retinopathy (p=0.004), serum creatinine (p=0.028), and serum urea (p=0.034) were the most powerful predictors of mortality, while duration of diabetes (p<0.0001), baseline HDL cholesterol (p=0.012), serum creatinine (p=0.02), apolipoprotein B (p=0.038), LDL cholesterol (p=0.039), and systolic blood pressure (p=0.055) were the strongest predictors of CAD. These findings emphasize the role of abnormal lipoprotein metabolism in the development of CAD in type 1 DM. Indicators of renal impairment and the presence of retinopathy seem to be of greater importance in predicting overall mortality.
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PMID:Long-term predictors of coronary artery disease and mortality in type 1 diabetes. 1170 92

Diabetes develops in more than half of the patients with chronic alcoholic pancreatitis (CAP), mostly due to increasing insulin deficiency. In this regard CAP-related diabetes (CAP-DM) is similar to the type 1 diabetes. Data on microvascular complications in CAP-DM are scarce. The aim of the study was the analysis of microvascular complications frequency in relation to metabolic control in comparison with type 1 diabetes mellitus. The study subjects were 50 patients divided into two groups: group 1-25 patients with CAP-DM (15 men, 10 women, mean age 44.6 +/- 8.4 yrs, duration of diabetes 3.7 +/- 2.1 yrs, body mass index (BMI) 22.4 +/- 2.9 kg/m2, duration of CAP 7.0 +/- 3.5 years), and group 2-25 well-matched type 1 diabetes patients (14 men, 11 women, mean age 42.3 +/- 7.6 yrs, duration of diabetes 4.1 +/- 2.8 yrs, BMI 24.0 +/- +/- 2.5 kg/m2). CAP was diagnosed on the basis of clinical examination, ultrasound and computed tomography scans, and in some cases upon the results of endoscopic retrograde pancreatography. Fasting plasma glucose, glycated hemoglobin (HbA1c), total serum cholesterol, triglycerides, urea and creatinine concentrations were measured. Fundoscopy was performed in all the subjects, in addition fluorescein examination was conducted in 15 and 18 patients from groups 1 as 2 respectively. Fasting plasma glucose, HbA1c level and insulin requirement were significantly lower in CAP-DM patients than in type 1 diabetes subjects (133 +/- 48 vs 174 +/- 59 mg/dl, p < 0.01; 8.3 +/- 2.0 vs 9.8 +/- 1.1%, p < 0.01; 36 +/- 15 vs 57 +/- 11 IU/day, p < 0.001 respectively). However, the prevalence of background retinopathy (group 1-13/25, group 2-11/25), and microalbuminuria (group 1-14/25, group 2-13/25) was similar in both groups. No statistically significant differences were found between CAP-DM and type 1 diabetic patients in regard to blood lipids, triglycerides, urea and creatinine concentrations. We conclude that microvascular complications may be encountered in pancreatic diabetes as often as in type 1 diabetes. Therefore this particular type of secondary diabetes should be regarded by no means as a "milder" type of the disease.
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PMID:[Microvascular complications in pancreatic diabetes]. 1186 77

Proinflammatory cytokine induction of NO synthesis may contribute to the destruction of pancreatic beta cells leading to type 1 diabetes. The NO synthase substrate arginine can also be metabolized to ornithine and urea in a reaction catalyzed by cytosolic (AI) or mitochondrial (AII) isoforms of arginase. Recent evidence suggests that the rate of NO generation is dependent on the relative activities of NO synthase and arginase. The objectives of this study were (i). to identify the arginase isoforms expressed in rat and human islets of Langerhans and a rat beta cell line, RINm5F and (ii). to investigate the competition for arginine between NO synthase and arginase in IL-1beta-treated rat islets. Arginase activity was detected in rat islets (fresh tissue, 346 mU/mg protein; cultured, 587 mU/mg), cultured human islets (56 mU/mg), RINm5F cells (376 mU/mg), rat kidney (238 mU/mg), and rat liver (6119 mU/mg). Using Western blots, AI was shown to be the predominant isoform expressed in rat islets and in RINm5F cells while human islets expressed far more AII than AI. Rat islets were cultured in medium containing 1.14, 0.1, and 0.01 mM arginine and treated with IL-1beta and the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH). IL-1beta-induced NO generation was unaffected by ABH at 1.14 mM arginine, but significantly increased at 0.1 and 0.01 mM arginine. These findings suggest that the level of islet arginase activity can regulate the rate of induced NO generation and this may be relevant to the insulitis process leading to beta cell destruction in type 1 diabetes.
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PMID:Arginase expression and modulation of IL-1beta-induced nitric oxide generation in rat and human islets of Langerhans. 1244 78

A subtype of idiopathic type 1 diabetes with a rapid onset and no diabetes-related antibodies has been recently advocated as non-autoimmune fulminant type 1 diabetes. However, it is not definite yet that this subtype is always caused by non-autoimmune mechanism. A 48-year-old man was admitted to our hospital because of high plasma glucose and renal insufficiency. Laboratory findings were as follows: plasma glucose 1052 mg/dL, urinary ketone bodies (+/-), arterial blood pH 7.44, bicarbonate 23.8 mmol/L, base excess 0.3 mmol/L, plasma osmolality 342 mOsm/L, serum creatinine 2.1 mg/dL, blood urea nitrogen 69.7 mg/dL, and serum creatine kinase 1024 IU/L, giving a diagnosis of acute renal failure secondary to rhabdomyolysis associated with diabetes. Urinary C-peptide reactivity was 4.7 microg/day. The level of HbAlc was 7.0%, not so high as compared to that of plasma glucose, indicating an aggravation of diabetes within the recent short period. Antibodies to islet cell antigen, IA-2 and insulin were negative, while those to glutamic acid decarboxylase (GAD) were positive at 13.1 U/mL, which were negative half a year and two years and a half later. Serum amylase level was within normal range at admission, increased to 380 IU/L and normalized in 4 to 5 weeks as serum creatinine lowered. These data are compatible to the diagnosis of fulminant type 1 diabetes. However, the present case is different from others in positive antibodies to GAD at admission that turned to be negative subsequently. Considering our results and others together, further investigations are necessary to clarify whether all cases of fulminant type 1 diabetes are non-autoimmune or some of them are caused by autoimmune mechanism.
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PMID:A case of fulminant type 1 diabetes with transiently positive anti-GAD antibodies. 1280 44


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