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)

In order to identify factors other than the HLA-linked susceptibility involved in the risk to the siblings of diabetic children, we compared the age at onset, birth order and HLA genotypes in 23 IDD multiplex (Mx) families and 140 simplex (Sx) families. The results showed a relationship between age and recurrence risk in sibs. Probands (= 1st affected sibs) of Mx families were significantly younger at onset (5.8 +/- 0.8 yr) than probands of Sx families (9.0 +/- 0.4 yr, p less than 0.01). The 2nd affected sibs of Mx families, although affected at an older age (12.4 +/- 1.6 yr), had been significantly younger at the time of the proband's onset, than the siblings who have remained unaffected (6.2 +/- 1.2 vs 11.5 +/- 0.5 yr, p less than 0.01). Probands of Mx families were more often the first born and probands of Sx families, more often came later in the birth order (p less than 0.02). Prevalence of IDD was higher among siblings born after than among those born before the proband (12% vs 4%, p less than 0.002). The HLA haplotype distribution in unaffected siblings deviated from the random assortment in relation to birth order, showing an excess of HLA-identical sibs born before the proband and, inversely, an excess of non-identical sibs born after the proband. The results suggest that age-dependent factors are likely to increase the penetrance of HLA-linked IDD susceptibility. These factors could be related to the environmental insult. However, a genetically determined form of type I diabetes characterized by higher familial penetrance and earlier onset cannot be ruled out.
Diabetes Res 1984 Sep
PMID:Evaluation of recurrence risk in siblings of diabetic children: importance of age and birth order in relation to HLA genotypes. 633 86

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.
Diabetes Care
PMID:Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients. 675 99

Erythrocyte deformability measured as filtration index is clearly diminished in diabetics, thus possibly contributing to diabetes-associated microvascular complications. Moreover, the erythrocyte sorbitol level in IDD is clearly higher than that of non-diabetics, suggesting an alteration in the polyol pathway as possible determinant of diabetes-associated complications. Following this line of research, intracellular sorbitol as well as glucose, inositol, galactitol, mannitol and 2,3-diphosphoglycerate have been studied in 21 diabetics and in 14 controls matched for age and sex. In addition to confirming the high levels of intraerythrocytic glucose and sorbitol in diabetic subjects, statistically significant correlations have been demonstrated between sorbitol and filtration index, between plasma glucose, intracellular glucose level and glycosylated hemoglobin, suggesting a relationship between metabolic control and hemorheologic alterations in diabetes.
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PMID:Role of red cell sorbitol as determinant of reduced erythrocyte filtrability in insulin-dependent diabetics. 675 60

The mechanisms contributing to the impairment in glucose metabolism in non-insulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, and diabetic ketoacidosis are summarized in Table 2. Impaired insulin secretion is characteristic of patients with IDD and DKA. In contrast, insulin secretion in NIDD may be normal, increased, or decreased. Peripheral tissue resistance to the action of insulin is present in all three diabetic conditions; it is moderate in NIDD and IDD and severe in DKA. Basal hepatic glucose production in NIDD and IDD can be either normal or increased, and correlates closely with the fasting plasma glucose concentration. In DKA, HGP is elevated. Suppression of HGP by insulin is normal in NIDD and IDD but severely impaired in DKA. Hepatic glucose uptake following oral glucose is decreased in NIDD; hepatic uptake of ingested glucose has not been examined in IDD and DKA.
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PMID:Insulin resistance: a universal finding in diabetic states. 682 Sep 36

The C-peptide is a polypeptide generated from enzymatic cleavage of proinsulin into insulin in pancreatic B. cell. C-peptide and insulin are secreted in an equimolar ratio. For this reason. C-peptide radio-immunoassay in blood or urine reflects the insulin secretion when direct insulin determination cannot be done (insulin treatment, circulating insulin antibodies). This assay is mainly used in clinical and investigational studies of insulin dependent diabets. It enabled demonstation of residual secretion of insulin in numerous insulin dependent patients (70% during the first year and 15% after the 15th year of the disease). Persistence of insulin secretion may play a role in the natural history of diabetes since patients with detectable C-peptide immunoreactivity have more stable diabetes, are controlled by lower insulin dose and are less ketosis prone than the others. Factors which influence persistence of B. cell activity in some IDD remain unknown.
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PMID:[The clinical value of C-peptide assay (author's transl)]. 700 55

Thirty-seven children and youths were ascertained because of stress hyperglycemia (3), asymptomatic glucosuria (21), or symptoms suggestive of hypoglycemia (13); 17 of them met the National Diabetes Data Group criteria for impaired glucose tolerance. Three ascertained because of glucosuria developed symptomatic insulin-dependent diabetes over the subsequent 14 months. They had more severe hyperglycemia and/or deficient insulin responses compared to those with normal tests or those with IGT who did not develop IDD. Insulin responses relative to glycemia were significantly age related and did not differ between the normal and IGT groups (excluding the three who developed IDD). The two-hour oral glucose tolerance test may be of value in young persons who have had stress hyperglycemia or asymptomatic glucosuria to rule out abnormality in a standardized manner or to detect preclinical IDD. Patients with autonomic symptoms may have transitory IGT as a concomitant manifestation of life stress; glucose tolerance testing of them appears unwarranted in the absence of other compelling symptoms or a family history of IDD.
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PMID:Prognosis of imparied glucose tolerance in children with stress hyperglycemia, symptoms of hypoglycemia, or asymptomatic glucosuria. 710 55

We examined HLA Class II antigens in 116 Japanese IDDM patients [84 typical IDDM (T-IDD); 32 slowly progressive IDDM (S-IDD)] by the hybridization protection assay (HPA) which is a novel HLA typing method based on hybridization of acridinium-ester-labeled DNA probes to amplified DNA. We detected HLA-DRB1, -DQA1 and -DQB1 genes by this method which is capable of analyzing over 50 samples within 4 h with high sensitivity. Positive associations were found in DRB1*0405, DRB1*0802, DRB1*0901, DQA1*0301, DQB1*0303 and DQB1*0401, negative correlations in DRB1*0403, DR2, DR12, DRB1*0801 or 03, DQA1*0101 or 02, DQA1*0501, DQB1*0301 and DQB1*0602 alleles. The absence of aspartic acid (Asp) at position 57 of the DRB1 chain and the presence of arginine (Arg) at position 52 of the DQA1 chain correlated positively with both types of IDDM. There were no significant differences in HLA between T-IDD and S-IDD. These results suggest that the absence of Asp at position 57 of the DRB1 chain and the presence of Arg at position 52 of the DQA1 chain are significant Japanese IDDM patients and that DRB1*0802, in which the amino acid at position 57 is aspartic acid, may play a role in the pathogenesis of IDDM. Also, T-IDD and S-IDD have common bases in the HLA gene.
Diabetes Res Clin Pract 1994 Mar
PMID:Analysis of MHC class II antigens in Japanese IDDM by a novel HLA-typing method, hybridization protection assay. 807 Mar 5

Diabetes mellitus has been reported to have controversial effects on left ventricular (LV) function in patients with no evidence of coronary artery disease. In this study, LV function at rest was evaluated in 2 groups of diabetic patients, with insulin-dependent (IDD; n = 16) and non-insulin-dependent (NIDD; n = 23) diabetes mellitus, with no evidence of coronary artery disease. All patients underwent an electrocardiographic stress test, and first-pass and equilibrium radionuclide angiography at rest and during supine exercise. Data in each group of diabetic patients were compared with those obtained from age- and sex-matched normal subjects. In both groups of diabetic patients plasma catecholamine levels were significantly greater than in control subjects. Ejection fraction at rest and during exercise did not differ between each group of diabetic patients and their respective control group. In patients with IDD, peak ejection rate (4 +/- 1 end-diastolic count/s) was significantly greater than in control subjects (2.6 +/- 0.1 end-diastolic count/s; p < 0.001); similarly, peak filling rate (4.3 +/- 1.0 end-diastolic count/s) was significantly greater than in controls (3.0 +/- 0.2 end-diastolic count/s; p < 0.001). Cardiac output and systemic vascular resistances did not differ between patients with IDD and control subjects. In contrast, patients with NIDD had significantly reduced cardiac output compared with that of control subjects (5.7 +/- 0.2 vs 5.9 +/- 0.2 liter/min; p < 0.01), and increased systemic vascular resistances (1,422 +/- 137 vs 1,314 +/- 68 dynes.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of left ventricular function in insulin- and non-insulin-dependent diabetes mellitus. 843 Jun 28

Insulin-dependent (Type 1) diabetes (IDD) in the NOD mouse is inherited as a complex polygenic trait making the identification of susceptibility genes difficult. Currently none of the non-MHC IDD susceptibility genes in NOD have been identified. In this paper we describe the congenic mouse approach that we are using for the dissection of complex traits, such as IDD. We produced a series of six congenic strains carrying NOD-derived diabetogenic genomic intervals, which were previously identified by linkage analysis, on a resistant background. These congenic strains were produced for the purpose of characterizing the function of each of these genes, alone and in combinations, in IDD pathogenesis and to allow fine mapping of the NOD IDD susceptibility genes. Histological examination of pancreata from 6 to 8-month-old congenic mice reveals that intervals on Chromosomes (Chrs) 1 and 17, but not 3, 6, and 11, contain NOD-derived genes that can increase the trafficking of mononuclear cells into the pancreas. Insulitis was observed only very rarely, even in older congenic mice, indicating that multiple genes are required for this phenotype. These results demonstrate the utility of this congenic approach for the study of complex genetic traits.
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PMID:Production of congenic mouse strains carrying NOD-derived diabetogenic genetic intervals: an approach for the genetic dissection of complex traits. 866 24

In a group of 365 subjects, 75 years old and ultra, living in Troina (Sicily), a study on prevalence of dementia has been carried out. In the questionnaire, used to collect information about subjects' health, one of the questions concerned the assumption of drugs. The interviewer transcribed the name of the drugs and then coded the related chemical-pharmacological classification, according to the 14 principal groups of the guide of the National Health Service. Up to 9 drugs, on a daily basis, were registered. The total amount of prescriptions was 889, equal to 2.4 per person, with a clear prevalence of the females. 26.1% of the sample did not take any drug. The mode of assumptions was 3 a day. The cardiovascular system is at the top of prescriptions, with 39% of the total, followed by the gastroenteric apparatus and metabolism (17.9%), the nervous system (16.7%), the haemopoietic system (8.4%), the musculo-skeletal system (6.2%), the respiratory apparatus (5.7%), and so on the others. For each principal group of drugs, those more represented are identified, obtaining other information about the practitioners' choices. Among the principal subgroups of cardiovascular system, it is worth mentioning anti-hypertensives, diuretics and antianginal, each of them with their own subgroups. In the gastroenteric apparatus and metabolism group, the latter comprises the drugs for the treatment of diabetes: oral hypoglicaemics and insulin. These drugs allow to identify 34 cases of diabetes: 29 NIDD and 5 IDD. Analogous evaluations for drugs of other groups and comparisons with a few data available in literature are carried out. Surveying the drugs used in a population is useful: (i) to evaluate the health state; (ii) to identify the dominant disease; (iii) to draw comparisons with other populations; (iiii) to follow the evolution of pharmacotherapy.
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PMID:Home pharmacological therapy in an ultra-75 years old population in Troina (inner Sicily). 963 Jul 56


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