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 this study, 52 nonproteinuric Japanese patients with non-insulin-dependent diabetes (NIDDM) were followed from 1985 to 1990 to investigate the rate of development and progression of microalbuminuria and the factors which influence it. In 1985, 34 patients were normoalbuminuric, and 18 patients were microalbuminuric. Five years later, 11 of 34 initially normoalbuminuric patients (32.4%) developed microalbuminuria, and 6 of 18 initially microalbuminuric patients (33.3%) developed overt proteinuria. At the beginning of the study, hypertension existed more frequently in the patients who later developed microalbuminuria (8 of 11, 72.7%) than in the patients who stayed normoalbuminuric (4 of 23, 17.4%). Age-adjusted values of mean blood pressure (+/- SEM) at the beginning of the study in the patients who developed microalbuminuria (98.2 +/- 3.4 mm Hg, n = 11) were significantly higher than those in the patients who stayed normoalbuminuric (87.3 +/- 2.4 mm Hg, n = 23). In six patients who developed overt proteinuria, initial urinary albumin excretion rates (AER) were higher than those in the patients who stayed microalbuminuric, and four patients who presented with initial AER greater than 100 micrograms/min all developed overt proteinuria. These results indicate that, in Japanese patients with NIDDM, the rate of development of microalbuminuria is faster than that reported in Caucasian IDDM, and preexisting hypertension with relatively poor control of blood pressure may be a risk factor for the development of microalbuminuria.
J Diabetes Complications
PMID:High blood pressure is a risk factor for the development of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes mellitus. 147 44

Insulin antibodies (IAA) can be detected in the serum of the majority of newly diagnosed IDDM patients prior to insulin therapy. In first degree relatives of IDDM patients, IAA are associated with an increased risk of development of IDDM. However, the disease specificity of IAA, detected by radiobinding assays, has not been addressed. We thus tested sera from patients with autoimmune disease for IAA. One of 29 (3%) patients with Graves' disease and five of 27 (19%) patients with SLE had IAA levels exceeding the range for normal controls. IAA were not detected in sera from 29 patients with Addison's disease, 15 patients with pernicious anaemia or 10 patients with increased gamma globulins. Non-specific binding of 125I-labelled insulin was increased in serum from 14 (21%) samples from patients with Graves' disease, 10 (37%) patients with SLE, one (3.2%) of 29 patients with Addison's disease and two (13%) of 15 patients with pernicious anaemia. The increased non-specific binding most likely relates to immunoglobulin binding as it was also found in eight of 10 patients with oligoclonal or polyclonal increase in gamma globulins. Our findings suggest that moderate elevations of IAA are not uncommon in patients with SLE, in whom increased non-specific binding of insulin is also common. This observation is of importance in preclinical diabetes screening studies.
Diabetes Res Clin Pract 1992 Nov
PMID:Insulin autoantibodies in patients with autoimmune diseases. 147 50

The residual B-cell function was examined by means of the plasma C-peptide response 6 min after a combined injection of glucagon and glucose (GG test) or conventional glucagon test (G test) in four insulin-dependent diabetic patients (IDDM group), in 18 diabetic patients treated with insulin (Insulin group), 31 treated with oral hypoglycemic agents (SU group) and 27 treated with diet only (Diet group) and in 22 borderline cases. By GG test, 6-min C-peptide values of the IDDM group were 0.27 +/- 0.05 nM (n = 4) and were significantly lower than those of the Insulin group (0.89 +/- 0.09 nM, n = 12), the SU group (1.42 +/- 0.10 nM, n = 13), the Diet group (2.47 +/- 0.22 nM, n = 11) and the borderline cases (3.38 +/- 0.22 nM, n = 11). Patients with a 6-min C-peptide concentration below 0.75 nM by GG test appeared to be insulin-requiring patients. In the G test, plasma C-peptide concentrations at 6 min were 0.35 +/- 0.08 nM in the IDDM group (n = 2), 0.72 +/- 0.20 nM in the Insulin group (n = 7), 1.08 +/- 0.09 nM in the SU group (n = 20), 1.40 +/- 0.19 nM in the Diet group (n = 17) and 2.05 +/- 0.21 nM in the borderline cases (n = 12). Some of the Diet group patients showed extremely low C-peptide responses. When comparing the GG test and G test in individual cases, a greater C-peptide response was seen with the GG test in all cases except for IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1992 Nov
PMID:Glucagon-glucose (GG) test for the estimation of the insulin reserve in diabetes. 147 58

The binding characteristics of insulin autoantibodies (IAA) were compared with those of antibodies to exogenous insulin (IBA) by analyzing the specific binding, binding capacity and affinity for insulin in 11 children (age range 1.5-13.0 years) with insulin-dependent diabetes (IDDM) both at diagnosis and after 1 year of insulin treatment. Maximal specific insulin binding was 7.8 (1.5; SE) pmol l-1 for IAA and 28.1 (6.7) pmol l-1 for IBA (P < 0.01), and the binding capacity of the high affinity class of IAA 0.01 (0.003) nmol l-1, as compared with 0.19 (0.08) nmol l-1 for the corresponding IBA class (P < 0.01). With regard to the low-affinity components the binding capacity was 0.11 (0.05) nmol l-1 for IAA and 1.50 (0.95) nmol l-1 for IBA (P < 0.01). No differences in the affinity constants could be observed between IAA and IBA. There was no correlation between the insulin binding of IAA and quantitative levels of islet cell antibodies (ICA) at the clinical presentation or subsequent IBA values. The specific insulin binding of IBA correlated negatively with serum C-peptide concentrations and positively with HbA1 levels at 1 year. The present observations suggest that IAA developing before the diagnosis of IDDM are characterized by a reduced binding capacity as compared with antibodies to exogenous insulin, whereas they have a similar affinity for insulin. IAA seem to be quantitatively unrelated to ICA and postdiagnostic IBA levels. High IBA levels appear to be associated with reduced endogenous insulin secretion and poor metabolic control during the early clinical course of the disease.
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PMID:Autoantibodies to insulin have similar affinity to that of antibodies to exogenous insulin but lower binding capacity. 147 47

Blood glycated haemoglobin (HbAlc), serum fructosamine (FA), serum glycated albumin (GA), and serum glycated total protein (GTP) were determined in 61 subjects (19 pregnant women with gestational diabetes, 24 pregnant women with insulin-dependent diabetes mellitus [IDDM] and 18 nonpregnant subjects with IDDM). FA, GA, and GTP correlated with HbAlc similarly (r = 0.791, 0.816, and 0.794, respectively, p < 0.001). In a subgroup of 22 subjects data on blood glucose home monitoring was recorded and used for calculating mean blood glucose as an index of average glycaemia preceding sampling of the glycation products. Mean blood glucose levels preceding sampling of HbAlc by 2 months and FA, GA, or GTP by three weeks correlated significantly with HbAlc (r = 0.668, p < 0.001) and GA (r = 0.441, p < 0.05) whereas no significant correlation was found between mean blood glucose and FA (r = 0.003) or GTP (r = 0.252). In conclusion, such methods which measure specifically the non-enzymatic glycation of a single species of protein (i.e. FPLC for HbAlc and affinity chromatography for GA) are to be preferred for assessing glycaemia.
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PMID:Blood glycated haemoglobin, serum fructosamine, serum glycated albumin and serum glycated total protein as measures of glycaemia in diabetes mellitus. 148 24

To investigate the frequency and etiology of diabetic osteopenia, we measured spinal bone mineral density (SBMD), total body bone mineral density (TBBMD), total body fat and lean body mass in 69 female diabetic patients (14 IDDMs and 55 NIDDMs). SBMD decreased with age in both IDDM and NIDDM, but when expressed as a percentage of age-matched normal Japanese females, some had lower SEMD, but others had normal or increased SBMD. Postmenopausal IDDM patients had lower SBMD than postmenopausal NIDDM patients. Thirteen out of 69 (18.8%) had an SBMD lower than 90% of age-matched controls. SBMD correlated positively with TBBMD. Those with lower SBMD had poor glycemic control, but there was no relation between SBMD and either duration of diabetes or presence of retinopathy and/or nephropathy. IDDM patients had lower 1.25 (OH)2D, osteocalcin than NIDDMs. SBMD correlated negatively with urinary pyridinoline and deoxypyridinoline excretion. SBMD correlated positively with body weight, and those with lower SBMD had significantly lower body mass index, body weight, fat weight and lean body mass than those with normal or increased SBMD. These results suggest that IDDM patients may be at higher risk of losing bone postmenopausally, and diabetic patients with lower SBMD have characteristics of poor diabetic control, lean habitus, low serum 1.25 (OH)2D.
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PMID:[Spinal bone mineral density in the female diabetic patients]. 149 83

The acetylator phenotype was determined in 31 insulin-dependent (IDDM) and 110 noninsulin-dependent (NIDDM) Jordanian diabetics, and was compared to that of 160 healthy volunteers of the same ethnic group. Dapsone was used as the test drug. The rapid acetylator phenotype was slightly less frequent in IDDM and slightly more frequent in NIDDM. Neither of the differences was significant. When acetylator status in the two types of diabetes mellitus was compared, there was a significant difference among the two groups. Patients with IDDM had a higher percentage of the slow acetylator phenotype when compared to NIDDM patients. The association between acetylator status and IDDM in Jordanians, which agrees with that reported for the Saudi Arabian population, is the reverse of what is found in European populations. The results demonstrate ethnic differences in acetylator status among IDDM patients.
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PMID:Acetylator phenotypes of Jordanian diabetics. 149 43

Of all the common diseases that have a genetic component, IDDM is probably the most tractable to the experimentalist. Large numbers of nuclear multiplex families are available, which can be stored as permanent cell lines; diagnosis is relatively unambiguous; and a mouse strain, the NOD, spontaneously develops autoimmune IDDM similar to the human disorder. In addition, the resolution and accessibility of the human genome map has been revolutionized by the discovery and widespread application of the PCR, particularly the amplification of short, tandemly repeated segments of DNA called microsatellites, which display high levels of allelic polymorphism. With these reagents, the stage is set for dissection of the genetic factors that control the pathophysiology of IDDM.
Diabetes 1992 Sep
PMID:A practical approach to identification of susceptibility genes for IDDM. 149 54

To detect serum antibodies to GAD in subjects with IDDM, three recombinant mBGAD 67 peptides encompassing the full-length protein were used in an ELISA. In this study 7 of 9 (78%) preclinical IDDM subjects (ICA+ first-degree relatives of a person with IDDM) and 6 of 13 (46%) recent-onset IDDM subjects, but no subjects with Graves' disease (n = 10) or scleroderma (n = 10), nor healthy nondiabetic control subjects (n = 10) had antibodies that reacted with one or more of the recombinant mBGAD peptides. We found no preferential reactivity with any recombinant peptide. Although only 3 preclinical subjects and 1 recent-onset subject had antibodies to all three mBGAD peptides, the results indicate that mBGAD 67 contains at least three B-cell autoepitopes. Compared with an immunoprecipitation assay of native human brain GAD, the ELISA detected 5 of 6 (83%) preclinical and 6 of 6 (100%) recent-onset IDDM subjects. The ELISA should facilitate screening to evaluate the role of autoimmunity to GAD in the development of IDDM.
Diabetes 1992 Sep
PMID:An ELISA for antibodies to recombinant glutamic acid decarboxylase in IDDM. 149 69

This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1992 Sep
PMID:Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin). 149 70


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