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Biomedical subjects

J S Soeldner

Publications and source records attributed to J S Soeldner.

At least 55 records · Page 3Linked to original sources
PubMed1985

The effect of hemoglobin ligands on the kinetics of human hemoglobin A1c formation.

HbA1c is the most prevalent of the minor human hemoglobins. It is formed by the nonenzymatic addition of glucose to the alpha-amino group of the beta chain by an initial condensation reaction and a subsequent intermolecular Amadori rearrangement. We have developed a method of analysis which utilizes high performance liquid chromatography to follow the formation of HbA1c and greatly simplifies the determination of the kinetic parameters associated with this reaction. This has allowed us to study the effects of several Hb ligands, including the hydrogen ion, on the kinetics of this glycosylation reaction. Both the initial condensation reaction and the subsequent rearrangement are shown to exhibit acid catalysis, but the rate of the condensation step is limited by the extent of protonation of the alpha-amino group. The variation in kinetic parameters as a function of hydrogen ion concentration has allowed us to determine the probable reaction mechanism of HbA1c formation by comparison to previously reported model systems of Schiff base formation and Amadori rearrangement. The formation of pre-HbA1c from deoxy-Hb shows an increased forward rate when compared to oxy-Hb. The presence of physiologic concentrations of CO2 causes a proportional decrease in both k1 and k-1. 2,3-Diphosphoglycerate causes a significant increase in the keq of the formation reaction. The effects of CO and the substitution of L-glucose for D-glucose are not significant.

2,3-Diphosphoglycerate↗
PubMed1985

First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion.

In a prospective study to evaluate the prevalence and predictive potential of circulating islet-cell antibodies, we have screened 1723 "normal" first-degree relatives (parents, siblings, and offspring) of patients with insulin-dependent diabetes mellitus. The prevalence of islet-cell antibodies on initial screening was 0.9 per cent (16 of 1723). Over a maximal follow-up period of two years, insulin-dependent diabetes mellitus developed in 2 of 16 relatives with islet-cell antibodies and in 1 of 1707 without antibodies. In addition, 6 of 12 nondiabetic relatives with islet-cell antibodies had abnormally low insulin responses--below the third percentile in 6 and below the first percentile in 4--on their initial intravenous glucose challenge. Thus, prospective islet-cell antibody screening of high-risk first-degree relatives, in combination with intravenous glucose-tolerance testing, is capable of identifying immunologically abnormal persons with profoundly diminished beta-cell function, who are presumably at increased risk of insulin-dependent diabetes mellitus.

Autoantibodies↗
PubMed1984

Pre-type 1 (insulin-dependent) diabetes: common endocrinological course despite immunological and immunogenetic heterogeneity.

In an ongoing prospective study 32 individuals have been evaluated for insulin secretory dynamics, islet cell antibodies and HLA antigens, during the preclinical phase of Type 1 diabetes mellitus. Twenty-four out of the 32 subjects were islet cell antibody-positive. To date, 14 subjects (10 islet cell antibody-positive, four islet cell antibody-negative) have progressed to develop overt diabetes. Several patterns of HLA-DR expression were noted (DR3/DR4, DR3/DR3, DR3/x, DR3/DR1, DR4/x, DR4/DR7, DR5/DR7, DR1/DR7 and DR1/DR2). Irrespective of differences in islet cell antibody status or HLA-DR alleles, pre-diabetic individuals exhibited a similar slow course of progressive beta-cell dysfunction.

Adolescent↗
PubMed1984

Differential sensitivity to beta-cell secretagogues in "early," type I diabetes mellitus.

The insulin secretory response to various beta-cell secretagogues was studied in four children (ages 11, 11, 12, and 10 yr) in "early" stages or remission of type I diabetes mellitus. One child was an anti-islet antibody positive monozygotic twin of a type I diabetic subject, two children had impaired glucose tolerance and elevated levels of Ia-positive T-cells, and the fourth was in remission (off insulin) of type I diabetes 6 mo after immunotherapy. The peak first-phase (0-10 min) insulin increment after intravenous (i.v.) glucose was negligible in each patient, whereas the peak responses to i.v. glucagon, tolbutamide, arginine, and oral glucose ranged between 10% and 43% of median responses in normal control subjects. The rank order of response to a variety of secretagogues was remarkably similar in all four subjects: i.v. arginine greater than i.v. glucagon greater than oral glucose greater than i.v. tolbutamide greater than i.v. glucose. These studies indicate that a "functional" beta-cell defect, namely a complete loss of response to i.v. glucose and a partial loss to other secretagogues, exists in type I diabetic patients before complete beta-cell destruction. This alteration in beta-cell responsiveness probably underlies our prior observation of slowly progressive loss of i.v.-glucose-induced insulin release in islet cell antibody-positive siblings to type I diabetic subjects.

Arginine↗
PubMed1984

Pre-type I diabetes. Linear loss of beta cell response to intravenous glucose.

Twenty-one intravenous (i.v.) glucose tolerance tests were performed on nine subjects before the onset of overt type I diabetes mellitus. Islet cell antibodies (6 of 9 subjects) and elevated levels of Ia-positive T-lymphocytes (3 of 3 subjects studied) were detected during the prediabetic period. Elevations of fasting blood glucose and peak glucose during oral glucose tolerance tests were not observed until the year before onset of clinically overt diabetes. During the prediabetic period, there was a progressive loss of early-phase insulin release to i.v. glucose (rate of decline, 20-40 microU/ml insulin release/yr; correlation coefficient, 0.9).

Administration, Oral↗
PubMed1984

Laser light scattering spectroscopy of in vivo human lenses.

Laser light scattering spectroscopy measures the thermal random movement of protein as characterized by the diffusion coefficient. This technique has been used in assessing cataract formation in animals. The changes detected appear to predict the later development of lens opacities. The sensitivity and quantitative aspects of this technique offer advantages over other presently available methods of detecting cataract formation. First studies in humans indicated a significant correlation between the diffusion coefficient and age (P less than 0.05). The age adjusted mean diffusion coefficient for nondiabetics (4.60 +/- 0.29; mean +/- SEM) was significantly higher compared to diabetics without retinopathy (3.59 +/- 0.41; P = 0.0473), diabetics with background or preproliferative retinopathy (2.73 +/- 0.27; P = 0.0001), or to diabetics with preproliferative or proliferative retinopathy receiving laser photocoagulation within 1 year of measurement (3.02 +/- 0.37; P = 0.0012). Diabetics with laser treatment more than 1 year prior to measurement (3.96 +/- 0.51) did not differ significantly from nondiabetics.

Adolescent↗
PubMed1983

Muscle capillary basement membrane width and its relationship to diabetes mellitus in monozygotic twins.

Quadriceps (Q) and gastrocnemius (G) muscle capillary basement membrane width (CBMW) were measured in 18 pairs of monozygotic (MZ) twins. Thirteen of these twin pairs were discordant for insulin-dependent diabetes (IDD) and five pairs were concordant for either IDD (two pairs) or for non-insulin-dependent diabetes (NIDD). In 12 of the 13 nondiabetic (ND) twin mates of IDD, 50 oral glucose tolerance tests performed in the years before or after determination of CBMW revealed mean blood glucose levels in the 36-52 percentile range, compared with normal controls. The mean (+/-SD) age at the onset of IDD in discordant twins was 18.7 +/- 10.1 (range 8-37) yr and the mean duration of discordance at the time of biopsy was 13.6 +/- 8.3 (range 3-32) yr. CBMW data were compared within each twin (Q versus G) and between twin mates and age- and sex-matched controls. Overall, CBMW of IDD twins was greater than that of their ND twin mates. Differences between IDD and ND twins, however, were much more marked in gastrocnemius (1859 +/- 643 versus 1222 +/- 307 A, P less than 0.0003) than in quadriceps (1291 +/- 319 versus 1112 +/- 302 A; P less than 0.04). CBMW in gastrocnemius was significantly thicker than that in the quadriceps of IDD twins (t = 4.55, P less than 0.0008) but not in their ND twin mates (t = 1.15, P less than 0.27). CMBW was significantly thicker in IDD than in their ND twin mates (in quadriceps and/or gastrocnemius) in 10 of the 12 twin pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Resting and exercise hyperemic pulsatile arterial blood flow in insulin-dependent diabetic subjects.

Pulsatile arterial blood flow was studied in 20 normal (N), 20 short-term (STIDDM; mean: 5.17 yr), and 20 long-term insulin-dependent diabetic patients (LTIDDM; mean: 14.76 yr) between the ages of 18 and 30 yr with no clinically detectable peripheral vascular disease. Measurements were taken from waveforms obtained noninvasively using an electromagnetic flowmeter at rest and immediately after a 3-min isometric exercise challenge of the right leg. At rest, both groups of diabetics exhibited minute flow values similar to those in the normal group. This was achieved, however, by increased vasodilation in peripheral tissues as indicated by a difference in waveform configuration. Diabetic subjects showed a significantly smaller peak flow, a less steep ascending and descending slope, and a higher minute heart rate than normal controls. After 3 min of isometric exercise, the diabetic groups exhibited significantly less minute flow, flow/pulse, and a more vasodilated flow pattern similar to that recorded at rest. In addition, the LTIDDM group showed significantly less arterial elasticity than N or STIDDM groups as indicated by a shorter propagation time. These findings imply that apparent functional changes in pulsatile arterial blood flow occur early in the time course of diabetes and are independent of duration.

Adult↗
PubMed1983

Type I diabetes mellitus in monozygotic twins: chronic progressive beta cell dysfunction.

In a prospective 21-year study, islet cell antibodies and beta cell function were serially assessed in 24 monozygotic twins initially discordant for type I diabetes mellitus. Eighteen of 21 twins typed had HLA-DR3 or HLA-DR4 antigens. During the follow-up, 4 twins developed type I diabetes mellitus, and in 3 of these 4 twins islet cell antibodies preceded the diagnosis of clinical diabetes mellitus by greater than 8, 5 and 7 years respectively. During the "prediabetic phase," the presence of islet cell antibodies was temporally associated with a progressive decline in first phase insulin response to intravenous glucose. Elevations in fasting blood glucose and abnormalities on oral glucose tolerance tests appeared only later during the course of the disease. Of the remaining 20 twins who continue to be discordant for type I diabetes mellitus, two have had islet cell antibodies for greater than 1.5 and 1 year respectively. One of these islet cell antibody-positive non-diabetic twins was restudied; despite a fasting blood glucose level of 64 mg/dL, she had a total absence of first phase insulin response to intravenous glucose. There was no evidence of transient islet cell antibody positivity in any of the twins studied. Type I diabetes mellitus in monozygotic twins has a prolonged prediabetic phase of progressive beta cell dysfunction with associated immunologic abnormalities.

Antibodies↗
PubMed1982

Glycosylated haemoglobin: an overview of a series of clinical studies.

A series of studies on the clinical relevance of chromatographically determined glycosylated haemoglobins is presented. Both whole blood samples and haemolysates were stable at 5 degrees C for up to two weeks. Prolonged storage required temperatures less than -80 degrees C. Haemoglobin (Hb) AIc percent values in non-diabetic subjects ranged from 4.0 to 6.0 percent (mean +/- 2 SD). HbAIc percent values proved to be as stable in diabetic as non-diabetic subjects on repetitive sampling over a three month period. A dissociable component was not observed in any of 78 samples. HbAIc percent values of carbohydrate intolerant subjects (n = 18) were not distinguishable from those in non-diabetic subjects. A close correlation was observed between HbAIc percent and the mean of multiple capillary glucose samples in 37 insulin dependent diabetic subjects. In clinical practice HbAic percent proved to be a stable objective measure of blood glucose concentrations in diabetic patients--the major present need is for a simple reliable technique of measurement.

Adult↗
PubMed1982

The relationship of idiopathic sudden hearing loss to diabetes mellitus.

A diabetic subgroup identified from a base population who have experienced idiopathic sudden hearing loss (ISHL) has been studied. In order to assess the relationship between diabetes and ISHL, two non-diabetic control groups were formed, and a comparison of the audiological data between the diabetic and non-diabetic ISHL patient was made. Mean degree of hearing loss and recovery, as well as the mean hearing level of the contralateral ear were analyzed. No statistically significant differences were noted in the audiological pattern of ISHL in diabetics and controls. A similar incidence of recovery was noted for the two groups throughout the mid frequencies; however, diabetic ISHL patients fail to recover as well as in the high frequencies. Preliminary data, while not statistically significant, suggest an increased hearing loss in both the affected and unaffected ear of the older diabetic patient.

Adult↗
PubMed1982

Regulation of hemoglobin AIc formation in human erythrocytes in vitro. Effects of physiologic factors other than glucose.

The formation of hemoglobin AIc was studied in intact human erythrocytes in vitro. Satisfactory methods were developed for maintaining erythrocytes under physiologic conditions for greater than 8 d with less than 10% hemolysis. Hemoglobin AIc levels were determined chromatographically on erythrocyte hemolysates after removal of reversible components by incubation for 6 h at 37 degree C. Hemoglobin AIc concentration was found to increase linearly with time during 8 d of incubation. The rate of formation of hemoglobin AIc increased linearly as glucose concentration was increased from 40 to 1,000 mg/dl. Deoxyhemoglobin was glycosylated twice as rapidly as oxyhemoglobin. The rate of hemoglobin AIc formation was further increased by elevated 2,3-diphosphoglycerate levels, an effect that was most marked with deoxyhemoglobin. We conclude that the nonenzymatic glycosylation of hemoglobin is influenced by factors other than glucose, including oxygen tension and 2,3-diphosphoglycerate levels.

2,3-Diphosphoglycerate↗
PubMed1982

Trapping of peripheral blood lymphocytes in the pancreas of patients with acute-onset insulin-dependent diabetes mellitus.

Involvement of humoral and cellular autoimmunity in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is demonstrated by the presence of circulating autoantibodies and the early pancreatic lesion of insulitis. In an effort to detect the early pancreatic lesion in acute onset IDDM, we have labeled peripheral blood lymphocytes with indium oxine 111, reinjected these autologous cells intravenously into the patients, and followed their kinetics over 96 h using an emission computerized tomography (ECT) scanner. The reinjected cells are acutely distributed in the patients' lungs, liver, and spleen (2-12 h). At 24, 48, and 72 h, the labeled lymphocytes are no longer detectable in the lungs or the liver, but are clearly present in the spleen and in the pancreas. Lymphocytic pancreatic infiltration was observed in two of three acute-onset IDDM patients, but not in large number of patients undergoing similar scans for other diseases, suggesting ongoing mononuclear cell infiltration of the pancreas, a possible marker of the lesion of insulitis. Lymphocyte scanning may provide a powerful noninvasive tool for studying patients with IDDM and for selecting those who might benefit from immunosuppressive therapy.

Acute Disease↗