Compiling a district diabetic register: theoretical and practical considerations.
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Diabetes Mellitus↗
Biomedical subjects
M Press
Publications and source records attributed to M Press.
The magnitude of the hypercholesterolemia of hypothyroidism is associated with variation in the low density lipoprotein receptor gene.
To assess whether the variable extent to which patients with hypothyroidism become hypercholesterolemic was associated with variation in the genes for the low density lipoprotein (LDL) receptor or apolipoprotein-B, we investigated prospectively 52 patients with primary hypothyroidism treated with L-T4. There was significant reduction in cholesterol, high density lipoprotein cholesterol, LDL cholesterol, and apolipoprotein-A1 and -B after thyroid hormone replacement. The reduction in cholesterol was associated significantly with the magnitude in the reduction of serum TSH levels (P < 0.001) and the variable AvaII restriction site in exon 13 of the LDL receptor gene. For a given reduction in TSH, patients of genotype -/- (no restriction site) demonstrated a reduction in serum LDL cholesterol that was 4-fold greater than that of patients homozygous for the AvaII restriction site (genotype +/+), with heterozygous (+/-) patients showing an intermediate response. The hypocholesterolemic response was significantly greater in patients of the -/- genotype than in patients carrying the +allele (genotypes +/- and +/+; for LDL cholesterol, P < 0.01; for cholesterol, P < 0.05). No such relationship was observed with a variation at any other polymorphic site studied (four in the LDL receptor gene and two in the apolipoprotein-B gene). The magnitude of the decrease in high density lipoprotein cholesterol and apolipoprotein-A1 and -B was independent of the AvaII genotype, the effect of which was specific to LDL cholesterol. Variation within the LDL receptor gene appears to influence the magnitude of both the hypercholesterolemia of hypothyroidism and, consequently, the reduction of serum LDL cholesterol in response to L-T4. Thus, it may be possible to predict which hypothyroid patients are at greatest risk for coronary artery disease.
Adult↗
How to increase referrals.
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Appointments and Schedules↗
Effect of growth hormone treatment on hyperinsulinemia associated with Turner syndrome.
To determine whether the insulin resistance in patients with Turner syndrome, which may be exaggerated by treatment with human growth hormone, leads to excessive insulin secretion, we applied the hyperglycemic glucose-clamp technique to produce a standard hyperglycemic stimulus (6.9 mmol/L, or 125 mg/dl, greater than fasting plasma glucose level for 120 minutes) in seven patients with Turner syndrome and in seven healthy children. These studies were repeated in the patients after 6 to 12 months of therapy with growth hormone. Fasting plasma levels of insulin were comparable in control subjects and patients before therapy but increased significantly in the patients after 6 to 12 months of treatment with growth hormone. Despite identical glucose increments in the two groups during the glucose-clamp procedure, both first- and second-phase insulin responses were significantly greater in the patients than in the control subjects. Moreover, the hyperinsulinemic responses to glucose were markedly exaggerated in the patients after their treatment with growth hormone, reaching values (first phase 474 +/- 100 pmol and second phase 826 +/- 100 pmol; p less than 0.02 vs pretreatment values) that were almost threefold greater than those in control subjects (p less than 0.001). Nevertheless, the rate of insulin-stimulated glucose metabolism during the last 60 minutes of the clamp procedure was similar in all three groups of studies. Glycosylated hemoglobin, total cholesterol level, and blood pressure remained normal in patients after therapy with growth hormone. We conclude that glucose-stimulated insulin response is increased in patients with Turner syndrome and that these alterations are further exaggerated by treatment with growth hormone. These hyperinsulinemic responses appear to compensate for reductions in insulin sensitivity.
Adolescent↗
Prevalence of haemochromatosis amongst patients with diabetes mellitus.
Four hundred and six white caucasian patients with diabetes mellitus (243 male, mean age 54 +/- 16 (SD) years) were screened for haemochromatosis. Four patients had a fasting transferrin saturation > 62% and all were HLA A3 positive. Two were probable homozygotes for haemochromatosis and two heterozygotes. Homozygote haemochromatosis prevalence in this diabetic population was therefore 2/406 (0.0049) which is identical to that reported in the general population. These findings do not support a genetic relationship between the two conditions.
Adult↗
Pituitary response to growth hormone-releasing hormone in IDDM. Abnormal responses to insulin and hyperglycemia.
In poorly controlled insulin-dependent diabetes mellitus (IDDM), hyperglycemia fails to inhibit the pituitary response to growth hormone-releasing factor (GRF). To evaluate whether this derangement is reversed by a simultaneous elevation of circulating insulin, 0.3 micrograms/kg i.v. GRF 1-40 was administered to nine poorly controlled IDDM subjects (HbA1 greater than 11.1%) with and without concomitant infusion of insulin. In the absence of insulin, the poorly controlled IDDM subjects demonstrated a growth hormone response to GRF similar to that of nondiabetic subjects, despite marked hyperglycemia (approximately 16.8 mM). When insulin was infused into these same patients (insulin clamp) to produce combined hyperinsulinemia (528 +/- 90 pM) and hyperglycemia (16.5 +/- 1.98 mM), the GRF-induced growth hormone rise was markedly exaggerated (65 +/- 11 vs. 20 +/- 4 micrograms/L without insulin infusion, P less than 0.001). This enhancement of GRF-stimulated growth hormone release by insulin was strikingly attenuated (22 +/- 7 micrograms/L) in five well-controlled diabetic subjects studied under conditions of similar hyperinsulinemia (486 +/- 84 pM) and hyperglycemia (16.41 +/- 0.95 mM). In contrast, in nondiabetic subjects, acute hyperinsulinemia reduced the growth hormone response to GRF. We conclude that the failure of hyperglycemia to block the pituitary response to GRF in poorly controlled diabetes is not attributable to the lack of a coincident increase in circulating insulin. The paradoxical stimulatory effect of insulin on GRF-induced growth hormone release may contribute to the high spontaneous growth hormone levels characteristically seen in poorly controlled insulin-treated patients, and its attenuation after intensive insulin therapy may contribute to the reversal of growth hormone hypersecretion in well-controlled diabetic patients.
Adult↗
Synthesis and immunogenicity of hepatitis B virus envelope antigen expressed by recombinant vaccinia virus. Finding of retention signal in the C-terminal portion of the preS1 domain of subtype adyw.
Five different recombinant vaccinia viruses expressing the envelope antigen of hepatitis B virus (HBsAg) under the control of the P7.5 promoter were constructed. Cell cultures infected with some of the recombinant viruses synthesized both middle (M) and major surface (S) protein of HBsAg. It was shown that the length of the nontranslated sequence preceding preS2-ATG influenced the extracellular or intracellular HBV antigen distribution and the preS2:S antigen ratio. Some recombinants synthesized an M protein that was enlarged by additional 35 amino acids of preS1 domain and was entirely retained within the infected cells. Antibody responses to the S and preS2 antigens in mice revealed significant differences in the immunogenicity of individual recombinants.
Animals↗
Insulin resistance: an early metabolic defect of Turner's syndrome.
To evaluate whether insulin resistance contributes to the increased risk of diabetes in patients with Turner's syndrome, we measured insulin sensitivity (using the euglycemic insulin clamp technique, 40 mU/m2.min) and whole body glucose and lipid oxidation (assessed by indirect calorimetry) in two groups of nondiabetic patients with Turner's syndrome and age-matched normal controls. Group 1 consisted of eight young patients (mean age, 10 +/- 0.8 yr) who had never received hormone therapy, and group 2 consisted of five patients (mean age, 17.6 +/- 1.4 yr) who had been or were on estrogen therapy. In group 2, [3-3H]glucose was also infused during the euglycemic clamp to assess hepatic sensitivity to insulin. During the euglycemic clamp, insulin-stimulated glucose metabolism was decreased in both groups of patients [group 1, 8.4 +/- 1.0 vs. 14.7 +/- 2 mM/m2.min in controls (P less than 0.05); group 2, 9 +/- 0.7 vs. 11.7 +/- 0.9 mM/m2.min in controls (P less than 0.05)]. The impairment of insulin-stimulated glucose metabolism in patients with Turner's syndrome was accounted for by reduced nonoxidative glucose disposal; glucose oxidation rose to a similar extent in Turner patients and normal controls. Insulin-induced suppression of hepatic glucose production (group 2) and plasma FFA and branched chain amino acid levels in Turner patients was also indistinguishable from that in normal controls. Our data suggest that in patients with Turner's syndrome, insulin resistance is a very early metabolic defect that may be restricted to nonoxidative pathways of intracellular glucose metabolism.
Adolescent↗
A recombinant vaccinia virus expressing hepatitis B virus middle surface protein. Restricted expression of HBV antigens in human diploid cells.
Several vaccinia virus recombinants inducing the synthesis of the middle surface (M) protein of hepatitis B virus (HBV) were constructed. One of them, denoted v137, was examined in some detail. The virus replicated nearly to the same extent in various cell lines, viz. human embryo diploid fibroblast LEP and MRC-5 cells, rabbit embryo fibroblast REF cells, TK- rat RAT-2 cells, and green monkey CV-1 cells. However, the production of M protein was found considerably lower in the human LEP and MRC-5 than in the other cells examined. In addition, the kinetics of M formation were different in these two cell systems, LEP cells lagging significantly behind CV-1 cells. The low-level production of M protein in LEP cells was not increased by repeated v137 passages in LEP cells, nor by a passage in a laboratory worker accidentally infected with the v137 virus, nor by shortening the leader sequence preceding the translation initiation codon. The greater part of the M antigen was found to be cell associated, more so in the cells of human than monkey origin. From the major HBV S antigen (HBsAg) isolated from the plasma of chronically infected subjects, the antigen released by cell destruction differed by binding to polymerized human albumin. This property was utilized in ELISA to detect anti-preS2 antibody. Rabbits inoculated intradermally with the v137 virus developed antibodies reactive in this assay as well as with a synthetic peptide corresponding in the amino acids 14-34 of the NH2 terminus of the HBsAg preS2 region.
Animals↗
Growth hormone and metabolism.
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Animals↗
Quantitative ultrastructural analysis of coronary atherosclerotic involvement in two macaque species.
Ultrastructural analyses were employed to observe and to compare in detail lesions of the coronary artery of cynomolgus and rhesus monkeys. Animals were fed individually with the same atherogenic ration under identical conditions for 4, 8, and 12 months, and controls of each species were fed with a low fat, cholesterol-free ration. Transmission electron microscopic studies of coronary arteries from these animals led to the following conclusions: (1) Synthetic smooth muscle cells (SMC) without lipid and macrophages without lipid appeared more frequently in the cynomolgus lesions than in the rhesus lesions. Furthermore, phenotypic expression of synthetic SMCs in the cynomolgus was more active with greater diversity, while the rhesus showed less phenotypic modulation. Macrophages without lipid appeared frequently in the cynomolgus media. (2) Increased percentages of both synthetic SMCs with lipid and macrophages with lipid were demonstrated in the cynomolgus lesions as compared to those in the rhesus. This indicates that foam cells, including SMC- and macrophage-derived foam cells, are more prevalent in cynomolgus than in rhesus. They are considered to play an important role in atherogenesis. (3) Medial disruption, synthetic SMCs, and macrophages containing lipid appeared more often in cynomolgus media than in rhesus media. (4) There were greater percentages of both synthetic SMCs and macrophages in the intima of the myocardial side of coronary arteries in both species. (5) Approximately 42% of all foam cells in the cynomolgus lesions were derived from SMCs. There were fewer macrophages in rhesus lesions. (6) The difference in expression between the two macaque species reflects different responses of macrophages to medial smooth muscle cell (SMC) components. The configuration of the artery wall could be one of the important indicators of these different expressions.
Animals↗
Risk of hypoglycaemia with alternate-day growth hormone injections.
Fasting hypoglycaemia developed in three growth hormone deficient children after the start of treatment with synthetic growth hormone. The effects, which occurred 36-60 h after each injection, may have been due to insulin-like effects of endogenous somatomedins after waning of insulin antagonism induced by growth hormone. Daily growth hormone injections may be necessary to maintain normal plasma glucose levels in young children.
Blood Glucose↗
Effect of insulin on growth hormone-induced metabolic derangements in diabetes.
To investigate the mechanism of growth hormone-induced hyperglycemia in diabetes, two studies were done in insulin-dependent diabetic patients receiving intensive insulin therapy with the insulin pump. First, the metabolic response to a standard breakfast following a subcutaneous insulin bolus was examined before and after 20 hourly boluses of intravenous growth hormone in eight patients. Despite unchanged insulin therapy, growth hormone administration produced a marked rise in fasting glucose concentrations (197 +/- 21 v 96 +/- 11 mg/dL), as well as increases in fasting levels of free fatty acids and branched chain amino acids. Nevertheless, postprandial blood glucose increments were only slightly greater after growth hormone (36 +/- 14 v 20 +/- 12 mgdL). Moreover, the increased levels of other insulin-sensitive fuels induced by growth hormone fell to normal following the meal. In a second study, six patients received a low-dose insulin clamp (designed to reproduce the mean postprandial concentrations of glucose and insulin observed in the meal study) before and after growth hormone administration. Despite endogenous glucose overproduction after growth hormone, modest elevations in free insulin (40 to 50 microU/mL) were sufficient to suppress glucose production to an extent comparable to the control day (from 2.8 +/- 0.2 to 0.6 +/- 0.3 mg/kg min after growth hormone v 1.6 +/- 0.1 to 0.4 +/- 0.2 mg/kg min on the control day). However, the normal stimulation of glucose uptake by insulin was abolished by growth hormone. We conclude that in diabetic patients growth hormone-stimulated hepatic glucose overproduction (and the increases in other insulin-sensitive fuels) can be relatively easily overcome with extra insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Deranged alpha-adrenergic regulation of growth hormone secretion in poorly controlled diabetes: reversal of the exaggerated response to clonidine after continuous subcutaneous insulin infusion.
Elevated plasma growth hormone (GH) and peripheral catecholamine levels are frequently observed in poorly controlled, insulin-dependent diabetes. Since the alpha adrenergic system plays an important role in hypothalamic regulation of GH secretion, we tested the hypothesis that altered central adrenergic activity contributes to the increased GH concentrations in diabetes. Clonidine, an alpha-adrenergic agonist, was administered to nine poorly controlled, young diabetic patients (age 12-19 yr) before and after 1 wk of continuous subcutaneous insulin infusion pump therapy. As expected, continuous subcutaneous insulin infusion lowered mean 24-h plasma glucose (from 203 +/- 21 to 112 +/- 7 mg/dl, p less than 0.01) and GH (from 17.7 +/- 2.1 to 9.2 +/- 1.2 ng/ml, p less than 0.01) to values observed in normal controls. In the diabetic patients during conventional treatment, both the peak plasma GH level postclonidine (48.3 +/- 8.7 ng/ml) and the incremental area under the GH response curve (3.23 +/- 0.58 mg X min/ml) were significantly increased above normal control values (25.2 +/- 2.1 ng/ml, p less than 0.05 and 1.63 +/- 0.11 mg X min/ml, p less than 0.0025, respectively). In contrast, the GH response to clonidine was indistinguishable from normal after only 1 wk of intensified insulin treatment. Our findings support the contention that metabolic control of diabetes influences hypothalamic regulation of GH secretion and suggests that such alterations are related, at least in part, to changes in central alpha-adrenergic activity.
Adolescent↗
Importance of raised growth hormone levels in mediating the metabolic derangements of diabetes.
To evaluate the importance of the raised levels of growth hormone that characterize poor diabetic control, we gave growth hormone for 21 to 45 hours in the form of hourly 100-micrograms pulses to 14 diabetics being treated by insulin pump. Insulin-pump settings and meals were kept constant. Mean 24-hour levels of growth hormone (+/- S.E.M.) rose from 8 +/- 1 to 16 +/- 2 ng per milliliter--values identical to those observed in 12 other patients with poorly controlled diabetes (17 +/- 3 ng per milliliter). Plasma glucose concentrations doubled within 8 to 10 hours and remained elevated until growth hormone was discontinued (fasting glucose level rose from 86 +/- 11 to 204 +/- 17 mg per deciliter at 18 hours and to 240 +/- 20 mg per deciliter at 42 hours). The hyperglycemia was due mainly to a marked stimulation of hepatic glucose production that occurred without changes in levels of free insulin or glucagon. Levels of circulating free fatty acids, ketones, and branched-chain amino acids were also increased. The moderate elevations in growth hormone levels that occur in poorly controlled diabetes can themselves reproduce the whole spectrum of abnormal metabolic fuel concentrations that are associated with poor diabetic control, despite optimized insulin treatment. Thus, hypersecretion of growth hormone may be the cause as much as the consequence of poor diabetic control.
Adolescent↗
Prospective study on the relationship between cervical neoplasia and herpes simplex type-2 virus. II. Herpes simplex type-2 antibody presence in sera taken at enrollment.
Sera obtained at enrollment in the study from patients suffering from moderate to sever dysplasia (cervical intraepithelial neoplasia grade II), carcinoma in situ (cervical intraepithelial neoplasia grade III) and invasive carcinoma, or developing any of these conditions in the course of the prospective study, and from control subjects, were examined for herpes simplex type-2 (HSV-2) antibody presence. The controls were matched with the patients by age, age at first intercourse, number of sexual partners, smoking habits and history of diathermoelectrocoagulation of the ectopic epithelium and transformation zone of cervix. Only those subjects were selected as controls who remained free of pathological colposcopical and cytological findings throughout the observation period, i.e. for at least 4 years after their serum sample was obtained. The microneutralization test (MNT) and type-2-specific solid-phase radioimmunoassay (SPRIA) were used as serological tests. No difference in the prevalence of HSV-2 antibody between the patients and controls was revealed by either test. Various combinations of the results from the two tests also failed to show any difference between patients and controls. Moreover, no significant differences were observed in the prevalence of HSV-2 antibody between patients suffering from the various pathological conditions and those diagnosed at enrollment and later in the course of the study. These results do not provide any support for the hypothesis of the involvement of HSV-2 in cervical neoplasia.
Animals↗
Pituitary response to growth hormone-releasing factor in diabetes. Failure of glucose-mediated suppression.
To evaluate the mechanism underlying raised growth hormone levels in diabetes, we compared the response to growth hormone-releasing factor (GRF) in type I diabetic and healthy control subjects. In 12 poorly controlled diabetic subjects (fasting plasma glucose 276 +/- 27 mg/dl) basal serum growth hormone levels were elevated by 200-300% (P less than 0.02), yet the incremental increase in growth hormone after GRF injection was no greater than in control subjects. Furthermore, five additional diabetic subjects with normal growth hormone levels after long-term insulin pump treatment also showed an identical response to GRF. Thus, raised basal growth hormone levels in diabetes and the fall that follows intensive insulin treatment may reflect changes in hypothalamic regulation of, rather than in pituitary responsiveness to, GRF. However, when five normal subjects were restudied during glucose infusion, even quite modest hyperglycemia (plasma glucose approximately 150 mg/dl) caused marked suppression of the response to GRF (P less than 0.005). Thus, the "normal" response to GRF in poorly controlled diabetes is actually inappropriate. Failure of the pituitary to suppress in response to hyperglycemia in diabetes implies a second abnormality that may further aggravate disordered growth hormone secretion.
Adolescent↗
Further observations on cytoplasmic hyaline in the lung.
Cytoplasmic hyaline material resembling Mallory's alcoholic hyaline has previously been described in pulmonary alveolar cells of patients with asbestosis. We present 14 new cases of cytoplasmic hyaline found in patients with a variety of processes causing damage to the alveolar lining; these include cases of radiation pneumonia, diffuse interstitial fibrosis, organizing bacterial pneumonia, as well as asbestosis. Hyaline was found only in the setting of an unusual type II cell change, which ultrastructurally appeared to represent squamous metaplasia. We conclude that pulmonary cytoplasmic hyaline is not specific for asbestosis but rather is a nonspecific reaction to injury;
Adult↗