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H Schmidt-Gayk

Publications and source records attributed to H Schmidt-Gayk.

At least 37 records · Page 2Linked to original sources
PubMed1998

Regulation of intestinal vitamin D receptor expression in experimental uraemia: effects of parathyroidectomy and administration of PTH.

In this study, the effects of PTH on binding of [3H]-1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and on vitamin D receptor (VDR) mRNA concentration were assessed in intestinal mucosa of subtotally nephrectomized rats (Nx) and in intestinal mucosa of sham-operated rats with normal kidney function (Intact). Intestinal 1,25(OH)2D3 binding capacity of Intact remained unchanged (i) after parathyroidectomy (PTx), (ii) after administration of PTH for up to 6 days, and (iii) after PTx and subsequent administration of PTH (n = 4 experiments). In contrast, PTx of subtotally nephrectomized animals (Nx-PTx) decreased 1,25(OH)2D3 binding capacity from 757 +/- 95 fmol/mg protein in Nx to 417 +/- 42 in Nx-PTx (P < 0.01, n = 5). PTH administration had no effect on intestinal 1,25(OH)2D3 binding capacity in Nx. However, PTH administration to Nx-PTx resulted in re-elevation of 1,25(OH)2D3 binding capacity to a level (790 +/- 113 fmol/mg protein) which was comparable to Nx. Kd-values remained unaltered under all experimental conditions. The intestinal VDR mRNA concentration (normalized to beta-actin mRNA) was decreased, on average, by 23% in Nx-PTx (P < 0.05 versus Nx). In further experiments, 1,25(OH)2D3 was administered to Nx-PTx. This resulted in upregulation of 1,25(OH)2D3 binding capacity as compared to vehicle-treated Nx-PTx (562 +/- 90 fmol/mg protein versus 249 +/- 32, P < 0.01). The latter results could indicate that PTH-mediated stimulation of residual renal 1,25(OH)2D3 production was involved in PTH-mediated up-regulation of intestinal 1,25(OH)2D3 binding capacity in Nx-PTx. To rule out this possibility, PTH was administered to totally nephrectomized and parathyroidectomized rats (TNx-PTx). Since PTH caused an approximately 80% increase (P < 0.05) in intestinal 1,25(OH)2D3 binding capacity under those experimental conditions a mediator role of 1,25(OH)2D3 could be excluded. Functional significance of decreased intestinal 1,25(OH)2D3 binding capacity in Nx-PTx as compared to Nx was demonstrated by significantly lower 1,25(OH)2D3-mediated stimulation of intestinal 25(OH)D3-24-hydroxylase activity in Nx-PTx (209 +/- 68 pmol/mg protein) than in Nx (385 +/- 81, P < 0.01). The modulation of intestinal 1,25(OH)2D3 binding capacity was not correlated with changes in calcium, phosphate or 1,25(OH)2D3 serum concentrations under our experimental conditions. Taken together, intact parathyroid gland function was required to maintain adequate intestinal VDR expression in experimental uraemia (but not in normal animals). The mechanism of the modulation of intestinal VDR by PTH remains to be elucidated although an indirect effect of PTH on VDR expression in intestinal mucosa seems most likely.

Animals↗
PubMed1998

Sequential changes of biochemical bone parameters after kidney transplantation.

BACKGROUND: Persistent hyperparathyroidism after renal transplantation (Rtx) has been reported in several studies. However these studies evaluated biochemical bone parameters either only during a short time period (up to 6 months) or for a longer time period, but with long intervals in between. Therefore, we prospectively evaluated biochemical bone parameters of kidney-transplant recipients at short intervals for 2 years after surgery. METHODS: Biochemical bone parameters were prospectively investigated in 129 patients 2, 3, 5, 8, 12, 18 and 24 months after Rtx. All patients received prednisone and cyclosporin A as immunosuppressive therapy, and 75 patients also received azathioprine. None of the patients was treated with calcium, phosphorus, or vitamin D preparations. RESULTS: Serum creatinine levels decreased from 166.8 +/- 5.4 mumol/l to 140.0 +/- 4.9 two years after Rtx; (data are expressed as mean +/- s.e.m.). Serum phosphorus levels increased slightly from 0.9 +/- 0.022 mmol/l to 0.98 +/- 0.025 (12 m), but remained within the lower normal range. We observed a rise in total and albumin adjusted calcium concentrations 3 months after Rtx. 52% of all patients had serum calcium levels above 2.62 mmol/l (upper normal limit in our laboratory) 3 months after renal transplantation with a gradual decrease thereafter. There was no correlation of calcium and PTH levels. We observed a significant rise in biochemical bone parameters from 2 to 5 months after renal transplantation (P < 0.001): alkaline phosphatase (AP) increased from 164.3 +/- 9.4 to 236 +/- 12.7 U/l (normal 50-180), bone specific alkaline phosphatase (BAP) rose from 17.7 +/- 1.36 to 23.2 +/- 1.7 ng/ml (normal:4-20) and osteocalcin (OC) increased from 20.2 +/- 1.5 to 26.7 +/- 1.9 ng/ml (normal 4-12). AP and BAP levels values normalized 12 months after renal transplantation, whereas OC was still above normal throughout the study period. Patients were subdivided into two groups: those with good and those with impaired graft functions. Patients with good graft function had stable serum creatinine levels (< or = 132 mumol/l or < or = 1.5 mg/dl) well below the mean serum creatinine concentration during the study period. The significant changes in AP, BAP, and OC occurred irrespective of renal function. However, patients with impaired graft function (n = 65) had significantly higher PTH-levels (70 pg/ml higher) than patients with good graft function (n = 64), P < 0.01. PTH was positively correlated with serum creatinine (r = 0.81, P < 0.001). Moreover, patients with low 25 (OH) vitamin D levels (n = 63) had significantly higher PTH concentrations (between 40 and 80 pg/ml, P < 0.01) throughout the study period compared to patients (n = 66) with a sufficient 25(OH)D supply irrespective of graft function. There was a negative correlation of 25 (OH)D levels and PTH; (r = -0.49, P < 0.001). 1,25(OH)2D3 (evaluated in 24 patients) levels increased from 46.5 +/- 6.6 to 76.9 +/- 7.6 pg/ml (normal:35-90) at 12 months. CONCLUSION: Hypercalcaemia is a common phenomenon in the early period after kidney transplantation and occurs in the presence of low normal phosphorus levels. It is most probably related to improved PTH action and 1-hydroxylation of vitamin D. The rise in biochemical bone parameters between 3 and 5 months occurs irrespective of graft function and normalization is only achieved 1 year after transplantation. PTH is constantly elevated for up to 2 years after kidney transplantation and is most probably related (a) to impaired graft function and (b) to suboptimal 25 OH vitamin D supply.

Adult↗
PubMed1998

Screening for colorectal neoplasms with a new immunological human faecal haemoglobin and albumin test.

In Germany, screening for colorectal cancer shows low efficiency, which is partly due to demographic changes with a rising mean age of the population, a low participation rate and an unsatisfactory sensitivity of guaiac tests for detecting faecal occult-blood. Therefore, a pilot screening study with a new immunological faecal haemoglobin and albumin test was performed in Ostringen, Germany to assess its compliance, performance characteristics and cost-effectiveness. Two thousand, seven hundred and eighty-five persons (1,498 women and 1,287 men) collected 1 ml samples from two different sites of one stool. The upper limit of normal was 10 micrograms/g stool for haemoglobin and 100 micrograms/g stool for albumin. The compliance was 82%; 224 persons (8%) had a positive test result. Of these, 184 underwent full colonoscopy. We detected 14 colorectal cancers, 10 of which were Dukes' stage A carcinomas removed by endoscopic polypectomy, 34 large adenomas and 43 small adenomas. The detection rate for colorectal neoplasms was above the rate described for other immunological haemoglobin tests and for Haemoccult tests. The specificity of the test--defined with false-positive results if a normal colon mucosa and no other reasons for upper or lower gastrointestinal bleeding were found--was 99.5%. The cost-effectiveness was assessed by comparing the diagnostic costs with the savings resulting from prevention of colorectal carcinomas by endoscopic polypectomy of malignant polyps (Dukes' stage A). The savings in our screening study exceeded the diagnostic costs by approximately 2.3 times. The combined immunological faecal haemoglobin and albumin test should substitute the Haemoccult test in colorectal cancer screening because of its higher sensitivity and specificity combined with cost-effectiveness and good patient compliance.

Adolescent↗
PubMed1998

Effects of acute ACE inhibition on pulsatile renin and aldosterone secretion and their synchrony.

Pulsatile (burstlike) secretion of renin and aldosterone is positively coupled with a short time lag of about 10 to 20 minutes. We investigated how acute interruption of the renin-angiotensin-aldosterone axis, ie, acute angiotensin-converting enzyme (ACE) inhibition, alters the pattern of renin and aldosterone secretion. Eight healthy men (mean age, 22+/-1 years) were studied while on standardized salt intake. They were allocated on 2 occasions in random order to injection of placebo or 1.25 mg of the ACE inhibitor enalaprilat. Blood samples were obtained every 10 minutes for 24 hours for measurement of plasma renin and aldosterone concentrations. The hormone concentration profiles were analyzed using a multiparameter deconvolution technique; basal (tonic) and pulsatile hormone secretion was assessed. The regularity of pulsatile hormone secretion was analyzed using approximate entropy (ApEn). Cross-correlation and cross-ApEn analysis of renin and aldosterone secretion were performed to assess synchrony. Acute ACE inhibition caused an immediate burst of renin release and, in addition, significantly (P<0.01) increased 24-hour pulsatile and total renin secretion. It did not affect basal (nonpulsatile) renin secretion. The amplitude of renin bursts and the mass of hormone secreted per burst were significantly (P<0.01) increased, whereas the burst frequency (ie, number of secretory events) was unchanged. ApEn analysis revealed significantly (P<0.05) more regular renin secretion after ACE inhibition. In contrast, neither basal nor pulsatile aldosterone secretion was affected by administration of enalaprilat. Cross-ApEn analysis documented not only a maintained pattern of reproducibility (ie, synchrony) but also greater conditional regularity between pulsatile renin and aldosterone secretions with acute ACE inhibition. However, the quantitative strength of hormone coupling (assessed by cross-correlation analysis) was markedly diminished by enalaprilat treatment. The present findings suggest that the renin-angiotensin-aldosterone axis may not be completely uncoupled by acute ACE inhibition or that pulsatile renin and aldosterone secretion is driven by a common signal generator that is unaffected by ACE inhibition. In addition, a background basal and pulsatile aldosterone secretion not regulated by the renin-angiotensin axis may exist.

Adult↗
PubMed1998

Changes in bone turnover induced by aerobic and anaerobic exercise in young males.

Physical activity is considered an important factor in attaining bone mass. However, the mechanisms by which exercise affects bone metabolism are not completely understood. The present study was performed to investigate the effects of aerobic and anaerobic exercise on bone turnover. Twenty healthy young males (aged 20-29 years) were followed through an 8-week program of aerobic (n = 10) and anaerobic training (n = 10). Ten age-matched individuals served as controls. Serum bone-specific alkaline phosphatase (BAP), serum osteocalcin (OC), and urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd) were determined as indices of bone metabolism. After 4 weeks of aerobic training, serum BAP and OC (p < 0.01), and urinary Pyd (p < 0.001) and Dpd (p < 0.01) were significantly reduced. After 8 weeks, BAP and OC levels had returned to baseline values, whereas the urinary cross-link excretion remained low. In the anaerobic training group, elevated levels of BAP (p < 0.05 vs. week 4), OC (p < 0.05 vs. week 4), and Pyd (p < 0. 01 vs. week 0) were observed after 8 weeks of exercise. Changes in urinary Pyd and Dpd (week 0 vs. week 8) were positively correlated with changes in the mean power level in the Wingate test, a parameter of the anaerobic performance capacity (r = 0.50 and r = 0. 55, p < 0.01, respectively). In the controls, no significant changes in biochemical markers were observed. We conclude that aerobic and anaerobic training excert different effects on bone metabolism. While aerobic training led to changes compatible with reduced bone resorption activity, anaerobic training seems to result in an overall accelerated bone turnover. Therefore, the impact of physical activity on bone turnover may depend on the kind of exercise performed.

Adult↗
PubMed1998

[Vitamin D receptor gene polymorphism and the rate of bone loss of the femur neck and lumbar spine in hemodialized patients with chronic renal failure].

It has been suggested that the vitamin D receptor (VDR) gene Bsml-polymorphism is a genetic determinant of bone metabolism. To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 136 haemodialyzed patients. Lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1.25(OH)2D3, osteocalcin serum concentrations, bone alkaline phosphatase activity and intact 1, 84-PTH levels were measured. VDR genotype BB, Bb and bb were found in 24%, 46% and 30% of patients respectively. Initial BMD (g/cm2) of lumbar spine and femoral neck did not differ between genotypes, however the decrease of femoral neck BMD during 18 months of observation differ significantly (p < 0.02) between the particular genotype groups (femoral neck: BB -0.031 +/- 0.029; Bb -0.027 +/- 0.017; bb -0.017 +/- 0.019 g/cm2). Significantly lower serum level of 25OHD3 was found in patients with the BB genotype before and after 18 months of observation in comparison to the respective values obtained in bb genotype patients, (respectively, 21.0 +/- 16.8 ng/ml vs 30.8 +/- 17.9 ng/ml; p < 0.01 and 24.0 +/- 10.8 ng/ml vs 32.4 +/- 16.0 ng/ml; p < 0.02). BB genotype patients were also characterised by significantly lower serum level of 1.25(OH)2D3 both initially and after 18 month of the study (respectively in BB and bb patients 25.9 +/- 9.7 pg/ml vs 30.7 +/- 10.0 pg/ml; p < 0.02 and 18.4 +/- 12.3 pg/ml vs 24.3 +/- 13.0 pg/ml; p < 0.01). No significant differences were found in Ca, P, osteocalcin, iPTH serum concentrations and bone fraction of alkaline phosphatase activity between particular genotypes. Results from this study suggest that faster bone mineral loss and more exaggerated disturbances of vitamin D metabolism are present in haemodialyzed uraemic patients with BB than bb genotype of VDR.

Adult↗
PubMed1998

[Effect of proctocolectomy on fluid balance--comparison of conventional ileostomy, ileorectal anastomosis and ileoanal pouch operation].

Total colectomy for ulcerative colitis (UC) and familiar adenomatous polyposis coli (FAP) is mainly performed as an ileoanal Pouch procedure (IAP). Alternatives are ileorectal anastomosis (IRA) and conventional proctocolectomy with Brooke ileostomy (CPS). The different surgical techniques may influence the excretion of water and electrolytes in stool and urine and may lead to a higher risk for urolithiasis. We investigated patients (12 IAP, 12 IRA and 8 CPS) several years after surgery and compared them to twelve normal controls. Total fecal and urinary output was collected at two consecutive days. Volume and electrolytes were determined in stool and urine. The risk for urinary stone formation was calculated by nomograms. Fecal volume and sodium (Na+) excretion was increased in all therapy groups compared to controls. IAP and IRA had significant less stool volume and Na+ excretion compared to CPS. Augmented fecal Na+ excretion was compensated by reduction of renal output after colectomy compared to controls. There were no significant differences in the daily urine volume between any groups. There was no urolithiasis in any groups. The nomograms showed a risk for all groups and controls to develop urinary stones.

Adenomatous Polyposis Coli↗
PubMed1998

Validity of new immunological human fecal hemoglobin and albumin tests in detecting colorectal neoplasms--an endoscopy-controlled study.

BACKGROUND: Screening for occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. To increase sensitivity and specificity the immunological determination of human hemoglobin and albumin in feces has been developed. The validity of analyzing only two samples from one bowel movement of either test is not known. METHODS: An immunological determination of human fecal hemoglobin and albumin using luminescence immunoassays (LIA) was performed in 739 patients with gastrointestinal complaints before scheduled colonoscopy. Each patient collected two 1 ml samples from one stool. There were no dietary restrictions. RESULTS: The sensitivity for detecting colorectal carcinomas was 95.3% (95% confidence interval 84.2-99.4%) with hemoglobin and 67.4% (95% confidence interval 51.2-80.9%) with albumin. The sensitivity for detecting large adenomatous polyps was 62.9% (95% confidence interval 50.5-74.1%) with hemoglobin and 32.9% (95% confidence interval 22.1-45.1%) with albumin. The specificity was 97% for hemoglobin, 96% for albumin and 94% for the combined test. CONCLUSIONS: The immunological determination of fecal hemoglobin is superior to albumin and has a better sensitivity for the detection of colorectal neoplasms than that reported for guaiac tests, even if two samples from one bowel movement are examined. The immunological determination of fecal hemoglobin should therefore be evaluated for use in colorectal cancer screening.

Colonoscopy↗
PubMed1998

[Levels of 1,25-dihydroxyvitamin D3 concentration in renal venous blood serum of patients with renovascular hypertension caused by unilateral renal artery stenosis].

UNLABELLED: Functionally significant, unilateral renal artery stenosis is characterized by reduced renal perfusion and lateralization of both excretory and endocrine function. The present study aimed to assess the influence of unilateral renal artery stenosis on plasma 1,25-dihydroxyvitamin D3 level. In sixteen patients (10 males and 6 females) with unilateral renovascular hypertension blood samples for estimation of plasma renin activity (PRA) and 1,25-dihydroxyvitamin D3 concentration were withdrawn from the renal vein of the ischaemic and normal kidney, from the femoral artery and from the vena cava inferior distally to the orifices of renal veins. Significantly elevated PRA (20.1 +/- 4.52 ng/ml/h vs 6.0 +/- 1.76 ng/ml/h, p < 0.005) but significantly reduced level of 1,25-dihydroxyvitamin D3 (99.25 +/- 4.8 pmol/l vs 115.75 +/- 6.7 pmol/l, p < 0.05) were found in renal vein blood of the ischaemic kidney as compared with the respective values of the normal kidney. No significant correlation was found between PRA and 1.25-dihydroxyvitamin D3 irrespective of the site of blood withdrawal. CONCLUSION: Renal ischaemia seems to exert a suppressive effect on 1,25-dihydroxyvitamin D3 synthesis by the kidney.

Adult↗
PubMed1997

Solid phase competitive luminescence immunoassay for immunoglobulin A in faeces: development and clinical validation.

We describe a new simple solid-phase competitive luminescence immunoassay (LIA) for the determination of immunoglobulin A (IgA) in faeces. The assay utilizes an anti-alpha-chain IgA antibody which is coated to polystyrene beads and acridinium ester-labelled human IgA as tracer and, therefore, measures both monomeric and polymeric IgA. Dilution recovery of an internal standard was 96, 100 and 103%. Interassay and intra-assay coefficients of variation (C.V.) ranged from 4.5 to 12.9%. The upper limit of normal of faecal IgA in 122 healthy controls was found to be 300 mg/l IgA (mean 73 mg/l, specificity of 99.2%). Patients with inactive Crohn's disease (Crohn's disease activity index (CDAI < 150, n = 14) had faecal IgA values up to 3317 mg/l (mean 1073 mg/l; P < 0.0001). In the active group (CDAI > 150, n = 26) faecal IgA values ranged from 49 to 4094 mg/l (mean 1253 mg/l; P < 0.0001). Patients with ulcerative colitis were divided into a group with active disease (n = 18) and a remission group (n = 16) with values up to 1843 mg/l faecal IgA (man 486 mg/l; P < 0.0032) and up to 602 mg/l faecal IgA (mean 176 mg/l; P < 0.4833), respectively. We also studied patients with non-inflammatory diseases of the gut with this assay. This LIA has proved to be a reliable method for the determination of elevated faecal IgA concentrations and for the detection of pathological findings in the gastrointestinal tract, especially in Crohn's disease.

Adolescent↗
PubMed1997

Measurement of vitamin D and its metabolites (calcidiol and calcitriol) and their clinical significance.

The serum concentration of vitamin D will only give information about the recent exposure to either nutritional vitamin D or to recent vitamin D production in the skin. Within hours vitamin D is removed from the circulation and reappears again a few hours later as 25(OH)D. Measurements of vitamin D therefore are not useful to judge the vitamin D status of man. Plasma concentrations of 25-hydroxyvitamin D (25(OH)D) are the best markers of imminent or existing vitamin D deficiency. Suboptimal vitamin D supply (or 25(OH)D plasma concentrations) are observed in most European countries and North America from November to April. Vitamin D substitution is recommended to persons with a serum concentration of 25(OH)D below 50 nmol/L (20 micrograms/L). Plasma concentrations of 1,25(OH)2D3 (calcitriol) depend mainly on renal function, concentrations of intact PTH and the supply of the organism with calcium and phosphate. High PTH, low calcium and low phosphate supply are the main stimulators of the production of calcitriol. Vitamin D substitution, or if necessary, therapy with active vitamin D metabolites or analogs, e.g. calcitriol or alfacalcidol, are often necessary in hypercalcemic persons with low serum concentrations of calcitriol, e.g. in patients with renal failure. Disorders with low or high vitamin D metabolite concentrations in serum are described in this paper.

Biomarkers↗
PubMed1996

Immunoluminometric assay (ILMA) for intact human proinsulin and its conversion intermediates.

We describe an immunoluminometric assay (ILMA) for determination of intact proinsulin and its conversion intermediates. 32,33-split and 65,66-split proinsulin, in human serum. After incubation of the serum samples with the IgG fraction of a guinea pig antiserum against human insulin coated to the surface of polystyrene beads, a sandwich complex was formed using a monoclonal antibody against human C-peptide labelled with acridinium ester as second antibody, yielding a detection limit of 0.11 pmol/l. Mean proinsulin concentration in the serum of 38 healthy fasting subjects was 7.3 pmol/l (S.D. +/- 5 pmol/l, median 5 pmol/l, 95th percentile 15 pmol/l); maximum serum proinsulin after oral glucose stimulation never exceeded 40 pmol/l. Eighteen of 20 patients with confirmed insulinoma had proinsulin concentrations over 50 pmol/l (mean 261 pmol/l, S.D. +/- 248 pmol/l, median 170 pmol/l, 95th percentile 663 pmol/l); serum proinsulin in two patients with completely enucleated B-cell adenoma declined to normal values after surgery.

Humans↗
PubMed1996

Immunochemiluminometric assay with two monoclonal antibodies against the N-terminal sequence of human parathyroid hormone.

We have developed an immunochemiluminometric assay (ICMA) with two monoclonal antibodies for the N-terminal sequence of human parathyroid hormone (hPTH). One monoclonal antibody (A1-70) was physically adsorbed onto polystyrene beads, the other (B1-70) was labelled with acridinium ester and synthetic hPTH (1-38) was used as standard. This assay has cross-reactions with synthetic hPTH (1-34) and hPTH (1-84) but no cross-reactions with hPTH (4-16), (28-48), (39-84), (44-68), (53-84) and hPTH-rP (1-86). The assay detection limit is 0.4 pmol/l. The normal range is 1.3-12 pmol/l based on 72 normal volunteers. About 91% of study patients (n = 58) with surgically proven primary hyperparathyroidism (1 degree HPT) had PTH values above normal and one of them showed a low normal intact PTH value but elevated PTH values with use of this assay. After immunoabsorption of plasma samples from patients with secondary hyperparathyroidism (2 degrees HPT) on hemodialysis with polystyrene beads containing antibodies against hPTH (39-84), some patients still showed significant amounts of PTH in this new ICMA but not intact PTH. The data reveal that significant amounts of amino-terminal immunoreactive PTH fragments rarely exist in 1 degree HPT but are present in some patients with 2 degrees HPT. The major advantage of this assay is to measure both amino-terminal PTH fragments and intact PTH with no interference from carboxy-terminal PTH fragments because two anti-N-terminal hormone sequence monoclonal antibodies are used.

Adult↗
PubMed1996

Growth hormone-binding protein related immunoreactivity is regulated by the degree of insulinopenia in diabetes mellitus.

OBJECTIVE: Derangements in the GH/IGF axis are common in patients with diabetes mellitus. In insulin-dependent diabetes mellitus (IDDM), these disturbances seem to be due to a partial defect in GH action on its own receptor or via a post-receptor defect. In non-insulin-dependent diabetes mellitus (NIDDM), data are limited, and the regulation of the GH receptor (GHR) remains unclear. However, animal studies with diabetic rats demonstrated that the GHR density may be influenced by insulin disposal at the hepatocyte. With respect to this hypothesis we studied the relation between peripheral insulin status and the serum GH-binding protein (GHBP), which reflects indirectly the GHR density in the tissues. Patients with IDDM were compared to a NIDDM group as well as to a group of healthy subjects. DESIGN AND PATIENTS: Basal blood samples for the determination of serum GHBP, GH, and IGF-I were obtained from patients with IDDM (n = 27), subjects with NIDDM (n = 112) and healthy controle (n = 42). Insulin, proinsulin, C-peptide and IGF-binding protein 1 (IGFBP-1) serum levels were used to estimate the insulin status in diabetic patients. RESULTS: GHBP serum levels were significantly lower in patients with IDDM than in either NIDDM or controls (P < 0.001). Conversely, the IGF-I levels were reduced in both groups of diabetics. A subgroup of hypoinsulinaemic NIDDM patients showed significantly decreased GHBP concentrations (P < 0.05) compared to the NIDDM sub-group with hyperinsulinaemia. Furthermore, GHBP levels were significantly decreased in insulin-treated patients with NIDDM compared to either non-insulin-requiring subjects or normal controls (P < 0.05). A significant direct relation was found between levels of GHBP and total insulin dose (P < 0.01) in patients with IDDM. In the NIDDM group, GHBP was correlated with proinsulin (P < 0.001), C-peptide (P < 0.01), Insulin (P < 0.05) and inversely with IGFBP-1 (P < 0.001). Multiple linear regression analysis indicated a significant contribution of proinsulin and IGFBP-1 to the variation of GHBP. CONCLUSIONS: Decreased GHBP levels in IDDM as well as in NIDDM correlate with insulinopenia. Since the degree of insulinopenia depends on the capability of the beta-cells to secrete proinsulin, C-peptide and insulin, we hypothesize that these hormones at least partially influence the serum level of GHBP. Low GHBP levels may reflect a reduced GH receptor density and a concomitant GH insensitivity, which leads to an impaired IGF generation in insulin-deficient patients.

Adult↗
PubMed1996

Prevalence of dialysis-related amyloidosis in diabetic patients. Diabetes Amyloid Study Group.

It has recently been shown that beta 2-microglobulin isolated from amyloid deposits in dialysis patients is modified by advanced glycation (AGE). In this context it appeared of interest to examine in a cross-sectional multicentre study whether dialysis-related amyloidosis, as evaluated by X-ray assessment of cysts in the metacarpal bones, was different in diabetic patients on maintenance haemodialysis for more than 5 years time compared with matched non-diabetic controls. We evaluated the hand skeleton of 75 diabetic patients (9 type I, 66 type II; 35 male, 40 female; median age 64 years, range 31-86; median duration of dialysis 7 years, range 5-17). They were compared with 150 patients without diabetes mellitus who were matched for age, gender and duration of dialysis. Hand X-rays were centrally evaluated by one radiologist unaware of the underlying clinical diagnosis. The overall frequency of amyloid cysts was 9/75 (12%) in diabetic patients (95% confidence interval 4.6-19.3%) and 28/150 (19%) in matched controls (95% confidence interval 12.4-24.9%). The results indicate that diabetes mellitus does not confer an increased risk of dialysis-related amyloid cysts. The results are of interest with respect to the mechanism of amyloid formation.

Adult↗