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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amylin is a 37-amino-acid peptide related to CGRP and calcitonin. It is co-secreted with insulin from pancreatic beta-cells. Amylin is deficient with type 1 diabetes mellitus. To study the in vivo effects of amylin in humans, diabetic patients are an adequate model of chronic amylin deficiency. We investigated the effect of a 12 months pramlintide therapy (amylin analogue) on bone metabolism in patients with type 1 diabetes mellitus. 23 patients with type 1 diabetes mellitus (age 45.2 +/- 10.3 years, duration of diabetes mellitus 20.7 +/- 9.8 years, 13 male, 10 female) injected themselves 0.1 ml pramlintide, a human amylin analogue, four times per day for a period of 12 months. Bone mineral density measurements of the lumbar spine by dual-energy X-ray absorptiometry (DXA), and biochemical markers of bone metabolism (serum-calcium, PTH, osteocalcin, urinary pyridinium cross-links) were obtained before and one year after starting pramlintide therapy. None of the following parameters changed significantly: bone density, serum calcium, PTH, osteocalcin or pyridinium cross-links. Only osteocalcin decreased from 7.205 ng/ml to 5.825 ng/ml, but this change was not statistically significant. We conclude that a one-year pramlintide therapy does not affect bone density or bone metabolism in patients with type 1 diabetes mellitus without osteopenia (based on the markers used).
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PMID:The effect of pramlintide (amylin analogue) treatment on bone metabolism and bone density in patients with type 1 diabetes mellitus. 1049 73

The purpose of this study was to determine whether human parathyroid hormone (h-PTH) enhances trabecular bone mass and connectivities that were reduced by streptozotocin (STZ)-induced diabetes in rats. Seven-month-old female Wistar rats were injected with STZ or its vehicle intraperitoneally. All vehicle-injected normal controls were sacrificed 0, 4, 6, 8, 12, 14, and 16 weeks after injection, and one-third of the STZ-injected rats were sacrificed as the baseline controls 4, 6, and 8 weeks after the injection. Eight-week h-PTH (6. 0 microg/kg, 6 times a week) or its vehicle treatment by subcutaneous injection for residual diabetic rats was started 4, 6, or 8 weeks after the STZ injection. The rats' proximal right tibiae were processed for undecalcified Villanueva bone staining sections for bone histomorphometry. Furthermore, changes in trabecular connectivities were determined by node-strut analysis. The decreased cancellous bone volume (BV/TV) and turnover in diabetic rats were recovered in all PTH-treated groups. In node-strut analysis, the node-related parameters (N.Nd/TV, NdNd/TV) were significantly increased by PTH when it was administered 4 weeks after STZ injection but were not increased when administration was started after 6 weeks. The results indicated that PTH enhanced bone turnover and bone mass but not trabecular connectivity in the late stage of diabetes in rats. Early treatment of osteoporosis is important in preventing fractures caused by decreased bone strength resulting from decreased trabecular connectivity.
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PMID:Histomorphometric evaluation of the recovering effect of human parathyroid hormone (1-34) on bone structure and turnover in streptozotocin-induced diabetic rats. 1066

Ca(2+)-Mg(2+)-ATPase is an important regulator of intracellular calcium concentration and therefore, of erythrocyte deformability. We have investigated the possible relationship between Ca(2+)-Mg(2+)-ATPase activity (ATPase) and ionized calcium (Ca(2+)), in diabetic patients with peripheral neuropathy. A total of 104 Type 2 diabetic patients (57 neuropathic and 47 non-neuropathic) and 25 non-diabetic subjects were studied. After an overnight fast, blood was taken for Ca(2+)-Mg(2+)-ATPase activity, Ca(2+), Mg(2+), PTH and HbA(1c). The neuropathy study group had significantly lower levels of ATPase, 6.6 (95% CI, 5.6-7.7) nmol/mg/min compared to controls 7. 1 (6.2-8.3) nmol/mg/min, P<0.001 and to diabetic patients without neuropathy 7.0 (6.0-8.1) nmol/mg/min, P<0.001. The study group had also lower levels of Ca(2+) (0.89+/-0.18 mmol/l vs. control 1.08+/-0. 24 mmol/l, P<0.01 and non-neuropathic 0.98+/-0.27 mmol/l, P<0.05) and Mg(2+) (0.73+/-0.13 mmol/l vs. control 0.81+/-0.14 mmol/l, P<0. 05), despite similar PTH levels. In diabetic subjects, no correlation was found between ATPase or Ca(2+) with glucose, HbA(1c), age or duration of diabetes. We conclude that in patients with diabetic neuropathy there are abnormalities of Ca(2+)-Mg(2+)-ATPase activity and Ca(2+). This provides further support for the role of microangiopathy in the pathogenesis of neuropathy.
Diabetes Res Clin Pract 2000 Aug
PMID:Ca(2+)-Mg(2+)-ATPase activity and ionized calcium in Type 2 diabetic patients with neuropathy. 1096 22

The recent identification of MEN1 gene mutations as the molecular cause of familial multiple endocrine neoplasia type 1 syndrome (MEN1) has had a significant impact on clinical patient care. In the following consensus statement we will present recommendations for clinical screening and follow-up in patients and relatives with suspected or established MEN1 syndrome. MEN1 mutational analysis should be performed in individuals with newly diagnosed MEN1-typical endocrine neoplasia (e.g., primary hyperparathyroidism, gastroenteropancreatic tumor, pituitary adenoma) if additional diagnostic criteria are met (e.g., age <40 years; positive family history; multifocal or recurrent neoplasia; two or more organ systems affected). Genetic family screening is advisable in first degree relatives of MEN1 patients during early adolescence to reliably assess future MEN1 disease risk. In symptomatic individuals carrying MEN1 germ line mutations, annual clinical and biochemical (calcium, PTH, gastrin, prolactin) follow-up as well as routine pancreatic and pituitary imaging may be complemented as individually needed. In contrast, relatives without family-specific MEN1 mutation do not require routine follow-up. Diagnostic procedures and treatment in symptomatic MEN1 mutation carriers and patients may differ from that in sporadic endocrine neoplasia, calling for individual management. Genetic counselling and dedicated endocrine surgery should be integral parts of current medical care in MEN1 syndrome.
Exp Clin Endocrinol Diabetes 2000
PMID:Concepts for screening and diagnostic follow-up in multiple endocrine neoplasia type 1 (MEN1). 1098 49

Loss of bone is a significant problem after renal transplant. Although bone loss in the first post transplant year has been well documented, conflicting data exist concerning bone loss after this time. It is equally unclear whether bone loss in long-term renal transplant recipients correlates with bone turnover as it does in postmenapausal osteoporosis. To examine these issues, we conducted a cross-sectional study to define the prevalence of osteoporosis in long-term (> 1 year) renal transplant recipients with preserved renal function (mean creatinine clearance 73 +/- 23 ml/min). Bone mineral density (BMD) was measured at the hip, spine and wrist by DEXA in 69 patients. Markers for bone formation (serum osteocalcin) and bone resorption [urinary levels of pyridinoline (PYD) and deoxypyridinoline (DPD)] were also measured as well as parameters of calcium metabolism. Correlations were made between these parameters and BMD at the various sites. The mean age of the patients was 45 +/- 11 years. Eighty eight percent of patients were on cyclosporine (12% on tacrolimus) and all but 2 were on prednisone [mean dose 9 +/- 2 mg/day)]. Osteoporosis (BMD more than 2.5 SD below peak adult BMD) at the spine or hip was diagnosed in 44% of patients and osteopenia was present in an additional 44%. Elevated levels of intact parathyroid hormone (i PTH) were observed in 81% of patients. Elevated urinary levels of PYD or DPD were present in 73% of patients and 38% had elevated serum levels of osteocalcin. Levels of calcium, and of 25(OH) and 1,25(OH)2 vitamin D were normal. In a stepwise multiple regression model that included osteocalcin, PYD, DPD, intact PTH, age, years posttransplant, duration of dialysis, cumulative prednisone dose, smoking, and diabetes: urinary PYD was the strongest predictor of bone mass. These results demonstrate that osteoporosis is common in long-term renal transplant recipients. The data also suggest that elevated rates of bone resorption contribute importantly to this process.
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PMID:Posttransplant bone disease: evidence for a high bone resorption state. 1115 4

Calcium supplementation is important in the treatment of osteoporosis, a disease that may also occur in diabetic patients. The acute effects of calcium supplementation and their relationship to gastric emptying time, however, have rarely been studied in type 2 diabetic patients. We evaluated the acute biochemical variations induced by the administration of two different calcium preparations, calcium citrate and calcium carbonate, in 16 (male/female: 13/3) Chinese diabetic patients. Serum free calcium, intact parathyroid hormone (i-PTH), and amount of urinary excretion of calcium (uCal/uCr) were evaluated after a single dose of 1200 mg of elemental calcium in each preparation. The free calcium levels did not change significantly in either group. However, significant suppression of i-PTH after calcium citrate administration at 1 h (17.1+/-2.0 pg/ml, P=.023), and after calcium carbonate administration at 2 h (14.2+/-2.5 pg/ml, P=.000), was noted when compared with individual basal level (21.2+/-2.5 and 19.3+/-2.4 pg/ml, respectively). The suppressive effect on i-PTH lasted for 6 h after calcium citrate and 5 h after calcium carbonate preparation of the 6-h study period. After administration of calcium citrate, the uCal/uCr of 2-to-4-h collection was significantly higher than that of the basal and 0-to-2-h collections: 0.25+/-0.04 vs. 0.19+/-0.03, P=.025; and 0.25+/-0.04 vs. 0.19+/-0.02, P=.014, respectively. A similar finding was observed for calcium carbonate: 0.23+/-0.03 vs. 0.18+/-0.02, P=.019; and 0.23+/-0.03 vs. 0.18+/-0.02, P=.011, respectively. We conclude that, in this group of Chinese type 2 diabetic patients in our study, the oral administration of 1200 mg elemental calcium in either calcium citrate or calcium carbonate preparation can induce a significant suppression of i-PTH. This may be helpful in preventing or treating osteoporosis. A prolonged gastric emptying time in these diabetic subjects may contribute to the non-significant alteration in free calcium levels after the administration of either calcium preparation.
J Diabetes Complications
PMID:Acute biochemical variations induced by calcium citrate and calcium carbonate in Type 2 diabetic patients: impaired calcium absorption in Type 2 diabetic patients with prolonged gastric emptying time. 1127 6

This cross-sectional study, performed on 146 healthy (n = 64) or osteoporotic but otherwise normal (n = 82) pre- (n = 38) or post-menopausal (n = 108) female subjects, analyzed the relationships between bone mineral density (BMD) (measured by dual-energy X-ray absorptiometry), parameters of bone remodelling, indices of calcium homeostasis and systemic IGF-I or insulin levels against a background of natural aging. BMD (g/cm(2)) at the hip correlated to serum IGF-I concentration (r = 0.207, p < 0.05), as well as to insulin levels (r = 0.241, p < 0.01), while BMD at the spine correlated only to IGF-I levels (r = 0.173, p < 0.05). After adjustment for age, body mass index, serum PTH, vitamin D status and calcitonin levels, neither IGF-I nor insulin levels could be significantly related to BMD at the spine or hip. On the other hand, 25-OH vitamin D(3) was found to be an important predictor of BMD at the hip (beta = 0.1686, p = 0.0437). In conclusion, this study failed to demonstrate a predictive importance of insulin-IGF-I axis to the development of bone mass. Instead, a significant predictive value to BMD at the hip was documented for serum 25-OH vitamin D(3).
Exp Clin Endocrinol Diabetes 2001
PMID:Systemic insulin-like growth factor-I, insulin and vitamin D status in relation to age-associated bone loss in women. 1150 50

Dutch adolescents who consumed a macrobiotic (vegan-type) diet in early life, demonstrate a lower relative bone mass than their omnivorous counterparts. We investigated whether subjects from the macrobiotic group showed signs of catching up with controls in terms of relative bone mass, reflected by higher levels of serum osteocalcin and alkaline phosphatase and lower levels of urinary cross-links. Group differences in calciotropic hormones and mineral excretion were also investigated. Bone measurements, blood, and urine samples were obtained from 69 macrobiotic (34 girls, 35 boys) and 99 control (57 girls, 42 boys) subjects, aged 9-15. Bone turnover markers and 1,25(OH)2D reached maximal levels at pubertal stages 3-4, and decreased thereafter. After adjusting for puberty, age, and lean body mass, no group differences were found in markers of bone turnover, 1,25(OH)2D, PTH, or calcium excretion, but phosphate excretion was 23% lower in macrobiotic girls. After adjustment for puberty, 1,25(OH)2D was positively related to osteocalcin. In summary, we found no evidence for group differences in bone turnover, or catch up in relative bone mass, which might be due to the fact that 60% of subjects were still in early stages of puberty.
Exp Clin Endocrinol Diabetes 2001
PMID:Are levels of bone turnover related to lower bone mass of adolescents previously fed a macrobiotic diet? 1150 53

Glucagon binding to hepatocytes has been known for a long time to not only stimulate intracellular cAMP accumulation but also, intriguingly, induce a significant release of liver-borne cAMP in the blood. Recent experiments have shown that the well-documented but ill-understood natriuretic and phosphaturic actions of glucagon are actually mediated by this extracellular cAMP, which inhibits the reabsorption of sodium and phosphate in the renal proximal tubule. The existence of this "pancreato-hepatorenal cascade" indicates that proximal tubular reabsorption is permanently influenced by extracellular cAMP, the concentration of which is most probably largely dependent on the insulin-to-glucagon ratio. The possibility that renal cAMP receptors may be involved in this process is supported by the fact that cAMP has been shown to bind to brush-border membrane vesicles. In other cell types (i.e., adipocytes, erythrocytes, glial cells, cardiomyocytes), cAMP eggress and/or cAMP binding have also been shown to occur, suggesting additional paracrine effects of this nucleotide. Although not yet identified in mammals, cAMP receptors (cARs) are already well characterized in lower eukaryotes. The amoeba Dictyostelium discoideum expresses four different cARs during its development into a multicellular organism. cARs belong to the superfamily of seven transmembrane domain G protein-coupled receptors and exhibit a modest homology with the secretin receptor family (which includes PTH receptors). However, the existence of specific cAMP receptors in mammals remains to be demonstrated. Disturbances in the pancreato-hepatorenal cascade provide an adequate pathophysiological understanding of several unexplained observations, including the association of hyperinsulinemia and hypertension, the hepatorenal syndrome, and the hyperfiltration of diabetes mellitus. The observations reviewed in this paper show that cAMP should no longer be regarded only as an intracellular second messenger but also as a first messenger responsible for coordinated hepatorenal functions, and possibly for paracrine regulations in several other tissues.
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PMID:Extracellular cAMP inhibits proximal reabsorption: are plasma membrane cAMP receptors involved? 1183 18

The case of a 25 year old female patient with pseudohypoparathyroidism type I (PHP) and hypercalcitoninaemia is reported. She was referred to our clinic because of recurrent hypocalcaemia associated with paraesthesias and muscle cramps. She had no signs of Albright hereditary osteodystrophy (AHO), a normal mental status and no family history of hypocalcaemia or any other endocrine disease. Considering the laboratory results with hypocalcaemia, hyperphosphataemia, normal vitamin D and normal creatinine with an extraordinary elevated PTH we diagnosed pseudohypoparathyroidism type I. She had delayed pubertal development with menarche in the age of 20 and hypothyroidism with an atrophic thyroid since she was 22 years old. Calcitonin (CT) was increased and the performed pentagastrin test showed an excessive CT-response with a peak of 725 pg/ml after 2 min. Up to now there are only three reports of patients with PHP and hypercalcitoninaemia. An abnormal pentagastrin response is known to be a specific marker for medullary thyroid carcinoma, but there were no signs of any malignant disease, even after one year of follow-up. The most reasonable cause for the pathological pentagastrin response might be chronic hypocalcaemia. When interpreting a pathological pentagastrin test in a patient with PHP the specifity of the test might be diminished and a careful observational strategy might be appropriate.
Exp Clin Endocrinol Diabetes 2002 Apr
PMID:Abnormal pentagastrin response in a patient with pseudohypoparathyroidism. 1260 52


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