| 1. |
- Hagander, B, et al.
(författare)
-
Effect of dietary fibre on blood glucose, plasma immunoreactive insulin, C-peptide and GIP responses in non insulin dependent (type 2) diabetics and controls
- 1984
-
Ingår i: Acta Medica Scandinavica. - 0001-6101. ; 215:3, s. 205-213
-
Tidskriftsartikel (refereegranskat)abstract
- A high fibre and a low fibre breakfast meal were given to eight non insulin dependent diabetics ( NIDD ), and eight controls. Blood glucose response was monitored continuously for three hours and characterized using a straight line model. After the high fibre meal the rates of increase and decrease in blood glucose concentration were slower both in diabetics and controls than after the low fibre meal. The delay time, however, i.e. the time from meal intake to the start of glucose increase, hypothetically corresponding to gastric emptying time, was the same after both test meals. The postprandial glucose increment calculated as the area under the 0-120 min curve was lower after the high fibre meal in the NIDD , but not in the controls. The two-hour C-peptide and gastric inhibitory polypeptide values were lower for the diabetics after the high fibre breakfast. The results indicate a prolonged carbohydrate digestion and/or absorption after high fibre breakfast.
|
|
| 2. |
|
|
| 3. |
- Ahren, Bo, et al.
(författare)
-
Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes : The adjunct two randomized trial
- 2016
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:10, s. 1693-1701
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS Mean baseline glycated hemoglobin (HbA1c ) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6mmol/mol]; 1.2mg: -0.22% [2.4mmol/mol]; 0.6 mg: -0.23% [2.5mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2mg vs. placebo and of hyperglycemia with ketosis >1.5mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
|
|
| 4. |
- Ahrén, Bo, et al.
(författare)
-
Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.
- 2011
-
Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 13:9, s. 775-783
-
Forskningsöversikt (refereegranskat)abstract
- Inhibition of dipeptidyl peptidase-4 (DPP-4) by vildagliptin prevents degradation of glucagon-like peptide-1 (GLP-1) and reduces glycemia in type 2 diabetes, with low risk for hypoglycemia and no weight gain. Vildagliptin binds covalently to the catalytic site of DPP-4, eliciting prolonged enzyme inhibition. This raises intact GLP-1 levels, both after meal ingestion and in the fasting state. Vildagliptin has been shown to stimulate insulin secretion and to inhibit glucagon secretion in a glucose-dependent manner. At hypoglycemic levels, the counterregulatory glucagon response is enhanced relative to baseline by vildagliptin. Vildagliptin also inhibits hepatic glucose production, mainly through changes in islet hormone secretion, and improves insulin sensitivity, as determined with a variety of methods. These effects underlie the improved glycemia with low risk for hypoglycemia. Vildagliptin also suppresses postprandial triglyceride-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced triglyceride stores in non-fat tissues. The large body of knowledge on vildagliptin regarding enzyme binding, incretin and islet hormone secretion and glucose and lipid metabolism is summarized, with discussion of the integrated mechanisms and comparison with other DPP-4 inhibitors and GLP-1 receptor activators, where appropriate.
|
|
| 5. |
- Alam, M, et al.
(författare)
-
Gastric bypass surgery, but not caloric restriction, decreases dipeptidyl peptidase 4 activity in obese patients with type 2 diabetes.
- 2011
-
Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 13:4, s. 378-381
-
Tidskriftsartikel (refereegranskat)abstract
- The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass surgery (GBP) is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10 kg equivalent weight loss by GBP (n=16) or by caloric restriction (CR, n=14) in obese patients with type 2 diabetes. DPP-4 activity decreased after GBP by 11.6% (p=0.01), but not after CR. The increased peak GLP-1 and GIP response to oral glucose after GBP did not correlate with DPP-4 activity. The decrease in fasting plasma DPP-4 activity after GBP occurred by a mechanism independent of weight loss and did not relate to change in incretins concentrations. Whether the change in DPP-4 activity contributes to improved diabetes control after GBP remains therefore to be determined.
|
|
| 6. |
- Bergenfelz, A, et al.
(författare)
-
Biochemical variables associated with bone density in patients with primary hyperparathyroidism
- 1992
-
Ingår i: European Journal of Surgery, Acta Chirurgica. - 1102-4151. ; 158:9, s. 6-473
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To clarify the association between primary hyperparathyroidism and cortical osteopenia.DESIGN: Open study.SETTING: Department of Surgery, University of Lund, Sweden.SUBJECTS: 38 patients with primary hyperparathyroidism.OUTCOME MEASURES: Correlation between bone density (measured by single photon absorption) and age; sex; serum concentrations of parathyroid hormone and ionised calcium; serum alkaline phosphatase activity; and serum concentration of calcium, phosphate, creatinine, urea, osteocalcin, 25 hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol.RESULTS: There was no difference in bone density between men and women. There was no correlation between bone density and severity of hypercalcaemia or age. No biochemical abnormality was peculiar to the seven patients whose bone density was more than two SD below the population mean. Serum concentrations of 1,25 dihydroxycholecalciferol and osteocalcin both correlated significantly with bone density (p < 0.05) and there was a strong correlation between serum osteocalcin and serum intact parathyroid hormone (p < 0.001). Serum osteocalcin had the strongest correlation with bone density of any of the biochemical variables.CONCLUSION: There is little association between bone density and serum concentration of parathyroid hormone.
|
|
| 7. |
- Bergenfelz, A, et al.
(författare)
-
Prediction of changes in bone density after operation for primary hyperparathyroidism
- 1993
-
Ingår i: Annales Chirurgiae et Gynaecologiae. - 0355-9521. ; 82:4, s. 9-245
-
Tidskriftsartikel (refereegranskat)abstract
- Primary hyperparathyroidism (pHPT) is associated with osteopenia. However, the individual variation in recovery in bone mass after surgery is large. Therefore, modes of prediction of the increase in bone mass after parathyroid surgery were investigated. Preoperatively and at one year after surgery bone mineral content (BMC) in the distal radius was measured with single photon absorptiometry technique in 40 patients with pHPT. Serum levels of calcium, intact parathyroid hormone (PTH), alkaline phosphatase, osteocalcin and Vitamin D metabolites were also determined. Preoperatively, Z-score of BMC was -0.85 +/- 1.20 SD below the normal mean. There was a modest association between BMC and serum levels of osteocalcin (r = -0.34; P < 0.05), and dihydroxycholecalciferol (r = -0.35; P < 0.05). At one year after surgery, mean BMC increased by 2% (P < 0.05), but with a wide dispersion. Preoperative Z-score of BMC correlated with the relative change in BMC (r = -0.33; P < 0.05). An increase in BMC with 95% confidence was evident in 10 of the patients. None of these patients had a preoperative Z-score of BMC above the mean expected for age and sex. We conclude that the increase in bone mass after surgery for pHPT is small and evident only in a portion (approximately 25%) of patients. Hence, a decrease in bone mass should not be a major indication for surgery in pHPT.
|
|
| 8. |
- Bülow, B, et al.
(författare)
-
The gender differences in growth hormone-binding protein and leptin persist in 80-year-old men and women and is not caused by sex hormones.
- 2003
-
Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 59:4, s. 6-482
-
Tidskriftsartikel (refereegranskat)abstract
- objective Leptin and growth hormone-binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80-year-old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated. design and subjects Ninety-four subjects (55 females and 39 males), all 80 years old, were investigated in a community-based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement. methods Levels of testosterone, oestradiol, SHBG, IGF-I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA). results As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P <= 0·007), although serum oestradiol was higher in the men (P < 0·001). There were no significant associations between sex hormones and leptin or GHBP either in women or in men (all, r < 0·13, P > 0·1). Leptin correlated to kilogram fat mass in both women (r = 0·55, P < 0·001) and men (r = 0·47, P = 0·003), but in contrast, there were no significant correlations between GHBP and fat mass and GHBP and IGF-I, either in women or in men (all, r < 0·24, P > 0·2). Insulin and leptin were significantly associated with GHBP, both in women (r = 0·48, P < 0·001 and r = 0·43, P = 0·001, respectively) and in men (r = 0·40, P = 0·01 and r = 0·34, P = 0·03, respectively). conclusions Although the 80-year-old men had higher oestradiol levels than the women, the women had higher levels of leptin and GHBP. There were no correlations between sex hormones and leptin and GHBP, which indicates that the gender differences are not caused by sex hormones in old age. In contrast to studies in younger subjects, GHBP did not correlate to fat mass in the investigated 80-year-old men and women. In the older subjects investigated, as in younger subjects, GHBP was significantly correlated with leptin and insulin.
|
|
| 9. |
- Davani, B, et al.
(författare)
-
Aged transgenic mice with increased glucocorticoid sensitivity in pancreatic beta-cells develop diabetes
- 2004
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 5353 Suppl 1, s. S51-S59
-
Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are diabetogenic hormones because they decrease glucose uptake, increase hepatic glucose production, and inhibit insulin release. To study the long-term effects of increased glucocorticoid sensitivity in β-cells, we studied transgenic mice overexpressing the rat glucocorticoid receptor targeted to the β-cells using the rat insulin I promoter. Here we report that these mice developed hyperglycemia both in the fed and the overnight-fasted states at 12–15 months of age. Progression from impaired glucose tolerance, previously observed in the same colony at the age of 3 months, to manifest diabetes was not associated with morphological changes or increased apoptosis in the β-cells. Instead, our current results suggest that the development of diabetes is due to augmented inhibition of insulin secretion through α2-adrenergic receptors (α2-ARs). Thus, we found a significantly higher density of α2-ARs in the islets of transgenic mice compared with controls, based on binding studies with the α2-AR agonist UK 14304. Furthermore, incubation of islets with benextramine, a selective antagonist of the α2-AR, restored insulin secretion in response to glucose in isolated islets from transgenic mice, whereas it had no effect on control islets. These results indicate that the chronic enhancement of glucocorticoid signaling in pancreatic β-cells results in hyperglycemia and impaired glucose tolerance. This effect may involve signaling pathways that participate in the regulation of insulin secretion via the α2-AR.
|
|
| 10. |
- Grama, D, et al.
(författare)
-
Clinical characteristics, treatment and survival of pancreatic tumors causing hormonal syndromes
- 1992
-
Ingår i: World Journal of Surgery. - 0364-2313 .- 1432-2323. ; 16:4, s. 632-639
-
Tidskriftsartikel (refereegranskat)abstract
- Eighty-five patients with endocrine pancreatic tumors associated with clinical syndromes of hormone excess were retrospectively analyzed regarding symptomatology, means of diagnosis, and results of surgical and medical treatment during follow-up of 3-18 years (median 8 years). The combination of angiography and computed tomography was most successful in pre-operative localization of both primary tumors and metastases. Surgery provided long term cure in 39 of 44 patients with benign islet cell lesions, the majority having insulinomas. Forty-one patients had malignant tumors, which at the time of diagnosis or operation were associated with liver and/or regional lymph gland metastases in 56% and 24%, respectively. Sixteen patients with metastatic disease and/or very large tumors were considered inoperable, 5 patients underwent palliative resection of their malignant tumors, while grossly radical tumor removal was accomplished in 20 patients. Long-term cure was achieved in 5 patients by excision of primary tumors and localized liver or lymph gland metastases. Half of the patients, particularly those with insulinoma, gastrinoma, or vipoma, showed response to streptozotocin, in combination with other cytostatics, for a median of 24 months or a response to interferon for a median of 10 months. The overall 5-year and 10-year survival among the patients with malignant islet cells tumors was 54% and 28%, respectively. Absence of liver metastases at time of operation/diagnosis, smaller size of the primary tumor, grossly radical tumor resection as well as response to medical therapy predicted the more favorable survival.
|
|
| 11. |
- Grama, D, et al.
(författare)
-
Pancreatic tumors in multiple endocrine neoplasia type 1 : clinical presentation and surgical treatment
- 1992
-
Ingår i: World Journal of Surgery. - 0364-2313 .- 1432-2323. ; 16:4, s. 611-618
-
Tidskriftsartikel (refereegranskat)abstract
- Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Lindgärde, F, et al.
(författare)
-
Overweight is associated with lower serum leptin in Peruvian Indian than in Caucasian women : A dissociation contributing to low blood pressure?
- 2001
-
Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 50:3, s. 325-329
-
Tidskriftsartikel (refereegranskat)abstract
- We tested whether plasma levels of leptin and insulin are associated with the lower blood pressure in women of Peruvian Indian heritage compared with Caucasian women. A total of 181 women from Peru and 85 from Sweden, aged 20 to 60 years, with normal plasma glucose levels participated in the study. Measurements of anthropometry, blood pressure, and blood tests were performed after overnight fasting. Compared with women from Umeå in Sweden, women from Lima, Peru had higher body mass index (BMI) (26.2 +/- 4.9 v 24.4 +/- 3.8 kg/m(2)), waist circumference (85 +/- 11 v 79 +/- 10 cm), lower systolic blood pressure (99 +/- 15 v 114 +/- 14 mm; P <.001) and diastolic blood pressure (67 +/- 7 v 74 +/- 10 mm; P <.001). In addition, they had a reduction of the ratio of plasma leptin to BMI (0.52 +/- 0.22 v 0.61 +/- 0.36; P <.001), greater plasma insulin (80 +/- 42 v 41 +/- 21 pmol/L), but lower plasma glucose (4.2 +/- 0.5 v 5.1 +/- 0.5 mmol/L; P <.001). Furthermore, the 181 women from Lima had higher plasma triglyceride levels (1.5 +/- 0.8 v 1.3 +/- 0.7; P =.039), but lower plasma high-density lipoprotein (HDL)-cholesterol (1.0 +/- 0.2 v 1.5 +/- 0.4 mmol/L; P <.001) and total plasma cholesterol (5.0 +/- 1.1 v 5.9 +/- 1.3 mmol/L; P <.001) levels. Plasma leptin correlated with blood pressure and BMI in both populations (P <.001). In multiple regression analysis, BMI, but not log leptin, emerged as the determinant for systolic blood pressure. We concluded that women living in Lima have significant lower blood pressure levels in association with elevated plasma insulin concentrations, but lower plasma leptin values adjusted for BMI in comparison with women from northern Sweden. This may suggest that the concept of metabolic syndrome is different among women with Peruvian Indian heritage in comparison to a Caucasian population.
|
|
| 15. |
- Omar, B. A., et al.
(författare)
-
Enhanced insulin sensitivity mediated by adipose tissue browning perturbs islet morphology and hormone secretion in response to autonomic nervous activation in female mice
- 2016
-
Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 310:1
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance results in a compensatory increase in insulin secretion to maintain normoglycemia. Conversely, high insulin sensitivity results in reduced insulin secretion to prevent hypoglycemia. The mechanisms for this inverse adaptation are not well understood. We utilized highly insulin-sensitive mice, due to adipocyte-specific overexpression of the FOXC2 transcription factor, to study mechanisms of the reversed islet adaptation to increased insulin sensitivity. We found that Foxc2TG mice responded to mild hyperglycemia with insulin secretion significantly lower than that of wild-type mice; however, when severe hyperglycemia was induced, Foxc2TG mice demonstrated insulin secretion equal to or greater than that of wild-type mice. In response to autonomic nervous activation by 2-deoxyglucose, the acute suppression of insulin seen in wild-type mice was absent in Foxc2TG mice, suggesting impaired sympathetic signaling to the islet. Basal glucagon was increased in Foxc2TG mice, but they displayed severely impaired glucagon responses to cholinergic and autonomic nervous stimuli. These data suggest that the autonomic nerves contribute to the islet adaptation to high insulin sensitivity, which is compatible with a neuro-adipo regulation of islet function being instrumental for maintaining glucose regulation.
|
|
| 16. |
- Söderberg, Stefan, et al.
(författare)
-
Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women.
- 2001
-
Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 144:3, s. 283-290
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone-IGF-I axis are linked to obesity and cardiovascular diseases. However, whether the association between leptin and the GH-IGF-I axis is altered with increasing obesity is not known. We therefore examined the relationship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a population study.DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design.METHODS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for specific insulin and proinsulin.RESULTS: Leptin inversely correlated to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal women (P<0.05). The association between leptin and IGFBP-1 was lost after adjustment for insulin. In multivariate analyses taking measures of adiposity into account, low proinsulin, and IGF-I in combination with old age, but not leptin, predicted high IGFBP-1 levels.CONCLUSIONS: Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated with IGFBP-1 in non-obese men and premenopausal women. However, these associations were lost with increasing central obesity in men and premenopausal women and after control for insulin. Therefore, this study suggests (i) that leptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationship between leptin, IGFBP-1 and insulin.
|
|
| 17. |
|
|
| 18. |
- Abels, Mia, et al.
(författare)
-
CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion
- 2016
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:9, s. 1928-1937
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart(-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice. Methods CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and rodent models of diabetes. Insulin and glucagon secretion was examined in isolated islets and in vivo in mice. Ca2+ oscillation patterns and exocytosis were studied in mouse islets. Results We report an important role of CART in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. CART increased insulin secretion in vivo in mice and in human and mouse islets. Furthermore, CART increased beta cell exocytosis, altered the glucose-induced Ca2+ signalling pattern in mouse islets from fast to slow oscillations and improved synchronisation of the oscillations between different islet regions. Finally, CART reduced glucagon secretion in human and mouse islets, as well as in vivo in mice via diminished alpha cell exocytosis. Conclusions/interpretation We conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Ahmadi, Shilan Seyed, et al.
(författare)
-
Effect of liraglutide on anthropometric measurements, sagittal abdominal diameter and adiponectin levels in people with type 2 diabetes treated with multiple daily insulin injections: evaluations from a randomized trial (MDI-liraglutide study 5)
- 2019
-
Ingår i: Obesity Science and Practice. - : Wiley. - 2055-2238. ; 5:2, s. 130-140
-
Tidskriftsartikel (refereegranskat)abstract
- Aim Use of the glucagon-like peptide 1 receptor agonist liraglutide has been shown to reduce weight. Different types of anthropometric measurements can be used to measure adiposity. This study evaluated the effect of liraglutide on sagittal abdominal diameter, waist circumference, waist-to-hip ratio and adiponectin levels in people with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDI). Materials and methods In the multicentre, double-blind, placebo-controlled MDI-liraglutide trial, 124 individuals with T2D treated with MDI were randomized to either liraglutide or placebo. Basal values of weight, waist circumference, waist-to-hip ratio, sagittal abdominal diameter and adiponectin were compared with measurements at 12 and 24 weeks after randomization. Results Baseline-adjusted mean weight loss was 3.8 +/- 2.9 kg greater in liraglutide than placebo-treated individuals (p < 0.0001). Waist circumference was reduced by 2.9 +/- 4.3 cm and 0.2 +/- 3.6 cm in the liraglutide and placebo groups, respectively, after 24 weeks (baseline-adjusted mean difference: 2.6 +/- 4.0 cm, p = 0.0005). Corresponding reductions in sagittal abdominal diameter were 1.1 +/- 1.7 cm and 0.0 +/- 1.8 cm (baseline-adjusted mean difference: 1.1 +/- 1.7 cm, p = 0.0008). Hip circumference was reduced in patients randomized to liraglutide (baseline-adjusted mean difference between treatment groups: 2.8 +/- 3.8 cm, p = 0.0001), but there was no significant difference between the groups in either waist-to-hip ratio (baseline-adjusted mean difference: 0.0 +/- 0.04 cm, p = 0.51) or adiponectin levels (baseline-adjusted mean difference: 0.8 +/- 3.3 mg L-1, p = 0.17). Lower HbA1c and mean glucose levels measured by masked continuous glucose monitoring at baseline were associated with greater effects of liraglutide on reductions in waist circumference and sagittal abdominal diameter. Conclusions In patients with T2D, adding liraglutide to MDI may reduce abdominal and hip obesity to a similar extent, suggesting an effect on both visceral and subcutaneous fat. Liraglutide had greater effects on reducing abdominal obesity in patients with less pronounced long-term hyperglycaemia but did not affect adiponectin levels.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Ahrén, B, et al.
(författare)
-
Effects of minor increase in serum calcium on the immunoheterogeneity of parathyroid hormone in healthy subjects and in patients with primary hyperparathyroidism
- 1995
-
Ingår i: Hormone Research. - 0301-0163. ; 43:6, s. 9-294
-
Tidskriftsartikel (refereegranskat)abstract
- To study possible influences of a mild increase in serum-ionized calcium concentration that is seen during daily life on circulating parathyroid hormone (PTH) immunoheterogeneity, we used sequence-specific PTH assays to determine serum intact PTH, C-terminal PTH and N-terminal PTH following oral calcium (1.5 g) in healthy subjects (n = 7). This was also performed in patients with primary hyperparathyroidism (pHPT; n = 10) to see if their regulation of circulating PTH molecular forms is normal. Compared to healthy subjects, the patients were hypercalcemic (p < 0.05) and had higher levels of PTH in all three assays (p < 0.001). Following the oral calcium load, serum-ionized calcium increased by 0.08 +/- 0.03 mmol/l in the patients and by 0.07 +/- 0.03 mmol/l in the healthy subjects after 90 min, whereas serum intact PTH, C-terminal PTH and N-terminal PTH were reduced, both in the healthy subjects and in the patients. Suppression by calcium of both intact PTH and C-terminal PTH were impaired in the patients (p < 0.05 and p < 0.001), whereas suppression of N-terminal PTH was normal. Furthermore, the C/i and N/i ratios were higher at the highest calcium concentration achieved after calcium intake in the healthy subjects than in the basal state in the patients (p < 0.05), in spite of the larger degree of hypercalcemia in the latter (1.40 +/- 0.06 vs. 1.31 +/- 0.02 mmol/l; p < 0.05). Thus, (1) a minor increase in serum-ionized calcium that is seen during daily life alters the relative circulating concentrations of PTH versus its fragments; (2) the impaired sensitivity to calcium in pHPT is not evident for the suppression of N-terminal PTH, and (3) pHPT is accompanied by altered immunoheterogeneity of circulating PTH.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Ahren, B, et al.
(författare)
-
No correlation between insulin and islet amyloid polypeptide after stimulation with glucagon-like peptide-1 in type 2 diabetes
- 1997
-
Ingår i: European journal of endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 137:6, s. 643-649
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine whether glucagon-like peptide-1 (GLP-1), which has been suggested as a new therapeutic agent in type 2 diabetes, affects circulating islet amyloid polypeptide (IAPP), a B-cell peptide of potential importance for diabetes pathophysiology. DESIGN: GLP-1 was administered in a buccal tablet (400 micrograms) to seven healthy subjects and nine subjects with type 2 diabetes. Serum IAPP and insulin levels were measured before and after GLP-1 administration. RESULTS: In the fasting state, serum IAPP was 4.1 +/- 0.3 pmol/l in the controls vs 9.8 +/- 0.9 pmol/l in the subjects with type 2 diabetes (P < 0.001). IAPP correlated with insulin only in controls (r = 0.74, P = 0.002) but not in type 2 diabetes (r = 0.26, NS). At 15 min after GLP-1, circulating IAPP increased to (6.0 +/- 0.5 pmol/l in controls P = 0.009) and to 13.8 +/- 1.2 pmol/l in type 2 diabetes (P = 0.021). In both groups, serum insulin increased and blood glucose decreased compared with placebo. In controls serum IAPP increased in parallel with insulin (r = 0.79, P = 0.032), whereas in type 2 diabetes the increase in IAPP did not correlate with the increase in insulin. CONCLUSION: Type 2 diabetes is associated with elevated circulating IAPP; GLP-1stimulates IAPP secretion both in healthy human subjects and in type 2 diabetes; IAPP secretion correlates with insulin secretion only in healthy subjects and not in type 2 diabetes.
|
|
| 28. |
- Ahrén, B, et al.
(författare)
-
Potential clinical use of the EDTA-infusion test
- 1993
-
Ingår i: European Journal of Clinical Chemistry and Clinical Biochemistry. - 0939-4974. ; 31:6, s. 8-353
-
Tidskriftsartikel (refereegranskat)abstract
- The introduction of assays for the intact parathyrin (parathyroid hormone) has dramatically improved the diagnosis and follow-up of patients with primary hyperparathyroidism. However, in some patients with mild or intermittent hypercalcaemia, when plasma concentrations of intact parathyrin may be within the normal reference concentrations, the diagnosis of primary hyperparathyroidism may still be problematic. In these patients, the EDTA-infusion test is of potential value, as it also might be in patients with equivocal operative findings.
|
|
| 29. |
|
|
| 30. |
- Ahrén, Bo, et al.
(författare)
-
Using albumin to improve the therapeutic properties of diabetes treatments.
- 2012
-
Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 14, s. 121-129
-
Tidskriftsartikel (refereegranskat)abstract
- Achieving tight glycaemic control remains an unmet need for many patients with type 2 diabetes, despite improved treatments. In order to meet glycaemic targets, attempts have been made to improve existing drugs and to develop new classes of drugs. Recent advances include insulin analogues that more closely mimic physiologic insulin levels, and incretin-based therapies, which capitalise on the glucoregulatory properties of native glucagon-like peptide-1 (GLP-1). Although promising, these agents are associated with limitations, including hypoglycaemia with insulin, gastrointestinal adverse events with GLP-1 receptor agonists and frequent dosing with both classes. Albumin is an abundant natural drug carrier that has been used to improve the half-life, tolerability and efficacy of a number of bioactive agents. Here we review the physiologic roles of albumin and how albumin technologies are being used to prolong duration of action of therapies for diabetes, including insulin and incretin-based therapies.
|
|
| 31. |
|
|
| 32. |
- Ahrén, C M, et al.
(författare)
-
Comparison of methods for detection of colonization factor antigens on enterotoxigenic Escherichia coli.
- 1986
-
Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 23:3, s. 586-91
-
Tidskriftsartikel (refereegranskat)abstract
- Fecal Escherichia coli isolates from 196 patients with watery diarrhea and 68 healthy individuals (controls) were analyzed in Bangladesh immediately after isolation for the presence of colonization factor antigen (CFA) I or II (CFA/I or CFA/II, respectively) by a mannose-resistant hemagglutination (MRHA) test with six species of erythrocytes and by a slide agglutination test with absorbed CFA/I or CFA/II antisera. The presence of CFAs was confirmed by immunodiffusion analyses done in Sweden. By these methods, it was found that 49 of 69 enterotoxin-producing E. coli strains isolated from patients carried CFA/I or CFA/II, whereas none of the nonenterotoxigenic E. coli isolates or the three toxin-positive strains isolated from healthy individuals carried these adhesins. All E. coli strains retained their MRHA ability after transportation to Sweden followed by one subculture and after storage at -70 degrees C (but not at room temperature) for 1 to 2 years without further subculturing. After 5 to 10 subcultures of the fresh isolates, however, 70% of the initially CFA/I- and 80% of the initially CFA/II-carrying strains analyzed did not hemagglutinate. The efficacy of different methods for detecting CFAs on the fresh isolates was compared with that of immunodiffusion. The sensitivity of MRHA with human blood group A erythrocytes for the detection of CFA/I was high (97%), but the specificity was only 69%. The sensitivity of MRHA with bovine erythrocytes for the detection of CFA/II in Bangladesh was very low but increased considerably when chicken erythrocytes were also used. Whereas both false-positive and false-negative reactions were obtained when absorbed CFA antisera were used for agglutination, antisera against purified CFAs were equally effective as immunodiffusion in identifying CFA/I and CFA/II-carrying strains.
|
|
| 33. |
- Alba, M., et al.
(författare)
-
Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function
- 2013
-
Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 15:12, s. 1101-1110
-
Tidskriftsartikel (refereegranskat)abstract
- AimsThe effects of sitagliptin and pioglitazone, alone and in combination, on - and -cell function were assessed in patients with type 2 diabetes. MethodsFollowing a 6-week diet/exercise period, 211 patients with HbA1c of 6.5-9.0% and fasting plasma glucose of 7.2-14.4mmol/l were randomized (1:1:1:1) to sitagliptin, pioglitazone, sitagliptin+pioglitazone or placebo. At baseline and after 12weeks, patients were given a mixed meal followed by frequent blood sampling for measurements of glucose, insulin, C-peptide and glucagon. ResultsAfter 12weeks, 5-h glucose total area under the curve (AUC) decreased in all active treatments versus placebo; reduction with sitagliptin+pioglitazone was greater versus either monotherapy. The 5-h insulin total AUC increased with sitagliptin versus all other treatments and increased with sitagliptin+pioglitazone versus pioglitazone. The 3-h glucagon AUC decreased with sitagliptin versus placebo and decreased with sitagliptin+pioglitazone versus pioglitazone or placebo. (s), a measure of dynamic -cell responsiveness to above-basal glucose concentrations, increased with either monotherapy versus placebo and increased with sitagliptin+pioglitazone versus either monotherapy. The insulin sensitivity index (ISI), a composite index of insulin sensitivity, improved with pioglitazone and sitagliptin+pioglitazone versus placebo. The disposition index, a measure of the relationship between -cell function and insulin sensitivity, improved with all active treatments versus placebo. ConclusionsSitagliptin and pioglitazone enhanced -cell function (increasing postmeal phi(s)), and sitagliptin improved -cell function (decreasing postmeal glucagon) after 12weeks in patients with type 2 diabetes. Through these complementary mechanisms of action, the combination of sitagliptin and pioglitazone reduced postmeal glucose more than either treatment alone.
|
|
| 34. |
|
|
| 35. |
- Bergenfelz, A, et al.
(författare)
-
Calcium metabolism after hemithyroidectomy
- 1993
-
Ingår i: Hormone Research. - : S. Karger AG. - 0301-0163 .- 1423-0046. ; 39:1-2, s. 56-60
-
Tidskriftsartikel (refereegranskat)abstract
- It is not known whether thyroid surgery evokes changes in calcium metabolism. We therefore studied 6 patients operated upon with hemithyroidectomy for benign thyroid diseases, preoperatively and at 3 months and 1 year postoperatively. We measured changes in serum levels of intact parathyroid hormone (PTH), vitamin D metabolites, ionized calcium, phosphate, osteocalcin, thyroid hormones and bone density. Further, the dynamic function of the parathyroid glands was investigated by an oral calcium load test pre- and at 3 months postoperatively. At follow-up, all patients were euthyroid. During the oral calcium load, serum levels of intact PTH were reduced by the same degree before and after hemithyroidectomy, showing normal parathyroid function. Serum levels of 1,25-dihydroxyvitamin D declined from 86 +/- 16 to 57 +/- 4 pmol/l (p < 0.01) at 1 year after hemithyroidectomy, and serum levels of phosphate increased slightly from 0.96 +/- 0.08 to 1.06 +/- 0.08 mmol/l (p < 0.05), whereas serum levels of ionized calcium, intact PTH, osteocalcin and bone density did not change. Our results demonstrate that thyroid operation evokes changes in vitamin D metabolism in spite of normal parathyroid function.
|
|
| 36. |
- Bergenfelz, A, et al.
(författare)
-
Functional recovery of the parathyroid glands after surgery for primary hyperparathyroidism
- 1994
-
Ingår i: Surgery. - 0039-6060. ; 116:5, s. 36-827
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The immediate postoperative function of the parathyroid glands after surgery for primary hyperparathyroidism (pHPT) has not been established. We therefore examined the influences of hypercalcemia and hypocalcemia on serum parathyroid hormone (PTH) levels in the immediate postoperative period in patients with pHPT.METHODS: Ethylenediaminetetraacetic acid was infused in patients on the first (n = 5) and fourth (n = 6) postoperative days, and in patients at 1 year after surgery (n = 6), and in healthy subjects (n = 7). Calcium was given orally before operation and on the second and fifth postoperative days in six patients and in seven healthy subjects.RESULTS: The increased set point seen in pHPT was normalized on the first postoperative day, and the decreased PTH suppressibility by calcium was normal on the second postoperative day. However, on the fifth postoperative day an increased suppressibility of PTH was evident. During the ethylenediaminetetraacetic acid infusion test the secretory reserve for PTH increased after operation with increasing hypocalcemia-induced levels of intact PTH between the first and fourth postoperative days (p < 0.001), and between the fourth postoperative day and the test at 1 year (p < 0.05).CONCLUSIONS: In the immediate postoperative period after surgery for pHPT, baseline serum levels of PTH are rapidly normalized; this is followed by an increase in the secretory reserve for PTH secretion and the development of an increased sensitivity to calcium.
|
|
| 37. |
- Bergenfelz, A, et al.
(författare)
-
Hyperthyroxinemia after surgery for primary hyperparathyroidism
- 1994
-
Ingår i: Langenbecks Archiv für Chirurgie. - 0023-8236. ; 379:3, s. 81-178
-
Tidskriftsartikel (refereegranskat)abstract
- Episodes of transient thyrotoxicosis after surgery for primary hyperparathyroidism have previously been described, and surgical trauma to the thyroid gland has been suggested as an etiologic factor. However, there are several links between the thyroid and parathyroid hormonal systems, and therefore other explanations are possible as well. In this study we investigate pre- and postoperative serum levels of thyroid hormones in 20 patients operated upon because of primary hyperparathyroidism. The mean (SD) serum levels of T4 increased from 16(2) pmol/l preoperatively to 21(6) pmol/l on the fourth postoperative day (P < 0.01), and four (20%) of the patients developed biochemical thyrotoxicosis in the immediate postoperative period. The serum levels of T4 on the fourth postoperative day correlated highly with preoperative serum levels of PTH (r = 0.75; P < 0.001). This suggests that biochemical thyrotoxicosis in the immediate postoperative period after operation for primary hyperparathyroidism is not uncommon and could be related to the disease rather than to surgical trauma.
|
|
| 38. |
- Bergenfelz, A, et al.
(författare)
-
Immunoheterogeneity of parathyroid hormone after surgery for primary hyperparathyroidism
- 1994
-
Ingår i: Clinica Chimica Acta. - 0009-8981. ; 231:2, s. 45-139
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating parathyroid hormone (PTH) immunoheterogeneity is altered in primary hyperparathyroidism (pHPT). It is not known, however, whether the relative secretion of various PTH fragments differs between the adenomatous and the non-adenomatous glands in pHPT. We therefore examined the immunoheterogeneity of PTH in patients operated upon because of parathyroid adenoma pre- and 4 days postoperatively during an EDTA-infusion test. Following surgery, baseline levels of amino-terminal PTH (N-PTH) were reduced by a smaller degree than the levels of intact PTH (i-PTH) (P < 0.05) resulting in a higher N/i ratio postoperatively (P < 0.05). Furthermore, the increase in i-PTH and C-PTH fragments during the EDTA infusion test was lower postoperatively than preoperatively (P < 0.05), whereas the increase in N-PTH did not differ. The results therefore suggest that compared with the parathyroid adenoma, the non-adenomatous glands secrete relatively more N-terminal PTH.
|
|
| 39. |
- Bergenfelz, A, et al.
(författare)
-
Immunoheterogeneity of parathyroid hormone pre- and postoperatively in primary hyperparathyroidism
- 1995
-
Ingår i: Langenbecks Archiv für Chirurgie. - 0023-8236. ; 380:2, s. 24-119
-
Tidskriftsartikel (refereegranskat)abstract
- In primary hyperparathyroidism (pHPT), a preferential release of intact PTH (i-PTH) versus carboxylterminal PTH fragments is known to occur. We studied whether the release of amino-terminal PTH fragments (N-PTH) is also changed. Serum levels of i-PTH and N-PTH were determined under basal conditions and following oral intake of calcium in six patients with pHPT before and immediately after surgery and in seven healthy subjects. In the patients, baseline levels of both i-PTH and N-PTH were increased preoperatively. The increase was larger in i-PTH compared to N-PTH. Therefore, the N/i ratio was reduced compared to healthy subjects (P < 0.05). On the first postoperative day, serum i-PTH decreased to a larger extent than N-PTH, which increased the N/i ratio above that in healthy subjects (P < 0.05). On the 5th postoperative day, the N/i ratio was normalized. Preoperatively, the suppressibility of i-PTH calcium was impaired in the patients (P < 0.05), whereas the suppressibility of N-PTH was normal, resulting in unchanged N/i ratio during the oral calcium load. In contrast, the N/i ratio increased normally during the calcium load at day 5 postoperatively (P < 0.05). We therefore conclude that: (1) in pHPT, circulating PTH immunoheterogeneity is altered with a preferential release of intact PTH compared to N-terminal PTH fragments and this alteration is normalized after surgery, (2) the secretion of intact PTH and N-terminal PTH shows different sensitivity to inhibition by calcium.
|
|
| 40. |
- Bergenfelz, A, et al.
(författare)
-
Intact parathyroid hormone assay is superior to mid region assay in the EDTA-infusion test in hyperparathyroidism
- 1991
-
Ingår i: Clinica Chimica Acta. - 0009-8981. ; 197:3, s. 35-229
-
Tidskriftsartikel (refereegranskat)abstract
- We examined the use of an intact parathyroid hormone two-site immunoradiometric assay compared with a mid region parathyroid hormone radioimmunoassay in ethylene diamine tetraacetic acid-infusion test in 15 patients with hyperparathyroidism. During the test, plasma intact parathyroid hormone levels increased by 240 +/- 43%, whereas the plasma levels of mid molecule parathyroid hormone increased by only 65 +/- 17%, which is significantly lower (P less than 0.01). Four patients had no increase in plasma mid molecule parathyroid hormone level but still a large increase in plasma intact parathyroid hormone level (P less than 0.01). Thus, plasma measurement of intact parathyroid hormone is superior to that of mid molecule parathyroid hormone in the ethylene diamine tetraacetic acid-infusion test in patients with hyperparathyroidism.
|
|
| 41. |
|
|
| 42. |
- Bergenfelz, A, et al.
(författare)
-
Intraoperative fall in plasma levels of intact parathyroid hormone after removal of one enlarged parathyroid gland in hyperparathyroid patients
- 1991
-
Ingår i: Acta Chirurgica Scandinavica. - 0001-5482. ; 157:2, s. 12-109
-
Tidskriftsartikel (refereegranskat)abstract
- Plasma levels of intact parathyroid hormone (PTH) were measured intraoperatively before and after removal of one enlarged gland in 20 hyperparathyroid patients. In 13 patients with a single parathyroid adenoma, plasma levels of intact PTH-(1-84) had declined at 15 min after removal of the adenoma by 86.5 +/- 4.4% of baseline in the antecubital vein and by 85.6 +/- 4.2% in the ipsilateral internal jugular vein. In seven patients with parathyroid hyperplasia, the corresponding figures for decline at 15 min after removal of one enlarged parathyroid gland were only 26.6 +/- 6.4% and 7.8 +/- 29.4%. The fall in PTH levels was significantly less in hyperplasia than in adenoma (p less than 0.001). Thus 15 min after removal of one enlarged parathyroid gland, the decline in plasma level of intact PTH may distinguish between single adenoma and multiglandular disease as the cause of hyperparathyroidism.
|
|
| 43. |
- Bergenfelz, A, et al.
(författare)
-
Intraoperative monitoring of intact PTH during surgery for primary hyperparathyroidism
- 1994
-
Ingår i: Langenbecks Archiv für Chirurgie. - 0023-8236. ; 379:1, s. 3-50
-
Tidskriftsartikel (refereegranskat)abstract
- The intraoperative differential diagnosis between adenoma and hyperplasia during surgery for primary hyperparathyroidism (pHPT) is sometimes difficult. Several methods have been proposed to aid the surgeon in deciding on the amount of parathyroid tissue to be resected. We examined the use of intraoperative monitoring of intact PTH in 47 patients operated upon for pHPT. The highly sensitive assay for intact PTH was modified to permit a total turn-around time from gland excision to obtained result of about 60 min. The correlation (r) between the results of the modified and the conventional method, which requires 24 h of incubation, was 0.98. At 15 min after removal of the parathyroid adenoma the levels of intact PTH had decreased by [mean (SD)] 85 (11)%. A decrease of 63% in intact PTH in patients with parathyroid adenoma predicted with 95% confidence the 4 patients with primary hyperplasia as not having parathyroid adenoma. We conclude that intraoperative measurement of intact PTH could be a valuable adjunct to surgical skill, especially for reoperative parathyroid surgery.
|
|
| 44. |
- Bergenfelz, A, et al.
(författare)
-
Intraoperative secretion of intact parathyroid hormone and amino-terminal parathyroid hormone fragments from normal parathyroid glands associated with solitary parathyroid adenoma
- 1997
-
Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 21:1, s. 30-35
-
Tidskriftsartikel (refereegranskat)abstract
- The nonadenomatous parathyroid glands associated with parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) are assumed to exhibit suppressed secretion of parathyroid hormone (PTH). Because the function of these glands is of clinical importance for calcium homeostasis after surgery for pHPT, we studied the decrease of serum levels associated with intact PTH (i-PTH) and amino-terminal PTH (N-PTH) after excision of a parathyroid adenoma. Blood samples were obtained from the cubital vein and the inferior thyroid vein in six patients with pHPT. The results show that the levels of both i-PTH and N-PTH decreased after removal of the parathyroid adenoma (p < 0.05 for both). Because the reduction was more pronounced for i-PTH than for N-PTH, the N/i ratio increased from 0.54 +/- 0.33 to 3.76 +/- 1.62 (p < 0.05). Furthermore, the levels of i-PTH and N-PTH were higher centrally than peripherally both before and after adenoma excision (p < 0.05). The results therefore suggest that the secretion of i-PTH and N-PTH in the remaining normal-size parathyroid glands is not completely suppressed. Furthermore, in these parathyroid glands the secretion of amino-terminal PTH fragments is relatively predominant when compared to the release of the intact PTH. The findings underscore the importance of the N-terminal PTH fragment for maintaining calcium homeostasis during the early postoperative period after surgery for pHPT and may explain the rarity of prolonged hypocalcemia after parathyroidectomy.
|
|
| 45. |
- Bergenfelz, A, et al.
(författare)
-
Measurement of intact parathyroid hormone in the diagnosis of hyperparathyroidism
- 1991
-
Ingår i: Acta Endocrinologica. - 0001-5598. ; 125:6, s. 74-668
-
Tidskriftsartikel (refereegranskat)abstract
- Plasma levels of parathyroid hormone were determined pre-operatively in 27 consecutive patients with clinical and biochemical signs of primary hyperparathyroidism, by the use of one assay recognizing the intact PTH molecule and one assay recognizing the mid-portion of PTH. Plasma levels of mid-molecule PTH were normal in 5 of the patients with primary hyperparathyroidism. In 4 of these patients, plasma levels of intact PTH were raised. Conversely, in 6 patients with primary hyperparathyroidism, intact PTH were normal pre-operatively. In 5 of these cases, plasma levels of mid-molecule PTH were raised. The EDTA infusion test was performed in 6 patients with normal baseline plasma level of intact PTH pre-operatively. The test correctly predicted all the patients in this group who were found to have primary hyperparathyroidism, as well as a patient with normal parathyroid glands found at operation. We conclude that some patients with primary hyperparathyroidism have normal baseline plasma levels of intact PTH. In these patients, plasma levels of mid-molecule PTH and an EDTA infusion test provide further diagnostic information.
|
|
| 46. |
- Bergenfelz, A, et al.
(författare)
-
Parathyroid hormone secretion after operation for primary hyperparathyroidism
- 1993
-
Ingår i: Surgery. - 0039-6060. ; 113:6, s. 54-649
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with a defective regulation of the secretion of parathyroid hormone (PTH). Thus in pHPT, higher than normal calcium concentrations are required to inhibit PTH release. However, it is not known if this defective regulation is normalized by removal of the parathyroid adenoma (i.e., whether the regulation of PTH secretion is normal in the remaining glands). In this study we therefore investigated the PTH secretion in patients operated on for parathyroid adenoma 1 year after operation.METHODS: Na2 ethylenediamine tetraacetic acid and CaCI2 were infused at constant rates in six patients operated on for parathyroid adenoma and six healthy individuals. Serum levels of intact PTH and ionized calcium were determined during the infusions.RESULTS: No significant differences between the two groups were found in baseline levels of serum ionized calcium and PTH. Furthermore, no significant differences between patients and control subjects were found in the maximum serum PTH levels during the hypocalcemic infusion of ethylenediamine tetraacetic acid or in the minimum serum PTH levels during the calcium infusion. In contrast, the set point (the calcium concentration required for half-maximal inhibition of PTH secretion) was significantly lower in the patients (1.20 +/- 0.01 mmol/L) compared with control subjects (1.22 +/- 0.01 mmol/L; p < 0.05).CONCLUSIONS: We conclude that the elevation of set point in patients with parathyroid adenoma is corrected by successful operation. This suggests a monoclonal origin of parathyroid adenomas.
|
|
| 47. |
- Bergenfelz, A, et al.
(författare)
-
Postoperative studies on parathyroid hormone secretion in patients operated on for primary hyperparathyroidism
- 1993
-
Ingår i: Clinica Chimica Acta. - 0009-8981. ; 219:1-2, s. 67-77
-
Tidskriftsartikel (refereegranskat)abstract
- The secretion of intact parathyroid hormone (PTH) was investigated in 11 patients operated on for parathyroid adenoma at 1 year after surgery and compared with that of seven healthy individuals and five patients operated on because of clinical and biochemical signs of primary hyperparathyroidism with equivocal diagnosis after surgery. The investigation was performed by infusing Na2EDTA and CaCl2 at constant rates. No significant difference was found in the suppressibility of PTH secretion by calcium. The set point (the calcium concentration required for half-maximal inhibition of PTH secretion) was slightly lower in patients (1.20 +/- 0.02 mmol/l) compared with healthy subjects (1.23 +/- 0.03 mmol/l; P < 0.05). During the hypocalcemic EDTA infusion, the secretion of PTH was higher in controls compared with patients (P < 0.01). By comparing the data from the infusion tests in patients operated on for parathyroid adenomas with the data obtained from the patients with equivocal diagnosis after parathyroid surgery, a good probability for the diagnosis could be obtained.
|
|
| 48. |
- Bergenfelz, A, et al.
(författare)
-
Preoperative localization of enlarged parathyroid glands with ultrasonically guided fine needle aspiration for parathyroid hormone assay
- 1991
-
Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 32:5, s. 5-403
-
Tidskriftsartikel (refereegranskat)abstract
- For preoperative localization of enlarged parathyroid glands, several imaging techniques have been used. In this study we demonstrate the feasibility of using ultrasonography with fine needle aspiration for parathyroid hormone assay as a preoperative localization procedure in 21 patients with primary hyperparathyroidism. A single adenoma was found in 18 patients while 3 patients had multiglandular disease. Ultrasonically guided fine needle biopsy was possible in 11 cases. In 8 of these aspirates, a high parathyroid hormone content was found. In all 8 cases the localization was confirmed at surgery. We conclude that the efficiency to preoperatively localize enlarged parathyroid glands is enhanced by fine needle aspiration.
|
|
| 49. |
- Bergenfelz, A, et al.
(författare)
-
Serum levels of thyrotropin are decreased by oral calcium in healthy subjects but not in patients with primary hyperparathyroidism
- 1994
-
Ingår i: Hormone Research. - : S. Karger AG. - 0301-0163 .- 1423-0046. ; 42:6, s. 7-273
-
Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that calcium changes the set point of the pituitary thyroid feedback. It is not known, however, if small and slow changes of calcium and/or parathyroid hormone (PTH) within the physiological range influence the serum levels of thyrotropin (TSH) and thyroid hormones in healthy subjects or patients with primary hyperparathyroidism (pHPT). Nine healthy subjects and nine patients with pHPT were therefore investigated with an oral calcium load test. The patients were investigated before and 4 days after operation. During the test, serum levels of ionized calcium increased and serum levels of intact PTH decreased in both healthy subjects and patients pre- and postoperatively (p < 0.001). Furthermore, in patients, the suppressibility of serum levels of PTH by calcium increased postoperatively (p < 0.05). Serum levels of TSH decreased during the oral calcium load in healthy subjects (p < 0.01) but not in patients, whereas the serum levels of thyroid hormones did not change. It is concluded that oral calcium influences TSH secretion in healthy humans but not in patients with pHPT.
|
|
| 50. |
- Bergenfelz, A, et al.
(författare)
-
Serum osteocalcin levels do not change during rapidly induced hypercalcemia in healthy subjects
- 1992
-
Ingår i: Hormone Research. - : S. Karger AG. - 0301-0163 .- 1423-0046. ; 37:1-2, s. 29-32
-
Tidskriftsartikel (refereegranskat)abstract
- Since osteocalcin has been suggested to play a role in calcium homeostasis, we investigated its serum levels in 6 healthy subjects during a rapid calcium infusion. Serum levels of intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25-(OH) D3] and 1,25-dihydroxyvitamin D [1,25-(OH)2 D3] were also determined. The calcium infusion increased plasma-ionized calcium levels from 1.25 +/- 0.04 to 1.54 +/- 0.07 mmol/l at 30 min (p less than 0.05). Concomitantly, serum levels of intact PTH declined from 2.1 +/- 0.9 to 0.2 +/- 0.3 mmol/l (p less than 0.05). In contrast, serum osteocalcin levels did not change. Further, during calcium infusion, serum levels of 1,25-(OH)2 D3 decreased from 81 +/- 17 to 75 +/- 15 pmol/l (p less than 0.05) whereas serum levels of 25-(OH) D3 did not change. The results therefore suggest that calcium per se does not influence osteocalcin secretion.
|
|
