| 1. |
- Bülow, Birgitta, et al.
(författare)
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Adrenal incidentaloma - follow-up results from a Swedish prospective study
- 2006
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 154:3, s. 419-23
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the risk of developing adrenal carcinomas and clinically overt hypersecreting tumours during short-term follow-up in patients with adrenal incidentalomas. DESIGN: 229 (98 males and 131 females) patients with adrenal incidentalomas were investigated in a prospective follow-up study (median time 25 months; range 3-108 months). The patients were registered between January 1996 and July 2001 and followed until December 2004. Twenty-seven Swedish hospitals contributed with follow-up results. METHODS: Diagnostic procedures were undertaken according to a protocol including reinvestigation with computed tomography scans after 3-6 months, 15-18 months and 27-30 months, as well as hormonal evaluation at baseline and after 27-30 months of follow-up. Operation was recommended when the incidentaloma size increased or if there was a suspicion of a hypersecreting tumour. RESULTS: The median age at diagnosis of the 229 patients included in the follow-up study was 64 years (range 28-84 years) and the median size of the adrenal incidentalomas when discovered was 2.5 cm (range 1-8 cm). During the follow-up period, an increase in incidentaloma size of > or =0.5 cm was reported in 17 (7.4%) and of > or =1.0 cm was reported in 12 (5.2%) of the 229 patients. A decrease in size was seen in 12 patients (5.2%). A hypersecreting tumour was found in 2% of the hormonally investigated patients: Cushing's syndrome (n = 2) and phaeochromocytoma (n = 1). Eleven patients underwent adrenalectomy, but no cases of primary adrenal malignancy were observed. CONCLUSIONS: Patients with adrenal incidentaloma had a low risk of developing malignancy or hormonal hypersecretion during a short-term follow-up period.
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| 2. |
- Dencker, Magnus, et al.
(författare)
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Body fat related to daily physical activity and insulin concentrations in non-diabetic children.
- 2008
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 28, s. 211-215
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Tidskriftsartikel (refereegranskat)abstract
- This study explored the associations between body fat versus daily physical activity and insulin concentrations in non-diabetic young children in a cross-sectional study of 172 children (93 boys and 79 girls) aged 8-11 years. Blood samples were analysed for serum insulin and daily physical activity was measured by accelerometers. Time spent performing vigorous activity was estimated from accelerometer data by using established cut-off points. Dual-energy x-ray absorptiometry (DXA) was used to quantify abdominal fat mass (AFM) and total body fat (TBF), also calculated as percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Body fat distribution was independently linked to both insulin concentrations and physical activity. In contrast, TBF, AFM, and BF% were linked to physical activity only and not to insulin concentrations. In conclusion in this population of non-diabetic children, body fat distribution was independently associated with increased concentrations of insulin and deceased amount of vigorous activity per day. Also, AFM, TBF, and BF% were independently related to minutes of vigorous activity per day.
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| 3. |
- Pacini, Giovanni, et al.
(författare)
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Reappraisal of the intravenous glucose tolerance index for a simple assessment of insulin sensitivity in mice
- 2009
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Ingår i: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 296:5, s. 1316-1324
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Tidskriftsartikel (refereegranskat)abstract
- Pacini G, Ahren M, Ahren B. Reappraisal of the intravenous glucose tolerance index for a simple assessment of insulin sensitivity in mice. Am J Physiol Regul Integr Comp Physiol 296: R1316-R1324, 2009. First published February 11, 2009; doi: 10.1152/ajpregu.90575.2008.- Mice are increasingly used in studies where measuring insulin sensitivity (IS) is a common procedure. The glucose clamp is labor intensive, cannot be used in large numbers of animals, cannot be repeated in the same mouse, and has been questioned as a valid tool for IS in mice; thus, the minimal model with 50-min intravenous glucose tolerance test (IVGTT) data was adapted for studies in mice. However, specific software and particular ability was needed. The aim of this study was to establish a simple procedure for evaluating IS during IVGTT in mice (CSI). IVGTTs (n = 520) were performed in NMRI and C57BL/6J mice (20-25g). After glucose injection (1 g/kg), seven samples were collected for 50 min for glucose and insulin measurements, analyzed with a minimal model that provided the validated reference IS (S-perpendicular to). By using the regression CS perpendicular to = alpha(1) + alpha(2) x K-G/AUC(D), where K-G is intravenous glucose tolerance index and AUC(D) is the dynamic area under the curve, IS was calculated in 134 control animals randomly selected (regression CSI vs. S-I: r = 0.66, P < 0.0001) and yielded alpha(1) = 1.93 and alpha(2) = 0.24. KG is the slope of log (glucose(5-20)) and AUCD is the mean dynamic area under insulin curve in the IVGTT. By keeping fixed alpha(1) and alpha(2), CSI was validated in 143 control mice (4.7 +/- 0.2 min . mu U- . ml(-1), virtually identical to S-I: 4.7 +/- 0.3, r = 0.89, P < 0.0001); and in 123 mice in different conditions: transgenic, addition of neuropeptides, incretins, and insulin (CSI: 6.0 +/- 0.4 vs. SI: 6.1 +/- 0.4, r = 0.94, P < 0.0001). In the other 120 animals, CSI revealed its ability to segregate different categories, as does S-I. This easily usable formula for calculating CSI overcomes many experimental obstacles and may be a simple alternative to more complex procedures when large numbers of mice or repeated experiments in the same animals are required.
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| 4. |
- Ahrén, Bo, et al.
(författare)
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A Novel Approach to Assess Insulin Sensitivity Reveals No Increased Insulin Sensitivity in Mice with a Dominant-Negative Mutant Hepatocyte Nuclear Factor-1{alpha}
- 2006
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Ingår i: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 291:1, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- In phenotype experiments in mice, determination of dynamic insulin sensitivity often uses the insulin tolerance test. However, the interpretation of this test is complicated by the counterregulation occurring at low glucose. To overcome this problem, we determined the dynamic insulin sensitivity after inhibition of endogenous insulin secretion by diazoxide (25 mg/kg) in association with intravenous administration of glucose plus insulin (the DSGIT technique). Estimation of insulin sensitivity index (SI) by this technique showed good correlation to SI from a regular intravenous glucose tolerance test (r = 0.87; P < 0.001; n = 15). With DSGIT, we evaluated dynamic insulin sensitivity in mice with a rat insulin promoter (beta-cell-targeted) dominant-negative mutation of hepatic nuclear factor (HNF)-1{alpha} [RIP-DN HNF-1{alpha} (Tg) mice]. When insulin was administered exogenously at the same dose in Tg and wild-type (WT) mice, plasma insulin levels were higher in WT, indicating an increased insulin clearance in Tg mice. When the diazoxide test was used, different doses of insulin were therefore administered (0.1 and 0.15 U/kg in WT and 0.2 and 0.25 U/kg in Tg) to achieve similar insulin levels in the groups. Minimal model analysis showed that SI was the same in the two groups (0.78 ± 0.21 x 10–4 min·pmol–1·l–1 in WT vs. 0.60 ± 0.11 in Tg; P = 0.45) as was the glucose elimination rate (P = 0.27). We conclude that 1) the DSGIT technique determines the in vivo dynamic insulin action in mice, 2) insulin clearance is increased in Tg mice, and 3) chronic islet dysfunction in RIP-DN HNF-1{alpha} mice is not compensated with increased insulin sensitivity.
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| 5. |
- Ahrén, Bo
(författare)
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beta- and alpha-Cell Dysfunction in Subjects Developing Impaired Glucose Tolerance Outcome of a 12-Year Prospective Study in Postmenopausal Caucasian Women
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:3, s. 726-731
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-This study assessed insulin and glucagon secretion in relation to insulin sensitivity in Caucasian women who develop impaired glucose tolerance (IGT) versus those who maintain normal glucose tolerance (NGT) over a 12-year period. RESEARCH DESIGN AND METHODS-At baseline and after 3, 8, and 12 years, glucose tolerance (75-g oral glucose tolerance test), insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin and glucagon secretion (2- to 5-min responses to 5 g arginine i.v. at fasting, 14 and >25 mmol/l glucose) were determined in 53 healthy Caucasian women (aged 58 years at. baseline) who all had NGT at baseline. RESULTS-During the 12-year period, 26 subjects developed IGT, whereas the remaining 27 subjects maintained NGT throughout the 12-year period. Subjects developing IGT had lower insulin sensitivity than those maintaining NGT in the tests preceding diagnosis of IGT (P <= 0.05). When judged in relation to insulin sensitivity, P-cell glucose sensitivity and maximal insulin secretion were lower in those who later developed IGT than in those maintaining NGT at all tests (P : 0.05). Furthermore, subject's who developed IGT had defective suppression of glucagon secretion by glucose in the test preceding diagnosis of IGT when they still had NGT (P : 0.05). CONCLUSIONS-beta- and alpha-cell dysfunction are evident several years before diagnosis of IGT, and islet dysfunction is manifeste as impaired glucose sensitivity of the beta- and (x-cells and reduced maximal insulin secretion. Diabetes 58:726-731, 2009
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| 9. |
- Ahrén, Bo, et al.
(författare)
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Clinical measures of islet function: usefulness to characterize defects in diabetes.
- 2008
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Ingår i: Current Diabetes Reviews. - 1573-3998. ; 4:2, s. 129-145
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Tidskriftsartikel (refereegranskat)abstract
- In healthy individuals, the ability of the pancreatic islets to sense and respond appropriately to changes in plasma glucose levels maintains plasma glucose levels within a narrow range despite broad fluctuations in nutrient intake and variable "demand" for insulin imposed by changes in insulin sensitivity. This ability of the pancreatic islets is lost in type 2 diabetes (T2DM). For studies on the pathophysiology of T2DM, methods for analyzing islet function are therefore required. Many methods of varying degrees of complexity have been developed and used to measure pancreatic beta-cell function in humans and to characterize the defects existing in patients with T2DM or precursors thereof (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]). Significant, although perhaps less progress has been made toward development of methods to characterize alpha-cell function. This work presents an overview of clinical measures of islet function, from simple static measures such as HOMA-beta to the more complex dynamic measures such as those utilizing stepped hyperglycemic clamps and acute administration of arginine to obtain more detailed information regarding the interaction of glucose and non-glucose secretagogues. We emphazise the need for accurate measures of alpha-cell function, and we discuss the strengths and limitations of the various methods, highlighting the many aspects of both alpha- and beta-cell function that become impaired during development of T2DM.
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| 10. |
- Ahrén, Bo
(författare)
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Clinical results of treating type 2 diabetic patients with sitagliptin, vildagliptin or saxagliptin - diabetes control and potential adverse events
- 2009
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Ingår i: Best Practice and Research in Clinical Endocrinology and Metabolism. - : Elsevier BV. - 1521-690X. ; 23:4, s. 487-498
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of dipeptidyl peptidase-4 (DPP-4) is a novel oral treatment for type 2 diabetes. DPP-4 inhibition increases insulin secretion and reduces glucagon secretion by preventing the inactivation of glucagon-like peptide-1 (GLP-1), thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical development; more studies exist for sitagliptin and vildagliptin. They improve metabolic control in type 2 diabetes in monotherapy and also in combination with metformin, sulphonylurea and thiazolidinediones. HbA(1c) is reduced by approximately 0.6-1.1% in studies up to 52 weeks. Similar, although more limited, results were obtained for saxagliptin. DPP-4 inhibitors are safe and tolerable with no increased risk of adverse events compared to placebo and have a low risk of hypoglycaemia. DPP-4 inhibitors are body weight-neutral. The DPP-4 inhibitors are recommended for use in the early stage of type 2 diabetes, in combination with metformin in subjects with inadequate glycaemic control. DPP-4 inhibition may also be used in combination with sulphonylurea and thiazolidinediones and potentially also in combination with insulin. The durability and long-term safety of DPP-4 inhibitors remain to be established.
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