| 1. |
- Sofizadeh, Sheyda, et al.
(författare)
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Effect of Liraglutide on Times in Glycaemic Ranges as Assessed by CGM for Type 2 Diabetes Patients Treated With Multiple Daily Insulin Injections
- 2019
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Ingår i: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 10:6, s. 2115-2130
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The effects of the GLP-1 analogue liraglutide on time in hypoglycaemia, time in hyperglycaemia, and time in range for type 2 diabetes patients initially treated with multiple daily insulin injections (MDI) were investigated. Variables associated with hypoglycaemia in the current population were also identified. Methods: Analyses were based on data from a previously performed double-blind, placebo-controlled trial in which 124 MDI-treated patients with type 2 diabetes were randomized to liraglutide or placebo. Masked continuous glucose monitoring (CGM) was performed at baseline and week 24 in 99 participants. Results: The mean time in hypoglycaemia was similar for participants receiving liraglutide and those receiving placebo after 24 weeks of treatment. Mean time in target was greater in the liraglutide group than in the placebo group: 430 versus 244 min/24 h (p < 0.001) and 960 versus 695 min/24 h (p < 0.001) for the two glycaemic ranges considered, 4–7 mmol/l and 4–10 mmol/l, respectively. Mean time in hyperglycaemia was lower in the liraglutide group: 457 versus 723 min/24 h (p = 0.001) and 134 versus 264 min/24 h (p = 0.023) for the two cutoffs considered, > 10 mmol/l and > 14 mmol/l, respectively. Lower mean glucose level, lower C-peptide, and higher glucose variability were associated with an increased risk of hypoglycaemia in both treatment groups. Higher proinsulin level was associated with a lower risk of hypoglycaemia in the liraglutide group. Conclusion: For type 2 diabetes patients initially treated with MDI, introducing liraglutide had a beneficial effect on glucose profiles estimated by masked CGM. Mean glucose level, glycaemic variability, C-peptide, and proinsulin level influenced the risk of hypoglycaemia in this population. Trial Registration: ClinicalTrials.gov, number (EudraCT nr: 2012-001941-42). Funding: Novo Nordisk funded this study. The Diabetes Research Unit, NU-Hospital Group funded the journal’s Rapid Service Fee.
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| 2. |
- Dahlqvist, S., et al.
(författare)
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Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3)
- 2018
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Ingår i: BMC Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate variables associated with hemoglobin A1c (HbA1c) and weight reduction when adding liraglutide to persons with type 2 diabetes treated with multiple daily insulin injections (MDI). Research design and methods This was a reanalysis of a previous trial where 124 patients were enrolled in a double-blind, placebo-controlled, multicenter randomized trial carried out over 24 weeks. Predictors for effect on change in HbA1c and weight were analyzed within the treatment group and with concurrent interaction analyses. Correlation analyses for change in HbA1c and weight from baseline to week 24 were made. Results The mean age at baseline was 63.7 years, 64.8% were men, the mean number of insulin injections was 4.4 per day, the mean daily insulin dose was 105 units and the mean HbA1c was 74.5 mmol/mol (9.0%). The mean HbA1c and weight reductions were 12.3 mmol/mol (1.13%; P<0.001) and 3.8 kg (P<0.001) greater in liraglutide than placebo-Treated persons. There was no significant predictor for greater effect on HbA1c that existed in all analyses (univariate, multivariate and interaction analyses against controls). For a greater weight reduction when adding liraglutide, a lower HbA1c level at baseline was a predictor (liraglutide group P=0.002, P=0.020 for liraglutide group vs placebo). During follow-up in the liraglutide group, no significant correlation was found between change in weight and change in HbA1c (r=0.09, P=0.46), whereas a correlation existed between weight and insulin dose reduction (r=0.44, P<0.001). Conclusion Weight reduction becomes greater when adding liraglutide in patients with type 2 diabetes treated with MDI who had a lower HbA1c level compared with those with a higher HbA1c level. There was no correlation between reductions in HbA1c and weight when liraglutide was added, that is, different patient groups responded with HbA1c and weight reductions. Trial registration number EudraCT nr: 2012-001941-42. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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| 3. |
- Lundquist, Ingmar, et al.
(författare)
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Monoamines in pancreatic islets of guinea pig, hamster, rat, and mouse determined by high performance liquid chromatography
- 1989
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Ingår i: Pancreas. - 0885-3177. ; 4:6, s. 662-667
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies on the occurrence of catecholamines and serotonin in pancreatic islets using various histochemical and chemical methods have given widely different results. We therefore performed a comparative analysis of these amines in whole pancreas and islet tissue from hamster, guinea pig, rat, and mouse by the use of high performance liquid chromatography. Whole pancreas of guinea pig, hamster, and rat had a norepinephrine concentration of approximately 1.1 [mu]mol/kg of pancreatic wet weight. The mouse pancreas had less than one-half of that concentration. Epinephrine and dopamine concentrations were on the order of 0.02 [mu]mol/kg of pancreatic wet weight in all four species. The serotonin concentration was 2.1 [mu]mol/kg of pancreatic wet weight in the guinea pig pancreas and approximately 0.2 [mu]mol/kg in the other three species studied. The catecholamine concentrations were much higher in the pancreatic islets than in the exocrine pancreas. Thus, the norepinephrine concentration was approximately 35 [mu]mol/kg of islet wet weight in hamster islets and 5-10 [mu]mol/kg in rat, guinea pig, and mouse islets. The epinephrine concentration in islet tissue ranged between 1 and 7 [mu]mol/kg of islet wet weight and the dopamine concentration between 0.5 and 4 [mu]mol/kg except for guinea pig islets (12 [mu]mol/kg). The islet tissue in the mouse, rat, and guinea pig contained disproportionately more epinephrine and dopamine relative to norepinephrine than did the exocrine pancreas. Chemical sympathectomy (6- hydroxydopamine treatment) in the mouse reduced the norepinephrine and epinephrine concentrations in islet tissue to nondetectable levels, whereas the dopamine concentration was essentially unchanged, thus suggesting an extraneuronal source of this amine in addition to its occurrence in adrenergic nerves. The islets of hamster, rat, and mouse contained no serotonin, whereas guinea pig islets contained approximately 275 [mu]mol/kg of islet wet weight. We conclude that, although species differences exist, the pancreatic islets have markedly higher levels of catecholamines than the exocrine pancreas, and that serotonin occurs in the exocrine pancreas of all four species studied but in the endocrine pancreas only in the guinea pig.
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| 4. |
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| 5. |
- Asp, N G, et al.
(författare)
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Dietary fibre in type II diabetes
- 1982
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Ingår i: Acta medica Scandinavica. Supplementum. - : Wiley. - 0365-463X .- 0001-6101. ; 210:S656, s. 47-50
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have indicated that diets rich in digestible carbohydrates and dietary fibre might be beneficial in the regulation of type II non insulin dependent diabetes (NIDD). Addition of the gel forming type of dietary fibre such as pectin and guar gum to meals or glucose solutions reduces post-prandial glucose and insulin response. Addition of cereal fibres in the form of bran seems to have long term beneficial effect improving glucose tolerance. Little is known, however, concerning effects of dietary fibre naturally occurring in food on postprandial glucose and hormone response. In the present study we prepared two breakfast meals which were similar regarding digestible carbohydrates but differed in their dietary fibre content. One of the meals, including whole grain bread and whole apples, contained 8.4 g of dietary fibre, and the other one, containing white bread and apple juice, 3.1 g. When given to eight NIDD, the fibre rich breakfast gave significantly lower blood glucose increment during the three hours following ingestion. The results indicate that foods rich in dietary fibre might be useful in the regulation of type II diabetes.
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| 7. |
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| 8. |
- Sörhede Winzell, Maria, et al.
(författare)
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Glucagon receptor antagonism improves islet function in mice with insulin resistance induced by a high-fat diet.
- 2007
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50, s. 1453-1462
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Increased glucagon secretion predicts deterioration of glucose tolerance, and high glucagon levels contribute to hyperglycaemia in type 2 diabetes. Inhibition of glucagon action may therefore be a potential novel target to reduce hyperglycaemia. Here, we investigated whether chronic treatment with a glucagon receptor antagonist (GRA) improves islet dysfunction in female mice on a high-fat diet (HFD). Materials and methods After 8 weeks of HFD, mice were treated with a small molecule GRA ( 300 mg/kg, gavage once daily) for up to 30 days. Insulin secretion was studied after oral and intravenous administration of glucose and glucagon secretion after intravenous arginine. Islet morphology was examined and insulin secretion and glucose oxidation were measured in isolated islets. Results Fasting plasma glucose levels were reduced by GRA (6.0 +/- 0.2 vs 7.4 +/- 0.5 mmol/l; p= 0.017). The acute insulin response to intravenous glucose was augmented ( 1,300 +/- 110 vs 790 +/- 64 pmol/l; p < 0.001). The early insulin response to oral glucose was reduced in mice on HFD + GRA ( 1,890 +/- 160 vs 3,040 +/- 420 pmol/ l; p= 0.012), but glucose excursions were improved. Intravenous arginine significantly increased the acute glucagon response ( 129 +/- 12 vs 36 +/- 6 ng/l in controls; p < 0.01), notably without affecting plasma glucose. GRA caused a modest increase in alpha cell mass, while beta cell mass was similar to that in mice on HFD + vehicle. Isolated islets displayed improved glucose-stimulated insulin secretion after GRA treatment (0.061 +/- 0.007 vs 0.030 +/- 0.004 pmol islet(-1) h(-1) at 16.7 mmol/l glucose; p < 0.001), without affecting islet glucose oxidation. Conclusions/interpretation Chronic glucagon receptor antagonism in HFD-fed mice improves islet sensitivity to glucose and increases insulin secretion, suggesting improvement of key defects underlying impaired glucose tolerance and type 2 diabetes.
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| 9. |
- 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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| 10. |
- García, Maria C, et al.
(författare)
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Mature-onset obesity in interleukin-1 receptor I knockout mice.
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:5, s. 1205-13
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI(-/-) mice of both sexes started to deviate from those of wild-type mice at 5-6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI(-/-) mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young pre-obese IL-1RI(-/-) mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in pre-obese IL-1RI(-/-) mice. In conclusion, lack of IL-1RI-mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity.
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