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- 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. |
- 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. |
- Agardh, Carl-David, et al.
(författare)
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Switching From High-Fat to Low-Fat Diet Normalizes Glucose Metabolism and Improves Glucose-Stimulated Insulin Secretion and Insulin Sensitivity But Not Body Weight in C57BL/6J Mice.
- 2012
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Ingår i: Pancreas. - 0885-3177. ; 41:2, s. 253-257
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Environmental factors such as a high-fat diet contribute to type 2 diabetes and obesity. This study examined glycemia, insulin sensitivity, and β-cell function after switching from a high-fat diet to a low-fat diet in mice. METHODS: C57BL/6J mice were fed a high-fat diet or low-fat diet for 18 months, after which mice on the high-fat diet either maintained this diet or switched to a low-fat diet for 4 weeks. Body weight and glucose and insulin responses to intraperitoneal glucose were determined. Insulin secretion (insulinogenic index: the 10-minute insulin response divided by the 10-minute glucose level) and insulin sensitivity (1 divided by basal insulin) were determined. RESULTS: After 18 months on a high-fat diet, mice had glucose intolerance, marked hyperinsulinemia, and increased body weight compared to mice on a low-fat diet (P < 0.001). Switching from a high-fat diet to low-fat diet normalized glucose tolerance, reduced but not normalized body weight (P < 0.001), increased insulin secretion (248 ± 39 vs 141 ± 46 pmol/mmol; P = 0.028) and improved but not normalized insulin sensitivity (3.2 ± 0.1 vs 1.0 ± 0.1 [pmol/L]; P = 0.012). CONCLUSION: Switching from a high-fat diet to low-fat diet normalizes glucose tolerance and improves but not normalizes insulin secretion and insulin sensitivity. These effects are more pronounced than the reduced body weight.
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| 5. |
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| 6. |
- 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. |
- 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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| 9. |
- Mattsson, Cecilia, et al.
(författare)
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Gender-specific links between hepatic 11beta reduction of cortisone and adipokines
- 2007
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 15:4, s. 887-894
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones. RESEARCH METHODS AND PROCEDURES: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol. RESULTS: Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. DISCUSSION: Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.
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| 10. |
- Ahmadi, Shilan Seyed, et al.
(författare)
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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
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Ingår i: Obesity Science and Practice. - : Wiley. - 2055-2238. ; 5:2, s. 130-140
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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.
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