| 1. |
- Follin, Cecilia, et al.
(author)
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Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after 2 years of GH treatment in GH deficient adult survivors of childhood acute lymphoblastic leukaemia.
- 2006
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 91:5, s. 1872-1875
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Journal article (peer-reviewed)abstract
- Context: Survivors of childhood- onset ( CO) acute lymphoblastic leukemia ( ALL) treated with prophylactic cranial radiotherapy often exhibit GH deficiency ( GHD), which is associated with increased prevalence of cardiovascular risk factors and cardiac dysfunction. Objective: The objective of the study was to evaluate the effect of GH replacement on cardiovascular risk factors and cardiac function in former CO ALL patients. Design: Eighteen former CO ALL patients ( aged 19 - 32 yr) treated with cranial radiotherapy ( 18 - 24 Gy) and chemotherapy and with confirmed GHD were studied at baseline and after 12 ( n = 18) and 24 months ( n = 13) of GH treatment ( median 0.5 mg/ d). A group of 18 age- and sex- matched subjects served as controls. Results: After 12 months of GH treatment, a significant decrease in serum leptin ( P = 0.002), leptin per kilogram fat mass ( FM) ( P = 0.01),plasma glucose ( P = 0.004), FM ( P = 0.002), and hip ( P = 0.04) and waist ( P = 0.02) circumference and increased muscle mass ( P = 0.004) were recorded in the patients. Before GH treatment six patients had a metabolic syndrome, but after 12 months only one had it and after 24 months none. After 24 months of GH treatment, an increase in left ventricular mass index ( P = 0.06) and significant improvements in cardiac systolic function, measured as fractional shortening ( P = 0.03) and ejection fraction ( P = 0.03), were recorded. Conclusions: Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome were recorded after 2 yr of GH replacement in former CO ALL patients with GHD. Long- term follow-up is highly warranted.
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| 2. |
- Ahrén, Bo
(author)
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Insulin secretion and insulin sensitivity in relation to fasting glucose in healthy subjects.
- 2007
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 30:3, s. 644-648
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Journal article (peer-reviewed)abstract
- OBJECTIVE - This study evaluated insulin secretion and insulin sensitivity in healthy subjects with normal fasting glucose. RESEARCH DESIGN AND METHODS - A total of 148 healthy women (aged 53-70 years) underwent a glucose-dependent arginine stimulation test and a 2-h euglycemic-hyperinsulinemic clamp. In the arginine test, arginine (5 g) was injected intravenously under baseline (fasting) conditions and after raising the glucose levels to 15 and > 28 mmol/l. From this test, the acute insulin response (AIR) to arginine during the three glucose levels (AIR(1), AIR(2), and AIR,) were estimated. The subjects were divided into quartiles of fasting glucose (n = 37 in each group [range < 432; 4.33-4.84; 4.85-5.22; and 5:23-6.1 mmol/l, respectively). RESULTS - The results show that 1) AIR(1) was higher in subjects in the two highest quartiles (P = 0.004), 2) AIR(3) was higher in the quartile with the highest fasting glucose (P = 0.012), and 3) insulin sensitivity was reduced in subjects in the highest quartile (P = 0.026) compared with the lower quartiles. The results also show, in contrast, that AIR(2) did not show a similar trend to be increased at higher fasting glucose. CONCLUSIONS - it is concluded that 1) raised fasting glucose (albeit still within normal values) augments baseline and maximal arginine-induced insulin secretion in healthy subjects, and 2) this is associated with reduced insulin sensitivity. This suggests that high, but still normal, fasting glucose may contribute to the augmented insulin secretion in subjects with low insulin sensitivity.
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| 3. |
- Ahrén, Bo
(author)
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Vildagliptin: an inhibitor of dipeptidyl peptidase-4 with antidiabetic properties.
- 2006
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In: Expert Opinion on Investigational Drugs. - : Informa Healthcare. - 1744-7658 .- 1354-3784. ; 15:4, s. 431-442
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Journal article (peer-reviewed)abstract
- Vilclagliptin is a competitive and reversible inhibitor of dipeptidyl peptidase-4. Dipeptidyl peptidase-4 inhibitors act mainly by preventing the rapid degradation of glucagon-like peptide-1. In clinical trials, vildagliptin improves glycaemic control both as monotherapy and in combination with metformin for periods of :! 52 weeks in subjects with Type 2 diabetes. This is evident by reduced fasting and prandial glucose levels, and reduced glycosylated haemoglobin levels. Vilclagliptin acts by increasing active glucagon-like peptide-1, improving p-cell function and inhibiting glucagon secretion. Furthermore, vildagliptin has proven to be safe and tolerable, with a low occurrence of hypoglycaemia. Further studies are now required to evaluate its long-term durability, effects, safety and tolerability in comparison with other antidiabetic agents and in different patient subgroups.
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| 4. |
- Ahrén, Bo, et al.
(author)
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Vildagliptin Enhances Islet Responsiveness to Both Hyper- and Hypoglycemia in Patients with Type 2 Diabetes.
- 2009
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 1236-1243
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Journal article (peer-reviewed)abstract
- Context: Dipeptidyl peptidase-4 (DPP-4) inhibitors act by increasing plasma levels of glucagon-like peptide-1 (GLP-1) and suppressing excessive glucagon secretion in patients with type 2 diabetes (T2DM). However, their effects on the glucagon response to hypoglycemia are not established. Objective: Assess effects of the DPP-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. Design: Single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout Setting: Participants received study drug as outpatients. Patients: Drug-naïve patients with T2DM and baseline HbA1c
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| 5. |
- Lindgärde, Folke, et al.
(author)
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Improved metabolic risk markers following two 6-month physical activity programs among socioeconomic marginalized women of native American ancestry in Lima, Peru
- 2007
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 30:9, s. 2230-2232
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Journal article (peer-reviewed)abstract
- It is known that ethnicity is a risk factor for diabetes. Thus, individuals of African, Latin American, and Asian descent are particularly susceptible (1). As an example, a health survey in six urban areas in Peru found a diabetes prevalence of 17% among women (2,3). It was also found that low socioeconomic status was associated with a high burden of noncommunicable diseases and appeared as an independent risk factor for diabetes. In several populations, it is known that increased physical activity reduces the risk for diabetes (4,5). Whether this applies for all populations is, however, not known. The aim of the present study was to explore if supervised endurance training is feasible among socioeconomically marginalized women of a poor urban area in Lima, Peru.
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| 6. |
- Westling, Sofie, et al.
(author)
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Altered glucose tolerance in women with deliberate self-harm
- 2009
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In: Psychoneuroendocrinology. - : Science direct. - 0306-4530 .- 1873-3360. ; 36:6, s. 878-883
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Journal article (peer-reviewed)abstract
- Disturbances in glucose metabolism are of importance for violent behaviour in men, but studies in women are lacking. We used the 5 h-oral glucose tolerance test (OGTT) in this study of 17 female psychiatric patients, selected for violent behaviour directed against themselves (deliberate self-harm) and 17 healthy controls matched for age and BMI. Following OGTT, patients had higher glucose levels at 30 min (p = 0.007) and increased glucagon area under the curve (p = 0.011). Since a co-morbid eating disorder might affect results, we as a post-hoc analysis subgrouped the patients and found that the increased glucagon levels only were present in patients with an eating disorder. In contrast, those without an eating disorder showed a significantly lower p-glucose nadir (p = 0.015) and unaltered glucagon levels compared to controls. There were no significant differences in insulin and C-peptide levels between patients and controls. We conclude that deliberate self-harm in women may be associated with alterations in carbohydrate metabolism in certain groups. Eating disorder is a confounding factor.
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| 7. |
- Mattsson, Cecilia, et al.
(author)
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Gender-specific links between hepatic 11beta reduction of cortisone and adipokines
- 2007
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In: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 15:4, s. 887-894
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Journal article (peer-reviewed)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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| 8. |
- Eriksson, Maria A, 1965-, et al.
(author)
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Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis
- 2008
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In: Blood Coagulation and Fibrinolysis. - : Lippincott Williams & Wilkins. - 1473-5733 .- 0957-5235. ; 19:7, s. 625-632
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Journal article (peer-reviewed)abstract
- The adipocyte-derived hormone leptin is associated with insulin resistance and reduced fibrinolytic status - or dysfibrinolysis - in humans. As leptin associates differentially to the development of cardiovascular disease and diabetes in men and women, we hypothesized that leptin and insulin sensitivity are related to dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were recruited from the Monitoring of trends and determinants in Cardiovascular disease (MONICA) population sample, representing the highest and lowest quartiles of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding globulin were measured. Insulin sensitivity was estimated using the euglycaemic clamp technique. Body composition was determined by bioimpedance. Determinants for circulating levels of fibrinolytic factors were explored in a multivariate linear regression analysis. Levels of fibrinolytic variables and estimated insulin sensitivity did not differ between men and women. Leptin was independently associated with reduced fibrinolytic status high PAI-1 activity, low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P<0.001-0.002). In women, fat mass and/or insulin sensitivity were related to these factors (P<0.001-0.03), and leptin only to reduced tPA activity (P = 0.002). Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate differentially in men and women. Blood Coagul Fibrinolysis 19:625-632 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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| 9. |
- Ahrén, Bo, et al.
(author)
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Clinical measures of islet function: usefulness to characterize defects in diabetes.
- 2008
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In: Current Diabetes Reviews. - 1573-3998. ; 4:2, s. 129-145
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Journal article (peer-reviewed)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
(author)
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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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In: Best Practice and Research in Clinical Endocrinology and Metabolism. - : Elsevier BV. - 1521-690X. ; 23:4, s. 487-498
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Journal article (peer-reviewed)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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