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Norhammar, A., Bodegård, J., Nyström, T., Thuresson, M., Nathanson, D. & Eriksson, J. (2019). Dapagliflozin and cardiovascular mortality and disease outcomes in a population with type 2 diabetes similar to that of the DECLARE-TIMI 58 trial: A nationwide observational study. Diabetes, obesity and metabolism, 21(5), 1136-1145
Open this publication in new window or tab >>Dapagliflozin and cardiovascular mortality and disease outcomes in a population with type 2 diabetes similar to that of the DECLARE-TIMI 58 trial: A nationwide observational study
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2019 (English)In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 21, no 5, p. 1136-1145Article in journal (Refereed) Published
Abstract [en]

Aims: To investigate cardiovascular (CV) safety and event rates for dapagliflozin versus other glucose-lowering drugs (GLDs) in a real-world type 2 diabetes population after applying the main inclusion criteria and outcomes from the DECLARE-TIMI 58 study.

Methods: Patients with new initiation of dapagliflozin and/or other GLDs were identified in Swedish nationwide healthcare registries for the period 2013 to 2016. Patients were included if they met the main DECLARE-TIMI 58 inclusion criteria: age 40years and established CV disease or presence of multiple-risk factors, e.g. men aged 55years and women aged 60years with hypertension or dyslipidaemia. Propensity scores for the likelihood of dapagliflozin initiation were calculated, then 1:3 matching was carried out. DECLARE-TIMI 58 outcomes were hospitalization for heart failure (HHF) or CV-specific mortality, and major adverse CV events (MACE; CV-specific mortality, myocardial infarction, or stroke). Cox survival models were used to estimate hazard ratios (HRs).

Results: After matching, a total of 28408 new-users of dapagliflozin and/or other GLDs were identified, forming the population for the present study (henceforth referred to as the DECLARE-like cohort. The mean age of this cohort was 66years, and 34% had established CV disease. Dapagliflozin was associated with 21% lower risk of HHF or CV mortality versus other GLDs (HR 0.79, 95% confidence interval [CI] 0.69-0.92) and had no significant association with MACE (HR 0.90, 95% CI 0.79-1.03). HHF and CV mortality risks, separately, were lower at HR 0.79 (95% CI 0.67-0.93) and HR 0.75 (95% CI 0.57-0.97), respectively. Non-significant associations were seen for myocardial infarction and stroke: HR 0.91 (95% CI 0.74-1.11) and HR 1.06 (95% CI 0.87-1.30), respectively.

Conclusion: In a real-world population similar to those included in the DECLARE-TIMI 58 study, dapagliflozin was safe with regard to CV outcomes and resulted in lower event rates of HHF and CV mortality versus other GLDs.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
cardiovascular disease, cohort study, dapagliflozin, pharmaco-epidemiology, type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-383151 (URN)10.1111/dom.13627 (DOI)000465395000009 ()30609272 (PubMedID)
Funder
AstraZeneca
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-10Bibliographically approved
Katsogiannos, P., Kamble, P. G., Boersma, G. J., Karlsson, F. A., Lundkvist, P., Sundbom, M., . . . Eriksson, J. (2019). Early Changes in Adipose Tissue Morphology, Gene Expression, and Metabolism After RYGB in Patients With Obesity and T2D. Journal of Clinical Endocrinology and Metabolism, 104(7), 2601-2613
Open this publication in new window or tab >>Early Changes in Adipose Tissue Morphology, Gene Expression, and Metabolism After RYGB in Patients With Obesity and T2D
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2019 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 7, p. 2601-2613Article in journal (Refereed) Published
Abstract [en]

Context: Roux-en-Y gastric bypass (RYGB) surgery effectively prevents or treats type 2 diabetes (T2D). Adipose tissue (AT) mechanisms may be of importance.

Objective: To assess the relationship between early changes in whole-body and AT metabolism in surgically treated patients with T2D.

Design and Setting: A randomized single-center study.

Patients: Nineteen patients with T2D with body mass index 30 to 45 kg/m(2).

Interventions: Thirteen patients were assessed at baseline and 4 and 24 weeks after RYGB (preceded by a 4-week low-calorie diet) and compared with 6 control patients continuing standard medical treatment: oral glucose tolerance test, subcutaneous AT biopsies for gene expression, adipocyte size, glucose uptake, lipolysis, and insulin action.

Results: At 4 and 24 weeks post-RYGB, all patients but one had stopped diabetes medication. Fasting glucose, HbA(1c), and insulin levels decreased and the Matsuda index increased compared with baseline (P < 0.01 for all), indicating improved whole-body insulin sensitivity. Mean adipocyte size significantly reduced, more at 4 than at 24 weeks; at 4 weeks, glucose uptake per adipocyte was lowered, and isoproterenol-stimulated lipolysis tended to increase, whereas the fold insulin effects on glucose uptake and lipolysis were unchanged. Expression of genes involved in fatty acid oxidation, CPT1b and adiponectin, was increased at 4 weeks, whereas leptin and E2F1 (involved in cell proliferation) were reduced (P < 0.05 for all).

Conclusion: Glycemic control and in vivo insulin sensitivity improved 4 weeks after RYGB, but adipocyte insulin sensitivity did not change despite a marked reduction in adipocyte size. Thus, mechanisms for a rapid improvement of T2D after RYGB may occur mainly in other tissues than adipose.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-390982 (URN)10.1210/jc.2018-02165 (DOI)000474806300015 ()30689903 (PubMedID)
Funder
EXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2019-08-19Bibliographically approved
Almby, K. E., Abrahamsson, N., Lundqvist, M. H., Hammar, U., Thombare, K., Panagiotou, A., . . . Eriksson, J. (2019). Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery. European Journal of Endocrinology, 181(2), 161-171
Open this publication in new window or tab >>Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
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2019 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 181, no 2, p. 161-171Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).

Design: Experimental hyperinsulinemic-hypoglycemic clamp study.

Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.

Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.

Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

Place, publisher, year, edition, pages
BIOSCIENTIFICA LTD, 2019
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-390513 (URN)10.1530/EJE-19-0171 (DOI)000472835100013 ()31176298 (PubMedID)
Funder
Swedish Diabetes AssociationErnfors FoundationEXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved
Mosenzon, O., Blicher, T. M., Rosenlund, S., Eriksson, J., Heller, S., Hels, O. H., . . . Desouza, C. (2019). Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. The Lancet Diabetes and Endocrinology, 7(7), 515-527
Open this publication in new window or tab >>Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial
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2019 (English)In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 7, no 7, p. 515-527Article in journal (Refereed) Published
Abstract [en]

Background: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment.

Methods: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m(2), and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without inetformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA k (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug.The trial is registered on ClinicalTrials. gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete.

Findings: Between Sept 20,2016, and Sept 29,2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA(1c) (estimated mean change of -1.0 percentage point (SE 0.1; -11 mmol/mol [SE 0.8]) vs-0.2 percentage points (SE 0.1; -2 mmol/mol [SE 0.8]); estimated treatment difference [ETD]: -0.8 percentage points, 95% CI -1.0 to -0.6; p<0.0001) and bodyweight (estimated mean change of -3.4 kg [SE 0.3] vs -0.9 kg [SE 0.3]; ETD, -2.5, 95% CI -3.2 to -1.8; p<0.0001) by the treatment policy estimand. Significant differences were seen for the trial product estimand: mean change in HbA(1c) -1.1 percentage points (SE 0.1; -12 mmol/mol [SE 0.8] versus -0.1 percentage points (SE 0.1; -1 mmol/mol [SE 0.8]; ETD -1.0 percentage points, 95% CI -1.2 to -0.8; p<0.0001); mean change in bodyweight -3.7 kg (SE 0.3) versus -1.1 kg (SE 0.3; ETD -2.7 kg, 95% CI -3.5 to -1.9; p<0-0001). More patients taking oral semaglutide than placebo had adverse events (120 [74%] of 163 vs 105 [65%] of 161), and discontinued treatment as a result (24 [15%] vs eight [5%]). Gastrointestinal events, mainly mild-to-moderate nausea, were more common with oral semaglutide than with placebo. Three deaths occurred during the treatment period that were not condsidered to be treatment related, one in the semaglutide group and two in the placebo group.

Interpretation: Oral semaglutide was effective in patients with type 2 diabetes and moderate renal impairment, potentially providing a new treatment option for this population. Safety, including renal safety, was consistent with the GLP-1 receptor agonist class. 

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2019
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-390086 (URN)10.1016/S2213-8587(19)30192-5 (DOI)000471906500012 ()31189517 (PubMedID)
Funder
Novo Nordisk
Available from: 2019-08-06 Created: 2019-08-06 Last updated: 2019-08-06Bibliographically approved
Pereira, M. J. & Eriksson, J. (2019). Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity. Drugs, 79(3), 219-230
Open this publication in new window or tab >>Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity
2019 (English)In: Drugs, ISSN 0012-6667, E-ISSN 1179-1950, Vol. 79, no 3, p. 219-230Article in journal (Refereed) Published
Abstract [en]

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering drugs that reduce plasma glucose levels by inhibiting glucose and sodium reabsorption in the kidneys, thus resulting in glucosuria. Their effects consequently include reductions in HbA1c, blood glucose levels, and blood pressure, but also reductions in body weight and adiposity. The ability to reduce body weight is consistently observed in individuals taking SGLT2 inhibitors, but this weight loss is moderate due to counter-regulatory mechanisms striving to maintain body weight. This has prompted exploration of SGLT2 inhibitors in combination with other agents acting via decreased food intake, e.g., glucagon-like peptide 1 receptor agonists (GLP1-RAs). The bodyweight effects are promising, and together with the signs of prevention of cardiovascular and renal events, such combinations including SGLT2 inhibitors are appealing. The weight loss is clinically important, as most individuals with type 2 diabetes are overweight or obese, but also because there is an unmet need for safe, effective, and durable weight loss interventions in obese individuals without diabetes.

Place, publisher, year, edition, pages
ADIS INT LTD, 2019
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-379267 (URN)10.1007/s40265-019-1057-0 (DOI)000459785400001 ()30701480 (PubMedID)
Funder
Swedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in SwedenErnfors FoundationAstraZeneca
Available from: 2019-03-18 Created: 2019-03-18 Last updated: 2019-03-18Bibliographically approved
Kamble, P. G., Pereira, M. J., Almby, K. E. & Eriksson, J. (2019). Estrogen interacts with glucocorticoids in the regulation of lipocalin 2 expression in human adipose tissue. Reciprocal roles of estrogen receptor alpha and beta in insulin resistance?. Molecular and Cellular Endocrinology, 490, 28-36
Open this publication in new window or tab >>Estrogen interacts with glucocorticoids in the regulation of lipocalin 2 expression in human adipose tissue. Reciprocal roles of estrogen receptor alpha and beta in insulin resistance?
2019 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 490, p. 28-36Article in journal (Refereed) Published
Abstract [en]

The adipokine lipocalin 2 (LCN2) is linked to insulin resistance. Its expression in human adipose tissue (AT) can be regulated in a sex-specific manner by a synthetic glucocorticoid, dexamethasone, suggesting an underlying role of sex steroids. We show that 17-beta-estradiol (E2) dose-dependently increased LCN2 gene expression in subcutaneous AT from postmenopausal women. This was also seen in the presence of estrogen receptor (ER) alpha antagonist alone but not with ER beta antagonist, suggesting that E2 effects on LCN2 are mediated via ER beta pathway. Dexamethasone alone or E2 + dexamethasone had no significant effect on LCN2. However, E2+ dexamethasone increased LCN2 expression with ER alpha-blockade. Dexamethasone reduced ER alpha but increased ER beta expression. Dexamethasone can regulate LCN2 expression via inhibition of ER alpha and stimulation of ER beta and may contribute to the development of glucocorticoid-induced insulin resistance in human AT. In conclusion, ER beta and ER alpha pathways have opposite effects on LCN2 expression and they interact with glucocorticoid action.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2019
Keywords
Human adipose tissue, Estrogen, Glucocorticoids, Lipocalin2
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-384989 (URN)10.1016/j.mce.2019.04.002 (DOI)000467539600004 ()30953748 (PubMedID)
Funder
Swedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in SwedenErnfors Foundation
Available from: 2019-06-13 Created: 2019-06-13 Last updated: 2019-06-13Bibliographically approved
Lundkvist, P., Pereira, M. J., Kamble, P. G., Katsogiannos, P., Langkilde, A. M., Esterline, R., . . . Eriksson, J. W. (2019). Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes.. Journal of Clinical Endocrinology and Metabolism, 104(1), 193-201
Open this publication in new window or tab >>Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes.
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2019 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 1, p. 193-201Article in journal (Refereed) Published
Abstract [en]

Context: The mechanism mediating sodium glucose cotransporter-2 (SGLT2) inhibitor-associated increase in glucagon levels is unknown.

Objective: To assess short-term effects on glucagon, other hormones, and energy substrates after SGLT2 inhibition and whether such effects are secondary to glucose lowering. The impact of adding a dipeptidyl peptidase-4 inhibitor was addressed.

Design, Setting, and Patients: A phase 4, single-center, randomized, three-treatment crossover, open-label study including 15 patients with type 2 diabetes treated with metformin.

Interventions: Patients received a single-dose of dapagliflozin 10 mg accompanied by the following in randomized order: isoglycemic clamp (experiment DG); saline infusion (experiment D); or saxagliptin 5 mg plus saline infusion (experiment DS). Directly after 5-hour infusions, a 2-hour oral glucose tolerance test (OGTT) was performed.

Results: Glucose and insulin levels were stable in experiment DG and decreased in experiment D [P for difference (Pdiff) < 0.001]. Glucagon-to-insulin ratio (Pdiff < 0.001), and levels of glucagon (Pdiff < 0.01), nonesterified fatty acids (Pdiff < 0.01), glycerol (Pdiff < 0.01), and β-OH-butyrate (Pdiff < 0.05) were lower in DG vs D. In multivariate analysis, change in glucose level was the main predictor of change in glucagon level. In DS, glucagon and active GLP-1 levels were higher than in D, but glucose and insulin levels did not differ. During OGTT, glucose levels rose less and glucagon levels fell more in DS vs D.

Conclusion: The degree of glucose lowering markedly contributed to regulation of glucagon and insulin secretion and to lipid mobilization during short-term SGLT2 inhibition.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-373521 (URN)10.1210/jc.2018-00969 (DOI)000461917800025 ()30137410 (PubMedID)
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-04-10Bibliographically approved
Diamanti, K., Cavalli, M., Pan, G., Pereira, M. J., Kumar, C., Skrtic, S., . . . Wadelius, C. (2019). Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes. Scientific Reports, 9, Article ID 9653.
Open this publication in new window or tab >>Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9653Article in journal (Refereed) Published
Abstract [en]

Type 2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from 43 multi-organ donors. The intra-individual analysis was assessed across five key metabolic tissues (serum, visceral adipose tissue, liver, pancreatic islets and skeletal muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. In diabetes cases, carnitines were significantly higher in liver, while lysophosphatidylcholines were significantly lower in muscle and serum. We tracked the primary tissue of origin for multiple metabolites whose alterations were reflected in serum. An investigation of three major stages spanning from controls, to pre-diabetes and to overt T2D indicated that a subset of lysophosphatidylcholines was significantly lower in the muscle of pre-diabetes subjects. Moreover, glycodeoxycholic acid was significantly higher in liver of pre-diabetes subjects while additional increase in T2D was insignificant. We confirmed many previously reported findings and substantially expanded on them with altered markers for early and overt T2D. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-391017 (URN)10.1038/s41598-019-45906-5 (DOI)000474222900010 ()31273253 (PubMedID)
Funder
AstraZenecaSwedish Research Council FormaseSSENCE - An eScience CollaborationSwedish Diabetes AssociationErnfors Foundation
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-09-22Bibliographically approved
Lundqvist, M. H., Almby, K. E., Abrahamsson, N. & Eriksson, J. (2019). Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?. Frontiers in Physiology, 10, Article ID 457.
Open this publication in new window or tab >>Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?
2019 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 457Article, review/survey (Refereed) Published
Abstract [en]

Ever since Claude Bernards discovery in the mid 19th-century that a lesion in the floor of the third ventricle in dogs led to altered systemic glucose levels, a role of the CNS in whole-body glucose regulation has been acknowledged. However, this finding was later overshadowed by the isolation of pancreatic hormones in the 20th century. Since then, the understanding of glucose homeostasis and pathology has primarily evolved around peripheral mechanism. Due to scientific advances over these last few decades, however, increasing attention has been given to the possibility of the brain as a key player in glucose regulation and the pathogenesis of metabolic disorders such as type 2 diabetes. Studies of animals have enabled detailed neuroanatomical mapping of CNS structures involved in glucose regulation and key neuronal circuits and intracellular pathways have been identified. Furthermore, the development of neuroimaging techniques has provided methods to measure changes of activity in specific CNS regions upon diverse metabolic challenges in humans. In this narrative review, we discuss the available evidence on the topic. We conclude that there is much evidence in favor of active CNS involvement in glucose homeostasis but the relative importance of central vs. peripheral mechanisms remains to be elucidated. An increased understanding of this field may lead to new CNS-focusing pharmacologic strategies in the treatment of type 2 diabetes.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
CNS, hypothalamus, glucose, regulation, fMRI, neuroimaging, neuroendocrine, autonomic nervous system
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-383553 (URN)10.3389/fphys.2019.00457 (DOI)000466111400001 ()
Funder
EU, Horizon 2020, 721236-TREATMENTSwedish Diabetes AssociationErnfors Foundation
Available from: 2019-05-20 Created: 2019-05-20 Last updated: 2019-05-20Bibliographically approved
Hadrévi, J., Jonsdottir, I. H., Jansson, P.-A., Eriksson, J. W. & Sjörs, A. (2019). Plasma metabolomic patterns in patients with exhaustion disorder. Stress, 22(1), 17-26
Open this publication in new window or tab >>Plasma metabolomic patterns in patients with exhaustion disorder
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2019 (English)In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 22, no 1, p. 17-26Article in journal (Refereed) Published
Abstract [en]

Exhaustion disorder (ED) is a stress-related disorder that often implies a great burden on the individual patient as well as on society. Previous studies have shown that ED is associated with metabolic deviations, such as lowered fasting glucose. Several mechanisms have been discussed as a plausible explanation of the lack of energy described by these patients. Metabolic processes and reduced ability to mobilize energy have been suggested as important factors. This study investigated metabolomics in 20 patients diagnosed with ED and compared them with 21 healthy controls. Plasma metabolic profiles were examined in both fasting and nonfasting (postprandial) conditions. Blood plasma samples were analyzed for metabolite content using gas chromatography mass spectrometry. A total of 62 different metabolites were simultaneously detected in each of the samples. Multivariate models indicated systematic differences between patients with ED and healthy controls in both their fasting and nonfasting plasma metabolite levels. Lysine and octadecenoic acid were more abundant and glutamine, glycine, serine and gluconic acid were less abundant in the patients across both conditions. In the present study, we comprehensively and simultaneously screen for changes in a large number of metabolites. Our results show a difference in systemic metabolites between patients with exhaustion disorder and healthy controls both in the fasting and in the postprandial states. Here, we present new potential biomarkers mirroring exhaustion disorder metabolism.Lay summary Exhaustion disorder (ED) patients suffer from stress-related symptoms including a reduced energy level. This study investigates the body's metabolism in patients with ED, both fasting and after a meal. New potential markers that may help future investigations on ED were identified.

Keywords
Clinical burnout, exhaustion disorder, metabolism, metabolomics, biomarkers, stress
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-382672 (URN)10.1080/10253890.2018.1494150 (DOI)000463861400003 ()30084722 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2013-1123
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-05-07Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2639-9481

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