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- Kalinovich, Anastasia, et al.
(författare)
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Treatment with a β-2-adrenoceptor agonist stimulates glucose uptake in skeletal muscle and improves glucose homeostasis, insulin resistance and hepatic steatosis in mice with diet-induced obesity
- 2020
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63:8, s. 1603-1615
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Chronic stimulation of beta(2)-adrenoceptors, opposite to acute treatment, was reported to reduce blood glucose levels, as well as to improve glucose and insulin tolerance in rodent models of diabetes by essentially unknown mechanisms. We recently described a novel pathway that mediates glucose uptake in skeletal muscle cells via stimulation of beta(2)-adrenoceptors. In the current study we further explored the potential therapeutic relevance of beta(2)-adrenoceptor stimulation to improve glucose homeostasis and the mechanisms responsible for the effect.Methods C57Bl/6N mice with diet-induced obesity were treated both acutely and for up to 42 days with a wide range of clenbuterol dosages and treatment durations. Glucose homeostasis was assessed by glucose tolerance test. We also measured in vivo glucose uptake in skeletal muscle, insulin sensitivity by insulin tolerance test, plasma insulin levels, hepatic lipids and glycogen.Results Consistent with previous findings, acute clenbuterol administration increased blood glucose and insulin levels. However, already after 4 days of treatment, beneficial effects of clenbuterol were manifested in glucose homeostasis (32% improvement of glucose tolerance after 4 days of treatment,p < 0.01) and these effects persisted up to 42 days of treatment. These favourable metabolic effects could be achieved with doses as low as 0.025 mg kg(-1) day(-1)(40 times lower than previously studied). Mechanistically, these effects were not due to increased insulin levels, but clenbuterol enhanced glucose uptake in skeletal muscle in vivo both acutely in lean mice (by 64%,p < 0.001) as well as during chronic treatment in diet-induced obese mice (by 74%,p < 0.001). Notably, prolonged treatment with low-dose clenbuterol improved whole-body insulin sensitivity (glucose disposal rate after insulin injection increased up to 1.38 +/- 0.31%/min in comparison with 0.15 +/- 0.36%/min in control mice,p < 0.05) and drastically reduced hepatic steatosis (by 40%,p < 0.01) and glycogen (by 23%,p < 0.05).Conclusions/interpretation Clenbuterol improved glucose tolerance after 4 days of treatment and these effects were maintained for up to 42 days. Effects were achieved with doses in a clinically relevant microgram range. Mechanistically, prolonged treatment with a low dose of clenbuterol improved glucose homeostasis in insulin resistant mice, most likely by stimulating glucose uptake in skeletal muscle and improving whole-body insulin sensitivity as well as by reducing hepatic lipids and glycogen. We conclude that selective beta(2)-adrenergic agonists might be an attractive potential treatment for type 2 diabetes. This remains to be confirmed in humans.
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- Xu, Tianwei, et al.
(författare)
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Workplace bullying and violence as risk factors for type 2 diabetes : a multicohort study and meta-analysis
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:1, s. 75-83
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The aim of this multicohort study was to examine whether employees exposed to social stressors at work, such as workplace bullying and violence, have an increased risk of type 2 diabetes.METHODS: The study included 45,905 men and women (40-65 years of age and free of diabetes at baseline) from four studies in Sweden, Denmark and Finland. Workplace bullying and violence were self-reported at baseline. Incident diabetes was ascertained through national health and medication records and death registers. Marginal structural Cox models adjusted for age, sex, country of birth, marital status and educational level were used for the analyses.RESULTS: Nine per cent of the population reported being bullied at work and 12% were exposed to workplace violence or threats of violence. Bullied participants had a 1.46 (95% CI 1.23, 1.74) times higher risk of developing diabetes compared with non-bullied participants. Exposure to violence or threats of violence was also associated with a higher risk of diabetes (HR 1.26 [95% CI 1.02, 1.56]). The risk estimates attenuated slightly when taking BMI into account, especially for bullying. The results were similar for men and women, and were consistent across cohorts.CONCLUSIONS/INTERPRETATION: We found a higher risk of incident type 2 diabetes among employees exposed to bullying or violence in the workplace. Further research is needed to determine whether policies to reduce bullying and violence at work may reduce the incidence of type 2 diabetes in working populations. Research on the mechanisms is also highly warranted.
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| 3. |
- Yang, Rongrong, et al.
(författare)
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A healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes : a prospective nested case-control study in a nationwide Swedish twin cohort
- 2021
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 530-539
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis We aimed to examine the association between type 2 diabetes and major subtypes of heart disease, to assess the role of genetic and early-life familial environmental factors in this association and to explore whether and to what extent a healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes.Methods In this prospective nested case-control study based on the Swedish Twin Registry, 41,463 twin individuals who were aged >= 40 and heart disease-free were followed up for 16 years (from 1998 to 2014) to detect incident heart disease. Type 2 diabetes was ascertained from self-report, the National Patient Registry and glucose-lowering medication use. Heart disease diagnosis (including coronary heart disease, cardiac arrhythmias and heart failure) and onset age were identified from the National Patient Registry. Healthy lifestyle-related factors consisted of being a non-smoker, no/mild alcohol consumption, regular physical activity and being non-overweight. Participants were divided into three groups according to the number of lifestyle-related factors: (1) unfavourable (participants who had no or only one healthy lifestyle factor); (2) intermediate (any two or three); and (3) favourable (four). Generalised estimating equation models for unmatched case-control design and conditional logistic regression for co-twin control design were used in data analyses.Results Of all participants, 2304 (5.5%) had type 2 diabetes at baseline. During the observation period, 9262 (22.3%) had any incident heart disease. In unmatched case-control analyses and co-twin control analyses, the multi-adjusted OR and 95% CI of heart disease related to type 2 diabetes was 4.36 (3.95, 4.81) and 4.89 (3.88, 6.16), respectively. The difference in ORs from unmatched case-control analyses vs co-twin control analyses was statistically significant (OR 1.57; 95% CI 1.42, 1.73; p < 0.001). In stratified analyses by type 2 diabetes, compared with an unfavourable lifestyle, an intermediate lifestyle or a favourable lifestyle was associated with a significant 32% (OR 0.68; 95% CI 0.49, 0.93) or 56% (OR 0.44; 95% CI 0.30, 0.63) decrease in heart disease risk among patients with type 2 diabetes, respectively. There were significant additive and multiplicative interactions between lifestyle and type 2 diabetes on heart disease.Conclusions/interpretation Type 2 diabetes is associated with more than fourfold increased risk of heart disease. The association still remains statistically significant, even after fully controlling for genetic and early-life familial environmental factors. However, greater adherence to a healthy lifestyle may significantly mitigate the risk of heart disease related to type 2 diabetes.
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| 4. |
- Yang, Rongrong, et al.
(författare)
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Type 2 diabetes in midlife and risk of cerebrovascular disease in late life : a prospective nested case-control study in a nationwide Swedish twin cohort
- 2019
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:8, s. 1403-1411
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association.Methods In this prospective nested case-control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40-59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age >= 60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case-control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case-control analyses in CBD-discordant twin pairs.Results Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes-cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p=0.780).Conclusions/interpretation Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes-cerebral infarction association, but further clarification is needed.
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