| 1. |
- Lindgärde, Folke, et al.
(författare)
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Disassociated relation between plasma tumor necrosis factor-alpha, interleukin-6 and increased body weight in Amerindian women: A long-term prospective study of natural body weight variation and impaired glucose tolerance
- 2010
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Ingår i: Diabetology and Metabolic Syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory cytokines are linked to obesity-related insulin resistance and may predict type 2 diabetes independently of obesity. We previously reported that a majority of a cohort of 73 non-diabetic women with normal plasma (p-) glucose with Amerindian heritage in Lima, Peru, during a 5-year period increased both body weight and p-glucose levels, yet p-insulin was unaltered. A high proportion of palmitoleic acid (16: 1n-7) in serum (s) and systolic blood pressure (SBP) were independent predictors of high p-glucose. Whether cytokines also contributed is, however, not known. Methods: During 5 years we prospectively investigated the relation between changed concentrations of p-tumor necrosis factor (TNF)-alpha, p-interleukin (IL)-6 and circulating insulin and glucose in relation to the natural variation of body weight. Study variables included anthropometric measurements, p-insulin, TNF-alpha, IL-6, SBP and the proportion of 16: 1n-7 in s-fatty acid composition. Results: Weight and waist differences correlated negatively to the difference in p-TNF-alpha but positively to differences in p-IL-6 and p-insulin, whereas the increase of p-glucose from baseline to follow-up did not correlate with changes in levels of the two cytokines. In multiple regression analysis changes of TNF-alpha and insulin contributed independently to the variance in weight. P-insulin at baseline and weight change were determinants of fasting p-insulin at follow-up. Multiple regression analysis revealed that weight change (t-value = -2.42; P = 0.018) and waist change (t-value = 2.41; P = 0.019) together with S-16: 1n-7 (p < 0.0001) and SBP (p = 0.0005) at baseline were significant predictors of p-glucose at follow-up. Conclusion: Our prospective study of Amerindian women revealed disassociations between changes in p-TNF-alpha and p-IL-6 in relation to variation in body weight. A high proportion of s-16: 1n-7, SBP at baseline together with weight and waist changes were independent predictors of p-glucose at follow-up. The exact role of the opposite effects and clinical impact of p-TNF-alpha and p-IL-6 on loss and gain of body weight and indirectly on the development of glucose intolerance is not known.
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| 2. |
- Wändell, Per, et al.
(författare)
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Effects of prescribed antithrombotics and other cardiovascular pharmacotherapies on all-cause mortality in patients with diabetes and atrial fibrillation - a cohort study from Sweden using propensity score analyses
- 2014
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Ingår i: Diabetology & Metabolic Syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 6, s. 2-
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo study mortality rates among patients with diabetes and concomitant atrial fibrillation (AF), prescribed different cardiovascular drugs in primary health care.MethodsStudy population consisted of men (n = 1319) and women (n = 1094) aged = >= 45 years from a database including 75 primary care centres in Sweden. Cox regression analysis, with hazard ratios (HRs), 95% confidence interval (95% CIs) and mortality (years to death) as outcome, and Laplace regression, with difference in time to first 10% mortality (with 95% CI), were performed. Independent variables were prescribed cardiovascular drugs. Regression models were adjusted for a propensity score calculated separately for each prescribed drug class (comprising age, cardiovascular co-morbidities, education, marital status and pharmacotherapy).ResultsOverall mortality was lower in the whole sample for anticoagulants vs no treatment (HR 0.45; 95% CI 0.26-0.77); and among patients < 80 years for anticoagulants vs. antiplatelets (HR 0.44; 95% CI 0.25-0.78); while among individuals aged >= 80 years, antiplatelets (HR 0.47; 95% CI 0.26-0.87) and anticoagulants (HR 0.49; 95% CI 0.24-1.00) vs. no treatment were equally effective. Statins were associated with lower mortality among those < 80 years (HR 0.45; 95% CI 0.29-0.71). Laplace regression models in the whole sample, with years to first 10% of total mortality as outcome, were significant for: among patients < 80 years anticoagulants vs. no treatment 2.70 years (95% CI 0.04-5.37), anticoagulants vs. antiplatelets 2.31 years (95% CI 0.84-3.79), and those >= 80 antiplatelets vs. no treatment 1.78 years (95% CI 1.04-2.52).ConclusionsOur findings suggest that antiplatelets could exert a beneficial effect among those above 80 years.
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| 3. |
- Abdelgadir, Moawia, et al.
(författare)
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Low serum adiponectin concentrations are associated with insulin sensitivity independent of obesity in Sudanese subjects with type 2 diabetes mellitus
- 2013
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Ingår i: Diabetology & Metabolic Syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 5, s. 15-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Prevalence of Type 2 diabetes mellitus among Sudanese population was found to be 3.4% and associated with high rates of complications and obesity. Different adipocytokines are secreted from adipose tissues, among them adiponectin, which was shown to have insulins ensitizing properties and anti-inflammatory, anti-atherogenic effect. The aim of this study was to characterize type 2 diabetes in Sudanese diabetic subjects and controls in respect to hormones influencing or influenced by glucose metabolism. Methods: 104 type 2 diabetic patients (45 men and 59 women), and 75 matched control subjects (34 men and 41 women) were studied. Fasting serum samples were used to measure adiponectin, leptin, insulin, proinsulin, ghrelin and glucose. Body mass index, insulin/proinsulin ratio and (HOMA) insulin resistance and beta cell function were also calculated. Results: Adiponectin serum concentrations were significantly lower in subjects with type 2 diabetes compared with controls subjects (P = 0.002), comparison between males and females did not reach significant levels in both diabetic (P = 0.06) or controls (P = 0.16) groups. In the diabetic group adiponectin correlated positively with serum glucose, negatively with serum proinsulin and HOMA beta cell function (P = 0.03) respectively and serum ghrelin (P = 0.003), but not with BMI, HOMA insulin resistance, insulin or leptin. In controls serum adiponectin correlated negatively with BMI (P = 0.002) but not with other variables. Conclusions: The findings of this study suggest that, adiponectin concentrations independent on BMI as a measure of adiposity, were mostly linked to insulin sensitivity and not to insulin resistance in Sudanese type 2 diabetic subjects, where race specific regulation mechanisms or different type 2 diabetes phenotype suggested being a major contributory factor in clarification the findings of this study.
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| 4. |
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| 5. |
- Hammarstedt, Ann, 1975, et al.
(författare)
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Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells.
- 2012
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Ingår i: Diabetology & metabolic syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to cause systemic insulin resistance in the absence of adipose tissue metabolic dysfunction. To determine if this holds true for humans, we studied the relationship between insulin resistance and markers of adipose tissue dysfunction in non-obese individuals. METHOD: 32 non-obese first-degree relatives of Type 2 diabetic patients were recruited. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was measured with the hyperinsulinaemic-euglycaemic clamp. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene/protein expression and adipocyte cell size measurements. RESULTS: Our findings show that also in non-obese individuals low insulin sensitivity is associated with signs of adipose tissue metabolic dysfunction characterized by low expression of GLUT4, altered adipokine profile and enlarged adipocyte cell size. In this group, insulin sensitivity is positively correlated to GLUT4 mRNA (R=0.49, p=0.011) and protein (R=0.51, p=0.004) expression, as well as with circulating adiponectin levels (R=0.46, 0=0.009). In addition, insulin sensitivity is inversely correlated to circulating RBP4 (R=-0.61, 0=0.003) and adipocyte cell size (R=-0.40, p=0.022). Furthermore, these features are inter-correlated and also associated with other clinical features of the metabolic syndrome in the absence of obesity. No association could be found between the hypertrophy-associated adipocyte dysregulation and HIF-1alpha in this group of non-obese individuals. CONCLUSIONS: In conclusion, these findings support the concept that it is not obesity per se, but rather metabolic dysfunction of adipose tissue that is associated with systemic insulin resistance and the metabolic syndrome.
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| 6. |
- Håglin, Lena M., et al.
(författare)
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High serum phosphate and triglyceride levels in smoking women and men with CVD risk and type 2 diabetes
- 2014
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Ingår i: Diabetology & Metabolic Syndrome. - : BioMed Central (BMC). - 1758-5996. ; 6, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both low and high serum phosphate levels may be associated with morbidity and mortality from cardiovascular disease. As smoking increases risk for type 2 diabetes (as shown by dyslipidemia and hyperglycemia), we wanted to study whether smoking and type 2 diabetes were associated with serum phosphate and triglyceride levels independently from other CVD risk factors. Methods: Upon admittance to the Vindeln Health Education Centre (VHE-centre) for a four-week comprehensive lifestyle intervention, the participants (1408 women and 1096 men) completed a questionnaire that included their smoking habits - current smoker or non-smoker. We used multiple linear regression analyses to investigate the association between smoking and other CVD risk factors with S-P and S-TG levels. Results: In the non-type 2 diabetes populations, the smokers, compared to the non-smokers, had higher S-P and higher serum triglycerides (S-TG). In women, serum-TG in smokers with type 2 diabetes was higher than in smokers with non-type 2 diabetes. Non-type 2 diabetes patients exhibited an inverse relation between S-Glucose (S-Glu) and S-P and a positive association with S-TG. For men only, an association was seen between age (-) and S-Crea (-) and S-P. For women only, an association was seen between BMI (-) and S-Cholesterol (+) (S-Chol) and S-P. Conclusions: Compared to non-smokers, smoking women with non-type 2 diabetes and smoking men with type 2 diabetes had a higher level of S-P and S-TG. The association between smoking and S-P and S-TG levels still existed after adjusting for age and CVD risk factors in the multiple linear regression analyses.
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| 7. |
- Håkansson, Joakim, 1975, et al.
(författare)
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Adipocyte mitochondrial genes and the forkhead factor FOXC2 are decreased in type 2 diabetes patients and normalized in response to rosiglitazone.
- 2011
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Ingår i: Diabetology & metabolic syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: FOXC2 has lately been implicated in diabetes and obesity as well as mitochondrial function and biogenesis and also as a regulator of mtTFA/Tfam. In this study, the expression of FOXC2 and selected genes involved in mitochondrial function and biogenesis in healthy subjects and in a matched cohort with type 2 diabetes patients before and after treatment with rosiglitazone was determined. Quantitative real time PCR was used to analyze both RNA and DNA from biopsies from subcutaneous adipose tissue. METHODS: Blood samples and subcutaneous abdominal fat biopsies were collected from 12 T2D patients, of which 11 concluded the study, pre-treatment and 90 days after initiation of rosiglitazone treatment, and from 19 healthy control subjects on the first and only visit from healthy subjects. Clinical parameters were measured on the blood samples. RNA and DNA were prepared from the fat biopsies and gene expression was measured with real time PCR. RESULTS: The expression level of genes in the mitochondrial respiratory complexes I - IV were significantly downregulated in the diabetic patients and restored in response to rosiglitazone treatment. Rosiglitazone treatment also increased the relative number of mitochondria in diabetic patients compared with controls. Furthermore, the transcription factors FOXC2 and mtTFA/Tfam displayed a response pattern identical to the mitochondrial genes. CONCLUSIONS: FOXC2, mtTFA/Tfam and subunits of the respiratory complexes I - IV show equivalent regulation in gene expression levels in response to TZD treatment. This, together with the knowledge that FOXC2 has a regulatory function of mtTFA/Tfam and mitochondrial biogenesis, suggests that FOXC2 has a possible functional role in the TZD activated mitochondrial response.
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| 8. |
- Kappe, Camilla, et al.
(författare)
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Effects of high-fat diet and the anti-diabetic drug metformin on circulating GLP-1 and the relative number of intestinal L-cells
- 2014
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Ingår i: Diabetology & Metabolic Syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 6, s. 70-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated serum free fatty acids (FFAs) contribute to the pathogenesis of type-2-diabetes (T2D), and lipotoxicity is observed in many cell types. We recently showed that simulated hyperlipidemia induces lipoapoptosis also in GLP-1-secreting L-cells in vitro, while metformin confers lipoprotection. The aim of this study was to determine if a high fat diet (HFD) reduces the number of enteroendocrine L-cells and/or GLP-1 plasma levels in a rodent model, and potential effects thereupon of metformin treatment. Methods: C57/Bl6 mice received control/HFD for 12-weeks, and oral administration of metformin/saline for the last 14 days. Blood glucose, glycosylated hemoglobin and plasma insulin and GLP-1 were determined before and after treatment with metformin using ELISAs. GLP-1-immunopositive cells in intestinal tissue sections were quantified using immunohistochemistry. Results: A HFD increased blood glucose, glycosylated hemoglobin, and fasting plasma insulin (33%, 15% and 70% increase, respectively), in conjunction with reduced oral glucose tolerance, indicating the manifestation of insulin resistance. Metformin counteracted these adverse effects, while also reducing prandial plasma FFAs. The number of GLP-1-positive cells was indicated to be reduced (55% reduction of the number of GLP-1-positive cells, p = 0.134), while there was a trend toward increased prandial plasma GLP-1 despite reduced food intake following a HFD. Conclusion: HFD-fed mice rapidly develop insulin resistance. Metformin exerts beneficial glucose lowering effects, and is indicated to improve the incretin response. Albeit no significant effect, a HFD tends to reduce the number of GLP-1-positive cells. However, considering concurrent normal or increased plasma GLP-1, any reduction in the number of GLP-1-positive cells, probably does not contribute to development of the glucose intolerance, but may contribute to progression of the diabetic state through eventual loss of a functional incretin response.
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| 9. |
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| 10. |
- Araujo de Pina Cabral, DB, et al.
(författare)
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Prospective evaluation of glutamine and phospholipids levels in first degree relatives of patients with Type 1 Diabetes from a multiethnic population
- 2015
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Ingår i: Diabetology and Metabolic Syndrome. - : BioMed Central (BMC). - 1758-5996 .- 1758-5996. ; 7:52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A dysregulation in the metabolism of lipids may be an early marker of autoimmunity in Type 1 Diabetes (T1D). It would be of general importance to identify metabolic patterns that would predict the risk for T1D later in life. The aim of this study was to perform a prospective evaluation of glutamine and phospholipids levels in Brazilian first degree relatives (FDR) of patients with T1D in a mean interval of 5 years.FINDINGS: Brazilian FDR (n = 30) of patients with T1D were evaluated and blood was sampled to measure the levels of glutamine and phospholipids in the fasting serum by quantitative colorimetric method. The tests were repeated after a mean interval of 5 years and compared to a control group (n = 20). The FDR presented lower levels of phospholipids than controls (p = 0.028), but not of glutamine (p = 0.075). Phospholipids levels decreased over time (p = 0.028) in FDR and were associated with Glutamic acid decarboxylase autoantibody (GADA) titers (p = 0.045), autoantibody positivity (p = 0.008) and PTPN22 polymorphisms (p = 0.014).CONCLUSIONS: In this Brazilian multiethnic population, there was a significant decrease in phospholipids levels in FDR in patients with T1D during a 5-year prospective follow-up, as well as a significant association between these metabolite, GADA and PTPN22 polymorphisms. For Glutamine no difference was found. These findings suggest that a dysregulation in the metabolism of lipids may precede the onset of the autoimmunity in T1D.
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