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1.
  • Dorkhan, Mozhgan, et al. (författare)
  • Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes
  • 2009
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Both insulin and thiazolidinediones (TZDs) are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods: Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results: After 26 weeks of treatment, the changes in HbAlc, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 +/- 19.6 to 22.8 +/- 44.0, p = 0.046), the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p < 0.05, between treatment groups). There was a borderline significant increase in ejection fraction in the pioglitazone group. Conclusion: This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.
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2.
  • Hyvärinen, Marjukka, et al. (författare)
  • The impact of diabetes on coronary heart disease differs from that on ischaemic stroke with regard to the gender.
  • 2009
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 8:17
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To study the diabetes related CVD risk between men and women of different ages. METHODS: Hazards ratios (HRs) (95%CI) for acute CHD and ischaemic stroke events were estimated based on data of Finnish and Swedish cohorts of 5111 women and 4167 men. RESULTS: 182 (3.6%) women and 348 (8.4%) men had CHD and 129 (2.5%) women and 137 (3.3%) men ischaemic stroke events. The multivariate adjusted HRs for acute CHD at age groups of 40-49, 50-59 and 60-69 years were 1.00 (1.94), 1.78 (4.23), 3.75 (8.40) in women (men) without diabetes and 4.35 (5.40), 5.49 (9.54) and 8.84 (13.76) in women (men) with diabetes. The corresponding HRs for ischaemic stroke were 1.00 (1.26), 2.48 (2.83) and 5.17 (5.11) in women (men) without diabetes and 4.14 (4.91), 3.32 (6.75) and 13.91 (18.06) in women (men) with diabetes, respectively. CONCLUSION: CHD risk was higher in men than in women but difference reduced in diabetic population. Diabetes, however, increased stroke risk more in men than in women.
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3.
  • Jönsson, Tommy, et al. (författare)
  • Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study
  • 2009
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Our aim was to compare the effects of a Paleolithic ('Old Stone Age') diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin. Methods: In a randomized cross-over study, 13 patients with type 2 diabetes, 3 women and 10 men, were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet designed in accordance with dietary guidelines during two consecutive 3-month periods. Outcome variables included changes in weight, waist circumference, serum lipids, C-reactive protein, blood pressure, glycated haemoglobin (HbA1c), and areas under the curve for plasma glucose and plasma insulin in the 75 g oral glucose tolerance test. Dietary intake was evaluated by use of 4-day weighed food records. Results: Study participants had on average a diabetes duration of 9 years, a mean HbA1c of 6,6% units by MonoS standard and were usually treated with metformin alone (3 subjects) or metformin in combination with a sulfonylurea (3 subjects) or a thiazolidinedione (3 subjects). Mean average dose of metformin was 1031 mg per day. Compared to the diabetes diet, the Paleolithic diet resulted in lower mean values of HbA1c (-0.4% units, p = 0.01), triacylglycerol (-0.4 mmol/L, p = 0.003), diastolic blood pressure (-4 mmHg, p = 0.03), weight (-3 kg, p = 0.01), BMI (-1 kg/m(2), p = 0.04) and waist circumference (-4 cm, p = 0.02), and higher mean values of high density lipoprotein cholesterol (+0.08 mmol/L, p = 0.03). The Paleolithic diet was mainly lower in cereals and dairy products, and higher in fruits, vegetables, meat and eggs, as compared with the Diabetes diet. Further, the Paleolithic diet was lower in total energy, energy density, carbohydrate, dietary glycemic load, saturated fatty acids and calcium, and higher in unsaturated fatty acids, dietary cholesterol and several vitamins. Dietary GI was slightly lower in the Paleolithic diet (GI = 50) than in the Diabetic diet (GI = 55). Conclusion: Over a 3-month study period, a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes.
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4.
  • Leosdottir, Margrét, et al. (författare)
  • The association between glucometabolic disturbances, traditional cardiovascular risk factors and self-rated health by age and gender: A cross-sectional analysis within the Malmo Preventive Project
  • 2011
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 10:118
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The increased risk of cardiovascular disease (CVD) in diabetic compared to non-diabetic subjects seems to decrease with age. Whether this age-related reduction applies to CVD risk factors, and whether it is limited to established diabetes mellitus (DM) or also applies to pre-diabetic conditions are not well known. Methods: Using a cross-sectional design we compared the strength of the correlation between glucometabolic disturbances (by grouping), CVD risk factor burden and self-rated health, in two age groups: middle-aged (57-69 years) and older (70-86 years) subjects, (63% men), participating in the Malmo Preventive Project Re-examination Study (n = 18,238). Simple (unadjusted) logistic regression analysis was applied to estimate between-group differences and trends. Interaction analysis was applied to estimate differences between age groups. Results: CVD risk factor burden and the proportion of subjects reporting poor self-rated health increased with increasing glucometabolic disturbance for men and women in both age groups (p-trend < 0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for older women than for older men (p-interaction = 0.002). The slope of the trend curve for poor self-rated health was significantly steeper for middle-aged than for older men (p-interaction = 0.005), while no difference was observed between the age groups among women (p-interaction = 0.97). Conclusions: We found no reduction in risk factor accumulation with increasing glucometabolic disturbance between middle-aged and older subjects. Our results indicate life-long CVD risk factor clustering with increased glucometabolic disturbance, and suggest that previously observed age-related reduction in excess CVD risk for subjects with DM might be due to a survival bias. However, our observations indicate more pronounced risk factor clustering and worse self-rated health with increased glucometabolic disturbance in older women than in older men.
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5.
  • Magnusson, Martin, et al. (författare)
  • Brain natriuretic peptide is related to diastolic dysfunction whereas urinary albumin excretion rate is related to left ventricular mass in asymptomatic type 2 diabetes patients
  • 2010
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aims of this study were to estimate the prevalence of left ventricular systolic (LVSD) and diastolic (LVDD) dysfunction, and to test if BNP and urinary albumin excretion rate (AER) are related to LVSD, LVD and left ventricular mass (LVM) in asymptomatic type 2 diabetes patients. Methods: Presence of LVSD, LVDD and LVM, determined with echocardiography, was related to levels of BNP and AER in 153 consecutive asymptomatic patients with type 2 diabetes. Results: LVSD was present in 6.1% of patients whereas 49% (29% mild, 19% moderate and 0.7% severe) had LVDD and 9.4% had left ventricular hypertrophy. Increasing age (P < 0.0001) was the only independent variable related to mild LVDD whereas increasing BNP (P = 0.01), systolic blood pressure (P = 0.01), age (P = 0.003) and female gender (P = 0.04) were independent determinants of moderate to severe LVDD. AER (P = 0.003), age (P = 0.01) and male gender (P = 0.006) were directly and independently related to LVM. Conclusion: About half of asymptomatic type 2 diabetes patients have LVDD. Of those, more than one third display moderate LVDD pattern paralleled by increases in BNP, suggesting markedly increased risk of heart failure, especially in females, whereas AER and male sex are related to LVM.
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6.
  • Snapir, Amir, et al. (författare)
  • The insertion/deletion variation in the alpha2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction, but may modify the risk for hypertension in sib-pairs from families with type 2 diabetes
  • 2003
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: An insertion/deletion polymorphism in the alpha2B-adrenoceptor (AR) has been associated with the risk for acute myocardial infarction (AMI) and sudden cardiac death. In this study we tested whether this polymorphism is associated with the risk for AMI among members of families with type 2 diabetes. METHODS: 154 subjects with a history of AMI were matched for age and sex with one of their siblings who did not have a history of AMI. The prevalence of the genotypes of the alpha2B-AR insertion/deletion polymorphism was compared between the siblings using McNemar's test. We also explored the data to see whether this genetic variation affects the risk for hypertension by using logistic regression models in the two subpopulations of subjects, with and without a history of AMI. RESULTS: Among all study subjects, 73 (24%) carried the alpha2B-AR deletion/deletion genotype, 103 (33%) carried the insertion/insertion genotype, and 132 (43%) were heterozygous. The distribution of genotypes of the alpha2B-AR insertion/deletion variation in the group of subjects with a history of AMI and their phenotype-discordant siblings did not statistically significantly differ from that expected by random distribution (p = 0.52): the deletion/deletion genotype was carried by 34 subjects with AMI (22%), and by 39 subjects without AMI (25%). Neither did we observe any significant difference in deletion allele frequencies of the alpha2B-AR insertion/deletion polymorphism between patients with a history of AMI (0.44) and their sib-pair controls (0.46, p = 0.65). In an exploratory analysis, the alpha2B-AR deletion/deletion genotype was associated with increased odds for hypertension compared with subjects carrying any of the other genotypes. CONCLUSIONS: The deletion/deletion genotype of the alpha2B-AR does not emerge in this study as a risk factor for AMI among members of families with type 2 diabetes; however, it might be involved in the development of hypertension.
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7.
  • Taloyan, Marina, et al. (författare)
  • Cardiovascular risk factors in Assyrians/Syrians and native Swedes with type 2 diabetes: a population-based epidemiological study.
  • 2009
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 8:Nov 12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A large number of people throughout the world have diabetes and the prevalence is increasing. Persons with diabetes have a twice higher risk of cardiovascular disease than those without diabetes. There is a lack of studies focusing on cardiovascular risk factors in Assyrians/Syrians with type 2 diabetes. The aim of this study is to estimate the prevalence of some cardiovascular risk factors among Assyrians/Syrians and native Swedes with type 2 diabetes and to study whether the association between ethnicity and cardio-vascular risk factors remains after adjustment for age, gender, employment status and housing tenure. METHODS: In the Swedish town of Södertälje 173 Assyrians/Syrians and 181 ethnic Swedes with type 2 diabetes participated in a study evaluating cardiovascular risk factors such as increased haemoglobin A1c (HbA1c), high blood lipids (total serum cholesterol and triglycerides), hypertension and high urinary albumin. The associations between the outcome variables and sociodemographic characteristics were estimated using unconditional logistic regression. RESULTS: The prevalence of increased triglycerides in Swedish-born subjects and Assyrian-Syrians was 61.5% and 39.7% respectively. Swedes had a prevalence of hypertension 76.8% compared to 57.8% in Assyrians/Syrians. In the final logistic models adjusted for gender, age, housing and employment the odds ratio (OR) for Swedish-born subjects for increased triglycerides was 2.80 (95% CI1.61-4.87) and for hypertension 2.32 (95% CI 1.35-4.00) compared to Assyrians-Syrians. CONCLUSION: Ethnic Swedes had higher prevalence of increased triglycerides and hypertension than Assyrians/Syrians. Total cholesterol, HbA1c and urinary albumin did not differ between the two ethnic groups.
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8.
  • Dorkhan, Mozhgan, et al. (författare)
  • Treatment with pioglitazone induced significant, reversible mitral regurgitation
  • 2008
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 7:12
  • Tidskriftsartikel (refereegranskat)abstract
    • There has in recent years been great concern about possible cardiac side effects of thiazolidinediones ( TZDs). We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.
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10.
  • Chen, Weena J Y, et al. (författare)
  • Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men
  • 2011
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 10, s. 67-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease. Negative associations exist between circulating OPG and cardiac function. The adipocytokine adiponectin (ADPN) is downregulated in type 2 diabetes mellitus (T2DM) and coronary artery disease and shows an inverse correlation with insulin sensitivity and cardiovascular disease risk. We assessed the relationship of plasma OPG and ADPN and arterial function, cardiac function and myocardial glucose metabolism in T2DM.METHODS:We included 78 asymptomatic men with uncomplicated, well-controlled T2DM, without inducible ischemia, assessed by dobutamine-stress echocardiography, and 14 age-matched controls. Cardiac function was measured by magnetic resonance imaging, myocardial glucose metabolism (MMRglu) by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography. OPG and ADPN levels were measured in plasma.RESULTS:T2DM patients vs. controls showed lower aortic distensibility, left ventricular (LV) volumes, impaired LV diastolic function and MMRglu (all P < 0.05). In T2DM men vs. controls, OPG levels were higher (P = 0.02), whereas ADPN concentrations were decreased (P = 0.04). OPG correlated inversely with aortic distensibility, LV volumes and E/A ratio (diastolic function), and positively with LV mass/volume ratio (all P < 0.05). Regression analyses showed the associations with aortic distensibility and LV mass/volume ratio to be independent of age-, blood pressure- and glycated hemoglobin (HbA1c). However, the associations with LV volumes and E/A ratio were dependent of these parameters. ADPN correlated positively with MMRglu (P < 0.05), which, in multiple regression analysis, was dependent of whole-body insulin sensitivity, HbA1c and waist.CONCLUSIONS:OPG was inversely associated with aortic distensibility, LV volumes and LV diastolic function, while ADPN was positively associated with MMRglu. These findings indicate that in asymptomatic men with uncomplicated T2DM, OPG and ADPN may be markers of underlying mechanisms linking the diabetic state to cardiac abnormalities.TRIAL REGISTRATION:Current Controlled Trials ISRCTN53177482.
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11.
  • Dahlén, Elsa M, et al. (författare)
  • Sagittal abdominal diameter is a more independent measure compared with waist circumference to predict arterial stiffness in subjects with type 2 diabetes - a prospective observational cohort study
  • 2013
  • Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAnthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.MethodsBaseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old.ResultsThere were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.ConclusionsWe conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.
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12.
  • Eliasson, Mats, et al. (författare)
  • Improved survival in both men and women with diabetes between 1980 and 2004--a cohort study in Sweden.
  • 2008
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 7, s. 32-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In Sweden, diabetes prevalence is increasing in spite of unchanged incidence, indicating improved survival. In recent US studies mortality in diabetic subjects has decreased over three decades, but only in men. Our aim was to study mortality over time in diabetic subjects. METHODS: The annual Swedish Living Conditions Survey from 1980 to 2004 has been record-linked to the Cause of Death Register in order to study trends in mortality risk for those reporting diabetes as a chronic illness. Survival and the relative mortality risk within 5 years of follow-up have been calculated for a random sample of men and women aged 40-84 years with (n = 3,589) and without diabetes (n = 85,685) for the period 1980 to 2004. Poisson regression models were used. RESULTS: The age-adjusted mortality risk relative to non-diabetics within 5 years of follow-up for men was doubled during all periods. The relative risk for women was initially about 2.5, with a substantial drop in mortality in 1995-1999 to 1.45 although it increased to 1.90 in the last period. Using models that took into consideration the presence of heart disease, hypertension, daily smoking, and socio-economic status at the initial interview did not change the relative mortality risk. The age-adjusted 10-year observed survival rate for men with diabetes increased from 41.4% 1980-1984 to 51.5% in 1995-1999. The observed survival for women increased from 43.7% to 61.0%. CONCLUSION: Survival rates have improved in subjects with diabetes since the early 1980s, more so in women than in men, thereby decreasing the gap to non-diabetic women.
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14.
  • Hernestål-Boman, Jenny, et al. (författare)
  • Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study
  • 2012
  • Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 11, s. 152-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM.Methods: We conducted a prospective incident case-referent study within the Vasterbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L).Results: After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments.Conclusions: Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance.
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15.
  • Håglin, Lena, et al. (författare)
  • A structural equation model for assessment of links between changes in serum triglycerides, -urate, and -glucose and changes in serum Calcium, -magnesium and -phosphate in Type 2 diabetes and non-diabetes metabolism
  • 2011
  • Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 10:1, s. 116-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study investigates the associations between changes in serum Triglycerides (S-TG), -Urate (S-Urate), and -Glucose (S-Glu) and changes in serum Calcium (S-Ca), -Magnesium (S-Mg), and -Phosphate (S-P) in patients with type 2 diabetes compared with non-diabetic patients. Methods: The analysis is based on data collected from a secondary prevention population of women and men (W/M) at risk for cardiovascular disease (type 2 diabetes, 212/200; non-diabetes 968/703). The whole population (n = 2083) had a mean age of 51.0 (9.7) years and was stratified for sex and according to type 2 diabetes or non-diabetes. The patients were followed for, either half a year or one year and changes in risk factors were calculated from follow-up to baseline, the time when patients were admitted to the health center. The pattern of relationships was evaluated using a structural equation model. Results: Higher S-TG and S-Glu but lower S-Urate was revealed at baseline in type 2 diabetes women and men as compared to their counterparts, non-diabetes patients. Women with type 2 diabetes had higher S-Ca and lower S-Mg than non-diabetes women. Changes in S-Glu were associated with changes in S-Ca (+), baseline S-Ca (+), and S-Urate (-) in type 2 diabetes men. Changes in S-Urate were associated with changes in S-Mg (+) in type 2 diabetes women and non-diabetes men. In men with non-diabetes, changes in S-Glu were associated with changes in S-Mg (-). In women with non-diabetes, changes in S-Glu were associated with changes in S-P (-) and changes in S-Urate with changes in S-Ca (+). Conclusion: With respect to metabolic disturbances in non-diabetes and the awareness of risk for type 2 diabetes, changes in S-Glu and changes in S-Ca, S-Mg, and S-P should be considered as risk factors for cardiovascular disease. Increased early detection and corrections of high S-Ca, low S-Mg, and S-P in obese patients may improve their metabolism and reduce the risk of CVD in patients with type 2 diabetes. Trial registration number: ISRCTN: ISRCTN79355192
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17.
  • Petersson, Helena, et al. (författare)
  • Sagittal abdominal diameter as a marker of inflammation and insulin resistance among immigrant women from the Middle East and native Swedish women : a cross-sectional study
  • 2007
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 6, s. 10-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Immigrant women from the Middle East have elevated risk of cardiovascular disease. Sagittal abdominal diameter (SAD), a simple marker of intra-abdominal fat, predicts insulin resistance and cardiovascular mortality in men. Its usefulness in immigrant women is however unknown. To investigate the predictive role of SAD compared to other anthropometric measures, we examined a random sample of native-Swedes and immigrant women from the Middle East living in Sweden. Methods 157 women participated in the study; 107 immigrants and 50 natives. Anthropometric measurements (SAD, body mass index [BMI], waist circumference [WC] and waist-to-hip ratio [WHR]; all measured in supine position) and cardiovascular risk factors (C-reactive protein [CRP], insulin, glucose, insulin resistance [HOMA-IR], blood pressure and serum lipids) were assessed. The anthropometric measures were compared in their relation to cardiovascular risk factors using linear regression analyses. Results Overall, SAD showed a slightly higher correlation with most cardiovascular risk factors, especially insulin resistance, insulin, CRP, apolipoprotein B and triglycerides (all P-values < 0.01) than other anthropometric measures. BMI was however a better predictor of HDL cholesterol. SAD explained a greater proportion of the variation of insulin resistance and CRP levels, even independently of the other anthropometric measures. Conclusion SAD identifies insulin resistance, subclinical inflammation or raised serum lipids in a Swedish population with a large proportion of immigrant women from the Middle East. If these results could be confirmed in a larger population, SAD could be a more clinically useful risk marker than other anthropometric measures in women at high risk of cardiovascular disease.
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19.
  • Adingupu, D. D., et al. (författare)
  • SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob(-/-) mice
  • 2019
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) is the first class of anti-diabetes treatment that reduces mortality and risk for hospitalization due to heart failure. In clinical studies it has been shown that SGLT2i's promote a general shift to fasting state metabolism characterized by reduced body weight and blood glucose, increase in glucagon/insulin ratio and modest increase in blood ketone levels. Therefore, we investigated the connection between metabolic changes and cardiovascular function in the ob/ob(-/-) mice; a rodent model of early diabetes with specific focus on coronary microvascular function. Due to leptin deficiency these mice develop metabolic syndrome/diabetes and hepatic steatosis. They also develop cardiac contractile and microvascular dysfunction and are thus a promising model for translational studies of cardiometabolic diseases. We investigated whether this mouse model responded in a human-like manner to empagliflozin treatment in terms of metabolic parameters and tested the hypothesis that it could exert direct effects on coronary microvascular function and contractile performance.MethodsLean, ob/ob(-/-) untreated and ob/ob(-/-) treated with SGLT2i were followed for 10weeks. Coronary flow velocity reserve (CFVR) and fractional area change (FAC) were monitored with non-invasive Doppler ultrasound imaging. Food intake, urinary glucose excursion and glucose control via HbA1c measurements were followed throughout the study. Liver steatosis was assessed by histology and metabolic parameters determined at the end of the study.ResultsSodium-glucose cotransporter 2 inhibitors treatment of ob/ob(-/-) animals resulted in a switch to a more catabolic state as observed in clinical studies: blood cholesterol and HbA1c were decreased whereas glucagon/insulin ratio and ketone levels were increased. SGLT2i treatment reduced liver triglyceride, steatosis and alanine aminotransferase, an indicator for liver dysfunction. l-Arginine/ADMA ratio, a marker for endothelial function was increased. SGLT2i treatment improved both cardiac contractile function and coronary microvascular function as indicated by improvement of FAC and CFVR, respectively.ConclusionsSodium-glucose cotransporter 2 inhibitors treatment of ob/ob(-/-) mice mimics major clinical findings regarding metabolism and cardiovascular improvements and is thus a useful translational model. We demonstrate that SGLT2 inhibition improves coronary microvascular function and contractile performance, two measures with strong predictive values in humans for CV outcome, alongside with the known metabolic changes in a preclinical model for prediabetes and heart failure.
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20.
  • Agvall, Björn, et al. (författare)
  • Factors influencing hospitalization or emergency department visits and mortality in type 2 diabetes following the onset of new cardiovascular diagnoses in a population-based study
  • 2024
  • Ingår i: Cardiovascular Diabetology. - London : BioMed Central (BMC). - 1475-2840. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Individuals with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD) which necessitates monitoring of risk factors and appropriate pharmacotherapy. This study aimed to identify factors predicting emergency department visits, hospitalizations, and mortality among T2D patients after being newly diagnosed with CVD.Methods: In a retrospective observational study conducted in Region Halland, individuals aged > 40 years with T2D diagnosed between 2011 and 2019, and a new diagnosis of CVD between 2016 and 2019, were followed for one year from the date of CVD diagnosis. The first encounter for CVD diagnosis was categorized as inpatient-, outpatient-, primary-, or emergency department care. Follow-up included laboratory tests, blood pressure, pharmacotherapies, and healthcare utilization. Hazard ratios (HR) in two Cox regression analyses determined relative risks for emergency visits/hospitalization and mortality, adjusting for age, sex, glucose regulation, lipid levels, kidney function, blood pressure, pharmacotherapy, and healthcare utilization.Results: The study included a total of 1759 T2D individuals who received a new CVD diagnosis, with 67% diagnosed during inpatient care. The average hospitalization stay was 6.5 days, and primary care follow-up averaged 10.1 visits. Patients with CVD diagnosed in primary care had a HR 0.52 (confidence interval [CI] 0.35–0.77) for emergency department visits/hospitalization, but age had a HR 1.02 (CI 1.00-1.03). Pharmacotherapy with insulin, DPP4-inhibitors, aldosterone antagonists, and beta-blockers had a raised HR. Highest mortality risk was observed when CVD was diagnosed inpatient care, systolic blood pressure < 100 mm Hg and elevated HbA1c. Age had a HR 1.05 (CI 1.03–1.08), eGFR < 30 ml/min HR 1.46 (CI 1.01–2.11), and LDL-Cholesterol > 2,5 h 1.46 (CI 1.01–2.11) and associated with increased mortality risk. Pharmacotherapy with metformin had a HR 0.41 (CI 0.28–0.62), statins a HR 0.39 (CI 0.27–0.57), and a primary care follow-up < 30 days a HR 0.53 (CI 0.37–0.77) and associated with lower mortality risk.Conclusions: T2D individuals who had a new diagnosis of CVD were predominantly diagnosed when hospitalized, while follow-up typically occurred in primary care. Identifying factors that predict risks of mortality and hospitalization should be a focus of follow-up care, underscoring the critical role of primary care in the effective management of T2D and CVD. © The Author(s) 2024.
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21.
  • Ahmadi, Shilan Seyed, et al. (författare)
  • Risk of atrial fibrillation in persons with type 2 diabetes and the excess risk in relation to glycaemic control and renal function: a Swedish cohort study
  • 2020
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background To examine the incidence of atrial fibrillation in individuals with type 2 diabetes compared with age- and sex-matched controls from the general population and its variation in relation to glycaemic control and renal function. Methods A total of 421,855 patients with type 2 diabetes from the Swedish National Diabetes Registry and 2,131,223 controls from the Swedish Population Registry, matched for age, sex and county, were included and followed from January 1, 2001 to December 31, 2013. Results Overall, 8.9% of individuals with type 2 diabetes and 7.0% of controls were diagnosed with atrial fibrillation during follow-up, unadjusted incidence risk ratio (IRR) 1.35 (95% 1.33-1.36). Women < 55 years old with type 2 diabetes had an IRR of 2.36 (95% CI 2.10-2.66), in relation to controls, whereas the corresponding value for men < 55 years old with type 2 diabetes was IRR 1.78 (95% CI 1.67-1.90). In the fully adjusted Cox regression, the risk of type 2 diabetes on incident atrial fibrillation was 28% greater vs controls, hazard ratio (HR) 1.28 (95% CI 1.26-1.30), p < 0.0001. The excess risk of atrial fibrillation in individuals with type 2 diabetes increased with worsening glycaemic control and renal complications. For individuals with HbA1c <= 6.9% (<= 52 mmol/mol) and normoalbuminuria the excess risk vs controls was still increased, adjusted HR 1.16 (95% CI 1.14-1.19); p < 0.0001. Conclusions Individuals with type 2 diabetes had an overall 35% higher risk of atrial fibrillation compared to age- and sex-matched controls from the general population. The excess risk for atrial fibrillation increased with renal complications or with poor glycaemic control. Individuals with type 2 diabetes with good glycaemic control and normoalbuminuria had slightly increased risk.
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22.
  • Avdic, Tarik, et al. (författare)
  • Risk factors for and risk of all-cause and atherosclerotic cardiovascular disease mortality in people with type 2 diabetes and peripheral artery disease: an observational, register-based cohort study
  • 2024
  • Ingår i: CARDIOVASCULAR DIABETOLOGY. - 1475-2840. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Type 2 diabetes (T2D) and peripheral artery disease (PAD) are recognized as independent risk factors contributing to excess mortality. Contemporary observational studies exploring the associations of risk factors, and risk of all-cause and atherosclerotic cardiovascular disease mortality in persons with T2D following the onset of incident peripheral artery disease are limited. The objectives of this study were to investigate the associations of risk factors, and assess mortality risks in people with T2D compared with controls without T2D after the onset of PAD. Methods All persons with T2D (n = 150,215) registered in the Swedish National Diabetes Register between 2005 and 2009 were included, along with 346,423 controls without T2D matched for sex and age. Data were retrieved from several national registries, capturing information on risk factors, onset of incident peripheral artery disease, other comorbidities, socioeconomic factors, and outcomes. To compare persons with T2D and controls following the onset of peripheral artery disease regarding the risk of all-cause, and atherosclerotic cardiovascular disease mortality, Cox proportional hazard models and Kaplan-Meier curves were employed. A gradient-boosting model was utilized to estimate the relative statistical contribution of risk factors to the modeling of incident mortality risk in people with both T2D and peripheral artery disease. Results Crude rates of incident all-cause mortality were higher in individuals with T2D compared with controls, following the onset of PAD (600.4 (95% CI, 581.4-619.8) per 10,000 person-years versus 549.1 (95% CI, 532.1-566.5) per 10,000 person-years). Persons with T2D had an adjusted hazard ratio (HR) for all-cause mortality of 1.12 (95% CI, 1.05-1.19, P < 0.01) compared with controls after onset of incident PAD. The comparable adjusted HR for cardiovascular mortality was 1.13 (95% CI, 1.07-1.19, P < 0.01). High age and hyperglycemia at baseline played a significant role in contributing to the predictive models for incident all-cause and cardiovascular mortality among individuals with both T2D and PAD. Conclusions The presence of T2D with concomitant PAD is related to an increased risk of both all-cause and cardiovascular mortality compared with individuals with only PAD. This argues for implementing optimized and intensive treatment strategies for individuals with both conditions.
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23.
  • Bao, Xue, et al. (författare)
  • Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases : A prospective study exploring the 'common soil' hypothesis
  • 2018
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic low-grade inflammation and associated insulin resistance and metabolic abnormalities have been proposed as 'common soil' for diabetes mellitus (DM) and cardiovascular disease (CVD). This paper aimed to investigate the inflammatory profiles of DM and CVD and to distinguish their shared and specific markers. Methods: Based on the Malmö Diet and Cancer cohort, total and differential leukocyte counts were measured in 25,969 participants without previous DM or CVD and were studied in relation to incident DM (mean follow-up 17.4±5.58years) and incident CVD (i.e., coronary events, including fatal and nonfatal myocardial infarction, or stroke); mean follow-up 17.7±5.46years, using multivariable Cox regression models. Furthermore, plasma concentrations of another seven inflammatory markers were examined in relation to incident DM and incident CVD in a sub-cohort of 4658 participants. The associations of each inflammatory marker with incident DM versus incident CVD were compared using the Lunn-McNeil competing risks approach. In sensitivity analyses, those who developed both DM and CVD during follow-up were excluded. Results: After adjustment for conventional risk factors, total and differential leukocyte counts, orosomucoid, and C-reactive protein were associated with an increased risk of both DM and CVD. Neutrophil to lymphocyte ratio, ceruloplasmin, alpha1-antitrypsin and soluble urokinase plasminogen activator receptor predicted increased risk of CVD but not DM, while haptoglobin and complement C3 showed the opposite pattern. In competing risks analyses, lymphocyte count and complement C3 had stronger associations with risk of DM than with risk of CVD (p for equal associations=0.020 and 0.006). The reverse was true for neutrophil to lymphocyte ratio (p for equal associations=0.025). Results were consistent in sensitivity analyses. Conclusions: The results indicated substantial similarities in the inflammatory profiles associated with DM and CVD. However, there are also significant differences. These findings may help discriminate between individuals at elevated risk of DM and those at elevated risk of CVD, which is a prerequisite for targeted therapies.
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25.
  • Blomstrand, Peter, et al. (författare)
  • Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain
  • 2018
  • Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsObesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons.MethodsWe prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25–29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group.ResultsUnivariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. − 18.6% (2.3%) for normal weight patients, 53% (8%) vs. − 17.5% (2.3%) for overweight, and 49% (9%) vs. − 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. − 22.3% (3.0%), 55% (7%) vs. − 20.8% (3.1%) and 54% (8%) − 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by − 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05).ConclusionOverweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.
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26.
  • Campmans-Kuijpers, M.J.E., et al. (författare)
  • Isocaloric substitution of carbohydrates with protein: The association with weight change and mortality among patients with type 2 diabetes
  • 2015
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2015 Campmans-Kuijpers et al.; licensee BioMed Central. Background: The health impact of dietary replacement of carbohydrates with protein for patients with type 2 diabetes is still debated. This study aimed to investigate the association between dietary substitution of carbohydrates with (animal and plant) protein and 5-year weight change, and all-cause and cardiovascular (CVD) mortality risk in patients with type 2 diabetes. Methods: The study included 6,107 diabetes patients from 15 European cohorts. Patients with type 1 diabetes were excluded. At recruitment, validated country-specific food-frequency questionnaires were used to estimate dietary intake. Multivariable adjusted linear regression was used to examine the associations between dietary carbohydrate substitution with protein and 5-year weight change, and Cox regression to estimate hazard ratios (HRs) for (CVD) mortality. Results: Annual weight loss of patients with type 2 diabetes was 0.17 (SD 1.24) kg. After a mean follow-up of 9.2 (SD 2.3)y, 787 (13%) participants had died, of which 266 (4%) deaths were due to CVD. Substitution of 10 gram dietary carbohydrate with total (ß = 187 [75;299]g) and animal (ß = 196 [137;254]g) protein was associated with mean 5-year weight gain. Substitution for plant protein was not significantly associated with weight change (β = 82 [-421;584]g). Substitution with plant protein was associated with lower all-cause mortality risk (HR = 0.79 [0.64;0.97]), whereas substitution with total or animal protein was not associated with (CVD) mortality risk. Conclusions: In diabetes patients, substitution with plant protein was beneficial with respect to weight change and all-cause mortality as opposed to substitution with animal protein. Therefore, future research is needed whether dietary guidelines should not actively promote substitution of carbohydrates by total protein, but rather focus on substitution of carbohydrates with plant protein.
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27.
  • Carlsson, Axel C., et al. (författare)
  • Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes
  • 2016
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.
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28.
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29.
  • Ceriello, A., et al. (författare)
  • HbA1c variability predicts cardiovascular complications in type 2 diabetes regardless of being at glycemic target
  • 2022
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background HbA1c variability has emerged as risk factor for cardiovascular diseases in diabetes. However, the impact of HbA1c variability on cardiovascular diseases in subjects within the recommended HbA1c target has been relatively unexplored. Methods Using data from a large database, we studied 101,533 people with type 2 diabetes without cardiovascular diseases. HbA1c variability was expressed as quartiles of the standard deviation of HbA1c during three years (exposure phase). The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, all-cause mortality and was assessed during five years following the first three years of exposure to HbA1c variability (longitudinal phase). An expanded composite outcome including non-fatal myocardial infarction, non-fatal stroke, coronary revascularization/reperfusion procedures, peripheral revascularization procedures, and all-cause mortality was also considered, as well as a series of specific cardiovascular complications. Cox models were adjusted for a large range of risk factors and results were expressed as adjusted hazard ratios. Results An association between HbA1c variability and all the outcomes considered was found. The correlation between HbA1c variability and cardiovascular complications development was confirmed in both the subgroups of subjects with a mean HbA1c <= 53 mmol/mol (recommended HbA1c target) or > 53 mmol/mol during the exposure phase. The risk related to HbA1c variability was higher in people with mean HbA1c <= 53 mmol/mol for the primary outcome (p for interaction 0.004), for the expanded secondary outcome (p for interaction 0.001) and for the stroke (p for interaction 0.001), even though HbA1c remained at the target during the follow-up. Conclusions These findings suggest that HbA1c variability may provide additional information for an optimized management of diabetes, particularly in people within the target of HbA1c.
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30.
  • Ceriello, A, et al. (författare)
  • Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management
  • 2021
  • Ingår i: Cardiovascular diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 20:1, s. 218-
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.
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31.
  • Ceriello, A., et al. (författare)
  • Variability in body weight and the risk of cardiovascular complications in type 2 diabetes: results from the Swedish National Diabetes Register
  • 2021
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes. Methods Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability. Results After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39-1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality). Conclusions High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations.
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32.
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33.
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34.
  • Davidson, Lee Ti, et al. (författare)
  • Plasma copeptin and markers of arterial disorder in patients with type 2 diabetes, a cross-sectional study
  • 2024
  • Ingår i: Cardiovascular Diabetology. - : Springer. - 1475-2840. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD).Methods In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55–65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV.Results Copeptin was associated with TBI (β–0.0020, CI–0.0035– (–0.0005), p = 0.010) and aPWV (β 0.023, CI 0.002–0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking.Conclusions Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders.
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35.
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36.
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37.
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38.
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39.
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40.
  • Fontes-Villalba, Maelán, et al. (författare)
  • Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes : A randomised cross-over trial
  • 2016
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2 diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study. Methods: In a randomised, open-label, cross-over study, 13 patients with type 2 diabetes were randomly assigned to eat a Palaeolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts, or a diabetes diet designed in accordance with current diabetes dietary guidelines during two consecutive 3-month periods. The patients were recruited from primary health-care units and included three women and 10 men [age (mean ± SD) 64 ± 6 years; BMI 30 ± 7 kg/m2; diabetes duration 8 ± 5 years; glycated haemoglobin 6.6 ± 0.6 % (57.3 ± 6 mmol/mol)] with unaltered diabetes treatment and stable body weight for 3 months prior to the start of the study. Outcome variables included fasting plasma concentrations of leptin, adiponectin, adipsin, visfatin, resistin, glucagon, insulin, C-peptide, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and ghrelin. Dietary intake was evaluated by use of 4-day weighed food records. Results: Seven participants started with the Palaeolithic diet and six with the diabetes diet. The Palaeolithic diet resulted in a large effect size (Cohen's d = -1.26) at lowering fasting plasma leptin levels compared to the diabetes diet [mean difference (95 % CI), -2.3 (-5.1 to 0.4) ng/ml, p = 0.023]. No statistically significant differences between the diets for the other variables, analysed in this study, were observed. Conclusions: Over a 3-month study period, a Palaeolithic diet resulted in reduced fasting plasma leptin levels, but did not change fasting levels of insulin, C-peptide, glucagon, incretins, ghrelin and adipokines compared to the currently recommended diabetes diet. Trial registration: Clinical Trials.gov NCT00435240.
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41.
  • Fortin, Elena, et al. (författare)
  • Empagliflozin improves insulin sensitivity in patients with recent acute coronary syndrome and newly detected dysglycaemia : Experiences from the randomized, controlled SOCOGAMI trial
  • 2023
  • Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 22:1, s. 208-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Empagliflozin reduces the risk of cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) and high cardiovascular risk via mechanisms which have not been fully explained. The mechanisms of such benefit have not been fully understood, and whether empagliflozin can be safely administered as first-line treatment in patients with CVD at the initial stages of glycaemic perturbations remains to be established. We investigated the effects of empagliflozin on insulin resistance, insulin sensitivity and β-cell function indexes in patients with a recent acute coronary event and newly detected dysglycaemia, i.e., impaired glucose tolerance (IGT) or T2DM. METHODS: Forty-two patients (mean age 67.5 years, 19% females) with a recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected dysglycaemia were randomized to either empagliflozin 25 mg daily (n = 20) or placebo (n = 22). Patients were investigated with stress-perfusion cardiac magnetic resonance imaging before randomization, 7 months after the start of study drug and 3 months following its cessation. Indexes of insulin resistance, sensitivity and β-cell function were calculated based on glucose and insulin values from 2-hour oral glucose tolerance tests (OGTT) and fasting C-peptide. The differences in glucose, insulin, C-peptide, mannose levels and indexes between the two groups were computed by repeated measures ANOVA including an interaction term between the treatment allocation and the time of visit. RESULTS: After 7 months, empagliflozin significantly decreased glucose and insulin values during the OGTT, whereas C-peptide, mannose and HbA1c did not differ. Empagliflozin significantly improved insulin sensitivity indexes but did not impact insulin resistance and β-cell function. After cessation of the drug, all indexes returned to initial levels. Insulin sensitivity indexes were inversely correlated with left ventricular mass at baseline. CONCLUSIONS: Empagliflozin improved insulin sensitivity indexes in patients with a recent coronary event and drug naïve dysglycaemia. These findings support the safe use of empagliflozin as first-line glucose-lowering treatment in patients at very high cardiovascular risk with newly diagnosed dysglycaemia. TRIAL REGISTRATION NUMBER: EudraCT number 2015-004571-73.
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42.
  • Fortin, Elena, et al. (författare)
  • Plasma mannose as a novel marker of myocardial infarction across different glycaemic states : A case control study
  • 2022
  • Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Plasma mannose, an emerging novel biomarker of insulin resistance, is associated with both diabetes mellitus and coronary atherosclerosis, but the relationship between mannose concentrations and myocardial infarction (MI) across different glycaemic states remains to be elucidated. The aim of this study was to investigate the independent association between mannose and a first MI in a group of subjects characterized according to their glycaemic state. Methods Fasting plasma mannose concentrations were analysed in 777 patients 6-10 weeks after a first myocardial infarction and in 770 matched controls by means of high-performance liquid chromatography coupled to tandem mass spectrometry. Participants without known diabetes mellitus were categorized by an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT, n = 1045), impaired glucose tolerance (IGT, n = 246) or newly detected type 2 diabetes (T2DM, n = 112). The association between mannose and MI was investigated across these glycaemic states by logistic regression. Results Mannose levels increased across the glycaemic states (p < 0.0001) and were significantly associated with a first MI in the whole study population (odds ratio, OR: 2.2; 95% CI 1.4 to - 3.5). Considering the different subgroups separately, the association persisted only in subjects with NGT (adjusted OR: 2.0; 95% CI 1.2-3.6), but not in subgroups with glucose perturbations (adjusted OR: 1.8, 95% CI 0.8-3.7). Conclusions Mannose concentrations increased across worsening levels of glucose perturbations but were independently associated with a first MI only in NGT individuals. Thus, mannose might be a novel, independent risk marker for MI, possibly targeted for the early management of previously unidentified patients at high cardiovascular risk.
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43.
  • Grundvold, Irene, et al. (författare)
  • Body weight and risk of atrial fibrillation in 7,169 patients with newly diagnosed type 2 diabetes; an observational study
  • 2015
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obesity, type 2 diabetes and atrial fibrillation (AF) are closely associated, but the underlying mechanisms are not fully understood. We aimed to explore associations between body mass index (BMI) or weight change with risk of AF in patients with type 2 diabetes. Methods: A total of 7,169 participations with newly diagnosed type 2 diabetes were stratified according to baseline BMI, and after a second BMI measurement within 18 months, further grouped according to relative weight change as "weight gain" (> 1 BMI unit), " stable weight" (+/- 1 BMI unit) and " weight loss" (< 1 BMI unit). The mean follow-up period was 4.6 years, and the risk of AF was estimated using adjusted Cox regression models. Results: Average age at diabetes diagnosis was 60 years and the patients were slightly obese (mean BMI 30.2 kg/m(2)). During follow-up, 287 patients developed incident AF, and those with overweight or obesity at baseline had 1.9 fold and 2.9-fold higher risk of AF, respectively, than those with normal BMI. The 14% of the patients with subsequent weight gain had 1.5-fold risk of AF compared with those with stable weight or weight loss. Conclusions: In patients with newly diagnosed type 2 diabetes, baseline overweight and obesity, as well as modest weight increase during the first 18 months after diagnosis, were associated with a substantially increased risk of incident AF. Patients with type 2 diabetes may benefit from efforts to prevent weight gain in order to reduce the risk of incident AF.
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44.
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45.
  • Hagg-Holmberg, S., et al. (författare)
  • The role of blood pressure in risk of ischemic and hemorrhagic stroke in type 1 diabetes
  • 2019
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHypertension is one of the strongest risk factors for stroke in the general population, while systolic blood pressure has been shown to independently increase the risk of stroke in type 1 diabetes. The aim of this study was to elucidate the association between different blood pressure variables and risk of stroke in type 1 diabetes, and to explore potential nonlinearity of this relationship.MethodsWe included 4105 individuals with type 1 diabetes without stroke at baseline, participating in the nationwide Finnish Diabetic Nephropathy Study. Mean age at baseline was 37.411.9years, median duration of diabetes 20.9 (interquartile range 11.5-30.4) years, and 52% were men. Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Based on these pulse pressure (PP) and mean arterial pressure (MAP) were calculated. Strokes were classified based on medical and autopsy records, as well as neuroimaging. Cox proportional hazard models were performed to study how the different blood pressure variables affected the risk of stroke and its subtypes.ResultsDuring median follow-up time of 11.9 (9.21-13.9) years, 202 (5%) individuals suffered an incident stroke; 145 (72%) were ischemic and 57 (28%) hemorrhagic. SBP, DBP, PP, and MAP all independently increased the risk of any stroke. SBP, PP, and MAP increased the risk of ischemic stroke, while SBP, DBP, and MAP increased the risk of hemorrhagic stroke. SBP was strongly associated with stroke with a hazard ratio of 1.20 (1.11-1.29)/10mmHg. When variables were modeled using restricted cubic splines, the risk of stroke increased linearly for SBP, MAP, and PP, and non-linearly for DBP.Conclusions The different blood pressure variables are all independently associated with increased risk of stroke in individuals with type 1 diabetes. The risk of stroke, ischemic stroke, and hemorrhagic stroke increases linearly at blood pressure levels less than the current recommended treatment guidelines.
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46.
  • Jendle, Johan, 1963-, et al. (författare)
  • Pharmacometabolomic profiles in type 2 diabetic subjects treated with liraglutide or glimepiride
  • 2021
  • Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) leads to multiple metabolic changes, reduction in glucose levels and body weight are well established. In people with type 2 diabetes, GLP-1 RAs reduce the risk of cardiovascular (CV) disease and may also potentially represent a treatment for fatty liver disease. The mechanisms behind these effects are still not fully elucidated. The aim of the study was to investigate whether treatment with liraglutide is associated with favourable metabolic changes in cases of both CV disease and fatty liver disease.METHODS: In a prespecified post-hoc analysis of a double-blind, placebo-controlled trial in 62 individuals with type 2 diabetes (GLP-1 RA liraglutide or glimepiride, both in combination with metformin), we evaluated the changes in plasma molecular lipids and polar metabolites after 18 weeks of treatment. The lipids and polar metabolites were measured by using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS).RESULTS: In total, 340 lipids and other metabolites were identified, covering 14 lipid classes, bile acids, free fatty acids, amino acids and other polar metabolites. We observed more significant changes in the metabolome following liraglutide treatment compared to with glimepiride, particularly as regards decreased levels of cholesterol esters hexocyl-ceramides, lysophosphatidylcholines, sphingolipids and phosphatidylcholines with alkyl ether structure. In the liraglutide-treated group, lipids were reduced by approximately 15% from baseline, compared to a 10% decrease in the glimepiride group. At the pathway level, the liraglutide treatment was associated with lipid, bile acid as well as glucose metabolism, while glimepiride treatment was associated with tryptophan metabolism, carbohydrate metabolism, and glycerophospholipid metabolism.CONCLUSIONS: Compared with glimepiride, liraglutide treatment led to greater changes in the circulating metabolome, particularly regarding lipid metabolism involving sphingolipids, including ceramides. Our findings are hypothesis-generating and shed light on the underlying biological mechanisms of the CV benefits observed with GLP-1 RAs in outcome studies. Further studies investigating the role of GLP-1 RAs on ceramides and CV disease including fatty liver disease are warranted.TRIAL REGISTRATION: NCT01425580.
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47.
  • Jin, Han, et al. (författare)
  • Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability
  • 2024
  • Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Metabolism is increasingly recognized as a key regulator of the function and phenotype of the primary cellular constituents of the atherosclerotic vascular wall, including endothelial cells, smooth muscle cells, and inflammatory cells. However, a comprehensive analysis of metabolic changes associated with the transition of plaque from a stable to a hemorrhaged phenotype is lacking. Methods: In this study, we integrated two large mRNA expression and protein abundance datasets (BIKE, n = 126; MaasHPS, n = 43) from human atherosclerotic carotid artery plaque to reconstruct a genome-scale metabolic network (GEM). Next, the GEM findings were linked to metabolomics data from MaasHPS, providing a comprehensive overview of metabolic changes in human plaque. Results: Our study identified significant changes in lipid, cholesterol, and inositol metabolism, along with altered lysosomal lytic activity and increased inflammatory activity, in unstable plaques with intraplaque hemorrhage (IPH+) compared to non-hemorrhaged (IPH−) plaques. Moreover, topological analysis of this network model revealed that the conversion of glutamine to glutamate and their flux between the cytoplasm and mitochondria were notably compromised in hemorrhaged plaques, with a significant reduction in overall glutamate levels in IPH+ plaques. Additionally, reduced glutamate availability was associated with an increased presence of macrophages and a pro-inflammatory phenotype in IPH+ plaques, suggesting an inflammation-prone microenvironment. Conclusions: This study is the first to establish a robust and comprehensive GEM for atherosclerotic plaque, providing a valuable resource for understanding plaque metabolism. The utility of this GEM was illustrated by its ability to reliably predict dysregulation in the cholesterol hydroxylation, inositol metabolism, and the glutamine/glutamate pathway in rupture-prone hemorrhaged plaques, a finding that may pave the way to new diagnostic or therapeutic measures.
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48.
  • Kammer, Michael, et al. (författare)
  • Different roles of protein biomarkers predicting eGFR trajectories in people with chronic kidney disease and diabetes mellitus : a nationwide retrospective cohort study
  • 2023
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 22, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in people with diabetes mellitus, and a key risk factor for further life-threatening conditions such as cardiovascular disease. The early prediction of progression of CKD therefore is an important clinical goal, but remains difficult due to the multifaceted nature of the condition. We validated a set of established protein biomarkers for the prediction of trajectories of estimated glomerular filtration rate (eGFR) in people with moderately advanced chronic kidney disease and diabetes mellitus. Our aim was to discern which biomarkers associate with baseline eGFR or are important for the prediction of the future eGFR trajectory.METHODS: We used Bayesian linear mixed models with weakly informative and shrinkage priors for clinical predictors (n = 12) and protein biomarkers (n = 19) to model eGFR trajectories in a retrospective cohort study of people with diabetes mellitus (n = 838) from the nationwide German Chronic Kidney Disease study. We used baseline eGFR to update the models' predictions, thereby assessing the importance of the predictors and improving predictive accuracy computed using repeated cross-validation.RESULTS: The model combining clinical and protein predictors had higher predictive performance than a clinical only model, with an [Formula: see text] of 0.44 (95% credible interval 0.37-0.50) before, and 0.59 (95% credible interval 0.51-0.65) after updating by baseline eGFR, respectively. Only few predictors were sufficient to obtain comparable performance to the main model, with markers such as Tumor Necrosis Factor Receptor 1 and Receptor for Advanced Glycation Endproducts being associated with baseline eGFR, while Kidney Injury Molecule 1 and urine albumin-creatinine-ratio were predictive for future eGFR decline.CONCLUSIONS: Protein biomarkers only modestly improve predictive accuracy compared to clinical predictors alone. The different protein markers serve different roles for the prediction of longitudinal eGFR trajectories potentially reflecting their role in the disease pathway.
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49.
  • Karampatsi, D., et al. (författare)
  • Diet-induced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke
  • 2021
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Post-stroke functional recovery is severely impaired by type 2 diabetes (T2D). This is an important clinical problem since T2D is one of the most common diseases. Because weight loss-based strategies have been shown to decrease stroke risk in people with T2D, we aimed to investigate whether diet-induced weight loss can also improve post-stroke functional recovery and identify some of the underlying mechanisms. Methods T2D/obesity was induced by 6 months of high-fat diet (HFD). Weight loss was achieved by a short- or long-term dietary change, replacing HFD with standard diet for 2 or 4 months, respectively. Stroke was induced by middle cerebral artery occlusion and post-stroke recovery was assessed by sensorimotor tests. Mechanisms involved in neurovascular damage in the post-stroke recovery phase, i.e. neuroinflammation, impaired angiogenesis and cellular atrophy of GABAergic parvalbumin (PV)+ interneurons were assessed by immunohistochemistry/quantitative microscopy. Results Both short- and long-term dietary change led to similar weight loss. However, only the latter enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and insulin resistance, and with the reduction of T2D-induced cellular atrophy of PV+ interneurons. Moreover, stroke recovery was associated with decreased T2D-induced neuroinflammation and reduced astrocyte reactivity in the contralateral striatum. Conclusion The global diabetes epidemic will dramatically increase the number of people in need of post-stroke treatment and care. Our results suggest that diet-induced weight loss leading to pre-stroke normalization of glucose metabolism has great potential to reduce the sequelae of stroke in the diabetic population.
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50.
  • Korduner, Johan, et al. (författare)
  • Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmo Preventive Project
  • 2022
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Obesity is strongly associated with the development of cardiovascular disease (CVD). However, the heterogenous nature of obesity in CVD-risk is still poorly understood. We aimed to explore novel CVD biomarkers and their possible association with presumed unhealthy obesity, defined as hospitalized subjects with obesity (HO). Methods Ninety-two proteins associated with CVD were analyzed in 517 (mean age 67 +/- 6 years; 33.7% women) individuals with obesity (BMI >= 30 kg/m(2)) from the Malmo Preventive Project cohort, using a proximity extension array technique from the Olink CVD III panel. Individuals with at least one recorded hospitalization for somatic disease prior to study baseline were defined as HO phenotypes. Associations between proteins and HO (n = 407) versus non-hospitalized subjects with obesity (NHO, n = 110), were analyzed using multivariable binary logistic regression, adjusted for traditional risk factors. Results Of 92 analyzed unadjusted associations between biomarkers and HO, increased levels of two proteins were significant at a false discovery rate < 0.05: Galectin-4 (Gal-4) and insulin-like growth factor-binding protein 1 (IGFBP-1). When these two proteins were included in logistic regression analyses adjusted for age and sex, Gal-4 remained significant. Gal-4 was independently associated with the HO phenotype in multivariable logistic regression analysis (OR 1.72; CI95% 1.16-2.54). Post-hoc analysis revealed that this association was only present in the subpopulation with diabetes (OR 2.26; CI95% 1.25-4.07). However, an interaction analysis was performed, showing no significant interaction between Gal-4 and prevalent diabetes (p = 0.16). Conclusions In middle-aged and older individuals with obesity, increased Gal-4 levels were associated with a higher probability of HO. This association was only significant in subjects with diabetes only, further implying a role for Gal-4 in diabetes and its complications.
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