Summary
What is known and Objective: There is a growing body of experimental and clinical evidence for the atherogenic and pro‐thrombotic potential of Lipoprotein(a) Lp(a), as well as for its ...causative role in coronary heart disease and stroke. We comment on novel strategies for reducing Lp(a) levels.
Comment: Irrespective of the underlying biological mechanisms explaining the athero‐thrombotic potential of this lipoprotein, most work has focused on the identification of suitable therapies for hyperlipoproteinemia(a). These include apheresis techniques, nicotinic acid and statins. None of these strategies have been shown to be definitely effective or convenient for the patient and new strategies are being attempted. Promising results are emerging with therapeutic interventions targeting the ‘inflammatory pathways’ by inhibition of Interleukin‐6 (IL‐6) signalling with natural compounds (e.g., Ginko biloba) or the IL‐6 receptor antibody Tocilizumab. These may both lower Lp(a) and cardiovascular risk of the patients. Besides inhibiting platelet function, antiplatelet therapy with aspirin may also decrease the plasma concentration of Lp(a) and modulate its influence on platelets.
What is new and Conclusion: We highlight the inadequacy of current approaches for lowering Lp(a) and draw attention to novel insights that may lead to better treatment.
Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies
in subjects with various degrees of glucose tolerance and insulin ...sensitivity.
E Bonora ,
G Targher ,
M Alberiche ,
R C Bonadonna ,
F Saggiani ,
M B Zenere ,
T Monauni and
M Muggeo
Division of Endocrinology and Metabolic Diseases, University of Verona Medical School, Italy. enbonor@tin.it
Abstract
OBJECTIVE: To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin
sensitivity in humans. RESEARCH DESIGN AND METHODS: In the present study, we compared insulin sensitivity as assessed by a
4-h euglycemic (approximately 5 mmol/l) hyperinsulinemic (approximately 300 pmol/l) clamp with HOMA in 115 subjects with various
degrees of glucose tolerance and insulin sensitivity. RESULTS: We found a strong correlation between clamp-measured total
glucose disposal and HOMA-estimated insulin sensitivity (r = -0.820, P<0.0001), with no substantial differences between men
(r = -0.800) and women (r = -0.796), younger (aged <50 years, r = -0.832) and older (r = -0.800) subjects, nonobese (BMI <27
kg/m2, r = -0.800) and obese (r = -0.765) subjects, nondiabetic (r = -0.754) and diabetic (r = -0.695) subjects, and normotensive
( r = -0.786) and hypertensive (r = -0.762) subjects. Also, we found good agreement between the two methods in the categorization
of subjects according to insulin sensitivity (weighted k = 0.63). CONCLUSIONS: We conclude that the HOMA can be reliably used
in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity
Abstract Background and aims We sought to explore associations between serum 25-hydroxyvitamin D 25(OH)D levels and non-alcoholic fatty liver disease NAFLD in an integrated healthcare delivery system ...in the U.S. Methods and results Six hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75 ± 17 vs. 85 ± 20 nmol/L 30 ± 7 vs. 34 ± 8 ng/mL, P < 0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L >30 ng/mL, reference group), insufficient (37–75 nmol/L 15–30 ng/mL; adjusted odds ratio OR: 2.40, 95% confidence interval CI: 0.90–6.34) or deficient (<37 nmol/L <15 ng/mL; adjusted OR: 2.56, 95% CI: 1.27–5.19). When modeled as a continuous variable, increased log10 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064–0.96, P = 0.02). Conclusion Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.
Aims To evaluate the cardiovascular risk associated with the presence of the Metabolic Syndrome in Type 2 diabetic subjects.
Methods Subjects with the Metabolic Syndrome, defined by WHO criteria, ...were identified in a large sample of non‐insulin‐treated Type 2 diabetic patients examined within the Verona Diabetes Complications Study (n = 946). At baseline and after a mean of 4.5 years follow‐up, cardiovascular disease (CVD) was assessed by medical history, physical examination, electrocardiogram (ECG) and echo‐duplex of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow‐up were scrutinized in order to identify CVD deaths. In statistical analyses, CVD was considered as an aggregate end‐point, including fatal and non‐fatal coronary, cerebrovascular and peripheral vascular disease as well as ischaemic ECG abnormalities and vascular lesions at the echo‐duplex.
Results The proportion of subjects with the Metabolic Syndrome was very high (92.3%). At the baseline, 31.7% of subjects were coded positive for CVD, which was more prevalent in subjects with the Metabolic Syndrome (32.9 vs. 17.8%, P = 0.005). Among subjects free of CVD at the baseline (n = 559), CVD events during the follow‐up were significantly increased in patients with the Metabolic Syndrome as compared with those without it (19.9% vs. 3.9%, P < 0.001). Multiple logistic regression analysis showed that, along with sex, age, smoking and HbA1c, the presence of the Metabolic Syndrome independently predicted prevalent (OR 2.01, P = 0.045) and incident CVD (OR 4.89, P = 0.031).
Conclusions In Type 2 diabetes, the presence of the Metabolic Syndrome is associated with an almost 5‐fold increase in CVD risk.
Purpose
Several studies have reported an association between hyperuricemia and increased risk of permanent atrial fibrillation (AF) in patients with and without type 2 diabetes mellitus (T2DM). ...Currently, no published data are available on the relationship between hyperuricemia and risk of paroxysmal AF.
Methods
We retrospectively evaluated 245 T2DM outpatients without pre-existing AF, cancer, cirrhosis and end-stage renal disease, who underwent a 24-h ECG-Holter monitoring for various clinical indications. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of paroxysmal AF was confirmed in affected individuals on the basis of 24-h ECG-Holter monitoring by experienced cardiologists.
Results
Hyperuricemia was observed in 59 (24.1%) patients, whereas paroxysmal AF was found in 11 (4.5%) patients. The prevalence of paroxysmal AF was higher in patients with hyperuricemia than in those without hyperuricemia (10.2 vs. 2.7%,
p
= 0.026). Logistic regression analysis showed that hyperuricemia was associated with an increased risk of prevalent paroxysmal AF. This association remained significant even after adjustment for age, metabolic syndrome and chronic kidney disease (adjusted-odds ratio 4.01, 95% CI 1.08–14.9;
p
= 0.039). Similar results were found when we used serum uric acid levels as a continuous measure.
Conclusions
This study shows for the first time that hyperuricemia is independently associated with an approximately fourfold increased risk of prevalent paroxysmal AF in patients with T2DM. These findings may partly explain the increased risk of permanent atrial fibrillation and cardiovascular death observed among patients with hyperuricemia.
Purpose
Increased arterial stiffness is an early sign of endothelial dysfunction. Nevertheless, measures of the elastic properties of the aortic root in patients with type 1 diabetes are still ...lacking. The aim of this study was to compare aortic root stiffness index in type 1 diabetes and healthy controls.
Methods
Ninety-three patients with type 1 diabetes without cardiovascular diseases were recruited and compared to 33 healthy controls. Aortic root elastic properties were estimated by measuring the systolic and diastolic diameters on M-mode acquisition.
Results
None of the subjects showed alterations of either systolic or diastolic echocardiographic parameters. Patients with type 1 diabetes had a very low prevalence of chronic complications and their metabolic control was good. Significantly increased aortic stiffness index was found in type 1 diabetes compared to controls, and the same different pattern was found in men and women. The presence of type 1 diabetes and increased pulse pressure was significantly associated with aortic stiffness index in a multivariate linear analysis.
Conclusion
This study strongly suggests that patients with type 1 diabetes develop aortic root stiffness in the absence of cardiovascular diseases. This alteration may be part of a more generalized arterial dysfunction in type 1 diabetes.
Purpose
Hyperuricemia/gout and atrial fibrillation (AF) are two pathological conditions that are highly prevalent in type 2 diabetes and share multiple cardiovascular risk factors. However, the ...relationship between elevated levels of serum uric acid and risk of AF in type 2 diabetes is currently poorly known.
Methods
We studied a hospital-based sample of 842 (male/female = 463/379) patients with type 2 diabetes discharged from our Division of Endocrinology during 2007–2011. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of AF was confirmed in affected participants on the basis of ECGs and medical history by experienced cardiologists.
Results
Overall, 243 (28.9 %) patients had hyperuricemia and 91 (10.8 %) patients had persistent or permanent AF. Compared with those with normal serum uric acid levels, patients with hyperuricemia had a remarkably greater prevalence of AF (20.6 vs. 7.1 %;
p
< 0.001). Hyperuricemia was significantly associated with an increased risk of prevalent AF (odds ratio 3.41, 95 % CI 2.19–5.32;
p
< 0.001). Adjustments for age, sex, smoking, hemoglobin A1c, hypertension status, chronic kidney disease, chronic obstructive pulmonary disease and previous histories of hyperthyroidism, ischemic heart disease and valvular heart diseases did not weaken this association (adjusted-odds ratio 6.27, 95 % CI 1.82–21.5;
p
< 0.01).
Conclusions
These results indicate that hyperuricemia is associated with an increased prevalence of AF in hospitalized patients with type 2 diabetes, independently of multiple risk factors and potential confounders.
Aims To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non‐diabetic subjects, and to examine the ...association of these biomarkers with early stages of microvascular complications.
Methods Plasma biomarkers of inflammation fibrinogen, hs‐C‐reactive protein (hs‐CRP) and endothelial dysfunction von Willebrand factor (v‐WF), intercellular adhesion molecule‐1, plasminogen activator inhibitor‐1 (PAI‐1) activity were measured in 88 non‐smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls.
Results Plasma levels of hs‐CRP, fibrinogen, v‐WF, soluble intracellular adhesion molecule‐1 (sICAM‐1) and PAI‐1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control.
Conclusions These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro‐ and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.
Abstract Background and aims Prognosis of type 2 diabetes is associated with the occurrence of cardiovascular diseases. Left atrial (LA) size is a predictor of outcome in several diseases, including ...diabetes. Long duration of diabetes is an established risk factor of poor prognosis. No data are available on the relationship between LA size and duration of diabetes. The present study was aimed to investigate the relationship between LA volume index (LAVI) and the duration of diabetes to test the hypothesis that LA volume will increase as a function of diabetes duration. Methods and results Forty-four male patients with newly diagnosed and 172 male patients with established type 2 diabetes were recruited for this cross-sectional study. All patients were evaluated with a transthoracic echocardiographic Doppler. About 28.2% of patients had increased LAVI. Indices of both diastolic and systolic function were significantly lower in patients with larger left atrium. The values of LAVI increased across classes of duration of diabetes. In multivariable analysis, longer duration was a predictor of LAVI ≥34 ml/m2 (odds ratio 1.65, 95% CI 1.11–2.46, p = 0.014) after adjusting for age, hemoglobin A1c, hypertension, microvascular complication status, and relevant echocardiographic parameters of systolic and diastolic function. Conclusions These results indicate that duration of diabetes is strongly and positively associated with larger LAVI in type 2 diabetic men with preserved systolic function. Future studies are needed to better elucidate the biological mechanisms underlying linking type 2 diabetes with abnormally increased LAVI in subjects with type 2 diabetes.
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