Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus

Neuropathy and peripheral artery disease represent the main pathophysiological conditions underlying diabetic foot. Several studies showed that Lipoprotein(a)-Lp(a)-and homocysteine (Hcy) can be associated with diabetic complications, but their relationship with diabetic foot is unclear. Aim of this study was to investigate whether Lp(a) and Hcy were associated with diabetic foot ulcerations, classified according to the presence of peripheral artery disease (PAD) or neuropathy. From among consecutive type 2 diabetic attending at the Diabetic Foot Clinic 27 subjects with vascular diabetic foot (VDF), 43 with neuropathic diabetic foot (NDF) and 52 controls without foot ulceration, neuropathy, and PAD were enrolled. Both Lp(a) (26.1 ± 22.7 vs. 14.9 ± 19.5 mg/dl; P = 0.003) and Hcy levels (15.4 ± 5.7 vs. 12.2 ± 5.1 μmol/l; P = 0.022) were significantly greater in the VDF group than in controls. Lp(a) levels were significantly lower in the NDF group than in controls (6.9 ± 8.1 versus 14.9 ± 19.5 mg/dl; P = 0.009), while no difference in Hcy levels was found. Multiple logistic regression analysis showed that Hcy was associated with VDF (OR: 1.11; 95% CI: 1.07-14.1; P = 0.048). Lp(a) did not enter the model, but its P-value was very near to the significant level (OR: 1.09; 95% CI: 0.99-12.05; P = 0.059). Moreover, low Lp(a) levels were associated with NDF (OR: 0.84; 95% CI: 0.21-0.96; P = 0.039). Our study has shown for the first time that high Lp(a) and Hcy levels are associated with the development of VDF, while low Lp(a) levels appear to be associated with delayed wound healing in patients with neuropathic foot ulcerations.     

Postmenopausal women with carotid atherosclerosis: Potential role of the serum calcium levels

Background and aimStudies on the association between serum calcium levels and cardiovascular diseases suggested a causative role for hypercalcemia but other studies showed that even serum calcium levels within normal range could be involved in atherosclerosis. However, while dietary calcium intake does not seem to be related to adverse cardiovascular effects, the association between calcium supplementation and the cardiovascular events has not been fully proven. Our aim was to determine the relation between serum calcium levels, within normal range, and the presence of carotid atherosclerosis in a population in whom investigations on this topic are lacking, the postmenopausal women.Methods and resultsIn this retrospective study, participants were recruited from women aged 49–65 years who underwent an ultrasonography evaluation of the carotid arteries between years 2008–2012. The study included 413 subjects with serum calcium level available, without symptomatic cardiovascular disease. A physical examination, including the evaluation of body mass index, waist and hip circumferences and the blood pressure, as well as, a collection of a venous blood sample was performed. The mean age was 56 ± 7 years. The prevalence of the carotid atherosclerosis was 50.8%. The comparison between women with and without carotid atherosclerosis showed differences for the classical risk factors and for serum calcium levels (p = 0.001). The logistic regression analysis, adjusting for these risk factors, confirmed the association between serum calcium levels and carotid atherosclerosis (p = 0.011). Furthermore, we showed an increasing prevalence of carotid atherosclerosis from lower to higher calcium quartiles (p = 0.016).ConclusionWe found a positive relation between serum calcium levels and the carotid atherosclerosis in postmenopausal women. This study may suggest a redetermination of the reference range of calcemia, at least in menopause.     

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 ± 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the “Mater Domini” University Hospital in Catanzaro, Calabria region, and the “P. Giaccone ”University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, p = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, p = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups.     

Transcutaneous Oxygen Tension as a Potential Predictor of Cardiovascular Events in Type 2 Diabetes: Comparison with ankle-brachial index

OBJECTIVE

Transcutaneous oxygen tension (TcPO2) measures tissue perfusion and is important in the management of peripheral artery disease (PAD). Ankle brachial index (ABI) is used for the diagnosis of PAD and represents a predictor of major adverse cardiovascular events (MACE), even if in diabetes its diagnostic and predictive value seems to be reduced. No study has evaluated TcPO2 as a predictor of cardiovascular events. Aim of this longitudinal study was to assess whether TcPO2 is better than ABI at predicting MACE in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

Among 361 consecutive patients with apparently uncomplicated diabetes, 67 MACE occurred during a follow-up period of 45.8 ± 23.2 months.

RESULTS

The percentage of both subjects with low ABI (≤0.9) and subjects with low TcPO2 (≤46 mmHg as measured by a receiver operating characteristic curve) was significantly (<0.001) greater among patients with than among those without MACEs (ABI 64.2 vs. 40.8; TcPO2 58.2 vs. 34%). The Kaplan-Meier method showed that both low ABI (Mantel log-rank test, 4.087; P = 0.043) and low TcPO2 (Mantel log-rank test, 33.748; P > 0.0001) were associated with a higher rate of MACEs. Cox regression analysis showed that low TcPO2 (hazard ratio 1.78 [95% CI 1.44–2.23]; P < 0.001) was a significant predictor of MACE, while ABI did not enter the model.

CONCLUSIONS

This longitudinal study showed that TcPO2 may be a potential predictor of MACE among patients with uncomplicated type 2 diabetes and that its predictive value seems to be greater than that of ABI.Diabetic patients have an increased cardiovascular risk (1,2). Indeed, cardiovascular disease is the main cause of mortality and morbidity related to diabetes, and approximately two-thirds or more of diabetic patients die of cardiovascular disease (1,2). Cardiovascular death rate of diabetic patients without prior myocardial infarction even seems to be similar to that of nondiababetic patients with prior myocardial infarction (3).Ankle brachial index (ABI), commonly used as a diagnostic test for peripheral arterial disease (PAD) (4), is considered an independent powerful marker of cardiovascular morbidity and mortality in the general population (5,6). An ABI of ≤0.90 is universally recognized as the cutoff for the diagnosis of PAD (4). However, in diabetic people the use of ABI has some important diagnostic limitations: indeed, the presence of typical medial artery calcifications causes arterial wall stiffness and a high prevalence of false-negative values (7–9). Transcutaneous oxygen tension (TcPO2) is a noninvasive method to measure tissue perfusion: it reflects very well the metabolic state of lower limbs (10,11). TcPO2 is currently used in clinical practice in the management of the vascular diabetic foot (11,12); in particular, it is important in determining amputation level, wound healing evaluation, and revascularization procedures (11,12). TcPO2 is not affected by arterial calcification and is particularly useful in evaluating PAD in diabetic patients (13); in addition, it has a good reproducibility (10–12). Nevertheless, there is not thus far a universally recognized specific cutoff of TcPO2 for the diagnosis of PAD (11). Finally, it is unknown whether TcPO2 may be a reliable marker as well of cardiovascular morbidity and mortality in diabetes. Aim of the current study was to assess whether TcPO2 is better than ABI in predicting major adverse cardiovascular events (MACEs) among diabetic patients.     

Subclinical Cardiovascular Damage and Fat Utilization in Overweight/Obese Individuals Receiving the Same Dietary and Pharmacological Interventions

Subclinical organ damage precedes the occurrence of cardiovascular events in individuals with obesity and hypertension. The aim of this study was to assess the relationship between fuel utilization and subclinical cardiovascular damage in overweight/obese individuals free of established cardiovascular disease receiving the same diet and pharmacological intervention. In this retrospective study a total of 35 subjects following a balanced diet were enrolled. They underwent a complete nutritional and cardiovascular assessment. Echocardiography and ultrasonography of the carotid arteries was performed. The respiratory quotient (fuel utilization index) was assessed by indirect calorimetry. A total of 18 had left ventricular concentric remodeling, 17 were normal. Between these two groups, a significant difference of intima-media thickness was showed (p = 0.015). Also a difference of respiratory quotient was shown with the highest value in those with remodeling (p = 0.038). At univariate and multivariate analysis, cardiac remodeling was associated with respiratory quotient (RQ) (p = 0.04; beta = 0.38; SE = 0.021; B = 0.044). The area under the receiver operating characteristic (ROC) curve for respiratory quotient to predict remodeling was 0.72 (SE = 0.093; p = 0.031; RQ = 0.87; 72% sensitivity, 84% specificity). The respiratory quotient is significantly different between those participants with and without cardiac remodeling. Its measurement may help for interpreting the (patho)physiological mechanisms in the nutrients utilization of obese people with different response to dietary or pharmacological interventions.     

Concomitant carotid plaque development and brachial artery diameter enlargement: A retrospective,recall-based study in postmenopausal women

Background and aimTo verify if the carotid plaque development is concomitant to brachial artery diameter enlargement, in healthy postmenopausal women.Methods and resultsThis is a retrospective, recall study. We enrolled 40 postmenopausal women, selected from a database for the period 2000–2008, not affected by subclinical carotid atherosclerosis and without risk factors for cardiovascular disease. At the recall visit, carotid and brachial duplex scan was again obtained.The incidence of plaque was 30% after a mean follow-up period of 60 months. There were no differences in baseline characteristics between subjects developing carotid atherosclerosis and subjects who did not, except for the brachial diameter change, follow-up and heart rate. The logistic-regression analysis confirmed that only brachial diameter change resulted to be correlated with the development of carotid atherosclerosis.ConclusionBrachial artery diameter increase is concomitant to carotid plaque development. Vascular enlargement could not be a focal change but a systemic process associated with atherosclerotic plaque development. Brachial diameter could be a tool with a predictive significance.     

Role of endogenous androgens on carotid atherosclerosis in non-obese postmenopausal women

BackgroundRecent randomized trials on hormone replacement therapy in postmenopausal women raised many doubts about their role in cardiovascular disease prevention. Therefore the role of other sex hormones needed to be investigated. In particular androgens seem to have a protective role on atherosclerosis. The present study was performed to assess the role of endogenous sex hormones on carotid atherosclerosis in postmenopausal women.Methods and resultsWe consecutively enrolled 101 postmenopausal women aged 45–75 (mean age 57.4) years referred to our University hospital menopausal health-screening clinic. The subjects underwent a medical history, a physical examination and biochemical analysis. Extracranial carotid arteries were assessed by ultrasound. Fifty percent of our sample had carotid plaques. On the multivariate logistic regression analysis age, glycaemia (positively) and testosterone (negatively) (P = 0.02) were significantly correlated to carotid atherosclerosis. In non-obese subjects we found that participants in the third tertile had a significantly lower prevalence of carotid atherosclerosis (P = 0.02) compared to those in the first tertile of testosterone.ConclusionsThese results suggest a possible protective role of endogenous androgens at least on carotid atherosclerosis. Of course these preliminary results should be supported by prospective studies. Also the different role of these hormones on obese and non-obese subjects needs to be clarified.     

Large brachial and common carotid artery diameter in postmenopausal women with carotid atherosclerosis

Background and purposeIt is recognized that arteries can enlarge to compensate atherosclerosis. The role of diameter enlargement of unaffected arteries is not well known. We hypothesized that brachial and common carotid arteries diameters were larger in subjects with carotid atherosclerosis compared to subjects without these lesions.MethodsWe measured diameters in the common carotid and brachial arteries. Intimal medial thickness (IMT) of carotid arteries and carotid atherosclerosis were also evaluated using ultrasound in 83 cases and 83 disease-free control subjects.ResultsCommon carotid and brachial diameter was greater in cases (subjects with carotid atherosclerosis) than controls (subjects without carotid atherosclerosis) after adjustment for confounding variables (P < 0.02). Common carotid diameter was also larger in individuals with greater IMT (P < 0.0001), whereas brachial artery diameter was not. Subjects with more than one carotid plaque had larger arterial diameters than those with one or without plaques.ConclusionsCommon carotid and brachial artery diameters are both larger in cases than controls. This result suggests that vascular remodeling is a systemic process and not only a local response to atherosclerosis. The relationship between diameters and burden of disease could also suggest a link between vascular remodeling and severity of disease. Finally, if confirmed in prospective studies, brachial artery diameter could help to identify subjects at high cardiovascular risk, at least in postmenopausal women.