2型糖尿病患者脂蛋白（a）水平、载脂蛋白（a）多态性和冠状动脉粥样硬化严重程度的关系

背景:针对糖尿病患者Lp(a)水平和冠状动脉疾病(CAD)严重程度之间关系的研究较少并且结论有争议。另外,目前尚无关于apo(a)多态性与上述疾病关系的研究。本研究旨在探讨大样本2型糖尿病患者中冠状动脉粥样硬化的程度与Lp(a)水平及apo(a)多态性的相关性。方法:连续选取227例2型糖     

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.     

Impact of anti-rheumatic drugs and steroids on clinical course and prognosis of COVID-19

Clinical Rheumatology -     

Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?

Growth hormone/insulin-like growth factor (IGF) axis may play a role in maintaining glucose homeostasis in synergism with insulin. IGF-1 can directly stimulate glucose transport into the muscle through either IGF-1 or insulin/IGF-1 hybrid receptors. In severely decompensated diabetes including diabetic ketoacidosis, plasma levels of IGF-1 are low and insulin delivery into the portal system is required to normalize IGF-1 synthesis and bioavailability. Normalization of serum IGF-1 correlated with the improvement of glucose homeostasis during insulin therapy providing evidence for the use of IGF-1 as biomarker of metabolic control in diabetes. Taking apart the inherent mitogenic discussion, diabetes treatment using insulins with high affinity for the IGF-1 receptor may act as an endocrine pacer exerting a cardioprotective effect by restoring the right level of IGF-1 in bloodstream and target tissues, whereas insulins with low affinity for the IGF-1 receptor may lack this positive effect. An excessive and indirect stimulation of IGF-1 receptor due to sustained and chronic hyperinsulinemia over the therapeutic level required to overtake acute/chronic insulin resistance may act as endocrine disruptor as it may possibly increase the cardiovascular risk in the short and medium term and mitogenic/proliferative action in the long term. In conclusion, normal IGF-1 may be hypothesized to be a good marker of appropriate insulin treatment of the subject with diabetes and may integrate and make more robust the message coming from HbA1c in terms of prediction of cardiovascular risk.     

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.     

Erectile dysfunction and angiographic extent of coronary artery disease in type II diabetic patients

Some studies observed an association between erectile dysfunction (ED) and coronary artery disease (CAD) extent in the general population, but others did not. There are no specific studies in diabetic populations. The aim of the present study was to evaluate whether ED is correlated with the extent of angiographic CAD in a large group of type II diabetic patients. We recruited 198 consecutive type II diabetic males undergoing an elective coronary angiography to evaluate chest pain or suspected CAD. Presence and degree of ED were assessed by the International Index Erectile Function - 5 (IIEF-5) questionnaire. ED was considered present, when IIEF-5 score was < or =21. Moreover, each domain of IIEF-5 was considered. Angiographic CAD extent was expressed both by the number of vessels diseased and by the Gensini scoring system. The percentage of subjects with ED was significantly higher (45.8 versus 15.8%; P=0.0120) in patients with (n=179) than in those without (n=19) significant angiographic CAD (stenosis of the lumen > or =50%). No significant association of CAD extent with presence of ED, total IIEF-5 score and each domain of IIEF-5 was observed. Our study shows that ED was significantly more prevalent in type II diabetic males with angiographic CAD than in those with normal arteries. However, no correlation was found between the extent of angiographic CAD and the presence or the severity of ED.