Nikolaos Tentolouris

Atherosclerosis in Rheumatoid Arthritis Versus Diabetes: A Comparative Study

Objective—The extent to which atherosclerosis is accelerated in chronic inflammatory diseases is not established. We compared preclinical atherosclerosis in rheumatoid arthritis with diabetes mellitus, a known coronary heart disease equivalent. Methods and Results—Endothelial function, arterial stiffness, carotid intima-media thickness, and analysis of atheromatous plaques were examined in 84 rheumatoid arthritis patients without cardiovascular disease versus healthy controls matched for age, sex, and traditional cardiovascular disease risk factors, as well as in 48 diabetes patients matched for age, sex, and disease duration with 48 rheumatoid arthritis patients. Rheumatoid arthritis duration associated with arterial stiffening, whereas disease activity associated with carotid plaque vulnerability. All markers of preclinical atherosclerosis were significantly worse in rheumatoid arthritis compared to controls, whereas they did not differ in comparison to diabetes despite a worse cardiovascular risk factor profile in diabetics. Both diseases were associated independently with increased intima-media thickness; rheumatoid arthritis, but not diabetes, was independently associated with endothelial dysfunction. Conclusions—Preclinical atherosclerosis appears to be of equal frequency and severity in rheumatoid arthritis and diabetes of similar duration with differential impact of traditional risk factors and systemic inflammation. Cardiovascular disease risk factors in rheumatoid arthritis may need to be targeted as aggressively as in diabetes.

Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: a response associated with up-regulation of Akt/mTOR and AMPK activation.

OBJECTIVEnThyroid hormone (TH) is shown to be protective against cardiac and pancreatic injury. Thus, this study explored the potential effects of TH treatment on the functional status of the postinfarcted diabetic myocardium. Diabetic patients have worse prognosis after acute myocardial infarction (AMI).nnnMATERIALS/METHODSnAMI was induced by left coronary ligation in rats previously treated with 35 mg/kg streptozotocin (STZ), (DM-AMI). TH treatment was initiated at 2 weeks after AMI and continued for 6 weeks (DM-AMI+TH), while sham-operated animals served as control (DM-SHAM).nnnRESULTSnTH treatment increased cardiac mass, improved wall stress and favorably changed cardiac geometry. TH significantly increased echocardiographic left ventricular ejection fraction (LVEF%): [54.2 (6.5) for DM-AMI+TH vs 37 (2.0) for DM-AMI, p<0.05]. TH treatment resulted in significantly increased insulin and decreased glucose levels in serum. The ratios of phosphorylated (p)-Akt/total Akt and p-mTOR/total mTOR were increased 2.0 fold and 2.7 fold in DM-AMI+TH vs DM-AMI respectively, p<0.05. Furthermore, the ratio of p-AMPK/total AMPK was found to be increased 1.6 fold in DM-AMI+TH vs DM-AMI, p<0.05.nnnCONCLUSIONnTH treatment improved the mechanical performance of the post-infarcted myocardium in rats with STZ-induced diabetes, an effect which was associated with Akt/mTOR and AMPK activation.

A simple plaster for screening for diabetic neuropathy: A diagnostic test accuracy systematic review and meta-analysis

OBJECTIVEnNeuropad is an adhesive indicator test applied at the plantar surface of the foot that detects sweating through color change. We examined the diagnostic accuracy of this simple plaster as triage test for screening for clinically relevant diabetic sensorimotor polyneuropathy in adult outpatients with type 1 or type 2 diabetes.nnnMATERIALS/METHODSnSystematic review and meta-analysis of diagnostic accuracy studies. We searched Medline, Embase, Cochrane Library, Biosis Previews, Web of Science, Scopus and gray literature without date or language restrictions. We pooled estimates of sensitivity and specificity, and fitted hierarchical models to produce summary receiver operating characteristic curves. We assessed methodological quality of included studies utilizing the Quality Assessment of Diagnostic Accuracy Studies 2 tool.nnnRESULTSnEighteen studies with 3470 participants met the inclusion criteria. Average sensitivity and specificity were 86% (95% CI 79 to 91) and 65% (95% CI 51 to 76) respectively. Likelihood ratios (LRs) were LR+=2.44 and LR-=0.22. Subgroup analyses per reference standard utilized provided similar estimates. Most studies were at risk of bias for patient selection and use of index or reference test, and had concerns regarding applicability due to patient selection.nnnCONCLUSIONnThe adhesive indicator test has reasonable sensitivity and could be used for triage of diabetic neuropathy to rule out foot at risk. Patients who tested positive should be referred to specialized care to establish a definite diagnosis. There is insufficient evidence for effectiveness on patient-important outcomes and cost-effectiveness of implementation in the diagnostic pathway compared with the standard clinical examination.

Impaired aortic elastic properties in patients with systemic sarcoidosis.

Backgroundu2002 Systemic sarcoidosis (Sar) is a granulomatous disorder involving multiple organs. Widespread vascular involvement and microangiopathy are common in patients with Sar. In addition, subclinical cardiac involvement is increasingly recognized in patients with Sar. However, data on the effect of Sar on the elastic properties of the arteries and myocardial performance are limited. In this study we looked for differences in aortic distensibility (AoD) which is an index of aortic elasticity, and myocardial performance of the ventricles, between patients with Sar and healthy subjects. In addition, we examined potential associations between AoD and clinical, respiratory and echocardiographic findings in patients with Sar.

Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial

OBJECTIVE In patients with uncontrolled type 2 diabetes on basal insulin, prandial insulin may be initiated. We assessed the efficacy and safety of initiating insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus basal-bolus insulin. RESEARCH DESIGN AND METHODS A phase 3b trial examined patients with uncontrolled type 2 diabetes on insulin glargine (IGlar U100) 20–50 units/day and metformin, randomized to IDegLira or IGlar U100 and insulin aspart ≤4 times per day. RESULTS Glycated hemoglobin (HbA1c) decreased from 8.2% (66 mmol/mol) to 6.7% (50 mmol/mol) with IDegLira and from 8.2% (67 mmol/mol) to 6.7% (50 mmol/mol) with basal-bolus (estimated treatment difference [ETD] −0.02% [95% CI −0.16, 0.12]; −0.2 mmol/mol [95% CI −1.7, 1.3]), confirming IDegLira noninferiority versus basal-bolus (P < 0.0001). The number of severe or blood glucose–confirmed symptomatic hypoglycemia events was lower with IDegLira versus basal-bolus (risk ratio 0.39 [95% CI 0.29, 0.51]; rate ratio 0.11 [95% CI 0.08, 0.17]). Body weight decreased with IDegLira and increased with basal-bolus (ETD −3.6 kg [95% CI −4.2, −2.9]). Fasting plasma glucose reductions were similar; lunch, dinner, and bedtime self-monitored plasma glucose measurements were significantly lower with basal-bolus. Sixty-six percent of patients on IDegLira vs. 67.0% on basal-bolus achieved HbA1c <7.0% (53 mmol/mol). Total daily insulin dose was lower with IDegLira (40 units) than basal-bolus (84 units total; 52 units basal). CONCLUSIONS In patients with uncontrolled type 2 diabetes on IGlar U100 and metformin, IDegLira treatment elicited HbA1c reductions comparable to basal-bolus, with statistically superior lower hypoglycemia rates and weight loss versus weight gain.

Diabetic Foot Infections: an Update in Diagnosis and Management

Foot infections are a common problem in patients with diabetes and a risk factor for limb amputation. They occur as a result of skin ulceration, which facilitates penetration of pathogens to deeper tissues. The diagnosis of infection is clinical. Aerobic gram-positive cocci are the most common pathogens. Ulcers which are chronic, preceded by administration of antibiotics and hospitalization or complicated by severe infection are polymicrobial. Antibiotic therapy is initially empiric based on the severity of the infection. Definitive therapy is modified according to the results of the microbiological culture and the response to empiric treatment. The optimal duration of antibiotic therapy ranges from 1–2 weeks for mild infections to 2–4xa0weeks and even longer for severe infections and osteomyelitis. Surgical consultation should be sought for infections complicated with abscesses, necrotizing fasciitis or osteomyelitis. With appropriate care, infection resolves in about 80–90% of non-limb threatening and in about 60% of severe infections.

Ambulatory Aortic Stiffness Is Associated With Narrow Retinal Arteriolar Caliber in Hypertensives: The SAFAR Study

BACKGROUNDnArterial stiffness measured under static conditions reclassifies significantly cardiovascular (CV) risk and associates with narrower retinal arterioles. However, arterial stiffness exhibits circadian variation, thus single static stiffness recordings do not correspond to the usual 24 hr, awake, and asleep average arterial stiffness. We aimed to test the hypothesis that ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV) associate with retinal vessel calibers, independently of confounders and of static arterial stiffness, in hypertensive individuals free from diabetes and CV disease.nnnMETHODSnDigital retinal images were obtained (181 individuals, age: 53.9±10.7 years, 55.2% men) and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and static office aPWV were estimated by Mobil-O-Graph; and static office carotid to femoral (cf) PWV by SphygmoCor.nnnRESULTSnRegression analysis performed in 320 gradable retinal images showed that, after adjustment for confounders: (i) ambulatory aPWV was significantly associated with narrower retinal arterioles but not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently with narrower retinal arterioles; aPWV introduction in the model of cfPWV, improved models R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and of cfPWV to detect the presence of retinal arteriolar narrowing was found.nnnCONCLUSIONnAmbulatory aPWV, estimated by an operator-independent method, provides additional information to cfPWV regarding the associations of arterial stiffness with the retinal vessel calibers.

The Keith-Wagener-Barker and Mitchell-Wong grading systems for hypertensive retinopathy: association with target organ damage in individuals below 55 years.

Background: The usefulness of the hypertensive retinopathy classification by Keith–Wagener–Barker (KWB) in clinical practice remains controversial. The simplified Mitchell–Wong grading, combining the two initial KWB’ grades in one stage, is proposed as an alternative method; both systems are poorly validated regarding their association with target organ damage. Objective: In a population free of cardiovascular disease and diabetes, we aimed to investigate the interobserver and intraobserver agreement of both grading systems, their association with aortic stiffness, carotid hypertrophy or plaques and the role of age and sex on this association. Methods: Digital retinal images were obtained and graded – according to both classifications – by two independent and blinded observers; aortic stiffness (carotid-femoral pulse wave velocity, m/s) and common carotid hypertrophy (cross-sectional area, mm2) or plaques were assessed by tonometry and ultrasound, respectively. Results: From the gradable retinal photos obtained by 200 eyes of 107 consecutive patients (age: 54u200a±u200a13 years, 51% men, 79% hypertensive patients) and after adjustments for confounders, the intraobserver and interobserver level of agreement was as following: KWB 88/64% and Mitchell–Wong 91/71%, respectively; exclusively in younger, not older, individuals aortic stiffness, carotid hypertrophy, but not plaques, were significantly associated with both systems, independently from confounders; no differences regarding target organ damage were found between stages 1 and 2 of KWB. Conclusion: Detecting early signs of hypertensive retinopathy may be of value in young individuals; the Mitchell–Wong seems preferable to the KWB classification system only for reasons of simplifying clinical practice.

A European, multicentre, retrospective, non-interventional study (EU-TREAT) of the effectiveness of insulin degludec after switching basal insulin in a population with type 1 or type 2 diabetes

To evaluate the clinical effectiveness of switching to insulin degludec (IDeg) in insulin‐treated patients with either type 1 diabetes (T1DM) or type 2 diabetes (T2DM) under conditions of routine clinical care.

Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus.

AIMSnFetuin-A is a hepatic glycoprotein that is involved in insulin resistance and atherosclerosis. Herein we examined the association of plasma fetuin-A levels with peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM).nnnMATERIAL AND METHODSnA total of 71 patients with T2DM and 57 non-diabetic individuals were recruited. Diagnosis of PAD was based on the absence of triphasic waveform at pedal arteries, while ankle-brachial index (ABI) was calculated. Radiographs of both feet and ankles were taken for the assessment of lower extremity arterial calcification (LEAC). Plasma fetuin-A levels were measured using ELISA.nnnRESULTSnPatients with T2DM had higher fetuin-A levels than non-diabetic participants. Participants with diabetes and PAD had lower fetuin-A levels than non-PAD diabetic patients. In subjects with T2DM fetuin-A levels were associated with ABI. Multivariate analysis demonstrated that in patients with T2DM the odds of PAD increased with long diabetes duration, smoking, presence of arterial hypertension and dyslipidemia, as well as with lower fetuin-A levels. A trend towards higher fetuin-A levels in subjects with less severe LEAC was found.nnnCONCLUSIONnPlasma fetuin-A levels are lower in patients with T2DM and PAD and are associated with PAD, irrespective of traditional cardiovascular risk factors. Moreover, fetuin-A may be involved in arterial calcification.