Triantafyllos Didangelos

Impact of autonomic neuropathy on left ventricular function in normotensive type 1 diabetic patients: a tissue Doppler echocardiographic study.

Cardiovascular autonomic neuropathy (CAN) is one of the most serious complications of diabetes and has been weakly linked with left ventricular (LV) diastolic dysfunction. Previous studies that explored this association either suffer from inadequate definition of CAN or have mainly used conventional Doppler or nuclear techniques to investigate LV diastolic function. Tissue Doppler imaging (TDI) has evolved as a new quantitative tool for the assessment of cardiac systolic function, diastolic function, and the hemodynamics of LV filling. We sought to investigate conventional and TDI-derived indexes of LV systolic and diastolic function in type 1 diabetic patients with and without CAN and also in normal control subjects. Our findings suggest that the presence of CAN seems to have an additive effect on LV diastolic dysfunction in type 1 diabetes.

Aortic elastic properties are related to left ventricular diastolic function in patients with type 1 diabetes mellitus.

Objective: The aim of the study was to evaluate left ventricular diastolic function and its relation to aortic wall stiffness in patients with type 1 diabetes mellitus without coronary artery disease or hypertension. Patients: Sixty-six patients with type 1 diabetes mellitus were examined by echocardiography and divided into two groups according to the diastolic filling pattern determined by mitral annulus tissue Doppler velocities. Group A patients (n = 21) presented diastolic dysfunction with a peak early diastolic mitral annular velocity (Em)/peak late diastolic mitral annular velocity (Am) ratio <1 whereas in group B patients (n = 45) the Em/Am ratio was >1. Coronary artery disease was excluded based on normal thallium scintigraphy. Aortic stiffness index was calculated from aortic diameters measured by echocardiography, using accepted criteria. Results: Aortic stiffness index differed significantly among the two groups. Significant correlations were found between parameters of left ventricular diastolic function (Em/Am, isovolumic relaxation time, deceleration time) and aortic stiffness index. Multiple stepwise linear regression analysis revealed aortic stiffness index (β = –0.39, p = 0.001) and isovolumic relaxation time (β = –0.46, p < 0.001) as the main predictors of Em/Am ratio. Conclusions: Aortic stiffness is increased in type 1 diabetic patients with left ventricular diastolic dysfunction. This impairment in aortic elastic properties seems to be related to parameters of diastolic function.

Myocardial perfusion scintigraphy in asymptomatic diabetic patients: a critical review

The increasing prevalence of diabetes mellitus and the associated high cardiovascular risk has made the non‐invasive identification of silent coronary heart disease in diabetic individuals an important issue. This strategy could identify higher risk asymptomatic patients with diabetes mellitus in whom coronary revascularization may improve the outcome beyond that achieved by currently recommended medical management. Stress myocardial perfusion imaging has been shown to be effective in detecting coronary heart disease and predicting adverse cardiac events in asymptomatic diabetic patients. However, the clinical utility of myocardial perfusion scintigraphy is debated intensively due to the paucity of prospective and outcome based evidence. The controversy stems from several observational studies, epidemiologic data and cost‐effectiveness analyses. Thus, although several authors and professional organizations advocate the use of stress imaging for screening higher risk asymptomatic diabetic patients, others are cautious in recommending any kind of stress testing in that population. This review is based on a broad survey of the literature and discusses the potential role of stress myocardial perfusion scintigraphy in screening asymptomatic diabetic subjects for coronary heart disease in the current era and in relation with other non‐invasive screening tools. Copyright

Initiative for a new diabetes therapeutic approach in a Mediterranean country: the INDEED study

ABSTRACT Aim: To assess the efficacy of a strategy to improve vascular risk management in patients with type 2 diabetes mellitus (T2DM). Methods: This was a pilot best practice implementation enhancement programme that enrolled 578 patients with T2DM. A baseline visit was followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimise drug treatment for all vascular risk factors. The patients were followed-up for 6 months. The UKPDS risk engine was used to estimate vascular risk in patients without established coronary heart disease (CHD) (n = 279). Results: There was an improvement in compliance to lifestyle measures and increased prescription of evidence-based medication. In patients without established CHD there was a 37% reduction in estimated risk for CHD, 44% for fatal CHD, 10% for stroke and 25% for fatal stroke (p ≤ 0.003 for all comparisons vs. baseline). There was also a substantial increase in the proportion of patients with established CHD who achieved their vascular risk factor targets. Conclusions: This is the first study to increase the adherence to multiple interventions in patients with T2DM in both primary care and hospital settings. Education of physicians and patients, distribution of guidelines/brochures, and the completion of a one-page form, motivated both physicians and patients to achieve multiple vascular risk factor goals.

Painful diabetic neuropathy: clinical aspects.

Painful diabetic neuropathy (PDN) is one of several clinical syndromes in patients with diabetic peripheral neuropathy (DPN) and presents a major challenge for optimal management. The epidemiology of PDN has not been extensively studied. On the basis of available data, the prevalence of pain ranges from 10% to 20% in patients with diabetes and from 40% to 50% in those with diabetic neuropathy. Neuropathic pain can be disabling and devastating, with a significant impact on the patients quality of life and associated healthcare cost. Pathophysiologic mechanisms underlying PDN are similar to other neuropathic pain disorders and broadly invoke peripheral and central sensitization. The natural course of PDN is variable, with the majority of patients experiencing spontaneous improvement and resolution of pain. Quantifying neuropathic pain is difficult, especially in clinical practice, but has improved recently in clinical trials with the development of neuropathic pain-specific tools, such as the Neuropathic Pain Questionnaire and the Neuropathic Pain Symptom Inventory. Hyperglycemia-induced pathways result in nerve dysfunction and damage, which lead to hyperexcitable peripheral and central pathways of pain. Glycemic control may prevent or partially reverse DPN and modulate PDN.

Thyroid Autoimmunity in the Context of Type 2 Diabetes Mellitus: Implications for Vitamin D

Vitamin D deficiency has been associated with both type 2 diabetes mellitus (T2DM) and autoimmune disorders. The association of vitamin D with T2DM and thyroid autoimmunity (TAI) has not been investigated. Thus, we aimed to explore the putative association between T2DM and thyroid autoimmunity (TAI) focusing on the role of 25-hydroxy-vitamin D (25(OH)D). Study population included 264 T2DM patients and 234 controls. To explore the potential association between 25(OH)D and thyroid autoimmunity while controlling for potential confounders—namely, age, gender, body mass index, and presence of T2DM—multivariate logistic regression analyses were undertaken. Patients with T2DM were younger (P < 0.001) and had significantly lower 25(OH)D levels (P < 0.001) and higher anti-TPO titers (P = 0.005). Multivariable logistic regression analyses suggested that T2DM and 25(OH)D levels were significantly associated with the presence of thyroid autoimmunity. In an elderly population of diabetic patients and controls with a high prevalence of vitamin D deficiency/insufficiency, a patient with T2DM was found to be 2.5 times more likely to have thyroid autoimmunity compared to a nondiabetic individual and the higher the serum 25(OH)D levels were, the higher this chance was.

Matrix Gelatinases in Atherosclerosis and Diabetic Nephropathy: Progress and Challenges

BACKGROUND Matrix metalloproteinases (MMPs) are zinc-dependent proteases that degrade components of the extracellular matrix (ECM). In glomerular disease, MMPs are major regulators of ECM degradation as well as structural and functional integrity in the glomerulus. In altered matrix composition diseases, glomerular damage is due to increased degradation of kidney and vessel basement membranes (BMs) by MMPs. MMP -2 and -9 are both considered as the main enzymes that degrade collagen type-IV (coll-IV), which represents the key collagenous component of ECM and constitutes the architectural structure of vessels and glomerular BM. There is growing evidence implicating MMPs in atherosclerosis as well as in cardiovascular disease (CVD) and chronic kidney disease (CKD). Specific endogenous tissue inhibitors of MMPs (TIMPs) are also implicated in CKD, CVD and diabetic nephropathy (DN). CONCLUSION The present review discusses the role of MMPs -2 and -9 in DN, as a leading cause of endstage renal disease and as a model of the link between progressive glomerulosclerosis and MMP expression.

Left ventricular systolic and diastolic function in normotensive type 2 diabetic patients with or without autonomic neuropathy: a radionuclide ventriculography study.

We investigated the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in 59 patients with type 2 diabetes mellitus (T2DM) free of coronary artery disease (CAD) or hypertension. Diabetic autonomic neuropathy was established by ≥2 abnormal autonomic nervous function tests. Left ventricular systolic and diastolic functions were assessed by resting radionuclide ventriculography. Compared with non-DAN patients (n = 24), patients with DAN (n = 35) had an increased adjusted atrial contribution to ventricular filling (A/V%, 30.1% ± 8.2% vs 26.5% ± 5.1%; P = .031), suggestive of diastolic dysfunction (DD). There were no differences between the 2 groups in peak filling rate, first 1/3 filling fraction, ejection fraction, cardiac output, and cardiac index. Patients with diabetic autonomic neuropathy had an increased heart rate (77.8 ± 6.3 vs 69.3 ± 3.3 bpm; P < .0001) and a higher rest LV workload (10 072 ± 1165 vs 8606 ± 1075 bpm mm Hg; P < .0001). Patients with DAN T2DM without CAD or hypertension have DD, increased A/V index, and a higher LV working load than non-DAN patients.

The prognostic efficacy of myocardial perfusion imaging in optimally treated diabetic patients with no manifestations of coronary artery disease.

ObjectiveThis study investigates the efficacy of radionuclide myocardial perfusion imaging (MPI) in the evaluation of cardiac outcome in optimally treated diabetic patients without manifestations of coronary artery disease (CAD) in relation to the inherent clinical risk. MethodsFollow-up data were collected from 86 diabetic patients who had undergone adenosine stressing MPI. These patients either had no symptoms or had noncardiac chest discomfort, had a normal resting electrocardiogram, had no known CAD or prior positive stress test results, and were receiving currently recommended therapy. Endpoints were cardiac death, myocardial infarction, new-onset heart failure, and CAD diagnosed by angiography at least 2 months from the MPI, irrespective of subsequent revascularization. ResultsTwenty-six (30%) diabetic patients had abnormal perfusion and the remaining had a normal scan. Over a median follow-up period of 32.5 months 14 cardiac events occurred. In patients with normal MPI, the annual cardiac event rate was 4.0% compared with 12.2% in those with abnormal MPI (P=0.008). In multivariate analysis, myocardial ischemia (hazard ratio 5.3; P=0.006), obesity (hazard ratio 6.8; P=0.005), the ALFEDIAM/SFC risk (hazard ratio 6.8; P=0.002), and type 2 diabetes (hazard ratio 5.3; P=0.035) were found to be independent predictors of cardiac events. The former two variables remained independent determinants of the outcome, together with peripheral arterial disease, when a different clinical risk classification system was applied. MPI provided incremental prognostic information over both clinical models formed. ConclusionAdenosine MPI can effectively risk-stratify optimally treated diabetic patients without manifestations of CAD. In this subset, clinical variables can also determine the outcome independently, but MPI adds incremental predictability over them.

A Comparative Assessment of Cardiovascular Autonomic Reflex Testing and Cardiac 123I-Metaiodobenzylguanidine Imaging in Patients with Type 1 Diabetes Mellitus without Complications or Cardiovascular Risk Factors

Aim To compare the cardiovascular autonomic reflex tests (CARTs) with cardiac sympathetic innervation imaging with 123I-metaiodobenzylguanidine (MIBG) in patients with type 1 diabetes mellitus (T1DM). Patients and Methods Forty-nine patients (29 males, mean age 36 ± 10 years, mean T1DM duration 19 ± 6 years) without cardiovascular risk factors were prospectively enrolled. Participants were evaluated for autonomic dysfunction by assessing the mean circular resultant (MCR), Valsalva maneuver (Vals), postural index (PI), and orthostatic hypotension (OH). Within one month from the performance of these tests, patients underwent cardiac MIBG imaging and the ratio of the heart to upper mediastinum count density (H/M) at 4 hours postinjection was calculated (abnormal values, H/M < 1.80). Results Twenty-nine patients (59%) had abnormal CARTs, and 37 (76%) patients had an H/M_4 < 1.80 (p = 0.456). MCR, PI, Vals, and OH were abnormal in 29 (59%), 8 (16%), 5 (10%), and 11 (22%) patients, respectively. When using H/M_4 < 1.80 as the reference standard, a cutoff point of ≥2 abnormal CARTs had a sensitivity of 100% but a specificity of only 33% for determining CAN. Conclusions CARTs are not closely associated with 123I-MIBG measurements, which can detect autonomic dysfunction more efficiently than the former. In comparison to semiquantitative cardiac MIBG assessment, the recommended threshold of ≥2 abnormal CARTs to define cardiovascular autonomic dysfunction is highly sensitive but of limited specificity and is independently determined by the duration of T1DM.