Assessment of Tissue Viability Following Amputation Surgery Using Near-Infrared Fluorescence Imaging With Indocyanine Green.

BACKGROUND: Patients with chronic limb threatening ischemia have a risk of undergoing a major amputation within 1 year of nearly 30% with a substantial risk of re-amputation since wound healing is often impaired. Quantitative assessment of regional tissue viability following amputation surgery can identify patients at risk for impaired wound healing. In quantification of regional tissue perfusion, near-infrared (NIR) fluorescence imaging using Indocyanine Green (ICG) seems promising. METHODS: This pilot study included adult patients undergoing lower extremity amputation surgery due to peripheral artery disease or diabetes mellitus. ICG NIR fluorescence imaging was performed within 5 days following amputation surgery using the Quest Spectrum PlatformⓇ. Following intravenous administration of ICG, the NIR fluorescence intensity of the amputation wound was recorded for 10 minutes. The NIR fluorescence intensity videos were analyzed and if a fluorescence deficit was observed, this region was marked as "low fluorescence." All other regions were marked as "normal fluorescence." RESULTS: Successful ICG NIR fluorescence imaging was performed in 10 patients undergoing a total of 15 amputations. No "low fluorescence" regions were observed in 11 out of 15 amputation wounds. In 10 out of these 11 amputations, no wound healing problems occurred during follow-up. Regions with "low fluorescence" were observed in 4 amputation wounds. Impaired wound healing corresponding to these regions was observed in all wounds and a re-amputation was necessary in 3 out of 4. When observing time-related parameters, regions with low fluorescence had a significantly longer time to maximum intensity (113 seconds vs. 32 seconds, P = 0.003) and a significantly lesser decline in outflow after five minutes (80.3% vs. 57.0%, P = 0.003). CONCLUSIONS: ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Quantitative assessment of regional perfusion remains challenging due toinfluencing factors on the NIR fluorescence intensity signal, including camera angle, camera distance and ICG dosage. This was also observed in this study, contributing to a large variety in fluorescence intensity parameters among patients. To provide surgeons with reliable NIR fluorescence cut-off values for prediction of wound healing, prospective studies on the intra-operative use of this technique are required. The potential prediction of wound healing using ICG NIR fluorescence imaging will have a huge impact on patient mortality, morbidity as well as the burden of amputation surgery on health care.

Assessment of toe brachial index validity in diabetic patients - interim results.

INTRODUCTION: The toe brachial index (TBI) is recommended for the detection of lower extremity arterial disease (LEAD) in case of reduced efficacy of the ankle brachial index (ABI), which most often occurs in diabetics. In this case, TBI is expected to give more accurate results. There are not many studies dealing with the use of TBI specifically in diabetics and the results are different. OBJECTIVE: The purpose of this work is to present the interim results of the study, whose main objective is to assess the validity of TBI in diabetics and to determine whether this method provides improvements over the ABI. METHODS: In the first phase of the study, 42 limbs were examined in 21 patients with type 2 diabetes. ABI was measured using the automatic oscillometric method (ABI OSC) and the manual method using the pencil doppler (ABI DPP). TBI was determined using an automatic plethysmographic method. The reference examination of the arteries of the lower limbs was performed using duplex ultrasonography (DUS). A paired t-test was used to compare the individual TBI and ABI methods. Cut-off points ABI < 0.9; TBI < 0.7; and DUS stenosis > 50 % were used to evaluate validity parameters. RESULTS: The individual ABI and TBI methods gave different results (p < 0.05). In eight limbs of the total number, LEAD was demonstrated using DUS. The best validity parameters were demonstrated by the TBI - sensitivity 0.88; specificity 0.88; positive predictive value 0.64; negative predictive value 0.97, positive likelihood ratio 7.44; negative likelihood ratio 0.14. The ABI method of calculation, that uses lower systolic blood pressure determined from two measurement sites on the ankle as a numerator, had a higher validity parameters. The ABI OSC did not correctly detect a single limb with stenosis > 50 % in this cohort. CONCLUSION: According to the interim results of this work, the TBI was more suitable for the detection of LEAD in diabetics in comparison with ABI.

Improving the Assessment of Flow-Mediated Dilation Through Detection of Peak Time in Healthy Subjects and Subjects With Type 2 Diabetes.

The assessment of flow-mediated dilation (FMD) is widely used to quantify endothelial function. Historically, FMD was determined at 60 seconds post-cuff deflation. We investigated whether FMD would be more accurate if determined at maximum dilatory peak (MDP) than at 60 seconds in healthy subjects and subjects with type 2 diabetes mellitus (T2DM). We studied 95 healthy and 72 subjects with T2DM and assessed FMD at MDP, 60 and 90 seconds. Twenty-four healthy and 12 subjects with T2DM underwent a repeat FMD after 28 days. In healthy subjects, FMD at MDP was higher than at 60 and 90 seconds, with mean difference MDP versus 60 seconds 1.14% (95% CI: 0.6-1.7); P < .0001 and MDP versus 90 seconds 1.9% (95% CI: 1.3-2.5) with similar results in T2DM, that is, 1.0% (95% CI: 0.1-1.9) and 2.3% (95% CI: 1.3-3.2), respectively. Intraindividual variability was lowest with MDP compared with 60 and 90 seconds, that is, 15.0 versus 23.2% and 40.0%, respectively, resulting in a more than 2-fold reduction in necessary sample size. In healthy subjects and subjects with T2DM, assessment of FMD using MDP results in a more accurate and precise assessment leading to a substantial reduction in sample size.

Near-instant noninvasive optical imaging of tissue perfusion for vascular assessment.

BACKGROUND: Noninvasive vascular tests are critical for identifying patients who may benefit from surgical revascularization, but current tests have significant limitations in people with diabetes. This study aimed to evaluate the ability of spatial frequency domain imaging (SFDI), an optical imaging method capable of measuring tissue oxygen saturation (StO2) and tissue hemoglobin, to assess lower extremity blood supply. METHODS: Ankle-brachial index, toe-brachial index, pedal Doppler waveforms, and SFDI images were prospectively evaluated in 47 consecutive patients with and without diabetes in whom there was concern for peripheral artery disease (PAD). SFDI is a noncontact optical imaging technology that uses structured illumination to quantify subsurface (2-3 mm in depth) StO2 and tissue hemoglobin in the dermal microcirculation (HbT1) and macrocirculation (HbT2) over a large field of view (15 × 20 cm) within 10 seconds. RESULTS: This demonstrates the ability of SFDI to capture reliable clinical measurements of perfusion in plantar aspects of the feet. SFDI StO2 values differentiate nondiabetic patients with and without arterial disease, defined as ankle-brachial index <0.9 (P = .06), but are limited in those with diabetes (P = .43). An elevated StO2 and reduced HbT1 are observed in people with diabetes compared with nondiabetic patients (P < .05). An SFDI-derived HbT2/HbT1 index differentiates diabetics with PAD vs no PAD (P < .01) using toe-brachial index <0.7 as a cutoff for PAD in diabetes. CONCLUSIONS: SFDI is a feasible, rapid, and easy to use widefield measurement of perfusion in a clinical setting. This first-of-use study suggests that the technology has potential to evaluate lower extremity perfusion in people with and without diabetes. Further studies with increased numbers of patients and end points including wound healing will need to be designed to fully evaluate the applicability of this new technology.

Assessment of factors associated with measurability of fractional flow reserve derived from coronary computed tomography angiography in type 2 diabetic patients with intermediate coronary artery stenosis.

Recently, fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFRCT) has been developed. However, FFRCT cannot be calculated for all patients from CCTA datasets. The purpose of the present study, therefore, was to evaluate the predictors that results in cases being inappropriate for FFRCT processing. This study was a sub-analysis of the TRACT trial, from which 50 patients were divided into 2 groups according to FFRCT measurability (measurable [group M] or not measurable [group N]) using CCTA examination at baseline. Thirty-nine (78%) patients comprised group M and 11 (22%) comprised group N. Heart rate at CCTA examination (72 beats/min vs. 63 beats/min; p = 0.007) and Agatston score (665 vs. 33; p = 0.002) in group N were significantly higher than those in group M. Multivariate logistic regression analyses revealed that heart rate at CCTA examination (OR 1.348 [95% CI 1.167-1.556]; p < 0.001) and Agatston score (OR 1.002 [95% CI 1.000-1.003]; p = 0.004) were significant, independent factors associated with non-measurability of FFRCT. The frequency of poor image quality was highest in patients with heart rate > 65 beats/min and Agatston score > 400 (p < 0.0001). In conclusions, high heart rate at the time of CCTA examination and higher Agatston score were associated with poor image quality that resulted in cases being inappropriate for FFRCT processing. Heart rate control at CCTA examination is necessary to acquire good-quality images required for computing FFRCT.

Atherosclerosis imaging to refine cardiovascular risk assessment in diabetic patients: Computed tomography and positron emission tomography applications.

The lifetime cardiovascular risk of a diabetic patient is approximately 4-5 times higher than that of an age and sex matched individual without diabetes mellitus. Despite the well-publicized cardiovascular risk equivalence of diabetes mellitus, it has become apparent that not all diabetic patients are equally at high-risk and many patients may have a level of risk similar to that of the general population. Cardiovascular imaging has been employed to address the dilemma of a more accurate risk stratification of diabetic patients. Two randomized clinical trials aiming at uncovering the presence of unknown obstructive coronary artery disease (CAD) gave disappointing results. In fact, the number of patients with inducible myocardial ischemia and/or severe obstructive disease was lower than expected and the overall outcome was not improved after having brought the existence of CAD to light. Other techniques that may help identify a diabetic patient susceptible to suffer future events have therefore being explored. In this review we discuss two imaging tools that provide anatomical and functional information on pre-clinical coronary atherosclerosis: computed tomography for calcium scoring, and plaque characterization and myocardial ischemia detection and positron emission tomography using tracers to identify functionally unstable plaques. Despite the availability of several imaging techniques there remain numerous questions as to the utility of imaging to define risk in diabetes mellitus and an optimal approach has yet to be found.

Multimodal Assessment of Mesenchymal Stem Cell Therapy for Diabetic Vascular Complications.

Peripheral arterial disease (PAD) is a debilitating complication of diabetes mellitus (DM) that leads to thousands of injuries, amputations, and deaths each year. The use of mesenchymal stem cells (MSCs) as a regenerative therapy holds the promise of regrowing injured vasculature, helping DM patients live healthier and longer lives. We report the use of muscle-derived MSCs to treat surgically-induced hindlimb ischemia in a mouse model of type 1 diabetes (DM-1). We serially evaluate several facets of the recovery process, including αVß3 -integrin expression (a marker of angiogenesis), blood perfusion, and muscle function. We also perform microarray transcriptomics experiments to characterize the gene expression states of the MSC-treated is- chemic tissues, and compare the results with those of non-ischemic tissues, as well as ischemic tissues from a saline-treated control group. The results show a multifaceted impact of mMSCs on hindlimb ischemia. We determined that the angiogenic activity one week after mMSC treatment was enhanced by approximately 80% relative to the saline group, which resulted in relative increases in blood perfusion and muscle strength of approximately 42% and 1.7-fold, respectively. At the transcriptomics level, we found that several classes of genes were affected by mMSC treatment. The mMSCs appeared to enhance both pro-angiogenic and metabolic genes, while suppressing anti-angiogenic genes and certain genes involved in the inflammatory response. All told, mMSC treatment appears to exert far-reaching effects on the microenvironment of ischemic tissue, enabling faster and more complete recovery from vascular occlusion.

Visual and Quantitative Assessment of Coronary Stenoses at Angiography Versus Fractional Flow Reserve: The Impact of Risk Factors.

BACKGROUND: The correlation between angiographic assessment of coronary stenoses and fractional flow reserve (FFR) is weak. Whether and how risk factors impact the diagnostic accuracy of angiography is unknown. We sought to evaluate the diagnostic accuracy of angiography by visual estimate and by quantitative coronary angiography when compared with FFR and evaluate the influence of risk factors (RF) on this accuracy. METHODS AND RESULTS: In 1382 coronary stenoses (1104 patients), percent diameter stenosis by visual estimation (DSVE) and by quantitative coronary angiography (DSQCA) was compared with FFR. Patients were divided into 4 subgroups, according to the presence of RFs, and the relationship between DSVE, DSQCA, and FFR was analyzed. Overall, DSVE was significantly higher than DSQCA (P<0.0001); nonetheless, when examined by strata of DS, DSVE was significantly smaller than DSQCA in mild stenoses, although the reverse held true for severe stenoses. Compared with FFR, a large scatter was observed for both DSVE and DSQCA. When using a dichotomous FFR value of 0.80, C statistic was significantly higher for DSVE than for DSQCA (0.712 versus 0.640, respectively; P<0.001). C statistics for DSVE decreased progressively as RFs accumulated (0.776 for ≤1 RF, 0.750 for 2 RFs, 0.713 for 3 RFs and 0.627 for ≥4 RFs; P=0.0053). In addition, in diabetics, the relationship between FFR and angiographic indices was particularly weak (C statistics: 0.524 for DSVE and 0.511 for DSQCA). CONCLUSIONS: Overall, DSVE has a better diagnostic accuracy than DSQCA to predict the functional significance of coronary stenosis. The predictive accuracy of angiography is moderate in patients with ≤1 RFs, but weakens as RFs accumulate, especially in diabetics.

Assessment of microvascular endothelial function in type 1 diabetes using laser speckle contrast imaging.

OBJECTIVE: To test whether laser speckle contrast imaging (LSCI) coupled with physiological post-occlusive reactive hyperemia (PORH) and pharmacological iontophoresis of acetylcholine (ACh) as local vasodilator stimuli could distinguish between cutaneous microvascular responses of Type 1 Diabetes (T1DM)'s patients with endothelial dysfunction and that of healthy controls. METHODS: Patients with T1DM aged ≥12years completed a clinical-epidemiological questionnaire. Data detailing patients' such as daily insulin dose, duration of diabetes, and use of pharmaceuticals such as antihypertensive drugs and statins that could interfere with endothelial function were obtained. Vascular reactivity was assessed in the forearm by LSCI and PORH at baseline and during iontophoresis of ACh using increasing anodic currents of 30, 60, 90, 120, 150 and 180µA in 10second intervals. RESULTS: This study included 50 patients with T1DM and 30 control subjects. The mean resting flux did not differ between patients and control subjects. T1DM patients exhibited endothelial dysfunction upon challenge with physiological or pharmacological stimuli. The microvascular response to both ACh and PORH (i.e., maximum response at peak and amplitude) were significantly reduced in patients with diabetes compared with control subjects (p<0.001). CONCLUSION: We demonstrated that endothelium-dependent skin microvascular vasodilator responses are significantly impaired in patients with T1DM compared to healthy subjects investigated using LSCI coupled with ACh iontophoresis and PORH. Additionally, we find that LSCI is a promising methodology for studying physiological vascular reactivity in T1DM.

Combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) prospective study. Rationale and design.

BACKGROUND: Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients. METHODS: COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A. CONCLUSION: COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.

Non-invasive vascular assessment in the foot with diabetes: sensitivity and specificity of the ankle brachial index, toe brachial index and continuous wave Doppler for detecting peripheral arterial disease.

BACKGROUND & AIMS: Non-invasive lower limb vascular assessment in people at risk of peripheral arterial disease (PAD) including those with diabetes is crucial. There is evidence that standard assessment techniques such as the ankle-brachial index (ABI) may be less effective in people with diabetes. However there is limited evidence for other frequently used tests including continuous wave Doppler (CWD), and the toe-brachial index (TBI). The aim of this study was to determine the sensitivity and specificity of, ABI, CWD and TBI in a population with, and without diabetes. METHODS: Participants with and without diabetes who met current guidelines for vascular screening were recruited, and CWD waveforms, an ABI and a TBI were obtained from the right lower limb. Diagnostic accuracy was determined using colour duplex ultrasound (CFDU). Receiver operating characteristic curves were calculated. RESULTS: 117 participants were recruited, seventy-two with diabetes and forty-five without diabetes. CWD had the highest sensitivity in people with diabetes (74%) and without (84%). CWD also had the highest specificity in people with diabetes (74%) and without (84%) compared to both TBI and ABI. In participants with diabetes, the ABI was a poor test, area under the curve: 0.58 (p=0.27). CONCLUSIONS: CWD waveform is more likely to detect significant PAD compared to ABI and TBI in people with and without diabetes.

Low-dose CT coronary angiography for assessment of coronary artery disease in patients with type 2 diabetes--a cross-sectional study.

BACKGROUND: Silent coronary artery disease (CAD) is prevalent in type 2 diabetes mellitus (T2DM). Although coronary computed tomography angiography (CCTA) over recent years has emerged a useful tool for assessing and diagnosing CAD it's role and applicability for patients with T2DM is still unclarified, in particular in asymptomatic patients. We aimed to assess the role of CCTA in detecting and characterizing CAD in patients with T2DM without cardiac symptoms when compared to gold standard invasive coronary angiography (ICA). METHODS: This was a cross-sectional analysis of patients with T2DM without symptomatic CAD enrolled in the Asker and Baerum Cardiovascular Diabetes Study who, following clinical examination and laboratory assessment, underwent subsequently CCTA and ICA. RESULTS: In total 48 Caucasian patients with T2DM (36 men, age 64.0 ± 7.3 years, diabetes duration 14.6 ± 6.4 years, HbA1c 7.4 ± 1.1 %, BMI 29.6 ± 4.3 kg/m(2)) consented to, and underwent, both procedures (CCTA and ICA). The population was at intermediate cardiovascular risk (mean coronary artery calcium score 269, 75 % treated with antihypertensive therapy). ICA identified a prevalence of silent CAD at 17 % whereas CCTA 35 %. CCTA had a high sensitivity (100 %) and a high negative predictive value (100 %) for detection of patients with CAD when compared to ICA, but the positive predictive value was low (47 %). CONCLUSIONS: Low-dose CCTA is a reliable method for detection and exclusion of significant CAD in T2DM and thus may be a useful tool for the clinicians. However, a low positive predictive value may limit its usefulness as a screening tool for all CAD asymptomatic patients with T2DM. Further studies should assess the applicability for risk assessment beyond the evaluation of the vascular bed.

Relationship between HgbA1c and myocardial blood flow reserve in patients with type 2 diabetes mellitus: noninvasive assessment using real-time myocardial perfusion echocardiography.

To study the relationship between glycosylated hemoglobin (HgbA1c) and myocardial perfusion in type 2 diabetes mellitus (T2DM) patients, we prospectively enrolled 24 patients with known or suspected coronary artery disease (CAD) who underwent adenosine stress by real-time myocardial perfusion echocardiography (RTMPE). HgbA1c was measured at time of RTMPE. Microbubble velocity (ß min(-1)), myocardial blood flow (MBF, mL/min/g), and myocardial blood flow reserve (MBFR) were quantified. Quantitative MCE analysis was feasible in all patients (272/384 segments, 71%). Those with HgbA1c > 7.1% had significantly lower ßreserve and MBFR than those with HgbA1c ≤ 7.1% (P < 0.05). In patients with suspected CAD, there was a significant inverse correlation between MBFR and HgbA1c (r = -0.279, P = 0.01); however, in those with known CAD, this relationship was not significant (r = -0.117, P = 0.129). Using a MBFR cutoff value > 2 as normal, HgbA1c > 7.1% significantly increased the risk for abnormal MBFR, (adjusted odds ratio: 1.92, 95% CI: 1.12-3.35, P = 0.02). Optimal glycemic control is associated with preservation of MBFR as determined by RTMPE, in T2DM patients at risk for CAD.

Discomfort assessment in peripheral angiography: randomized clinical trial of Iodixanol 270 versus Ioversol 320 in diabetics with critical limb ischemia.

OBJECTIVES: To assess and compare the intra-arterial injection-associated discomfort of iodinated contrast media (CM) and the impact on diagnostic efficacy in diabetics with critical limb ischemia (CLI). BACKGROUND: Arterial revascularization is a mainstay in patients with CLI. Previous diagnostic angiography is a crucial step that can be affected by CM injection discomfort compromising the revascularization results, and it could vary related to the CM agents. METHODS: One hundred forty-eight patients received Iodixanol 270 mg iodine pro ml or Ioversol 320 mg iodine pro ml in a prospective, double-blind, randomized, parallel-group clinical trial. Injection-associated discomfort was assessed by Visual Analogic Scale (VAS). Diagnostic efficacy and safety up to 1 week were evaluated. RESULTS: The incidence of pain has been around 50% of the all population in study, with lesser incidence of pain (25.7% vs 74.3%; P < 0.0001) and of heat sensation (55.4% vs 85.1%; P < 0.0001), after Iodixanol than after Ioversol injection. Discomfort mean score, according to VAS assessment, was less in the Iodixanol group (8.1 ± 15.3) than in the Ioversol group (36.0 ± 29.7), after first injection (P < 0.001) and for all injections (P < 0.001). A significant difference was also observed in favor of Iodixanol (P < 0.001), respect to mean score of discomfort and heat sensation, assessed by the operators after all the CM injections. CONCLUSIONS: Iodixanol caused less frequent and severe discomfort, characterized as pain and heat during intra-arterial administration compared with Ioversol. The pain severity is tightly related to image and diagnosis quality with an impact on the patients for additional injections and larger CM volumes.

Clinical assessment of delayed gastric emptying and diabetic complications using gastric emptying scintigraphy: involvement of vascular disorder.

AIM: Delayed gastric emptying, including gastroparesis, is a common complication in diabetes mellitus. The association between delayed gastric emptying and overall diabetic complications remains to be studied in detail. We analysed this association. METHODS: We performed gastric emptying scintigraphy of (99m) Tc-diethylenetriaminepentaacetic acid in 34 patients with diabetes to measure the gastric emptying half-times (T1/2) of the whole stomach (WS), proximal stomach (PS) and distal stomach (DS). We assessed T1/2, diabetic-related factors and complications. RESULTS: The prevalence of autonomic neuropathy was higher in the group with delayed T1/2 of the WS than in the normal group. Analysis of intima-media thickness (IMT) and ankle brachial pressure index (ABI), which are risk indicators for vascular disorder, showed that IMT of the carotid bulb was greater in the group with delayed T1/2 of the WS than in the normal group (2·41 mm [1·50-2·81] versus 1·40 mm [0·81-2·08], P = 0·015). T1/2 of the WS correlated positively with IMT of the carotid bulb (r = 0·391, P = 0·027) and negatively with ABI (r = -0·389, P = 0·028). These correlations were mainly attributed to PS and were the same in patients without autonomic neuropathy. In seven of nine patients who received scintigraphy again after diabetic treatment, glycosylated haemoglobin (HbA1c) levels decreased and T1/2 of the WS shortened compared with before treatment. CONCLUSION: Vascular disorder, among other cofactors such as autonomic neuropathy, could be involved in the pathophysiology of delayed gastric emptying. Medium- to long-term glycaemic control was associated with gastric emptying.

Combined assessment of baroreflex sensitivity with iodine 123 metaiodobenzylguanidine scintigraphic findings strengthens the power of predictive value for cerebral and cardiovascular events in type 2 diabetic patients.

BACKGROUND: We previously reported that baroreflex sensitivity (BRS) or cardiac iodine 123 metaiodobenzylguanidine ((123)I-MIBG) scintigraphic findings can predict cardiovascular prognosis in type 2 diabetic patients. We therefore tested the hypothesis that the combination of BRS and (123)I-MIBG scintigraphic findings could strengthen the predictive power for major adverse cerebral and cardiovascular events (MACCE). METHODS AND RESULTS: From 1998, we have evaluated both BRS and (123)I-MIBG scintigraphy in 165 type 2 diabetic patients (77 females, 88 males, mean age 59 ± 12 years). Based on the ROC curves, depressed BRS was defined as <5.63 mmHg/s, and enhanced washout ratio (WR) was defined as ≥ 41.4%. Each patient was divided into 3 groups based on the "BRS-MIBG combination score" as follows: 0, patients having both preserved BRS and preserved WR; 1, patients having either depressed BRS or enhanced WR; 2, patients having both depressed BRS and enhanced WR. During the mean of 4.7 ± 2.7 years of follow-up, 19 patients developed MACCE. The MACCE-free ratio was significantly higher in the lower BRS-MIBG combination score group (log-rank 16.41, P=0.0003). Cox proportional hazards regression analysis revealed that BRS-MIBG combination score was independently associated with the incidence of MACCE (hazard ratio 4.06, P=0.0237). CONCLUSIONS: Our results suggest that combined assessment of the BRS and (123)I-MIBG scintigraphic findings is more useful for identifying the type 2 diabetic patients at high risk for MACCE.

US assessment of medial arterial calcification: a sensitive marker of diabetes-related microvascular and macrovascular complications.

PURPOSE: To examine the sensitivity of ultrasonography (US) compared with conventional radiography in detection of lower limb (thigh) medial arterial calcification (MAC) in type 2 diabetic patients and evaluate its association with diabetes-related complications. MATERIALS AND METHODS: The study was approved by the local research ethics committee, and informed written consent was obtained. US was performed in 289 patients with type 2 diabetes mellitus, and MAC severity was assigned a score from 0 to 8. Among the patients, 263 underwent radiographic examinations. All subjects underwent clinical evaluation to detect the presence of diabetes-related complications. RESULTS: US helped detect MAC in more subjects compared with radiography (65.8% vs 12.2%). US helped detect MAC from mild (scores 1-4) to severe (scores 5-8) degrees, while mild degree of MAC was poorly demonstrated with radiography. The incidence of nephropathy, retinopathy, sensory neuropathy, and macrovascular complications increased with the severity of MAC (based on US scoring). With univariate analysis, the presence of MAC was associated with nephropathy (P<.001), retinopathy (P<.001), sensory neuropathy (P=.004), and macrovascular complications (P<.001). After adjustment for potential confounders, the presence of severe MAC was associated with nephropathy, retinopathy, and macrovascular complications, with the odds ratios of 3.4 (95% confidence interval [CI]: 1.53, 7.43; P=.003), 2.6 (95% CI: 1.22, 5.32; P=.013), and 3.8 (95% CI: 1.37, 10.6; P=.01), respectively. CONCLUSION: In type 2 diabetic Chinese patients, US was more sensitive than conventional radiography in the detection of MAC, particularly when the MAC was mild. The presence of severe MAC was associated with diabetic nephropathy, retinopathy, and macrovascular complications. US detection of MAC was a potential early marker to identify diabetes-related complications.

Noninvasive assessment of the prevalence and characteristics of coronary atherosclerotic plaques by multidetector computed tomography in asymptomatic type 2 diabetic patients at high risk of significant coronary artery disease: a preliminary study.

BACKGROUND: There is a need to identify diabetic patients at risk of cardiovascular events before symptom onset. AIMS: To evaluate the prevalence and characteristics of coronary atherosclerotic plaques in asymptomatic type 2 diabetic patients with coronary risk factors but without known coronary artery disease, using multidetector computed tomography. METHODS: High-resolution 40-slice coronary computed tomography was performed prospectively in 42 consecutive type 2 diabetic patients (mean age 62 years; range 50-77 years; 28 men) with over one or more carotid atherosclerotic plaque and no coronary artery disease symptoms. Computed tomography data were evaluated for calcium score and the presence of coronary plaques. Plaque type, distribution, extensive character and obstructive nature were determined per patient for each segment. RESULTS: No plaques were detected in 11 (26.2%) patients. Atherosclerotic plaques were detected in 31 (73.8%) patients. A total of 147 coronary segments with plaque were identified, of which 11 (7.5%) contained hypodense plaques, 28 (19%) mixed plaques and 108 (73.5%) calcified plaques. Hypodense plaques were noted in 4/15 (26.7%) patients without coronary calcifications. Most calcified and hypodense plaques resulted in lumen narrowing of less than 50%; most mixed plaques resulted in lumen narrowing greater than 50%. Obstructive disease was detected in 9/11 patients with a high calcium score (>400). CONCLUSION: This preliminary study demonstrates that a high proportion of asymptomatic type 2 diabetic patients present without coronary plaques detectable by multidetector computed tomography, despite concomitant carotid atherosclerotic lesions. Computed tomography seems to detect a high proportion of plaques compared with conventional angiography in these specific patients.

[Echocardiographic assessment of myocardial function in patients with type 2 diabetes]. / Echokardiograficzna ocean funkcji serca u osób chrorujcych na cukrzyce typu 2.

BACKGROUND: According to the data obtained from the country-wide NATPOL III research, the prevalence of diabetes in Poland stands at 5,6% The objective of the work was to assess the heart function of patients with type 2 diabetes by means of echocardiography. MATERIAL AND METHODS: 106 patients were examined: 44 people with type 2 diabetes (gr D) and 62 healthy subjects, constituting the control group (gr C). Using the criteria of diabetes control, the first group was divided into 2 subgroups: 17 patients with controlled diabetes (gr cD) and 27 patients with uncontrolled diabetes (gr uD). Next, 2 subgroups were formed according to the duration of the disease: 23 patients suffering from diabetes >or= 10 years (gr mD) and 21 people suffering from diabetes < 10 years (gr lD). The examinations of the patients included electrocardiography and assessments of myocardial size and contractibility and diastolic activity of the left ventricle. RESULTS: The echocardiographic examination revealed statistically significant differences between the groups D and C, between the groups mD, lD, and C, and between the groups cD, uD, and C. Moreover, group D additionally exhibited positive linear dependences between the duration of the disease and the diastolic interventricular septum thickness and between the duration of the disease and the mass index of the left ventricle. CONCLUSIONS: Myocardial differences observed in the echocardiographic image of a diabetic compared to a healthy person suggest myocardial dysfunction caused by diabetes. The existing differences between the group with controlled diabetes and the group with uncontrolled diabetes indicate that development of organic complications in diabetic patients can only be slowed down with procedures to normalise carbohydrate and lipid metabolic parameters and the arterial blood pressure.