Influence of angiotensin II and telmisartan on in vivo high-resolution renal arterial impedance in rats.

Angiotensin II (ANGII) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high-resolution renal arterial (RA) impedance. This study examines the effects of ANGII and its type 1 receptor blocker, telmisartan (TELM), on RA impedance. In baroreflex deactivated rats, we measured RA pressure (Pr) and blood flow (Fr) during random ventricular pacing to induce pressure fluctuation at three different mean Pr (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from Fr to Pr. The RA impedance was found to align with a three-element Windkessel model consisting of proximal (Rp) and distal (Rd) resistance and compliance (C). Our study showed Rd reflected the composite characteristics of afferent and efferent arterioles. Rd increased with increasing Pr under the baseline condition with a slope of 1.03 ± 0.21 (× 10-1) min·mL-1. ANGII significantly increased the slope by 0.72 ± 0.29 (× 10-1) min·mL-1 (P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10-1) mmHg·min·mL-1 (P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10-1) mmHg·min·mL-1, whereas it did not affect the slope. In contrast, Rp was less sensitive than Rd to ANGII or TELM, suggesting Rp may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANGII on the dynamics of the renal vasculature.

Postoperative Insulin Dose for Cardiac Artery Bypass Graft and Other Cardiac Surgeries in Patients with Type 2 Diabetes: A Retrospective Study.

Purpose: Recommendations on perioperative glycemic control in cardiac surgery are based on coronary artery bypass graft surgery (CABG), though coronary artery disease and valvular disease are pathologically distinct. We aimed to compare the postoperative insulin requirement between CABG and other cardiac surgeries in type 2 diabetic patients and identify predictive factors for the maximum postoperative insulin dose. Patients and Methods: We retrospectively included 60 Japanese patients with diabetes/glucose intolerance (HbA1c > 37 mmol/mol [5.6%]) who were hospitalized for cardiovascular surgery between April 2017 and March 2019. We categorized the subjects into the CABG and non-CABG groups, and performed subgroup analysis on patients who received postoperative insulin therapy. Results: The CABG group required a significantly higher insulin dose on postoperative days 2, 5, 6, and 7, and a significantly higher maximum postoperative insulin dose (24.6 U vs 9.7 U, P < 0.001) than the non-CABG group. Multivariate linear regression analyses showed that the independent determinants of the maximum postoperative insulin dose were HbA1c and duration of diabetes in the non-CABG group, and HbA1c in the CABG group. Conclusion: CABG had a higher postoperative insulin requirement than other cardiovascular surgeries; early aggressive insulin therapy is indicated, especially for patients with higher HbA1c levels/longer duration of diabetes.

Recurrence Pattern, Treatment Modalities, and Prognostic Factors After Definitive Chemoradiotherapy for Recurrent Esophageal Cancer.

BACKGROUND: Recurrent esophageal cancer (EC) has a poor prognosis. However, the recurrence patterns and therapeutic outcomes after definitive chemoradiotherapy (CRT) are not fully understood. We analyzed survival and prognostic factors associated with post-definitive CRT recurrent EC. METHODS: We retrospectively reviewed 71 consecutive patients with post-definitive CRT EC recurrence between 2008 and 2021 at our institution. Recurrence was locoregional, distant, and combined in 42 (59%), 18 (25%), and 11 (16%) patients, respectively. The median time from definitive CRT to recurrence was 8.3 months. Treatment modalities included local therapy, systemic therapy, and palliative care. Overall survival (OS) after recurrence was analyzed using the Kaplan-Meier and Cox proportional hazards models. RESULTS: The median follow-up time from recurrence was 7.1 months, and the median survival time (MST) was 12.5 months. In the univariate analysis, longer time to recurrence, earlier stage at initial treatment, surgical tolerance at initial diagnosis, treatment modalities, and oligo-recurrence were associated with a better prognosis. The MST of the local therapy, systemic therapy, and palliative care groups were not reached, 11.8 months and 4.1 months, respectively (P < 0.001). In the multivariate analysis, treatment modalities and oligo-recurrence emerged as independent prognostic factors (P < 0.001 and P = 0.009). CONCLUSIONS: Aggressive local therapy should be considered to improve the prognosis for patients with oligo-recurrence and/or indication of local therapy to treat recurrent EC.

Inverse ESPVR Estimation with Singularity Avoidance via Constrained EDPVR Parameter Optimization.

Left ventricular end-systolic elastance Ees, as an index of cardiac contractility, can play a key role in continuous patient monitoring during cardiac treatment scenarios such as drug therapies. The clinical feasibility of Ees estimation remains challenging because most techniques have been built on left ventricular pressure and volume, which are difficult to measure or estimate in the regular ICU/CCU setting. The purpose of this paper is to propose and validate a novel approach to estimate Ees, which is independent of left ventricular pressure and volume. Our methods first derive an analytical representation of Ees as the inverse function of the gradient of the Frank-Starling Curve based on cardiac mechanics. Second, elucidating the mechanism of singularities in the inverse function, we derive multiple conditions in both end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR) parameters to avoid these singularities analytically. Third, we formulate a constrained nonlinear least squares problem to optimize both ESPVR and EDPVR parameters simultaneously to avoid singularities. The effectiveness of the proposed method in avoiding singularities was evaluated in an animal experiment. Compared to the conventional Ees estimation by linear regression, our proposed method reproduced in-vivo hemodynamics more accurately when simulating the estimated Ees variation during drug administration. Our method can be applied using the available data in the regular ICU/CCU setting. The improved clinical feasibility can support not only physicians' decision-making, including adjusting drug dosages in current clinical treatment, but also a closed-loop hemodynamic control system requiring accurate continuous Ees estimation.

Analytical Representation of Four-dimensional Hemodynamics for Drug Therapy Simulation in Acute Heart Failure Treatment.

Acute heart failure imperils multiple organs, including the heart. Elucidating the impact of drug therapies across this multidimensional hemodynamic system remains a challenge. This paper proposes a simulator that analyzes the impact of drug therapies on four dimensions of hemodynamics: left atrial pressure, cardiac output, mean arterial pressure, and myocardial oxygen consumption. To mathematically formulate hemodynamics, the analytical solutions of four-dimensional hemodynamics and the direction of its change are derived as functions of cardiovascular parameters: systemic vascular resistance, cardiac contractility, heart rate, and stressed blood volume. Furthermore, a drug library which represents the multi-dependency effect of drug therapies on cardiovascular parameters was identified in animal experiments. In evaluating the accuracy of our derived hemodynamic direction, the average angular error of predicted versus observed direction was 18.85[deg] after four different drug infusions for acute heart failure in animal experiments. Finally, the impact of drug therapies on four-dimensional hemodynamics was analyzed in three different simulation settings. One result showed that, even when drug therapies were simulated with simple rules according to the Forrester classification, the predicted direction of hemodynamic change matched the expected direction in more than 80% in 963 different AHF patient scenarios. Our developed simulator visualizes the impact of drug therapies on four-dimensional hemodynamics so intuitively that it can support clinicians' decision-making to protect multiple organs.

Abscopal Effect after Stereotactic Body Radiotherapy with Nivolumab for Lung Metastasis of Head and Neck Cancer: A Case Report.

Introduction: The abscopal effect (AE) is a phenomenon, in which radiotherapy exerts an antitumour effect on distant lesions outside the primary irradiated area. Although immune checkpoint inhibitors have been widely studied for their potential to enhance the AE and improve patient outcomes, findings in cases of head and neck cancers remain limited. Case Presentation: We report the case of a 72-year-old man who experienced lung oligoprogression during nivolumab treatment for metastatic hypopharyngeal cancer. Stereotactic body radiotherapy (SBRT) was administered to one of the lung lesions, after which both irradiated and nonirradiated lesions regressed. Upon an 18-month follow-up period after SBRT, the patient showed no disease progression or toxicity, and continued receiving nivolumab therapy. Conclusion: The intent behind presenting this case report was to contribute to the accumulation of evidence regarding the AE in cases of head and neck cancer.

Clinical Outcomes of Radiotherapy for Stage 1 Glottic Carcinoma: Comparing Accelerated Hyperfractionation and Once-daily Fractionation.

BACKGROUND/AIM: Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.4 Gy. PATIENTS AND METHODS: A total of 102 patients with stage 1 GC underwent RT alone between 2007 and 2021, with 43 in the AHF group and 59 in the ODF group. A p-value less than 0.05 was considered to indicate a significant difference. RESULTS: The 5-year LC rate was 98% in the AHF group and 91% in the ODF group (p=0.19). During RT, significantly more patients in the AHF group required opioids due to mucositis than in the ODF group (74% vs. 25%, p<0.001), and the rate of aspiration pneumonia tended to be higher in the AHF group than in the ODF group (7% vs. 0%, p=0.072). CONCLUSION: There was no difference in the LC rate between AHF and ODF for stage 1 GC. Moreover, the AHF group required opioids at a higher rate and tended to have a higher risk of developing aspiration pneumonia.

The efficacy of radiation therapy using the Quad Shot regimen in cutaneous metastasis from parotid gland cancer: A case report.

Cutaneous metastasis from malignant tumors can cause symptoms such as exudates, bleeding, and pain, which remarkably reduce patient's quality of life. Herein, we report a case in which radiation therapy using the Quad Shot regimen was effective in the treatment of cutaneous metastasis from parotid gland cancer.

Successful Preoperative QUAD SHOT for Bulky Parotid Carcinoma: Potential Preoperative Ultra-Hypofractionated Radiotherapy for Conversion Surgery.

QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days. Although this technique has already gained some status as an effective palliative treatment for inoperable head and neck cancer (HNC), its application in other situations has not been given much consideration. Herein, we report a case of a 62-year-old woman who received preoperative QUAD SHOT therapy for poorly differentiated parotid carcinoma. In this case, after two courses of QUAD SHOT plus a standard chemotherapy regimen with pembrolizumab, the patient's inoperable, bulky tumor shrank dramatically and became operable. Best of all, while adequate therapeutic effects were achieved, the patient's time commitment and physical exertion were limited. RT during this period consisted of only eight fractions over 4 days. According to previous reports, the response rate for QUAD SHOT is sufficiently high, and the rate of serious adverse events is quite low. This case asks the question of whether the indications for QUAD SHOT irradiation can be expanded as one of the preoperative interventions undertaken by HNC surgeons to achieve conversion surgery.

System Design for Optimizing Drug Infusions Using Cardiovascular Space Mapping for Acute Heart Failure.

Acute heart failure is caused by various factors and requires multiple drug therapies to remedy underlying causes. Due to the complexity of pharmacologic effects of cardiovascular agents, few studies have theoretically addressed the multidrug optimization problem. This paper proposes a drug infusion system for acute heart failure that controls cardiovascular performance metrics (cardiac output, left atrial pressure, and mean arterial pressure) within desired ranges as dictated by the cardiovascular parameters (systemic vascular resistance, cardiac contractility, heart rate, and stressed blood volume). The key to our system design is modeling and controlling cardiovascular parameters to yield the desired cardiovascular metrics. A 'tailored drug infusion' technique controls parameters by solving the optimization problem in order to conquer the complexity of multi-dependencies and the different dosage limits among multiple drugs. A 'cardiovascular space mapping' technique identifies the desired parameters from the desired metrics by deriving the analytical solutions of the metrics as functions of the parameters. To facilitate clinical discussions, parameters were set to realistic values in 5,600 simulated patients. Our results showed not only that the optimized drug combinations and dosages controlled the cardiovascular metrics to within the desired ranges, but also that they mostly corresponded to the recommended clinical use guidelines. An additional value of our system is that it proactively predicts the limitations of the tailored drug therapy, which supports the clinical decision of pivoting to alternative treatment strategies such as mechanical circulatory support.

Nintedanib-Induced Delayed Mucosal Healing after Adjuvant Radiation in a Case of Oropharyngeal Carcinoma.

Since the launch of imatinib in 2001, tyrosine kinase inhibitors are being used in chemotherapy for a wide range of malignant tumors. Drugs that inactivate multiple molecular mechanisms are called multikinase inhibitors (MKIs). Nintedanib is a type of MKI that inhibits downstream cascades in three systems: vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor inhibitions. It was initially developed as an anticancer drug for non-small-cell lung carcinoma; however, it was also found to inhibit the proliferation of fibroblasts associated with chronic inflammation in the lungs. Therefore, it is being more widely used to treat idiopathic pulmonary fibrosis, a benign disease, than as an antineoplastic agent. Several studies have reported adverse events associated with the concurrent use of MKIs with surgery or radiotherapy. Specifically, there has been a report cautioning against delayed wound healing associated with the use of nintedanib in patients undergoing surgery. However, there is no specific mention of its concurrent use during irradiation. We describe a case of a 72-year-old man with severely delayed recovery from radiation mucositis when nintedanib was being administered for benign disease.

Radiation Myelopathy Caused by Palliative Radiotherapy and Intrathecal Methotrexate.

Radiation myelopathy is a rare, late-stage adverse event that develops following irradiation at or above 50 Gy. Here, we report a case of irreversible paraplegia caused by palliative radiation (20 Gy in 5 fractions) to the spinal cord combined with intrathecal methotrexate (IT-MTX). A 69-year-old man presented with back pain, prompting a diagnosis of acute myeloid leukemia. At the first visit, he complained of muscle weakness and hypoesthesia in both legs; spinal magnetic resonance imaging (MRI) revealed an epidural mass compressing the spinal cord at the fifth to seventh level of the thoracic vertebrae. This was considered to be an extramedullary lesion of leukemia, and he received remission induction therapy including IT-MTX; palliative radiation (20 Gy in 5 fractions) of the epidural mass was initiated the following day. Then, during the course of consolidation therapy, a second IT-MTX was performed after 1 month and a third after 3 months. While the consolidation therapy was complete, yielding remission, he developed sudden paraplegia, as well as bladder and bowel dysfunction (BBD), 10 months later. Spinal MRI showed extensive intramedullary high signal intensity on T2-weighted image, including the irradiation field. It was thought myelopathy was due to irradiation of the spinal cord combined with IT-MTX. He immediately received steroid pulse therapy; however, the paraplegia and BBD did not improve. It is extremely rare for irreversible radiation myelopathy to occur with IT-MTX and palliative radiation to the spinal cord. We believe that even with low-dose palliative radiation, caution is required for combined use with IT-MTX.

Dosimetric Evaluation of the Uterus in Patients Receiving Total Body Irradiation with Ovarian Shielding.

Infertility is a well-known late complication in patients receiving hematopoietic stem cell transplantation (HSCT). We previously reported that total body irradiation (TBI) with ovarian shielding reduces the radiation dose to the ovaries to 2.4 Gy - one-fifth of the dose compared to conventional TBI - and preserves fertility without increasing the risk of relapse. Exposure to the uterus and ovaries can reportedly affect pregnancy and childbirth. However, the dose constraint of the uterus that causes infertility remains unknown. Herein, we report the pregnancy and birth outcomes of 2 patients who gave birth following TBI with ovarian shielding and evaluated the dose to the uterus using a dose-volume histogram. Case 1 involved a 30-year-old woman with acute myeloid leukemia who underwent HSCT at 21 years of age with a uterus mean dose (D mean) of 7.0 Gy. She had a natural pregnancy and elective cesarean section at 38 weeks of gestation due to hypertensive disorders of pregnancy. She gave birth to a normal-birthweight infant. Case 2 involved a 32-year-old woman with T-cell acute lymphoblastic leukemia who underwent HSCT at 30 years of age with a uterus D mean of 7.6 Gy. Her baby was delivered at full term with normal birthweight. These results indicate that a uterus D mean between 7.0 and 7.6 Gy does not have a significant impact on pregnancy and delivery with the ovarian function being preserved for patients who received TBI with ovarian shielding after puberty.

Tonometric Condition of Cellular Polypropylene Film Sensors in Measuring Arterial Pressure Waveform.

Tonometric continuous measurement of arterial pressure becomes feasible using a cellular polypropylene (Cellular PP) film sensor. A pulsatile arterial vascular phantom model was used to find the range of optimal tonometric conditions and the responsiveness to dynamic pressure changes. The optimal tonometric condition was assessed by the correlation coefficient between the hydraulic pressure and the Cellular PP output using two different types of tubes (the latex tube and the hydrogel tube) to simulate arteries. With a setting of the normal blood pressure range, the output of Cellular PP correlated strongly with the level of hydraulic pressure, 0.998 and 0.989 in the latex tube and the hydrogel tube, respectively. For maintaining the optimal tonometric condition, the depressed depths of the latex and the hydrogel tube were less than 1.2 and 0.6 mm, respectively. The phantom model also demonstrated that the Cellular PP sensor followed changes in a hydraulic pressure dynamically under the optimal tonometric conditions. The present results demonstrated the Cellular PP film sensor is applicable to the arterial tonometry in measuring the instantaneous blood pressure while the sensor is adjusted to maintain the minimal flatness of the underlying arterial wall.Clinical Relevance- To understand the physiological characteristics of blood pressure and arterial system, the instantaneous measurement of blood pressure is necessary. The present study suggests that Cellular PP films are applicable to peripheral arteries tonometrically to obtain simultaneously the respective blood pressure waveforms.

Palliative Radiotherapy Provided Good Pain Relief for Painful Adrenal Metastasis.

Adrenal metastases often occur in patients with metastasized lung cancer, but symptoms rarely develop. A 45-year-old man presented with right abdominal pain requiring strong opioids due to large right adrenal metastasis of lung adenocarcinoma. The tumor was 7.3 × 5.6 × 8.4 cm in size. He was treated with palliative radiotherapy (RT) up to 39 Gy in 13 fractions for this lesion without severe adverse effects. After RT, he had good pain relief, and opioids were no longer needed. Palliative RT for a large adrenal tumor can provide a good analgesic effect without relevant toxicity.

The Association Between Taste Impairment and Serum Zinc Concentration in Adult Patients With Type 2 Diabetes.

OBJECTIVES: In this study, we aimed to elucidate the association between taste acuity and serum zinc concentration in patients with type 2 diabetes. METHODS: We enrolled 29 patients who were hospitalized and asked them to attend a 2-week diabetes education program. Fasting blood samples were obtained on the morning of the first day and 2 weeks after hospitalization. The acuity of sweet, salty, sour or bitter taste was evaluated by a filter-paper disc method. Correlations among taste acuity, glycemic control and serum zinc concentration were analyzed using the Spearman rank correlation coefficient. RESULTS: The following parameters (mean ± standard deviation) were improved after 2 weeks' hospitalization: taste acuity (sweet: 3.5±1.0 to 2.9±1.1; salty: 3.3±1.1 to 2.6±1.0; sour: 3.6±1.2 to 2.7±0.8; and bitter: 3.3±1.3 to 2.7±1.1; all p<0.001); glycemic control (fasting plasma glucose, 9.4±3.0 to 7.1±1.8 mmol/L, and glycoalbumin, 26.3±7.7 to 22.7±5.9 %; both p<0.001); and serum zinc concentration (1.2±0.2 to 1.3±0.2 mmol/L; p<0.001). Sour and bitter taste acuity were significantly associated with serum zinc concentration (sour, r=-0.50, p=0.005; bitter, r=-0.40, p=0.033). CONCLUSIONS: Glycemic control, serum zinc concentration and taste acuity were improved after the short-duration education program. Sour and bitter taste acuity were significantly associated with serum zinc concentrations.

Postprandial hyperglycemia was ameliorated by taking metformin 30 min before a meal than taking metformin with a meal; a randomized, open-label, crossover pilot study.

Taking metformin with a meal has been shown to decrease bioavailability of metformin. We hypothesized that taking metformin 30 min before a meal improves glucose metabolism. As an animal model, 18 Zucker-rats were divided into three groups as follows: no medication (Control), metformin (600 mg/kg) with meal (Met), and metformin 10 min before meal (pre-Met). In addition, five diabetic patients were recruited and randomized to take metformin (1000 mg) either 30 min before a meal (pre-Met protocol) or with a meal (Met protocol). In the animal model, the peak glucose level of pre-Met (7.8 ± 1.5 mmol/L) was lower than that of Control (12.6 ± 2.5 mmol/L, P = 0.010) or Met (14.1 ± 2.9 mmol/L, P = 0.020). Although there was no statistical difference among the three groups, total GLP-1 level at t = 0 min of pre-Met (7.4 ± 2.7 pmol/L) tended to be higher than that of Control (3.7 ± 2.0 pmol/L, P = 0.030) or Met (3.9 ± 1.2 pmol/L, P = 0.020). In diabetic patients, the peak glucose level of pre-Met protocol (7.0 ± 0.4 mmol/L) was lower than that of Met protocol (8.5 ± 0.9 mmol/L, P = 0.021). Total GLP-1 level at t = 30 min of pre-Met protocol (11.0 ± 6.1 pmol/L) was higher than that of Met protocol (6.7 ± 3.9 pmol/L, P = 0.033). Taking metformin 30 min before a meal ameliorated postprandial hyperglycemia. This promises to be a novel approach for postprandial hyperglycemia.

Triglycerides to high-density lipoprotein cholesterol ratio is an independent predictor of incident fatty liver; a population-based cohort study.

BACKGROUND: Triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been recommended for surrogates of insulin resistance. However, it remains to be elucidated the association between TG/HDL-C and incident fatty liver. AIMS: To investigate the association between TG/HDL-C and incident fatty liver. METHODS: We performed population-based historical cohort study consisted with 4518 healthy Japanese who received yearly health-checkup programmes over decade. Fatty liver was diagnosed using ultrasonography. RESULTS: During the observation periods, 38.8% (case/N = 1023/2637) of men and 17.2% (case/N = 324/1881) of women developed fatty liver. Adjusting odds ratio of TG/HDL-C for incident fatty liver were 1.59 (95% confidence interval (CI) 1.42-1.79, P < 0.0001) in men and 2.50 (95% CI 1.80-3.51, P < 0.0001) in women. In addition, adjusting odds ratio of TG/HDL-C for incident non-alcoholic fatty liver disease were 1.55 (95% CI 1.35-1.77, P < 0.0001) in men and 2.72 (95% CI 1.88-3.95, P < 0.0001) in women. According to the receiver operator characteristic (ROC) analysis, the optimal cut-off point of TG/HDL-C for incident fatty liver was 0.88 (area under the ROC curve (AUC) 0.67 [95% CI 0.65-0.69], sensitivity = 0.64, specificity = 0.60, P < 0.0001) in men and 0.64 (AUC 0.69 [95% CI 0.66-0.72], sensitivity = 0.50, specificity = 0.78, P < 0.0001) in women. CONCLUSIONS: The TG/HDL-C could predict the incident fatty liver. Thus, it is important to check TG/HDL-C and lifestyles modification is needed for preventing future fatty liver disease in patients with high TG/HDL-C.

The inter-arm difference in systolic blood pressure is a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.

Recent studies have suggested that the inter-arm blood pressure difference (IAD) is associated with cardiovascular events and mortality. The aim of this study was to assess whether the IAD could be a marker for subclinical atherosclerosis in patients with type 2 diabetes who are at high risk of cardiovascular disease (CVD). In a cross-sectional retrospective study of 206 Japanese patients with type 2 diabetes aged 49-76 years, we examined the correlation of the IAD with the carotid intima-media thickness (IMT), ankle-brachial index (ABI) or cardio ankle vascular index (CAVI). The IAD was positively correlated with the maximum IMT (r=0.266, P<0.0001), mean IMT (r=0.209, P=0.00726) or CAVI (r=0.240, P=0.0005). The IAD was higher in patients with CVD than in those without (P=0.0020). A multiple linear regression analysis demonstrated that the IAD was an independent determinant of maximum IMT (ß=0.169, P=0.0167), mean IMT (ß=0.178, P=0.0153), ABI (ß=-0.222, P=0.0033) or CAVI (ß=0.213, P=0.0011) after adjusting for known risk factors. The area under the receiver operating characteristic curve (AUC) of the IAD as a predictor of subclinical atherosclerosis was similar to the AUC of the Framingham 10-year coronary heart disease risk score. In conclusion, the IAD could be a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.