Assessment of arterial stiffness in paediatric patients with type 1 diabetes mellitus.

AIMS: To investigate early indicators of cardiovascular disease (CVD) in children and adolescents with type 1 diabetes mellitus (T1DM), focusing on pulse wave velocity (PWV) and its associations with various anthropometric and glycemic parameters. PATIENTS AND METHODS: A total of 124 children and adolescents with T1D (mean age 10.75 ± 3.57 years) were included in this cross-sectional study. Anthropometric data, including height, weight, body mass index (BMI), glycemic parameters, such as HbA1c and time in range (TIR) were assessed. PWV was assessed by oscillometric method using the Mobil-O-Graph PWA device. Univariate and multivariate linear regression were used to explore the association of PWV z-score with anthropometric, demographic, and glycaemic variables. RESULTS: Significant negative association between PWV and age and height (ß = -0.336, 95 % CI -0.44 to -0.25, p < 0.001 and ß = -0.491, 95 % CI -0.62 to -0.36, p < 0.001, respectively), while gender showed a significant positive association with PWV, with females displaying higher PWV values compared to males (ß = 0.366, 95 % CI 0.17 to 0.56, p < 0.001). TIR was positively associated with PWV (ß = 0.092, 95 % CI 0.01 to 0.16, p = 0.017 only for patients having TIR ≤ 50 %. Finally, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively associated with PWV (ß = 0.086, 95 % CI 0.02 to 0.14, p = 0.007 and ß = 0.152, 95 % CI 0.07 to 0.23, p < 0.001, respectively). CONCLUSION: Youth with T1DM who spend <50 % of time in range exhibit uniquely increased signs of arterial stiffness, indicating that poor glycemic control may contribute to early vascular damage. Differences related to age, gender and height should be considered.

Quantitative model for assessment of lower-extremity perfusion in patients with diabetes.

BACKGROUND: Although diabetic and atherosclerotic vascular diseases have different pathophysiological mechanisms, the screening methods currently used for diabetic lower-extremity vascular diseases are mainly based on the evaluation methods used for atherosclerotic vascular diseases. Thus, assessment of microvascular perfusion is of great importance in early detection of lower-extremity ischemia in diabetes. PURPOSE: This cross-sectional study aimed to develop a quantitative model for evaluating lower-extremity perfusion. METHODS: We recruited 57 participants (14 healthy participants and 43 diabetes patients, of which 16 had lower-extremity arterial disease [LEAD]). All participants underwent technetium-99 m sestamibi (99mTc-MIBI) scintigraphy and ankle-brachial index (ABI) examination. We derived two key perfusion kinetics indices named activity perfusion index (API) and basal perfusion index (BPI). This study was registered in ClinicalTrials.gov (URL: https://www. CLINICALTRIALS: gov, NCT02752100). RESULTS: The estimated limb perfusion values in our lower-extremity perfusion assessment (LEPA) model showed excellent consistency with the actual measured data. Diabetes patients showed reduced lower-extremity perfusion in comparison with the control group (BPI: 106.21 ± 11.99 vs. 141.56 ± 17.38, p < 0.05; API: 12.34 ± 3.27 vs. 14.56 ± 3.12, p < 0.05). Using our model, the reductions in lower-extremity perfusion could be detected early in approximately 96.30% of diabetes patients. Patients with LEAD showed more severe reductions in lower-extremity perfusion than diabetes patients without LEAD (BPI: 47.85 ± 20.30 vs. 106.21 ± 11.99, p < 0.05; API: 7.06 ± 1.70 vs. 12.34 ± 3.27, p < 0.05). Discriminant analysis using API and BPI could successfully screen all diabetes patients with LEAD with a sensitivity of 100% and specificity of 80.77%. CONCLUSIONS: We established a LEPA model that could successfully assess lower-extremity microvascular perfusion in diabetes patients. This model has important application value for the recognition of early-stage LEAD in patients with diabetes.

Progression of Diabetic Complications in Subgroups of People with Long Term Diabetes Type 1 According to Clinical Course.

AIMS: Prevention and prediction of microvascular complications are important aims of medical care in people with type 1 diabetes. Since the course of the disease is heterogenous, we tried to identify subgroups with specific risk profiles for microvascular complications. METHODS: Retrospective analysis of a cohort of 285 people (22637 consultations) with >10 years of type 1 diabetes. Persons were grouped into slow (<15 years), fast (>15 years) and non progressors according to the average onset of microvascular complications. Generalized estimating equations for binary outcomes were applied and pseudo coefficients of determination were calculated. RESULTS: Progression to microvascular disease was associated with age (OR: 1.034 [1.001-1.068]; p=0.04), diabetes duration (OR: 1.057 [1.021-1.094]; p=0.002), HbA1c (OR: 1.035 [1.011-1.060]; p=0.005), BMI (OR: 0.928 [0.866-0.994]; p=0.034) and the social strata index (OR: 0.910 [0.830-0.998]; p=0.046). Generalized estimating equations predicted 31.02% and exclusion of HbA1c marginally reduced the value to 28.88%. The proportion of patients with LADA was higher in fast than slow progressors [13 (26.5%) vs. 14 (11.9%); p=0.019]. A generalized estimating equation comparing slow to fast progressors revealed no significant markers. CONCLUSION: In our analysis, we were able to confirm known risk factors for microvascular disease in people with type 1 diabetes. Overall, prediction of individual risk was difficult, the effect of individual markers minor and we could not find differences regarding slow or fast progression. We therefore emphasis the need for additional markers to predict individual risk for microvascular disease.

Interdisciplinary assessment and diagnostic algorithm: The role of the diabetologist.

In recent years, many studies have revealed the importance of heart failure (HF) development in type 2 diabetes (T2D), which increases the morbidity and mortality during the course of diabetes. In this context, it became important to emphasize the role of both cardiologists and diabetologists in the early diagnosis and further adequate treatment of HF in T2D. While HF appears in two major forms, with reduced or preserved ejection fraction (EF), namely HFrEF and HFpEF, it became important to define the optimal approach to the diagnostics. Regarding HFrEF, the role of cardiological methods remained dominant, while the complexity of early diagnosis requires nowadays more active participation of diabetologists. The absence of abundant symptoms and echocardiographic findings imposed the need for the use of risk markers based on metabolic variables and low-grade inflammation parameters. Following that unmet need, numerous studies have defined the possible relationship between metabolic variables in diabetes and the risk for HF. Moreover, attempts have been made to integrate biochemical and clinical parameters into risk score engines and some of them gave promising results. However, the follow-up studies in T2D subjects are needed to determine the clinical relevance of these new approaches.

Interdisciplinary assessment and diagnostic algorithm: The role of the cardiologist.

Patients with diabetes have an increased risk of developing heart failure and those with heart failure are at higher risk of developing diabetes. In patients with diabetes antidiabetic medications and the metabolic alterations of diabetes increase the risk of developing heart failure. In diabetic patients with heart failure and in those with an increased likelihood of developing the disease a stepwise approach based on the use of natriuretic peptides and echocardiography to rule out the presence of heart failure should be used. Once the diagnosis of heart failure is established it will be important to define the phenotype according to the left ventricular function and, where appropriate, use additional tests to identify possible additional underlying causes of heart failure like coronary artery disease. A multidisciplinary heart failure management programs is recommended in all patients with diabetes mellitus and heart failure to enable appropriate investigations, accurate diagnosis, and appropriate agreed evidence-based therapy and care plan. The implementation of a multidisciplinary heart failure management program requires a multidisciplinary team that will have to follow the patients throughout the whole heart failure trajectory and that should consider a holistic approach to the diabetic patient with heart failure rather than focussing merely on either heart failure or diabetes.

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

Cardiovascular risk assessment by coronary artery calcium score in subjects with maturity-onset diabetes of the young caused by glucokinase mutations.

AIMS: Maturity-Onset Diabetes of the Young (MODY) caused by glucokinase (GCK) mutations is characterized by lifelong mild non-progressive hyperglycemia, with low frequency of coronary artery disease (CAD) compared to other types of diabetes. The aim of this study is to estimate cardiovascular risk by coronary artery calcification (CAC) score in this group. MATERIALS AND METHODS: Twenty-nine GCK-MODY cases, 26 normoglycemic controls (recruited among non-affected relatives/spouses of GCK mutation carriers), and 24 unrelated individuals with type 2 diabetes were studied. Patients underwent CAC score evaluation by computed tomography and were classified by Agatston score ≥ or < 10. Framingham Risk scores of CAD in 10 years were calculated. RESULTS: Median [interquartile range] CAC score in GCK-MODY was 0 [0,0], similar to controls (0 [0,0], P = 0.49), but lower than type 2 diabetes (39 [0, 126], P = 2.6 × 10-5). A CAC score ≥ 10 was seen in 6.9% of the GCK group, 7.7% of Controls (P = 1.0), and 54.2% of individuals with type 2 diabetes (P = 0.0006). Median Framingham risk score was lower in GCK than type 2 diabetes (3% vs. 13%, P = 4 × 10-6), but similar to controls (3% vs. 4%, P = 0.66). CONCLUSIONS: CAC score in GCK-MODY is similar to control individuals from the same family and/or household and is significantly lower than type 2 diabetes. Besides demonstrating low risk of CAD in GCK-MODY, these findings may contribute to understanding the specific effect of hyperglycemia in CAD.

Risk assessment of macrovascular and microvascular events in patients with type 2 diabetes by analyzing the amplitude variation of the fourth harmonic component of radial pulse wave.

This investigation explored the hypothesis that whether the coefficient of variation of the fourth harmonic amplitude of the radial pulse wave (C4CV) predicts the risk of macrovascular and microvascular events in patients with type 2 diabetes mellitus (T2DM). Radial pulse wave and brachial blood pressure were measured at baseline in 2324 patients with T2DM and C4CV was calculated using the Fourier series method. Macrovascular and microvascular events during follow-up were determined by medical records. We plotted the Kaplan-Meier curve and performed a Cox proportional hazard model and a log-rank test to estimate the effectiveness of C4CV as a risk predictor. We divided patients into quartile groups based on C4CV (<4.3%, 4.3% to 6.8%, 6.8% to 11.4%, and >11.4%). Compared with patients with C4CV < 4.3%, patients with C4CV> 11.4% had a double incidence of macrovascular events (hazard ratio, 2.13; 95% CI, 1.70-2.67) and microvascular events (hazard ratio, 2.08; 95% CI, 1.67-2.58), and the incidence of cardiovascular death was three times (hazard ratio, 3.03; 95% CI, 1.10-8.83). The Cox regression analysis demonstrated that the risk of both macrovascular and microvascular outcomes increases with the increase in quartile level of C4CV value (P < 0.0001). These associations remained after adjustment for age, gender, smoking, systolic blood pressure, diastolic blood pressure, dyslipidemia, diabetes duration, Hba1c, and cardiovascular disease (P < 0.0001). C4CV is a novel independent predictor of cardiovascular mortality, macrovascular events, and microvascular events in patients with T2DM.

Lower limb vascular assessment techniques of podiatrists in the United Kingdom: a national survey.

BACKGROUND: Podiatric vascular assessment practices in the United Kingdom (UK) are currently unknown. This study aimed to describe the current practices for performing lower limb vascular assessments by podiatrists in the UK, and, to investigate the effect of practitioner characteristics, including education level and practice setting, on the choice of tests used for these assessments. METHODS: A cross-sectional observational online survey of registered podiatrists in the UK was conducted using SurveyMonkey® between 1st of July and 5th of October 2018. Item content related to: practitioner characteristics, vascular testing methods, barriers to completing vascular assessment, interpretation of vascular assessment techniques, education provision and ongoing management and referral pathways. Descriptive statistics were performed, and multinomial logistic regression analyses were used to determine whether practitioner characteristics could predict the choice of vascular tests used. RESULTS: Five hundred and eighty five participants accessed the online survey. After drop-outs and exclusions, 307 participants were included in the analyses. Comprehensive vascular assessments had most commonly been performed once (15.8%) or twice (10.4%) in the past week. The most common indicators for performing vascular assessment were symptoms of suspected claudication (89.3%), suspected rest pain (86.0%) and history of diabetes (85.3%). The most common barrier to performing vascular assessment was time constraints (52.4%). Doppler examination (72.3%) was the most frequently reported assessment type, with ankle-brachial index (31.9%) and toe brachial index (5.9%) less frequently performed. There were variable interpretations of vascular test results. The most common topic for education was smoking cessation (69.5%). Most participants (72.2%) were confident in determining ongoing management, with the majority referring to the patient's general practitioner (67.6%). Practitioner characteristics did not predict the types of vascular tests performed. CONCLUSION: The majority of vascular assessments currently performed by podiatrists in the UK are inconsistent with UK or international vascular guidelines and recommendations. Despite this, most podiatrists felt confident in diagnosing, referring and managing patients with peripheral arterial disease (PAD), however many felt they needed more education to feel confident to assist patients with PAD to manage their cardiovascular risk factors.

Assessment of the Utility of a Vascular Early Warning System Device in the Assessment of Peripheral Arterial Disease in Patients with Diabetes and Incompressible Vessels.

BACKGROUND: The objective of this study was to assess the ability of a novel, automated Conformité Européenne marked vascular early warning system (VEWS) device to detect peripheral arterial disease in patients with incompressible ankle arteries and non-measurable ankle brachial pressure index (ABPI) secondary to diabetes. METHODS: Recruited patients had diabetes, recent magnetic resonance angiography evidence of peripheral arterial disease (PAD), and incompressible vessels on ABPI. VEWS indices of each leg were automatically calculated by using optical infrared and red sensors applied to the foot, with readings obtained with the subject's leg both flat and elevated. Indices <1.03 and ≤0.94 were considered upper and lower diagnostic cutoff limits for PAD. Bollinger scores were calculated from the magnetic resonance angiography. A Best Bollinger Score (BBS) of <4 was defined as no significant PAD. RESULTS: All patients had tissue loss. Per protocol analysis of 28 limbs in 14 patients: VEWS had a sensitivity of 94% and specificity 20% for the detection of PAD at <1.03 cutoff and sensitivity 89% and specificity 80% at ≤0.94 cutoff. There was a good correlation between the VEWS index and BBS (-0.637; P = 0.0003). CONCLUSION: VEWS is a safe, simple-to-use, promising tool to assist in the diagnosis of PAD in patients with incompressible vessels due to diabetes.

Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial.

OBJECTIVE: We evaluated whether the increasing number of genetic loci for coronary artery disease (CAD) identified in the general population could be used to predict the risk of major CAD events (MCE) among participants with type 2 diabetes at high cardiovascular risk. RESEARCH DESIGN AND METHODS: A weighted genetic risk score (GRS) derived from 204 variants representative of all the 160 CAD loci identified in the general population as of December 2017 was calculated in 5,360 and 1,931 white participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Outcome Reduction With Initial Glargine Intervention (ORIGIN) studies, respectively. The association between GRS and MCE (combining fatal CAD events, nonfatal myocardial infarction, and unstable angina) was assessed by Cox proportional hazards regression. RESULTS: The GRS was associated with MCE risk in both ACCORD and ORIGIN (hazard ratio [HR] per SD 1.27, 95% CI 1.18-1.37, P = 4 × 10-10, and HR per SD 1.35, 95% CI 1.16-1.58, P = 2 × 10-4, respectively). This association was independent from interventions tested in the trials and persisted, though attenuated, after adjustment for classic cardiovascular risk predictors. Adding the GRS to clinical predictors improved incident MCE risk classification (relative integrated discrimination improvement +8%, P = 7 × 10-4). The performance of this GRS was superior to that of GRS based on the smaller number of CAD loci available in previous years. CONCLUSIONS: When combined into a GRS, CAD loci identified in the general population are associated with CAD also in type 2 diabetes. This GRS provides a significant improvement in the ability to correctly predict future MCE, which may increase further with the discovery of new CAD loci.

Management of peripheral arterial disease in diabetes: a national survey of podiatry practice in the United Kingdom.

BACKGROUND: We aimed to investigate podiatry practice in diagnosing peripheral arterial disease (PAD) in diabetes, decision making once PAD is suspected and limitations of referral pathways. METHODS: A survey, comprising 26 questions was distributed to podiatrists across the UK via mailing lists of collaborating organizations including the College of Podiatry (UK). Response rates were estimated based on NHS workforce data. Analysis of responses from the open-ended questions was performed using inductive content analysis. RESULTS: Data from 283 respondents were analyzed. Response rate for all NHS podiatrists across the UK was estimated to be 6%. For the detection of arterial disease only 18.8% (n = 49/260) of participants reported using a full combination of history, pulse palpation, Doppler and ABPI assessment. Self-reported confidence in detecting arterial disease was highest amongst podiatrists who felt they had received adequate training compared to podiatrists who felt they had not (median 85 (IQR 75-90) vs 67 (50-77), respectively; p < 0.001) as well as those who see > 20 diabetic patients per week compared to those who see < 20 (median 80 (IQR 70-90) vs 72 (60-82.8), respectively; p < 0.001). Over one third of respondents (35.8%, n = 93/260) were aware of missed cases of PAD in the past year and 17.5% (n = 38/217) believed that this resulted in an amputation in some cases.The survey highlighted a lack of clarity amongst podiatrists regarding referral guidelines. Additionally, 69% (n = 169/242) reported that their patients had to wait longer than 2-weeks for specialist vascular assessment and 67.6% (n = 54/80) reported similar waits for a Duplex Ultrasound scan. There was a statistically significant variation in DUS waiting time across the UK (X2 (10, N = 80) = 21.59, p = 0.017). Inability to make a direct referral to vascular services and long delays were reported as major limitations of the referral pathway. CONCLUSION: We have identified important targets for further investigation and quality improvement.

Assessment of Conjunctival Microvascular Hemodynamics in Stages of Diabetic Microvasculopathy.

Diabetes impairs the microcirculation and function of various vital tissues throughout the body. The conjunctival microcirculation can be non-invasively imaged and thus enables assessment of microvascular hemodynamics. In this study, alterations in conjunctival microvascular hemodynamics were quantitatively assessed at stages of increasing diabetic microvasculopathy based on diabetic retinopathy (DR). Subjects were categorized into non-diabetic control (C, N = 34), no clinically visible DR (NDR, N = 47), non-proliferative DR (NPDR, N = 45), and proliferative DR (PDR, N = 35). Conjunctival hemodynamic descriptors, namely vessel diameter (D), blood velocity (V), blood flow (Q), wall shear rate (WSR), and wall shear stress (WSS) were measured in arterioles and venules, and compared between DR and C subjects using generalized linear mixed models. In arterioles, V, WSR, and WSS were lower in NDR (P ≤ 0.01). V was lower in NDR than NPDR and PDR subjects (P ≤ 0.02). In venules, D was higher in NDR and NPDR (P ≤ 0.03), while V was lower in PDR (P = 0.04). Venular V and Q were higher in NPDR than PDR subjects (P ≤ 0.04). WSR and WSS were lower in all stages of DR (P ≤ 0.05), suggestive of the potential of WSS as a marker of diabetic microvasculopathy. Quantitative assessment of conjunctival hemodynamics can potentially be useful for evaluation of diabetic microvasculopathy.

Cost-Effectiveness Analysis of the Use of a Prophylactic Antibiotic for Patients Undergoing Lower Limb Amputation due to Diabetes or Vascular Illness in Colombia.

BACKGROUND: The use of a prophylactic antibiotic in an amputation surgery is a key element for the successful recovery of the patient. We aim to determine, from the perspective of the Colombian health system, the cost-effectiveness of administering a prophylactic antibiotic among patients undergoing lower limb amputation due to diabetes or vascular illness in Colombia. METHODS: A decision tree was constructed to compare the use and nonuse of a prophylactic antibiotic. The probabilities of transition were obtained from studies identified from a systematic review of the clinical literature. The chosen health outcome was reduction in mortality due to prevention of infection. The costs were measured by expert consensus using the standard case methodology, and the resource valuation was carried out using national-level pricing manuals. Deterministic sensitivity, scenarios, and probabilistic analyses were conducted. RESULTS: In the base case, the use of a prophylactic antibiotic compared with nonuse was a dominant strategy. This result was consistent when considering different types of medications and when modifying most of the variables in the model. The use of a prophylactic antibiotic ceases to be dominant when the probability of infection is greater than 48%. CONCLUSIONS: The administration of a prophylactic antibiotic was a dominant strategy, which is a conclusion that holds in most cases examined; therefore, it is unlikely that the uncertainty around the estimation of costs and benefits change the results. We recommend creating policies oriented toward promoting the use of a prophylactic antibiotic during amputation surgery in Colombia.

Advances in the non-invasive assessment of vascular dysfunction in metabolic syndrome and diabetes: Focus on endothelium, carotid mechanics and renal vessels.

AIM: The present paper is a selective review on the methodology and clinical significance of techniques to assess specifically endothelial function, carotid mechanics and renal vascular function, particularly in the light of vascular dysfunction in metabolic syndrome and type 2 diabetes. DATA SYNTHESIS: Endothelial dysfunction appears to be earlier detectable in the microcirculation of patients with altered glucose metabolism, while it attains significance in the macrocirculation at more advanced disease stages. Smooth muscle cell dysfunction is now increasingly recognized to play a role both in the development of endothelial dysfunction and abnormal arterial distensibility. Furthermore, impaired glucose metabolism affects carotid mechanics through medial calcification, structural changes in extracellular matrix due to advanced glycation and modification of the collagen/elastin material stiffness. The assessment of renal vascular function by dynamic ultrasound or magnetic resonance imaging has recently emerged as an appealing target for identifying subtle vascular alterations responsible for the development of diabetic nephropathy. CONCLUSIONS: Vascular dysfunction represents a major mechanism for the development of cardiovascular disease in patients with abnormal glucose metabolism. Hence, the currently available non-invasive techniques to assess early structural and vascular abnormalities merit recommendation in this population, although their predictive value and sensitivity to monitor treatment-induced changes have not yet been established and are still under investigation.

The relationship of regional hemoglobin A1c testing and amputation rate among patients with diabetes.

Objective The risk of leg amputation among patients with diabetes has declined over the past decade, while use of preventative measures-such as hemoglobin A1c monitoring-has increased. However, the relationship between hemoglobin A1c testing and amputation risk remains unclear. Methods We examined annual rates of hemoglobin A1c testing and major leg amputation among Medicare patients with diabetes from 2003 to 2012 across 306 hospital referral regions. We created linear regression models to study associations between hemoglobin A1c testing and lower extremity amputation. Results From 2003 to 2012, the proportion of patients who received hemoglobin A1c testing increased 10% (74% to 84%), while their rate of lower extremity amputation decreased 50% (430 to 232/100,000 beneficiaries). Regional hemoglobin A1c testing weakly correlated with crude amputation rate in both years (2003 R = -0.20, 2012 R = -0.21), and further weakened with adjustment for age, sex, and disability status (2003 R = -0.11, 2012 R = -0.17). In a multivariable model of 2012 amputation rates, hemoglobin A1c testing was not a significant predictor. Conclusion Lower extremity amputation among patients with diabetes nearly halved over the past decade but only weakly correlated with hemoglobin A1c testing throughout the study period. Better metrics are needed to understand the relationship between preventative care and amputation.

Possible consequences of regionally based bundled payments for diabetic amputations for safety net hospitals in Texas.

OBJECTIVE: Ongoing health reform in the United States encourages quality-based reimbursement methods such as bundled payments for surgery. The effect of such changes on high-risk procedures is unknown, especially at safety net hospitals. This study quantified the burden of diabetes-related amputation and the potential financial effect of bundled payments at safety net hospitals in Texas. METHODS: We performed a cross-sectional analysis of diabetic amputation burden and charges using publically available data from Centers for Medicare and Medicaid and the Texas Department of Health from 2008 to 2012. Using hospital referral region (HRR)-level analysis, we categorized the proportion of safety net hospitals within each region as very low (0%-9%), low (10%-20%), average (20%-33%), and high (>33%) and compared amputation rates across regions using nonparametric tests of trend. We then used charge data to create reimbursement rates based on HRR to estimate financial losses. RESULTS: We identified 51 adult hospitals as safety nets in Texas. Regions varied in the proportion of safety net hospitals from 0% in Victoria to 65% in Harlingen. Among beneficiaries aged >65, amputation rates correlated to the proportion of safety net hospitals in each region; for example, patients in the lowest quartile of safety net had a yearly rate of 300 amputations per 100,000 beneficiaries, whereas those in the highest quartile had a yearly rate of 472 per 100,000 (P = .007). Charges for diabetic amputation-related admissions varied almost 200-fold, from $5000 to $1.4 million. Using reimbursement based on HRR to estimate a bundled payment, we noted net losses would be higher at safety net vs nonsafety net hospitals ($180 million vs $163 million), representing a per-hospital loss of $1.6 million at safety nets vs $700,000 at nonsafety nets (P < .001). CONCLUSIONS: Regions with a high proportion of safety net hospitals perform almost half of the diabetic amputations in Texas. Changes to traditional payment models should account for the disproportionate burden of high-risk procedures performed by these hospitals.

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.

Integrating Biomarkers and Imaging for Cardiovascular Disease Risk Assessment in Diabetes.

Cardiovascular disease (CVD) risk assessment has changed substantially in recent years. While older guidelines considered diabetes a coronary disease risk equivalent, more recent guidelines recommend risk stratification on the basis of global risk scoring to target intensity of therapy. While patients with diabetes as a whole are at greater risk for CVD events, these patients may also benefit from risk stratification based on circulating biomarkers like high-sensitivity C-reactive protein, high-sensitivity cardiac troponin T, and N-terminal pro-B-type natriuretic peptide, as well as newer imaging modalities (coronary artery calcium, carotid intima-media thickness, and myocardial perfusion imaging). The addition of these CVD risk assessment modalities could play an important role for deciding how aggressive a physician should be with pharmacological therapy. Here, we discuss many of the current recommendations of CVD risk assessment in patients with diabetes including newer modalities for CVD risk assessment.

Hemoglobin A1c Testing and Amputation Rates in Black, Hispanic, and White Medicare Patients.

BACKGROUND: Major (above-knee or below-knee) amputation is a complication of diabetes and is seen more common among black and Hispanic patients. While amputation rates have declined for patients with diabetes in the last decade, it remains unknown if these improvements have equitably extended across racial groups and if measures of diabetic care, such as hemoglobin A1c testing, are associated with these improvements. We set out to characterize secular changes in amputation rates among black, Hispanic, and white patients, and to determine associations between hemoglobin A1c testing and amputation risk. METHODS: We identified 11,942,840 Medicare patients (55% female) with diabetes over the age of 65 years between 2002 and 2012 and followed them for a mean of 6.6 years. Of these, 86% were white, 11.5% were black, and 2.5% were Hispanic. We recorded the occurrence of major amputation and hemoglobin A1c testing during this time period and studied secular changes in amputation rate by race (black, Hispanic, and white). Finally, we examined associations between amputation risk and hemoglobin A1c testing. We measured both the presence of any testing and testing consistency using 3 categories: poor consistency (hemoglobin A1c testing in 0-50% of years), medium consistency (testing in 50-90% of years), and high consistency (testing in >90% of the years in the cohort). RESULTS: Between 2002 and 2012, the average major lower-extremity amputation rate in diabetic Medicare patients was 1.78 per 1,000 per year for black patients, 1.15 per 1,000 per year for Hispanic patients, and 0.56 per 1,000 per year for white patients (P < 0.001). Over the study period, the incidence of major amputation in Medicare patients with diabetes declined by 54%, from 1.15 per 1,000 in 2002 to 0.53 per 1,000 in 2012 (rate ratio = 0.53, 95% CI = 0.51-0.54). The reduction in amputation rate was similar across racial groups: 52% for black patients, 61% for Hispanic patients, and 55% for white patients. In multivariable analysis adjusting for patient characteristics, including race, any use of hemoglobin A1c testing was associated with a 15% decline in amputation risk (hazard ratio, 0.85; 95% CI, 0.83-0.87; P < 0.001). High consistency hemoglobin A1c testing was associated with a 39% decline in amputation (hazard ratio, 0.61; 95% CI, 0.59-0.62; P < 0.0001). CONCLUSIONS: Although more frequent among racial minorities, major lower-extremity amputation rates have declined similarly across black, Hispanic, and white patients over the last decade. Hemoglobin A1c testing, particularly the consistency of testing over time, may be an effective component metric of longitudinal quality measures toward limiting amputation in all races.