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Silvio E Inzucchi

Publications and source records attributed to Silvio E Inzucchi.

At least 19 recordsLinked to original sources
PubMed2025

Cellular Adhesion Molecules and Adverse Outcomes in Chronic Heart Failure: Findings From the DAPA-HF Randomized Clinical Trial.

IMPORTANCE: Vascular cell adhesion molecule 1 (VCAM-1) and intracellular cell adhesion molecule 1 (ICAM-1) are responsible for immune cell-cell interactions. Systemic levels of VCAM-1 are associated with incident heart failure (HF). OBJECTIVES: To determine if VCAM-1 and ICAM-1 levels are associated with progression of established HF. DESIGN, SETTING, AND PARTICIPANTS: Participants enrolled in the biomarker substudy of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) randomized clinical trial had VCAM-1 and ICAM-1 levels measured at baseline and 12 months. The DAPA-HF trial was conducted at 410 sites in 20 countries. Patients with HF and reduced ejection fraction (HFrEF) in New York Heart Association (NYHA) class II to IV with elevated natriuretic peptides were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Data were analyzed from January 2023 to January 2025. INTERVENTIONS: Dapagliflozin, 10 mg, once daily vs placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of a worsening HF event or cardiovascular death. The associations between VCAM-1 and ICAM-1 levels at baseline and the primary outcome, its components, and all-cause death were analyzed using Cox proportional hazards regression models adjusted for known prognostic variables including estimated glomerular filtration rate (eGFR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT), as well as high-sensitivity C-reactive protein. RESULTS: A total of 3051 participants (mean [SD] age, 67.2 [10.5] years; 2386 male [78.2%]) were included in this study. Mean (SD) follow-up time was 17.6 (5.2) months. The median (IQR) baseline VCAM-1 level was 997 (816.7-1218.8) ng/mL. Compared with patients with lower concentrations of VCAM-1, those with higher concentrations of VCAM-1 were older (mean [SD] age T3 vs T1, 69.7&#x2009;[9.7] years vs 64.1&#x2009;[10.7] years; P&#x2009;<&#x2009;.001), in worse NYHA class (T3 vs T1, NYHA class III/IV 35.6% [362 of 1017] vs 26.5% [269 of 1017]; P&#x2009;<&#x2009;.001), and had higher NT-proBNP (median [IQR] T3 vs T1, 2018 [1126-3753] pg/mL vs 1118 [693-1830] pg/mL) and hs-TnT (median [IQR] T3 vs T1, 24.7 [17.1-37.5] ng/L vs 16.6 [11.6-24.9] ng/L) concentrations, and lower eGFR (mean [SD] T3 vs T1, 58.4 [17.6] mL/min/1.73 m2 vs 71.7 [18.0] mL/min/1.73 m2). Patients in tertile 3 of VCAM-1, compared with tertile 1, had the highest risk of each outcome (eg, adjusted hazard ratio [HR] for primary outcome 1.40; 95% CI, 1.11-1.77; P&#x2009;=&#x2009;.004). ICAM-1 level was not associated with an elevated risk of any outcome. The benefit of dapagliflozin vs placebo in reducing the risk of the primary outcome was consistent across VCAM-1 tertiles: HR, 0.76 (95% CI, 0.54-1.06), 0.82 (95% CI, 0.59-1.12), and 0.77 (95% CI, 0.61-0.98) for tertiles 1, 2 and 3, respectively (P for interaction&#x2009;=&#x2009;.93). There was no significant change in VCAM-1 level with dapagliflozin at 52 weeks. CONCLUSIONS AND RELEVANCE: Results of this substudy of the DAPA-HF randomized clinical trial demonstrate that higher VCAM-1 levels, possibly reflecting a distinct inflammatory/immune pathophysiological pathway in HFrEF, were associated with worse outcomes, even after adjustment for conventional prognostic variables. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03036124.

Aged↗
PubMed2006

The potential of myocardial perfusion scintigraphy for risk stratification of asymptomatic patients with type 2 diabetes.

Patients with diabetes, in particular patients with type 2 diabetes, are at a 2- to 4-fold higher risk of cardiovascular mortality compared with their nondiabetic peers. Patients with diabetes are also more likely to have silent ischemia and less likely to survive a myocardial infarction than nondiabetic patients. Recent studies with electron beam computed tomography (EBCT) have shown that subclinical atherosclerosis is common in patients with diabetes, and studies with myocardial perfusion scintigraphy (with single-photon emission computed tomography) or stress echocardiography have demonstrated that between 25% and 50% of asymptomatic diabetic patients have ischemia during exercise or pharmacological stress and that a substantial proportion of these patients go on to develop major cardiovascular events within several years. Clearly, asymptomatic diabetic patients include a subset of individuals at high risk of cardiovascular disease who would benefit from improved risk stratification beyond that possible with risk factor scoring systems alone. Single-photon emission computed tomography, stress echocardiography, and possibly EBCT or multi-slice computed tomography, are emerging as valuable diagnostic tools for identifying asymptomatic diabetic patients who might require early and aggressive intervention to manage their cardiovascular risk.

Algorithms↗
PubMed2006

"Glucometrics"--assessing the quality of inpatient glucose management.

BACKGROUND: For patients with diabetes, the quality of outpatient glycemic control is readily assessed by hemoglobin A1c. In contrast, standardized measures for assessing the quality of blood glucose (BG) management in hospitalized patients are lacking. Because of recent studies demonstrating the benefits of strict glycemic control in critically ill patients, hospitals nationwide are dedicating resources to address this important issue. To facilitate advances in this nascent field, standardized metrics for inpatient glycemic control should be developed and validated. METHODS: We used 1 month of fingerstick BG levels from a general hospital ward to develop and test three analytic models, based on three units of inpatient BG analysis: population (i.e., ward), patient-day, and patient. To assess the effect of the source of blood samples, we repeated these analyses after adding venous plasma glucose levels. Finally, we employed an idealized intensive care unit data set to establish "gold standard" metrics for inpatient glycemic control. RESULTS: Mean and median BG levels and the proportion of BG levels within an "optimal" range (80-139 mg/dL) were similar among the three models, whereas hypoglycemic and hyperglycemic event rates varied considerably. Inclusion of venous glucose levels did not substantially affect the results. Of the three models tested, the patient-day model appears to most faithfully reflect the quality of inpatient glycemic control. Achieving 85% of BG levels within optimal range may be considered gold standard. CONCLUSIONS: If validated elsewhere, these "glucometrics" would permit objective comparisons of inpatient glycemic control among hospitals and patient care units, and would allow institutions to gauge the success of their quality improvement initiatives.

Blood Glucose↗
PubMed2006

"Waste not, want not": determining the optimal priming volume for intravenous insulin infusions.

BACKGROUND: Insulin adsorbs to plastics used for intravenous (IV) tubing. As a result, clinical IV insulin infusion procotols advise an initial priming volume of up to 50 mL, which may be wasteful-especially since most institutions use 100-mL IV solution bags. In this brief report, we sought to determine the optimal priming volume required for clinical IV insulin infusions. METHODS: One hundred units of regular human insulin was dissolved into 100 mL of 0.9% NaCl. Employing a standard polypropylene infusion set, a priming infusion was started. At 10- mL intervals, from 0 to 50 mL, effluent was collected directly into glass vials. After dilution (1:10,000) using a proprietary buffer, insulin concentrations were then measured using a double antibody radioimmunoassay. Twenty individually prepared insulin bags were tested in this manner. RESULTS: Insulin levels without prime were 15.8% [95% confidence interval (CI), 9.1-22.6%] lower than insulin levels following 50 mL of prime (designated as "maximal values"). After a priming volume of 10 mL, insulin adsorption losses fell to a marginally significant 6.6% (95% CI, 0.1-13.1%). Following 20 mL of prime, insulin concentrations were indistinguishable from maximal values (3.4% loss, 95% CI, -0.2% to 7.1%). CONCLUSIONS: For standard IV insulin infusions, a priming volume of 20 mL is sufficient to minimize the effect of insulin adsorption losses to IV lines. Priming volumes exceeding 20 mL are wasteful, increase costs, and generate unnecessary work for nurses and pharmacists.

Adsorption↗
PubMed2006

Improving clinical productivity in the academic setting: a novel incentive plan based on utility theory.

PURPOSE: Academic internal medicine practices face growing challenges to financial viability due to high overhead, competing institutional missions, and suboptimal physician productivity. The authors describe the development of a clinical incentive plan for a group of academic subspecialty physicians at the Dana Clinic, an outpatient setting at Yale School of Medicine, and report on results of the first year's experience under the plan. METHOD: Utility theory was used to assess the risk profile of clinic faculty and identify incentive payments that would optimize faculty benefit or "utility" while minimizing departmental costs. Under the plan, physicians who reached a productivity target based on work Relative Value Units (wRVUs) between October 2003 and November 2004 had overhead costs covered and received a fixed payment to support salary; additional incentive payments were available for those exceeding the target. Physicians failing to reach the target were responsible for their own overhead costs and received no fixed payment. Physician productivity as measured by wRVU per full-time equivalent (FTE) was compared for the year prior to, and the year following, incentive plan introduction. RESULTS: Forty-seven members of eight academic sections were included in the analysis. Median productivity improved by 34%, with 42 of 47 physicians showing improvement. Significant improvements were also noted in collections (62%) and visit volume (23%), and shifts were observed in coding patterns. CONCLUSIONS: The unique threshold-based structure of the incentive plan, as determined through utility theory modeling, as well as permitting physicians to choose how to achieve the wRVU target were key features of its success, resulting in improved productivity without increasing practice resources or faculty salaries.

Costs and Cost Analysis↗
PubMed2005

Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes.

BACKGROUND: The relationship between admission glucose levels and outcomes in older diabetic and nondiabetic patients with acute myocardial infarction is not well defined. METHODS AND RESULTS: We evaluated a national sample of elderly patients (n=141,680) hospitalized with acute myocardial infarction from 1994 to 1996. Admission glucose was analyzed as a categorical (< or =110, >110 to 140, >140 to 170, >170 to 240, >240 mg/dL) and continuous variable for its association with mortality in patients with and without recognized diabetes. A substantial proportion of hyperglycemic patients (eg, 26% of those with glucose >240 mg/dL) did not have recognized diabetes. Fewer hyperglycemic patients without known diabetes received insulin during hospitalization than diabetics with similar glucose levels (eg, glucose >240 mg/dL, 22% versus 73%; P<0.001). Higher glucose levels were associated with greater risk of 30-day mortality in patients without known diabetes (for glucose range from < or =110 to >240 mg/dL, 10% to 39%) compared with diabetics (range, 16% to 24%; P for interaction <0.001). After multivariable adjustment, higher glucose levels continued to be associated with a graded increase in 30-day mortality in patients without known diabetes (referent, glucose < or =110 mg/dL; range from glucose >110 to 140 mg/dL: hazard ratio [HR], 1.17; 95% CI, 1.11 to 1.24; to glucose >240 mg/dL: HR, 1.87; 95% CI, 1.75 to 2.00). In contrast, among diabetic patients, greater mortality risk was observed only in those with glucose >240 mg/dL (HR, 1.32; 95% CI, 1.17 to 1.50 versus glucose < or =110 mg/dL; P for interaction <0.001). One-year mortality results were similar. CONCLUSIONS: Elevated glucose is common, rarely treated, and associated with increased mortality risk in elderly acute myocardial infarction patients, particularly those without recognized diabetes.

Aged↗
PubMed2005

Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study.

BACKGROUND: Insulin-sensitizing drugs of the thiazolidinedione class and metformin are commonly prescribed to treat diabetes in patients with heart failure despite strong warnings from the Food and Drug Administration against this practice. Whether this results in adverse outcomes is unknown. METHODS AND RESULTS: We conducted a retrospective cohort study of 16,417 Medicare beneficiaries with diabetes discharged after hospitalization with the principal discharge diagnosis of heart failure. The association between antidiabetic drug prescriptions and outcomes was assessed in multivariable hierarchical Cox proportional hazards models, with adjustment for patient, physician, and hospital variables and accounting for the clustering of patients within hospitals. The primary outcome of the study was time to death due to all causes. Secondary outcomes included time to readmission for all causes or for heart failure. Crude 1-year mortality rates were lower among the 2226 patients treated with a thiazolidinedione (30.1%) or the 1861 treated with metformin (24.7%) compared with that among the 12,069 treated with neither insulin-sensitizing drug (36.0%, P= or <0.0001 for both comparisons). In multivariable models, treatment with the thiazolidinediones (hazard ratio [HR] 0.87, 95% CI 0.80 to 0.94) or metformin (HR=0.87, 95% CI 0.78 to 0.97) was associated with significantly lower risks of death. There was no association with treatment with sulfonylureas (HR=0.99, 95% CI 0.91 to 1.08) or insulin (HR=0.96, 95% CI 0.88 to 1.05) and mortality. Admissions for all causes did not differ with either insulin sensitizer. There was a higher risk of readmission for heart failure with thiazolidinedione treatment (HR 1.06, 95% CI 1.00 to 1.09) and a lower risk with metformin treatment (HR 0.92, 95% CI 0.92 to 0.99). CONCLUSIONS: This observational study suggests that thiazolidinediones and metformin are not associated with increased mortality and may improve outcomes in older patients with diabetes and heart failure. Randomized trials are warranted to corroborate these findings.

Aged↗
PubMed2005

Prevalence of abnormal glucose tolerance following a transient ischemic attack or ischemic stroke.

BACKGROUND: Despite current preventive therapies, patients with transient ischemic attack (TIA) and ischemic stroke remain at high risk for recurrent brain disease and cardiovascular events. In an effort to develop new therapies, abnormal glucose tolerance has recently been proposed as an interventional target. Among persons not otherwise known to be diabetic, impaired glucose tolerance (IGT) and diabetic glucose tolerance (DGT) are each associated with an increased risk for incident vascular disease, vascular disease mortality, and all-cause mortality. We conducted this study to determine if IGT and DGT are sufficiently common among patients with TIA and ischemic stroke to warrant therapeutic trials of antihyperglycemic agents. METHODS: Men and women older than 45 years were recruited from 3 hospitals in south central Connecticut. Eligibility criteria included a recent TIA or nondisabling ischemic stroke, no history of physician-diagnosed diabetes mellitus, and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). After an overnight fast, subjects were admitted to a clinical research center for a standard 75-g oral glucose tolerance test. Impaired glucose tolerance was defined by a 2-hour plasma glucose value of 140 to 199 mg/dL (7.8-11.0 mmol / L) and DGT by a value of 200 mg/dL or greater (> or =11.1 mmol/L). RESULTS: Between June 2000 and August 2003, we enrolled 98 eligible patients. The average time from TIA or stroke to measurement of glucose tolerance was 105 days (range, 24-180 days) and the median age was 71 years. Twenty-seven subjects (28%) had IGT and 24 (24%) had diabetes. In a forward stepwise logistic regression model, only a fasting plasma glucose level of 110 mg/dL or greater (> or =6.1 mmol / L) and lower waist circumference were associated with an increased risk for IGT or DGT. CONCLUSIONS: Impaired glucose tolerance and DGT are present in most persons with a recent TIA or ischemic stroke who have no history of diabetes and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). Our findings bring new urgency to the initiation of research to examine the effectiveness of antihyperglycemic therapies among patients with cerebrovascular disease and abnormal glucose tolerance.

Age Distribution↗
PubMed2005

The prevention of type 2 diabetes mellitus.

With a worldwide pandemic of type 2 diabetes upon us, it is imperative that effective and practical preventive strategies be developed for this disease which, once established, carries with it excess morbidity and mortality. This article reviews recently published data on the prevention of type 2 diabetes and compares the demonstrated effectiveness of each strategy, including lifestyle modification and several pharmacologic agents. Although much new information is available, many translational questions remain that chiefly concern the generalizability and applicability of these programs to clinical practice. Recent diabetes prevention guidelines are discussed, and a practical framework for their implementation is presented.

Adult↗
PubMed2005

Insulin-sensitizing antihyperglycemic drugs and mortality after acute myocardial infarction: insights from the National Heart Care Project.

OBJECTIVE: Thiazolidinediones (TZDs) and metformin are insulin-sensitizing antihyperglycemic agents with reported benefits on atherosclerosis. Despite extensive use in patients with diabetes and cardiovascular disease, there is a paucity of outcomes data with metformin and none yet with TZDs. We sought to determine the impact of these insulin sensitizers on outcomes in diabetic patients after hospitalization with acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of 24,953 Medicare beneficiaries with diabetes discharged after hospitalization with AMI between April 1998 and March 1999 or July 2000 and June 2001. The independent association between discharge prescription for metformin, TZD, or both agents and outcomes at 1 year was assessed in multivariable Cox proportional hazards models, adjusting for patient, physician, and hospital variables. The primary outcome was time to death within 1 year of discharge; secondary outcomes were time to first rehospitalization within 1 year of discharge for AMI, heart failure, and all causes. RESULTS: There were 8,872 patients discharged on an antihyperglycemic agent, of which 819 were prescribed a TZD, 1,273 metformin, and 139 both drugs. After multivariable analysis, compared with patients prescribed an antihyperglycemic regimen that included no insulin sensitizer, mortality rates were not significantly different in patients treated with either metformin (hazard ratio [HR] 0.92 [95% CI 0.81-1.06]) or a TZD (0.92 [0.80-1.05]) but were lower in those prescribed both drugs (0.52 [0.34-0.82]). The results were similar among patients with heart failure. The prescription of a TZD was associated with a borderline higher risk of all-cause readmission (1.09[1.00-1.20]), predominately due to a higher risk for heart failure readmission (1.17 [1.05-1.30]). CONCLUSIONS: Individually, prescription of insulin-sensitizing drugs is not associated with a significantly different risk of death in older diabetic patients within 1 year following AMI compared with other antihyperglycemic agents. Combined, however, metformin and TZDs may exert benefit. TZD prescription is associated with a higher risk of readmission for heart failure after myocardial infarction.

Administration, Oral↗
PubMed2005

Treatment of diabetes in the elderly. Addressing its complexities in this high-risk group.

Diabetes is becoming increasingly common in the elderly, affecting more than one person in five. In this group, type 2 diabetes is by far the more prevalent form. Despite this major public health concern, evidence-based information specific to older adults with diabetes is surprisingly lacking. Complicating the medical picture, the elderly commonly have a host of comorbidities that can influence diabetes treatment and therapeutic goals. Here, the authors present an overview of therapy, discussing the antidiabetic agents available and their best use in the older population with diabetes.

Aged↗
PubMed2004

Brachial artery reactivity in asymptomatic patients with type 2 diabetes mellitus and microalbuminuria (from the Detection of Ischemia in Asymptomatic Diabetics-brachial artery reactivity study).

Microalbuminuria is a novel atherosclerotic risk factor in patients with type 2 diabetes mellitus (DM) and predicts future cardiovascular events. Endothelial dysfunction and systemic inflammation have been proposed as common links between microalbuminuria and cardiovascular disease. However, no study has assessed the relation between microalbuminuria and vascular dysfunction as measured by brachial artery reactivity (BAR) in DM. We evaluated 143 patients (85 men; mean age 60.0 +/- 6.7 years) with DM (mean duration 8.2 +/- 7.4 years) enrolled in the Detection of Ischemia in Asymptomatic Diabetics study. Subjects were categorized as those with microalbuminuria (ratio of urinary albumin to creatinine 30 to 299 microg/mg creatinine, n = 28) and those with normoalbuminuria (ratio of urinary albumin to creatinine 0 to 29.9 microg/mg creatinine, n = 115). High-resolution ultrasound BAR testing was used to measure endothelium-dependent and endothelium-independent vasodilations. C-reactive protein was measured as a marker of systemic inflammation. Patients with microalbuminuria and normoalbuminuria had similar baseline characteristics, with the exception that those with microalbuminuria had a longer duration of DM (p = 0.03). Endothelium-dependent vasodilation at 1 minute (p = 0.01) and endothelium-independent vasodilation at 3 minutes (p = 0.007) were significantly less in patients with microalbuminuria. In addition, 96% of patients with microalbuminuria and 76% of those with normoalbuminuria had impaired endothelium-dependent vasodilation (<8%, p = 0.01). Microalbuminuria was an independent predictor of endothelium-dependent vasodilation in the entire cohort (p = 0.045) and after excluding patients on hormone replacement therapy (p = 0.01). Levels of C-reactive protein were significantly higher in patients with microalbuminuria than in those with normoalbuminuria (p = 0.02). We conclude that in DM the presence of microalbuminuria is associated with impaired endothelium-dependent and endothelium-independent vasodilations of the brachial artery and a higher degree of systemic inflammation. In addition, microalbuminuria is an independent predictor of endothelial dysfunction in asymptomatic patients with DM, especially in the absence of hormone replacement therapy.

Age Factors↗