Relationship of glycemic control, exogenous insulin, and C-peptide levels to ischemic heart disease mortality over a 16-year period in people with older-onset diabetes: the Wisconsin Epidermologic Study of Diabetic Retinopathy (WESDR)

OBJECTIVE - the purpose of this study was to examine the relationship of glycemic control and exogenous and endogenous insulin levels with all-cause and cause-specific mortality (ischemic heart disease and stroke) in an older-onset diabetic population.RESEARCH DESIGN and METHODS - the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) is an ongoing, prospective, population-based cohort study of individuals with diabetes first examined in 1980-1982. A stratified sample of all individuals with diabetes diagnosed at 30 years of age or older was labeled older-onset (n = 1,370). Those participating in the 1984-1986 examination phase (n = 1,007) were included in the analysis. Endogenous insulin was determined by measurements of plasma C-peptide (in nanomoles per liter), and exogenous insulin was calculated in units per kilogram per day. Glycemic control was determined by levels of glycosylated hemoglobin (HbA(1)).RESULTS - After 16 years of follow-up, 824 individuals died (all-cause mortality); 358 deaths involved ischemic heart disease and 137 involved stroke. C-peptide and HbA(1) were significantly associated with all-cause and ischemic heart disease mortality in our study. the hazard ratio (95% CI) values for all-cause mortality were 1.12 (1.07-1.17) per 1% increase in HbA, 1.20 (0.85-1.69) per 1 unit . kg(-1) - day(-1) increase in exogenous insulin, and 1.15 (1.04-1.29) per 1 nmol/l increase in C-peptide and for ischemic heart disease mortality were 1.14 (1.06-1.22), 1.50 (0.92-2.46), and 1.19 (1.02-1.39) for HbA(1), exogenous insulin, and C-peptide, respectively, after adjusting for relevant confounders. C-peptide was associated with stroke mortality only among men (1.65 [1.07-2.53]).CONCLUSIONS - Our results show that individuals with higher endogenous insulin levels are at higher risk of all-cause, ischemic heart disease, and stroke mortality.Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USAUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Severe hypoglycemia and smoking in a long-term type 1 diabetic population - Wisconsin Epidemiologic Study of Diabetic Retinopathy

OBJECTIVE - the purpose of this study was to evaluate the relationship of severe hypoglycemia and smoking in a population-based cohort of individuals with long-term type 1 diabetes.RESEARCH DESIGN and METHODS - This was a cross-sectional analysis of the population-based cohort of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. the analyses in this report were limited to 537 type 1 diabetic individuals with complete data who participated in the last examination phase (2000-2001). Severe hypoglycemia was defined as having one or more episodes of loss of consciousness or overnight hospitalization attributable to hypoglycernia in a 1-year period before the examination.RESULTS - the prevalence of severe hypoglycemia in this population was 14.3%. in univariate analysis, current snickers had a greater chance of having severe hypoglycemia compared with never smokers (odds ratio 2.40 [95% CI 1.30-4.401). When we controlled for relevant confounders such as age, sex, AIC, waist-to-hip ratio, orthostatic hypotension, alcohol consumption, intensive insulin treatment, past history of severe hypoglycemia, and late complications of diabetes (nephropathy, neuropathy, and retinopathy), the association remained statistically significant, with current smoking presenting similar to 2.6 times greater odds of developing severe hypoglycernia.CONCLUSIONS - Current smokers with type 1 diabetes have higher odds of severe hypoglycemia episodes.Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Cardiac CT Improves Outcomes in Stable Coronary Heart Disease: Results of Recent Clinical Trials

Purpose of Review The purpose of this study was to review the recent randomised controlled trials of coronary computed tomography angiography (CCTA) for patients with stable coronary artery disease. Recent Findings The initial results and subsequent papers from the SCOT-HEART (Scottish COmputed Tomography of the HEART) and PROMISE (PROspective Multicentre Imaging Study for Evaluation of chest pain) trials have shown that CCTA is a safe and appropriate addition to standard care or alternative to functional testing. The SCOT-HEART study showed that CCTA changes diagnoses, improves diagnostic certainty, changes management, leads to more appropriate use of invasive coronary angiography, and reduces fatal and non-fatal myocardial infarction. A meta-analysis of the four randomised controlled trials showed that CCTA leads to a major reduction in myocardial infarction in patients with stable chest pain. Summary CCTA is now an established technique for the assessment of coronary artery disease. Recent ‘test and treat’ randomised controlled trials have shown that CCTA guided changes in management can improve clinical outcomes

The updated NICE guidelines: Cardiac CT as 1st line test for coronary artery disease

Purpose of Review Cost-effective care pathways are integral to delivering sustainable healthcare programmes. Due to the overestimation of coronary artery disease using traditional risk tables, non-invasive testing has been utilised to improve risk stratification and initiate appropriate management to reduce the dependence on invasive investigations. In line with recent technological improvements, cardiac CT is a modality that offers a detailed anatomical assessment of coronary artery disease comparable to invasive coronary angiography. Recent Findings The recent publication of the National Institute for Health and Care Excellences (NICE) Clinical Guideline 95 update assesses the performance and cost utility of different non-invasive imaging strategies in patients presenting with suspected anginal chest pain. The low cost and high sensitivity of cardiac CT makes it the non-invasive test of choice in the evaluation of stable angina. This has now been ratified in national guidelines with NICE recommending cardiac CT as the first-line investigation for all patients presenting with chest pain due to suspected coronary artery disease. Additionally, randomised controlled trials have demonstrated that cardiac CT improves diagnostic certainty when incorporated into chest pain pathways. Summary NICE recommend cardiac CT as the first-line test for the evaluation of stable coronary artery disease in chest pain pathways

Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: The pilot phase of a randomised controlled trial

Summary: Background Preoperative (neoadjuvant) chemotherapy and radiotherapy are more eff ective than similar postoperative treatment for oesophageal, gastric, and rectal cancers, perhaps because of more eff ective micrometastasis eradication and reduced risk of incomplete excision and tumour cell shedding during surgery. The FOxTROT trial aims to investigate the feasibility, safety, and effi cacy of preoperative chemotherapy for colon cancer. Methods In the pilot stage of this randomised controlled trial, 150 patients with radiologically staged locally advanced (T3 with ≥5 mm invasion beyond the muscularis propria or T4) tumours from 35 UK centres were randomly assigned (2:1) to preoperative (three cycles of OxMdG [oxaliplatin 85 mg/m², l-folinic acid 175 mg, fl uorouracil 400 mg/m² bolus, then 2400 mg/m² by 46 h infusion] repeated at 2-weekly intervals followed by surgery and a further nine cycles of OxMdG) or standard postoperative chemotherapy (12 cycles of OxMdG). Patients with KRAS wild-type tumours were randomly assigned (1:1) to receive panitumumab (6 mg/kg; every 2 weeks with the fi rst 6 weeks of chemotherapy) or not. Treatment allocation was through a central randomisation service using a minimised randomisation procedure including age, radiological T and N stage, site of tumour, and presence of defunctioning colostomy as stratifi cation variables. Primary outcome measures of the pilot phase were feasibility, safety, and tolerance of preoperative therapy, and accuracy of radiological staging. Analysis was by intention to treat. This trial is registered, number ISRCTN 87163246. Findings 96% (95 of 99) of patients started and 89% (85 of 95) completed preoperative chemotherapy with grade 3–4 gastrointestinal toxicity in 7% (seven of 94) of patients. All 99 tumours in the preoperative group were resected, with no signifi cant diff erences in postoperative morbidity between the preoperative and control groups: 14% (14 of 99) versus 12% (six of 51) had complications prolonging hospital stay (p=0·81). 98% (50 of 51) of postoperative chemotherapy patients had T3 or more advanced tumours confi rmed at post-resection pathology compared with 91% (90 of 99) of patients following preoperative chemotherapy (p=0·10). Preoperative therapy resulted in signifi cant downstaging of TNM5 compared with the postoperative group (p=0·04), including two pathological complete responses, apical node involvement (1% [one of 98] vs 20% [ten of 50], p<0·0001), resection margin involvement (4% [ four of 99] vs 20% [ten of 50], p=0·002), and blinded centrally scored tumour regression grading: 31% (29 of 94) vs 2% (one of 46) moderate or greater regression (p=0·0001). Interpretation Preoperative chemotherapy for radiologically staged, locally advanced operable primary colon cancer is feasible with acceptable toxicity and perioperative morbidity. Proceeding to the phase 3 trial, to establish whether the encouraging pathological responses seen with preoperative therapy translates into improved long-term oncological outcome, is appropriate

Postural blood pressure changes and associated factors in long-term Type 1 diabetes: Wisconsin Epidemiologic Study of Diabetic Retinopathy

Purpose: To describe the frequency of orthostatic hypotension and hypertension and associations with risk factors in a cohort of persons with long-term Type 1 diabetes (n-440) participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Methods:);Evaluations included detailed medical history, electrocardiography (FCG), and laboratory tests. Blood pressure (BP) was measured in supine and standing positions. Standing decrease in systolic (SBP) or diastolic (DBP) BP of at least 20 or 10 mmHG, respectively, was defined as orthostatic hypotension; increase of SBP from 140 mmHg or DBP from 90 mmHg was defined as orthostatic hypertension. Results: Prevalence of orthostatic hypotension and orthostatic hypertension was 16.1% and 15.2%, respectively. Some ECG measurements of cardiac autonomic dysfunction were significantly associated with orthostatic hypotension. Association between SBP and orthostatic hypotension and orthostatic hypertension were significant [odds ratio, 1.02 (95% confidence interval, or CI, 1.01 1.05) and 1.02 (95% CI, 1.01 1.04), per 1 mmHg, respectively] after adjusting for confounders. Interaction between SBP and age was observed. SBP was significantly associated with orthostatic hypotension and orthostatic hypertension in people <= 40 years old [1.35 (1.02 1.78) and 1.12 (1.05-1.18), respectively]. Conclusions: Results showed that measurements derived from the ECG can help describe an individual at increased risk of having postural BP changes. Moreover, SBP was associated with postural BP changes among individuals who were <40 years of age with long-term Type I diabetes. (C) 2009 Elsevier Inc. All rights reserved.National Institutes of Health, Bethesda, MDMentor-Based Postdoctoral Fellowship AwardUniv Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilNational Institutes of Health, Bethesda, MD: EY015117Web of Scienc

Retinopathy and survival in a population without diabetes the beaver dam eye study

Retinopathy is relatively common in nondiabetic populations, and its long-term prognostic implications are not certain. for this reason, the authors hypothesized that retinal alterations were associated with all-cause and cause-specific mortality in nondiabetic individuals participating in the Beaver Dam Eye Study in Wisconsin. Included in the analysis were 4,294 nondiabetic subjects aged 43-84 years examined at baseline (1988-1990). Retinopathy was classified into four groups by using retinal photographs: 1) no retinopathy, 2) presence of retinal hemorrhages only, 3) presence of retinal microaneurysms only, and 4) presence of moderate or worse retinopathy. the authors analyzed survival during 14 years of follow-up and in 5-year intervals by using time-varying covariates. Baseline prevalence of retinopathy was 7.7%. Adjusting for age, sex, and significant confounders, they observed that moderate retinopathy at baseline was associated with all-cause (hazard ratio = 1.76, 95% confidence interval: 1.16, 2.69) and ischemic heart disease (hazard ratio = 3.17, 95% confidence interval: 1.73, 5.78) mortality after 14 years of follow-up. in the 5-year-interval analysis, the presence of hemorrhages only was significantly related to increased all-cause (hazard ratio = 1.49, 95% confidence interval: 1.05, 2.12) and ischemic heart disease (hazard ratio = 2.43, 95% confidence interval: 1.48, 4.01) mortality. Study results suggest that retinal changes have possible prognostic implications regarding survival of persons without diabetes.Univ Wisconsin, Madison Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Neuroretinal Rim Area in Diabetes Mellitus

Neuroretinal rim area (NRA) may indicate the amount of viable optic nerve tissue. Changes in the NRA have been found to occur in people with glaucoma. We sought to determine whether there were effects of retinopathy and intraocular pressure (IOP) on NRA in eyes of people with diabetes. Measurements of optic discs and cups were taken from 35-mm stereoscopic slides taken with a Zeiss fundus camera. The photographs were taken during a population-based study. The difference between disc and cup area was taken to be the NRA. Median photographic NRA from 2085 right eyes was 10.5 mm 2 . In younger-and older-onset persons, NRA showed a tendency to increase with age and, inconsistently, with the severity of diabetic retinopathy; it decreased with increasing IOP in older-onset persons not taking insulin. The cohort was reevaluated 4 yr later. NRA increased in all groups. Measurements from photographs taken of a nondiabetic comparison group showed no change over the same interval. These data suggest that NRA may be affected by diabetes. This could be due to nerve swelling. Invest Ophthalmol Vis Sci 31: [805][806][807][808][809]199