Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis.

The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options.

We have the evidence, we need to act to improve diabetes care.

The recent United Nations (UN) Resolution on diabetes sets a precedent by recognising a non-communicable disease, type 2 diabetes mellitus (T2DM), as a serious epidemic requiring urgent steps to improve management and prevent disease development. There is now a wealth of evidence that management of diabetes can be substantially improved by strategies of intensive glycaemic control, and these data must not be ignored. This article reviews this emerging evidence, including results of long-term intervention showing that durable glycaemic control in T2DM is possible. Urgent steps must be taken globally to intensify diabetes treatment as well as to develop rationale to prevent new cases. It is essential that all members of society are made acutely aware of the impending threat that the T2DM epidemic poses to society and that action is taken to control it without delay.

Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal. Recommendations from the Global Partnership for Effective Diabetes Management.

Despite increasingly stringent clinical practice guidelines for glycaemic control, the implementation of recommendations has been disappointing, with over 60% of patients not reaching recommended glycaemic goals. As a result, current management of glycaemia falls significantly short of accepted treatment goals. The Global Partnership for Effective Diabetes Management has identified a number of major barriers that can prevent individuals from achieving their glycaemic targets. This article proposes 10 key practical recommendations to aid healthcare providers in overcoming these barriers and to enable a greater proportion of patients to achieve glycaemic goals. These include advice on targeting the underlying pathophysiology of type 2 diabetes, treating early and effectively with combination therapies, adopting a holistic, multidisciplinary approach and improving patient understanding of type 2 diabetes. Implementation of these recommendations should reduce the risk of diabetes-related complications, improve patient quality of life and impact more effectively on the increasing healthcare cost related to diabetes.

Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal.

Despite increasingly stringent clinical practice guidelines for glycaemic control, the implementation of recommendations has been disappointing, with over 60% of patients not reaching recommended glycaemic goals. As a result, current management of glycaemia falls significantly short of accepted treatment goals. The Global Partnership for Effective Diabetes Management has identified a number of major barriers that can prevent individuals from achieving their glycaemic targets. This article proposes 10 key practical recommendations to aid healthcare providers in overcoming these barriers and to enable a greater proportion of patients to achieve glycaemic goals. These include advice on targeting the underlying pathophysiology of type 2 diabetes, treating early and effectively with combination therapies, adopting a holistic, multidisciplinary approach and improving patient understanding of type 2 diabetes. Implementation of these recommendations should reduce the risk of diabetes-related complications, improve patient quality of life and impact more effectively on the increasing healthcare cost related to diabetes.

Effect of diabetes mellitus and its treatment on ventricular arrhythmias complicating acute myocardial infarction.

AIMS: To evaluate the effect of diabetes mellitus and its treatment on the risk of arrhythmias among early survivors of acute myocardial infarction. RESEARCH DESIGN AND METHOD: The Onset Study was conducted in 64 US medical centres. Between August 1989 and September 1996, 3882 patients were interviewed after having an acute myocardial infarction. We used logistic regression models to examine the association of diabetes and its treatment with the risk of ventricular arrhythmia after adjustment for age, gender, hypertension, thrombolytic therapy, smoking, obesity, cardiac medicines and congestive heart failure. RESULTS: During the index hospitalization, patients with diabetes (n=814) were less likely to develop ventricular arrhythmias than patients without diabetes (6.8 vs. 13.3%, P<0.001). The risk of ventricular arrhythmia in patients treated with first generation sulphonylureas or diet alone was similar to patients without diabetes (OR=0.91; 95% CI, 0.39-2.15, and 0.76; 95% CI, 0.46-1.26, respectively). However, compared with patients without diabetes, the adjusted odds ratio (OR) for ventricular arrhythmias was lower among patients treated with insulin or patients treated with second generation sulphonylureas (OR=0.54, 95% CI 0.32-0.92; OR=0.45, 95% CI 0.27-0.75, respectively). CONCLUSIONS: Compared with patients without diabetes, the risk of ventricular arrhythmias complicating acute myocardial infarction is lower in patients with diabetes treated with second generation sulphonylureas or insulin, but not in those treated with first generation sulphonylureas or diet alone. This suggests that differences in the mechanism of action of different sulphonylureas may result in clinically relevant differences in arrhythmic risk.

C-reactive protein, its role in inflammation, Type 2 diabetes and cardiovascular disease, and the effects of insulin-sensitizing treatment with thiazolidinediones.

Increased concentrations of the marker of inflammation, C-reactive protein (CRP), are associated with insulin resistance, Type 2 diabetes and the development of cardiovascular disease. In particular, inflammation is closely associated with endothelial dysfunction and is recognized as one of the cardiovascular risk factors clustering in the Insulin Resistance Syndrome or Metabolic Syndrome. The exact mechanisms linking insulin resistance and inflammation remain unclear. However, the close association between insulin resistance and inflammation in atherogenesis suggests that therapies that address both parameters may have benefits in reducing diabetes-related macrovascular complications. The thiazolidinedione class of oral anti-diabetic agents are powerful insulin sensitizers that also have anti-inflammatory properties. Treatment with these agents has a range of anti-atherogenic effects, including reduced levels of CRP, plasminogen activator inhibitor-1 (PAI-1), TNF-alpha and reactive oxygen species. Additionally, the insulin-sensitizing effect of thiazolidinediones improves other factors of the Insulin Resistance Syndrome, including dyslipidaemia and hypertension. Outcome studies are underway to determine if the effects of improving insulin sensitivity and reducing inflammation will translate into clinical benefits and reduce the cardiovascular morbidity and mortality associated with insulin resistance and Type 2 diabetes.

Impact of the atherosclerotic process in patients with diabetes.

Between 120 and 140 million people suffer from diabetes mellitus (type 1 and type 2) worldwide, and this number may well double by the year 2025. Patients with diabetes are at increased risk of atherosclerosis and its clinical sequelae: coronary, peripheral vascular, and cerebrovascular diseases. Concurrently, the most common cause of death in persons with diabetes is myocardial infarction. The pathogenesis, progression, and epidemiology of atherosclerotic disease are distinct in patients with diabetes. Atherosclerosis can develop much earlier in life, and at an accelerated rate, compared with non-diabetic individuals. One of the factors responsible for increased atherosclerosis is related to the atherogenic lipid profile in diabetes. The pathobiological processes that are responsible for transforming dormant atherosclerotic plaques into active rupture-prone plaques may be enhanced in diabetes as well. It follows that a major challenge in the treatment of patients with diabetes is to reduce the risk of atherosclerotic disease. The third National Cholesterol Education Program (NCEP) report recently recommended that the management of dyslipidaemia in patients with diabetes should be as aggressive as in those with established coronary heart disease (CHD). The NCEP Adult Treatment Panel III guidelines recommend statins for patients at elevated risk for CHD.

Impact of diabetes on long-term survival after acute myocardial infarction: comparability of risk with prior myocardial infarction.

OBJECTIVE: To determine the effect of diabetes on long-term survival after acute myocardial infarction and to compare its effect with that of a previous myocardial infarction. RESEARCH DESIGN AND METHODS: In a prospective cohort study, we followed 1,935 patients hospitalized with a confirmed acute myocardial infarction at 45 U.S. medical centers between 1989 and 1993, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers performed chart reviews and face-to-face interviews with all patients. We analyzed survival using Cox proportional hazards regression to control for potentially confounding factors. RESULTS: Of the 1,935 patients, 320 (17%) died during a mean follow-up of 3.7 years. A total of 399 patients (21%) had previously diagnosed diabetes. Diabetes was associated with markedly higher total mortality in unadjusted (hazard ratio [HR] 2.4; 95% CI 1.9-3.0) and adjusted (1.7; 1.3-2.1) analyses. The magnitude of the effect of diabetes was identical to that of a previous myocardial infarction. The effect of diabetes was not significantly modified by age, smoking, household income, use of thrombolytic therapy, type of hypoglycemic treatment, or duration of diabetes, but the risk associated with diabetes was higher among women than men (adjusted HRs 2.7 vs. 1.3, P = 0.01). CONCLUSIONS: Diabetes is associated with markedly increased mortality after acute myocardial infarction, particularly in women. The increase in risk is of the same magnitude as a previous myocardial infarction and provides further support for aggressive treatment of coronary risk factors among diabetic patients.

Urgent coronary bypass surgery for failed percutaneous coronary intervention in the stent era: Is backup still necessary?

BACKGROUND: Current practice guidelines for performance of percutaneous coronary intervention (PCI) in the United States mandate availability of on-site surgical backup. With the decreasing frequency of urgent coronary bypass surgery (UCABG) with newer technologies, it is unclear whether such backup continues to be necessary. METHODS: A database of 5655 consecutive patients undergoing PCI at a single center between August 1, 1992, and December 31, 1997, was analyzed. Outcomes were determined as well as clinical, lesion, and procedural characteristics of patients during 4 time periods preceding and during use of coronary stenting. RESULTS: Frequency of UCABG for failed PCI decreased from 2.2% to 0.6% in the most recent time period (P <.01) with no change in incidence of in-hospital death or myocardial infarction. Incidence of stenting progressively increased to 72% in the latest period. Patients requiring UCABG had a higher prevalence of acute coronary syndromes (95%) and type B lesions (79%), but these characteristics were also common in patients who did not undergo UCABG. Although coronary stents were available during the last 3 periods studied, only 30% of UCABG patients had lesions or complications amenable to stenting, and stenting attempts in these patients were all unsuccessful. Despite stenting and use of perfusion balloons and intra-aortic balloon pumps, only 40% of patients having UCABG were stable and pain free on transfer to the operating room. CONCLUSIONS: Although use of UCABG for a failed PCI is currently very low, there are no satisfactory predictors, patients requiring UCABG are frequently clinically unstable, and availability of stenting does not reliably eliminate the need for UCABG or result in a decrease in mortality. This small group of patients continues to require readily available surgical standby.

Age and history of cardiac disease as risk factors for cardiac complications after peripheral vascular surgery in diabetic patients.

OBJECTIVE: To examine the relationship of age and clinical factors to postoperative cardiovascular events in a cohort of diabetic patients undergoing peripheral vascular surgery. PATIENTS AND METHODS: In this cohort study, 316 diabetic patients were followed up prospectively after femoral-to-distal artery bypass surgery. The major end points of the study were all-cause mortality and cardiac morbidity (cardiac events defined as nonfatal myocardial infarction, unstable angina, and congestive heart failure). RESULTS: The overall postoperative cardiac event rate was 17.1% (54/316), with a 7.6% (24/316) rate of postoperative death or nonfatal myocardial infarction. Older diabetic patients (> or = 65 years) had a complication rate of 19.9% (43/216) compared with an 11.0% (11/100) complication rate in younger diabetic patients (< 65 years) (P = .02). Younger diabetic patients with a clinical history of coronary artery disease had an event rate of 18.2% (39/216) compared with an event rate of 2.4% (1/42) in younger diabetic patients without known cardiac disease (P = .02). In contrast, event rates were similar (20.7% [150/208] vs 18.2% [66/108]) in older diabetic patients with or without prior evidence of cardiac disease. CONCLUSION: Advanced age and clinical evidence of coronary artery disease are important determinants of postoperative outcome in diabetic patients undergoing peripheral vascular surgery.

CHD: a major burden in type 2 diabetes.

Patients with type 2 diabetes have a two- to four-fold greater risk of cardiovascular mortality than non-diabetic individuals. In order to prevent coronary events in the diabetic population, it is important to treat modifiable cardiovascular risk factors. Data from the Multiple Risk Factor Intervention Trial (MRFIT) show that serum cholesterol level, systolic blood pressure level and cigarette smoking were significant predictors of cardiovascular disease mortality in men with and without diabetes. At every risk factor level, the absolute risk of age-adjusted coronary death rate was three times greater for diabetic men than non-diabetic men (p<0.0001). Patients with diabetes have an abnormal (dyslipidaemic) lipoprotein profile with high levels of very low density lipoprotein cholesterol and triglycerides, and a low level of high density lipoprotein cholesterol. Although levels of total cholesterol or low density lipoprotein (LDL) cholesterol do not differ significantly between patients with and without diabetes, those with diabetes have higher levels of atherogenic small dense LDL particles. MRFIT data show that at any serum cholesterol level, diabetes confers two-three times the risk for a coronary event. These findings constitute the rationale for considering hypolipaemic therapy, e.g. with HMG-CoA reductase inhibitors (statins), in diabetic patients with dyslipidaemia, particularly in those with evidence of coronary heart disease. Evidence shows that statins significantly lower cholesterol, exhibit beneficial effects on many components of atherosclerosis, and can significantly reduce the incidence of stroke.

Stenting for in-stent restenosis: A long-term clinical follow-up.

We studied the feasibility, safety, and short- and long-term outcomes of treating coronary in-stent restenosis with primary restenting. Thirty-one patients (32 lesions) were treated. Eleven patients had adjunctive rotational atherectomy. Clinical follow-up was obtained in all 31 patients at a mean of 9.1 +/- 5.5 months by direct phone contact with the patients, medical records, and subsequent hospitalization for recurrent symptoms and/or revascularization. There were no cardiac deaths or myocardial infarctions. In native vessels (26 patients), repeat target lesion revascularization was required in eight patients (31%); two other patients (7.7%) had angina and were treated medically. All vein graft lesions had recurrent restenosis. Significant predictors of recurrent clinical events were lesions in vein grafts, multivessel disease, and use of higher poststent deployment inflation pressures. Primary restenting for in-stent restenosis in native vessels is a safe approach with good short-term outcome. Recurrent restenosis remains a problem, as it does with other devices, particularly in vein graft lesions and in patients with multivessel disease. Restenting for in-stent restenosis should probably be used selectively. Cathet. Cardiovasc. Intervent. 48:143-148, 1999.

The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes.

OBJECTIVES: The purpose of this study was to assess safety and efficacy of enhanced external counterpulsation (EECP). BACKGROUND: Case series have shown that EECP can improve exercise tolerance, symptoms and myocardial perfusion in stable angina pectoris. METHODS: A multicenter, prospective, randomized, blinded, controlled trial was conducted in seven university hospitals in 139 outpatients with angina, documented coronary artery disease (CAD) and positive exercise treadmill test. Patients were given 35 h of active counterpulsation (active CP) or inactive counterpulsation (inactive CP) over a four- to seven-week period. Outcome measures were exercise duration and time to > or =1-mm ST-segment depression, average daily anginal attack count and nitroglycerin usage. RESULTS: Exercise duration increased in both groups, but the between-group difference was not significant (p > 0.3). Time to > or =1-mm ST-segment depression increased significantly from baseline in active CP compared with inactive CP (p = 0.01). More active-CP patients saw a decrease and fewer experienced an increase in angina episodes as compared with inactive-CP patients (p < 0.05). Nitroglycerin usage decreased in active CP but did not change in the inactive-CP group. The between-group difference was not significant (p > 0.7). CONCLUSIONS: Enhanced external counterpulsation reduces angina and extends time to exercise-induced ischemia in patients with symptomatic CAD. Treatment was relatively well tolerated and free of limiting side effects in most patients.

Detecting and differentiating white from red coronary thrombus by angiography in angina pectoris and in acute myocardial infarction.

To determine the ability to detect thrombus by angiography, angioscopy was performed before angiography in patients undergoing interventional procedures and the data collected in a blinded fashion. These data demonstrated that the sensitivity of angiography to detect white thrombus was 50% and the specificity was 95%, whereas the sensitivity and specificity to detect red thrombus was 100%, respectively; the positive and negative predictive value of detecting thrombus in general was 89% and 83%, respectively.

Types of anesthesia and cardiovascular outcomes in patients with congestive heart failure undergoing vascular surgery.

BACKGROUND. Whether regional anesthesia is preferable to general anesthesia for patients with congestive heart failure (CHF) undergoing noncardiac surgery remains controversial. The purpose of this study was to determine whether anesthetic technique affects postoperative cardiac outcome in patients with CHF; we hypothesized that cardiac outcomes would be superior with regional anesthesia compared with general anesthesia. DESIGN. 106 patients with prior or persistent CHF, undergoing femoral to distal artery bypass surgery, were randomized to general anesthesia (29 patients) or regional anesthesia (epidural, 42 patients, or spinal anesthesia, 35 patients). The primary end point was death or adverse cardiac events (myocardial infarction, unstable angina, or CHF). RESULTS. There was no statistically significant difference between groups in incidence of combined cardiac events, death, myocardial infarction, death or myocardial infarction combined, unstable angina, or CHF. CONCLUSION. Although larger studies are required to establish equivalence of the anesthetic strategies, this large single center study preliminarily indicates that regional anesthesia may not be superior to general anesthesia in patients with heart failure undergoing femoral to distal artery bypass surgery. (c)1999 by CHF, Inc.

Determination of blood flow and endothelial shear stress in human coronary artery in vivo.

This paper describes a system that permits, for the first time, the in vivo determination of local velocity and endothelial shear stress in the major human coronary arteries. The purpose of the system is to facilitate the study of plaque growth and the relationships between local hemodynamic factors and atherogenesis and restenosis. The three-dimensional anatomy of a segment of the right coronary artery was determined immediately after directional atherectomy via a combination of intracoronary ultrasound and biplane angiography. The highly irregular geometry of the segment was then represented in curvilinear coordinates and a computational fluid dynamics technique was used to investigate the detailed, intravascular velocity profile and shear stress distribution. We found minor flow reversals, significant swirling and a large variation of local velocity and shear stress, both axially and circumferentially, within the artery, even in the absence of significant luminal obstruction. The flow phenomena exhibit characteristics consistent with the focal nature of atherogenesis and restenosis. It is concluded that the technology now exists to determine luminal geometry and local variations in flow fields and endothelial shear stress, in vivo.

Validation of Doppler FloWire for measurement of coronary flow reserve in humans.

Previous studies have validated the 133Xenon (133Xe) method to assess regional myocardial blood flow and coronary flow reserve (CFR). Doppler FloWire (DFW) has been used recently for measuring CFR to assess the physiological significance of coronary stenosis. Data obtained by DFW has never been correlated to 133Xe. Our study compared data from DFW measurement of CFR to that obtained by 133Xe in 31 consecutive patients with variable coronary stenosis. Regional myocardial blood flow was measured by assessing the rate constants of 133Xe washout using multicrystal gamma camera after injection (20 millicuries) in the right or left coronary artery. CFR was assessed by measuring resting and hyperemic coronary blood flow by 133Xe and DFW using i.v. adenosine (140 mcg/k/min x 3 min). CFR was also measured by DFW giving intracoronary (i.c.) adenosine (12 microg in the right coronary, 18 microg in the left). In both methods--133Xe and DFW--coronary flow reserve was defined as the ratio of maximal hyperemic-to-baseline flow. DFW and 133Xe assessment of CFR correlated highly, whether adenosine was used i.c.(r=0.87; P=0.0001) or i.v.(r=0.78; P=0.0001). CFR obtained by DFW following i.c. and i.v. adenosine correlated well (r=0.79; P=0.0001). i.c. adenosine has fewer side effects. Both DFW and 133Xe are comparable in measuring CFR in humans.

Angioscopy of culprit coronary lesions in unstable angina pectoris and correlation of clinical presentation with plaque morphology.

This study demonstrates that plaque disruption and thrombus are absent in a considerable number of patients with unstable angina and that culprit lesion morphologies as assessed by angioscopy may differ among the various clinical subsets of patients. Although plaque disruption and thrombus undoubtedly play an important role in the pathogenesis of unstable angina, alternative mechanisms may be responsible for ischemia in some patients.