Glycated hemoglobin as a marker of cardiovascular risk

PURPOSE OF REVIEW: Diabetes mellitus is an established risk factor for cardiovascular disease. This review examines glycated hemoglobin, an indicator of long-term average blood glucose concentrations, in risk prediction for cardiovascular disease. RECENT FINDINGS: Glycated hemoglobin concentrations predict cardiovascular disease risk in people with diabetes, and trial data suggest that good blood glucose control is associated with reduction in cardiovascular disease. Elevated glycated hemoglobin levels below the thresholds accepted for diabetes are also associated with increasing cardiovascular disease risk independent of classical risk factors in a continuous relationship across the whole normal distribution. A 1% increase in absolute concentrations of glycated hemoglobin is associated with about 10-20% increase in cardiovascular disease risk. The continuous relationship is most evident for coronary heart disease in men; the shape of the risk curve is less clear for women and for other cardiovascular endpoints such as stroke or peripheral vascular disease. SUMMARY: Glycated hemoglobin concentration predicts cardiovascular risk both in people with diabetes and in the general population, and may help identify individuals at higher risk of cardiovascular disease for targeted interventions, including blood pressure or cholesterol reduction. Understanding the nature of this relationship may inform new preventive and therapeutic interventions.     

Glycemia Management and Cardiovascular Risk in Type 2 Diabetes: An Evolving Perspective

ObjectiveTo review recent glycemia trials focused on reducing cardiovascular disease (CVD) risk in patients with type 2 diabetes and to describe how the results of these studies have altered our approach to the management of glycemia in patients with diabetes.MethodsResults of some of the previous as well as recent trials, including the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease (ADVANCE), and Veterans Affairs Diabetes Trial (VADT), are reviewed.ResultsThe results demonstrate that the establishment of glycemia (hemoglobin A1c) goals in patients with type 2 diabetes aimed at reducing CVD events is complex, should be highly individualized, and should probably be varied depending on the duration of diabetes as well as the presence or absence of CVD and microvascular complications.ConclusionResults of the ACCORD, ADVANCE, and VADT studies have considerably increased our knowledge and refined our approach to establishing glycemia goals in patients with type 2 diabetes. In patients with recently recognized diabetes with no prior CVD events, glycemic control to normal or near-normal levels appears to be effective in preventing CVD events and mortality. In patients with established diabetes (8 to 10 or more years) and recognized CVD, however, glycemic control to normal or near-normal levels does not reduce the risk of further CVD events or mortality. Importantly, strict control of all known risk factors for CVD and microvascular complications by aggressive management of hypertension, dyslipidemia, and glycemia, use of aspirin, and cessation of smoking in patients with type 2 diabetes has proved to be highly beneficial. (Endocr Pract. 2008;14:639-643)     

Choice of antihypertensive drug in the diabetic patient

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.     

Which is the best lipid-modifying strategy in metabolic syndrome and diabetes: fibrates, statins or both?

Although less clinical intervention studies have been performed with fibrates than with statins, there are evidences indicating that fibrates may reduce risk of cardiovascular events. The potential clinical benefit of the fenofibrate will be specified by the ongoing Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, which rationale, methods and aims have been just published. Controlled clinical trials show similar or even greater cardiovascular benefits from statins-based therapy in patient subgroups with diabetes compared with overall study populations. Therefore, statins are the drug of first choice for aggressive lipid lowering actions and reducing risk of coronary artery disease in these patients. However, current therapeutic use of statins as monotherapy is still leaving many patients with mixed atherogenic dyslipidemia at high risk for coronary events. A combination statin/fibrate therapy may be often necessary to control all lipid abnormalities in patients with metabolic syndrome and diabetes adequately, since fibrates provide additional important benefits, particularly on triglyceride and HDL-cholesterol levels. Thus, this combined therapy concentrates on all the components of the mixed dyslipidemia that often occurs in persons with diabetes or metabolic syndrome, and may be expected to reduce cardiovascular morbidity and mortality. Safety concerns about some fibrates such as gemfibrozil may lead to exaggerate precautions regarding fibrate administration and therefore diminish the use of the seagents. However, other fibrates, such as bezafibrate and fenofibrate appear to be safer and better tolerated. We believe that a proper co-administration of statins and fibrates, selected on basis of their safety, could be more effective in achieving a comprehensive lipid control as compared with monotherapy.     

Role for fibrate therapy in diabetes: evidence before FIELD

PURPOSE OF REVIEW: Diabetic dyslipidaemia, among the main factors contributing to vascular risk in type 2 diabetes, is characterized by hypertriglyceridaemia, low HDL-cholesterol and increased prevalence of small dense LDL particles. Because fibrates have positive effects on triglycerides, HDL-cholesterol and LDL particle size, they may be an appropriate treatment for diabetic dyslipidaemia. Statins have been shown to diminish significantly the risk for coronary disease in patients with type 2 diabetes, and so what are the real effects of fibrates on cardiovascular risk in type 2 diabetes? RECENT FINDINGS: Although statins reduce the incidence of coronary disease in type 2 diabetes, data from clinical trials demonstrate 'residual' cardiovascular risk in these patients treated with statins. Clinical trials with fibrates show that they are particularly effective in reducing cardiovascular risk in patients with type 2 diabetes/metabolic syndrome and in those exhibiting the lipid abnormalities typical of diabetic dyslipidaemia (elevated triglycerides, low HDL-cholesterol). SUMMARY: Data on the effects of fibrates on cardiovascular risk in diabetes were obtained from subgroup analyses. Thus far, the only study performed specifically in patients with type 2 diabetes is the angiographic Diabetes Atherosclerosis Intervention Study which demonstrated a significant reduction in progression of atherosclerosis in patients receiving fenofibrate, but it was not powered to analyse the effects of fibrates on clinical outcomes. This is why the Fenofibrate Intervention and Event Lowering in Diabetes study is needed; it will provide robust data on the ability of fibrates to reduce cardiovascular risk in patients with type 2 diabetes.     

Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide

ABSTRACT: The risk of cardiovascular complication in a diabetes patient is similar to that in a nondiabetic patient with a history of myocardial infarction. Although intensive control of glycemia achieved by conventional antidiabetic agents decreases microvascular complications such as retinopathy and nephropathy, no marked effect has been reported on macrovascular complications or all-cause mortality. Evidence from VADT, ACCORD, and ADVANCE would suggest that glycemic control has little effect on macrovascular outcomes. Moreover, in the case of ACCORD, intensive glycemic control may be associated with an increased risk of mortality. There is sufficient evidence that suggests that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease in diabetes patients. However, there are no prospective clinical trials supporting the recommendation that lowering postprandial blood glucose leads to lower risk of cardiovascular outcomes. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes. Because of its short action time, it is unlikely to exert adverse effects related to hypoglycemia early in the morning and between meals. Mitiglinide reduces excess oxidative stress and inflammation, plays a cardioprotective role, and improves postprandial metabolic disorders. Moreover, mitiglinide add-on therapy with pioglitazone favorably affects the vascular endothelial function in type 2 diabetes patients. These data suggest that mitiglinide plays a potentially beneficial role in the improvement of postprandial hyperglycemia in type 2 diabetes patients and can be used to prevent cardiovascular diseases. Although the results of long-term, randomized, placebo-controlled trials for determining the cardiovascular effects of mitiglinide on clinical outcomes are awaited, this review is aimed at summarizing substantial insights into this topic.     

Is there a vitamin E paradox?

In addition to epidemiologic studies that suggest a benefit for high intakes of alpha-tocopherol, studies of supplementation in humans have clearly shown that alpha-tocopherol decreases lipid peroxidation, platelet aggregation, and functions as a potent anti-inflammatory agent. In the five large prospective clinical trials with alpha-tocopherol therapy, four have shown a beneficial effect on cardiovascular end-points (two studies on a primary end-point and two studies on other cardiovascular end-points). Thus, the totality of evidence based on the epidemiologic data, in-vitro studies and animal models, and the clinical trials appears to support a benefit for alpha-tocopherol supplementation in patients with pre-existing cardiovascular disease. However, definitive recommendations must await ongoing clinical trials.     

Prevention of type 2 diabetes

Changes in the human environment and in human behavior and lifestyle, in conjunction with genetic susceptibility, have resulted in a dramatic increase in the incidence and prevalence of diabetes in the world. The rapid escalation of the number of people with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease demands urgent action on prevention. The Finnish Diabetes Prevention Study and The Diabetes Prevention Program showed that the prevention (or delaying) of T2DM is feasible and effective. Both of these trials led to a reduction of 58% in the conversion to diabetes in subjects with impaired glucose tolerance. Compared to lifestyle changes, drug treatment in the prevention of diabetes in people at high risk for T2DM has been less beneficial. Metformin (31%) or acarbose (25%) treatment obtained only about a half of the reduction in the conversion to diabetes compared to lifestyle changes. These drugs require monitoring, and have significant side-effects. Also the effect of orlistat (37%) did not reach the effect of lifestyle modification. Results of the Troglitazone in Prevention of Diabetes study are suggestive for the prevention, but the trial was too small, and included only one ethnic group (Hispanic) and one gender (women). On the basis of the evidence available, we do not have a definite proof that T2DM is prevented in any of these trials. However, we can safely conclude that the current evidence strongly favors the notion that lifestyle changes are the primary means to tackle the epidemic of T2DM.     

Statin diabetogenicity: guidance for clinicians

Type 2 diabetes (T2D) is a strong, independent risk factor for cardiovascular (CV) and cerebrovascular outcomes. Meta-analysis of five randomised clinical trials (n = 33,040) showed that, although intensive versus standard glycaemic control significantly reduced CV events in people with T2D, the reduction was less than that achieved with lipid-lowering or antihypertensive treatment. Furthermore, fasting plasma glucose (FPG) concentrations were a modest predictor for CV risk in people without T2D. Thus, although effective glycaemic control is important for the prevention/management of T2D, other risk factors must be addressed to effectively reduce CV risk. Reducing low-density lipoprotein-cholesterol levels using statins significantly reduces CV risk in people with and without T2D. Although statins are generally safe and well tolerated, conflicting data exist regarding the diabetogenic effects of some statins. Based on recent clinical trial data, the US Food and Drug Administration have changed the labelling of all statins to include ‘an effect of statins on incident diabetes and increases in haemoglobin A1c and/or FPG’. However, the literature suggests that the beneficial effects of most statins on CV risk continue to outweigh their diabetogenic risks and that statins should remain as first-line therapy for the majority of people with dyslipidaemia and metabolic syndrome or T2D. Mechanisms explaining the potentially higher incidence of T2D with statin therapy have not been confirmed. However, independent predictors for statin-associated T2D appear to include elevated levels of baseline FPG, BMI, blood pressure and fasting triglycerides. Moreover, although some statins (for example, atorvastatin) are associated with increased haemoglobin A1c levels in patients receiving intensive but not moderate therapy, other statins (for example, pitavastatin) have demonstrated neutral or favourable effects on glucose control in patients with and without T2D or metabolic syndrome. The potential diabetogenic effects of statins may therefore differ between drugs. In conclusion, conflicting data exist regarding the diabetogenic effects of statins. Further studies are required to understand whether all statins have the same effect and whether some patient groups are at higher risk than others. Meanwhile, results suggest that the net CV benefit favours the use of statin therapy in patients with dyslipidaemia, irrespective of T2D risk.     

Nutritional effects on blood pressure

PURPOSE OF REVIEW: There has not been a thorough recent evaluation of the nutritional effects on blood pressure. Apart from outstanding clinical trials like Dietary Approaches to Stop Hypertension, there have been controversial papers on a number of factors influencing blood pressure. This paper is a systematic review of the current literature as it relates to hypertension. RECENT FINDINGS: Results from many meta-analyses and well controlled clinical trials on the effects of a variety of nutritional factors are presented in this review. Evidence suggests that dietary sodium intake needs reduction. There is a seemingly inverse relationship between protein intake and blood pressure, but data are inconclusive. High monounsaturated fat and fish oil appear to be beneficial. Several studies on dietary fiber indicate that the strongest evidence for blood pressure lowering effects is in hypertensive as opposed to normotensive participants. Vegetarians seem to have lower levels of hypertension and cardiovascular disease risk. Low carbohydrate diets show short-term beneficial effects but are not sustained. High levels of potassium, magnesium, calcium and soy seem to have some benefit, but results remain inconclusive. Weight reduction positively impacts blood pressure. SUMMARY: More compelling research defining specific factors is needed to inform the public as to steps needed to reduce blood pressure and improve cardiovascular risk.     

Statin therapy for prevention and treatment of acute and chronic cardiovascular disease: update on recent trials and metaanalyses

PURPOSE OF REVIEW: To summarize the evidence from recent clinical trials and metaanalyses on the efficacy of statin therapy to reduce death, myocardial infarction and stroke, and to review the effects of statins in patients with low LDL cholesterol, diabetes, end-stage renal disease, and acute coronary syndrome. RECENT FINDINGS: In large metaanalyses of randomized controlled trials relative risk reductions from statins compared with placebo for patients with manifest or with risk factors for coronary artery disease were 13% for overall mortality, 26% for fatal and nonfatal myocardial infarction, and 18% for fatal and nonfatal stroke. Evidence from large trials suggests that patients with type II diabetes compared with patients without diabetes have similar risk reductions from statins for cardiovascular events, but this benefit is not seen in patients with diabetes and end-stage renal disease. In patients with acute coronary syndrome, early treatment with high-dose atorvastatin reduces cardiovascular morbidity after the first 4 months following the event, but the impact on mortality endpoints remains less clear. Results from recent trials in patients with stable coronary artery disease or type II diabetes suggest that statins provide benefit at considerable low LDL cholesterol levels. Therefore, target values for LDL cholesterol of less than 1.8 mmol/l (<70 mg/dl) should be considered for all patients with coronary artery disease or equivalent coronary risk. SUMMARY: For patients at high risk of coronary artery disease there is growing evidence for the concept of 'the lower, the better' regarding LDL cholesterol levels. Ongoing trials are further investigating the safety of lower target values in patients at various risk of coronary artery disease.     

Type 2 diabetes in Xinjiang Uygur autonomous region, China

Background

The aim of this study was to estimate the prevalence and distribution of type 2 diabetes and to determine the status of type 2 diabetes awareness, treatment, and control in Xinjiang, China. Our data came from the Cardiovascular Risk Survey (CRS) study designed to investigate the prevalence and risk factors for cardiovascular diseases in Xinjiang from October 2007 to March 2010. A total of 14 122 persons (5583 Hans, 4620 Uygurs, and 3919 Kazaks) completed the survey and examination. Diabetes was defined by the American Diabetes Association 2009 criteria.

Methodology/Principal Findings

Overall, 9.26% of the Han, 6.23% of the Uygur, and 3.65% of the Kazak adults aged ≥35 years had diabetes. Among diabetes patients, only 53.0% were aware of their blood glucose level, 26.7% were taking hypoglycemic agents, and 10.4% achieved blood glucose control in Han, 35.8% were aware of their blood glucose level, 7.3% were taking hypoglycemic agents, and 3.13% achieved blood glucose control in Uygur, and 23.8% were aware of their blood glucose level, 6.3% were taking hypoglycemic agents, and 1.4% achieved blood glucose control in Kazak, respectively.

Conclusions/Significance

Our results indicate that diabetes is highly prevalent in Xinjiang. The percentages of those with diabetes who are aware, treated, and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of diabetes in Xinjiang, the west China.     

L-cysteine supplementation as an adjuvant therapy for type-2 diabetes

Diabetes remains a major public health issue. According to the American Diabetes Association, 23.5 million, or 10.7% of people in the USA aged 20 years and older, have diabetes. Type-2 diabetes is treated both by controlling the diet and with oral hypoglycemic drugs. However, for many patients, achieving a tight control of glucose is difficult with current regimens. This chapter discusses a relatively low-cost dietary supplement that could be used as an adjuvant therapy for type-2 diabetes. A review of the literature indicates that cysteine-rich whey protein improves glucose metabolism in diabetic animals and type-2 diabetic patients. Similarly, in animal studies, improvement in glucose metabolism is observed after supplementation with L-cysteine, or molecules containing a cysteine moiety. This chapter discusses the biochemical mechanisms by which L-cysteine can upregulate the insulin-dependent signaling cascades of glucose metabolism. Further studies are needed to examine whether clinical interventions using L-cysteine as an adjuvant therapy indeed help to control glycemia and vascular inflammation in the diabetic patient population.     

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. METHODS: This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control).Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice.orControl group: Standard GP care, with referral to secondary care as required, but no access to ICCD.Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (<=7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients. DISCUSSION: Forty-nine practices have been randomized, 1,997 patients have been recruited to the trial, and 20 patients have been recruited to the qualitative study. Results will be available late 2012.Trial registration[ClinicalTrials.gov: Identifier NCT00945204].     

Insulin resistance and decreased spexin in Indian Patients with Type 2 Diabetes Mellitus

Spexin is novel biomarker, which plays a potential role in glucose and lipid metabolisms. However, there was paucity of serum spexin levels in obesity and diabetes mellitus subjects. Hence the current study was aimed to find the relationship between the serum spexin levels in type 2 Diabetes mellitus (type 2 DM) with extrapolation of cardiovascular disease (CVD) risk. A cross-sectional study included 330 participants, subdivided as control (n=110), type 2 DM (n=110) and type 2 DM with CVD groups (n=110). HbA1c, insulin, lipid profile, spexin & leptin including blood pressure and body mass index were analyzed from all the participants. The serum spexin levels (ng/ml) were significantly decreased in type 2 DM (mean ± sd: 0.65 ± 0.03) and type 2 DM with CVD (0.48 ± 0.02) groups compared to the control (0.79 ± 0.03) group (p<0.001). The decreased spexin levels were observed in type 2 DM, and further more decreased in type 2 DM with CVD patients compared to controls indicating that spexin levels could be served as an early prediction of obesity-induced T2DM with CVD risk.     

Hypertriglyceridemia and the fibrate trials

Epidemiological studies published since 1996 have established that hypertriglyceridemia can predict risk of cardiovascular disease in a manner statistically independent of HDL cholesterol. Nevertheless, the relationship of concentrations of plasma triglycerides to risk of cardiovascular disease remains less than straightforward, partly because triglycerides are carried in lipoproteins of different atherogenicity, partly because hypertriglyceridemia is associated with non-lipid atherogenic and thrombogenic processes. For example, the association of highest risk of cardiovascular disease to moderate rather than to severe hypertriglyceridemia can be understood in terms of the distribution of triglycerides between different classes of plasma lipoproteins. It is counter-intuitive to most clinicians, however, and hence it can result in the misdirection of clinical efforts including drug therapy.Fibrates lower plasma triglycerides, and raise HDL, efficiently and with few immediate side-effects. Central to their mode of action is activation of certain nuclear receptors in cells. There is no necessary connection, however, between that fascinating biochemistry and clinical benefit as defined by reductions in rates of death by coronary artery disease. A review of trials of cholesterol-lowering by diet and drugs, published between 1966 and 1996, included 12 trials of therapy with fibrates or placebo in more than 21000 patients. Overall, these trials indicated no benefit in terms of reduction in risk of coronary deaths. The period since 1996 has seen the publication of four additional trials of treatment of 6144 patients with fibrates or placebo. Two of them were major trials. The VA-HIT was very encouraging, because treatment with gemfibrozil produced a signficant reduction in the combined incidence of fatal and non-fatal coronary events. There was no significant reduction in coronary deaths, however. The results of BIP were frankly disappointing, because they demonstrated no significant effect of treatment with bezafibrate on either the primary end-point of the trial or on rates of coronary death.Clinical indications for the use of fibrates can obviously not be based on biochemical insights, however intriguing in their own right, but they have also not been satisfactorily defined by the randomized clinical trials published to date. Hope remains, however, that some clarification will result from ongoing trials of fibrate treatment of patients with type II diabetes.     

Weight Gain and Management Concerns in Patients on Insulin Therapy

Background: The benefits of tight glycemic control in preventing the onset and progression of microvascular complications in patients with type 2 diabetes mellitus (DM) are unarguable. The majority of patients with type 2 DM will eventually require insulin to achieve adequate glycemic control. Using insulin earlier rather than later in the course of type 2 DM may diminish the deleterious effects of hyperglycemia on β-cell function and therefore help prolong good glycemic control and prevent the occurrence of microvascular complications. However, weight gain is a potential adverse effect of insulin therapy.Objective: The goal of this article was to describe the benefit of insulin therapy early in the course of type 2 DM, review the association of weight gain with insulin therapy, and examine potential detrimental effects that insulin-associated weight gain could have in patients with type 2 DM.Methods: Materials used for this article were identified through a search of MEDLINE (1966–2006). English-language articles were chosen using the search terms diabetes mellitus type 2, insulin, and obesity.Results: Intensive insulin therapy is often associated with weight gain. Although there is concern that weight gain in patients with type 2 DM may have adverse effects on risk factors for cardiovascular disease, unfavorable changes in blood pressure and lipid levels have not been consistently observed in clinical trials. Furthermore, clinical evidence, including data from the United Kingdom Prospective Diabetes Study, supports the view that intensive insulin therapy does not increase the risk for cardiovascular disease.Conclusions: Early insulin therapy in patients with type 2 DM may be a strategy that will help patients achieve and maintain good glycemic control, thereby reducing the risk of developing microvascular complications. Although weight gain is commonly associated with insulin therapy, it does not appear to put these patients at greater risk for cardiovascular disease.     

Cardiovascular disease with diabetes or the metabolic syndrome: should statins or fibrates be first line lipid therapy?

PURPOSE OF REVIEW: Subgroups with diabetes or with features of the metabolic syndrome have been increasingly highlighted in large clinical endpoint trials with lipid therapy. This review will focus on the results of trials with statins or fibrates and examine the strength of the evidence for major cardiovascular event reduction with each kind of therapy in these high-risk subgroups that typically have low-to-moderate levels of LDL cholesterol. RECENT FINDINGS: Of six statin trials in populations with moderately increased LDL cholesterol only one, the Heart Protection Study, has shown that statin therapy will significantly reduce the major coronary heart disease events of non-fatal myocardial infarction or coronary heart disease death in diabetes. None of these trials has shown that statins have a particular predilection for reducing cardiovascular events in individuals with higher levels of body weight or other features of the metabolic syndrome. There are far fewer trial data with fibrates than with statins. However, the Veterans Affairs High Density Lipoprotein Intervention Trial has shown that a fibrate can significantly reduce major cardiovascular events, most particularly coronary heart disease death, in those with diabetes as well as those without diabetes who have insulin resistance. Indeed, all fibrate trials show that this therapy appears to selectively benefit the individual with obesity and features of the metabolic syndrome. SUMMARY: Based principally on evidence from the Veterans Affairs High Density Lipoprotein Intervention Trial and the cumulative experience with statins, trial data would thus far suggest that the patient with a modest increase in LDL cholesterol who has diabetes or features of the metabolic syndrome might be likely to achieve more substantial cardiovascular benefit from fibrate than from statin therapy.     

Potential Place of SGLT2 Inhibitors in Treatment Paradigms for type 2 Diabetes Mellitus

Objective: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms.Methods: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin.Results: Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time.Conclusion: The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm.Abbreviations: AE = adverse event A1C = glycated hemoglobin CI = confidence interval CKD = chronic kidney disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate FDA = Food and Drug Administration FPG = fasting plasma glucose GLP-1 = glucagon-like peptide 1 HDL-C = high-density lipoprotein cholesterol HR = hazard ratio LADA = late-onset autoimmune diabetes of adulthood LDL-C = low-density lipoprotein cholesterol MACE = major adverse cardiovascular events SGLT1 = sodium glucose cotransporter 1 SGLT2 = sodium glucose cotransporter 2 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus UACR = urine albumin to creatinine ratio     

Awareness,Treatment, and Control of Diabetes in Bangladesh: A Nationwide Population-Based Study

ObjectivesTo examine awareness, treatment, and control of diabetes mellitus among the adult population in Bangladesh.MethodsThe study used data from the 2011 nationally representative Bangladesh Demographic and Health Survey (BDHS). The BDHS sample is comprised of 7,786 adults aged 35 years or older. The primary outcome variables were fasting blood glucose, diagnosis, treatment, and control of diabetes. Multilevel logistic regression models were used to identify the risk factors for diabetes awareness.ResultsOverall, age-standardized prevalence of diabetes was 9.2%. Among subjects with diabetes, 41.2% were aware of their condition, 36.9% were treated, and 14.2% controlled their condition. A significant inequality in diabetes management was found from poor to wealthy households: 18.2% to 63.2% (awareness), 15.8% to 56.6% (treatment), and 8.2% to 18.4% (control). Multilevel models suggested that participants who had a lower education and lower economic condition were less likely to be aware of their diabetes. Poor management was observed among non-educated, low-income groups, and those who lived in the northwestern region.ConclusionsDiabetes has become a national health concern in Bangladesh; however, treatment and control are quite low. Improving detection, awareness, and treatment strategies is urgently needed to prevent the growing burden associated with diabetes.