Effect Of Intensive Glycemic Control Research Articles

Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial

Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial

Effect of intensive glycaemic control on endothelial progenitor cells in patients with long-standing uncontrolled type 2 diabetes

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. However, in patients with diabetes, EPC number and function are markedly reduced. It is unclear whether intensive glycaemic control can modify EPC properties in diabetic patients. We aimed to examine whether glycaemic control can improve EPC number and function in patients with long-standing uncontrolled type 2 diabetes. Thirty-five patients with treated type 2 diabetes and HgA1c ≥ 8.5% were included. Patients were tested at baseline and after 3-4 months of an intensive glycaemic control programme, with the aim of achieving HgA1c of 7%. The diabetes group was compared to 20 patients without diabetes (control). Circulating EPC levels were assessed by flow cytometry for expression of VEGFR2, CD133, and CD34. The capacity of the cells to form colony-forming units (CFUs), and their migration and viability were quantified after 1 week of culture. Patients with diabetes (mean age 61.1 ± 7 years, 28.6% women, disease duration of 19.2 ± 8 years) had a baseline HgA1c of 9.4 ± 0.8%. After the glycaemic control period, HgA1c decreased to 8 ± 0.8%. Circulating EPC levels increased significantly after the intensive control period and reached a level similar to the control group. The number of EPC CFUs also increased significantly after glycaemic control but remained lower than the control group. All EPC functional assays improved following the glycaemic control. In patients with uncontrolled long-standing type 2 diabetes, intensive glycaemic control was associated with an increase in the levels of circulating EPCs, and improvement in their functional properties.

Erectile Dysfunction

Erectile Dysfunction

Targets for Glycemic Control

Targets for Glycemic Control

Effects of intensive glycemic control on outcomes of cardiac surgery

ObjectivesTo investigate the effects of postoperative intensive glycemic control on patient outcomes. BackgroundIneffective perioperative glycemic control has been associated with high mortality and morbidity rates among cardiac surgery patients. Methods212 cardiac surgery patients were allocated by a quasi-experimental design to: a) a control group (n = 107) with targeted blood glucose levels 161–200 mg/dl or b) a therapy group (n = 105) with blood glucose target 120–160 mg/dl. We compared the two groups on their mortality, length of stay, duration of intubation, incidence of severe hypoglycemia and frequency of postoperative infections. ResultsThe mean postoperative blood glucose levels were significantly lower for the therapy group compared with the control group (153.9 mg/dl vs. 173.9 md/dl, p < 0.001). The intensive glycemic control was strongly associated with decreased in-hospital mortality (7 deaths/105 patients for the control group vs. 1 death/105 patients for the therapy group; p = 0.033). We did not identify any statistically significant associations regarding the other patient outcomes. ConclusionsThis randomized quasi-experimental trial found lower in-hospital mortality with more intense blood glucose control. Effective postoperative glycemic control did not affect the other studied patient outcomes.

Effects of the glucose-lowering rate on cTnI and hs-CRP serum levels in type 2 diabetics

The current objective is to evaluate the effect of intensive glycemic control on serum levels of both Cardiac Troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP) in subjects with type 2 diabetes. Hence, we are trying to find a reasonable glucose-lowering rate associated with type 2 diabetics with and without coronary heart disease. A total of 132 type 2 diabetes mellitus without coronary heart disease (T2DM) cases and 135 type 2 diabetes mellitus with coronary heart disease (T2DM+CHD) cases received intensive glycemic control. Serum cTnI and hs-CRP levels were tested before and after intensive glycemic control. There was no significant difference in the changing amplitude of cTnI and hs-CRP serum levels variation between four glucose-lowering rates in T2DM group (P > 0.05), while this difference was observed in T2DM+CHD group(P < 0.05). During the follow-up, cTnI and hs-CRP serum levels were lower than those before glycemic control in both T2DM and T2DM+CHD groups (P < 0.05). The glucose-lowering rate in T2DM+CHD group should be no more than 4 mmolL(-1)d(-1) and the appropriate glucose-lowering rate in T2DM group is no more than 6 mmolL(-1)d(-1). Serum levels of cTnI and hs-CRP will be increased if the glucose-lowering rate is over this range, which means that cardiovascular endpoints might be induced.

Measuring urinary tubular biomarkers in type 2 diabetes does not add prognostic value beyond established risk factors

Tubulointerstitial disease plays an important role in the pathophysiology of diabetic kidney disease. To determine whether biomarkers of tubular injury could predict renal outcome and mortality in patients with type 2 diabetes, we measured urinary levels of kidney injury molecule-1 (KIM-1) and glycoprotein non-metastatic melanoma B (Gpnmb), both normalized to the urinary creatinine, in 978 individuals from the Edinburgh Type 2 Diabetes Study. At baseline, 238 patients had an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 while 147 and 15 patients had microalbuminuria or overt proteinuria, respectively. Both the urine KIM-1 and Gpnmb to creatinine ratios correlated with the urinary albumin to creatinine ratio, the duration of diabetes, and the stringency of glycemic control but not with blood pressure or baseline eGFR. Higher ratios of each marker were associated with a faster decline in kidney function during 4 years of follow-up; however, this was not independent of the urinary albumin to creatinine ratio. Higher KIM-1, but not Gpnmb ratios were associated with an increased risk of mortality, but this association was no longer significant after adjustment for other risk factors, in particular albuminuria. Thus, tubular injury in persons with type 2 diabetes may contribute to the decline in kidney function; however, measuring the urinary concentration of these two tubular biomarkers does not confer additional prognostic information beyond established risk factors.

Influence of intensive glycemic control on development and progression of diabetic nephropathy in patients with type 2 diabetes mellitus (based on results from ADVANCE study)

Current article presents data on effects of intensive glycemic control with Diabeton MR on development and progression of diabeticnephropathy in patients with type 2 diabetes mellitus (T2DM), accumulated from ADVANCE (Action in Diabetes and Vascular Disease:Preterax and DiamicroN Modified Release Controlled Evaluation study). Influence of intensive therapy with Diabeton MR wasassessed in that study separately and in conjunction with active antihypertensive treatment with perindopril and indapamide.

Glucagon-like peptide-1 receptor agonists and their effects on weight reduction.

Glucagon-like peptide-1 receptor agonists and their effects on weight reduction.

New ADA/EASD Position Statement Endorses a Patient-Centered Approach

Glycemic management in type 2 diabetes mellitus (T2DM) has become increasingly complex and, to some extent, controversial. A widening array of pharmacological agents [Nyenwe EA et al. Metabolism 2011; Blonde L. Am J Med 2010; Bergenstal RM et al. Am J Med 2010] has raised concerns about their potential adverse effects, as well as new uncertainties about the effects of intensive glycemic control on macrovascular complications [Yudkin JS et al. Lancet 2011]. This article reviews key points from the new Position Statement from the American Diabetes Association and the European Association for the Study of Diabetes [Inzucchi SE et al. Diabetes Care 2012; Inzucchi SE et al. Diabetologia 2012].

Diabetes and cardiovascular disease: focus on glucagon-like peptide-1 based therapies.

Type 2 diabetes is a well known risk factor for cardiovascular disease (CVD). While glycemic control has consistently been shown to prevent microvascular complications, large randomized trials have not demonstrated the same consistent beneficial effects of intensive glycemic control in improving cardiovascular (CV) outcomes. Thus, optimal glucose control alone is not sufficient to reduce CV risk. Aggressive management of CV risk factors such as blood pressure, lipids, and body weight is also necessary. A growing body of evidence suggests that the recently available glucagon-like peptide 1 receptor (GLP-1R) agonists have beneficial CV effects beyond glucose control. Studies have demonstrated beneficial effects in the myocardium, endothelium, vasculature and various markers of cardiovascular risk such as body weight, blood pressure and dyslipidemia. Despite the growing evidence, large, randomized, blinded clinical trials with hard CV endpoints have not been performed. Most human studies have been small, and have focused on surrogate endpoints. The findings need to be confirmed by prospective, randomized cardiovascular outcomes trials. In this review we examine the GLP-1R agonist data on weight reduction, blood pressure lowering, beneficial changes in dyslipidemia, and improvements in myocardial and endothelial function. The safety as well as potential role of these agents in treatment regimens for type 2 diabetes is also addressed.

Cardiovascular Benefits of Exogenous Insulin

Recent studies on mediators of inflammation, experimental models of atherosclerosis, and acute ischemia have identified novel mechanisms through which insulin may exert cardiovascular protective effects. This review aims to summarize current knowledge regarding the cardiovascular, antiinflammatory, and antiatherogenic effects of insulin, and the effect of intensive glycemic control in acute cardiovascular disease. Publications of interest were identified using preselected MeSH terminology and keywords to search online databases such as PubMed and OVID for the period January 1988 to February 2012. Relevant publications were obtained and reviewed by two independent observers, then evaluated a priori against the following criteria: study quality, main clinical outcomes, and applicability to clinical practice. Insulin has been shown to exert vasodilatory, antiinflammatory, and antiatherogenic effects in experimental models, independent of its glucose-lowering effects. Additionally, glucose is known to exert potent proinflammatory, prothrombotic, and proapoptotic effects during myocardial infarct, indicative that hyperglycemia is likely to be injurious to the heart. In this context, through its nonmetabolic and metabolic (glucose-lowering) effects, insulin is likely to be cardioprotective and to improve clinical outcomes in acute myocardial infarction. Despite promising experimental data and evidence of benefit from single-center randomized clinical trials, clinical evidence supporting the cardioprotective effects of insulin from a multicenter randomized clinical trial is still lacking. Future prospective studies with insulin infused at adequate concentrations, individually titrated to achieve and maintain euglycemia (blood glucose < 140 mg/dl) and minimize hypoglycemia, are required to investigate the role of insulin in the management of patients with acute cardiovascular disease.

Does Glycemic Control Offer Similar Benefits Among Patients With Diabetes in Different Regions of the World?

OBJECTIVEParticipants in ADVANCE were drawn from many countries. We examined whether the effects of intensive glycemic control on major outcomes in ADVANCE differ between participants from Asia, established market economies (EMEs), and eastern Europe.RESEARCH DESIGN AND METHODSADVANCE was a clinical trial of 11,140 patients with type 2 diabetes, lasting a median of 5 years. Demographic and clinical characteristics were compared across regions using generalized linear and mixed models. Effects on outcomes of the gliclazide modified release–based intensive glucose control regimen, targeting an HbAlc of ≤6.5%, were compared across regions using Cox proportional hazards models.RESULTSWhen differences in baseline variables were allowed for, the risks of primary outcomes (major macrovascular or microvascular disease) were highest in Asia (joint hazard ratio 1.33 [95% CI 1.17–1.50]), whereas macrovascular disease was more common (1.19 [1.00–1.42]) and microvascular disease less common (0.77 [0.62–0.94]) in eastern Europe than in EMEs. Risks of death and cardiovascular death were highest in eastern Europe, and the mean difference in glycosylated hemoglobin between the intensive and standard groups was lowest in EMEs. Despite these and other differences, the effects of intensive glycemic control were not significantly different (P ≥ 0.23) between regions for any outcome, including mortality, vascular end points, and severe hypoglycemic episodes.CONCLUSIONSIrrespective of absolute risk, the effects of intensive glycemic control with the gliclazide MR-based regimen used in ADVANCE were similar across Asia, EMEs, and eastern Europe. This regimen can safely be recommended for patients with type 2 diabetes in all of these regions.

Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus

The incidence type 2 diabetes is increasing world-wide. We did a Cochrane review focusing on whether intensive glycaemic control is superior to conventional glycaemic control in reducing mortality and complications in patients with type 2 diabetes (1). Cardiovascular disease is important, because it is the main cause of premature death for these patients. Patients with type 2 diabetes develop elevated levels of plasma glucose with disturbances in carbohydrate, fat, and protein metabolism. As type 2 diabetes is a progressive disease the glucose-lowering treatment needs to be intensified in order to achieve near normal glycaemia. The first step for patients with type 2 diabetes is ‘lifestyle’ intervention, with advice to lose weight and increase physical activity. However, in order to maintain optimal glycaemic control, most patients will require additional glucose-lowering therapy. Our review assesses the effects of targeted intensive glycaemic control compared with targeted conventional glycaemic control. We searched for randomised clinical trials comparing these two approaches in patients with type 2 diabetes, looking for published and unpublished trials in any language; and ended up with 20 included trials, that recruited almost 30,000 patients. The duration of the interventions lasted from 3 days to 12.5 years. The patients in these trials represent a very diverse part of the population with type 2 diabetes. The diagnosis of type 2 diabetes varied among the included trials, and some trials used a definition which may have led to the inclusion of participants with impaired glucose tolerance rather than type 2 diabetes. The results of the review should be interpreted with caution. When we combined the results of the trials, we found that the treatments did not have significantly different effects on all-cause mortality or mortality from cardiovascular disease; the same was the case for several other patient important outcomes. Among the outcomes that may be favoured when targeting intensive glycaemic control are non-fatal myocardial infarction, amputation of the lower leg, and microvascular disease assessed as a composite outcome. We were not able to perform meta-analyses for either health-related quality of life or the costs of the interventions. We used a statistical technique in the review called trial sequential analysis to examine whether the significant effect estimates in cumulative might be due to a lack of data. Trial sequential analysis does also help to estimate how many more patients needs to be randomised before firm evidence is established. In conclusion, uncertainty remains about the effect of intensive glycaemic control versus conventional glycaemic control on cardiovascular disease and mortality in patients with type 2 diabetes. It would be preferable to have more randomised clinical trials assessing cardiovascular disease and mortality in patients with type 2 diabetes, for example younger patients without complications and older patients with complications. Future trials should adopt more uniform and rigorous standards for reporting to ease the comparisons between different glycaemic intervention targets.

The effect of intensive risk factor management in type 2 diabetes on inflammatory biomarkers

AimsTo determine whether intensive risk factor management reduced markers of inflammation in middle-aged and older people with type 2 diabetes who either had, or were at risk for cardiovascular disease (CVD), and whether these effects were mediated by adiposity. MethodsThe Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was a multicenter double 2 by 2 factorial randomized controlled trial of 10,251 middle-aged and older people who had type 2 diabetes, a GHbA1c of 7.5% or greater, and evidence of CVD or CVD risk factors. Biomarkers were assessed in a subset of 562 participants.Intervention effects on high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were tested using linear regression models. ResultsA significantly lower average hs-CRP was noted in the intensive versus the standard glycemic group (p=0.029). Adjusting for change in BMI or waist circumference resulted in larger differences in adjusted hs-CRP (p<0.001 and p<0.002, respectively) between the glycemic intervention groups. ConclusionsIntensive glycemic control was associated with a reduction in hs-CRP in this study population. Intervention associated increases in adiposity suppressed the beneficial effect of intensive glycemic control on lowering hs-CRP.

Effects of intensive glycemic control on serum levels of insulin-like growth factor-I and dehydroepiandrosterone sulfate in Type 2 diabetes mellitus.

Although accumulating evidence shows that aging hormones are involved in glucose metabolism, effects of glycemic control on serum IGF-I and DHEAS levels are still unclear. To investigate the effects of glycemic control on these hormone levels, we conducted a 1-month longitudinal study of 49 Japanese patients with Type 2 diabetes mellitus. We measured serum levels of IGF-I and DHEA-S before and after 1-month glycemic control and analyzed the association of changes in IGF-I and DHEA-S with glycated hemoglobin (HbA1c). HbA1c was decreased at 1 month with mean changes of -1.2% (p<0.001). Serum IGF-I was increased with mean changes of 11 ng/ml (p<0.05), while serum DHEA-S was decreased with mean changes of -19 μg/dl (p<0.05). Multiple regression analysis showed that changes in DHEA-S were inversely associated with changes in fasting plasma glucose (β=-0.36, p=0.027) and HbA1c (β=-0.33, p=0.028), while changes in IGF-I were not. The present longitudinal study showed that intensive glycemic control for 1 month increased serum IGF-I level and decreased serum DHEA-S level in Japanese patients with poorly controlled Type 2 diabetes. Further studies are needed to clarify the hormonal changes in IGF-I and DHEA-S after intensive glycemic control would affect diabetic complications.

Observation on Renal Outcomes in the Veterans Affairs Diabetes Trial

OBJECTIVEThe Veterans Affairs Diabetes Trial (VADT) was a randomized, prospective, controlled trial of 1,791 patients with type 2 diabetes to determine whether intensive glycemic control would reduce cardiovascular events compared with standard control. The effect of intensive glycemic control and selected baseline variables on renal outcomes is reported.RESEARCH DESIGN AND METHODSBaseline mean age was 60.4 years, mean duration of diabetes was 11.5 years, HbA1c was 9.4%, and blood pressure was 132/76 mmHg. The renal exclusion was serum creatinine >1.6 mg/dL. Renal outcomes were sustained worsening of the urine albumin-to-creatinine ratio (ACR) and sustained worsening by one or more stages in the estimated glomerular filtration rate (eGFR).RESULTSIntensive glycemic control did not independently reduce ACR progression but was associated with a significant attenuation in the progression of ACR in those who had baseline photocoagulation, cataract surgery, or both. The beneficial effect of intensive glycemic control increased with increasing BMI and with decreasing diastolic blood pressure (DBP). Intensive glycemic control was associated with less worsening of eGFR with increasing baseline ACR and insulin use. Baseline systolic blood pressure, triglycerides, and photocoagulation were associated with worsening of eGFR.CONCLUSIONSIntensive glycemic control had no significant effect on the progression of renal disease in the whole cohort but was associated with some protection against increasing ACR in those with more advanced microvascular disease, lower baseline DBP, or higher baseline BMI and on worsening of eGFR in those with high baseline ACR.

Clinical practice and implications of recent diabetes trials

Diabetes is an increasingly prevalent risk factor for coronary and other vascular disease. Recent trials in patients with diabetes have examined the effects of intensive glycemic control on cardiovascular outcomes, and treatment of common concomitant risk factors, in particular hypertension and dyslipidemia. Optimal revascularization strategies have also been examined. Intensive glycemic control has a beneficial effect on microvascular but not macrovascular endpoints, with one major trial reporting increased mortality out to 5 years with intensive treatment. Similarly, aggressive lowering of SBP to below 120 mmHg produced no advantage over treatment to 130-140 mmHg. Statins are the best treatment for diabetic dyslipidemia, with little benefit from adding a fibrate. Medical treatment may be appropriate for many with diabetes and stable coronary disease. When revascularization is needed, coronary bypass graft surgery has an advantage over percutaneous coronary intervention in those at the severe end of the coronary disease spectrum. Patients with type 2 diabetes often have multiple cardiovascular risk factors and require multiple cardiac and diabetes medications. Caution over aggressive glucose and blood pressure lowering is needed, at least with currently available drugs.

Effects of medical therapies on retinopathy progression in type 2 diabetes: Is blood pressure control the lower the better?

Effects of medical therapies on retinopathy progression in type 2 diabetes: Is blood pressure control the lower the better?

Progression of retinopathy in persons with type 2 diabetes: new data, same conclusions?

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial was designed primarily to examine the effects of intensive glycemic control on cardiovascular events in persons with type 2 diabetes who were, for additional reasons, at high risk for such events. The trial also examined effects on the same endpoints of intervention on blood pressure and on serum lipids. The study intervention on glycemic control was stopped early because of the effects of this intervention on mortality. The trial provided important data on the effects of the various interventions on diabetic retinopathy, confirming the importance of intensive glycemic control in diminishing the progression of retinopathy. In addition, it provided evidence of a protective effect of fenofibrate treatment on the same retinopathy endpoint. However, the apparent paradoxical effects of intensive glycemic control on macrovascular and microvascular disease suggests caution in the care of persons with type 2 diabetes who are judged to be at high risk for cardiovascular events.