Intensive Glucose Control Group Research Articles

Impact of Intensive Glucose Control on Brain Health: Meta-Analysis of Cumulative Data from 16,584 Patients with Type 2 Diabetes Mellitus.

IntroductionDespite growing evidence that type 2 diabetes is associated with dementia, the question of whether intensive glucose control can prevent or arrest cognitive decline remains unanswered. In the analysis reported here, we explored the effect of intensive glucose control versus standard care on brain health, including structural abnormalities of the brain (atrophy, white matter hyperintensities, lacunar infarction, and cerebral microbleeds), cognitive dysfunction, and risk of dementia.MethodsWe searched the PubMed and Embase databases, the Web of Science website, and the Clinicaltrial.gov registry for studies published in English prior to July 2020. Only studies with a randomized controlled trial (RCT) design were considered. We analyzed structural abnormalities of the brain (atrophy, white matter hyperintensities, lacunar infarction, and cerebral microbleeds), cognitive function (cognitive impairment, executive function, memory, attention, and information-processing speed), and dementia (Alzheimer’s disease, vascular dementia, and mixed dementia).ResultsSix studies (5 different RCTs) with 16,584 participants were included in this meta-analysis. One study that compared structural changes between groups receiving intensive versus conventional glucose control measures reported non-significant results. The results of the five studies, comprising four cohorts, indicated a significantly poorer decline in cognitive function in the intensive glucose control group (β − 0.03, 95% confidence interval [CI] − 0.05 to − 0.02) than in the conventional glucose control group. Further subgroup analysis showed a significant difference in the change in cognitive performance in composite cognitive function (β − 0.03, 95% CI − 0.05 to − 0.01) and memory (β − 0.13, 95% CI − 0.25 to − 0.02). One trial evaluated the prevalence of cognitive impairment and dementia between groups receiving intensive and conventional glucose control, respectively, and the differences were insignificant.ConclusionThis meta-analysis suggests that intensive glucose control in patients with type 2 diabetes can slow down cognitive decline, especially the decline in composite cognition and memory function. However, further studies are necessary to confirm the impact of strict glucose control on structural abnormalities in the brain and the risk of dementia.

Intensive Versus Standard Glucose Control in Patients with Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Hyperglycemia is common in patients with ischemic stroke (IS) and has been proven to be associated with worse clinical outcomes. However, it is controversial whether intensive glucose control (IGC) is superior to standard glucose control (SGC). Therefore, we carried out this meta-analysis based on randomized controlled trials (RCTs). We systematically searched databases for RCTs that evaluated the efficacy of IGC versus SGC in patients with IS. The retrieval time was limited from the establishment of the database to October 2019. The retrieval databases included PubMed, Medline, Embase, OVID, Web of Science, Google Scholar, and a Chinese literature database. Two researchers independently screened and evaluated the quality of literature. We used Stata 11.0 software for data analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to compare the results. Finally, 7 RCTs including 1691 participants were included in this study. Among the patients, 857 patients were in the IGC group and 834 were in the SGC group. Our results show that IGC significantly increased the risk of hypoglycemia compared with SGC (OR, 4.76; 95% CI, 1.17-19.45). No significant differences were observed in modified Rankin scale score ≤2 (OR, 0.97; 95% CI, 0.75-1.25), National Institutes of Health Stroke Scale score ≤2(OR, 1.48; 95% CI, 0.54-4.06), and death (OR, 0.74; 95% CI, 0.53-1.02) between the 2 groups within 3 months. Our results suggest there is no evidence that IGC is superior to SGC in patients with IS, but IGC increases the risk of hypoglycemia.

Is intensive glucose control bad for critically ill patients? A systematic review and meta-analysis.

Background: The monitoring and management of blood glucose concentration are standard practices in critical settings as hyperglycaemia has been shown close association with poorer outcomes. Several meta-analyses have revealed that intensive glucose control has no benefit in decreasing short-term mortality among critically ill patients, while the studies these meta-analyses have incorporated have been largely divergent. We aim to perform a more comprehensive meta-analysis addressing this problem to provide stronger evidence.Methods: We conducted comprehensive searches for relevant randomized controlled studies in online databases, including the Cochrane Library, EMBASE, and PubMed databases, up to September 1, 2018. The clinical data, which included all-cause mortality, severe hypoglycemia, need for RRT, infection resulting in sepsis, ICU mortality, 90-day mortality, 180-day mortality, and hospital and ICU lengths of stay, were screened and analyzed after data extraction. We applied odds ratios (ORs) to analyze dichotomous outcomes and mean differences for continuous outcomes with a random effects model.Results: A total of 57 RCTs involving a total of 21840 patients were finally included. Patients admitted to the ICU who underwent intensive glucose control showed significantly reduced all-cause mortality (OR: 0.89; 95% CI: 0.80-1.00; P=0.04; I2=32%), reduced infection rate (OR: 0.65, 95% CI: 0.51-0.82, P=0.0002; I2=47%), a lower occurrence of acquired sepsis (OR: 0.80, 95% CI: 0.65-0.99, P=0.04; I2=0%) and shortened length of ICU stay (MD: -0.70, 95% CI: -1.21--0.19, P=0.007, I2=70%) when compared to the same parameters as those treated with the usual care strategy. However, patients in the intensive glucose control group presented with a significantly higher risk of severe hypoglycemia (OR: 5.63, 95% CI: 4.02-7.87, P<0.00001; I2=67%).Conclusions: Critically ill patients undergoing intensive glucose control showed significantly reduced all-cause mortality, length of ICU stay and incidence of acquired infection and sepsis compared to the same parameters in patients treated with the usual care strategy, while the intensive glucose control strategy was associated with higher occurrence of severe hypoglycemic events.

Diabetes and dementia: managing these comorbidities

Diabetes and dementia: managing these comorbidities

Optimal target range for blood glucose in hyperglycaemic patients in a neurocritical care unit

Hyperglycaemia is common among patients with critical neurological injury, even if they have no history of diabetes. The optimal target range for normalizing their blood glucose is unknown. Retrospective data were extracted from 890 hyperglycaemic individuals (glucose > 200 mg/dL) admitted to neuroscience critical care unit (NCCU) and these patients were divided into two groups: intensive glucose control group with target glucose of < 140 mg/dL achieved and moderate control with glucose levels 140-180 mg/dL. The groups were also stratified according to the hyperglycaemia type (pre-existing diabetes or stress-related). We defined the primary endpoint as death from any cause during NCCU admission. In NCCU, tighter control of blood glucose at ≤ 140 mg/dL was associated with increased, mortality of individuals with pre-existing diabetes compared with moderate control [29 of 310 patients (9.4%) vs 15 of 304 patients (4.9%), p = 0.034]. Patient age [adjusted odds ratio (OR) = 1.12; 95% confidence interval (CI) = 1.05-1.19; p < 0.001], level of glycated haemoglobin (adjusted OR = 1.24; 95% CI = 1.04-1.48; p = 0.017) and hypoglycaemia (adjusted OR = 10.3; 95% CI = 2.92-36.6; p < 0.001) were positively associated with higher mortality. Death rate was lower among stress-related hyperglycaemic patients with tighter glucose controlled at ≤ 140 mg/dL [6 of 140 patients (4.3%) vs 15 of 136 patients (11.0%), p = 0.035]. A differential association is evident between glucose levels and mortality in diabetes and stress-related hyperglycaemia patients. However, given the observational nature of our work, no clinical recommendations can be given and prospective studies are required to further investigate these findings.

Intensive Glucose Control in Diabetics with an Acute Myocardial Infarction Does not Improve Mortality and Increases Risk of Hypoglycemia-A Meta-Regression Analysis

Some early trials comparing intensive glucose control in type 2 diabetics with an acute myocardial infarction (MI) reported a decrease in mortality over a short period of follow up leading to a presumption of improved survival with intensive glucose control. Later data refuted this hypothesis. The 2009 ACC/AHA focused update on ST elevation MI gave a weak recommendation for the use of an insulin based regimen to achieve and maintain blood glucose less than 180 mg/dL. We decided to assess the validity of this recommendation.The authors searched the Pub- Med, Cochrane CENTRAL and EMBASE databases for randomized controlled trials from 1965 through 2011.Trials included were direct head-to-head comparisons of an intensive blood glucose control strategy using pharmacological means (insulin in most cases) with a less intensive regimen. The primary outcome assessed was the risk of all -cause mortality in the two groups at the end of follow up. Also assessed was the rate of hypoglycemia. The methodological quality of the studies was assessed. Event rates were compared using a forest plot of relative risk (RR; 95% confidence interval [CI]) using a random effects model (Mantel-Haenszel) assuming inter-study heterogeneity. Statistical analysis was done with Review Manager V5.1 and SYSTAT. Meta-regression was done with duration of therapy as covariate.Three studies (total N = 2113) met the inclusion exclusion criteria. Mortality was not different between the groups (RR 0.94, 95% CI of 0.66-1.34; p=0.73.). Rate of hypoglycemia was significantly higher in the intensive glucose control group (RR 13.40, 95% CI 3.69-48.61; p < 0.01), with a 12% absolute risk increase and a number needed to harm (NNH) of 9 (95% CI 6.8- 9.8)-even without achieving target glycemic control. Neither did intensive control improve CHF, arrhythmias and reinfarction rates. Meta regression revealed that mortality with intensive glycemic control was worse with increased duration of therapy (p=0.001, for trend).This systematic review suggests limited benefit of intensive glycemic control in type 2 diabetics with an MI, with a significant risk of serious hypoglycemia.

Intensive Glucose Control in Diabetics with an Acute Myocardial Infarction Does not Improve Mortality and Increases Risk of Hypoglycemia-A Meta-Regression Analysis

Some early trials comparing intensive glucose control in type 2 diabetics with an acute myocardial infarction (MI) reported a decrease in mortality over a short period of follow up leading to a presumption of improved survival with intensive glucose control. Later data refuted this hypothesis. The 2009 ACC/AHA focused update on ST elevation MI gave a weak recommendation for the use of an insulin based regimen to achieve and maintain blood glucose less than 180 mg/dL. We decided to assess the validity of this recommendation. The authors searched the Pub- Med, Cochrane CENTRAL and EMBASE databases for randomized controlled trials from 1965 through 2011.Trials included were direct head-to-head comparisons of an intensive blood glucose control strategy using pharmacological means (insulin in most cases) with a less intensive regimen. The primary outcome assessed was the risk of all -cause mortality in the two groups at the end of follow up. Also assessed was the rate of hypoglycemia. The methodological quality of the studies was assessed. Event rates were compared using a forest plot of relative risk (RR; 95% confidence interval [CI]) using a random effects model (Mantel-Haenszel) assuming inter-study heterogeneity. Statistical analysis was done with Review Manager V5.1 and SYSTAT. Meta-regression was done with duration of therapy as covariate. Three studies (total N = 2113) met the inclusion exclusion criteria. Mortality was not different between the groups (RR 0.94, 95% CI of 0.66-1.34; p=0.73.). Rate of hypoglycemia was significantly higher in the intensive glucose control group (RR 13.40, 95% CI 3.69-48.61; p < 0.01), with a 12% absolute risk increase and a number needed to harm (NNH) of 9 (95% CI 6.8- 9.8)-even without achieving target glycemic control. Neither did intensive control improve CHF, arrhythmias and reinfarction rates. Meta regression revealed that mortality with intensive glycemic control was worse with increased duration of therapy (p=0.001, for trend). This systematic review suggests limited benefit of intensive glycemic control in type 2 diabetics with an MI, with a significant risk of serious hypoglycemia.

Intensive Glucose Control in Diabetics with an Acute Myocardial Infarction Does not Improve Mortality and Increases Risk of Hypoglycemia-A Meta-Regression Analysis

Objectives: Some early trials comparing intensive glucose control in type 2 diabetics with an acute myocardial infarction (MI) reported a decrease in mortality over a short period of follow up leading to a presumption of improved survival with intensive glucose control. Later data refuted this hypothesis. The 2009 ACC/AHA focused update on ST elevation MI gave a weak recommendation for the use of an insulin based regimen to achieve and maintain blood glucose less than 180 mg/dL. We decided to assess the validity of this recommendation. Methods: The authors searched the Pub- Med, Cochrane CENTRAL and EMBASE databases for randomized controlled trials from 1965 through 2011.Trials included were direct head-to-head comparisons of an intensive blood glucose control strategy using pharmacological means (insulin in most cases) with a less intensive regimen. The primary outcome assessed was the risk of all -cause mortality in the two groups at the end of follow up. Also assessed was the rate of hypoglycemia. The methodological quality of the studies was assessed. Event rates were compared using a forest plot of relative risk (RR; 95% confidence interval [CI]) using a random effects model (Mantel-Haenszel) assuming inter-study heterogeneity. Statistical analysis was done with Review Manager V5.1 and SYSTAT. Meta-regression was done with duration of therapy as covariate. Results: Three studies (total N = 2113) met the inclusion ⁄ exclusion criteria. Mortality was not different between the groups (RR 0.94, 95% CI of 0.66-1.34; p=0.73.). Rate of hypoglycemia was significantly higher in the intensive glucose control group (RR 13.40, 95% CI 3.69-48.61; p<0.01), with a 12% absolute risk increase and a number needed to harm (NNH) of 9 (95% CI 6.8- 9.8)-even without achieving target glycemic control. Neither did intensive control improve CHF, arrhythmias and reinfarction rates. Meta regression revealed that mortality with intensive glycemic control was worse with increased duration of therapy (p=0.001, for trend). Conclusions: This systematic review suggests limited benefit of intensive glycemic control in type 2 diabetics with an MI, with a significant risk of serious hypoglycemia. Keywords: Myocardial infarction, intensive glycemic control, meta-analysis, regression, hypoglycemia, mortality

Intensive versus conventional glucose control in critically ill patients: A meta-analysis of randomized controlled trials

BackgroundCritically ill patients commonly develop hyperglycemia. It remains unclear, however, to what extent correcting hyperglycemia will benefit these patients. We performed this meta-analysis to evaluate the benefits and risks of intensive glucose control versus conventional glucose control in critically ill adult patients. MethodsA systematic literature search of MEDLINE, PubMed, and Cochrane databases (until June 2011) was conducted using specific search terms. Randomized controlled trials that compared intensive glucose control with a target glucose goal <6.1mmol/l (110mg/dl) to conventional glucose control in adult intensive care patients were included. The random-effect model was used to estimate the pooled risk ratio of the two treatment arms. ResultsTwenty two studies that randomized 13,978 participants were included in the meta-analysis. Overall, intensive glucose control did not reduce the short-term mortality (RR=1.02, 95% CI: 0.95–1.10, p=0.51), 90day or 180day mortality (RR=1.06, 95% CI: 0.99–1.13, p=0.08), sepsis (RR=0.96, 95% CI: 0.83–1.12, p=0.59) or new need for dialysis (RR=0.96, 95% CI: 0.83–1.11, p=0.57). The incidence of hypoglycemia was significantly higher in intensive glucose control group compared with conventional glucose control group (RR=5.01, 95% CI: 3.45–7.28, p<0.00001). ConclusionsThis meta-analysis found that intensive glucose control in critically ill adults did not reduce mortality but is associated with a significantly increased risk of hypoglycemia.

Intensive Glucose Control and Cardiovascular Outcomes in Type 2 Diabetes

Numerous observational studies have clearly shown a relationship between hyperglycaemia and cardiovascular (CV) disease. However, the United Kingdom Prospective Diabetes Study (UKPDS), which involved subjects with newly diagnosed type 2 diabetes, just failed to show that intensive glucose control significantly reduces CV events. The results of three subsequent large randomised controlled trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) and the Veterans Administration Diabetes Trial (VADT), that involved approximately 25,000 subjects with established type 2 diabetes also failed to show that intensive glucose control, aiming for a glycated haemoglobin (HbA(1c)) level<7%, significantly reduces CV events. The ACCORD trial even suggested that under certain circumstances, intensive glucose control is associated with an increased risk for CV and all-cause mortality. Although the exact mechanisms responsible for an increase in mortality in the ACCORD trial remain unknown, there was an association between increased rates of mortality with higher rates of severe hypoglycaemia in the intensive glucose control group. In contrast, a 10-year post-randomisation follow-up study of the tight glucose intervention arm of the UKPDS showed that intensive glucose control was associated with a significant reduction in the risk for myocardial infarction (MI), diabetes-related deaths and all-cause mortality. This suggests that early strict glucose control generates a legacy effect that is eventually translated into protection from CV events. Recent meta-analyses of the above randomised trails have also shown that intensive glucose control is associated with a reduced risk of MI, without a clear benefit on other CV diseases such as stroke. Furthermore, these analyses have also shown that intensive glucose control is associated with increased rates of severe hypoglycaemia but not increased rates of CV or all-cause mortality. Aiming for HbA(1c) levels of <7.0% still remains the general target for good glucose control. Under certain circumstances, aiming for lower HbA(1c) levels may be appropriate. This applies in the setting of newly diagnosed diabetes in relatively young individuals without significant co-morbidities and in patients treated with agents that minimise the risk of severe hypoglycaemia such as metformin. Whether this also applies to newer glucose-lowering agents that target the incretin system will depend on CV outcomes of long-term studies which are in progress.

The efficacy of lowering glycated haemoglobin with a gliclazide modified release-based intensive glucose lowering regimen in the ADVANCE trial

The aim of these analyses was to examine the efficacy of the intensive gliclazide MR-based glucose lowering regimen used in the ADVANCE trial in lowering the level of glycated haemoglobin (HbA1c). All 11,140 randomised patients were included in analyses of treatment efficacy. Treatment efficacy was also examined in subgroups defined by baseline characteristics and treatments. At the end of 5 years follow-up, the mean HbA1c was reduced from 7.5% at baseline to 6.5% in those on intensive glucose control and to 7.3% in those on standard glucose control. With intensive glucose lowering greater proportions achieved HbA1c levels of ≤7.0%, ≤6.5% and ≤6.0%. With intensive glucose lowering substantial reductions in HbA1c were observed across subgroups defined by baseline age, sex, duration of diabetes, BMI, HbA1c or treatment regimen ( p < 0.0001). The main independent predictors of reduction in HbA1c during follow-up were baseline HbA1c, duration of diabetes and BMI. There was no weight gain in the intensive glucose control group and severe hypoglycaemia was uncommon, though more frequent than in the standard control group. Intensive glucose control with a gliclazide MR-based regimen was well tolerated and consistently effective in lowering HbA1c across a broad range of patient with type 2 diabetes.

A five-year follow-up study on diabetic retinopathy with intensive glucose control in outpatients with type 2 diabetes

Objective To observe effects of long-term intensive glucose control therapy on diabetic retinopathy in outpatients with type 2 diabetes mellitus (72DM) . Methods Forty-nine patients with T2DM, aged 58 to 70 years with illness course length of 0. 6 to 12.0 years, were randomly assigned to groups receiving either intensive (24 patients) or standard glucose control (25 patients) . They were all under management with hypoglycemic treatment in the outpatient department of Beijing Tongren Hospital for five years during 2002 to 2007. Serum level of glycosylated hemoglobin Ale ( HbA1c) were measured for the patients in intensive-therapy group every three months targeting at it controlled below 6. 5% with any drugsneeded. For the patients in standard glucose control group aged 60 years or over, with history of myocardial infarction, but without other complications, serum level of HbA 1 c was measured every a half year and should be controlled under 7.0%. Their visual acuity, lens, vitreous body and fundus oculi were examined after dilatation of the pupil by ophthalmologists to identify any new diabetic retinopathy ( DR) , including micro-aneurysm, fundus hemorrhage, edema of the macula lutea, or diabetic associated blindness. Results Serum level of HbAlc had been significantly lower in intensive glucose control group [ (6. 3±0. 6 ) % ] than that in standard glucose control one [ ( 7. 1±2. 0) % ] since the second year of therapy (P < 0. 05), which could be maintained in the next four years of therapy. No new case of fundus hemorrhage or diabetic associated blindness could be found in intensive glucose control group during the five-year period of therapy.Number of new episodes of lowering in visual acuity ( 15 cases), occurrence of micro-aneurysm (five cases), edema of the macula lutea (one case), as well as those who needed retinal laser photocoagulation (four cases) , were significantly less in intensive glucose control group than that in standard glucose control one (25, 10, three and 23 cases, respectively) during five-year follow-up (P<0. 05). Conclusions Long-term intensive glucose control in patients with T2DM can significantly reduce new occurrence of diabetic retinopathy in them, which is feasible in outpatient clinics. Key words: Diabetes mellitus,type 2; Blood glucose; Diabetic retinopathy

Critical Care Medicine

Critical Care Medicine

Intensive insulin therapy on infection rate, days in NICU, in-hospital mortality and neurological outcome in severe traumatic brain injury patients: A randomized controlled trial

Objectives Evaluate the impact of an intensive insulin therapy and conventional glucose control protocol during staying in neurological intensive care unit (NICU) on infection rate, days in NICU, in-hospital mortality and long-term neurological outcome in severe traumatic brain injury (TBI) patients. Methods A total of 240 patients with severe TBI (GCS score 3–8) admitted to NICU were prospectively enrolled and randomly assigned either to conventional insulin therapy or to intensive insulin therapy. Patients in intensive glucose control group ( n = 121) received continuous insulin infusion to maintain glucose levels between 4.4 mmol/l (80 mg/dl) and 6.1 mmol/l (110 mg/dl). Patients in the conventional treatment group ( n = 119) were not given insulin unless glucose levels were greater than 11.1 mmol/l (200 mg/dl). Both groups were treated with insulin infusion to maintain normoglycemia after leaving NICU. Comparison was made against conventional insulin therapy using a randomized trial design. The primary outcomes is the mortality rate at 6 months follow-up. The second outcomes including ICU infection rate, duration of ICU stay, in-hospital mortality rate and neurologic outcome at 6 months follow-up. Results There was no significant difference in gender (66% vs. 67% male), age (46 ± 11 years vs. 45 ± 10 years), APACHE II score (30 vs. 29), TISS-28 score (47 vs. 46), and Glasgow Coma Score (GCS, 5.3 vs. 5.3) between the two groups. Overall mortality rates at 6 months follow-up were similar in the 2 groups (61 of 117, 52.1% vs. 62 of 116, 53.4%; P = 0.8). The infection rate during the study was significantly higher in patients who received conventional insulin therapy than that in patients who received intensive insulin therapy (46.2% vs. 31.4%; P < 0.05). The days stay in NICU was shorter in intensive insulin control group than that in conventional therapy group [4.2 days vs. 5.6 days (medians) P < 0.05]. The in-hospital mortality during the study was similar in conventional and intensive therapy groups (34 of 119, 28.6% vs. 35 of 121, 28.9% in the conventional and intensive insulin therapy groups; P = 0.85). The neurologic outcome according to Glasgow Outcome Score (GOS) at 6 months (GOS 5 and 4) was better in the intensive insulin therapy group (34 of 117, 29.1%) than that in the conventional therapy group (26 of 116, 22.4%, P < 0.05). Conclusions Mortality rates at 6 months follow-up are not affected by intensive glucose control in patients with severe TBI. Intensive insulin therapy decreases infection rate and days in NICU and improves the neurological outcome at 6 months follow-up, while has no obvious influence on in-hospital mortality of severe TBI patients.

Intensive glucose control after allogeneic hematopoietic stem cell transplantation: a retrospective matched-cohort study

Some studies have shown that intensive glucose control (IGC) improves outcome in the intensive care unit setting. However, it is the benefit of IGC in hematopoietic SCT (HSCT) that is not well defined. Between June 2006 and May 2007, IGC was maintained prospectively after allogeneic HSCT and clinical outcomes were compared with a cohort matched for conditioning regimen, source of stem cells, age and relation to donor. A stratified Cox regression model was used. There were no significant differences in baseline clinical characteristics. The median age was 43.5 years in both groups. The primary diagnosis was a hematologic malignancy. Patients in the IGC group had a lower glucose level (least-square mean, 116.4 vs 146.8 mg per 100 ml, P<0.001) compared to the standard glucose control group. The incidences of documented infections and bacteremia were significantly lower in the IGC group (14 vs 46%, P=0.004, 9 vs 39%, P=0.002, respectively). IGC tended to reduce the incidence of renal dysfunction (19 vs 37%, P=0.36) and the elevation of C-reactive protein (18 vs 38%, P=0.13). This study suggests that IGC has may have a beneficial effect after HSCT. IGC should be evaluated further in a large prospective, randomized study.