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In EMPA-REG OUTCOME, empagliflozin reduced the composite of total events leading to/prolonging hospitalisation for any cause and all-cause mortality by 24 % versus placebo in patients with T2DM and ASCVD, with 67.7 events prevented/1000 patient-years and a low NNT. Effects were sustained and were consistent regardless of the reason for hospitalisation. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of empagliflozin on uric acid (UA) levels, antigout medication and gout episodes in the EMPA‐REG OUTCOME trial (NCT01131676). Materials and methods: A total of 7020 patients with type 2 diabetes (T2D) were randomized to either empagliflozin (10 or 25 mg) or placebo. The effects of empagliflozin versus placebo on UA concentration were assessed using mixed linear models. A composite outcome of new prescription of antigout medication or gout episode was studied with Cox proportional hazards models. Results: Empagliflozin reduced serum UA levels versus placebo: week 52 adjusted mean treatment difference = −0.37 (95% confidence interval [CI] −0.42, −0.31) mg/dL; this was more pronounced in patients with baseline UA ≥ 7.0 mg/dL versus <7.0 mg/dL: week 52 adjusted mean treatment difference = −0.56 (95% CI −0.68, −0.43) and −0.30 (95% CI −0.37, −0.24) mg/dL, respectively. Among 6607 patients not taking antigout medications at baseline, 5.2% had a gout episode or initiated antigout treatment versus 3.6% in the placebo and empagliflozin groups, respectively: hazard ratio 0.67 (95% CI 0.53, 0.85; P = 0.001). Both components of the composite outcome contributed to the reduction with empagliflozin in the composite. Risk reduction was similar with both empagliflozin doses. Conclusions: Empagliflozin reduced UA levels and the composite of gout episodes or prescription of antigout medication. These clinically important findings expand the utility of empagliflozin as a potential antigout treatment in patients with T2D, beyond its well‐established cardio‐renal benefits. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of empagliflozin versus placebo on subsequent insulin initiation or dosing changes in a large cardiovascular outcomes trial. Materials and Methods: In EMPA‐REG OUTCOME, 7020 patients with type 2 diabetes and cardiovascular disease received empagliflozin 10 mg, 25 mg, or placebo. Median follow‐up was 3.1 years. After 12 weeks of treatment, changes in background antihyperglycaemic therapy were permitted. Among insulin‐naïve patients, we assessed the effects of pooled empagliflozin arms versus placebo on time to initiation of insulin. Among insulin‐treated patients, we assessed effects on time to an increase or decrease in insulin dose of more than 20%. Results: In 3633 (52%) participants not treated with insulin at baseline, empagliflozin reduced new use of insulin versus placebo by 60% (7.1% vs. 16.4%; adjusted HR 0.40 [95% CI 0.32‐0.49]; P <.0001). In 3387 (48%) patients using insulin at baseline, empagliflozin reduced the need for a greater than 20% insulin dose increase by 58% (14.4% vs. 29.3%; adjusted HR 0.42 [95% CI 0.36‐0.49]; P <.0001) and increased the proportion achieving sustained greater than 20% insulin dose reductions without subsequent increases in HbA1c compared with placebo (9.2% vs. 4.9%; adjusted HR 1.87 [95% CI: 1.39‐2.51]; P <.0001). Sensitivity analyses confirmed consistent findings when insulin dose changes of more than 10% or more than 30% were considered. Conclusions: In patients with type 2 diabetes and cardiovascular disease, empagliflozin markedly and durably delays insulin initiation and substantial increases in insulin dose, while facilitating sustained reductions in insulin requirements over time. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose‐lowering therapy (GLT) in this population is uncertain.DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) >40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death. In this pre‐specified analysis of participants with T2D, treatment effects were assessed by number and class of background GLT(s). Of 3150 participants with T2D at baseline, 22.9% were on no GLT, 36.5% were treated with 1 GLT, and 40.6% with ≥2 GLTs. During follow‐up (median: 2.3 years), treatment benefits of dapagliflozin (vs. placebo) on the primary outcome were consistent irrespective of the number of background GLTs (0 GLTs: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50–1.00; 1 GLT: HR 1.04, 95% CI 0.80–1.34; ≥2 GLTs: HR 0.71, 95% CI 0.56–0.90; pinteraction = 0.59). Similar findings were observed among participants with (HR 0.73, 95% CI 0.59–0.92) and without background metformin use (HR 0.89, 95% CI 0.72–1.11; pinteraction = 0.22) and in participants with (HR 0.89, 95% CI 0.69–1.16) and without background insulin use (HR 0.78, 95% CI 0.65–0.95; pinteraction = 0.45). Dapagliflozin was well‐tolerated irrespective of the number of background GLTs.Dapagliflozin safely and consistently improved clinical outcomes among individuals with T2D and HF with LVEF >40% irrespective of the number and class of background GLTs, and the benefits were not influenced by concomitant metformin or insulin use. These data bolster contemporary guidelines supporting first‐line SGLT2i among individuals with T2D and HF, irrespective of background GLT. [ABSTRACT FROM AUTHOR]

Objective: The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial.Research Design and Methods: The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new-onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model.Results: At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebo group and 64 of 1,298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50-0.94; P = 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7-6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not.Conclusions: In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of different categories of baseline cardio‐metabolic risk factors on the treatment effects of empagliflozin 10 and 25 mg when added as second‐line therapy to metformin in patients with type 2 diabetes (T2D). Materials and Methods: Patients aged 18 years or older with HbA1c 7.0%‐10.0% were included. Analysis of covariance compared change from baseline to weeks 24 and 76 in HbA1c, body weight (BW) and systolic blood pressure (SBP) by respective baseline categories (HbA1c <8.5/≥8.5%; BW <80/80‐90/>90 kg, SBP <130/130‐140/>140 mmHg). Analyses were also conducted with a model using continuous covariates of cardio‐metabolic factors. Results: In total, 637 patients (56.7% males; mean [SD] age 55.7 [9.9] years, HbA1c 7.9% [0.9%], BW 81.2 [18.8] kg, SBP 129.4 [14.6] mmHg) received one or more dose of either empagliflozin 10 mg (n = 217) or 25 mg (n = 213), or placebo (n = 207). At both time points, empagliflozin 10/25 mg versus placebo significantly (P <.0001) reduced HbA1c and BW, with greater reductions in HbA1c at higher baseline HbA1c (P interaction week 24/76 categorical and continuous models:.0290/.1431 and.0004/.0042, respectively) and in BW (P interaction.1340/.0012 and.0202/<.0001, respectively). Both empagliflozin doses also significantly lowered SBP versus placebo at both time points, with similar efficacy by subgroups of baseline SBP. Adverse events were consistent with the established empagliflozin safety profile across treatment groups. Conclusions: Empagliflozin, as add‐on to metformin, decreases HbA1c and BW, particularly in patients with higher HbA1c and BW baseline values, and effectively lowers SBP. [ABSTRACT FROM AUTHOR]

Aim: To explore the cardiovascular (CV) and kidney effects of empagliflozin in patients with different clinical phenotypes of diabetic kidney disease (DKD) (i.e. with the presence or absence of overt albuminuria) participating in the EMPA‐REG OUTCOME trial. Materials and methods: EMPA‐REG OUTCOME randomized participants (1:1:1) to empagliflozin 10 mg, 25 mg or placebo, added to standard of care. Post hoc, patients with different clinical phenotypes of DKD at baseline were categorized in three subgroups: (a) overt DKD (overt albuminuria [urinary albumin‐to‐creatinine ratio of >300 mg/g] with any estimated glomerular filtration rate [eGFR]; n = 769); (b) non‐overt DKD (kidney impairment [eGFR < 60 mL/min/1.73 m2] without overt albuminuria [urinary albumin‐to‐creatinine ratio of ≤300 mg/g]; n = 1290); and (c) 'all others' (eGFR ≥ 60 mL/min/1.73 m2 without overt albuminuria; n = 4893). Analyses included CV (death, hospitalization for heart failure, all‐cause hospitalization) and selected kidney outcomes, change in eGFR and kidney safety. Cox proportional hazards models assessed the consistency of treatment effect across subgroups. Results: Empagliflozin significantly reduced the risk of CV and kidney outcomes across all subgroups (P‐values for interaction >.05), consistent with the overall trial population findings. Empagliflozin also significantly reduced the yearly loss of eGFR, assessed by chronic slopes, in all subgroups. The adverse event profile of empagliflozin was similar across all subgroups. Conclusions: Empagliflozin may improve CV and kidney outcomes and slow the progression of kidney disease in type 2 diabetes patients with DKD, irrespective of its clinical form, both with or without the presence of overt albuminuria. [ABSTRACT FROM AUTHOR]

Aims: In the EMPA‐REG OUTCOME® trial, the sodium‐glucose cotransporter 2 inhibitor empagliflozin when given in addition to standard care improved cardiovascular (CV) and renal outcomes, and reduced mortality. Trial participants were on a variety of glucose‐lowering therapies at baseline, some of which could potentially affect CV risk. This analysis investigated whether the use of background diabetes therapy affected the risk of CV death, hospitalizations for heart failure, and progression of chronic kidney disease, among patients treated with empagliflozin. Materials and methods: Patients meeting inclusion and exclusion criteria were randomized to placebo, empagliflozin 10 mg or empagliflozin 25 mg; glucose‐lowering therapy was to remain unchanged for 12 weeks and then adjusted to achieve glycaemic control according to local guidelines. Differences in risk of cardio‐renal outcomes between empagliflozin and placebo by baseline use of metformin, sulphonylurea (SU) and insulin were assessed using a Cox proportional hazards model. Results: Of 7020 eligible patients, 74% were receiving metformin, 43% SU and 48% insulin at baseline (each alone or in combination); the most common regimens were metformin plus SU (20%) and metformin plus insulin (20%). Empagliflozin reduced the risk of CV death irrespective of the use of: metformin [with: hazard ratio (HR) 0.71 (95% confidence interval, CI, 0.54–0.94); without: 0.46 (0.32–0.68); Pinteraction= 0.07]; SU [with: HR 0.64 (0.44–0.92); without: 0.61 (0.46–0.81); Pinteraction = 0.85]; or insulin [with: HR 0.63 (0.46–0.85); without: 0.61 (0.44–0.85); Pinteraction = 0.92]. Reductions in three‐point major adverse CV events, hospitalizations for heart failure, and all‐cause mortality were consistent across subgroups of baseline therapies. Empagliflozin reduced the risks of incident or worsening nephropathy versus placebo irrespective of the use of SU or insulin at baseline (Pinteraction > 0.05), but there was a greater reduction in this risk for patients not using metformin [HR 0.47 (95% CI 0.37–0.59)] versus those using metformin [HR 0.68 (95% CI 0.58–0.79)] at baseline (Pinteraction = 0.01). Conclusions: The addition of empagliflozin to antihyperglycaemic regimens of patients with type 2 diabetes and CV disease consistently reduced their risks of adverse CV outcomes and mortality irrespective of baseline use of metformin, SU or insulin. For chronic kidney disease progression, there may be a larger benefit from empagliflozin in those patients who are not using metformin. [ABSTRACT FROM AUTHOR]

Hyperglycemia is an undisputed epidemiological risk factor for microvascular complications in both type 1 and type 2 diabetes, integral in their causal pathways. Importantly, interventions that reduce the hyperglycemic burden in patients with either type of diabetes reduce the risk of microvascular complications (e.g., retinopathy, nephropathy, neuropathy). Hence, for microvascular risk, hyperglycemia is a proven risk factor and a proven treatment target, as reflected by treatment recommendations and guidelines across most scientific societies world-wide. However, although reducing the hyperglycemic burden to reduce microvascular risk remains a cornerstone of care for patients with type 2 diabetes, this therapeutic imperative does not apply to cardiovascular risk mitigation. This latter aspect is important in the context of interpreting therapeutic impact of treating hyperglycemia on risk for macrovascular complications in patients with type 2 diabetes. This letter, in response to a previous paper, discuss how modest differential glucose control contribute little if anything to the results observed of contemporary cardiovascular outcome trials in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: In the EMPA-REG OUTCOME trial (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease, in comparison with placebo, empagliflozin reduced the risks of 3-point major adverse cardiovascular events (3-point MACE), cardiovascular and all-cause death, and hospitalization for heart failure. We investigated whether these effects varied across the spectrum of baseline cardiovascular risk.Methods: Cardiovascular death, all-cause mortality, 3-point MACE, and hospitalization for heart failure in the pooled empagliflozin and placebo groups were analyzed in subgroups by prior myocardial infarction and stroke at baseline, and by estimated baseline cardiovascular risk based on the 10-point TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention.Results: Of 7020 patients who received the study drug, 65% had a prior myocardial infarction or stroke, and 12%, 40%, 30%, and 18% were at low, intermediate, high, and highest estimated cardiovascular risk according to TIMI Risk Score for Secondary Prevention (≤2, 3, 4, and ≥5 points, respectively). In the placebo group, 3-point MACE occurred during the trial in 7.3%, 9.4%, 12.6%, and 20.6% of patients at low, intermediate, high, and highest estimated baseline risk, respectively. Relative reductions in risk of cardiovascular death, all-cause mortality, 3-point MACE and hospitalization for heart failure with empagliflozin versus placebo were consistent in patients with and without prior myocardial infarction and/or stroke and across subgroups by TIMI Risk Score for Secondary Prevention at baseline ( P>0.05 for randomized group-by-subgroup interactions).Conclusions: Despite all patients having atherosclerotic cardiovascular disease, patients in EMPA-REG OUTCOME demonstrated a broad risk spectrum for cardiovascular events. Reductions in key cardiovascular outcomes and mortality with empagliflozin versus placebo were consistent across the range of cardiovascular risk.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01131676. [ABSTRACT FROM AUTHOR]

The article presents a study which examines cardiovascular outcome with empagliflozin in patients with type 2 diabetes mellitus (T2DM). Empagliflozin Cardiovascular Outcome Event Trial in T2DM Patients and analysis of the risk of cardiovascular disease were conducted in the study which involved 7020 patient with T2DM and cardiovascular disease (CVD). Results highlight the benefit of empagliflozin on the risks of cardiovascular death but demonstrate minor impact of glycemic control.

Aims: Randomized controlled trials have reported an association between pioglitazone and reduced incidence of stroke in type 2 diabetic (T2DM) and insulin‐resistant populations. We investigated this association within a real‐world database. Materials and methods: T2DM patients who initiated pioglitazone between 2000 and 2012 were extracted from the Clinical Practice Research Datalink (CPRD), a UK routine data source. Two non‐exposed control cohorts were matched according to age, gender, HbA1c, diabetes duration, stroke history, co‐morbidities and prior T2DM regimen. Control cohort‐1 comprised patients initiating a new T2DM therapy as their respective case initiated pioglitazone. Control cohort‐2 maintained the same T2DM regimen as their respective case prior to the case initiating pioglitazone. Primary outcome was incident stroke; other outcomes included mortality, length of hospital stay and stroke recurrence. Results: A total of 4234 patients initiating pioglitazone were matched to controls in cohort‐1 and 3604 in cohort‐2. For the primary outcome there were significantly reduced hazard ratios (HRs) for cases: controls. For cohort 1, the HR was 0.666 (95% CI, 0.466‐0.952) during the therapy period and was 0.750 (0.612‐0.919) over the entire observation period; for cohort 2, respective HRs were 0.516 (0.336‐0.794) and 0.773 (0.611‐0.978). There was no significant difference in 30‐day mortality rate or rate of recurrent stroke. For stroke events that required hospitalization, there was a significant difference in length of stay for patients discharged to usual residence (median, 3.0 days vs 7.0 days; P = .008) for control cohort‐2 while undergoing treatment. Conclusions: In support of evidence from 2 large randomized trials, these observational data show that pioglitazone has a potent effect in reducing stroke events in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE In the BI 10773 (Empagliflozin) CardiovascularOutcomeEvent Trial in Type 2Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial involving 7,020 patients with type 2 diabetes and established cardiovascular (CV) disease, empagliflozin given in addition to standard of care reduced the risk of CV death by 38% versus placebo (hazard ratio [HR] 0.62 [95%CI 0.49, 0.77]). This exploratorymediation analysis assesses the extent to which treatment group differences in covariates during the trial contributed to CV death risk reduction with empagliflozin. RESEARCH DESIGN AND METHODS Effectsof potential mediators, identifiedpost hoc,ontheHRforCVdeath withempagliflozin versus placebo were analyzed by Cox regression models, with treatment group adjusted for the baseline value of the variable and its change from baseline or updated mean (i.e., considering all prior values), each as a time-dependent covariate. HRs were compared with amodelwithout adjustment for covariates.Multivariable analyses also were performed. RESULTS Changes in hematocrit and hemoglobinmediated 51.8% and 48.9%, respectively, of the effect of empagliflozin versus placebo on the risk of CV death on the basis of changes from baseline, with similar results in analyses on the basis of updated means. Smaller mediation effects (maximum 29.3%) were observed for uric acid, fasting plasma glucose, and HbA1c. Inmultivariable models, which incorporated effects of empagliflozin on hematocrit, fasting glucose, uric acid, and urine albumin:creatinine ratio, the combined changes from baseline provided 85.2% mediation, whereas updated mean analyses provided 94.6% mediation of the effect of empagliflozin on CV death. CONCLUSIONS In this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo. [ABSTRACT FROM AUTHOR]

Objective:To examine the efficacy and safety of the once-weekly (q.w.) dipeptidyl peptidase-4 inhibitor, omarigliptin, in patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy. Methods:In a randomized, double-blind trial, patients with T2DM on a stable dose of metformin monotherapy (≥1500 mg/day) with glycated hemoglobin (HbA1c) of 7.0–10.5% were randomized to omarigliptin 25 mg q.w. or matching placebo (n = 201 in both) for 24 weeks (primary timepoint) followed by an additional 80-week treatment period. Results:At week 24, from a mean baseline HbA1c of 8.0–8.1%, the least squares (LS) mean (95% CI) change from baseline in HbA1c (primary end-point) was –0.54% (–0.69%, –0.40%) in the omarigliptin group and 0.00% (–0.14%, 0.15%) in the placebo group, for a between-group difference of –0.55% (–0.75%, –0.34%);p < .001. Between-group differences (LS mean 95% CI) for the secondary end-points of 2-h post-meal glucose and fasting plasma glucose (omarigliptin vs placebo) were –0.8 mmol/L (–1.4, –0.2) (p = .011) and –0.5 mmol/L (–0.9, –0.1) (p = .010), respectively. At week 24, the incidences of symptomatic hypoglycemia and subjects with one or more adverse event (AE), serious AEs, and discontinuations due to an AE were similar in the omarigliptin and placebo groups. Over 104 weeks, omarigliptin treatment provided a clinically meaningful reduction in HbA1c. Conclusions:In patients with T2DM, adding omarigliptin 25 mg q.w. to metformin monotherapy improved glycemic control over 104 weeks and was generally welltolerated with a low risk of hypoglycemia. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 77-year-old Latina woman with poorly controlled type 2 diabetes. Topics discussed include increase in her blood glucose levels as determined by fingerstick glucose monitoring; abrupt nature of the worsening hyperglycemia was perplexing and considered whether subtle changes in her self-management habits could be the underlying cause; and Type 2 diabetes is known to be a progressive disease.

Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin's affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U.S. However, based on the release of newer agents over the recent past, some have suggested that the modern approach to disease management should be based upon identification of its etiology and correcting the underlying biological disturbances. That is, we should use interventions that normalize or at least ameliorate the recognized derangements in physiology that drive the clinical manifestation of disease, in this circumstance, hyperglycemia. Thus, it is argued that therapeutic interventions that target glycemia but do not correct the underlying pathogenic disturbances are unlikely to result in a sustained benefit on the disease process. In our field, there is an evolving debate regarding the suggested first step in diabetes management and a call for a new paradigm. Given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative that precedes the counterpoint narrative below, Drs. Abdul-Ghani and DeFronzo provide their argument that a treatment approach for type 2 diabetes based upon correcting the underlying pathophysiological abnormalities responsible for the development of hyperglycemia provides the best therapeutic strategy. Such an approach requires a change in the recommendation for first-line therapy from metformin to a GLP-1 receptor agonist. In the counterpoint narrative below, Dr. Inzucchi argues that based on the medical community's extensive experience and the drug's demonstrated efficacy, safety, low cost, and cardiovascular benefits, metformin should remain the "foundation therapy" for all patients with type 2 diabetes, barring contraindications.-William T. CefaluChief Scientific, Medical & Mission Officer, American Diabetes Association. [ABSTRACT FROM AUTHOR]

Objective: The Insulin Resistance Intervention after Stroke (IRIS) trial recently found that pioglitazone reduced risk for stroke and myocardial infarction in patients with insulin resistance but without diabetes who had had a recent ischemic stroke or transient ischemic attack (TIA). This report provides detailed results on the metabolic effects of pioglitazone and the trial's prespecified secondary aim of diabetes prevention.Research Design and Methods: A total of 3,876 patients with recent ischemic stroke or TIA, no history of diabetes, fasting plasma glucose (FPG) <126 mg/dL, and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) score >3.0 were randomly assigned to pioglitazone or placebo. Surveillance for diabetes onset during the trial was accomplished by periodic interviews and annual FPG testing.Results: At baseline, the mean FPG, HbA1c, insulin, and HOMA-IR were 98.2 mg/dL (5.46 mmol/L), 5.8% (40 mmol/mol), 22.4 μIU/mL, and 5.4, respectively. After 1 year, mean HOMA-IR and FPG decreased to 4.1 and 95.1 mg/dL (5.28 mmol/L) in the pioglitazone group and rose to 5.7 and 99.7 mg/dL (5.54 mmol/L), in the placebo group (all P < 0.0001). Over a median follow-up of 4.8 years, diabetes developed in 73 (3.8%) participants assigned to pioglitazone compared with 149 (7.7%) assigned to placebo (hazard ratio [HR] 0.48 [95% CI 0.33-0.69]; P < 0.0001). This effect was predominately driven by those with initial impaired fasting glucose (FPG >100 mg/dL [5.6 mmol/L]; HR 0.41 [95% CI 0.30-0.57]) or elevated HbA1c (>5.7% [39 mmol/mol]; HR 0.46 [0.34-0.62]).Conclusions: Among patients with insulin resistance but without diabetes who had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events. Pioglitazone is the first medication shown to prevent both progression to diabetes and major cardiovascular events as prespecified outcomes in a single trial. [ABSTRACT FROM AUTHOR]

Background: The management of hyperglycemia in the intensive care unit has been a controversial topic for more than a decade, with target ranges varying from 80-110 mg/dL to <200 mg/dL. Multiple insulin infusion protocols exist, including several computerized protocols, which have attempted to achieve these targets. Importantly, compliance with these protocols has not been a focus of clinical studies.Methods: GlucoCare™, a Food and Drug Administration (FDA)-cleared insulin-dosing calculator, was originally designed based on the Yale Insulin Infusion Protocol to target 100-140 mg/dL and has undergone several modifications to reduce hypoglycemia. The original Yale protocol was modified from 100-140 mg/dL to a range of 120-140 mg/dL (GlucoCare 120-140) and then to 140 mg/dL (GlucoCare 140, not a range but a single blood glucose [BG] level target) in an iterative and evidence-based manner to eliminate hypoglycemia <70 mg/dL. The final modification [GlucoCare 140(B)] includes the addition of bolus insulin "midprotocol" during an insulin infusion to reduce peak insulin rates for insulin-resistant patients. This study examined the results of these protocol modifications and evaluated the role of compliance with the protocol in the incidence of hypoglycemia <70 mg/dL.Results: Protocol modifications resulted in mean BG levels of 133.4, 136.4, 143.8, and 146.4 mg/dL and hypoglycemic BG readings <70 mg/dL of 0.998%, 0.367%, 0.256%, and 0.04% for the 100-140, 120-140, 140, and 140(B) protocols, respectively (P < 0.001). Adherence to the glucose check interval significantly reduced the incidence of hypoglycemia (P < 0.001). Protocol modifications led to a reduction in peak insulin infusion rates (P < 0.001) and the need for dextrose-containing boluses (P < 0.001).Conclusion: This study demonstrates that refinements in protocol design can improve glucose control in critically ill patients and that the use of GlucoCare 140(B) can eliminate all significant hypoglycemia while achieving mean glucose levels between 140 and 150 mg/dL. In addition, attention to the timely performance of glucose levels can also reduce hypoglycemic events. [ABSTRACT FROM AUTHOR]

The article presents the authors' views on the treatment of heart failure with antihyperglycemic medications. It discusses transformation in diabetes mellitus care in patients with cardiovascular disease. It also discusses recommendations of a consensus report from the American Diabetes Association and the European Association for the Study of Diabetes.

The article focuses on the study of retinopathy outcomes related to empagliflozin and placebo. It mentions that sodium–glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular (CV) events in CV outcome trials in type 2 diabetes patients. It mentions that the SGLT2 inhibitor empagliflozin decrease the risk of 3-point major adverse CV events.

Background: Diabetes confers an increased risk of adverse cardiovascular and renal events. In the EMPA-REG OUTCOME trial, empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial.Methods: We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2) of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria.Results: Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). Doubling of the serum creatinine level occurred in 70 of 4645 patients (1.5%) in the empagliflozin group and in 60 of 2323 (2.6%) in the placebo group, a significant relative risk reduction of 44%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population.Conclusions: In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care. (Funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.). [ABSTRACT FROM AUTHOR]

Diabetes affects a large and diverse number of individuals who share in common its risks for complications but who differ greatly from one another in age, health, and a number of circumstances influential to successful treatment. Because type 2 diabetes comprises the majority of diabetes cases, a number of agents have been developed for its treatment. Their unique properties offer opportunities to overcome some of the treatment limitations of older medicines and enable a more individualized and flexible approach to glucose-lowering. At the same time, new medications are accompanied by greater costs and uncertainties about their long-term benefits or safety, and thus the present state of care for type 2 diabetes places focus on a process of shared decision-making between the clinician and patient as to which treatments can optimize health while minimizing harms. We review the major classes of diabetes agents and provide some guidance for how one might approach decision-making in choosing among them. [ABSTRACT FROM AUTHOR]

Hyperglycemia is a commonly encountered metabolic derangement in the ICU. Important cellular pathways, such as those related to oxidant stress, immunity, and cellular homeostasis, can become deranged with prolonged and uncontrolled hyperglycemia. There is additionally a complex interplay between nutritional status, ambient glucose concentrations, and protein catabolism. While the nuances of glucose management in the ICU have been debated, results from landmark studies support the notion that for most critically ill patients moderate glycemic control is appropriate, as reflected by recent guidelines. Beyond the target population and optimal glucose range, additional factors such as hypoglycemia and glucose variability are important metrics to follow. In this regard, new technologies such as continuous glucose sensors may help alleviate the risks associated with such glucose fluctuations in the ICU. In this review, we will explore the impact of hyperglycemia upon critical cellular pathways and how nutrition provided in the ICU affects blood glucose. Additionally, important clinical trials to date will be summarized. A practical and comprehensive approach to glucose management in the ICU will be outlined, touching upon important issues such as glucose variability, target population, and hypoglycemia. [ABSTRACT FROM AUTHOR]

Aim: Despite links to clinical outcomes in patients with type 2 diabetes mellitus (T2DM), the clinical utility of glycaemic variability (GV) measures is unknown. We evaluated the correlation between baseline GV, and glycated haemoglobin (HbA1c) attainment and hypoglycaemic events during treatment intensification in a large group of patients.Methods: Patient-level data from six 24-week clinical trials of T2DM patients undergoing treatment intensification with basal insulin or comparators (N = 1699) were pooled. Baseline GV measures included standard deviation (SD), mean amplitude of glycaemic excursions (MAGE), mean absolute glucose (MAG), coefficient of variation (CV), high blood glucose index (HBGI), and low blood glucose index (LBGI) and were correlated with HbA1c change and hypoglycaemic events.Results: All mean GV measures, excluding CV which worsened, improved significantly from baseline to Week 24, with the largest proportional reduction obtained for HBGI (-65.5%). When assessed as mean individual percentage changes, only HBGI improved significantly. Baseline GV correlated positively with Week 24 HbA1c for SD, MAGE, and HBGI. Baseline HBGI and CV correlated negatively and positively, respectively, with Week 24 HbA1c change. Correlations also existed between most baseline GV measures and age, body mass index, Week 24 fasting plasma glucose, Week 24 postprandial plasma glucose, and hypoglycaemic events; statistical significance depended on the specific measure.Conclusions: Pre-treatment GV is associated with glycaemic outcomes in T2DM patients undergoing treatment intensification over 24 weeks. HBGI might be the most robust predictor, warranting validation in dedicated prospective studies or randomized trials to assess the predictive value of measuring GV. [ABSTRACT FROM AUTHOR]

Aim: Despite links to clinical outcomes in patients with type 2 diabetes mellitus (T2DM), the clinical utility of glycaemic variability (GV) measures is unknown. We evaluated the correlation between baseline GV, and glycated haemoglobin (HbA1c) attainment and hypoglycaemic events during treatment intensification in a large group of patients.Methods: Patient-level data from six 24-week clinical trials of T2DM patients undergoing treatment intensification with basal insulin or comparators (N=1699) were pooled. Baseline GV measures included standard deviation (SD), mean amplitude of glycaemic excursions (MAGE), mean absolute glucose (MAG), coefficient of variation (CV), high blood glucose index (HBGI), and low blood glucose index (LBGI) were correlated with HbA1c change and hypoglycaemic events.Results: All mean GV measures, excluding CV which worsened, improved significantly from baseline to Week 24, with the largest proportional reduction obtained for HBGI (-65.5%). When assessed as mean individual percentage changes only HBGI improved significantly. Baseline GV correlated positively with Week 24 HbA1c for SD, MAGE, and HBGI. Baseline HBGI and CV correlated negatively and positively, respectively, with Week 24 HbA1c change. Correlations also existed between most baseline GV measures and age, body mass index, Week 24 fasting plasma glucose, Week 24 postprandial plasma glucose, and hypoglycaemic events; statistical significance depended on the specific measure.Conclusions: Pre-treatment GV is associated with glycaemic outcomes in T2DM patients undergoing treatment intensification over 24 weeks. HBGI might be the most robust predictor, warranting validation in dedicated prospective studies or randomized trials to assess the predictive value of measuring GV. [ABSTRACT FROM AUTHOR]

The article offers information on hyperglycemia management for type 2 diabetes in the U.S. and updates for 2015. Topics include patient-centered approaches to management, the position statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), and glucose control and glycemic targets as the main focus of management. Other topics include therapeutic options like sodium-glucose cotransporter 2 inhibitors and thiazolidinediones (TSDs).

Importance: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.Objective: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.Evidence Acquisition: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.Results: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100,000 person-years to 10 per 100,000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus--use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.Conclusions and Relevance: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function. [ABSTRACT FROM AUTHOR]

IMPORTANCE Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m²). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 00 0 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus--use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use. CONCLUSIONS AND RELEVANCE Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function. [ABSTRACT FROM AUTHOR]

The article presents author's comments on the use of thiazolidinediones (TZDs) as glucose-lowering agent. It mentions that the peroxisome proliferator activated receptor (PPAR) agonists is used for patients with type 2 diabetes mellitus (T2DM) as metformin and sulfonylureas. It mentions that TZDs had insulin-sensitizing properties and insulin resistance.

Background Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. The aim of the ongoing EMPA-REG OUTCOME™ trial is to determine the long-term CV safety of empagliflozin, as well as investigating potential benefits on microvascular outcomes. Methods Patients who were drug-naïve (HbA1c⩾7.0% and ⩽9.0%), or on background glucose-lowering therapy (HbA1c⩾7.0% and ⩽10.0%), and were at high risk of CV events, were randomized (1:1:1) and treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo (double blind, double dummy) superimposed upon the standard of care. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. CV events will be prospectively adjudicated by an independent Clinical Events Committee. The trial will continue until ⩾691 confirmed primary outcome events have occurred, providing a power of 90% to yield an upper limit of the adjusted 95% CI for a hazard ratio of <1.3 with a one-sided α of 0.025, assuming equal risks between placebo and empagliflozin (both doses pooled). Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes (time to first occurrence of CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina pectoris) where non-inferiority is achieved. Results Between Sept 2010 and April 2013, 592 clinical sites randomized and treated 7034 patients (41% from Europe, 20% from North America, and 19% from Asia). At baseline, the mean age was 63 ± 9 years, BMI 30.6 ± 5.3 kg/m2, HbA1c 8.1 ± 0.8%, and eGFR 74 ± 21 ml/min/1.73 m2. The study is expected to report in 2015. Discussion EMPA-REG OUTCOME™ will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk, with the potential to show cardioprotection. [ABSTRACT FROM AUTHOR]

Objective: To determine which measures-impaired fasting glucose (IFG), elevated HbA1c, or both-best predict incident diabetes in older adults.Research Design and Methods: From the Health, Aging, and Body Composition study, we selected individuals without diabetes, and we defined IFG (100-125 mg/dL) and elevated HbA1c (5.7-6.4%) per American Diabetes Association guidelines. Incident diabetes was based on self-report, use of antihyperglycemic medicines, or HbA1c ≥6.5% during 7 years of follow-up. Logistic regression analyses were adjusted for age, sex, race, site, BMI, smoking, blood pressure, and physical activity. Discrimination and calibration were assessed for models with IFG and with both IFG and elevated HbA1c.Results: Among 1,690 adults (mean age 76.5, 46% men, 32% black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of diabetes were 6.2 (95% CI 4.4-8.8) in those with IFG (versus those with fasting plasma glucose [FPG] <100 mg/dL) and 11.3 (7.8-16.4) in those with elevated HbA1c (versus those with HbA1c <5.7%). When FPG and HbA1c were considered together, odds ratios were 3.5 (1.9-6.3) in those with IFG only, 8.0 (4.8-13.2) in those with elevated HbA1c only, and 26.2 (16.3-42.1) in those with both IFG and elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated HbA1c to the model with IFG resulted in improved discrimination and calibration.Conclusions: Older adults with both IFG and elevated HbA1c have a substantially increased odds of developing diabetes over 7 years. Combined screening with FPG and HbA1c may identify older adults at very high risk for diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To determine which measures impaired fasting glucose (IFG), elevated HbA1c or both--best predict incident diabetes in older adults. RESEARCH DESIGN AND METHODS--From the Health, Aging, and Body Composition study, we selected individuals without diabetes, and we defined IFG (100-125 mg/dL) and elevated HbA1c (5.7-6.4%) per American Diabetes Association guidelines. Incident diabetes was based on self-report, use of antihyperglycemic medicines, or HbA1c ≥6.5% during 7 years of follow-up. Logistic regression analyses were adjusted for age, sex, race, site, BMI, smoking, blood pressure, and physical activity. Discrimination and calibration were assessed for models with IFG and with both IFG and elevated HbA1c. RESULTS--Among 1,690 adults (mean age 76.5, 46% men, 32% black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of diabetes were 6.2 (95% CI 4.4-8.8) in those with IFG (versus those with fasting plasma glucose [FPG],100 mg/dL) and 11.3 (7.8-16.4) in those with elevated HbA1c (versus those with HbA1c,5.7%). When FPG and HbA1c were considered together, odds ratios were 3.5 (1.9-6.3) in those with IFG only, 8.0 (4.8-13.2) in those with elevated HbA1c only, and 26.2 (16.3-42.1) in those with both IFG and elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated HbA1c to themodel with IFG resulted in improved discrimination and calibration. CONCLUSIONS--Older adults with both IFG and elevated HbA1c d have a substantially increased odds of developing diabetes over 7 years. Combined screening with FPG and HbA1c may identify older adults at very high risk for diabetes. [ABSTRACT FROM AUTHOR]

Illness, particularly when severe, leads to increased concentrations of counter-regulatory factors which induce insulin resistance and predispose patients to stress hyperglycemia. Elevated glucose concentrations are common in hospitalized patients, both those with as well as without recognized diabetes. Substantial data has emerged over the past decade that quality glucose management in these individuals actually improves clinical outcomes. Controlling glucose in this setting is challenging, given the phenotypic variability amongst patients, with fluctuating courses of acute illnesses and unpredictable nutritional schedules. We review the evidence basis that has informed national standards and glucose targets in both critically and non-critically ill patients. In the intensive care setting, insulin infusions are now widely endorsed to quickly achieve and maintain glucose control. On the hospital wards, physiological subcutaneous insulin therapy, incorporating both basal and nutritional components, is emerging as the optimal treatment strategy. The transition to outpatient care is another important aspect of any hospital glycemic management program. [ABSTRACT FROM AUTHOR]

Background: The management of critically ill hyperglycemic patients in the intensive care unit (ICU) has been fraught with recent controversy. Only one randomized trial has demonstrated a mortality benefit to intensive glycemic control, with all subsequent studies failing to confirm this benefit and revealing a markedly increased risk of severe hypoglycemia (SH) in intensively treated patients. In most of these trials, adherence to the protocols were neither tracked nor reported.Methods: A retrospective analysis of all patients admitted to an ICU who were treated with an insulin infusion directed by the GlucoCare™ IGC System, an FDA-cleared insulin-dosing calculator (Yale 100-140 mg/dL protocol). Mean blood glucose (BG) levels, time to target range and incidence of SH (<40 mg/dL) and moderate hypoglycemia (MH) (40-69 mg/dL) were determined, and potential causes of hypoglycemic episodes were assessed.Results: Mean post-target BG was approximately 123 mg/dL. Of >55,000 readings in 1,657 patients, overall incidence of SH was 0.01% of readings and 0.3% of patients. MH occurred in 1.1% of readings and 17.6% of patients. The top potential causes of MH were: (1) Protocol-directed recommendations including continuation of insulin with BG <100 mg/dL and decreases in the frequency of BG checks (63.7%), and (2) Staff non-adherence to protocol directives (15.3%).Conclusions: The results of the GlucoCare-directed Yale 100-140 mg/dL protocol experience revealed an extremely low incidence of SH and an incidence of MH of 1.1%. The incidence of SH in this study was lower than the control group of the NICE-SUGAR study and are supportive of the new Society of Critical Care guidelines to target BG levels of 100-150 mg/dL in critically ill patients. Further refinements to the original protocol and emphasis on staff adherence to protocol directives could potentially further reduce these very low hypoglycemia rates. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 42-year-old man with hypertension. The patient received atenolol and chlorthadilone and his parents have type 2 diabetes. His body-mass index and blood pressure were given and the ways for screening this patient for diabetes were assessed. Information about the implications of making diagnosis for diabetes in a patient is mentioned, as well as the various screening tests for diabetes.

The article discusses the position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) on a patient-centered approach for the management of hyperglycemia in type 2 diabetes. A background on epidemiology and health care of type 2 diabetes is provided. An overview of its pathogenesis is presented. Also included are the different therapeutic options for the disorder.

Hyperglycemia is common in critical illness and has been associated with increased morbidity and mortality. An era of tight glucose control began when intensive insulin therapy was shown to improve outcomes in a single-center randomized trial. More recently, with the publication of additional studies, questions have been raised regarding the efficacy and safety of intensive glycemic management. This article will review the biologic mechanisms that may help us understand why and how hyperglycemia and insulin are relevant in critical illness. We will then explore insights gleaned from available clinical trials. Finally, we will discuss specific areas of controversy that relate to the implementation of glycemic control in the intensive care unit, such as the ideal glucose target and the importance of hypoglycemia. [ABSTRACT FROM PUBLISHER]

The article focuses on the quality assessment of comprehensive cardiometabolic care of patients suffering from type 2 diabetes in the U.S. Topics discussed include an overview of type 2 diabetes, the impact of its prevalence on its mortality and complications, and the formation of the Diabetes Collaborative Registry.

The article reports on the results of research which was conducted in an effort to determine whether the mortality risk associated with hypoglycemic events is similar in patients who develop hypoglycemia spontaneously and those who develop it as a result of insulin therapy. Researchers used a retrospective cohort study which used data from Health Facts, a database of patients hospitalized across the U.S. They found that while hypoglycemia was associated with increased mortality in patients with acute myocardial infarction, this risk was confined to patients who developed hypoglycemia spontaneously. They also found that iatrogenic hypoglycemia after insulin therapy was not associated with higher mortality risk.

The authors express their opinion regarding the Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial reported in the issue. The trial found increased mortality in a group receiving intensive blood glucose control. The authors believe that further exploration is needed to determine the precise causes of death in the patients. They caution against overreaction to the NICE-SUGAR findings.

The article presents a study which examines the glucose normalization among patients with acute myocardial infarction in the U.S. It states that high blood glucose levels on hospital admission have connection with increased mortality in patients with acute myocardial infarction. It concludes that glucose normalization after hospital admission is associated with better survival in hyperglycemic patients with acute myocardial infarction whether or not they receive insulin therapy. It highlights the need for effective strategy on intentional glucose lowering with insulin therapy.

This article presents a letter to the editor in response to "Finding new treatments for diabetes: how many, how fast...how good?" by D.M. Nathan in the February 1, 2007 issue.

The article discusses the available imaging techniques in assessing coronary artery disease (CAD) in symptomatic patients with diabetes. It states that a number of imaging techniques can assess myocardial perfusion, including positron emission tomography (PET), first-pass perfusion imaging with magnetic resonance imaging (MRI), and myocardial contrast echocardiography.

Diabetes mellitus and heart failure (HF), both of which are associated with high rates of adverse cardiovascular outcomes, commonly coexist. Given the marked increases in diabetes prevalence in developed countries, the proportion of the population with both conditions is likely to increase substantially. This article reviews the epidemiology of HF and diabetes, the mechanisms whereby diabetes causes HF, and the pharmacotherapy of both HF and diabetes. Specific challenges in treating patients with both HF and diabetes are also addressed. [Copyright &y& Elsevier]

OBJECTIVE -- Thiazolidinediones (TZDs) and metformin are insulin-sensitizing antihyperglycemic agents with reported benefits on atherosclerosis. Despite extensive use in patients with diabetes and cardiovascular disease, there is a paucity of outcomes data with metformin and none yet with TZDs. We sought to determine the impact of these insulin sensitizers on outcomes in diabetic patients after hospitalization with acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS -- We conducted a retrospective cohort study of 24,953 Medicare beneficiaries with diabetes discharged after hospitalization with AMI between April 1998 and March 1999 or July 2000 and June 2001. The independent association between discharge prescription for metformin, TZD, or both agents and outcomes at 1 year was assessed in multivariable Cox proportional hazards models, adjusting for patient, physician, and hospital variables. The primary outcome was time to death within 1 year of discharge; secondary outcomes were time to first rehospitalization within 1 year of discharge for AMI, heart failure, and all causes. RESULTS -- There were 8,872 patients discharged on an antihyperglycemic agent, of which 819 were prescribed a TZD, 1,273 metformin, and 139 both drugs. After multivariable analysis, compared with patients prescribed an antihyperglycemic regimen that included no insulin sensitizer, mortality rates were not significantly different in patients treated with either metformin (hazard ratio [HR] 0.92 [95% CI 0.81-1.06]) or a TZD (0.92 [0.80-1.05]) but were lower in those prescribed both drugs (0.52 [0.34-0.82]). The results were similar among patients with heart failure. The prescription of a TZD was associated with a borderline higher risk of all-cause readmission (1.09[1.00-1.20]), predominately due to a higher risk for heart failure readmission (1.17 [1.05-1.301). CONCLUSIONS -- Individually, prescription of insulin-sensitizing drugs is not associated with a significantly different risk of death in older diabetic patients within 1 year following AMI compared with other antihyperglycemic agents. Combined, however, metformin and TZDs may exert benefit. TZD prescription is associated with a higher risk of readmission for heart failure after myocardial infarction. [ABSTRACT FROM AUTHOR]

Criticizes recommendations of the American College of Endocrinology regarding implementation of a stricter blood glucose control to improve the hospital management of hyperglycemia. Overview of clinical trials indicating benefit from short-term strict glucose control in hospitalized patients; Limitation of an uncontrolled study of implementing an insulin infusion protocol in the cardiothoracic intensive care unit; Guidelines on the management of hospitalized diabetes patients.