Identifying Risk Factors for Severe Hypoglycemia in Hospitalized Patients with Diabetes

ObjectiveSome of the deleterious effects of hypoglycemia in hospitalized patients include increased rates of mortality and longer length of stay. Our primary objective was to identify the risk factors associated with severe hypoglycemia to identify those patients at highest risk.MethodsThe medical records of 5,026 patients with diabetes mellitus (DM) admitted in 2010 were reviewed to identify those patients that developed severe hypoglycemia (blood glucose [BG] < 40 mg/dL). We performed c2 tests to assess statistical significance. Adjusted logical regression was used to determine the risk factors for hypoglycemia in the hospital.ResultsOut of 5,026 DM patients included in our review, 81 experienced severe hypoglycemia (1.6%). Statistically higher proportions of chronic kidney disease (CKD; 69.1% vs. 46.9%, P < .001), congestive heart failure (CHF; 48.1% vs. 28.5%, P < .001), sepsis (49.4% vs. 12.5%, P < .001), insulin use (45.7% vs. 26.04%, P = .000), type 1 DM (21% vs. 5.1%, P = .000), and cirrhosis (14.8% vs. 7.2%, P = .009) were seen in the severe hypoglycemic group compared to the nonsevere hypoglycemic group. Overall, 84% of patients who experienced an episode of severe hypoglycemia in the hospital (BG < 40 mg/dL) had a previous episode of hypoglycemia (BG < 70 mg/dL). The odds ratios (ORs) for type 1 DM, sepsis, previous hypoglycemia, and insulin use were 3.43 (95% confidence interval [CI] 1.81, 6.49), 2.64 (95% CI 1.6, 4.35), 46.1 (95% CI 24.76, 85.74), and 1.66 (95% CI 1.02, 2.69), respectively.ConclusionPrior episodes of hypoglycemia in the hospital, the presence of type 1 DM, insulin use, and sepsis were identified as independent risk factors for the development of severe hypoglycemia in the hospital. (Endocr Pract. 2014;20:1051-1056)     

Effect of Baseline Glycosylated Hemoglobin A1C on Glycemic Control and Diabetes Management following Initiation of Once-daily Insulin Detemir in Real-Life Clinical Practice

ObjectiveThe SOLVE study investigated the initiation of basal insulin in patients with type 2 diabetes on oral antidiabetic (OAD) treatment and outcomes in patients with varying levels of glycemic control at baseline.MethodsThis was an observational cohort study conducted in 10 countries using insulin detemir. Data were collected at 3 clinic visits (baseline, 12-week interim, and 24-week final visit).ResultsA total of 13,526 (77.9%) patients were included in the glycosylated hemoglobin A1c (HbA1c) subset analysis. Patients were grouped according to pre-insulin HbA1c values as follows: HbA1c <7.6% (n = 2,797); HbA1c 7.6-9% (n = 5,366), and HbA1c >9% (n = 5,363). A total of 27 patients experienced serious adverse drug reactions (SADRs) and/or severe hypoglycemia (3, 10, and 11 patients with pre-insulin HbA1c <7.6%, 7.6-9.0%, and >9.0%, respectively). All patient subgroups realized improvements in HbA1c, with the pre-insulin HbA1c >9% subgroup having the largest HbA1c reduction (-2.4% versus -0.9% and -0.2% for HbA1c subgroups 7.6-9% and <7.6%, respectively). In the total cohort (n = 17,374), the incidence of severe hypoglycemia decreased from 4 events per 100 person years to <1 event per 100 person years by final visit; the incidence of minor hypoglycemia increased from 1.6 to 1.8 events per person year.ConclusionsIn this study, insulin initiation was delayed until late in disease course, and overall concordance with internationally recognized guidelines was low. The initiation of once-daily insulin detemir was associated with substantial improvements in glycemic control and was not associated with an increase in severe hypoglycemia or weight gain. (Endocr Pract. 2013;19:462-470)     

Impact of a Hypoglycemia Reduction Bundle and a Systems Approach to Inpatient Glycemic Management

Objective: Uncontrolled hyperglycemia and iatrogenic hypoglycemia represent common and frequently preventable quality and safety issues. We sought to demonstrate the effectiveness of a hypoglycemia reduction bundle, proactive surveillance of glycemic outliers, and an interdisciplinary data-driven approach to glycemic management.Methods: Population: all hospitalized adult non–intensive care unit (non-ICU) patients with hyperglycemia and/or a diagnosis of diabetes admitted to our 550-bed academic center across 5 calendar years (CYs). Interventions: hypoglycemia reduction bundle targeting most common remediable contributors to iatrogenic hypoglycemia; clinical decision support in standardized order sets and glucose management pages; measure-vention (daily measurement of glycemic outliers with concurrent intervention by the inpatient diabetes team); educational programs. Measures and analysis: Pearson chi-square value with relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare glycemic control, hypoglycemia, and hypoglycemia management parameters across the baseline time period (TP1, CY 2009–2010), transitional (TP2, CY 2011–2012), and mature postintervention phase (TP3, CY 2013). Hypoglycemia defined as blood glucose <70 mg/dL, severe hypoglycemia as <40 mg/dL, and severe hyperglycemia >299 mg/dL.Results: A total of 22,990 non-ICU patients, representing 94,900 patient-days of observation were included over the 5-year study. The RR TP3:TP1 for glycemic excursions was reduced significantly: hypoglycemic stay, 0.71 (95% CI, 0.65 to 0.79); severe hypoglycemic stay, 0.44 (95% CI, 0.34 to 0.58); recurrent hypoglycemic day during stay, 0.78 (95% CI, 0.64 to 0.94); severe hypoglycemic day, 0.48 (95% CI, 0.37 to 0.62); severe hyperglycemic day (>299 mg/dL), 0.76 (95% CI, 0.73 to 0.80).Conclusion: Hyperglycemia and hypoglycemia event rates were both improved, with the most marked effect on severe hypoglycemic events. Most of these interventions should be portable to other hospitals.Abbreviations: BG = blood glucose CDS = clinical decision support CI = confidence interval CY = calendar year DIG = diabetes initiative group EHR = electronic health record ICU = intensive care unit RR = relative risk SHM = Society of Hospital Medicine TP = time period     

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients

ObjectiveNondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.MethodsThis case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).ResultsThe HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL).ConclusionCKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.     

Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes

Purpose

To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain).

Methods

This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73m² and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy.

Results

CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4–1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6–2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73m² [OR], 95% confidence interval [CI], 1.3 (1.1–1.6).

Conclusions

These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.     

Association of Individual Non-Steroidal Anti-Inflammatory Drugs and Chronic Kidney Disease: A Population-Based Case Control Study

Background

Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs.

Aim

The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.

Methods

A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.

Results

Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21).

Conclusions

The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.     

Five-Year Incidence of Chronic Kidney Disease (Stage 3-5) and Associated Risk Factors in a Spanish Cohort: The MADIABETES Study

Objective

To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m²) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use.

Design

The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).

Results

The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12–11.44) and the incidence density was 2.07 (95% CI = 1.83–2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19–2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13–4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42–2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25–2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30–2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02–2.24).

Conclusions

After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.     

Improved Glycemic Control with Insulin Glargine Versus Pioglitazone as Add-On Therapy to Sulfonylurea or Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus

ObjectiveTo compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes.MethodsThis 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite ≥ 3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels ≤ 7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia.ResultsAt end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/ dL; 95% confidence interval, -47.6 to -22.2; P < .0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatmentemergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose < 70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P <.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups.ConclusionThe addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in < 5% of patients in the insulin glargine treatment group. (Endocr Pract. 2010;16:588-599)     

Decreased vascular endothelial growth factor response to acute hypoglycemia in type 2 diabetic patients with hypoglycemic coma

IntroductionPlasma vascular endothelial growth factor (VEGF) was shown to increase during acute hypoglycemia and could mediate rapid adaptation of the brain. In this study we examined the neuroendocrine response in patients with type 2 diabetes mellitus (T2DM) in hypoglycemic coma or with acute neuroglycopenic symptoms.MethodsWe prospectively studied 135 consecutive T2DM patients admitted for severe hypoglycemia during a 2-year period. We collected clinical variables and measured plasma concentrations of VEGF, epinephrine, norepinephrine, cortisol and growth hormone at admission and 30 min afterwards.ResultsThirty two patients developed hypoglycemic coma and 103 did not lose consciousness. Median plasma VEGF level of coma patients was 3.1-fold lower at baseline than that of non-coma patients, and even 5.3-fold lower 30 min afterwards. Plasma epinephrine concentration was significantly lower just at baseline in coma patients. On the contrary, there were no differences in concentrations of the other hormones. Multivariate logistic regression analysis showed that VEGF concentration (OR 0.68; CI 0.51–0.95) was a protective factor against the development of coma.ConclusionsVEGF and epinephrine responses to acute hypoglycemia are reduced in T2DM patients who develop hypoglycemic coma. An increased plasma VEGF concentration appeared to be a protective factor against the development of hypoglycemic coma.     

Outcome of Tuberculosis Treatment in Patients with Diabetes Mellitus Treated in the Revised National Tuberculosis Control Programme in Malappuram District,Kerala, India

Settings

Kerala State, India has reported the greatest dual burden of Tuberculosis (TB) and Diabetes Mellitus (DM). Malappuram district in Kerala has monitored and recorded DM status and its control from 2010 under Revised National Tuberculosis Control Program (RNTCP).

Objectives

To assess, under programme conditions, comprehensiveness of recording DM status among TB cases and the TB treatment outcomes among DM patients (disaggregated by glycemic control) and compare with-non DM patients.

Design

This retrospective record review included 3,116TB patients from April 2010 to September 2011.DM was defined as per international guidelines and TB treatment outcomes were categorized as favourable(cured and treatment completed) and unfavourable(death, default, failure and transfer out). Relative Risk (RR) and 95% confidence intervals(CI) were calculated to assess the risk of unfavourable outcomes.

Results

DM status was recorded in 90% of TB cases and 667 (24%) had DM. 17% of DM patients and 23% of patients with unknown DM status had unfavourable outcomes but this difference was not statistically significant. Unadjusted RR for poor glycemic control or unknown control status for unfavourable outcome were (2.00; 95% CI 0.97–4.13) and (2.14; 95% CI 1.11–4.13).

Conclusion

This study could not confirm an adverse association between DM or its control during treatment and the course of response to TB treatment.DM screening in TB cases and recording of DM care needs to be improved to enable more conclusive evidence.     

Management of Type 2 Diabetes Mellitus with Basal-Prandial Insulin Therapy: A Case-Based Review

Background: Diabetes mellitus (DM) is a growing epidemic in the United States—20.8 million people are affected and 90% to 95% of all diagnosed cases are type 2 DM. Nevertheless, implementation of insulin therapy is often delayed in patients with type 2 DM. This delay can increase the risk of DM-related complications, including microvascular neuropathy, nephropathy, retinopathy, and cardiovascular disease.Objective: This article provides a case-based review outlining a novel strategy for advancing therapy with a modified basal and prandial insulin regimen to achieve recommended glycemic targets in type 2 DM as quickly as possible. Evidence-based treatment strategies are also discussed.Methods: Materials used for this article were identified through an English-language literature search of MEDLINE (1967-2007) using the following terms: insulin, postprandial glucose control, and type 2 diabetes.Results: As shown with this male 46-year-old case study patient, type 2 DM is treated initially with diet and exercise, followed by oral antidiabetic drugs (OADs). However, oral therapy typically reduces glycosylated hemoglobin values only by -1.5% to 2.0%. Intensive therapy with once-daily basal insulin in combination with a previously prescribed OAD regimen can achieve normoglycemia and reduce the long-term complications of DM. In patients with postprandial glucose excursions, prandial insulin can be added using a rapid-acting insulin analogue (aspart, lispro, or glulisine).Conclusions: A key factor in this case patient's ability to reach glycemic targets within I year of diagnosis of type 2 DM was the accelerated implementation of insulin therapy. Such a therapeutic approach obviates the risk for uncontrolled hyperglycemia, which is associated with the standard practice of beginning treatment with diet and exercise alone and slowly advancing by i OAD at a time, ending with insulin therapy as a last resort. (Insulin. 2007;2:118-126)     

Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m²/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.     

Hemoglobin Targets for Chronic Kidney Disease Patients with Anemia: A Systematic Review and Meta-analysis

Background

Numerous studies have identified a relationship between hemoglobin (Hb) levels and mortality in patients with chronic kidney disease (CKD), which have raised concerns about the optimal Hb targets in correction of anemia. Our study is designed to investigate the potential effects of targeted Hb levels, aiming to give some evidence for therapy of renal anemia.

Methodology/Principal Findings

A comprehensive search of Medline, Embase and the Cochrane Database of Systematic Reviews was performed in December 2011 and updated in February 2012 for any new trials. Randomized trials designed to evaluate effects of high (generally the Hb about 13.0 g/dL) and low Hb (generally the Hb about 10.0 g/dL) targets on clinical outcomes in CKD patients with anemia were collected. All statistical analysis was calculated using the RevMan software available free from the Cochrane Collaboration. 24 trials involving 10361 patients were identified. Our findings demonstrated a statistically significant increased risk of mortality in the high Hb levels (RR 1.18; 95% CI 1.02 to 1.37) while the high and low Hb groups were both treated with ESAs. Overall, compared with low Hb levels, high Hb levels are associated with increased risk of hypertension (RR 1.40; 95% CI 1.11 to 1.75), stroke (RR 1.73; 95% CI 1.31 to 2.29), and hospitalizations (RR 1.07; 95% CI 1.01 to 1.14). However, there are no significant differences in the risk of non-fatal myocardial infarction (RR 1. 13; 95% CI 0.79 to 1.61) and renal replacement therapy (RR 1. 00; 95% CI 0.85 to 1.18).

Conclusions/Significances

Targeting low Hb levels are beneficial to CKD patients especially in the predialysis population. The optimal Hb targets to aim for in CKD patients and at what Hb level the risks of adverse events begin to increase remain elusive. Future studies are still needed to elucidate these questions.     

Treatment of Type 2 Diabetes Mellitus With Orally Administered Agents: Advances in Combination Therapy

ObjectiveTo discuss the effects and clinical benefit provided by combining various orally administered antidiabetic drugs (OADs) for the treatment of type 2 diabetes and to examine the advantages of single-tablet combinations with respect to targeting hyperglycemia and adherence.MethodsA review of randomized controlled trials that studied OAD combinations for the treatment of type 2 diabetes was conducted by using search terms in PubMed.ResultsReported data have documented that OAD combination therapies have additional benefits over monotherapy in terms of glycemic efficacy. Results from randomized controlled trials on a range of OAD combinations have demonstrated differences in safety and efficacy. The use of single-tablet OAD combinations has been shown to improve adherence in patients.ConclusionThe development of single-tablet OAD combinations that can address all aspects of glycemia with a favorable tolerability profile has the potential to help patients manage their glycemic control more effectively and to minimize the risk of long-term diabetes-related complications. In addition, single-tablet combinations of agents offer improved convenience for patients as well as potential cost benefits. Thus, they represent an important treatment option for type 2 diabetes. (Endocr Pract. 2009;15:750-762)     

Soluble Tumor Necrosis Factor Receptor 1 and 2 Predict Outcomes in Advanced Chronic Kidney Disease: A Prospective Cohort Study

Background

Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function.

Patients and methods

In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates.

Results

During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1.

Conclusion

sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease.     

Pulmonary Hypertension: Epidemiology in Different CKD Stages and Its Association with Cardiovascular Morbidity

BackgroundPulmonary hypertension (PH) was recently recognized as a common complication of end-stage renal disease (ESRD) that causes an increased risk of mortality. Epidemiological data for this disorder in earlier stages of chronic kidney disease (CKD) and its association with cardiovascular (CV) morbidity are scarce.MethodsWe retrospectively analyzed 2,351 Chinese CKD patients with complete clinical records and echocardiography data between Jan 2008 and May 2012. The patients were divided into the following 6 groups: CKD Stages 1–4; Stage 5 for those not on or initiated on hemodialysis for <3 months; and Stage 5D for the patients undergoing hemodialysis for ≥3 months. The prevalence of PH and CV morbidity was investigated, and their association was evaluated with a logistic regression model.ResultsPH was detected in 426 patients (18.1%). Mild, moderate and severe PH was diagnosed in 12.1%, 4.9% and 1.1% of the patients, respectively. Severe PH was detected in CKD Stages 5 and 5D. CV morbidity was found in 645 patients (27.4%). Compared with the non-PH group, the PH group had a higher risk for cardiac disease but not for cerebrovascular disease risk. PH severity was associated with cardiac morbidity risk [odds ratio (95% CI) for mild PH: 1.79 (1.30–2.47); moderate PH: 2.75 (1.73–4.37); severe PH: 3.90 (1.46–10.42)].ConclusionsOur study showed for the first time the epidemiology profile of PH across the spectrum of CKD. Mild-to-moderate PH occurs with more frequency in advanced CKD, and severe PH is scarce in non-ESRD CKD. PH in CKD is associated with cardiac but not cerebrovascular disease, with increasing cardiac morbidity seen with increasing PH severity. Evidence from prospective studies addressing PH in this population is needed to predict cardiac events.     

Prehypertension and Chronic Kidney Disease in Chinese Population: Four-Year Follow-Up Study

Hypertension is a well established cause of chronic kidney disease (CKD). However, the effect of prehypertension on risk of CKD is controversial. The aim of this study is to determine whether prehypertension increases the risk of CKD events in the Chinese population. We enrolled 20,034 with prehypertension and 12,351 with ideal blood pressure in this prospective study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min 1.73m². The new occurrences of CKD events were collected during follow-up. Cumulative survival and freedom for the occurrence of new CKD events was analyzed using the Kaplan-Meier approach. Multivariate Cox Regression was used to analyze the effect of prehypertension on CKD. The median follow-up time was 47 (interquartile range 44–51) months. 601 new onset CKD events occurred during the follow-up period. The cumulative incidence of new CKD events was higher in the prehypertensive population than that in the ideal blood pressure population (2.10% vs 1.46%, P = 0.0001). Multivariate Cox Regression showed that relative risks (RRs) for the new onset CKD events in the prehypertensive population were 1.69 (95% confidence intervals (CI): 1.41~2.04, P = 0.001) higher than those in the ideal blood pressure population. Similarly, the risks were 1.68 (95% CI: 1.33~2.13 P = 0.001) times higher in females and 2.14 (95% CI: 1.58~2.91 P = 0.001) times higher in males by adjustment for traditional CV risk factors. Our findings demonstrated prehypertension is an independent risk factor for the occurrence of new CKD events in the Chinese population.     

The role of rapid-acting insulin analogues and inhaled insulin in type 2 diabetes mellitus

sBackground:The availability of rapid-acting insulin analogues and inhaled insulin gives clinicians additional treatmentoptions in the management of patients with diabetes mellitus (DM). Combining rapid-acting insulin analogues with basal insulin can more closely mimic physiologic insulin release to maximize glycemic control.Objective:The objective of this article was to discuss the role of rapid-acting insulin analogues and inhaled insulin inthe treatment of patients with type 2 DM.Methods:Materials for this article were obtained through an online search of MEDLINE/PubMed and Google(1996-2006) using the search terms bolus insulin, postprandial, rapid-acting insulin analogues, titration, hypoglycemia, glycemic control, inhaled insulin, and insulins lispro, aspart, and glulisine.Results:Glycosylated hemoglobin (A1C) levels and number of all hypoglycemic episodes were similar in patients withtype 2 DM taking either mealtime rapid-acting insulin analogues or regular human insulin (RHI). Rapid-acting insulins have been successfully used in basal-bolus regimens with a variety of long- and intermediate-acting insulins, as well as with oral hypoglycemic agents. Injectable rapid-acting insulin analogues markedly decreased postprandial glucose (PPG) levels compared with RHI. Better reduction in PPG levels may be key to achieving target A1C levels in some patients, but long-term outcome studies are needed to assess whether lowering PPG levels decreases cardiovascular risk in patients with type 2 DM. Inhaled insulin may be an option for patients who cannot inject insulin, but route of administration and dosing issues limit its use in many patients. The effect of inhaled insulin on PPG is unclear at this time.Conclusions:Although rapid-acting insulin analogues are effective in the management of patients with type 2 DM, the limited numbers of studies have yet to demonstrate that these agents have any significant long-term advantage compared with RHI. In addition, they cost more than RHI. Further studies are needed to compare the efficacy of the rapid-acting insulin analogues, to compare the different dosing regimens used with mealtime insulin administration, and to ascertain if the decrease in PPG levels seen with the use of rapid-acting insulin analogues translates into improved glycemic control and perhaps even a reduction in cardiovascular risk in patients with type 2 DM. (Insulin. 2007;2:61-67) Copyright 2007 Excerpta Medica, Inc.     

Effect of Bromocriptine-Qr On Glycemic Control in Subjects with Uncontrolled Hyperglycemia On One or Two Oral Anti-Diabetes Agents

ObjectiveTo investigate the effect of Bromocriptine QR on glycemic control in patients with type 2 diabetes whose glycemia is poorly controlled on one or two oral anti-diabetes agents.MethodsFive hundred fifteen Type 2 Diabetes Mellitus (T2DM) subjects (ages 18 to 80 and average body mass index [BMI] of 32.7) with baseline HbA1c ≥ 7.5 and on one or two oral anti-diabetes (OAD) medications (metformin, sulfonylurea, and/or thiazolidinediones) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 24 week treatment period. Study investigators were allowed to adjust, if necessary, subject anti diabetes medications during the study to attempt to achieve glycemic control in case of glycemic deterioration. The impact of bromocriptine-QR treatment intervention on glycemic control was assessed in subjects on any one or two OADs (ALL treatment category) (N = 515), or on metformin with or without another OAD (Met/OAD treatment category) (N = 356), or on metformin plus a sulfonylurea (Met/SU treatment category) (N = 245) 1) by examining the between group difference in change from baseline a) concomitant OAD medication changes during the study, and b) HbA1c and 2) by determining the odds of reaching HbA1c of ≤ 7.0% on bromocriptine-QR versus placebo.ResultsSignificantly more patients (approximately 1.5 to 2-fold more; P < .05) intensified concomitant anti diabetes medication therapy during the study in the placebo versus the bromocriptine-QR arm. In subjects that did not change the intensity of the baseline diabetes therapy (72%), and that were on any one or two OADs (ALL), or on metformin with or without another OAD (Met/OAD), or on metformin plus sulfonylurea (Met/SU), the HbA1c change for bromocriptine-QR versus placebo was − 0.47 versus + 0.22 (between group delta of − 0.69, P < .0001), − 0.55 versus + 0.26 (between group delta of − 0.81, P < .0001) and − 0.63 versus + 0.20 (between group delta of − 0.83, P < .0001) respectively, after 24 weeks on therapy. The odds ratio of reaching HbA1c of ≤ 7.0% was 6.50, 12.03 and 11.45 (P < .0002) for these three groups, respectively.ConclusionIn T2DM subjects whose hyperglycemia is poorly controlled on one or two oral agents, bromocrip tine-QR therapy for 24 weeks can provide significant added improvement in glycemic control relative to adding placebo. (Endocr Pract. 2012;18:931-943)     

Exenatide Twice Daily Plus Glargine Versus Aspart 70/30 Twice Daily in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Premixed Human Insulin and Metformin

ObjectiveMany patients with type 2 diabetes treated with premixed insulin gradually have inadequate glycemic control and switch to a basal-bolus regimen, which raises some concerns for weight gain and increased hypoglycemic risk. Switching to combination use of glp-1 agonist and basal insulin may be an alternative option.MethodsAfter a 12-week premixed human insulin 70/30 dosage optimization period, 200 patients with HbA1c of 7.0% to 10.0% were randomized into 24-week treatment groups with exenatide twice a day plus glargine or with aspart 70/30 twice a day.ResultsAfter 24 weeks, the patients receiving exenatide plus glargine (n = 90) had improved HbA1c control compared with those receiving aspart 70/30 (n = 90) (least squares mean change: ‒0.59 vs ‒0.13%; difference [95% CI]: ‒0.45 [‒0.74 to ‒0.17]) in the full analysis set population. Weight decreased 3.5 kg with exenatide and decreased 0.4 kg with aspart 70/30 (P < .001). The insulin dose was reduced 10.7 units/day (95% CI, ‒12.2 to ‒9.2 units; P < .001) with exenatide, and increased 9.7 units/day (95% CI, 8.2 to 11.2 units; P < .001) with aspart 70/30. The most common adverse events were gastrointestinal adverse effects in the exenatide group (nausea [21%], vomiting [16%], diarrhea [13%]). The incidence of hypoglycemia was similar in 2 groups (27% for exenatide and 38% for aspart 70/30; P = .1).ConclusionIn premixed human insulin‒treated patients with type 2 diabetes with inadequate glycemic control, switching to exenatide twice a day plus glargine was superior to aspart 70/30 twice a day for glycemic and weight control.