Shuqian Liu

The Hemoglobin Glycation Index Identifies Subpopulations With Harms or Benefits From Intensive Treatment in the ACCORD Trial

OBJECTIVE This study tested the hypothesis that intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial disproportionately produced adverse outcomes in patients with diabetes with a high hemoglobin glycation index (HGI = observed HbA1c − predicted HbA1c). RESEARCH DESIGN AND METHODS ACCORD was a randomized controlled trial of 10,251 patients with type 2 diabetes assigned to standard or intensive treatment with HbA1c goals of 7.0% to 7.9% (53 to 63 mmol/mol) and less than 6% (42 mmol/mol), respectively. In this ancillary study, a linear regression equation (HbA1c = 0.009 × fasting plasma glucose [FPG] [mg/dL] + 6.8) was derived from 1,000 randomly extracted participants at baseline. Baseline FPG values were used to calculate predicted HbA1c and HGI for the remaining 9,125 participants. Kaplan-Meier and Cox regression were used to assess the effects of intensive treatment on outcomes in patients with a low, moderate, or high HGI. RESULTS Intensive treatment was associated with improved primary outcomes (composite of cardiovascular events) in the low (hazard ratio [HR] 0.75 [95% CI 0.59–0.95]) and moderate (HR 0.77 [95% CI 0.61–0.97]) HGI subgroups but not in the high HGI subgroup (HR 1.14 [95% CI 0.93–1.40]). Higher total mortality in intensively treated patients was confined to the high HGI subgroup (HR 1.41 [95% CI 1.10–1.80]). A high HGI was associated with a greater risk for hypoglycemia in the standard and intensive treatment groups. CONCLUSIONS HGI calculated at baseline identified subpopulations in ACCORD with harms or benefits from intensive glycemic control. HbA1c is not a one-size-fits-all indicator of blood glucose control, and taking this into account when making management decisions could improve diabetes care.

Economic burden of hypoglycemia in patients with Type 2 diabetes

Hypoglycemia is an acute complication of diabetes that increases morbidity, mortality and economic costs of diabetes. It presents major clinical problems for the management of Type 2 diabetes as this disease represents the great majority of all diabetes cases. Hypoglycemia makes it difficult for some individuals to achieve good glycemic control, reduces quality of life and increases the burden of diabetes to healthcare systems. Understanding hypoglycemia risk factors can help patients with Type 2 diabetes to correct and avoid hypoglycemia. Recently, an increased risk of hypoglycemia with intensive glycemic control has been identified as an important problem in optimally controlling blood glucose levels in patients with Type 2 diabetes.

Association between Inflammation and Biological Variation in Hemoglobin A1c in U.S. Nondiabetic Adults

CONTEXT Inflammation is associated with higher glycated hemoglobin (HbA1c) levels. Whether the relationship is independent of blood glucose concentration remains unclear. OBJECTIVE The hemoglobin glycation index (HGI) was used to test the hypothesis that interindividual variation in HbA1c is associated with inflammation. PARTICIPANTS This study used nondiabetic adults from the National Health and Nutrition Examination Survey (1999-2008). MAIN OUTCOME MEASURES A subsample of participants was used to estimate the linear regression relationship between HbA1c and fasting plasma glucose (FPG). Predicted HbA1c were calculated for 7323 nondiabetic participants by inserting FPG into the equation, HbA1c = 0.017 × FPG (mg/dL) + 3.7. HGI was calculated as the difference between the observed and predicted HbA1c and the population was divided into low, moderate, and high HGI subgroups. Polymorphonuclear leukocytes (PMNL), monocytes, and C-reactive protein (CRP) were used as biomarkers of inflammation. RESULTS Mean HbA1c, CRP, monocyte, and PMNL levels, but not FPG, progressively increased in the low, moderate, and high HGI subgroups. There were disproportionately more Blacks than whites in the high HGI subgroup. CRP (ß, 0.009; 95% confidence interval [CI], 0.0001-0.017), PMNL (ß, 0.036; 95% CI, 0.010-0.062), and monocyte count (ß, 0.072; 95% CI, 0.041-0.104) were each independent predictors of HGI after adjustment for age, sex, race, triglycerides, hemoglobin level, mean corpuscular volume, red cell distribution width, and obesity status. CONCLUSIONS HGI reflects the effects of inflammation on HbA1c in a nondiabetic population of U.S. adults and may be a marker of risk associated with inflammation independent of FPG, race, and obesity.

Evaluation of a Remote Monitoring System for Diabetes Control

PURPOSE The use of technology to implement cost-effective health care management on a large scale may be an alternative for diabetes management but needs to be evaluated in controlled trials. This study assessed the utility and cost-effectiveness of an automated Diabetes Remote Monitoring and Management System (DRMS) in glycemic control versus usual care. METHODS In this randomized, controlled study, patients with uncontrolled diabetes on insulin were randomized to use of the DRMS or usual care. Participants in both groups were followed up for 6 months and had 3 clinic visits at 0, 3, and 6 months. The DRMS used text messages or phone calls to remind patients to test their blood glucose and to report results via an automated system, with no human interaction unless a patient had severely high or low blood glucose. The DRMS made adjustments to insulin dose(s) based on validated algorithms. Participants reported medication adherence through the Morisky Medication Adherence Scale-8, and diabetes-specific quality of life through the diabetes Daily Quality of Life questionnaire. A cost-effectiveness analysis was conducted based on the estimated overall costs of DRMS and usual care. FINDINGS A total of 98 patients were enrolled (59 [60%] female; mean age, 59 years); 87 participants (89%) completed follow-up. HbA1c was similar between the DRMS and control groups at 3 months (7.60% vs 8.10%) and at 6 months (8.10% vs 7.90%). Changes from baseline to 6 months were not statistically significant for self-reported medication adherence and diabetes-specific quality of life, with the exception of the Daily Quality of Life-Social/Vocational Concerns subscale score (P = 0.04). IMPLICATIONS An automated system like the DRMS may improve glycemic control to the same degree as usual clinic care and may significantly improve the social/vocational aspects of quality of life. Cost-effectiveness analysis found DRMS to be cost-effective when compared to usual care and suggests DRMS has a good scale of economy for program scale up. Further research is needed to determine how to sustain the benefits seen with the automated system over longer periods.

Changes in Mortality in People With IGT Before and After the Onset of Diabetes During the 23-Year Follow-up of the Da Qing Diabetes Prevention Study

OBJECTIVE People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2–12.0) before and 19.4/1,000 person-years (95% CI 11.9–23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1–42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6–35.0%) in those who progressed to type 2 diabetes in 10–20 years, and 13.9% (95% CI 7.0–20.3%) in those who did not develop to type 2 diabetes within 20 years. Time-dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18–2.52]). CONCLUSIONS As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes.

Effects of antiviral treatment on influenza-related complications over four influenza seasons: 2006–2010

Abstract Purpose: The objective of the study is to evaluate the effect of antiviral treatment, pre-existing diseases, and sociodemographic factors on the risk of influenza-related complications and healthcare utilization. Methods: Case data was obtained from U.S. MarketScan Research Databases. Cases had a clinical diagnosis of influenza between 2006 and 2010 and continuous healthcare insurance from 90 days before to 30 days after diagnosis. Logistic regression models were applied to explore the impact of antiviral treatment on complications and healthcare utilization. Modified generalized estimating equation regression models in propensity score matched samples were used to address the robustness of the study. Results: Analyses included 1,557,437 cases from four influenza seasons. In each season, 34.82%–43.42% of patients received antiviral treatment, mostly oseltamivir. On average, 1.86% of patients were hospitalized, 9.56% visited the emergency room and 41.14% made ≥2 outpatient visits. The incidence of complications ranged from 17.62 to 19.67 per 100 patient-months. The relative risk of complications was increased in patients aged 0–4 years and those with pre-existing diseases, including asthma, Parkinson’s disease, and cystic fibrosis. Overall, patients receiving antiviral treatment had an 11% reduction in the risk of complications. Among oseltamivir-treated patients, the risk of complications was significantly reduced by 81% in those treated ≤2 days after diagnosis compared with later. Antiviral treatment significantly reduced the risk of hospitalization, emergency room visits and need for ≥2 outpatient visits by 29%, 24% and 11%, respectively. The propensity score matching method improved the strength of the study. Conclusions: Early treatment with antivirals, and specifically oseltamivir, significantly reduced the risk of influenza-related complications and healthcare utilization. However, lacking information about disease severity and the time from onset of symptoms to fulfillment of a prescription may bias the outcomes.

Outcomes associated with warfarin time in therapeutic range among US veterans with nonvalvular atrial fibrillation.

Abstract Background: Poor quality of warfarin control (time in therapeutic range [TTR] < 65%) can lead to increased risk of adverse events. The objective of this study was to examine the overall quality of international normalized ratio (INR) control and the association of TTR with clinical outcomes including stroke, major bleeding, and all-cause mortality among US warfarin users. Methods and results: This retrospective observational cohort study utilized the US Veterans Affairs electronic medical records database (VA EMR). Patients with NVAF who newly initiated warfarin from 1 January 2005 to 31 December 2015 were grouped into two cohorts based on TTR <65% or ≥65%. TTR was computed from INR test results. Clinical outcomes assessed were stroke/systemic embolism (SE), hemorrhagic stroke, ischemic stroke, and major bleeding, defined based on hospitalization with those conditions as primary diagnosis, as well as all-cause mortality. Patients were followed from warfarin initiation to the first occurrence of an outcome or censoring. Propensity score weighted time-varying Cox regression was used to evaluate the risk of the clinical events. A total of 127,385 NVAF patients with mean TTR of 51% were included. TTR <65% was observed in 65% of patients. Mean CHA2DS2-VASC score (SD) was 2.9 (1.5) in the low TTR cohort and 2.7 (1.4) in the high TTR cohort. Patients with TTR <65% had a higher risk for any stroke/SE (HR: 1.57; 95% CI: 1.41–1.75), major bleeding (HR: 2.78; 95% CI: 2.55–3.03) and all-cause mortality (HR: 1.73; 95% CI: 1.67–1.79). Conclusions: The observed quality of warfarin control in VA EMR suggests room for improvement given the association with elevated risk of adverse clinical outcomes.

Cost-effectiveness analysis of dapagliflozin versus glimepiride as monotherapy in a Chinese population with type 2 diabetes mellitus

Abstract Objective: To evaluate the long-term cost-effectiveness of dapagliflozin (a novel sodium–glucose co-transporter-2 inhibitor) versus glimepiride (a widely used sulfonylurea), when applied as monotherapy in patients with type 2 diabetes mellitus (T2DM) in China. Methods: Literature screening, meta-analysis and indirect comparison were used to compare efficacy and safety between dapagliflozin and glimepiride. Direct medication costs and medical expenditure on treating diabetes related comorbidities were calculated based on published and local sources and reported in 2015 Chinese Renminbi (RMB). A discount rate of 3% was applied to both costs and health effects. The Cardiff model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes, was used to generate outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs and quality-adjusted life years (QALYs) over a time horizon of 40 years from the health provider perspective. Univariate and probabilistic sensitivity analyses were performed to assess uncertainty in the model results. Results: Compared with glimepiride, patients on dapagliflozin gained 1.01 QALYs, at a cost saving of RMB 49,065 in our simulated cohort. This resulted in a cost saving of RMB 48,585 per QALY gained with dapagliflozin. The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis (PSA). Conclusions: Compared with glimepiride, dapagliflozin as monotherapy for T2DM is a more cost-effective treatment for T2DM patients on monotherapy in China. The weight control has been identified as the major contributor for the higher cost-effectiveness of dapagliflozin.

Response to Comment on Hempe et al. The Hemoglobin Glycation Index Identifies Subpopulations With Harms or Benefits From Intensive Treatment in the ACCORD Trial. Diabetes Care 2015;38:1067–1074

Drs. Riddle and Gerstein (1) suggest renaming the hemoglobin glycation index (HGI) to reflect the possibility that interindividual variation in HGI in the ACCORD trial could be an artifact of how blood glucose was measured. HGI is the difference between an individual’s observed HbA1c and a predicted HbA1c derived by inserting a time-matched blood glucose measurement into a regression equation describing the linear population relationship between blood glucose and HbA1c. In our analysis of ACCORD (2), we used baseline HbA1c and fasting plasma glucose (FPG) to show that high HGI at baseline (i.e., HbA1c higher than predicted by FPG) was …

Long-term outcomes associated with triple-goal achievement in patients with type 2 diabetes mellitus (T2DM)

AIMS This study was designed to compare the risk of long-term health outcomes, including microvascular, macrovascular complications and mortality, across 4 cohorts: triple-goal, dual-goal, single-goal, and no-goal achievers. METHODS A retrospective cohort of 53,120 patients with T2DM were identified (97.51% male, 61.49% whites) from the Veterans Affairs (VA) electronic medical records VISN 16 data warehouse (2004-2010). Propensity score weight (PSW) was used to balance demographic characteristics and complication history at baseline. The PSW adjusted hazard ratios (aHR) from Cox proportional hazard models were used to compare complications and all-cause mortality over an average of 4 years of follow-up. RESULTS At baseline, 25.43% (13,507) patients achieved triple-goal, while 41.36% (21,972) and 26.37% (14,010) patients achieved dual-goal and single-goal, respectively. During the follow-up period, triple-goal achievement was associated with risk reductions of complications and all-cause mortality when compared to all other groups of achieving dual or single-goal. Across different combinations of dual-goal achievement, the cohort with LDL-C goal achievement had lower risk of complication events and mortality, compared to those that achieved other goals but failed to reach LDL-C goal. CONCLUSIONS Achievement of triple-goal was associated with better health outcomes among veterans with T2DM compared to those that did not, while LDL-C has more weight of influence. Multi-faceted treatment strategies targeting hypertension, hyperglycemia and hyperlipidemia may improve health outcome in veterans with T2DM.