Impact of hypoglycemia associated with antihyperglycemic medications on vascular risks in veterans with type 2 diabetes.

School of Pharmacy, Saint Joseph College, Hartford, Connecticut, USA.
Diabetes care (Impact Factor: 7.74). 03/2012; 35(5):1126-32. DOI: 10.2337/dc11-2048
Source: PubMed

ABSTRACT Hypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice.
Patients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score-matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model.
Among the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA(1c) of 10.69 ± 2.61%. The 1-year change in HbA(1c) was similar (hypoglycemia group -0.51 vs. control group -0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63-2.44]) and microvascular complications (1.76 [1.46-2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10-1.66]).
Hypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.

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    ABSTRACT: Objective Patients may fear the symptoms and consequences associated with hypoglycemia. We tested whether fear of hypoglycemia is independently associated with poorer health-related quality of life (HRQOL).Research design and methodsData were collected using direct-mail survey and enrollment information from adult commercial health plan enrollees with type 2 diabetes during a 12-month period (12/01/2008 to 11/30/2009). HRQOL was evaluated by the EuroQol (EQ)¿5D index and 12-item Short Form Health Survey Mental Component Summary (SF-12 MCS) and Physical Component Summary (SF-12 PCS). Fear of hypoglycemia was assessed using the Hypoglycemia Fear Survey (HFS). Two ordinary least-squares (OLS) models of HRQOL controlling for demographics and illness characteristics were specified, and OLS regression coefficients and statistical inferences were compared. Model 1 included 1 variable of hypoglycemia symptoms; Model 2 included both hypoglycemia symptoms and HFS score.ResultsOf 3999 patients contacted, 813 responded to the survey. Model 1: hypoglycemia symptoms alone were associated with worse HRQOL (SF-12 MCS and SF-12 PCS scores and EQ-5D utility score; all P¿<¿0.05). Model 2: hypoglycemia symptoms were significantly associated only with SF-12 MCS score. HFS total score was significantly associated with all 3 HRQOL scores. Hypoglycemia symptoms, Hispanic ethnicity, and longer diabetes duration were associated with greater hypoglycemia fear. Higher income, white race, and treatment without sulfonylurea or insulin were associated with less hypoglycemia fear (all P¿<¿0.05).Conclusions In addition to the effect of symptomatic hypoglycemia on HRQOL, fear of hypoglycemia was independently associated with lower overall health status and mental and physical health.
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    ABSTRACT: Background Obesity and sedentary lifestyle are major health problems and key features to develop cardiovascular disease. Data on the effects of lifestyle interventions in diabetics with chronic kidney disease (CKD) have been conflicting. Study DesignSystematic review. PopulationDiabetes patients with CKD stage 3 to 5. Search Strategy and SourcesMedline, Embase and Central were searched to identify papers. InterventionEffect of a negative energy balance on hard outcomes in diabetics with CKD. OutcomesDeath, cardiovascular events, glycaemic control, kidney function, metabolic parameters and body composition. ResultsWe retained 11 studies. There are insufficient data to evaluate the effect on mortality to promote negative energy balance. None of the studies reported a difference in incidence of Major Adverse Cardiovascular Events. Reduction of energy intake does not alter creatinine clearance but significantly reduces proteinuria (mean difference from -0.66 to -1.77 g/24 h). Interventions with combined exercise and diet resulted in a slower decline of eGFR (-9.2 vs. -20.7 mL/min over two year observation; p<0.001). Aerobic and resistance exercise reduced HbA1c (-0.51 (-0.87 to -0.14); p = 0.007 and -0.38 (-0.72 to -0.22); p = 0.038, respectively). Exercise interventions improve the overall functional status and quality of life in this subgroup. Aerobic exercise reduces BMI (-0.74% (-1.29 to -0.18); p = 0.009) and body weight (-2.2 kg (-3.9 to -0.6); p = 0.008). Resistance exercise reduces trunk fat mass (-0,7±0,1 vs. +0,8 kg ±0,1 kg; p = 0,001-0,005). In none of the studies did the intervention cause an increase in adverse events. LimitationsAll studies used a different intervention type and mixed patient groups. Conclusions There is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Overall, these interventions have beneficial effects on glycaemic control, BMI and body composition, functional status and quality of life, and no harmful effects were observed.
    PLoS ONE 11/2014; 9(11):e113667. · 3.53 Impact Factor
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    ABSTRACT: In this study, we aimed to investigate the effect of hypoglycemia on cardiovascular outcomes in a sample of patients with chronic kidney disease (CKD).METHODS: Information about study participants was extracted from the National Health Insurance Research Database of Taiwan for the years 1998 through 2008. We conducted this retrospective cohort study of patients with CKD, with and without hypoglycemia, to evaluate the risk of overall mortality and cardiovascular complications including stroke, coronary heart disease, and congestive heart failure in both groups.RESULTS: This study included 46,135 patients with CKD, of whom 2,117 (4.59%) were hospitalized and had hypoglycemia. Results of multivariate Cox proportional hazard regression analyses indicated that stroke (hazard ratio [HR] = 1.62, 95% confidence interval [CI] = 1.29-2.03), coronary heart disease (HR = 1.25, 95% CI = 1.00-1.57), congestive heart failure (HR = 1.49, 95% CI = 1.13-1.98), and death (HR = 2.53, 95% CI = 1.99-3.21) were associated with hypoglycemia in patients with CKD. Recurrent episodes of hypoglycemia were associated with a higher risk of death (HR = 33.0, 95% CI = 22.3-48.8 for >2 episodes, p for trend <0.0001), and a similar trend was observed for other multiple cardiovascular events. We observed an increased risk of stroke and overall mortality in patients with hypoglycemia compared to those without hypoglycemia, regardless of whether the patient had diabetes.CONCLUSIONS: CKD was associated with a higher risk of stroke and mortality in patients with hypoglycemia. Recurrent hypoglycemia considerably increased the risk of stroke and overall mortality in patients with CKD regardless of whether they had diabetes. These results suggest that hypoglycemia has a crucial role in stroke and death in patients with CKD.
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