Impact of hypoglycemia in hospitalized patients.

Hypoglycemia is a common problem in hospitalized patients, particularly the elderly, frail, and severely ill. Hypoglycemia has been implicated in the development of adverse clinical outcomes, including increased mortality. Fear of iatrogenic hypoglycemia remains an obstacle to adequate inpatient glycemic control. However, evidence from large clinical trials is mixed: several intensive care unit studies have shown either reduced or no change in mortality with intensive glycemic control, despite high rates of iatrogenic hypoglycemia, and only 1 large study showed higher mortality. In the general ward setting, the association of hypoglycemia with worse outcomes and mortality has been frequently reported, but after multivariate adjustment for comorbidities this association disappears. Spontaneous hypoglycemia, rather than iatrogenic hypoglycemia, is strongly associated with mortality suggesting that hypoglycemia behaves as a biomarker rather than a causative factor of adverse outcomes. Inpatient glycemic management should be patient-centered, follow the current guidelines, and aimed at preventing hypoglycemia.

The impact of race/ethnicity on baseline characteristics and the burden of coronary atherosclerosis in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.

OBJECTIVES: We aimed to test the impact of race/ethnicity on coronary artery disease (CAD) after adjusting for baseline risk factors. BACKGROUND: Whether race/ethnicity remains an important determinant of the burden of CAD even among patients with long-standing type 2 diabetes (diabetes mellitus) and established CAD is unknown. METHODS: Analysis of baseline data from the BARI 2D trial (January 1, 2001, to March 31, 2005) was performed. Myocardial jeopardy index (MJI) was evaluated by a blinded core angiographic laboratory. Multivariate regression analysis was performed to determine the independent association of race/ethnicity on the burden of CAD after adjusting for baseline risk factors. Data were collected from US and Canadian academic and community hospitals. The baseline analysis was performed on patients with long-standing diabetes and documented CAD with no prior revascularization at study entry (n = 1,331). The main outcome measure was MJI, which represents the percentage of myocardium jeopardized by significant lesions (≥50%). The secondary outcome measure was ≥2 lesions with ≥50% stenosis. RESULTS: Risk factors varied significantly among racial/ethnic groups. Blacks were significantly more likely to be women, have no health insurance, be current smokers, have higher body mass index, have hypertension, have a longer duration of diabetes, a higher hemoglobin A(1c) level, and were more likely to be taking insulin. Their mean total, low-density lipid, and high-density lipid cholesterol levels were higher, whereas their triglycerides were lower than others. After controlling for baseline risk factors, blacks had a significantly lower burden of CAD; the adjusted MJI was 5.43 U lower (95% CI -9.13 to -1.72), and the adjusted number of lesions was 0.53 fewer (95% CI -0.88 to -0.18) in blacks compared to whites. CONCLUSIONS: In the BARI 2D trial, self-reported race/ethnicity is associated with important differences in baseline risk factors and is a powerful predictor of the burden of CAD adjusting for such baseline differences. These findings may help direct medical intervention and resources and further investigation into the basis of racial/ethnic differences in CAD burden.

Glycemic management and clinical outcomes in underserved minority kidney transplant recipients with type 2 and posttransplantation diabetes: A single-center retrospective study.

AIMS: Little is known about glycemic management, particularly with novel cardio-nephroprotecive agents, in underserved minority kidney transplant recipients with pre-transplant type 2 (T2DM) and posttransplantation diabetes mellitus (PTDM). We assessed glycemic management and outcomes in this high-risk population. METHODS: We reviewed records of patients who received kidney transplants between June 2012 and December 2014 at a single center. Hemoglobin A1c (HbA1c) and prescribed glucose-lowering medications were examined, and mortality was compared between T2DM, PTDM, and no diabetes (NoDM) patients. RESULTS: We followed 302 patient records (41.1% Hispanic, 41.1% non-Hispanic black) for a median (IQR) of 45.5 (37.0, 53.0) months post-transplant. Pre-transplant T2DM was present in 152 (50.3%), while 58 (19.2%) developed PTDM and 92 (30.4%) remained NoDM. At 1-year post-transplant, the average HbA1c was 8.1 ± 1.8% in T2DM and 6.6 ± 1.3% in PTDM. No glucose-lowering agents were prescribed in 3.4% of T2DM and 44.8% of PTDM. When treated, both received mostly insulin and metformin. Diabetes, HbA1c and insulin therapy were not independently associated with risk of mortality. CONCLUSIONS: Glycemic management was suboptimal and relied on older medications. Further studies are needed to assess longer-term outcomes of more rigorous glycemic management, and the value of novel cardio-nephroprotective agents in kidney transplant recipients.

A DRAMATIC RESPONSE TO DENOSUMAB: PROTRACTED HYPOCALCEMIA RELATED TO HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE 1-ASSOCIATED ADULT T-CELL LEUKEMIA/LYMPHOMA.

OBJECTIVE: Adult T-cell leukemia/lymphoma (ATL) is known for its aggressive behavior, frequently presenting with hypercalcemia. ATL tumor cells uniquely secrete parathyroid hormone-related protein, viral peptides, and inflammatory cytokines, inducing a state of high bone turnover and activation of the receptor activator of nuclear factor kappa-B signaling pathway resulting in hypercalcemia. METHODS: A 54-year-old woman diagnosed with ATL presented with severe hypercalcemia refractory to bisphosphonate therapy. Treatment with denosumab was followed by protracted hypocalcemia and hypophosphatemia lasting approximately 5 months. RESULTS: Hypercalcemia due to acute ATL was responsive in this case to denosumab therapy. CONCLUSION: Clinicians should be aware of the possibility of protracted hypocalcemia in patients with ATL exposed to denosumab therapy.

Strategies for Diabetes Management: Using Newer Oral Combination Therapies Early in the Disease.

INTRODUCTION: The duration of uncontrolled type 2 diabetes mellitus (T2DM) can adversely impact small and large vessels, eventually leading to microvascular and macrovascular complications. Failure of therapeutic lifestyle changes, monotherapy, and clinical inertia contribute to persistent hyperglycemia and disease progression. The aim was to review the complex pathophysiology of type 2 diabetes and how different oral agents can be used effectively as first-line therapy in combination with metformin, as well as in patients not achieving glycemic goals with metformin therapy. METHODS: For this review, a non-systematic literature search of PubMed, NCBI, and Google Scholar was conducted. RESULTS: New oral agents have made it possible to improve glycemic control to near-normal levels with a low risk of hypoglycemia and without weight gain, and sometimes with weight loss. Early combination therapy is effective and has been shown to have a favorable legacy effect. A number of agents are available in a single-pill combination (SPC) that provides fewer pills and better adherence. Compared with adding a sulfonylurea, still the most common oral combination used, empagliflozin has been shown to decrease cardiovascular (CV) events in a dedicated CV outcome study, and pioglitazone has been effective in reducing the risk of secondary CV endpoints, whereas sulfonylureas have been associated with an increased risk of CV disease. In those failing metformin, triple oral therapy by adding a non-metformin SPC such as empagliflozin/linagliptin or pioglitazone/alogliptin is a good option for reducing glycated hemoglobin (HbA1c) without significant hypoglycemia. CONCLUSION: Clinicians have a comprehensive armamentarium of medications to treat patients with T2DM. Clinical evidence has shown that dual or triple oral combination therapy is effective for glycemic control, and early treatment is effective in getting patients to goal more quickly. Use of SPCs is an option for double or triple oral combination therapy and may result in better adherence.

Triglyceride High-Density Lipoprotein Ratios Predict Glycemia-Lowering in Response to Insulin Sensitizing Drugs in Type 2 Diabetes: A Post Hoc Analysis of the BARI 2D.

Glycemic management is central in prevention of small vessel and cardiovascular complications in type 2 diabetes. With the plethora of newer medications and recommendations for a patient centered approach, more information is necessary to match the proper drug to each patient. We showed that BARI 2D, a five-year trial designed to compare two different glycemic treatment strategies, was suitable for assessing different responses according to different phenotypic characteristics. Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas. Triglyceride and high density lipoprotein ratio (TG/HDL-cholesterol ratio) was found to be a readily available and practical biomarker that helps to identify the insulin resistant patient. These results support the concept that not all medications for glycemic control work the same in all patients. Thus, tailored therapy can be done using phenotypic characteristics rather than a "one-size-fits-all approach."

The clinical impact of inpatient hypoglycemia.

Hypoglycemia is common in hospitalized patients and is associated with poor outcomes, including increased mortality. Older individuals and those with comorbidities are more likely to suffer the adverse consequences of inpatient hypoglycemia. Observational studies have shown that spontaneous inpatient hypoglycemia is a greater risk factor for death than iatrogenic hypoglycemia, suggesting that hypoglycemia acts as a marker for more severe illness, and may not directly cause death. Initial randomized controlled trials of intensive insulin therapy in intensive care units demonstrated improvements in mortality with tight glycemic control, despite high rates of hypoglycemia. However, follow-up studies have not confirmed these initial findings, and the largest NICE-SUGAR study showed an increase in mortality in the tight control group. Despite these recent findings, a causal link between hypoglycemia and mortality has not been clearly established. Nonetheless, there is potential for harm from inpatient hypoglycemia, so evidence-based strategies to treat hyperglycemia, while preventing hypoglycemia should be instituted, in accordance with current practice guidelines.

Is there a paradox in obesity?

In an industrialized society, the increase in obesity incidence has led to an increase in premature morbidity and mortality rates. There is a relationship between body mass index (BMI) and the increased incidence of hypertension, dyslipidemia, type 2 diabetes mellitus, and cardiovascular disease, an increase in mortality. However, obese individuals with these conditions may have better outcomes than their lean counterparts, thus the term "obesity paradox." Most studies supporting this paradox are cross-sectional and do not take into account the quantity or type of adiposity, the disease severity, and comorbidities. Although BMI is an indicator of the amount of body fat, it does not differentiate between adiposity types. Adipocytes that are highly functional have good fuel storage capacity are different from adipocytes found in visceral obesity, which are poorly functioning, laden with macrophages, and causing low-grade inflammation. Individuals with high BMI may be physically fit and have a lower mortality risk when compared with individuals with a lower BMI and poorly functioning adiposity. We review the complexity of adipose tissue and its location, function, metabolic implications, and role in cardiovascular morbidity and mortality. The terminology "obesity paradox" may reflect a lack of understanding of the complex pathophysiology of obesity and the association between adiposity and cardiovascular disease.

Understanding hypoglycemia in hospitalized patients.

Controlling blood glucose in hospitalized patients is important as both hyperglycemia and hypoglycemia are associated with increased cost, length of stay, morbidity and mortality. A limiting factor in stringent control is the concern of iatrogenic hypoglycemia. The association of hypoglycemia with mortality has led to clinical guideline changes recommending more conservative glycemic control than had previously been suggested, with the use of patient specific approaches when appropriate. Healthier, stable patients may be managed with stricter control while the elderly and severely ill may be managed less aggressively. While the avoidance of hypoglycemia is essential in clinical practice, recent studies suggest that a higher mortality rate occurs in spontaneous rather than iatrogenic hypoglycemia. Therefore, inpatient hypoglycemia may be viewed more as a biomarker of disease rather than a true cause of fatality.

Determinants of successful glycemic control among participants in the BARI 2D trial: a post-hoc analysis.

OBJECTIVE: The BARI 2D trial compared insulin provision (IP) versus insulin sensitization (IS) for the primary outcome of total mortality in participants with T2DM and cardiovascular disease (CVD). In this analysis we examine baseline characteristics that are associated with successful long-term glycemic control. RESEARCH DESIGN AND METHODS: In a 2×2 factorial design, 2368 participants were randomized to either IP or IS therapy, and to either prompt revascularization with medical therapy or medical therapy alone. Successful long-term glycemic control (success) was defined by simultaneously meeting 1) a mean HbA1c level of <7.0% after each participant's third year of follow-up period, and 2) adherence with medications only from the assigned glycemic treatment arm during >80% of the BARI 2D follow-up. The association between baseline variables and success was determined using unadjusted and adjusted logistic regression models. RESULTS: 1917 participants (962 IP and 955 IS participants) had sufficiently long follow-up and data for this analysis. Among these IP and IS participants, 235 and 335 participants met both criteria of success, respectively (p<0.001). Those not on insulin at entry had higher odds of success (OR 2.25; CI 1.79-2.82) when treated with IS versus IP medications, irrespective of baseline HbA1c levels. Younger age, shorter duration of T2DM, and lower HbA1c at baseline were also each independently associated with higher success when treated with IS versus IP medications. CONCLUSION: Patients similar to those in the BARI 2D trial may have a higher chance of achieving success with IS versus IP medications if they are younger, have shorter duration of T2DM, have lower HbA1c levels, have moderate or strenuous physically activity, and are not on insulin. In contrast, increasing age, longer duration of T2DM, higher HbA1c, and insulin therapy are associated with increased chance of success if treated with IP medications.

Population management of diabetes in a high-need urban community in the Bronx: the experience of Montefiore Medical Center.

PURPOSE: The purpose of this study is to examine the impact of a Care Management Organization (CMO) Diabetes Disease Management Program (DDMP) in improving diabetes outcomes among high-risk patients with type 2 diabetes (T2DM) in the Bronx, New York. METHODS: An interventional, nonrandomized study design was used to assess the effectiveness of the DDMP. Patients older than 18 years who had T2DM and an A1C persistently 8% or greater or with a cardiovascular comorbidity were characterized as high risk and received intensive disease management. Patients served as their own controls, with data collection and analysis occurring 12 months prior to and 12 months after enrollment in DDMP. Data collection included screening rates for A1C, low-density lipoprotein (LDL) cholesterol, depression, smoking status, and annual influenza vaccine administration. Changes in A1C and LDL cholesterol were also analyzed. Statistical analyses were conducted using Minitab. McNemar's chi-square and paired t tests were used to assess within-group changes from baseline to final outcomes. RESULTS: Significant improvements in screening rates for A1C, LDL, depression, smoking status, and annual influenza vaccine administration were found among high-risk/intensively managed patients in the DDMP. Improvements in clinical measures were also achieved in this group. Provider and patient satisfaction surveys were positive, with 92% of patients believing that the program helped them better understand their disease. CONCLUSIONS: A DDMP among high-risk patients has shown promise in improving the quality of care for patients with diabetes. This program has relevance for other integrated delivery systems that are developing accountable care approaches.

Hypoglycemia-associated mortality is not drug-associated but linked to comorbidities.

OBJECTIVE: Although tight glucose control is used widely in hospitalized patients, there is concern that medication-induced hypoglycemia may worsen patient outcomes. We sought to determine if the mortality risk associated with hypoglycemia in hospitalized noncritically ill patients is linked to glucose-lowering medications (drug-associated hypoglycemia) or merely an association mediated by comorbidities (spontaneous hypoglycemia). METHODS: A retrospective cohort of patients admitted to the general wards of an academic center during 2007 was studied. The in-hospital mortality risk of a hypoglycemic group (at least 1 blood glucose ≤ 70 mg/dL) was compared with that of a normoglycemic group using survival analysis. Stratification by subgroups of patients with spontaneous and drug-associated hypoglycemia was performed. RESULTS: Among 31,970 patients, 3349 (10.5%) had at least 1 episode of hypoglycemia. Patients with hypoglycemia were older, had more comorbidities, and received more antidiabetic agents. Hypoglycemia was associated with increased in-hospital mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.33-2.09; P<.001). However, this greater risk was limited to patients with spontaneous hypoglycemia (HR, 2.62; 95% CI, 1.97-3.47; P<.001) and not to patients with drug-associated hypoglycemia (HR, 1.06; 95% CI, 0.74-1.52; P=.749). After adjustment for patient comorbidities, the association between spontaneous hypoglycemia and mortality was eliminated (HR, 1.11; 95% CI, 0.76-1.64; P=.582). CONCLUSION: Drug-associated hypoglycemia was not associated with increased mortality risk in patients admitted to the general wards. The association between spontaneous hypoglycemia and mortality was eliminated after adjustment for comorbidities, suggesting that hypoglycemia may be a marker of disease burden rather than a direct cause of death.

Mortality trends and disparities among racial/ethnic and sex subgroups in New York City, 1990 to 2000.

New York City census data for 1990 and 2000 for all-cause and disease-specific mortality adjusted by age were examined by race/ethnicity. Primary cause of death was coded as HIV/AIDS, cardiovascular disease, coronary heart disease, acute myocardial infarction, stroke, diabetes, or cancer. For White, Black, Hispanic and Asian groups, relative mortality ratios (RMR) were derived for 2000 relative to 1990. Ratios of RMR's for minority groups were derived relative to Whites. From 1990 to 2000, HIV, cancer, CVD, CHD, AMI, and stroke-related mortality decreased. Decreases in HIV-related mortality were notably less for minority males. Diabetes mortality rates rose dramatically, with Hispanic and Asian males having notably greater increases than White males. Increases in mortality among Asians exceeded those of other groups, and appear to correspond with increased immigration/acculturation. Mortality shifts among different diseases and racial groups should alert public health officials to consider immigration patterns in designing, implementing, and evaluating interventions to prevent disease-related mortality, with a goal to eliminate disparities.

Training community health promoters to implement diabetes self-management support programs for urban minority adults.

OBJECTIVE: To develop, implement, and evaluate a peer-led diabetes self-management support program in English and Spanish for a diverse, urban, low-income population. The program goals and objectives were to improve diabetes self-management behaviors, especially becoming more physically active, healthier eating, medication adherence, problem solving, and goal setting. METHODS: After a new training program for peers led by a certified diabetes educator (CDE) was implemented with 5 individuals, this pilot evaluation study was conducted in 2 community settings in the East and South Bronx. Seventeen adults with diabetes participated in the new peer-led 5-session program. Survey data were collected pre- and postintervention on diabetes self-care activities, quality of well-being, and number of steps using a pedometer. RESULTS: This pilot study established the acceptance and feasibility of both the peer training program and the community-based, peer-led program for underserved, minority adults with diabetes. Significant improvements were found in several physical activity and nutrition activities, with a modest improvement in well-being. Feedback from both peer facilitators and participants indicated that a longer program, but with the same educational materials, was desirable. CONCLUSIONS: To reduce health disparities in urban communities, it is essential to continue program evaluation of the critical elements of peer-led programs for multiethnic adults with diabetes to promote self-management support in a cost-effective and culturally appropriate manner. Practice Implications A diabetes self-management support program can be successfully implemented in the community by peers, within a model including remote supervision by a CDE.

Racial disparity in amputation-free survival after infrainguinal bypass procedure: contribution of socioeconomic status.

OBJECTIVE: To investigate amputation-free survival after infrainguinal bypass in African Americans and Hispanics compared with non-Hispanic whites and to determine the contribution of socioeconomic status to potential racial disparity. DESIGN: This is a retrospective cohort study of subjects who underwent infrainguinal bypass due to critical limb ischemia from 1997 through 2004. The primary end point was major amputation or death, whichever occurred first. Neighborhood socioeconomic status obtained from the 2000 United States Census was used as a proxy for an individual's socioeconomic status. RESULTS: There were 595 subjects (237 non-Hispanic whites, 205 African Americans, 153 Hispanics) in the study. Median amputation-free survival was 1.3, 3.3, and 3.2 yrs among Hispanics, African Americans, and non-Hispanic whites, respectively. Hazard ratio for amputation or death was 1.38 (95% confidence interval, 1.02-1.87) in Hispanics and 0.81 (95% confidence interval, 0.63-1.16) in African Americans compared with non-Hispanic whites after multivariable adjustment. For those residing in their homes, adjusting for socioeconomic status attenuated the hazard ratio in Hispanics to 1.08, explaining 78% of increased hazard. CONCLUSIONS: There was no significant difference between African Americans and non-Hispanic whites in amputation-free survival after infrainguinal bypass. Hispanics were 1.4 times more likely to have amputation or death than non-Hispanic whites, which was largely explained by low socioeconomic status.

Comparative study of the effects of a 1-year dietary intervention of a low-carbohydrate diet versus a low-fat diet on weight and glycemic control in type 2 diabetes.

OBJECTIVE: To compare the effects of a 1-year intervention with a low-carbohydrate and a low-fat diet on weight loss and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This study is a randomized clinical trial of 105 overweight adults with type 2 diabetes. Primary outcomes were weight and A1C. Secondary outcomes included blood pressure and lipids. Outcome measures were obtained at 3, 6, and 12 months. RESULTS: The greatest reduction in weight and A1C occurred within the first 3 months. Weight loss occurred faster in the low-carbohydrate group than in the low-fat group (P = 0.005), but at 1 year a similar 3.4% weight reduction was seen in both dietary groups. There was no significant change in A1C in either group at 1 year. There was no change in blood pressure, but a greater increase in HDL was observed in the low-carbohydrate group (P = 0.002). CONCLUSIONS: Among patients with type 2 diabetes, after 1 year a low-carbohydrate diet had effects on weight and A1C similar to those seen with a low-fat diet. There was no significant effect on blood pressure, but the low-carbohydrate diet produced a greater increase in HDL cholesterol.