Retrospective analysis and patient satisfaction assessment of insulin pump therapy in patients with type 2 diabetes.

OBJECTIVES: To evaluate and assess glycemic control, total daily insulin requirements, weight, and patient satisfaction after changing from multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 2 diabetes. METHODS: This was a retrospective cross-sectional cohort analysis of an electronic medical records database from a private physician's clinic. Patients over 18 years of age who had type 2 diabetes and who utilized CSII for at least six months were analyzed. Variables of interest included glycosylated hemoglobin, total daily insulin requirements, and weight at the time of conversion from MDI to CSII. Patients were also asked to complete a satisfaction survey comparing MDI to CSII. RESULTS: Thirty patients who met the inclusion criteria were identified. Hemoglobin A1c (HbA1c) decreased from 9.25% ± 2.20 to 7.94% ± 1.65 (P < 0.001) at six months, total daily insulin dose decreased from 1.33 ± 0.66 u/kg/day to 1.08 ± 0.70 u/kg/day (P < 0.001) at six months, and weight increased from 106.66 ± 19.17 kg to 109.75 ± 18.01 kg (P < 0.001). After twelve months, HbA1c did not significantly change and weight returned to baseline; however, total daily insulin dose significantly decreased. 95% of patients preferred CSII therapy to previous injection regimen for various reasons. CONCLUSION: Insulin pump therapy provided better glycemic control and reduced the total amount of insulin utilized. Patients who utilized CSII thought that the treatment was more convenient, less burdensome, and provided better control of fluctuations in blood glucose. CSII was preferred by patients over multiple daily injections.

The use of a single-pill calcium channel blocker/statin combination in the management of hypertension and dyslipidemia: a randomized, placebo-controlled, multicenter study.

Poor control of hypertension or dyslipidemia may at least in part be due to these risk factors being treated in isolation. The Caduet in Untreated Subjects Population (CUSP) trial was an 8-week, randomized, double-blind, placebo-controlled trial evaluating the efficacy/safety of the combination of a calcium channel blocker (amlodipine besylate) and a statin (atorvastatin calcium) in a single-pill form (5/20 mg) plus therapeutic lifestyle changes (TLC) compared with placebo plus TLC in patients with comorbid hypertension and dyslipidemia without evidence of cardiovascular disease. At week 4, additional antihypertensive/lipid-lowering medication was permitted. The primary end point was the proportion of patients in whom the dual goal of blood pressure (<140/90 mm Hg) and low-density lipoprotein cholesterol control (<100 mg/dL) was met at week 4. This dual goal attainment was significantly greater with amlodipine/atorvastatin plus TLC compared with placebo plus TLC at week 4 (47.6% vs 1.7%; P<.001), with further improvements at week 8. Most adverse events were mild to moderate. Therapy with single-pill amlodipine/atorvastatin plus TLC in these patients significantly increased dual blood pressure/low-density lipoprotein cholesterol goal attainment compared with placebo plus TLC.

Loss of confidence in diabetes management.

UNLABELLED: Using current treatment approaches, many patients with type 2 diabetes do not achieve glycemic goals--and do experience macrovascular complications that contribute to morbidity and mortality. It's time to consider other options. IMPLICATIONS: Aggressive therapeutic interventions aimed at insulin resistance and cell dysfunction may alter outcomes. Managed care organizations may need to modify the way they look at diabetes and should consider changing their focus from drug costs to wellness. Value-based insurance design may provide opportunities to optimize diabetes management, resulting in improved outcomes for patients and economic benefits for managed care organizations.

Evaluation of the Quality Blue Primary Care program on health outcomes.

OBJECTIVES: This study aimed to investigate the role of the Quality Blue Primary Care (QBPC) program on healthcare utilization and overall cost among the beneficiaries of Blue Cross and Blue Shield of Louisiana (BCBSLA). STUDY DESIGN: Retrospective observational cohort study using claims data from adults residing in QBPC-implemented regions continuously enrolled through BCBSLA from June 2012 to December 2014 (N = 89,034). METHODS: Controlling for age, gender, and risk score by propensity score weighting, inpatient, outpatient, and corresponding medical expenditures were each compared between the QBPC group and the control group using a difference-in-differences regression model. RESULTS: Average total cost increased in both the QBPC and control groups in 2014, but the increase was significantly less in the intervention group-a difference of $27.09 per member per month (PMPM) (P ≤.001). Savings in total cost were derived largely from a decrease in hospitalizations-a difference of $18.85 PMPM (P = .0023). Furthermore, savings were associated with shifts in healthcare utilization by the intervention group toward proactive management, including increased primary care physician visits (P = .0106) and higher screening rates for diabetes (P = .0019). Inpatient admissions also decreased in the QBPC group, most significantly among those with chronic conditions (P <.05). Conversely, an unexpected increase was observed in emergency department visits. CONCLUSIONS: The QBPC program was associated with a shift in primary care delivery and reductions in overall cost. Savings were achieved largely through reductions in hospitalization costs.

Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome in the southeastern United States, part II: treatment recommendations for management of the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome.

An aggressive global approach to screening and to the management of the metabolic syndrome is recommended to slow the growth of the syndrome throughout the United States. Prevention should begin in childhood with healthy nutrition, daily physical activity, and annual measurement of weight, height, and blood pressure beginning at 3 years of age. Such screenings will identify cardiovascular risk factors early, allow the health care provider to define global cardiovascular risk with the COSEHC Cardiovascular Risk Assessment Tool, and allow treatment of each risk factor. Lifelong lifestyle modifications and pharmacologic therapy will be required in most patients. Antihypertensive therapy for these patients should begin with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker unless a compelling indication for another drug is present. Metformin should be considered the first drug for glucose control in the patient with type 2 diabetes. A statin should be used initially for hyperlipidemia unless contraindicated. Combinations of antihypertensive, antiglycemic, and lipid-lowering agents will often be required.

Addressing the global cardiovascular risk of hypertension, dyslipidemia, and insulin resistance in the southeastern United States.

An expanded occurrence of the metabolic syndrome in the U.S. population, especially in the Southeastern United States, has raised awareness of a need to revise our approach to the management of global cardiovascular risk factors while underscoring a need for more aggressive interventions and prevention measures. In defining the components of the metabolic syndrome and the interrelationship among obesity, hypertension, dyslipidemia, and insulin resistance, a basic framework for the medical management of this syndrome has been defined. In Part I of the consensus report prepared by the Workgroup on Medical Guidelines of the Consortium for Southeastern Hypertension Control (COSEHC), we analyze the components of the metabolic syndrome, discuss its pathophysiology, and recommend an approach to the quantitative analysis of the risk factors contributing to excess cardiovascular death in the region.

Insulin Dose and Cardiovascular Mortality in the ACCORD Trial.

OBJECTIVE: In the ACCORD trial, intensive treatment of patients with type 2 diabetes and high cardiovascular (CV) risk was associated with higher all-cause and CV mortality. Post hoc analyses have failed to implicate rapid reduction of glucose, hypoglycemia, or specific drugs as the causes of this finding. We hypothesized that exposure to injected insulin was quantitatively associated with increased CV mortality. RESEARCH DESIGN AND METHODS: We examined insulin exposure data from 10,163 participants with a mean follow-up of 5 years. Using Cox proportional hazards models, we explored associations between CV mortality and total, basal, and prandial insulin dose over time, adjusting for both baseline and on-treatment covariates including randomized intervention assignment. RESULTS: More participants allocated to intensive treatment (79%) than standard treatment (62%) were ever prescribed insulin in ACCORD, with a higher mean updated total daily dose (0.41 vs. 0.30 units/kg) (P < 0.001). Before adjustment for covariates, higher insulin dose was associated with increased risk of CV death (hazard ratios [HRs] per 1 unit/kg/day 1.83 [1.45, 2.31], 2.29 [1.62, 3.23], and 3.36 [2.00, 5.66] for total, basal, and prandial insulin, respectively). However, after adjustment for baseline covariates, no significant association of insulin dose with CV death remained. Moreover, further adjustment for severe hypoglycemia, weight change, attained A1C, and randomized treatment assignment did not materially alter this observation. CONCLUSIONS: These analyses provide no support for the hypothesis that insulin dose contributed to CV mortality in ACCORD.

The COSEHC™ Global Vascular Risk Management quality improvement program: first follow-up report.

The Global Vascular Risk Management (GVRM) Study is a 5-year prospective observational study of 87,863 patients (61% females) with hypertension and associated cardiovascular risk factors began January 1, 2010. Data are gathered electronically and cardiovascular risk is evaluated using the Consortium for Southeastern Hypertension Control™ (COSEHC™)-11 risk score. Here, we report the results obtained at the completion of 33 months since study initiation. De-identified electronic medical records of enrolled patients were used to compare clinical indicators, antihypertensive medication usage, and COSEHC™ risk scores across sex and diabetic status subgroups. The results from each subgroup, assessed at baseline and at regular follow-up periods, are reported since the project initiation. Inference testing was performed to look for statistically significant differences between goal attainments rates between sexes. At-goal rates for systolic blood pressure (SBP) were improved during the 33 months of the study, with females achieving higher goal rates when compared to males. On the other hand, at-goal control rates for total and low-density lipoprotein (LDL) cholesterol (chol) were better in males compared to females. Diabetic patients had lower at-goal rates for SBP and triglycerides but higher rates for LDL-chol. The LDL-chol at-goal rates were higher for males, while high-density lipoprotein (HDL)-chol rates were higher for females. Utilization of antihypertensive medications was similar during and after the baseline period for both men and women. Patients taking two or more antihypertensive medications had higher mean COSEHC™-11 scores compared to those on monotherapy. With treatment, hypertensive patients can reach SBP and cholesterol goals; however, population-wide improvement in treatment goal adherence continues to be a challenge for physicians. The COSEHC™ GVRM Study shows, however, that continuous monitoring and feedback to physicians of accurate longitudinal data is an effective tool in achieving better control rates of cardiovascular risk factors.

The ADMA-Metformin Hypothesis: Linking the Cardiovascular Consequences of the Metabolic Syndrome and Type 2 Diabetes.

Metformin and asymmetric dimethylarginine (ADMA) are structural analogs. They have opposite effects at multiple points on complex signaling pathways that coordinate energy, molecular synthesis, growth, and metabolism with nutrient intake. Excess saturated fats and glucose may initiate the methylation of arginine residues in proteins involved in the transcription of genes mediating inflammation, cell proliferation, apoptosis, and oncogenesis. Free ADMA may appear in the circulation after proteolysis of these proteins when the work of transcription is complete and ADMA subsequently functions as a signaling molecule. In children, ADMA levels are not significantly related to the usual metabolic syndrome risk factors but instead there is a significant association between ADMA and alkaline phosphatase - a marker of normal growth. There is only one direct study that shows that ADMA negates the metabolic effects of metformin. There are no investigations that demonstrate that metformin blocks the effect of ADMA and so this review must be considered hypothesis generating. The potential implications of the metformin-ADMA relationship merit further investigation.

COSEHC global vascular risk management quality improvement program: rationale and design.

BACKGROUND: The Consortium for Southeastern Hypertension Control (COSEHC) promotes global risk factor management in patients with metabolic syndrome. The COSEHC Global Vascular Risk Management Study (GVRM) intends to quantify these efforts on long-term patient outcomes. The objectives of this study were to present baseline demographics of patients enrolled in the GVRM, calculate a modified COSEHC risk score using 11 variables (COSEHC-11), and compare it with the original COSEHC-17 and Framingham, Prospective Cardiovascular Münster (PROCAM), and Systemic Coronary Risk Evaluation (SCORE) risk scores. METHODS: Deidentified electronic medical records of enrolled patients were used to calculate the risk scores. The ability of the COSEHC-11 score to predict the COSEHC-17 score was assessed by regression analysis. Raw risk scores were converted to probability estimates of fatal coronary heart disease (CHD) and compared with predicted risks from other algorithms. RESULTS: Of the 177,404 patients enrolled, 43,676 had data for all 11 variables. The COSEHC-11 score (mean ± standard deviation) of these 43,676 patients was 31.75 ± 11.66, implying a five-year fatal CHD risk of 1.4%. The COSEHC-11 score was highly predictive of the COSEHC-17 score (R(2) = 0.93; P < 0.0001) and correlated well with the SCORE algorithm. CONCLUSION: The COSEHC-11 risk score is statistically similar to the COSEHC-17 risk score and should be a viable tool for evaluating its ability to predict five-year cardiovascular mortality in the coming years.

Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling.

OBJECTIVE: Clinical studies have reported that metformin reduces cardiovascular end points of type 2 diabetic subjects by actions that cannot solely be attributed to glucose-lowering effects. The therapeutic effects of metformin have been reported to be mediated by its activation of AMP-activated protein kinase (AMPK), a metabolite sensing protein kinase whose activation following myocardial ischemia has been suggested to be an endogenous protective signaling mechanism. We investigated the potential cardioprotective effects of a single, low-dose metformin treatment (i.e., 286-fold less than the maximum antihyperglycemic dose) in a murine model of myocardial ischemia-reperfusion (I/R) injury. RESEARCH DESIGN AND METHODS: Nondiabetic and diabetic (db/db) mice were subjected to transient myocardial ischemia for a period of 30 min followed by reperfusion. Metformin (125 microg/kg) or vehicle (saline) was administered either before ischemia or at the time of reperfusion. RESULTS: Administration of metformin before ischemia or at reperfusion decreased myocardial injury in both nondiabetic and diabetic mice. Importantly, metformin did not alter blood glucose levels. During early reperfusion, treatment with metformin augmented I/R-induced AMPK activation and significantly increased endothelial nitric oxide (eNOS) phosphorylation at residue serine 1177. CONCLUSIONS: These findings provide important information that myocardial AMPK activation by metformin following I/R sets into motion events, including eNOS activation, which ultimately lead to cardioprotection.

The role of noninvasive hemodynamic monitoring in the evaluation and treatment of hypertension.

Advances in the understanding of the mechanisms accounting for the elevation of arterial pressure in essential hypertension suggest that there is value in assessing the relative contribution of hemodynamic factors in tailoring specific therapies to control arterial pressure. The non-invasive method of impedance cardiography (ICG) to measure hemodynamic abnormalities in hypertensive patients has emerged as a valuable adjuvant in the decision-making process of selecting antihypertensive agents. The technique is both accurate and reproducible in delineating the hemodynamic mechanisms of hypertension, comparing age-and gender-related changes in hemodynamics, detecting the presence of left ventricular dysfunction, and demonstrating clinically significant improvement in blood pressure control using ICG-guided therapy.

A systematic approach to managing hypertension and the metabolic syndrome in primary care.

OBJECTIVES: Obesity is driving a high prevalence of hypertension and metabolic syndrome-related risk and disease. This report summarizes the impact of a standardized, evidence-based approach to managing high blood pressure and associated metabolic syndrome abnormalities that was developed and implemented by one Clinical Hypertension Specialist. METHODS: Longitudinal data on blood pressure, low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), cardiovascular and renal comorbidities, and treatment medications were obtained on all 817 hypertensive patients seen from January 1, 2000 to June 30, 2003. RESULTS: The hypertensive patients were 72 +/- 11 (SD) years old, and more than 55% of them were high risk based on target organ damage, clinical cardiovascular disease, or diabetes mellitus. Blood pressure was < 140/90 mm Hg in 77% of all patients. Among the high-risk patients, mean blood pressure was 126 +/- 14/71 +/- 10 on 2.8 +/- 1.4 antihypertensive medications, with 88% on angiotensin converting enzyme inhibitors or angiotensin receptor blockers, 59% on diuretics, 49% on calcium channel blockers, and 36% on beta-blockers. Among dyslipidemic hypertensives, LDL-C was controlled to < 130 mg/dL in 84% (510/605) overall and to < 100 mg/dL in 70% of the high-risk group (299/427). Among diabetic hypertensives, the mean HbA1c was 6.8%, with 64% (155/242) less than 7%. New patients demonstrated improved blood pressure, LDL-C, and hemoglobin A1c control over time as the management algorithm was applied. CONCLUSIONS: A high prevalence of complicated hypertension was documented. Blood pressure, LDL-C, and HbA1c were controlled to goal in a high proportion of patients. The findings demonstrate that application of an evidence-based management algorithm can facilitate higher rates of cardiovascular risk factor control than are generally reported in primary care practices.