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The article discusses the issue of national health reform in the U.S. and its implications for the management of diabetes. It offers a historical background on national health care policy in the country and explores the reason behind the necessity of health reform considering national health care expenditures and outcomes. It examines the debate regarding the U.S. Patient Protection and Affordable Act of 2010 and its implications for diabetics. It also notes the large contribution of obesity and diabetes in driving the unsustainable health care costs.

OBJECTIVE--To determine whether skin intrinsic fluorescence (SIF) was associated with autonomic neuropathy and confirmed distal symmetrical polyneuropathy (CDSP) in 111 individuals with type 1 diabetes (mean age 49 years, mean diabetes duration 40 years). RESEARCH DESIGN AND METHODS--SIF was measured using the SCOUT DM device. Autonomic neuropathy was defined as an electrocardiographic abnormal heart rate response to deep breathing (expiration-to-inspiration ratio <1.1). CDSP was defined using the Diabetes Control and Complications Trial clinical exam protocol (the presence of two or more of the following: symptoms, sensory and/or motor signs, and/or reduced/absent tendon reflexes consistent with DSP) confirmed by the presence of an abnormal age-specific vibratory threshold (using a Vibration II tester). RESULTS--The prevalence of autonomic neuropathy and CDSP were 61 and 66%, respectively. SIF was higher in those with autonomic neuropathy (P < 0.0001). In multivariable analyses controlling for age and updated mean (18-year average) HbA1c, and allowing for other univariately and clinically significant correlates of autonomic neuropathy, each SD change in SIF was associated with a 2.6-greater likelihood of autonomic neuropathy (P = 0.006). Receiver operating characteristic (ROC) analyses revealed that SIF and updated mean HbA1c accounted for 80 and 57%, respectively, of the area under the curve (AUC) for autonomic neuropathy. SIF also was higher in those with CDSP (P < 0.0001) and remained so in multivariable analyses (odds ratio 2.70; P = 0.005). ROC analyses revealed that SIF and updated mean HbA1c accounted for 78 and 59%, respectively, of the AUC for CDSP. CONCLUSIONS--SIF, a marker of dermal advanced glycation end products, appears to be more strongly associated with the presence of both CDSP and autonomic neuropathy than mean HbA1c. [ABSTRACT FROM AUTHOR]

The article focuses on the quality assessment of comprehensive cardiometabolic care of patients suffering from type 2 diabetes in the U.S. Topics discussed include an overview of type 2 diabetes, the impact of its prevalence on its mortality and complications, and the formation of the Diabetes Collaborative Registry.

OBJECTIVE -- To evaluate the efficacy and safety of taspoglutide (R1583/BIM51077), a human once-weekly glucagon-like peptide-1 analog, in patients with type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODS -- Type 2 diabetic (n = 306) patients who failed to obtain glycemic control (A1C 7-9.5%) despite 1,500 mg metformin daily were randomly assigned to 8 weeks of double-blind subcutaneous treatment with placebo or taspoglutide, either 5, 10, or 20 mg once weekly or l0 or 20 mg once every 2 weeks, and followed for 4 additional weeks. All patients received their previously established dose of metformin throughout the study. Glycemic control was assessed by change in A1C (percent) from baseline. RESULTS -- Significantly greater (P < 0.0001) reductions in A1C from a mean ± SD baseline of 7.9 ± 0.7% were observed in all taspoglutide groups compared with placebo after 8 weeks of treatment: -1.0 ± 0.1% (5 mg once weekly), -1.2 ± 0.1% (10 mg once weekly), -1.2 ± 0.1% (20 mg once weekly), -0.9 ± 0.1% (10 mg Q2W), and -1.0 ± 0.1% (20 mg Q2W) vs. -0.2 ± 0.1% with placebo. After 8 weeks, body weight loss was significantly greater in the 10 mg (-2.1 ± 0.3 kg, P = 0.0035 vs. placebo) and 20 mg (-2.8 ± 0.3 kg, P < 0.0001) once-weekly groups and the 20 mg once every 2 weeks (-1.9 ± 0.3 kg, P = 0.0083) group than with placebo (-0.8 ± 0.3 kg). The most common adverse event was dose-dependent, transient, mild-to-moderate nausea; the incidence of hypoglycemia was very low. CONCLUSIONS -- Taspoglutide used in combination with metformin significantly improves fasting and postprandial glucose control and induces weight loss, with a favorable tolerability profile. [ABSTRACT FROM AUTHOR]

Background: Rosiglitazone, a thiazolidinedione, has effects on insulin sensitivity and cardiovascular risk factors that may favorably impact the progression of coronary atherosclerosis. Methods: APPROACH is a double-blind randomized clinical trial comparing the effects of the insulin sensitizer rosiglitazone with the insulin secretagogue glipizide on the progression of coronary atherosclerosis. Patients with type 2 diabetes and coronary artery disease undergoing clinically indicated coronary angiography or percutaneous coronary intervention are randomized to receive rosiglitazone or glipizide for 18 months using a titration algorithm designed to provide comparable glycemic control between treatment groups. The primary end point is change in percent atheroma volume from baseline to study completion in a nonintervened coronary artery, as measured by intravascular ultrasound. Cardiovascular events are adjudicated by an end point committee. Results: A total of 672 patients were randomized. The mean age was 61 years, hemoglobin A(1c) (HbA(1c)) 7.2%, body mass index 29.5 kg/m(2), and median duration of diabetes 4.8 years. At baseline, approximately half of the participants were receiving oral antidiabetic monotherapy (53.9%) with 27.5% receiving dual combination therapy and 17.9% treated with diet and exercise alone. Approximately two thirds of the participants (68%) had dyslipidemia, 79.9% hypertension, and 24% prior myocardial infarction. Conclusions: APPROACH has fully enrolled a high-risk patient population and will compare the glucose-independent effects of rosiglitazone and glipizide on the progression of coronary atherosclerosis, as well as provide additional data on the cardiovascular safety of rosiglitazone in patients with type 2 diabetes and coronary artery disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The purpose of this study was to assess whether the prevalence of inducible myocardial ischemia increases over time in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS -- Participants enrolled in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study underwent repeat adenosine-stress myocardial perfusion imaging 3 years after initial evaluation. Patients with intervening cardiac events or revascularization and those who were unable or unwilling to repeat stress imaging were excluded. RESULTS -- Of the initial 522 DIAD patients, 358 had repeat stress imaging (DIAD-2), of whom 71 (20%) had ischemia at enrollment (DIAD-1). Of 287 patients with normal DIAD-1 studies, 259 (90%) remained normal in DIAD-2, whereas 28 (10%) developed new ischemia in DIAD-2. Of the 71 patients with abnormal DIAD-1 studies, 56 (79%) demonstrated resolution of ischemia, whereas 15 (21%) remained abnormal. During this 3-year interval, medical treatment was intensified, with more patients using statins, aspirin, and ACE inhibitors than at baseline. Patients with resolution of ischemia had significantly greater increases in these medications than patients who developed new ischemia (P = 0.04). CONCLUSIONS -- Thus, the majority of asymptomatic patients with type 2 diabetes demonstrated resolution of ischemia upon repeat stress imaging after 3 years. This resolution was associated with more intensive treatment of cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Diabetes has been defined as a coronary heart disease (CHD) risk equivalent, and more aggressive treatment goals have been proposed for diabetic patients. RESEARCH DESIGN AND METHODS -- We studied the influence of single and multiple risk factors on the 10-year cumulative incidence of fatal and nonfatal CHD and cardiovascular disease (CVD) in diabetic and nondiabetic men and women, with and without baseline CHD or CVD, in a population (n = 4,549) with a high prevalence of diabetes. RESULTS -- In both sexes, diabetes increased the risk for CHD (hazard ratio 1.99 and 2.93 for men and women, respectively). Diabetic men and women had a 10-year cumulative incidence of CHD of 25.9 and 19.1%, respectively, compared with 57.4 and 58.4% for nondiabetic men and women with previous CHD. The pattern was similar when only fatal events were considered. Diabetic individuals with one or two risk factors had a 10-year cumulative incidence of CHD that was only 1.4 times higher than that of nondiabetic individuals (14%). However, the 10-year incidence of CHD in diabetic subjects with multiple risk factors was >40%, and the incidence of fatal CHD was higher in these subjects than in nondiabetic subjects with previous CHD. Data for CVD showed similar patterns, as did separate analyses by sex. CONCLUSIONS-- Our results and comparisons with other available data show wide variation in the rate of CHD in diabetes, depending on the population and existing risk factors. Most individuals had a 10-year cumulative incidence >20%, but only those with multiple risk factors had a 10-year cumulative incidence that was equivalent to that of patients with CHD. Until more data are available, it may be prudent to consider targets based on the entire risk factor profile rather than just the presence of diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- This study evaluates the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses. RESEARCH DESIGN AND METHODS -- A triple-blind, placebo-controlled, 30-week study at 82 U.S. sites was performed with 336 randomized patients. In all, 272 patients completed the study. The intent-to-treat population baseline was 53 ± 10 years with BMI of 34.2 ± 5.9 kg/m² and HbA[sup 1c] of 8.2 ± 1.1%. After 4 weeks of placebo, subjects self-administered 5 µg exenatide or placebo subcutaneously twice daily for 4 weeks followed by 5 or 10 µg exenatide, or placebo subcutaneously twice daily for 26 weeks. All subjects continued metformin therapy. RESULTS -- At week 30, HbA[sub 1c] changes from baseline ± SE for each group were -0.78 ± 0.10% (10 µg), -0.40 ± 0.11% (5 µg), and +0.08 ± 0.10% (placebo; intent to treat; adjusted P < 0.002). Of evaluable subjects, 46% (10 µg), 32% (5 µg), and 13% (placebo) achieved HbA[sub 1c] ≤7% (P < 0.01 vs. placebo). Exenatide-treated subjects displayed progressive dose-dependent weight loss (-2.8 ± 0.5 kg [10 µg], -1.6 ± 0.4 kg [5 µg]; P < 0.001 vs. placebo). The most frequent adverse events were gastrointestinal in nature and generally mild to moderate. Incidence of mild to moderate hypoglycemia was low and similar across treatment arms, with no severe hypoglycemia. CONCLUSIONS -- Exenatide was generally well tolerated and reduced HbA[sub 1c] with no weight gain and no increased incidence of hypoglycemia in patients with type 2 diabetes failing to achieve glycemic control with metformin. [ABSTRACT FROM AUTHOR]

Objective-To assess the prevalence and clinical predictors of silent myocardial ischemia in asymtomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines. Research Design and Methods-In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50-75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission-computed tomography myocardial perfusion imaging. Results-A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio [OR] 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion (n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia. Conclusions-Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia. [ABSTRACT FROM AUTHOR]

Objective: Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin.Research Design and Methods: This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l.Results: A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P > 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level <2.0 mmol/l compared with subjects receiving NPH insulin.Conclusions: Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to the cost-effectiveness of strategies for managing people at high risk for diabetes.

Alternate site studies of the fingertip vs. forearm have identified time lags of up to 38 minutes, which is thought to be due to a greater Contribution from interstitial fluid ISF in the forearm. This time-lag can be overcome by perturbing the fluid distribution in the forearm using modulated pressure application (Stout et al, Diabet Tech Ther 2004 6:635). Because needle inserted transcutaneous glucose sensors are thought to mainly measure ISF, we examined the magnitude of the time-lag between sensor values obtained with the DexCom™ STS™ 7 sensor and samples obtained from venous blood measured by a Yellow Springs Instrument (YSI). Seventy-two insulin dependent diabetes subjects at 5 sites were enrolled in a non-randomized study. Subjects inserted and wore 1 or 2 Sensors for 7 days. Sensors were inserted in abdominal subcutaneous tissue. All subjects participated in one 10-hour in-clinic session on Day 1, 4, or 7 in which YSI samples were determined every 20 minutes. Time-lag analysis was performed on 88 sensors that had at least 8 hours of corresponding YSI data. Time-lag was determined by finding the optimal correlation coefficient (R) between raw sensor data and YSI data when the sensor data were shifted in 5 -minute increments. Mean R ± Standard Deviation was 0.95 ± 0.10. Mean time-lag (minutes) was 5.18 ± 4.85, and median time-lag was 5.0. Ninety-two percent (92%) of sensors had a time-lag of 10 minutes or less, and no time-lag exceeded 15 minutes. These data show that most sensors have negligible ISF time-lags when sensors are implanted in the abdominal region. It is likely that, like the forearm, the ISF in the abdominal region is in slow equilibrium with blood, resulting in a lag in blood glucose concentration under native conditions. We hypothesize that the perturbation of the subcutaneous tissue by the sensor insertion, with continued stimulation by the presence of the sensor in the tissue, promotes more rapid equilibrium between blood and ISF than is normally seen in native ISF. [ABSTRACT FROM AUTHOR]

Aims: To assess efficacy and safety of lixisenatide once-daily versus placebo in Type 2 diabetes mellitus (T2DM) patients inadequately controlled on sulfonylurea (SU) ± metformin. Methods: In this randomized, double-blind, two-arm, parallel-group, multicenter study, patients received lixisenatide 20 μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs ± metformin. Primary outcome was change in HbA1c from baseline to Week 24. Results: Lixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo (LS mean: −0.85% vs. −0.10%; p b 0.0001) and more patients achieved HbA1c b7.0% (36.4% vs. 13.5%; p b 0.0001). Lixisenatide significantly lowered FPG and body weight versus placebo. In breakfast meal test patients, lixisenatide reduced 2-hour PPG versus placebo (LS mean: −111.48 vs. −3.80 mg/dL [−6.19 vs. −0.21 mmol/L]; p b0.0001) and glucose excursion (−94.11 vs.+6.24 mg/dL [−5.22 vs.+0.35 mmol/L]), and reduced 2-hour glucagon, insulin, proinsulin, and C-peptide. The percentage of AEs was 68.3% for lixisenatide and 61.1% for placebo; and for SAEs: 3.5% versus 5.6%, respectively. Lixisenatide did not significantly increase symptomatic hypoglycemia versus placebo (15.3% vs. 12.3%, respectively); one severe episode of hypoglycemia was reported with lixisenatide. Conclusions: Once-daily lixisenatide significantly improved glycemic control, with a pronounced postprandial effect, without significant increase in symptomatic/severe hypoglycemia risk and with weight loss over 24 weeks. [ABSTRACT FROM AUTHOR]

Objectives: Cardiovascular disease prevention for patients with type 2 diabetes is accomplished through hypertension and dyslipidemia management. Although studies have established strategies for lowering low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP), none have examined whether glycemia influences ability to achieve lipid and BP targets. This post hoc analysis from the Stop Atherosclerosis in Native Diabetics Study examines the role of baseline glycemia in achieving standard and aggressive targets and outcomes after 36 months.Methods: Diabetic individuals aged > 40 years with no cardiovascular events (n = 499) were randomized to aggressive versus standard targets for LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C) and systolic BP (SBP). Management algorithms were used for both groups. Carotid ultrasound and echocardiography were performed at baseline and after 36 months.Results: No differences were observed in baseline hemoglobin A1c between treatment groups nor any significant change in A1c after 36 months in either group. Baseline A1c, however, was significantly and negatively related to achieving LDL-C (P = .007), non-HDL-C (P = .03) and SBP targets (P = .007) and to changes in LDL-C (P = .007), non-HDL-C (P = .03) and SBP (P = .001) in both groups. Baseline A1c failed to predict progression of carotid intima medial thickness (CIMT) (P = .42) or left ventricular mass index (LVMI) (P = .10), nor was it related to the effects of lipid and BP lowering on CIMT and LVMI over 36 months.Conclusions: In diabetic adults with no cardiovascular disease events, A1c was negatively associated with ability to achieve LDL-C, non-HDL-C and SBP goals but was not independently related to treatment-associated changes in CIMT or LVMI over 36 months. [ABSTRACT FROM AUTHOR]