Association of modifiable risk factors and left ventricular ejection fraction among hospitalized Native Hawaiians and Pacific Islanders with heart failure.

BACKGROUND: Heart failure (HF) disproportionately affects Native Hawaiians and Other Pacific Islanders (NHOPIs). This study examines risk factors associated with left ventricular ejection fraction (LVEF) among 151 hospitalized NHOPI HF patients enrolled at a single tertiary care hospital between June 2006 and April 2010. METHODS: Enrollment criteria: (1) NHOPI by self-identification. (2) Age ≥ 21 yrs. (3) Diagnosis of HF defined: (a) left ventricular ejection fraction (LVEF) ≤ 40% or LVEF ≤ 60% with abnormal diastolic function and (b) classic HF signs/symptoms. LVEF was measured by echocardiography within 6 weeks of hospitalization. Clinical measures, medical history, and questionnaires were assessed using standardized protocols. Linear regression modeling was used to examine the association of significant correlates of LVEF, which were then included en bloc into the final model. A P-value < .05 was considered statistically significant. RESULTS: Of 151 participants, 69% were men, mean age 54.3 ± 13.5 years, blood pressure 112 ± 20/69 ± 15 mmHg, and body mass index (BMI) 36.9 ± 9 kg/m(2). Twenty-five percent of participants were smokers, 45% used alcohol and 23% reported a history of methamphetamine use. Clinically, 72% had hypertension, 49% were diabetic and 37% had a prior myocardial infarction. Nearly 60% had moderate to severe LVEF (< 35%). Higher LVEF was independently associated with female sex and greater BMI (P < .04) while pacemaker/defibrillator and methamphetamine use was independently associated with lower LVEF (P < .05). CONCLUSIONS: Methamphetamine use and BMI may be important modifiable risk factors associated with LVEF and may be important targets for improving HF morbidity and mortality.

Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S).

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<0.0001) and more patients achieved HbA1c <7.0% (36.4% vs. 13.5%; p<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<0.0001) 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.

The association of basal insulin glargine and/or n-3 fatty acids with incident cancers in patients with dysglycemia.

OBJECTIVE Epidemiologic studies linking insulin glargine and glucose-lowering therapies to cancers and n-3 fatty acids to cancer prevention have not been confirmed. We aimed to assess the effect of insulin glargine and n-3 fatty acids on incident cancers within the context of the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial. RESEARCH DESIGN AND METHODS The ORIGIN trial is an international, long-term, randomized two-by-two factorial study comparing insulin glargine with standard care and n-3 fatty acids with placebo (double blind) in people with dysglycemia at high risk for cardiovascular events. The primary outcome measure (cancer substudy) was the occurrence of any new or recurrent adjudicated cancer. Cancer mortality and cancer subtypes were also analyzed. RESULTS Among 12,537 people (mean age 63.5 years, SD 7.8; 4,388 females), 953 developed a cancer event during the median follow-up of 6.2 years. In the glargine and standard care groups, the incidence of cancers was 1.32 and 1.32 per 100 person-years, respectively (P = 0.97), and in the n-3 fatty acid and placebo groups, it was 1.28 and 1.36 per 100 person-years, respectively (P = 0.39). No difference in the effect of either intervention was noted within predefined subgroups (P for all interactions ≥0.17). Cancer-related mortality and cancer-specific outcomes also did not differ between groups. Postrandomization HbA1c levels, glucose-lowering therapies (including metformin), and BMI did not affect cancer outcomes. CONCLUSIONS Insulin glargine and n-3 fatty acids have a neutral association with overall and cancer-specific outcomes, including cancer-specific mortality. Exposure to glucose-lowering therapies, including metformin, and HbA1c level during the study did not alter cancer risk.

Cross-sectional evaluation of noninvasively detected skin intrinsic fluorescence and mean hemoglobin a1c in type 1 diabetes.

BACKGROUND: This study evaluated the relationship between skin intrinsic fluorescence (SIF) and long-term mean hemoglobin A1c (HbA1c) in individuals with type 1 diabetes. SUBJECTS AND METHODS: We undertook a cross-sectional analysis of 172 individuals with type 1 diabetes followed longitudinally with HbA1c data available over an average of 16.6 years. SIF was evaluated cross-sectionally using the SCOUT DS device (VeraLight Inc., Albuquerque, NM) and correlated with most recent HbA1c and long-term mean HbA1c. Potential determinants of this relationship, including age, gender, smoking status, duration of diabetes, and renal function, were also evaluated. RESULTS: Age-adjusted skin intrinsic fluorescence significantly correlated with long-term mean HbA1c (R=0.44, P<0.0001). In contrast, there was no significant relationship between SIF and most recent HbA1c (R=0.14, P=0.075). The best-fit model describing the relationship between SIF and mean HbA1c controlled for factors of age, duration of disease, renal function, and site of study conduct. Controlling for these factors was also important in understanding the relationship between most recent HbA1c and SIF. Evaluating longer-term HbA1c data also strengthened the relationship between SIF and mean HbA1c. In the presence of renal dysfunction or damage, as indicated by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or presence of gross proteinuria, there was no significant correlation between SIF and mean HbA1c. CONCLUSIONS: Noninvasive detection of SIF significantly correlates with long-term mean HbA1c, providing insight into long-term glycemic exposure. Age, duration of diabetes, and renal function are potential contributors to this relationship.

Treatment recommendations for prediabetes.

A variety of definitions and diagnostic cutpoints have been promulgated for prediabetes without universal agreement. Professional organizations agree that current scientific evidence justifies intervention in high-risk populations for the delay or prevention of progression to diabetes. Lifestyle intervention is universally accepted as the primary intervention strategy. Secondary intervention is advocated in high-risk individuals or in the absence of a clinical response to lifestyle modification.

Effects of therapy in type 1 and type 2 diabetes mellitus with a peptide derived from islet neogenesis associated protein (INGAP).

BACKGROUND: Islet neogenesis associated protein (INGAP) has beta cell regenerating effects in experimental models. METHODS: Subjects with T1DM (N = 63) and T2DM (N = 126) received 300 or 600 mg/day of INGAP peptide in a 90 day, randomized, double-blind, placebo-controlled trial. RESULTS: In T1DM, on-treatment Arginine-stimulated C-peptide (AUC(0-30)) significantly increased from baseline in the 600 mg group (p = 0.0058 versus placebo); no significant changes were seen in the 300 mg group. In T2DM, stimulated C-peptide was significantly better preserved in the 600 mg group compared to placebo at day 120, 30 days after washout (p = 0.031 versus placebo), but did not reach statistical significance during treatment or in the 300 mg group. In T2DM, A1C decreased significantly more in the 600 mg group compared to placebo at day 90 (-0.94% versus -0.47%, respectively, p = 0.009) and day 120, 30 days after washout (-0.73% versus -0.24%, respectively, p = 0.013). This was accompanied by significant reductions in mean glucose. No difference from placebo was detected in the 300 mg group or in T1DM. Injection site reactions were the most common adverse event, occurring in 8 (36%) of placebo, 19 (90%) of 300 mg, and 15 (75%) of 600 mg groups (T1DM) and 14 (33%) of placebo, 27 (64%) of 300 mg, and 29 (69%) of 600 mg groups (T2DM). CONCLUSIONS: INGAP peptide increases C-peptide secretion in T1DM and improves glycaemic control in T2DM. Longer-term exposure, more frequent dosing, better tolerated formulations or combination with other therapies may be necessary to achieve optimal clinical response.

Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial.

CONTEXT: Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial. OBJECTIVE: To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. DESIGN, SETTING, AND PATIENTS: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007. MAIN OUTCOME MEASURE: Cardiac death or nonfatal myocardial infarction (MI). RESULTS: The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. CONCLUSION: In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00769275.

Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study.

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 10 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.

Combination pharmacotherapy with incretins: what works best and when?

The incretin hormone glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors fill an unaddressed therapeutic gap in the treatment of type 2 diabetes mellitus (T2DM) by potentiating insulin secretion in pancreatic beta cells, suppressing glucagon secretion, delaying gastric emptying, and reducing appetite. The incretin therapies, alone or in combination with metformin and/or thiazolidinediones, yield improved glycemic control without risk of hypoglycemia and the potential for weight neutrality or even weight loss. New incretin-based approaches offer promising new strategies for treating T2DM by recruiting new, physiologically based mechanisms of action for glucoregulation in the context of a favorable safety profile.

Effect of exenatide on 24-hour blood glucose profile compared with placebo in patients with type 2 diabetes: a randomized, double-blind, two-arm, parallel-group, placebo-controlled, 2-week study.

OBJECTIVE: The aim of this study was to examine the glucose-lowering effect of exenatide over 24 hours in patients with type 2 diabetes with inadequate glycemic control using metformin, with or without a thiazolidinedione (TZD). METHODS: This randomized, double-blind, 2-arm, parallel-group, placebo-controlled, 2-week study was conducted in patients with type 2 diabetes with inadequate glycemic control, despite metformin with or without a TZD. Patients underwent a baseline and a week-2 (study end) 24-hour admission during which serial serum glucose measurements were taken. Preprandial and postprandial concentrations of triglycerides and free fatty acids were also measured. Meals provided for each patient were identical at the baseline and week-2 assessments. Following the baseline admission, patients were randomized to receive SC injections of either exenatide (5 microg BID for 1 week, then 10 microg BID for the next week) or placebo (volume equivalent) for 14 days. RESULTS: A total of 30 patients (19 women [63%], 11 men [37%]; mean [SD] age, 52.6 [11.2] years; weight, 94.3 [23.0] kg; body mass index, 34.2 [6.1] kg/m(2); glycosylated hemoglobin value, 8.0% [0.9%]; diabetes duration, 8.7 [5.6] years; race, Hispanic 18 [60%], white 10 [33%], black 2 [7%]) were eligible. Seventeen patients (57%) were randomized to treatment with exenatide and 13 patients (43%) received placebo. Concurrent antidiabetic medications were metformin only (n = 19 [63%]) and metformin plus a TZD (n = 11 [37%]). All postbaseline values were least squares mean (SE). After 2 weeks (study end), the 24-hour time-average glucose values were 7.0 (0.2) and 8.8 (0.3) mmol/L for exenatide-treated and placebo-administered patients, respectively (P < 0.001). The glucose values for patients treated with exenatide were lower compared with those in patients who received placebo 2 hours after the morning meal (6.6 [0.4] vs 12.0 [0.5] mmol/L; P < 0.001), the midday meal (8.8 [0.5] vs 11.8 [0.6] mmol/L; P = 0.001), and the evening meal (6.8 [0.4] vs 11.3 [0.4] mmol/L; P < 0.001). The mean durations of patient exposure to glucose concentrations >7.8 and >11.1 mmol/L were significantly shorter for the exenatide group compared with the placebo group (>7.8 mmol/L: 6.8 [0.9] vs 14.1 [1.1] hours; >11.1 mmol/L: 1.0 [0.7] vs 4.7 [0.8] hours; both, P < 0.001). After 2 weeks, the postprandial triglyceride excursions after the morning and evening meals for patients treated with exenatide were significantly lower compared with those treated with placebo. There was no apparent effect on free fatty acid concentrations. CONCLUSIONS: In these patients with type 2 diabetes, exenatide was associated with significantly reduced glucose concentrations at multiple time points during 24 hours, with the greatest effect seen on postprandial glucose concentrations. In addition, exenatide was associated with decreased overall hyperglycemic exposure and significantly decreased postprandial triglyceride excursions. These results are consistent with those seen in other studies that reported the effectiveness of exenatide in controlling hyperglycemia in patients with type 2 diabetes.

Cost-effectiveness of screening for pre-diabetes among overweight and obese U.S. adults.

OBJECTIVE: To estimate the cost-effectiveness of screening overweight and obese individuals for pre-diabetes and then modifying their lifestyle based on the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS: A Markov simulation model was used to estimate disease progression, costs, and quality of life. Cost-effectiveness was evaluated from a health care system perspective. We considered two screening/treatment strategies for pre-diabetes. Strategy 1 included screening overweight subjects and giving them the lifestyle intervention included in the DPP if they were diagnosed with both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Strategy 2 included screening followed by lifestyle intervention for subjects diagnosed with either IGT or IFG or both. Each strategy was compared with a program of no screening. RESULTS: Screening for pre-diabetes and treating those identified as having both IGT and IFG with the DPP lifestyle intervention had a cost-effectiveness ratio of $8,181 per quality-adjusted life-year (QALY) relative to no screening. If treatment was also provided to subjects with only IGT or only IFG (strategy 2), the cost-effectiveness ratio increased to $9,511 per QALY. Changes in screening-related parameters had small effects on the cost-effectiveness ratios; the results were more sensitive to changes in intervention-related parameters. CONCLUSIONS: Screening for pre-diabetes in the overweight and obese U.S. population followed by the DPP lifestyle intervention has a relatively attractive cost-effectiveness ratio.

Resolution of asymptomatic myocardial ischemia in patients with type 2 diabetes in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study.

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.

Pramlintide: A new tool in diabetes management.

The amylin analogue pramlintide acts in concert with insulin to regulate glucose metabolism. It reduces postprandial hyperglycemia by suppressing postprandial glucagon secretion, regulating gastric emptying, and reducing food intake. In clinical use, pramlintide reduces postprandial glycemic excursions and improves A(1c) without the weight gain and increased risk of hypoglycemia typically seen with intensification of diabetes therapy.

Value of peripheral vascular endothelial function in the detection of relative myocardial ischemia in asymptomatic type 2 diabetic patients who underwent myocardial perfusion imaging.

BACKGROUND: Endothelial dysfunction precedes overt atherosclerosis and is present in patients with type 2 diabetes mellitus (T2DM). Myocardial perfusion imaging (MPI) is an effective method of detection of coronary artery disease (CAD); however, the relationship between endothelial function and MPI in asymptomatic patients with T2DM has not been examined. METHODS AND RESULTS: This study used a subset of the population from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) were measured by use of brachial artery ultrasonography in 75 asymptomatic patients with T2DM (56 men; mean age, 58.6 +/- 6.4 years; mean duration of diabetes, 8.4 +/- 7.5 years) who underwent adenosine MPI. Of the patients, 15 (20%) had evidence of relative ischemia (MPI(+)) whereas 60 (80%) had a normal study (MPI(-)). Both EDV (3.5% +/- 3.7% vs 4.5% +/- 6.6%, P = not significant) and EIV (15.1% +/- 7.5% vs 16.8% +/- 8.4%, P = not significant) were similar in the 2 groups. On the basis of a receiver-operator analysis, an EDV response of 8% was selected as a cut point, with a negative predictive value of 93% (13/14 subjects with EDV >or=8% were MPI(-)). CONCLUSIONS: Endothelial function in asymptomatic patients with T2DM is not associated with the presence of relative myocardial ischemia by MPI; however, an EDV of 8% or greater has a high negative predictive value for the exclusion of CAD.

An evaluation of cost sharing to finance a diet and physical activity intervention to prevent diabetes.

OBJECTIVE: The Diabetes Prevention Program (DPP) lifestyle intervention is a cost-effective strategy to prevent type 2 diabetes, but it is unclear how this intervention could be financed. We explored whether this intervention could be offered in a way that allows return on investment for private health insurers while remaining attractive for consumers, employers, and Medicare. RESEARCH DESIGN AND METHODS: We used the DPP and other published reports to build a Markov simulation model to estimate the lifetime progression of disease, costs, and quality of life for adults with impaired glucose tolerance. The model assumed a health-payer perspective and compared DPP lifestyle and placebo interventions. Primary outcomes included cumulative incidence of diabetes, direct medical costs, quality-adjusted life-years (QALYs), and cost per QALY gained. RESULTS: Compared with placebo, providing the lifestyle intervention at age 50 years could prevent 37% of new cases of diabetes before age 65, at a cost of $1,288 per QALY gained. A private payer could reimburse $655 (24%) of the $2,715 in total discounted intervention costs during the first 3 intervention years and still recover all of these costs in the form of medical costs avoided. If Medicare paid up to $2,136 in intervention costs over the 15-year period before participants reached age 65, it could recover those costs in the form of future medical costs avoided beginning at age 65. CONCLUSIONS: Cost-sharing strategies to offer the DPP lifestyle intervention for eligible people between ages 50 and 64 could provide financial return on investment for private payers and long-term benefits for Medicare.

Achievement of American Diabetes Association clinical practice recommendations among U.S. adults with diabetes, 1999-2002: the National Health and Nutrition Examination Survey.

OBJECTIVE: To estimate the proportion of U.S. adults with diabetes who meet American Diabetes Association (ADA) clinical practice recommendations. RESEARCH DESIGN AND METHODS: Using data from the 1999-2002 National Health and Nutrition Examination Survey, 998 adults aged >/=18 years with self-reported diabetes were identified. The proportion of adults with diabetes meeting ADA recommendations for HbA(1c) (A1C), HDL cholesterol, LDL cholesterol, triglycerides, blood pressure, renal function, nutrient intake, smoking, pneumococcal vaccination, and physical activity was estimated. RESULTS: Among U.S. adults with diabetes in 1999-2002, 49.8% had A1C <7%; 27.4, 36.0, and 65.0% were classified as low risk for HDL cholesterol, LDL cholesterol, and triglycerides, respectively. Nearly 40% met blood pressure recommendations, 66% had normal renal function, and daily nutrient recommendations for protein, saturated fat, unsaturated fat, and fiber were met by 64.0, 48.3, 28.3, and 18.3%, respectively. Although >81% of the sample reported not smoking at the time of the exam, only 38.2% reported ever having had a pneumococcal immunization, and 28.2% reported getting the recommended level of physical activity. Race, age, duration of diabetes, and education affected achievement of ADA recommendations. CONCLUSIONS: Achievement of ADA clinical practice recommendations is far from adequate in U.S. adults with diabetes.

Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes.

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/m(2) and HbA(1c) of 8.2 +/- 1.1%. After 4 weeks of placebo, subjects self-administered 5 microg exenatide or placebo subcutaneously twice daily for 4 weeks followed by 5 or 10 microg exenatide, or placebo subcutaneously twice daily for 26 weeks. All subjects continued metformin therapy. RESULTS: At week 30, HbA(1c) changes from baseline +/- SE for each group were -0.78 +/- 0.10% (10 microg), -0.40 +/- 0.11% (5 microg), and +0.08 +/- 0.10% (placebo; intent to treat; adjusted P < 0.002). Of evaluable subjects, 46% (10 microg), 32% (5 microg), and 13% (placebo) achieved HbA(1c) < or =7% (P < 0.01 vs. placebo). Exenatide-treated subjects displayed progressive dose-dependent weight loss (-2.8 +/- 0.5 kg [10 microg], -1.6 +/- 0.4 kg [5 microg]; 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(1c) with no weight gain and no increased incidence of hypoglycemia in patients with type 2 diabetes failing to achieve glycemic control with metformin.

Novel pharmacologic agents for type 2 diabetes.

After many decades of relative therapeutic stagnation since the initial discovery of insulin, followed by some modifications on its structure and only having sulfonylureas and biguanides for many years, the last decade has seen a surge in new therapeutic options for the management of diabetes. The results of the United Kingdom Prospective Diabetes Study and Kumamoto study indicate the need for aggressive glycemic control and the slow inexorable clinical deterioration associated with type 2 diabetes overtime. The propensity for weight gain and hypoglycemia are the two major limitations that subcutaneous insulin and sulfonylureas have been particularly prone to. The newer antidiabetic medications and those on the horizon attempt to address these limitations. GLP-1 agonists and the DPP-IV inhibitors exploit the innate incretin system to improve glycemia while promoting satiety and weight management. Like GLP-1 related compounds, pramlintide offers the potential to address postprandial hyperglucagonemia associated with type 2 diabetes only limited by the multiple injections and gastrointestinal side effects. The glitazars offer the hope ofa new approach to diabetes care addressing not just glycemia, but dyslipidemia and other components of the metabolic syndrome, though the side effect profile remains a major unknown. The INGAP peptide represents the holy grail of diabetes care as it offers the potential of a new paradigm: that of islet regeneration and potential for a cure. But at this stage, with no human data available, it remains highly speculative. Beyond these and other novel agents being developed to meet the challenge of the worldwide epidemic of diabetes, the central place of insulin in diabetes care cannot be forgotten. In view of this the continued efforts of improvement in insulin delivery, kinetics and action have spurred such innovations as the various inhaled insulins and new insulin analogues. There is cause for guarded optimism and excitement about the years ahead. There is reason to expect that despite the growing burden of diabetes worldwide, we will be better equipped to manage it and its comorbidities and prevent its onset and possibly even cure it.