Change In Hemoglobin A1c Research Articles

HIV infection and glycemic response to newly initiated diabetic medical therapy

Type 2 diabetes (DM2) is increasingly common in HIV-infected individuals. Antiretroviral agents and chronic inflammation may adversely affect glycemic control. However, little is known about the effectiveness of diabetic medical therapy in HIV-infected patients. The objective of this study was to compare the effectiveness of initial diabetic medical therapy in patients with and without HIV infection. A retrospective cohort study was conducted among adults with DM2 initiating diabetic medications within the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Generalized estimating equations were used to compare changes in hemoglobin A1c (HbA1c) through the year after initiation of therapy, controlling for baseline HbA1c and demographic and clinical covariates. Two hundred and eighty-six HIV-infected patients and 858 age and sex-matched HIV-uninfected patients initiated diabetic medications during the study period. Overall, patients had an adjusted absolute mean reduction in HbA1c of 1.04% [95% confidence interval (CI) -0.87 to -1.22] during the first year of therapy. HIV-infected patients achieved significantly smaller reductions in HbA1c, with an absolute mean difference of -0.17% (95% CI -0.28 to -0.06; P = 0.003). On subanalyses, HIV-infected patients on a protease inhibitor-based regimen had significantly smaller reductions in HbA1c compared to HIV-uninfected patients (adjusted absolute difference -0.21%, 95% CI -0.35 to -0.08; P = 0.002). Patients with HIV infection who initiate diabetic medical therapy achieve smaller reductions in HbA1c than patients without HIV infection in the course of routine clinical care. This less robust response may in part be related to use of antiretrovirals that exacerbate insulin resistance, specifically protease inhibitors.

Clinical Outcomes Associated with Referral-Based Continuous Glucose Monitoring Using a Central Standardized Interpretation Strategy

Continuous glucose monitoring (CGM) devices can present a challenge to health providers given the sheer amount of data collected. A referral-based system using a centralized standard interpretation completed by a specialist could highlight the most pertinent information and provide recommendations. Professional (retrospective) CGM reports from an outpatient academic endocrinology clinic were formally interpreted by one of two specialists. General recommendations for therapy adjustments were made to each patient's referring provider without a face-to-face visit using only the CGM download and patient logs. Findings were characterized as well as change in hemoglobin A1c (HbA1c) by 6 and 12 months. Patients with baseline HbA1c values above 8.1% experienced a significant reduction (-0.36 ± 0.80%) at 6 months post-CGM (P = 0.035), whereas those with baseline HbA1c below 8.1% experienced an equally significant increase (0.36 ± 0.83%, P = 0.032), most likely because of interventions that addressed hypoglycemia. Hypoglycemia was common, and unrecognized overnight hypoglycemia lasting over 2 h occurred in 48% of patients. There were no differences in findings or in HbA1c changes among pump compared with non-pump users. In total, 69% of patients had a change in management by the referring provider within 1 month. The data suggest that some patients benefited, in the form of reductions in HbA1c, from centralized referral and interpretation of professional CGM regardless of modality of insulin therapy. Considerations for methods to improve coordination with referring providers for follow-up care are needed.

Clinical Outcomes of Concomitant Therapy of Exenatide Twice Daily and Basal Insulin In Patients with Type 2 Diabetes Mellitus: A Retrospective Database Analysis In the United States

To examine the clinical effectiveness of concomitant therapy of exenatide twice daily and basal insulin in patients with type 2 diabetes mellitus in the United States. Data from adults with type 2 diabetes were selected from an electronic medical record database. Concomitant therapy was defined as a basal insulin prescription within 6 months before or after an exenatide prescription between May 2005 and April 2009. Upon initiation, patients were treated with both medications. Clinical effectiveness was measured as mean changes in hemoglobin A1c (primary outcome), body weight, body mass index, blood pressure, and lipid values from a 6-month baseline to mean-adjusted values in a 12-month follow-up period. These changes were assessed by a bootstrapping test. There were 1752 patients (mean age, 57 years) who initiated concomitant therapy (75% added exenatide to basal insulin, 25% added basal insulin to exenatide). Patients achieved significant mean reductions in hemoglobin A1c (0.5%), body weight (1.8 kg), body mass index (0.6 kg/m2), diastolic blood pressure (0.5 mm Hg), and various lipid measures (all P<.05). Hemoglobin A1c reduction was consistent irrespective of the treatment order. However, body weight, body mass index, and blood pressure reductions were observed in only patients who added exenatide to basal insulin. Overall, exenatide and basal insulin concomitant therapy was associated with significant reductions in hemoglobin A1c, body weight, body mass index, diastolic blood pressure, and lipids in a large, diverse patient population treated in ambulatory care settings in the United States. In the subgroup analysis, body weight, body mass index, and diastolic blood pressure reductions were observed in only patients who added exenatide to basal insulin.

Efficacy and Tolerability of Linagliptin Added to a Sulfonylurea Regimen in Patients With Inadequately Controlled Type 2 Diabetes Mellitus: An 18-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundSome patients with type 2 diabetes mellitus (T2DM) receiving monotherapy with a sulfonylurea (SU) are unable to meet recommended glycemic targets over the long term and require additional pharmacologic agents to maintain glycemic control. This study was designed to assess the utility of adjunctive therapy with the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in patients with T2DM inadequately controlled with SU monotherapy. ObjectiveTo assess the efficacy and tolerability of linagliptin as add-on therapy in patients with inadequately controlled T2DM despite background therapy with an SU. MethodsIn this Phase III, multicenter, randomized, double-blind, placebo-controlled trial, patients with inadequately controlled T2DM on SU monotherapy were randomly assigned to receive treatment with linagliptin 5 mg once daily (n = 161) or placebo (n = 84) for 18 weeks. The primary end point was the mean change in hemoglobin (Hb) A1c from baseline to week 18, evaluated using ANCOVA. Tolerability was assessed using laboratory analysis, spontaneous reporting, and physical examination and interview. ResultsMean baseline characteristics were similar in the linagliptin and placebo groups. Linagliptin treatment was associated with a placebo-corrected mean (95% CI) change in HbA1c from baseline (8.6%) to 18 weeks of −0.47% (−0.70 to −0.24; P < 0.0001). Patients in the linagliptin group were more likely compared with placebo to achieve the HbA1c target level of <7.0% after 18 weeks of treatment (15.2% vs 3.7%, respectively; odds ratio [OR] = 6.5; 95% CI, 1.7–24.8; P = 0.007). Similarly, patients in the linagliptin group were more likely to achieve an HbA1c reduction of ≥0.5% compared with those in the placebo group (57.6% vs 22.0%; OR = 5.1, 95% CI 2.7–9.6; P < 0.0001). The overall frequency of adverse events was similar between the linagliptin and placebo groups (42.2% vs 42.9%). The incidences of hypoglycemic events were not significantly different between the 2 groups (5.6% vs 4.8%), and none of the hypoglycemic episodes were assessed as severe by the investigator. The difference in the changes in mean body weight was not significant (+0.43 vs −0.01 kg; P = 0.12). ConclusionsThe addition of linagliptin to SU therapy for 18 weeks in these patients with T2DM was associated with statistically significant and clinically meaningful reductions in HbA1c compared with placebo. The overall tolerability of linagliptin was similar to that of placebo, with a low risk for hypoglycemia and no significant weight gain. These findings support the use of linagliptin as adjunctive therapy in patients with T2DM inadequately controlled on SU monotherapy. ClinicalTrials.gov identifier: NCT00819091.

An Update in Incretin-Based Therapy: A Focus on Glucagon-Like Peptide-1 Receptor Agonists

The glucagon-like peptide-1 receptor agonists, exenatide and liraglutide, offer a unique mechanism in the treatment of type 2 diabetes mellitus (T2DM) as part of the incretin system. Their mechanism of action is to increase insulin secretion, decrease glucagon release, reduce food intake, and slow gastric emptying. They target postprandial blood glucose values and have some effect on fasting levels as well. In addition, they promote weight loss and may help to preserve β-cell function, both major problems in T2DM patients. Changes in hemoglobin A1c are similar to those produced by other T2DM agents, including thiazolidinediones, low-dose metformin, and sulfonylureas, and better than those caused by α-reductase inhibitors and dipeptidyl peptidase-4 inhibitors. These agents have been safely studied in combination with metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin therapy. Overall, data are limited for head-to-head comparisons, but it appears that liraglutide may have better efficacy and tolerability compared with exenatide; however, more studies are needed. They are overall well tolerated, with the main adverse events being similar to those with metformin (gastrointestinal intolerances that are transient and dose dependent). However, patients must be monitored for pancreatitis as a rare but possible side effect. For T2DM patients willing to use an injectable agent, exenatide and liraglutide offer another therapeutic option to control hyperglycemia with the potential for weight loss and may be combined with other agents safely.

Long-Term Prognosis of Autoimmune Pancreatitis in Terms of Glucose Tolerance

Glucose intolerance is often observed in autoimmune pancreatitis (AIP), although its long-term prognosis after steroid treatment (ST) is still unclear. A total of 47 patients with AIP were enrolled. On the basis of the change in hemoglobin A1c (HbA1c) and the use of diabetic medication, prognosis was classified into 3 categories, namely, "improved," "aggravated," and "unchanged." The relation between the result of an initial glucagon tolerance test (ΔCPR) and the later use of insulin during maintenance ST was examined in 20 patients. The transitions of homeostasis model assessment β cell and insulin resistance (HOMA-β and HOMA-R) were analyzed in 16 patients. Glucose tolerance was improved in 6 patients (13%), aggravated in 9 patients (19%), and unchanged in 32 patients (68%). All patients with ΔCPR less than 0.6 ng/mL were obliged to use insulin even after long-term observation, whereas all patients with ΔCPR more than 1.0 ng/mL were free from insulin therapy. Moreover, HOMA-β showed significant improvement after ST (43.9% → 56.0% in median, P = 0.030), and HOMA-R showed significant aggravation (1.30 → 1.78, P = 0.039). Glucose tolerance that is too severely damaged may not recover fully even after ST. Thus, ST should be performed to preserve insulin secretion at the early stage of AIP.

Impact of Insulin Resistance, Body Mass Index, Disease Duration, and Duration of Metformin Use on the Efficacy of Vildagliptin

IntroductionThe optimal stage for dipeptidyl peptidase-4 (DPP-4) inhibitor therapy in the course of type 2 diabetes mellitus (T2DM) is still under discussion, with often a perception that treatment with these agents may be less beneficial with increasing disease progression, due to loss of beta-cell function, and with increasing insulin resistance (IR), where beta-cell function is less prominent. This work, therefore, aimed to assess the impact of such factors on the efficacy of the DPP-4 inhibitor, vildagliptin, in add-on therapy to metformin.MethodsA pooled analysis of 24-week efficacy data of vildagliptin 50 mg twice daily (b.i.d.) (n = 2,478) from four add-on to metformin studies was performed. Analyses for changes in hemoglobin A1c (HbA1c) were stratified according to baseline IR stage (homeostasis model assessment [Homa IR] <5, ≥5), body mass index (BMI) (<27, ≥27 to <30, ≥30 kg/m2), T2DM duration (0 to <1, ≥1 to <5, ≥5 years), and duration of metformin use (0 to <1, ≥1 to <5, ≥5 years). Data from patients treated with sulfonylureas (SUs) (n = 2,010) in the pooled studies are provided as reference.ResultsPatients in the vildagliptin and SU groups had mean age, HbA1c, BMI, Homa IR, duration of T2DM and metformin use of 58 years, 7.7%, 32 kg/m2, 4.3, 5.9 years and 3.0 years, respectively. Reductions from baseline in HbA1c with vildagliptin were very similar across Homa IR (mean 2.8 and 8.6), BMI (mean 24.9, 28.5, and 35.3 kg/m2), T2DM duration (mean 0.6, 2.9, and 9.7 years), and duration of metformin use (mean 0.6, 2.6, and 7.9 years) categories, showing significant drops in HbA1c of approximately −0.7% (baseline 7.7%). The results in patients receiving SUs were comparable to those seen in the vildagliptin group.ConclusionVildagliptin add-on therapy to metformin was efficacious independent of IR stage and BMI, as well as disease duration and duration of prior metformin use, indicating that, contrary to a not uncommon perception, more obese patients and patients with long-standing T2DM can benefit from treatment with the DPP-4 inhibitor, vildagliptin.

Using electronic medical records analysis to investigate the effectiveness of lifestyle programs in real-world primary care is challenging: a case study in diabetes mellitus

ObjectiveThe increasing prevalence of diabetes suggests a gap between real world and controlled trial effectiveness of lifestyle interventions, but real-world investigations are rare. Electronic medical registration facilitates research on real-world effectiveness, although such investigations may require specific methodology and statistics. We investigated the effects of real-world primary care for patients with type 2 diabetes mellitus (T2DM). Study Design and SettingWe used medical records of patients (n=2,549) with T2DM from 10 primary health care centers. A mixed-effects regression model for repeated measurements was used to evaluate the changes in weight and Hemoglobin A1c (HbA1c) over time. ResultsThere was no statistically significant change in weight (+0.07kg, P=0.832) and HbA1c (+0.03%, P=0.657) during the observation period of 972 days. Most patients maintained their physical activity level (70%), and 54 % had an insufficient activity level. The variability in the course of weight and HbA1c was because of differences between patients and not between health care providers. ConclusionDespite effective lifestyle interventions in controlled trial settings, we found that real-world primary care is only able to stabilize weight and HbA1c in patients with T2DM over time. Medical registration can be used to monitor the actual effectiveness of interventions in primary care.

Pharmacists’ Impact on Improving Outcomes in Patients With Type 2 Diabetes Mellitus

The purpose of this study was to evaluate a diabetes education program that includes a pharmacist as a member of the diabetes management team by assessing the change in hemoglobin A1c (A1C), cholesterol, and blood pressure for patients with type 2 diabetes in outpatient clinics. This was a retrospective study in outpatient clinics at Shands Jacksonville Medical Center. The patients were assigned into either the pharmacist group or the nonpharmacist group, according to the presence or the absence of a pharmacist in the clinic. The primary end point was the absolute change in A1C versus baseline. Secondary end points included change in cholesterol and blood pressure and the number of patients to attain American Diabetes Association goals. End points were recorded to correlate within 3 months of the initial visit and final visit with a provider. Compared to the nonpharmacist group, patients in the pharmacist group had more advanced and uncontrolled diabetes at baseline. The pharmacist group showed a greater percent change in A1C and improvement between the initial and final clinic visits, after adjusting for baseline confounders. Despite the statistically significant improvement in A1C in the pharmacist group, there was no difference found between the 2 groups for the end points of cholesterol and blood pressure. Including a pharmacist as a part of the diabetes management team may result in lower A1C in patients with more advanced and uncontrolled type 2 diabetes mellitus versus a health care team without a pharmacist.

Comparison between Two Calcium Antagonists: Blood Pressure Reduction and Renal Effects in Hypertensive Patients with Type 2 Diabetes

Several types of Ca channel blockers (CCBs) which have unique organ protective effects are commercially available all over the world. However, the hypotensive and pleotropic effect in CCBs are not sufficiently assessed in the diabetic patient with refractory hypertension for angiotensin receptor blocker (ARB). We conducted a pilot study to compare the efficacy of two different CCBs (azelnidipine and nifedipine controlled release (CR)) in 55 hypertensive patients with type 2 diabetes who had not achieved their target blood pressure (BP) with ARB monotherapy. Patients were randomly assigned to receive azelnidipine (8–16 mg/day) or nifedipine CR (10–40 mg/day) concomitantly with valsartan (80 mg/day). There were no significant differences in baseline characteristics between the two groups. The final dose of azelnidipine and nifedipine CR was 13.3±3.9 and 17.1±9.4 mg/day, respectively. However the target BP (<130/80mmHg) achievement rate was higher in the earlier phase of the combination therapy with nifedipine CR than that of the azelnidipine group, the rates after 6 months were comparable between the groups (83 vs. 66%). The systolic blood pressure was significantly lower in the nifedipine CR group from 2 to 6 months after the combination therapy (P<0.05, respectively). Both groups showed no significant changes in blood glucose and hemoglobin A1c. There were no significant differences in the urinary albumin/creatinine ratio and estimated Glomerular Filtration Rate (eGFR). In conclusion, the adjunctive therapy of nifedipine CR was superior to that of azelnidipine for decreasing blood pressure and achieving the target blood pressure, especially in the earlier phase of the diabetic patient with refractory hypertension for ARB. However the nephroprotective effect of nifedipine CR combination therapy was comparable to that of azelnidipine. Keywords: Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, albumin creatinine ratio, calcium channel blocker, estimated Glomerular Filtration Rate, diabetes, Glucose metabolism, hypertension, Renal function

Higher Morning to Evening Ratio in Total Dose of Twice-Daily Biphasic Insulin Analog Might Be Effective in Achieving Glucose Control in Patients with Poorly Controlled Type 2 Diabetes

The aims of this study are to investigate not only the glucose-lowering effectiveness of twice-daily premixed insulin lispro 25 (Humalog(®) Mix25(™), Eli Lilly and Co., Indianapolis, IN), but also the optimal divided ratio of total Mix25 dose in Korean patients with poorly controlled type 2 diabetes. In this retrospective study, we retrieved data for subjects who were on intensive insulin therapy with twice-daily Mix25 regimen for at least 24 weeks. Changes of hemoglobin A1c (HbA(1c)) and other clinical and laboratory parameters were evaluated. Two groups were defined according to dose ratio of pre-breakfast to pre-dinner insulin at 24 weeks: Group I, pre-breakfast:pre-dinner insulin dose ratio=50:50; Group II, ratio=53:47-75:25. In total, 143 subjects were ultimately analyzed in this study. Twice-daily Mix25 significantly improved HbA(1c) levels from 10.1% to 7.7%, and 34% of patients had reached the target glycemic goal (HbA(1c)<7%) after 24 weeks. Compared with Group I, a significant reduction in HbA(1c) (Group I vs. Group II, -1.9±0.3% vs. -2.8±0.3%, P=0.02) and a larger proportion of subjects with HbA(1c)<7% (23.2% vs. 46.7%, P=0.01) were observed in subjects in Group II. Among clinical and laboratory factors, duration of diabetes (odd ratios [OR]=0.93, 95% confidence interval [CI] 0.86-0.99, P=0.04) and history of sulfonylurea use (OR=0.27, 95% CI 0.10-0.72, P=0.01) were independently associated with achieving target HbA(1c) levels less than 7%. Twice-daily Mix25 is an effective option for Korean subjects with type 2 diabetes having uncontrolled hyperglycemia. A higher pre-breakfast/pre-dinner dose ratio (53:47-75:25) might be taken into consideration as an initial protocol to accomplish better glycemic control in twice-daily Mix25.

U-500 Insulin as a Component of Basal Bolus Insulin Therapy in Type 2 Diabetes

Changes in hemoglobin A1c (A1C), weight, and total daily insulin dose (TDD) were investigated following initiation of insulin U-500 (U500) alone or as part of a basal/bolus insulin (BBI) regimen. Records of patients with type 2 diabetes who were prescribed U500 were retrospectively reviewed. Logistic regression analysis was used to investigate relationships between changes in A1C and use of U500 alone or as BBI. Twelve patients were identified as using U500 alone (n=2) or in combination with long-acting (LAI) (n=7) or rapid-acting (RAI) (n=3) insulin. Reductions in A1C (9.5% at baseline vs. 7.7% at 6-9 months, P<0.0001) and increases in weight (128.8±32.7 vs. 131.5±31.3 kg, P<0.014) and TDD (260±111 to 333±106 units/day, P<0.0002) were observed. Concurrent use of LAI or RAI with U500 did not predict improvements in A1C. U500 resulted in improvements in A1C and weight gain and increased TDD when used alone or as part of combination insulin therapy. Further investigations to define the optimal use of U500 are recommended.

Case-Matched Outcomes in Bariatric Surgery for Treatment of Type 2 Diabetes in the Morbidly Obese Patient

To compare the relative efficacy of medical management, the duodenal switch (DS), and the laparoscopic adjustable gastric band (LAGB) to the Roux-en-Y gastric bypass (RYGB) for treatment of type 2 diabetes mellitus (T2DM). The RYGB resolves T2DM in a high proportion of patients and is considered the standard operation for T2DM resolution in morbidly obese patients. However, no data exist comparing the efficacy of medical management and other bariatric operations to the RYGB for treatment of T2DM in comparable patient populations. We performed a retrospective case-matched study of morbidly obese patients with T2DM who had undergone medical management (nonsurgical controls [NSC]; N = 29), LAGB (N = 30), or DS (N = 27) and were compared with matched T2DM patients who had undergone RYGB. Matching was performed with respect to age, sex, body mass index, and hemoglobin A1C (HbA1C). Outcomes assessed were changes in body mass index, HbA1C, and diabetes medication scores at 1 year. The Roux-en-Y gastric bypass produced greater weight loss, HbA1C normalization, and medication score reduction compared to both NSC and LAGB-matched cohorts. Duodenal switch produced greater reductions in HbA1C and medication score than RYGB, despite no greater weight loss at 1 year. Surgical complications were rarely life threatening. This study provides an important perspective about the comparative efficacy of LAGB, DS, and NSC to the RYGB for treatment of T2DM among obese patients. After 1 year of follow-up, RYGB is superior to NSC and LAGB with respect to weight loss and improvement in diabetes whereas DS is superior to RYGB in reducing HbA1C and medication score.

Aerobic neuromuscular electrical stimulation—an emerging technology to improve haemoglobin A1c in type 2 diabetes mellitus: results of a pilot study

ObjectivesA new generation of neuromuscular electrical stimulation (NMES) devices can exercise aerobically at equivalent rates to voluntary exercise. Many with type 2 diabetes cannot or will not exercise sufficiently. The...

Glycemic Control and Preventive Care Measures of Indigent Diabetes Patients Within a Pharmacist-Managed Insulin Titration Program vs Standard Care

Studies assessing pharmacist-led services have noted positive clinical diabetes outcomes; however, studies assessing pharmacist impact on glycemic control through insulin titration and adherence to American Diabetes Association (ADA) preventive care measures in an indigent population are limited. To assess the impact of a pharmacist-managed insulin titration program compared to standard medical care on glycemic control and preventive care measures in an indigent population with diabetes. This retrospective cohort study compared pharmacist-managed insulin titration to standard care; all patients received primary care services through a county-funded health center serving a low-income minority population. The pharmacist-managed patients, referred by the primary care provider, received telephone calls to assess blood glucose levels, encourage preventive care examinations, and titrate insulin doses through collaborative drug therapy management. Standard care patients received diabetes care solely from the primary care provider. Student t test was used to evaluate the primary outcome, glycemic control, assessed by change in hemoglobin A(1c) (A1C) between groups from baseline to various time points and study end. Secondary outcomes included attainment of preventive care measures and A1C goal of less than 7% and change in weight and total daily insulin dose from baseline to study end. Sixty-nine patients in the pharmacist-managed group (intervention) and 57 standard care patients (control) were evaluated. The pharmacist-managed group showed a significant difference in A1C at all time points, including, study end, compared to standard care (-1.3% vs -0.18%, respectively; p = 0.001). In addition, the intervention group more often completed the ADA's recommended preventive care measures; all differences were statistically significant. Pharmacist-provider collaboration can result in significant clinical improvements, including A1C reduction and adherence to preventive care measures, when compared to standard care in a medically underserved population with diabetes.

Longitudinal analysis of cardiovascular parameters after gastric bypass surgery

BackgroundIdentifying the predictors of co-morbidity improvement after gastric bypass surgery (Roux-en-Y gastric bypass) might give insight into disease pathophysiology. MethodsWe performed an observational study of 949 patients undergoing primary RYGB from 2005 to 2010. Multivariate mixed models were used to determine the predictors of change in hemoglobin A1c (HbA1c), lipids, systemic blood pressure, and C-reactive protein. ResultsGreater weight loss, decreased severity of initial disease, and a greater initial body mass index predicted a significantly greater likelihood of improvement in nearly all measured parameters. Male gender predicted greater improvement in diastolic blood pressure and low-density lipoprotein and triglyceride levels. Younger patients had a greater improvement in blood pressure. Improvement in the lipid profile was independent of weight loss, and improved glycemic control was strongly dependent on weight loss. Of the 949 patients, 33% had diabetes before RYGB. A mean of 388 days after RYGB, 66% of these patients had an HbA1c of <6.5, with their mean HbA1c decreasing from 8.0 to 5.9. A greater decrease in HbA1c was also seen in patients who initially were only treated with oral hypoglycemic agents compared with those receiving insulin. The low-density lipoprotein cholesterol levels decreased significantly from a mean of 108 to 87 mg/dL. High-density lipoprotein increased by a mean of 10 mg/dL in both men and women. Also, 15% of the patients had a triglyceride level of ≥200 mg/dL before RYGB and only 1.1% did so afterward. The mean C-reactive protein level decreased from 5.0 to 1.6 mg/dL. We measured a 20% reduction in patients with measured hypertension after RYGB. ConclusionRYGB resulted in dramatic improvement in cardiovascular risk factors, with several significant predictors of outcome.

Glucagon-like peptide-1 receptor agonists versus insulin in inadequately controlled patients with type 2 diabetes mellitus: a meta-analysis of clinical trials

To compare the effect and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RA) with insulin therapy on type 2 diabetes mellitus (T2DM) patients inadequately controlled with metformin and/or sulfonylurea. A systematic literature search on MEDLINE, Embase and Cochrane for randomized controlled trials (RCTs) was conducted using specific search terms 'GLP-1 insulin type 2 diabetes clinical trials' and eight eligible studies were retrieved. Data on mean change in haemoglobin A1c (HbA1C), weight loss, fasting plasma glucose (FPG), incidence of hypoglycaemia and gastrointestinal adverse events were extracted from each study and pooled in meta-analysis. Data on postprandial plasma glucose (PPG) and adverse events were also described or tabulated. Data from eight RCTs enrolling 2782 patients were pooled using a random-effects model. The mean net change [95% confidence interval (CIs)] for HbA1c, weight loss and FPG for patients treated with GLP-1 RA as compared with insulin was -0.14% (-2 mmol/mol) [95% CI; (-0.27, -0.02)%; p = 0.03]; -4.40 kg [95% CI; (-5.23, -3.56) kg; p < 0.01] and 1.18 mmol/l [95% CI; (0.43, 1.93) mmol/l; p < 0.01], respectively, with negative values favouring GLP-1 and positive values favouring insulin. The GLP-1 group was associated with a greater reduction in PPG than the insulin group. Overall, hypoglycaemia was reported less in the GLP-1 group [Mantel-Haenszel odds ratio (M-H OR) 0.45 (0.27, 0.76); p < 0.01], while there was no significant difference in occurrence of severe hypoglycaemia [M-H OR 0.65 (0.29,1.45); p = 0.29]. A significantly higher number of gastrointestinal adverse events were reported with GLP-1 group [M-H OR 15.00 (5.44,41.35) p < 0.01]. GLP-1 RA are promising new agents compared with insulin. Further prospective clinical trials are expected to fully evaluate the long-term effectiveness and safety of these therapies within the T2DM treatment paradigm.

Metabolic Improvements in Obese Type 2 Diabetes Subjects Implanted for 1 Year with an Endoscopically Deployed Duodenal–Jejunal Bypass Liner

The purpose of this study was to evaluate the effect of the duodenal-jejunal bypass liner (DJBL), a 60-cm, impermeable fluoropolymer liner anchored in the duodenum to create a duodenal-jejunal bypass, on metabolic parameters in obese subjects with type 2 diabetes. Twenty-two subjects (mean age, 46.2±10.5 years) with type 2 diabetes and a body mass index between 40 and 60 kg/m(2) (mean body mass index, 44.8±7.4 kg/m(2)) were enrolled in this 52-week, prospective, open-label clinical trial. Endoscopic device implantation was performed with the patient under general anesthesia, and the subjects were examined periodically during the next 52 weeks. Primary end points included changes in fasting blood glucose and insulin levels and changes in hemoglobin A1c (HbA1c). The DJBL was removed endoscopically at the end of the study. Thirteen subjects completed the 52-week study, and the mean duration of the implant period for all subjects was 41.9±3.2 weeks. Reasons for early removal of the device included device migration (n=3), gastrointestinal bleeding (n=1), abdominal pain (n=2), principal investigator request (n=2), and discovery of an unrelated malignancy (n=1). Using last observation carried forward, statistically significant reductions in fasting blood glucose (-30.3±10.2 mg/dL), fasting insulin (-7.3±2.6 μU/mL), and HbA1c (-2.1±0.3%) were observed. At the end of the study, 16 of the 22 subjects had an HbA1c<7% compared with only one of 22 at baseline. Upper abdominal pain (n=11), back pain (n=5), nausea (n=7), and vomiting (n=7) were the most common device-related adverse events. The DJBL improves glycemic status in obese subjects with diabetes and therefore represents a nonsurgical, reversible alternative to bariatric surgery.

Efficacy and Safety of Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Compared with Exenatide Twice Daily and Sitagliptin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Long-acting glucagon-like peptide-1 receptor agonists (LA-GLP-1RAs) may deliver additional therapeutic benefits over other available incretin-based therapies. To pool results of randomized controlled trials comparing the efficacy and safety of maximum dose LA-GLP-1RAs (liraglutide, exenatide once weekly) with exenatide twice daily and dipeptidyl-peptidase-IV inhibitors in patients with type 2 diabetes. We searched PubMed, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE (all from inception-December 2010), and abstracts presented at the American Diabetes Association Scientific Sessions in 2009 and 2010 to identify English-language reports of studies of at least 24 weeks' duration. The primary endpoint was mean change in hemoglobin A(1c) (A1C) from baseline to study endpoint. Weighted mean differences or odds ratios and their 95% confidence intervals for each outcome relative to control were calculated as appropriate. A1C was reduced favoring LA-GLP-1RAs compared with exenatide twice daily and sitagliptin (weighted mean difference [WMD] -0.47% [95% CI -0.69 to -0.25] and WMD -0.60% [95% CI -0.75 to -0.45], respectively). Odds ratios greater than 1 favored LA-GLP-1RAs for reaching the A1C target goal of less than 7%. Fasting plasma glucose (FPG) was reduced and favored the LA-GLP-1RA-based regimens. Exenatide demonstrated significantly greater reductions in postprandial glucose (PPG) after the morning and evening meals, compared with LA-GLP-1RAs. Body weight was reduced similarly between LA-GLP-1RAs and exenatide, but favored LA-GLP-1RAs in the sitagliptin comparator trials. LA-GLP-1RA therapy was not associated with severe hypoglycemia or acute pancreatitis. Compared with exenatide twice daily, vomiting was reduced significantly with LA-GLP-1RAs (OR 0.55; 95% CI 0.34 to 0.89); there was a trend toward decreased nausea (OR 0.58; 95% CI 0.32 to 1.06) and no difference in the incidence of diarrhea (OR 1.03; 95% CI 0.67 to 1.58). Compared with other incretin-based therapies, LA-GLP-1RAs produce greater improvement in A1C and FPG. They provide lesser effect on PPG, similar reduction in body weight, and result in a potentially favorable adverse event profile compared with exenatide twice daily.

Comparison of the effects of long-term pioglitazone and rosiglitazone therapy on liver enzymes in type 2 diabetes

Aims Insulin resistance is a major factor influencing the progression of non-alcoholic fatty liver disease (NAFLD). Hence, insulin sensitisers such as thiazolidinediones (TZDs) are a potential treatment for NAFLD although their long-term benefits remain unknown. Methods We retrospectively studied 396 and 364 type 2 diabetes patients who received pioglitazone and rosiglitazone therapy respectively from diabetes clinics between May 2001 and November 2007. Results One hundred and seventy-seven pioglitazone-treated and 152 rosiglitazone-treated patients were included. After a year of treatment, significant improvement in glycated haemoglobin A1C (HbA1C), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) was observed in both groups despite weight gain. Changes in HbA1C and liver function test (LFT) were positively correlated in pioglitazone-treated (ALT p=0.01; GGT p&lt;0.001; ALP p=0.006) and rosiglitazone-treated (GGT p= 0.01, ALP p=0.002) groups. Multiple regression showed no significant difference in the changes in ALT (p=0.43) and GGT (p=0.13) between the groups but a larger reduction in ALP (p=0.03) was noted in rosiglitazone-treated patients. Sixty patients remained on pioglitazone and 46 patients continued on rosiglitazone after four years. Sustained improvement in ALT, GGT and HbA 1C was observed in both groups despite weight gain over four years.