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Paired box 4 (Pax4) is a key transcription factor involved in the embryonic development of the pancreatic islets of Langerhans. Consisting of a conserved paired box domain and a homeodomain, this transcription factor plays an essential role in early endocrine progenitor cells, where it is necessary for cell-fate commitment towards the insulin-secreting β cell lineage. Knockout of Pax4 in animal models leads to the absence of β cells, which is accompanied by a significant increase in glucagon-producing α cells, and typically results in lethality within days after birth. Mutations in Pax4 that cause an impaired Pax4 function are associated with diabetes pathogenesis in humans. In adulthood, Pax4 expression is limited to a distinct subset of β cells that possess the ability to proliferate in response to heightened metabolic needs. Upregulation of Pax4 expression is known to promote β cell survival and proliferation. Additionally, ectopic expression of Pax4 in pancreatic islet α cells or δ cells has been found to generate functional β-like cells that can improve blood glucose regulation in experimental diabetes models. Therefore, Pax4 represents a promising therapeutic target for the protection and regeneration of β cells in the treatment of diabetes. The purpose of this review is to provide a thorough and up-to-date overview of the role of Pax4 in pancreatic β cells and its potential as a therapeutic target for diabetes. [ABSTRACT FROM AUTHOR]

The article focuses on series of short videos available on website of the periodical, in which authors discuss the pathophysiological changes that occur during the progression of type 2 diabetes. Topics include deleterious health consequences for patients with high A1C levels; relationship between cumulative burden of microvascular disease and risk of cardiovascular disease; and association of transition from impaired glucose tolerance to diabetes with progressive loss of b-cell mass.

Objective: We successfully implemented the American Diabetes Association's (ADA) Diabetes INSIDE (INspiring System Improvement with Data-Driven Excellence) quality improvement (QI) program at a university hospital and safety-net health system (Tulane and Parkland), focused on system-wide improvement in poorly controlled type 2 diabetes (HbA1c >8.0% [64 mmol/mol]). In this study, we estimated the 5-year risk reduction in complications and mortality associated with the QI program.Research Design and Methods: The QI implementation period was 1 year, followed by the postintervention period of 6 months to evaluate the impact of QI on clinical measures. We measured the differences between the baseline and postintervention clinical outcomes in 2,429 individuals with HbA1c >8% (64 mmol/mol) at baseline and used the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes model to project the 5-year risk reduction of diabetes-related complications under the assumption that intervention benefits persist over time. An alternative assumption that intervention benefits diminish by 30% every year was also tested.Results: The QI program was associated with reductions in HbA1c (-0.84%) and LDL cholesterol (LDL-C) (-5.94 mg/dL) among individuals with HbA1c level >8.0% (64 mmol/mol), with greater reduction in HbA1c (-1.67%) and LDL-C (-6.81 mg/dL) among those with HbA1c level >9.5% at baseline (all P < 0.05). The implementation of the Diabetes INSIDE QI program was associated with 5-year risk reductions in major adverse cardiovascular events (MACE) (relative risk [RR] 0.78 [95% CI 0.75-0.81]) and all-cause mortality (RR 0.83 [95% CI 0.82-0.85]) among individuals with baseline HbA1c level >8.0% (64 mmol/mol), and MACE (RR 0.60 [95% CI 0.56-0.65]) and all-cause mortality (RR 0.61 [95% CI 0.59-0.64]) among individuals with baseline HbA1c level >9.5% (80 mmol/mol). Sensitivity analysis also identified a substantially lower risk of diabetes-related complications and mortality associated with the QI program.Conclusions: Our modeling results suggest that the ADA's Diabetes INSIDE QI program would benefit the patients and population by substantially reducing the 5-year risk of complications and mortality in individuals with diabetes. [ABSTRACT FROM AUTHOR]

Background: This analysis assessed the cost‐effectiveness of insulin glargine 300 units/mL (Gla‐300) versus insulin glargine 100 units/mL (Gla‐100) in insulin‐naïve adults with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs (OADs). Methods: Costs and outcomes for Gla‐300 versus Gla‐100 from a US healthcare payer perspective were assessed using the BRAVO diabetes model. Baseline clinical data were derived from EDITION‐3, a 12‐month randomized controlled trial comparing Gla‐300 with Gla‐100 in insulin‐naïve adults with inadequately controlled T2D on OADs. Treatment costs were calculated based on doses observed in EDITION‐3 and 2020 US net prices, while costs for complications were based on published literature. Lifetime costs ($US) and quality‐adjusted life‐years (QALYs) were predicted and used to calculate incremental cost‐effectiveness ratio (ICER) estimates; extensive scenario and sensitivity analyses were conducted. Results: Lifetime medical costs were estimated to be $353,441 and $352,858 for individuals receiving Gla‐300 and Gla‐100 respectively; insulin costs were $52,613 and $50,818. Gla‐300 was associated with a gain of 8.97 QALYs and 21.12 life‐years, while Gla‐100 was associated with a gain of 8.89 QALYs and 21.07 life‐years. This resulted in an ICER of $7522/QALY gained for Gla‐300 versus Gla‐100. Thus, Gla‐300 was cost‐effective versus Gla‐100 based on a willingness‐to‐pay threshold of $50,000/QALY. Compared with Gla‐100, Gla‐300 provided a net monetary benefit of $3290. Scenario and sensitivity analyses confirmed the robustness of the base case. Conclusion: Gla‐300 may be a cost‐effective treatment option versus Gla‐100 over a lifetime horizon for insulin‐naïve people in the United States with T2D inadequately controlled on OADs. [ABSTRACT FROM AUTHOR]

Background: LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results) results demonstrated cardiovascular benefits for patients with type 2 diabetes mellitus at high cardiovascular risk on standard of care randomized to liraglutide versus placebo. The effect of glucagon-like peptide-1 receptor agonist liraglutide on cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease is unknown. Liraglutide's treatment effects in patients with and without kidney disease were analyzed post hoc.Methods: Patients were randomized (1:1) to liraglutide or placebo, both in addition to standard of care. These analyses assessed outcomes stratified by baseline estimated glomerular filtration rate (eGFR; <60 versus ≥60 mL/min/1.73 m2) and baseline albuminuria. The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and secondary outcomes, including all-cause mortality and individual components of the primary composite outcome, were analyzed using Cox regression.Results: Overall, 2158 and 7182 patients had baseline eGFR <60 or ≥60 mL/min/1.73 m2, respectively. In patients with eGFR <60 mL/min/1.73 m2, risk reduction for the primary composite cardiovascular outcome with liraglutide was greater (hazard ratio [HR], 0.69; 95% CI, 0.57-0.85) versus those with eGFR ≥60 mL/min/1.73 m2 (HR, 0.94; 95% CI, 0.83-1.07; interaction P=0.01). There was no consistent effect modification with liraglutide across finer eGFR subgroups (interaction P=0.13) and when analyzing eGFR as a continuous variable (interaction P=0.61). Risk reductions in those with eGFR <60 versus ≥60 mL/min/1.73 m2 were as follows: for nonfatal myocardial infarction, HR, 0.74; 95% CI, 0.55-0.99 versus HR, 0.93; 95% CI, 0.77-1.13; for nonfatal stroke, HR, 0.51; 95% CI, 0.33-0.80 versus HR, 1.07; 95% CI, 0.84-1.37; for cardiovascular death, HR, 0.67; 95% CI, 0.50-0.90 versus HR, 0.84; 95% CI, 0.67-1.05; for all-cause mortality, HR, 0.74; 95% CI, 0.60-0.92 versus HR, 0.90; 95% CI, 0.75-1.07. Risk reduction for the primary composite cardiovascular outcome was not different for those with versus without baseline albuminuria (HR, 0.83; 95% CI, 0.71-0.97; and HR, 0.92; 95% CI, 0.79-1.07, respectively; interaction P=0.36).Conclusions: Liraglutide added to standard of care reduced the risk for major cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease. These results appear to apply across the chronic kidney disease spectrum enrolled.Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT01179048. [ABSTRACT FROM AUTHOR]

Background: There is an urgent need to update diabetes prediction, which has relied on the United Kingdom Prospective Diabetes Study (UKPDS) that dates back to 1970 s' European populations.Objective: The objective of this study was to develop a risk engine with multiple risk equations using a recent patient cohort with type 2 diabetes mellitus reflective of the US population.Methods: A total of 17 risk equations for predicting diabetes-related microvascular and macrovascular events, hypoglycemia, mortality, and progression of diabetes risk factors were estimated using the data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (n = 10,251). Internal and external validation processes were used to assess performance of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine. One-way sensitivity analysis was conducted to examine the impact of risk factors on mortality at the population level.Results: The BRAVO risk engine added several risk factors including severe hypoglycemia and common US racial/ethnicity categories compared with the UKPDS risk engine. The BRAVO risk engine also modeled mortality escalation associated with intensive glycemic control (i.e., glycosylated hemoglobin < 6.5%). External validation showed a good prediction power on 28 endpoints observed from other clinical trials (slope = 1.071, R2 = 0.86).Conclusion: The BRAVO risk engine for the US diabetes cohort provides an alternative to the UKPDS risk engine. It can be applied to assist clinical and policy decision making such as cost-effective resource allocation in USA. [ABSTRACT FROM AUTHOR]

Women with Type 2 diabetes (T2D) face up to 50% higher risk of cardiovascular disease than men. This study evaluated the extent to which prediabetes and undiagnosed T2D are associated with a greater excess risk of cardiovascular disease in women versus in men. Data were pooled from 18,745 cardiovascular disease−free individuals from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. The risk of coronary heart disease, ischemic stroke, and atherosclerotic cardiovascular disease (coronary heart disease or stroke) associated with prediabetes or undiagnosed T2D was estimated using Cox models adjusting for sociodemographic factors, concomitant risk factors, medication use, and menopausal status. Data were collected in 2022, and the analysis was performed in 2023. During a median follow-up of 18.6 years, the associations between prediabetes and risk of atherosclerotic cardiovascular disease were only significant in women (hazard ratio=1.18, 95% CI=1.01, 1.34, p =0.03) but not in men (hazard ratio=1.08, 95% CI=1.00, 1.28, p =0.06) (p -interaction=0.18). The associations between undiagnosed T2D and cardiovascular disease outcomes were significant in both sexes, but the effect was more pronounced in women (coronary heart disease: hazard ratio=1.83, 95% CI=1.4, 2.41, p <0.0001 in women vs hazard ratio=1.6, 95% CI=1.38, 2.07, p =0.007 in men; stroke: hazard ratio=1.99, 95% CI=1.39, 2.72, p <0.0001 vs hazard ratio=1.81, 95% CI=1.36, 2.6, p <0.0001; atherosclerotic cardiovascular disease: hazard ratio=1.86, 95% CI=1.5, 2.28, p <0.0001 vs hazard ratio=1.65, 95% CI=1.4, 1.98, p <0.0001) (all p -interactions≤0.2). Both White and Black patients exhibit similar sex differences. Prediabetes or undiagnosed T2D was associated with a greater excess risk of cardiovascular disease in women than in men. The sex differential in cardiovascular disease risk among those without the T2D diagnosis suggests the need for sex-specific guidelines in T2D screening and treatment. [ABSTRACT FROM AUTHOR]

Aim: Early identification of incident chronic kidney disease (CKD) in individuals with diabetes may help improve patients' clinical outcomes. This study aimed to develop a prediction equation for incident CKD among people with type 2 diabetes (T2D). Materials and Methods: A time‐varying Cox model was applied to data from the ACCORD trial to predict the risk of incident CKD. A list of candidate variables was chosen based on literature reviews and experts' consultations, including demographic characteristics, vitals, laboratory results, medical history, drug use and health care utilization. Model performance was evaluated. Decomposition analysis was conducted, and external validation was performed. Results: In total, 6006 patients with diabetes free of CKD were included, with a median follow‐up of 3 years and 2257 events. The risk model included age at T2D diagnosed, smoking status, body mass index, high‐density lipoprotein, very‐low‐density lipoprotein, alanine aminotransferase, estimated glomerular filtration rate, urine albumin‐creatinine ratio, hypoglycaemia, retinopathy, congestive heart failure, coronary heart disease history, antihyperlipidaemic drug use, antihypertensive drug use and hospitalization. The urine albumin‐creatinine ratio, estimated glomerular filtration rate and congestive heart failure were the top three factors that contributed most to the incident CKD prediction. The model showed acceptable discrimination [C‐statistic: 0.772 (95% CI 0.767‐0.805)] and calibration [Brier Score: 0.0504 (95% CI 0.0477‐0.0531)] in the Harmony Outcomes Trial. Conclusion: Incident CKD prediction among individuals with T2D was developed and validated for use in decision support of CKD prevention. [ABSTRACT FROM AUTHOR]

The article offers information on the updates in the American Diabetes Association's (ADA) Standards of Medical Care in Diabetes for 2023. Topics include changes to the urinary albumin-to-creatinine ratio (UACR) threshold for sodium–glucose cotransporter 2 (SGLT2) inhibitor use, the revised estimated glomerular filtration rate (eGFR) threshold, updates on the use of nonsteroidal mineralocorticoid receptor antagonist (nsMRA) finerenone, and the recommendation for referral to a nephrologist.

Aims: A cost‐effectiveness analysis was conducted to compare insulin glargine 300 U/mL (Gla‐300) versus insulin degludec 100 U/mL (IDeg‐100) in insulin‐naïve adults with type 2 diabetes (T2D) sub‐optimally controlled with oral anti‐diabetic drugs (OADs). Methods: The BRAVO diabetes model was used to assess costs and outcomes for once‐daily Gla‐300 versus once‐daily IDeg‐100 from a US healthcare sector perspective. Baseline clinical data were based on BRIGHT, a 24‐week, non‐inferiority, randomised control trial comparing Gla‐300 and IDeg‐100 in adults with T2D sub‐optimally controlled with OADs (with or without glucagon‐like peptide‐1 receptor agonists). Treatment costs were based on doses observed in BRIGHT as well as net prices. Costs associated with complications were based on published literature. Lifetime costs (US$) and quality‐adjusted life‐years (QALYs) were predicted and used to calculate incremental cost‐effectiveness ratio estimates; extensive scenario and sensitivity analyses were conducted. Results: Overall lifetime medical costs were estimated to be $327,904 and $330,154 for people receiving Gla‐300 and IDeg‐100, respectively; insulin costs were $43,477 and $44,367, respectively. People receiving Gla‐300 gained 8.024 QALYs and 18.55 life‐years, while people receiving IDeg‐100 gained 7.997 QALYs and 18.52 life‐years. Because Gla‐300 was associated with a cost‐saving of $2250 and 0.027 additional QALYs, it was considered to be dominant compared with IDeg‐100. Results of the scenario and sensitivity analyses confirmed the robustness of the base case results. Conclusion: Gla‐300 was the dominant treatment option compared with IDeg‐100 based on the willingness‐to‐pay threshold of $50,000/QALY. Results remained robust against a wide range of alternative assumptions on key parameters. [ABSTRACT FROM AUTHOR]

Introduction: We have developed the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes model, an individual-level, discrete-time microsimulation model specifically designed for type 2 diabetes (T2D) management. This study aims to validate the model's performance when populated exclusively with a fully de-identified dataset to ensure its applicability in secure settings. Methods: Patient-level data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial were fully de-identified by removing all identifiable information and masking numerical values (e.g., age, body mass index) within ranges to minimize the risk of re-identification. To populate the simulation, we imputed the masked numerical values using data from the National Health and Nutrition Examination Survey (NHANES). We applied the BRAVO model to the baseline data to predict 7-year study outcomes for the EXSCEL trial and assessed its discrimination power and calibration using C-statistics and Brier scores. Results: The model demonstrated acceptable discrimination and calibration in predicting the first occurrence of non-fatal myocardial infarction, non-fatal stroke, heart failure, revascularization, and all-cause mortality. Even with the fully deidentified data from the EXSCEL trial primarily presented in ranges rather than specific values, the BRAVO model exhibited robust prediction performance for diabetes complications and mortality. Conclusions: This study demonstrates the feasibility of using the BRAVO model in settings where only fully de-identified patient-level data are available. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the safety, tolerability, and feasibility of adult allogeneic bone marrow- derived mesenchymal precursor cells (MPCs) in type 2 diabetes inadequately controlled with metformin either alone or with one additional oral antidiabetic agent. RESEARCH DESIGN AND METHODS The study was a dose-escalating randomized placebo-controlled trial assessing one intravenous (IV) infusion of MPCs (rexlemestrocel-L; Mesoblast Inc.) 0.3 × 106/kg (n = 15), 1.0 × 106/kg (n = 15), or 2.0 × 106/kg (n = 15) or placebo (n = 16). Study duration was 12 weeks. RESULTS Subjects (21 women, 40 men) with a mean±SD baseline HbA1c 8.3±1.0% (67±10.9 mmol/mol), BMI 33.5±5.5 kg/m2, and diabetes duration 10.1±6.0 years were enrolled at 18 U.S. sites. No acute adverse events (AEs) were associated with infusion. No serious AEs, serious hypoglycemia AEs, or discontinuations due to AEs over 12 weeks were found. No subjects developed donor-specific anti-HLA antibodies or became sensitized. The safety profilewas comparable among treatment groups. Compared with placebo, a single IV infusion of rexlemestrocel-L reduced HbA1c at all time points after week 1. The adjusted least squares mean ± SE doserelated differences in HbA1c from placebo in the rexlemestrocel-L groups ranged from -0.1±0.2% (-1.1±2.2 mmol/mol) to -0.4 60.2% (4.4±2.2 mmol/mol) at 8 weeks and from 0.0±0.25% to -0.3±0.25% (-3.3 ± -2.7 mmol/mol) at 12weeks (P < 0.05 for 2.0×106/kg dose at 8 weeks). The clinical target HbA1c <7% (53mmol/mol)was achieved by 33% (5 of 15) of the subjectswho received the 2.0× 106/kg dose vs. 0% of those who received placebo (P < 0.05). CONCLUSIONS This short-term study demonstrates the safety and feasibility of up to 246 million MPCs in subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Worldwide, both underdiagnosis and undertreatment leave many patients exposed to long periods of hyperglycemia and contribute to irreversible diabetes complications. Early glucose control reduces the risk of both macrovascular and microvascular complications, while tight control late in diabetes has little or no macrovascular benefit. Insulin therapy offers the most potent antihyperglycemic effect of all diabetes agents, and has a unique ability to induce diabetes remission when used to normalize glycemia in newly diagnosed patients. When used as a second-line therapy, basal insulin is more likely to safely and durably maintain A1C levels =7% than when insulin treatment is delayed. The use of basal insulin analogs is associated with a reduced risk of hypoglycemia and weight gain compared to NPH insulin and pre-mixed insulin. Patient selftitration algorithms can improve glucose control while decreasing the burden on office staff. Finally, recent data suggest that addition of incretin agents to basal insulin may improve glycemic control with very little, if any increased risk of hypoglycemia or weight gain. [ABSTRACT FROM AUTHOR]

Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus, affecting, by some estimates, up to one quarter of diabetic patients. Since 2010, no fewer than 5 major international treatment guidelines for painful DPN have been issued, and there are meaningful differences among them. Duloxetine, pregabalin, gabapentin, and tricyclic antidepressants are the mainstays of treatment, but the choice of which class or agent to use in any given patient should be informed by patient characteristics. This review seeks to describe the differences among the recently issued guidelines, to assess the evidence on which they are based, and to offer insight into the most appropriate treatment choices based on patient characteristics. [ABSTRACT FROM AUTHOR]

Aim: To examine the effects of changes in body size phenotypes between childhood and adulthood on risks of diabetes and left ventricular hypertrophy (LVH) in adulthood.Methods: We included 3,351 individuals who participated as both children and adults in the Bogalusa Heart Study.Results: Compared with participants with persistently metabolically healthy normal weight (MHNW) from childhood to adulthood, MHNW children who became metabolically unhealthy in adulthood had increased diabetes burden and LVH risk in adulthood; Metabolically unhealthy normal weight (MUNW) children who became MHNW or metabolically healthy obese (MHO) as adults and individuals with persistent MHO from childhood to adulthood were not at increased risks of diabetes or LVH. The risks were increased if MHO during childhood transitioned to metabolically unhealthy obesity (MUO) by adulthood or MUO stayed from childhood to adulthood. MUO children who became MHO or MHNW as adults had decreased diabetes burden and LVH risk in adulthood.Conclusions: Individuals maintained MHO from childhood to adulthood and MUNW children who became MHO as adults had a diabetes burden and LVH risk similar to individuals with persistent MHNW. Progression to metabolically unhealthy status and maintenance of metabolically unhealthy status, regardless of childhood BMI status, were associated with increased cardiometabolic outcomes. [ABSTRACT FROM AUTHOR]

Aims: This analysis evaluated HbA1c-adjusted hypoglycemia risk with glargine versus neutral protamine Hagedorn (NPH) over a 5-year study in patients with Type 2 diabetes mellitus (T2DM). Clinical significance was assessed using number needed to harm (NNH) to demonstrate the risk of one additional patient experiencing at least one hypoglycemic event. Methods: Individual patient-level data for symptomatic documented hypoglycemia and HbA1c values from a 5-year randomized study comparing once-daily glargine (n = 513) with twice-daily NPH (n = 504) were analyzed. Symptomatic hypoglycemia was categorized according to concurrent self-monitoring blood glucose levels and need for assistance. Hypoglycemic events per patient-year as a function of HbA1c were fitted by negative binomial regression using treatment and HbA1c at endpoint as independent variables. An estimate of NNH was derived from logistic regression models. Results: The cumulative number of symptomatic hypoglycemia events was consistently lower with glargine compared with NPH over 5 years. Compared with twice-daily NPH, once-daily glargine treatment resulted in significantly lower adjusted odds ratios (OR) for all daytime hypoglycemia (OR 0.74; p = 0.030) and any severe event (OR 0.64; p = 0.035), representing a 26% and 36% reduction in the odds of daytime and severe hypoglycemia, respectively. Our model predicts that, if 25 patients were treated with NPH instead of glargine, then one additional patient would experience at least one severe hypoglycemic event. Conclusions: This analysis of long-term insulin treatment confirms findings from short-term studies and demonstrates that glargine provides sustained, clinically meaningful reductions in risk of hypoglycemia compared with NPH in patients with T2DM. [ABSTRACT FROM AUTHOR]

OBJECTIVE GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs. thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine. RESEARCH DESIGN AND METHODS Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26. RESULTS At week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 ± 0.19 kg vs. +0.81 ± 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%). CONCLUSIONS Weekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk. [ABSTRACT FROM AUTHOR]

Insulin therapy is an effective method for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM), and most patients with T2DM eventually require insulin replacement to attain and preserve satisfactory glycaemic control. All patients with T2DM should be considered as potential candidates for intensive insulin treatment; however, there are certain considerations regarding replacement therapy for different types of people and special populations, such as patients with multiple comorbidities, adolescents, pregnant women and the elderly. Lowering HbA1c levels in isolation without assessing the patient as a whole is becoming redundant. HbA1c targets should be individualized to the specific patient, and insulin treatment ought to be customized accordingly. There are several questions that need to be taken into account when considering adding insulin therapy to other oral antidiabetic agents, for example, for whom and when insulin therapy is indicated and which basal insulin should be utilized. Potential barriers exist related to patients, providers and health-care systems that can delay the start of insulin therapy, and every effort should be made to identify and address these obstacles. [ABSTRACT FROM AUTHOR]

Aims: To quantify the effect of liraglutide on systolic blood pressure (SBP) and pulse in patients with type 2 diabetes (T2D), and assess the influence of covariates on observed SBP reductions. Methods: A patient-level pooled analysis of six phase 3, randomized trials was conducted. Results: The analysis included 2792 randomized patients. In the intention-to-treat population (n = 2783), mean [±SE] SBP reductions from baseline with liraglutide 1.2 mg (2.7 [0.8] mmHg) and 1.8 mg (2.9 [0.7] mmHg) once daily were significantly greater than with placebo (0.5 [0.9] mmHg; P = 0.0029 and P = 0.0004, respectively) after 26 weeks, and were evident after 2 weeks. Liraglutide was also associated with significantly greater SBP reductions than glimepiride and, at a dose of 1.8 mg, insulin glargine and rosiglitazone. SBP reductions with liraglutide weakly correlated with weight loss (Pearson’s correlation coefficient: 0.08–0.12; P ≤ 0.0148). No dependence of these reductions on concomitant antihypertensive medications was detected (P = 0.1304). Liraglutide 1.2 and 1.8 mg were associated with mean increases in pulse of 3 beats per minute (bpm), versus a 1 bpm increase with placebo (P b 0.0001 for each dose versus placebo). Conclusions: Liraglutide reduces SBP in patients with T2D, including those receiving concomitant antihypertensive medication. © 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license [ABSTRACT FROM AUTHOR]

Background: Suboptimal blood glucose control among patients with type 2 diabetes continues to support the need for new pharmacologic approaches. Objective: The purpose of this commentary was to highlight newly available and soon-to-be available agents that are promising tools for targeting specific pathophysiologic pathways in the management of diabetes. Methods: Published evidence to support the application of novel incretin-based therapies, dipeptidyl peptidase (DPP)-4 inhibitors, sodium-glucose cotransporter (SGLT)-2 inhibitors, other oral agents and insulins for managing specific aspects of type 2 diabetes, as well as disadvantages associated with those novel medications, are discussed. Results: Several new glucagon-like peptide (GLP)-1 receptor agonists with different time frames of action, although each has unique advantages and disadvantages, have been through clinical trials. Examples of these are lixisenatide and albiglutide. Currently available DPP-4 inhibitor agents, important for inhibiting the breakdown of endogenous GLP-1, have not been associated with weight gain or hypoglycemia. SGLT-2 inhibitors, which do not depend on insulin secretion or insulin action, may be advantageous in that they appear to be broadly efficacious at all stages of diabetes. New insulin analogues, such as degludec and U-500, improve glycemic control without contributing to hypoglycemia. Conclusions: Advances in pharmacologic options offer the promise of improving glycemic control for longer periods, with limited glycemic fluctuations, hypoglycemia, and weight gain. However, the effectiveness of these agents ultimately depends on their availability to providers managing the health care of patients at high risk for poor diabetes outcomes and patients' use of them as directed. Long-term effectiveness and safety trials are ongoing. [ABSTRACT FROM AUTHOR]

Abstract: Predisposition to genital infections and urinary tract infections (UTIs) in type 2 diabetes mellitus (T2DM) results from several factors such as glucosuria, adherence of bacteria to the uroepithelium and immune dysfunction. The tendency to develop these infections could be even higher in patients with T2DM treated with the emerging class of sodium–glucose cotransporter-2 (SGLT2) inhibitors. Studies have shown that pharmacologically-induced glucosuria with SGLT2 inhibitors raises the risk of developing genital infections and, to a relatively lesser extent, UTIs. However, a definitive dose relationship of the incidence of these infections with the SGLT2 doses is not evident in the existing data. Therefore, the precise role of glucosuria as a causative factor for these infections is yet to be fully elucidated. [Copyright &y& Elsevier]

OBJECTIVE -- Identify determinants of weight gain in people with type 2 diabetes mellitus (T2DM) allocated to intensive versus standard glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS -- We studied determinants of weight gain over years in 8,929 participants (4,425 intensive arm and 4,504 standard arm) with T2DM in the ACCORD trial. We used general linear models to examine the association between each baseline characteristic and weight change at the 2-year visit. We fit a linear regression of change in weight and A1C and used general linear models to examine the association between each medication at baseline and weight change at the 2-year visit, stratified by glycemia allocation. RESULTS -- There was significantly more weight gain in the intensive glycemia arm of the trial compared with the standard arm (3.0 ± 7.0 vs. 0.3 ± 6.3 kg). On multivariate analysis, younger age, male sex, Asian race, no smoking history, high A1C, baseline BMI of 25-35, high waist circumference, baseline insulin use, and baseline metformin use were independently associated with weight gain over 2 years. Reduction of A1C from baseline was consistently associated with weight gain only when baseline A1C was elevated. Medication usage accounted for,15% of the variability of weight change, with initiation of thiazolidinedione (TZD) use the most prominent factor. Intensive participants who never took insulin or a TZD had an average weight loss of 2.9 kg during the first 2 years of the trial. In contrast, intensive participants who had never previously used insulin or TZD but began this combination after enrolling in the ACCORD trial had a weight gain of 4.6-5.3 kg at 2 years. CONCLUSIONS -- Weight gain in ACCORD was greater with intensive than with standard treatment and generally associated with reduction of A1C from elevated baseline values. Initiation of TZD and/or insulin therapy was the most important medication-related factor associated with weight gain. [ABSTRACT FROM AUTHOR]

Background: Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM).Objective: To assess 1-year efficacy and safety of salsalate in T2DM.Design: Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643).Setting: 3 private practices and 18 academic centers in the United States.Patients: Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (≤225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% who were treated for diabetes.Intervention: 286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n = 140) or salsalate, 3.5 g/d (n = 146), in addition to current therapies, and 283 participants were analyzed (placebo, n = 137; salsalate, n = 146).Measurements: Change in hemoglobin A1c level (primary outcome) and safety and efficacy measures.Results: The mean HbA1c level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, -0.53% to -0.21%; P < 0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged.Limitation: Trial duration and number of patients studied were insufficient to determine long-term risk-benefit of salsalate in T2DM.Conclusion: Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted. [ABSTRACT FROM AUTHOR]

Background: Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM). Objective: To assess 1-year efficacy and safety of salsalate in T2DM. Design: Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643) Setting: 3 private practices and 18 academic centers in the United States. Patients: Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (≤225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% who were treated for diabetes. Intervention: 286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n = 140) or salsalate, 3.5 g/d (n = 146), in addition to current therapies, and 283 participants were analyzed (placebo, n = 137; salsalate, n = 146). Measurements: Change in hemoglobin A1c level (primary out-come) and safety and efficacy measures. Results: The mean HbA1c level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, -0.53% to -0.21%; P< 0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also Increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged. Limitation: Trial duration and number of patients studied were insufficient to determine long-term risk-benefit of salsalate in T2DM. Conclusion: Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted. Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Despite a rapid increase in the number of drugs available to treat hyperglycemia there remain several unmet needs in the prevention and treatment of diabetes. There have also been tremendous advances in our understanding of the pathophysiology of type 2 diabetes, allowing the recognition of novel treatment targets. The purpose of this review is to highlight some of the novel approaches that are being developed to improve glucose control in patients with diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine whether a combination of L-methylfolate, methylcobalamin, and pyridoxal-5′-phosphate (LMF-MC-PLP [Metanx; Pamlab LLC, Covington, La]) improves sensory neuropathy. Research Design and Methods: This multicenter, randomized, double-blind, placebo-controlled trial involved 214 patients with type 2 diabetes and neuropathy (baseline vibration perception threshold [VPT]: 25-45 volts), who were randomly assigned to 24 weeks of treatment with either L-methylfolate calcium 3 mg, methylcobalamin 2 mg, and pyridoxal-5′-phosphate 35 mg or placebo. The primary end point was effect on VPT. Secondary end points included Neuropathy Total Symptom Score (NTSS-6) and Short Form 36 (SF-36), as well as plasma levels of folate, vitamins B6 and B12, methylmalonic acid (MMA), and homocysteine. Results: There was no significant effect on VPT. However, patients receiving LMF-MC-PLP consistently reported symptomatic relief, with clinically significant improvement in NTSS-6 scores at week 16 (P =.013 vs placebo) and week 24 (P =.033). Improvement in NTSS scores was related to baseline MMA and inversely related to baseline PLP and metformin use. Quality-of-life measures also improved. Homocysteine decreased by 2.7±3.0 μmol/L with LMF-MC-PLP versus an increase of 0.5±2.4 μmol/L with placebo (P =.0001). Adverse events were infrequent, with no single event occurring in ≥2% of subjects. Conclusions: LMF-MC-PLP appears to be a safe and effective therapy for alleviation of peripheral neuropathy symptoms, at least in the short term. Additional long-term studies should be conducted, as the trial duration may have been too short to show an effect on VPT. In addition, further research on the effects in patients with cobalamin deficiency would be useful. [Copyright &y& Elsevier]

Aims: To assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in combination therapy with metformin (≥1500 mg/day) and pioglitazone (≥30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic control (hemoglobin A1c [HbA1c] ≥7.5% and ⩽11%). Methods: This placebo-controlled, double-blind study included 313 patients, mean baseline HbA1c=8.7%, who were randomized to receive sitagliptin 100 mg/day or placebo for 26 weeks. Results: The addition of sitagliptin led to significant (P b .001) mean changes from baseline relative to placebo in HbA1c (-0.7%), fasting plasma glucose (-1.0 mmol/L), and 2-h post-meal glucose (-2.2 mmol/L). In patients with baseline HbA1c ≥9.0%, mean changes from baseline in HbA1c were -1.6% and -0.8% for the sitagliptin and placebo groups, respectively (between-group difference -0.8%; P b .001). The incidences of reported adverse events were generally similar between the treatment groups. Incidences of symptomatic hypoglycemia were 7/157 [4.5%] and 6/156 [3.8%] in the sitagliptin and placebo groups, respectively (P=.786). Two patients, both in the placebo group, experienced an episode of hypoglycemia that required non-medical assistance. Conclusions: In this 26-week study, addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated. [ABSTRACT FROM AUTHOR]

Background: Approximately 7.4 million Americans with diabetes used insulin. This study aimed to document the 10‐year trend of insulin and other glucose‐lowering medications expenditure among insured and uninsured populations and to examine the impact of insulin out‐of‐pocket (OOP) payment and insurance status on glucose‐lowering medication OOP expenditure. Methods: We extracted data from the Medical Expenditure Panel Survey (2009–2018) to document trends in the expenditure of insulin among people with diabetes. Total expenditures and OOP spending per person were documented on insulin and noninsulin glucose‐lowering medications among insured and uninsured populations. Multivariable regression was applied to assess the association of insulin OOP payment and insurance status on glucose‐lowering medication OOP expenditure. Results: Although insulin usage was stable over the decades, total insulin expenditure almost doubled per person per year after the Affordable Care Act (ACA) regardless of the insurance status. The OOP cost of insulin by the uninsured population increased from $1678 per person per year in the pre‐ACA period to $2800 per person per year in the post‐ACA period. After the ACA was enacted, the uninsured population had $403.96 and $143.64 more on OOP costs than the people with public and private insurance, respectively. Conclusion: For insured people, the rising financial burden of insulin was borne mainly by insurance. The uninsured population is bearing a heavy burden due to the high price of insulin. Policymakers should take action to reduce the insulin price and improve the transparency of the insulin pricing process. [ABSTRACT FROM AUTHOR]

The article discusses the position statement on diabetes research by the American Diabetes Association (ADA). Data on the prevalence diabetes in the U.S. are provided. It notes the commitment of the ADA to improving the lives of people with or at risk for the disease. An overview of ADA's research programs on diabetes,as well as its research strategy is provided.

OBJECTIVE - To assess efficacy and safety of lixisenatide monotherapy in type 2 diabetes. RESEARCH DESIGN AND METHODS - Randomized, double-blind, 12-week study of 361 patients not on glucose-lowering therapy (HbA1c 7-10%) allocated to one of four once-daily subcutaneous dose increase regimens: lixisenatide 2-step (10 μg for 1week,15 μg for 1 week, and then 20μg; n = 120), lixisenatide 1-step (10 μg for 2weeks and then 20μg; n = 119), placebo 2-step (n = 61), or placebo 1-step (n = 61) (placebo groups were combined for analyses). Primary end point was HbA1c change from baseline to week 12. RESULTS - Once-daily lixisenatide significantly improved HbA1c (mean baseline 8.0%) in both groups (least squares mean change vs. placebo: 20.54% for 2-step, 20.66% for 1-step; P< 0.0001). Significantly more lixisenatide patients achieved HbA1c <7.0% (52.2% 2-step, 46.5% 1-step) and ≤6.5% (31.9% 2-step, 25.4% 1-step) versus placebo (26.8% and 12.5%, respectively; P<0.01). Lixisenatide led tomarked significant improvements of 2-h postprandial glucose levels and blood glucose excursions measured during a standardized breakfast test. A significant decrease in fasting plasma glucose was observed in both lixisenatide groups versus placebo.Mean decreases in body weight (~2 kg) were observed in all groups. Themost common adverse events were gastrointestinald-nausea was the most frequent (lixisenatide 23% overall, placebo 4.1%). Symptomatic hypoglycemia occurred in 1.7%of lixisenatide and 1.6%of placebo patients, with no severe episodes. Safety/tolerability was similar for the two dose regimens. CONCLUSIONS - Once-daily lixisenatide monotherapy significantly improved glycemic control with a pronounced postprandial effect (75% reduction in glucose excursion) and was safe and well tolerated in type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article discusses research studies on the role of the American Diabetes Association (ADA) in diabetes research, prevention, care and public health. ADA initiated research studies across the broad area of diabetes and related diseases and topics since 1952, and has released funds based on scientific merits and peer reviews. The results of these studies are disseminated to the research community and to the public through advocacies.

Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are considered the standard of care for treatment of cardiovascular disease and chronic kidney disease. Combination therapy with both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers effectively inhibits the renin-angiotensin system as well as potentiates the vasodilatory effects of bradykinin. It has been advocated that this dual blockade approach theoretically should result in improved clinical outcomes in both cardiovascular disease and chronic kidney disease. Clinical trial evidence for the use of combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in cardiovascular disease has provided conflicting results in hypertension, congestive heart failure, and ischemic heart disease. Clinical trial evidence to support combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chronic kidney disease has largely been based on proteinuria reduction as a surrogate marker for clinically meaningful outcomes. Recent large-scale randomized clinical trials have not been able to validate protection in halting progression in chronic kidney disease with a dual blockade approach. This review serves as an appraisal on the clinical evidence of combination angiotensin-converting enzyme inhibition and angiotensin II receptor blockade in both cardiovascular disease and chronic kidney disease. [ABSTRACT FROM AUTHOR]

The article examines randomized controlled trials (RCT) describing or reviewing methods to prevent diabetic foot ulcers. Review articles were obtained from Medline and PubMed between January 1, 1960 and April 30, 2010. One study was conducted by J. M. Malone and colleagues which focused on diabetic education to prevent foot amputation. Another study was conducted by L. E. Uccioli and colleagues which focused on the use of therapeutic shoes by patients with previous foot ulceration.

OBJECTIVES: to evaluate the reproducibility of a physical activity assessment questionnaire for children aged between 7 and 10 years among participants of the Saúdes Vitória Study in Espírito Santo State, Brazil. METHODS: a cross-sectional study was carried out in a random sample of 91 children enrolled in public and private sector schools in the municipality. A structured questionnaire with 13 questions was sent to the home of selected children, to be filled out twice, with an interval of 15 days. To evaluate the reproducibility the Kappa agreement test was used for the qualitative variables, and Pearson's correlation or Spearman's r for the quantitative ones, followed by a scatter analysis. RESULTS: the Kappa agreement indices were significant for all qualitative variables and varied from moderate to high (k= 0.72 - 0.98). Likewise, the correlation coefficients ranged from moderate to high (r= 0.51 - 1.00), except for time spent playing video games and duration of second sport, which showed no significant correlation. CONCLUSIONS: Saúdes questionnaire enabled data on physical and sedentary activities to be collected with a good level of reproducibility, although there are limitations in the population under study regarding the quantification of the time spent on less frequent activities, such as playing video games or practicing a second sport. [ABSTRACT FROM AUTHOR]

Simultaneous control of blood glucose and other risk factors such as hypertension and dyslipidaemia is essential for reducing the risk of complications associated with type 2 diabetes mellitus (T2DM). As relatively few patients with T2DM have their risk factors managed to within the limits recommended by the American Diabetes Association, American College of Endocrinology or National Cholesterol Education Program Adult Treatment Panel III guidelines, treatment that can simultaneously control more than one risk factor is of therapeutic benefit. Clinical studies have shown that bile acid sequestrants have glucose-lowering effects in addition to their low-density lipoprotein cholesterol-lowering effects in patients with T2DM. The bile acid sequestrant colesevelam hydrochloride is approved as an adjunct to antidiabetes therapy for improving glycaemic control in adults with T2DM. This review examines data from three phase III clinical trials that evaluated the glucose- and lipid-lowering effects of colesevelam when added to the existing antidiabetes treatment regimen of patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: Salsalate, a nonacetylated prodrug of salicylate, has been shown to decrease blood glucose concentration in small studies. Objective: To compare the efficacy and safety of salsalate at different doses in patients with type 2 diabetes. Design: Parallel randomized trial with computer-generated randomization and centralized allocation. Patients and investigators, including those assessing outcomes and performing analyses, were masked to group assignment. (ClinicalTrials.gov registration number: NCT00392678) Setting: 3 private practices and 14 universities in the United States. Patients: Persons aged 18 to 75 years with fasting plasma glucose concentrations of 12.5 mmol/L or less (⩽225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% treated by diet, exercise, and oral medication at stable doses for at least 8 weeks. Intervention: After a 4-week, single-masked run-in period, patients were randomly assigned to receive placebo or salsalate in dosages of 3.0, 3.5, or 4.0 g/d for 14 weeks (27 patients each) in addition to their current therapy. Measurements: Change in HbA1c was the primary outcome. Adverse effects and changes in measures of coronary risk and renal function were secondary outcomes. Results: Higher proportions of patients in the 3 salsalate treatment groups experienced decreases in HbA1c levels of 0.5% or more from baseline (P = 0.009). Mean HbA1c changes were -0.36% (P = 0.02) at 3.0 g/d, =0.34% (P = 0.02) at 3.5 g/d, and -0.49% (P = 0.001) at 4.0 g/d compared with placebo. Other markers of glycemic control also improved in the 3 salsalate groups, as did circulating triglyceride and adiponectin concentrations. Mild hypoglycemia was more common with salsalate; documented events occurred only in patients taking sulfonylureas. Urine albumin concentrations increased in all salsalate groups compared with placebo. The drug was otherwise well tolerated. Limitation: The number of patients studied and the trial duration were insufficient to warrant recommending the use of salsalate for type 2 diabetes at this time. Conclusion: Salsalate lowers HbA1c levels and improves other markers of glycemic control in patients with type 2 diabetes and may therefore provide a new avenue for treatment. Renal and cardiac safety of the drug require further evaluation. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. [ABSTRACT FROM AUTHOR]

The article analyzes data that explore possible mechanisms involved in regulation of glucose metabolism by bile acids and potential effect of disruption of their enterohepatic circulation on diabetes. The clinical trial data that supported the regulatory approval of colesvelam for the treatment of hyperglycemia in type 2 diabetes are summarized. It notes that the primary bile acids formed in human beings are cholic acid and chenodeoxycholic acid. Also cited is the role of bile acids in metabolic regulation through modulation of energy expenditure.

The article discusses the progression of type 2 diabetes. The role played by β-cell function in the progression of the disease is examined. The increasing loss of glycemic control during the course of treatment for type 2 diabetes based on major clinical trials is tackled. Other topics tackled include the pathophysiology of the &beta-cell dysfunction, the mechanisms involved in the decline of insulin secretion, and the microvascular and macrovascular complications of diabetes.

OBJECTIVE -- To examine the impact of Hurricane Katrina on the health of individuals with diabetes. RESEARCH DESIGN AND METHODS -- This was an observational study in 1,795 adults with an AlC measurement 6 months before and 6-16 months after Hurricane Katrina in three health care systems: private (Tulane University Hospital and Clinic [TUHC]), state (Medical Center of Louisiana at New Orleans [MCLNO]), and Veterans Affairs (VA). Glycemic control (AlC), blood pressure, and lipids before the hurricane were compared with the patients' first measurement thereafter. The CORE Diabetes Model was used to project life expectancy and health economic impact. RESULTS -- Mean predisaster AlC levels differed between MCLNO and VA patients (mean 7.7 vs. 7.3%, P < 0.001) and increased significantly among MCLNO patients to 8.3% (P < 0.001) but not among VA and TUHC patients. Mean systolic blood pressure increased in all three systems (130-137.6 mmHg for TUHC and 130.7-143.7 for VA, P < 0.001; 132-136 for MCLNO, P = 0.008). Mean LDL cholesterol increased in the VA (97.1-104.3 mg/dl) and TUHC patients (103.4-115.5; P < 0.001). Hurricane Katrina increased modeled direct, indirect, and total health care costs and also reduced life expectancy as well as quality-adjusted life expectancy, with the economic impact being quite substantial because of the large population size affected. We estimate a lifetime cost of USD $504 million for the adult population affected, with the largest economic impact seen among MCLNO patients. CONCLUSIONS -- A major disaster had a significant effect on diabetes management and exacerbated existing disparities. These effects may have a lasting impact on both health and economic implications. [ABSTRACT FROM AUTHOR]

The kidneys play a major role in the regulation of glucose in humans, reabsorbing 99% of the plasma glucose that filters through the renal glomeruli tubules. The glucose transporter, SGLT2, which is found primarily in the S1 segment of the proximal renal tubule, is essential to this process, accounting for 90% of the glucose reabsorption in the kidney. Evidence has suggested that selective inhibition of SGLT2 induces glucosuria in a dose-dependent manner and may have beneficial effects on glucose regulation in individuals with type II diabetes. Preclinical data with SGLT2 inhibitors, such as dapagliflozin and sergliflozin, show that these compounds are highly selective inhibitors for SGLT2, have beneficial effects on the glucose utilization rate, and reduce hyperglycemia while having no hypoglycemic adverse effects. Clinical research remains to be carried out on the long-term effects of glucosuria and other potential effects of this class of drug. Nonetheless, these compounds represent a very promising approach for the treatment of diabetes.Kidney International (2009) 75, 1272–1277; doi:10.1038/ki.2009.87; published online 8 April 2009 [ABSTRACT FROM AUTHOR]

The potential cardiovascular risks that are associated with drugs for type 2 diabetes have recently raised considerable clinical and regulatory concerns. As some risk factors for cardiovascular disease and type 2 diabetes are related, identifying agents that target shared underlying pathways and processes is an attractive therapeutic strategy. In this article, we review the background to and the implications of recent regulatory guidance on the development of new drugs for diabetes, and discuss the potential cardiovascular effects of selected classes of diabetes drugs that are currently being investigated. [ABSTRACT FROM AUTHOR]

In the Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial, carvedilol added to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers had neutral or beneficial effects on glycemic measures compared with metoprolol tartrate. For the 1235 diabetic hypertensive GEMINI patients, the authors assessed treatment differences by race (white/black/other), age (continuous variable), and sex on hemoglobin A1c, insulin resistance (homeostasis model assessment–insulin resistance [HOMA-IR]), and blood pressure. Both treatments significantly reduced blood pressure in all subgroups, but the metabolic effects of carvedilol were more beneficial in subgroups of race and sex. Carvedilol did not affect hemoglobin A1c but improved HOMA-IR results in all subgroups, significantly in males and “other race” subgroups. Metoprolol significantly increased hemoglobin A1c in all subgroups except “other race,” with no effect on HOMA-IR findings. Differences vs metoprolol significantly favored carvedilol for hemoglobin A1c in white and female subgroups and favored carvedilol for HOMA-IR in black, “other race,” and male subgroups. Carvedilol effects were favorable to adjustment of age as a covariate. In hypertensive patients with diabetes, carvedilol may be a more appropriate choice when β-blockade is indicated. [ABSTRACT FROM AUTHOR]

The authors reflect on the importance of continuing research and education to improve the methods of glycosylated hemoglobin (A1C) assay assessment used to determine the effectiveness of diabetes therapy. They cites the pitfalls of the methods and studies of various diabetes organizations. They urge clinicians not to stop looking for reliable A1C measurement to ensure that the average blood glucose of patient is accurate. They also advise clinicians to educate patients about the fluctuations in their glucose levels.

OBJECTIVE -- Hyperglycemia is a risk factor for microvascular complications and may increase the risk of cardiovascular disease in patients with type 2 diabetes. This study tested the LDL cholesterol-lowering agent colesevelam HCl (colesevelam) as a potential novel treatment for improving glycemic control in patients with type 2 diabetes on sulfonylurea-based therapy. RESEARCH DESIGN AND METHODS -- A 26-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study was carried out between August 2004 and August 2006 to evaluate the efficacy and safety of colesevelam for reducing A1C in adults with type 2 diabetes whose glycemic control was inadequate (A1C 7.5-9.5%) with existing sulfonylurea monotherapy or sulfonylurea in combination with additional oral antidiabetes agents. In total, 461 patients were randomized (230 given colesevelam 3.75 g/day and 231 given placebo). The primary efficacy measurement was mean placebo-corrected change in A1C from baseline to week 26 in the intent-to-treat population (last observation carried forward). RESULTS -- The least squares (LS) mean change in A1C from baseline to week 26 was -0.32% in the colesevelam group and +0.23% in the placebo group, resulting in a treatment difference of -0.54% (P < 0.001). The LS mean percent change in LDL cholesterol from baseline to week 26 was - 16.1% in the colesevelam group and + 0.6% in the placebo group, resulting in a treatment difference of -16.7% (P < 0.001). Furthermore, significant reductions in fasting plasma glucose, fructosamine, total cholesterol, non-HDL cholesterol, and apolipoprotein B were demonstrated in the colesevelam relative to placebo group at week 26. CONCLUSIONS -- Colesevelam improved glycemic control and reduced LDL cholesterol levels in patients with type 2 diabetes receiving sulfonylurea-based therapy. [ABSTRACT FROM AUTHOR]

The article reports on the efficacy and safety of colesevelam in patients with type 2 diabetes mellitus. The vault aims to store seeds in case of global disaster. It is mentioned that the vault can carry up to 4.5 million types of seeds for hundreds and thousands of years. It containes a refrigerator that is powered by coal that keeps the seeds at 20 degrees celcius. This vault will only rise up to -3 degrees celcius even if the power breakout. It has an entrance made of 200 optical fibers that creates a green glow effect.

A panel was convened on January 10, 2007, to discuss the challenges to the diagnosis, evaluation, treatment, and management of clustered cardiometabolic risk factors. George Bakris, MD, Professor of Medicine, University of Chicago, Chicago, IL, moderated the panel. Vivian Fonseca, MD, Tulane University Health Science Center, New Orleans, LA, and JoAnne Foody, MD, Harvard School of Medicine, Boston, MA, participated in the discussion. This expert panel discussion was supported by and each author received an honorarium from Merck & Co, Inc, and Sanofi-Aventis for time and effort spent participating in the discussion and reviewing the transcript for important intellectual content before publication. The authors maintained full control of the discussion and the resulting content of this article. [ABSTRACT FROM AUTHOR]