IN BRIEF This article reviews the evidence regarding the impact of postprandial glucose (PPG) on overall A1C and its relation to cardiovascular disease (CVD). To date, four randomized, controlled trials have evaluated the impact of PPG reduction on CVD; however, only one of these successfully demonstrated a positive effect. Despite this, epidemiological evidence does indicate a cardiovascular benefit of PPG reduction, and agents that can be used to manage PPG in people with type 2 diabetes are also discussed.

01 May 2011·Endocrine PracticeQ4 · MEDICINE

Mechanistic and Clinical Aspects of Renin-Angiotensin-Aldosterone System Blockade in the Prevention of Diabetes Mellitus and Cardiovascular Disease

Q4 · MEDICINE

Review

Author: Hershon, Kenneth S

OBJECTIVETo review the rationale for the use of renin-angiotensin-aldosterone system (RAAS) inhibition to prevent type 2 diabetes mellitus and cardiovascular events and to discuss clinical data evaluating the relationship between RAAS blockade and diabetes prevention.METHODSPubMed was searched to identify preclinical and clinical data addressing this aim.RESULTSPotential mechanisms of angiotensin II-mediated insulin resistance and type 2 diabetes may include impaired blood flow and sympathetic activity, increased oxidative stress, alterations in insulin signaling, and effects on adipose tissue. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have demonstrated reduced incidences of new-onset diabetes in patients with prediabetes or hypertension and in other cardiovascular populations; however, insight into the corresponding impact on cardiovascular-related morbidity and mortality has been lacking. A recent trial (NAVIGATOR) was designed to evaluate incident diabetes and cardiovascular outcomes as part of its primary endpoint. In this trial, valsartan-based therapy reduced the incidence of new-onset diabetes by 14% relative to placebo over the 5-year follow-up period (P<.001). Cardiovascular outcomes, however, were not significantly affected by active treatment, which may be attributed to a number of potential confounding factors including the low rate of cardiovascular disease at baseline, concurrent implementation of lifestyle modification in all patients, and the substantial use of other risk-reducing agents.CONCLUSIONSAngiotensin II has been implicated in a number of pathophysiologic processes with the potential to indirectly or directly influence the pathogenesis of insulin resistance and type 2 diabetes. Most clinical trials show a reduced risk of new-onset diabetes with RAAS blockade; however, recent results of the NAVIGATOR trial show that the addition of valsartan to lifestyle modification reduces the risk of diabetes, but does not improve cardiovascular outcomes.

01 Oct 2004·Diabetes CareQ1 · MEDICINE

Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 2 Diabetes

Q1 · MEDICINE

Article

Author: Hershon, Kenneth S. ; Levin, Seymour R. ; Mehta, Adi E. ; Blonde, Lawrence ; Hollander, Priscilla A. ; Rowe, Richard ; Chiasson, Jean-Louis ; Milburn, Joseph L.

OBJECTIVE— Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections.RESEARCH DESIGN AND METHODS— Patients were randomized to 6 months’ treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA1c from baseline to the end of study.RESULTS— HbA1c decreased similarly in the inhaled (−0.7%) and subcutaneous (−0.6%) insulin groups (adjusted treatment group difference: −0.07%, 95% CI −0.32 to 0.17). HbA1c <7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24–4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82–0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group.CONCLUSIONS— Inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen.

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