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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: Insulin resistance is characterized by impaired responsiveness to endogenous or exogenous insulin. Loss of responsiveness is associated with a "clustering" of cardiovascular risk factors that includes abdominal obesity, hypertension, dyslipidemia, glucose intolerance, and hyperinsulinemia; this association is referred to as the insulin resistance syndrome (IRS).Methods: We searched MEDLINE, using the term insulin resistance, and reviewed relevant publications.Results: We review the mechanisms and clinical consequences attributed to IRS, along with patient assessment and treatment options.Conclusions: It is possible to improve insulin sensitivity by caloric restriction, weight loss, exercise, and drug therapy. Metformin and troglitazone, approved for use in the treatment of type 2 diabetes mellitus (DM), improve insulin sensitivity and lower plasma glucose concentrations. Several other medications that may improve insulin sensitivity are currently under clinical investigation. Studies are needed to determine the effect of these medications on morbidity and mortality of patients with insulin resistance and type 2 DM. [ABSTRACT FROM AUTHOR]

Studies the measurement of plasma concentrations of thiobarbituric acid reactive substances (TBARS) in patients with diabetes. Purpose of the study; Information about the patients and the methods used in the study; Results and discussion; Concluding remarks.

Reports on the discovery in the United States of good glycemic control which may prevent diabetic retinopathy or delay its progression. Role of primary care physicians in translating the results into practice; Biochemical reactions resulting from hyperglycemia; Management of other diabetes risk factors.

The authors convey their response to a feedback about their report on the impact of liraglutide versus placebo on cardiovascular events in patients with type 2 diabetes mellitus and chronic kidney disease. Topics mentioned include the proportion of patients with severe hypoglycemia, evidence of differential treatment effect by race, and coronary revascularization and hospitalization for unstable angina.

Previous studies indicate that the intrarenal renin-angiotensin system (RAS) is activated in type-1 diabetes mellitus (T1DM) experimental animal models and human subjects, and is reflected by augmentation of urinary angiotensinogen (uAGT) excretion rate. Studies were performed to evaluate uAGT in young patients with short duration diabetes mellitus (DM) and its relationships with HbA1c and urinary 8-isoprostane excretion rate. Blood and urine samples were collected from 77 young (15±1 years) patients (44 male, 33 female) with short duration T1DM treated only with insulin and 36 (17 male, 19 female) control subjects. Serum glucose levels were 85±4 mg/dl in control subjects and 192±11 mg/dl in DM patients. Urinary Alb/Cr and uPro/Cr ratios were not significantly different in DM patients compared to control (8.6±.9 vs 9.7±.6 and 51±8 vs 62±14 mg/g). However, the uAGT/Cr ratios were significantly elevated in the DM patients (6.8±.8 vs 16.5±1.5 ug/g). Correlation analysis demonstrated highly significant relationships (P<.0001) between uAGT/Cr and HbA1c (R=.44) and urinary 8-isoprostane excretion rate (R=.52) in the DM patients. These results indicate that, even in young non-albuminuric patients with relatively short duration of DM, uAGT excretion rates are increased, suggesting early activation of the intrarenal RAS, and are correlated with HbA1c and urinary 8-isoprostane levels indicative of increased reactive oxygen species. Accordingly, uAGT levels may serve as an early marker of an activated intrarenal RAS and provide a specific index of renal RAS status potentially useful in monitoring clinical response to therapy. [ABSTRACT FROM AUTHOR]

The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: The ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

Insulin resistance is an increasingly common metabolic abnormality characterized by an impaired physiological response to insulin. The constellation of insulin resistance and several other metabolic and vascular disorders is known as the insulin resistance syndrome. The characteristic features of the insulin resistance syndrome include central obesity, hypertension, dyslipidemia, glucose intolerance and specific abnormalities of both endothelial cell and vascular function. Although insulin resistance can arise in response to aging, obesity and inactivity, there is a clear genetic component. Insulin resistance is not generally attributable to a single genetic defect. Indeed, it is very likely to be a polygenic disorder in most individuals. A genetic predisposition is suggested to be the demonstration of increased insulin resistance in first-degree relatives of patients with diabetes and by a high incidence of insulin resistance in specific populations. Epidemiological data have demonstrated a strong association between a clustering of specific factors and the risk of cardiovascular disease. The diagnosis of the insulin resistance syndrome remains a significant clinical challenge. At present, clinicians are faced with establishing a clinical diagnosis despite varying definitions of the disorder and controversy regarding how many components presage clinical events. A proposed approach to the management of patients with the insulin resistance syndrome is discussed.