Isolated perfused working hearts provide valuable additional information during phenotypic assessment of the diabetic mouse heart.

Although murine models for studying the development of cardiac dysfunction in diabetes mellitus are well established, their reported cardiac phenotypes vary. These reported divergences may, in addition to the severity of different models, also be linked to the methods used for cardiac functional assessment. In the present study, we examined the functional changes using conventional transthoracic echocardiography (in vivo) and isolated heart perfusion techniques (ex vivo), in hearts from two mouse models; one with an overt type 2 diabetes (the db/db mouse) and one with a prediabetic state, where obesity was induced by a high-fat diet (HFD). Analysis of left ventricular function in the isolated working hearts from HFD-fed mice, suggested that these hearts develop diastolic dysfunction with preserved systolic function. Accordingly, in vivo examination demonstrated maintained systolic function, but we did not find parameters of diastolic function to be altered. In db/db mice, ex vivo working hearts showed both diastolic and systolic dysfunction. Although in vivo functional assessment revealed signs of diastolic dysfunction, the hearts did not display reduced systolic function. The contrasting results between ex vivo and in vivo function could be due to systemic changes that may sustain in vivo function, or a lack of sensitivity using conventional transthoracic echocardiography. Thus, this study demonstrates that the isolated perfused working heart preparation provides unique additional information related to the development of cardiomyopathy, which might otherwise go unnoticed when only using conventional echocardiographic assessment.

Simulated Effects of Policies to Reduce Diabetes Risk Among Adults With Schizophrenia Receiving Antipsychotics.

OBJECTIVE: Second-generation antipsychotics increase the risk of diabetes and other metabolic conditions among individuals with schizophrenia. Although metabolic testing is recommended to reduce this risk, low testing rates have prompted concerns about negative health consequences and downstream medical costs. This study simulated the effect of increasing metabolic testing rates on ten-year prevalence rates of prediabetes and diabetes (diabetes conditions) and their associated health care costs. METHODS: A microsimulation model (N=21,491 beneficiaries) with a ten-year time horizon was used to quantify the impacts of policies that increased annual testing rates in a Medicaid population with schizophrenia. Data sources included California Medicaid data, National Health and Nutrition Examination Survey data, and the literature. In the model, metabolic testing increased diagnosis of diabetes conditions and diagnosis prompted prescribers to switch patients to lower-risk antipsychotics. Key inputs included observed diagnoses, prescribing rates, annual testing rates, imputed rates of undiagnosed diabetes conditions, and literature-based estimates of policy effectiveness. RESULTS: Compared with 2009 annual testing rates, ten-year outcomes for policies that achieved universal testing reduced exposure to higher-risk antipsychotics by 14%, time to diabetes diagnosis by 57%, and diabetes prevalence by .6%. These policies were associated with higher spending because of testing and earlier treatment. CONCLUSIONS: The model showed that policies promoting metabolic testing provided an effective approach to improve the safety of second-generation antipsychotic prescribing in a Medicaid population with schizophrenia; however, the policies led to additional costs at ten years. Simulation studies are a useful source of information on the potential impacts of these policies.

Risk factor assessment for new onset diabetes: literature review.

Metabolic syndrome (MS), typified by hypertension, abdominal obesity, dyslipidaemia and impaired glucose metabolism, is a precursor of type 2 diabetes. Thiazide diuretics (TD) and beta-blockers are associated with increased risk of diabetes in patients with hypertension; however, the role of these agents in development of diabetes in MS patients is unknown. We reviewed the literature regarding risk factors for diabetes development and compared this with data from the Study of Trandolapril/Verapamil SR And Insulin Resistance (STAR), which investigated the effects of two fixed-dose combinations (FDCs) [trandolapril/verapamil SR and losartan/hydrochlorothiazide (L/H)] on glucose control and new diabetes in MS patients. In STAR, logistic regression modelling identified haemoglobin A1c [odds ratio (OR) 4.21 per 1% increment; p = 0.003), L/H treatment (OR 4.04; p = 0.002) and 2-h oral glucose tolerance test glucose levels (OR 1.39 per 10 mg/dl increments; p < 0.001) as baseline predictors of diabetes. These data support prior analyses and suggest that choice of antihypertensive agent is important. Patients with MS may be at lower risk of diabetes when using a FDC calcium channel blocker + angiotensin-converting enzyme inhibitor compared with an angiotensin receptor blocker + TD.