Objectives The purpose of this study was to investigate the relationship between hepatic triglyceride content and both myocardial function and metabolism in type 2 diabetes mellitus (T2DM). ...Background Heart disease is the leading cause of mortality in T2DM. Central obesity and hepatic steatosis, both hallmark abnormalities in T2DM, have been related to increased risk of heart disease. Methods Sixty-one T2DM patients underwent myocardial perfusion and substrate metabolism measurements by positron emission tomography, using 15 Owater, 11 Cpalmitate, and 18 F-2-fluoro-2-deoxy- d -glucose. In addition, whole-body insulin sensitivity (M/I) was determined. Myocardial left ventricular function and high-energy phosphate metabolism were measured using magnetic resonance imaging and 31 P-magnetic resonance spectroscopy, respectively. Hepatic triglyceride content was measured by proton magnetic resonance spectroscopy. Patients were divided according to hepatic triglyceride content (T2DM-low ≤5.56% vs. T2DM-high >5.56%). Results In addition to decreased M/I (p = 0.002), T2DM-high patients had reduced myocardial perfusion (p = 0.001), glucose uptake (p = 0.005), and phosphocreatine/adenosine triphosphate (PCr/ATP) ratio (p = 0.003), compared with T2DM-low patients, whereas cardiac fatty acid metabolism and left ventricular function were not different. Hepatic triglyceride content correlated inversely with M/I (Pearson's r = −0.620, p < 0.001), myocardial glucose uptake (r = −0.413, p = 0.001), and PCr/ATP (r = −0.442, p = 0.027). Insulin sensitivity correlated positively with myocardial glucose uptake (r = 0.528, p < 0.001) and borderline with myocardial PCr/ATP (r = 0.367, p = 0.072), whereas a positive association was found between cardiac glucose uptake and PCr/ATP (r = 0.481, p = 0.015). Conclusions High liver triglyceride content in T2DM was associated with decreased myocardial perfusion, glucose uptake, and high-energy phosphate metabolism in conjunction with impaired M/I. The long-term clinical implications of hepatic steatosis with respect to cardiac metabolism and function in the course of T2DM require further study.
Objectives This study was designed to evaluate myocardial substrate and high-energy phosphate (HEP) metabolism in asymptomatic men with well-controlled, uncomplicated type 2 diabetes with verified ...absence of cardiac ischemia, and age-matched control subjects, and to assess the association with myocardial function. Background Metabolic abnormalities, particularly an excessive exposure of the heart to circulating nonesterified fatty acids and myocardial insulin resistance are considered important contributors to diabetic cardiomyopathy in animal models of diabetes. The existence of myocardial metabolic derangements in uncomplicated human type 2 diabetes and their possible contribution to myocardial dysfunction still remain undetermined. Methods In 78 insulin-naive type 2 diabetes men (age 56.5 ± 5.6 years, body mass index 28.7 ± 3.5 kg/m2 , glycosylated hemoglobin A1c 7.1 ± 1.0%; expressed as mean ± SD) without cardiac ischemia and 24 normoglycemic control subjects (age 54.5 ± 7.1 years, body mass index 27.0 ± 2.5 kg/m2 , glycosylated hemoglobin A1c 5.3 ± 0.2%), we assessed myocardial left ventricular (LV) function by magnetic resonance imaging, and myocardial perfusion and substrate metabolism by positron emission tomography using H215 O, carbon11 C-palmitate, and 18-fluorodeoxyglucose 2-fluoro-2-deoxy-D-glucose. Cardiac HEP metabolism was assessed by phosphorous P 31 magnetic resonance spectroscopy. Results In patients, compared with control subjects, LV diastolic function (E/A ratio: 1.04 ± 0.25 vs. 1.26 ± 0.36, p = 0.003) and myocardial glucose uptake (260 ± 128 nmol/ml/min vs. 348 ± 154 nmol/ml/min, p = 0.015) were decreased, whereas myocardial nonesterified fatty acid uptake (88 ± 31 nmol/ml/min vs. 68 ± 18 nmol/ml/min, p = 0.021) and oxidation (85 ± 30 nmol/ml/min vs. 63 ± 19 nmol/ml/min, p = 0.007) were increased. There were no differences in myocardial HEP metabolism or perfusion. No association was found between LV diastolic function and cardiac substrate or HEP metabolism. Conclusions Patients versus control subjects showed impaired LV diastolic function and altered myocardial substrate metabolism, but unchanged HEP metabolism. We found no direct relation between cardiac diastolic function and parameters of myocardial metabolism.
Abstract Purpose Although diabetes is recognized as a risk factor for the development of cognitive impairment and for accelerated progression to Alzheimer disease (AD), it is unclear whether patients ...with diabetes who have already progressed to AD have a different rate of cognitive and functional decline compared with that in those without diabetes. This post hoc exploratory analysis compared cognitive and functional decline over an 18-month period in patients with mild AD dementia with and without comorbid diabetes. Decline in quality of life was assessed as a secondary objective. Methods In a post hoc exploratory analysis, we analyzed data from the placebo groups of three 18-month, randomized, placebo-controlled trials of solanezumab and semagacestat in patients with AD. Data from patients with mild AD dementia (Mini-Mental State Examination MMSE score, 20–26) and comorbid diabetes at baseline were compared with data from patients with mild AD dementia without diabetes at baseline. Cognition was assessed using the 14-item AD Assessment Scale–Cognitive Subscale (ADAS-Cog14 ) and the MMSE. Functioning was assessed with the AD Cooperative Study–Activities of Daily Living Inventory (instrumental subset) (ADCS-iADL). Quality of life was assessed using the European Quality of Life–5 Dimensions scale, proxy version (proxy utility score and visual analog scale score), and the Quality of Life in AD scale, self-report and proxy (caregiver) versions. Group comparisons of changes from baseline to 18 months in cognitive, functional, and quality-of-life measures employed a repeated-measures model adjusted for propensity score, study, baseline cognition score (functional or quality of life), age, sex, level of education, genotype of the apolipoprotein E gene, and concurrent use of an acetylcholinesterase inhibitor or memantine. Findings At baseline, patients with mild AD dementia with and without diabetes did not significantly differ on the cognitive measures, but those without diabetes were functioning at a significantly higher level. At 18 months, compared with patients without diabetes, those with diabetes showed a numerically but statistically nonsignificantly lesser cognitive decline (least squares mean between-group differences: ADAS-Cog14 score, 1.61 P = 0.21; MMSE score, –0.40 P = 0.49) and a statistically significantly lesser functional decline (least squares mean between-group difference in ADCS-iADL score, –3.07; P = 0.01). The 2 groups did not differ on declines in the quality-of-life measures. Implications The present findings suggest that diabetes may influence the rate of functional decline among patients with mild AD dementia. These results require replication in studies that address the limitations of the present post hoc exploratory analysis and that explore the potential causes of the observed differences.
Summary Background Results of intervention studies in patients with type 2 diabetes have led to concerns about the safety of aiming for normal blood glucose concentrations. We assessed survival as a ...function of HbA1c in people with type 2 diabetes. Methods Two cohorts of patients aged 50 years and older with type 2 diabetes were generated from the UK General Practice Research Database from November 1986 to November 2008. We identified 27 965 patients whose treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents, and 20 005 who had changed to regimens that included insulin. Those with diabetes secondary to other causes were excluded. All-cause mortality was the primary outcome. Age, sex, smoking status, cholesterol, cardiovascular risk, and general morbidity were identified as important confounding factors, and Cox survival models were adjusted for these factors accordingly. Findings For combined cohorts, compared with the glycated haemoglobin (HbA1c ) decile with the lowest hazard (median HbA1c 7·5%, IQR 7·5–7·6%), the adjusted hazard ratio (HR) of all-cause mortality in the lowest HbA1c decile (6·4%, 6·1–6·6) was 1·52 (95% CI 1·32–1·76), and in the highest HbA1c decile (median 10·5%, IQR 10·1–11·2%) was 1·79 (95% CI 1·56–2·06). Results showed a general U-shaped association, with the lowest HR at an HbA1c of about 7·5%. HR for all-cause mortality in people given insulin-based regimens (2834 deaths) versus those given combination oral agents (2035) was 1·49 (95% CI 1·39–1·59). Interpretation Low and high mean HbA1c values were associated with increased all-cause mortality and cardiac events. If confirmed, diabetes guidelines might need revision to include a minimum HbA1c value. Funding Eli Lilly and Company.
: Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. ...However, published statements and scientific opinions disagree about the clinical usefulness.
: A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.
: A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.
: Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.
: Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.
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