No abstract

O besity and type 2 diabetes mellitus (DM) have reached epidemic levels worldwide. These 2 metabolic disorders are independent risk factors for the development of heart failure. [1][2][3] Epidemiological and clinical studies strongly support the existence of obesity and diabetic cardiomyopathies unrelated to coronary artery disease, hypertension, and other comorbidities. 4,5 Clinical Perspective on p 564Studies in rodent models of obesity and DM have identified intrinsic cardiomyocyte dysfunctions secondary to alterations in energy substrate utilization, mitochondrial dysfunction, increased oxidative stress, and intracellular accumulation of lipotoxic byproducts. Similarly, human studies have shown that dysregulation of the energy conversion process is one of the major characteristics of the failing heart of subjects with cardiomyopathy related to DM or obesity. 6,7Background-Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy. Methods and Results-Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A 1C , but neither body mass index nor the insulin resistance index (homeostasis model assessment-insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A 1C . Conclusion-Worsening

The objective of this study was to assess a circadian variation of diet-induced thermogenesis (DIT) that could favor weight gain among night workers used to eating a night time snack. Nine young men were given the same mean at 0900, 1700, or 0100. Energy expenditure was measured by indirect calorimetry 1 h before and during the 6 h after the snack. DIT was calculated as the 3 h of energy expenditure above basal metabolic rate. Morning DIT was significantly higher than afternoon DIT (P = 0.04) and night DIT (P = 0.002). Afternoon DIT was higher than night DIT (P = 0.06). We conclude that the time when a meal is consumed affects the thermogenic response and must be considered in the energy balance.

Emphysema and/or ground-glass attenuation are linked with impairment of ventilatory lung function over time in persistent current smokers.

To determine the histopathologic basis for computed tomographic (CT) interpretation of smokers' lung and the accuracy of CT in the detection of alterations related to cigarette smoking, parenchymal lung lesions were studied from 41 heavy smokers who underwent thoracotomy for removal of a solitary pulmonary nodule. CT scanning of the resected lungs, corresponding exactly to the sections seen on preoperative CT scans, resulted in the following pathologic-CT correlations. Areas of ground-glass attenuation seen on preoperative CT scans (n = 11 [27%]) were related to three main histologic features: (a) accumulation of pigmented macrophages and mucus in the alveolar spaces, associated with mild interstitial inflammation and/or fibrosis (n = 7); (b) thickening of the alveolar walls with inflammatory cells with normal alveolar spaces (n = 3); and (c) presence of organizing alveolitis (n = 1). Parenchymal micronodules depicted presurgically (n = 4 [10%]) corresponded to bronchiolectases with peribronchiolar fibrosis (n = 4) associated with obliterative bronchiolitis in one patient. When emphysema was detected presurgically (n = 21 [51%]), it was always present at pathologic study to a higher extent than initially suspected.

OBJECTIVE: To investigate whether acute feeding induces changes in circulating leptin levels in humans and whether these changes vary according to nycthemeral cycle. METHODS: First experiment. Eighteen male subjects were given a fatty meal at 08.00 h. Blood sampling was performed for 10 h following this meal. Second experiment. Thirteen male subjects were given either a mixed meal or remained fasting either at night (starting at 01.00 h) or during the day (starting at 13.00 h). Blood samples were drawn every hour for a period of 8 h. RESULTS: First experiment. Serum leptin levels increased progressively from a mean (s.d.) baseline of 3.8 AE 2.2 ngaml to a value of 4.5 AE 2.7 ngaml (P`0.01) 8 h after the fatty meal. Second experiment. During the day, serum leptin levels increased progressively from 2.65 AE 1.7 to 3.34 AE 2.2 ngaml (P`0.001) 6 h after the test-meal and decreased from 2.68 AE 1.5 to 1.9 AE 1.1 ngaml (P`0.001) 8 h after the beginning of the fasting experiment. Similar results were obtained at night. No statistically signi®cant differences in leptin levels were observed between day and night sessions in response to feeding (mean area under the curve: 3.0 AE 4.1 vs 4.1 AE 4.1 ngaml) and fasting (72.9 AE 2.2 vs 71.5 AE 2.2 ngaml). CONCLUSION: In two independent experiments, human serum leptin levels increase following food intake. This response is not in¯uenced by nycthemeral cycle.

Whereas a significant relationship was observed between segmental and lobar air trapping and cigarette consumption, lobular air trapping was not found to reflect functional impairment at the small-airways level.

The goal of the present study was to assess the influence of mealtime on postprandial lipemia. Thirteen healthy subject aged 19-32 y were given the same meal at night (0100) or during the day (1300) in random order: the meal contained 40% of estimated daily energy expenditure. Blood samples were drawn at baseline and hourly for 8 h after the meal. Serum total cholesterol, very-low-density-lipoprotein cholesterol (VLDL-C), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), triacylglycerols, VLDL-triacylglycerols, apolipoprotein (apo) A-I, and apo B were measured at each time point. In a subgroup of seven subjects a control fasting reference line was measured according to the same nocturnal and diurnal time schedule. The mean postprandial concentrations of triacylglycerol (P < 0.001), VLDL-triacylglycerol (P < 0.001), and VLDL-C (P < 0.001) were higher at night than during the day. In contrast, mean cholesterol (P < 0.01), LDL-C (P < 0.01), HDL-C (P < 0.001), apo A-I (P < 0.001), and apo B (P < 0.001) concentrations were lower after the night meal than after the day meal. The magnitude of the postprandial response was estimated by the area between the fasting and postprandial curves. The triacylglycerol and VLDL-triacylglycerol responses were not significantly different between night and day. The VLDL-C (P < 0.01) response was greater and LDL-C (P < 0.0001) and HDL-C (P < 0.01) responses were lower at night than during the day. These results indicate that circadian factors specifically affect serum cholesterol transport. Apo B (P < 0.01) and apo A-I (P < 0.01) responses followed LDL-C and HDL-C changes during the day but were dissociated from lipoprotein responses at night, suggesting that circadian apolipoprotein regulation is dissociated from that of serum lipids. The results of the present study indicate that postprandial lipid, lipoprotein, and apolipoprotein concentrations are affected by circadian factors.