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Summary: Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference ‘Diet and Cardiometabolic Health – Beyond Calories’, and this paper summarizes the presentations and follow‐up discussions. Regarding the health effects of dietary fat, sugar and non‐nutritive sweeteners, it is concluded that food‐specific saturated fatty acids and sugar‐sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential ‘beyond calories’ mechanisms may lead to new strategies for attenuating the obesity crisis. [ABSTRACT FROM AUTHOR]

To assess the association of markers for dietary protein intake, measures of dietary adherence and demographic variables with weight loss in the POUNDS Lost study over the first 6 months and again between 6 and 24 months using data from those who completed each period. This is a secondary analysis of pooled data on completers assigned to one of four diets: 65%C/15%P/20%F (AP/LF), 55%C/25%P/20%F (HP/LF), 45%C/15%P/40%F (AP/HF) or 35%C/25%P40%F (HP/HF) in the POUNDS Lost study. Urinary nitrogen excretion, dietary adherence measured by 24-h recall and attendance at sessions, age (above and below 50 years), gender, race/ethnicity and activity by pedometry were analysed. Increased spread between protein intake at baseline and protein at 6 or 24 months, assessed by urinary nitrogen excretion, was associated with greater weight loss from baseline to 2 years. At 6 and 24 months, older age, male gender, body mass index > 30 kg m-2 and adherence to the fat and protein diets were associated with more weight loss. None of these variables was associated with a regain from 6 to 24 months. Weight regain for women in the highest carbohydrate (65%) group was significantly greater (-4.4 kg [95% CI: -5.9, -3.0]) than for women in the lowest carbohydrate group (-1.8 kg [95% CI: -3.2, -0.4 kg]) (P for interaction = 0.012). An increased spread in the difference between baseline and follow-up protein intake was associated with greater weight loss, consistent with the 'protein spread theory'. Women eating the highest carbohydrate diet regained more weight from 6 to 24 months. [ABSTRACT FROM AUTHOR]

Objective Diabetic nephropathy is characterized at its onset by glomerular hyperfiltration. Prospective studies in humans measuring filtration rates with weight gain are lacking. We investigated renal filtration following weight gain induced by overfeeding. Design Eight weeks of overfeeding (40% above energy requirements, 44% fat, 15% protein and 41% carbohydrate) as well as a 6-month follow-up after the overfeeding intervention. Subjects Thirty-five participants (age: 26.7 ±5.3 years; body mass index: 25.5 ± 2.2 kg m−2; 29 m/6f). Measurements Creatinine clearance rate (Ccr) from 24-h urine collection, estimated glomerular filtration rate ( eGFR) from the modification of diet in renal disease ( MDRD), insulin sensitivity/glucose disposal rate ( GDR) by a euglycemic-hyperinsulinemic clamp, components from basic metabolic panels and serum lipid panels. Results Both eGFR and Ccr increased with overfeeding ( P = 0.04) and serum lipids (all P < 0.05), along with a decrease in insulin sensitivity ( P = 0.003). Fasting glucose concentration was not affected ( P = 0.98), but the per cent change in Ccr correlated positively with the change in GDR with overfeeding ( r = 0.39, P = 0.02). Six months following overfeeding, serum glucose was maintained, and no evidence of urinary glucose was observed at any time-point. Conclusions These data suggest that renal hyperfiltration may act as a mechanism to preserve insulin sensitivity through maintenance of systemic glucose homoeostasis with caloric excess. [ABSTRACT FROM AUTHOR]

Aims This study examined the effects of pioglitazone on body weight and bone mineral density ( BMD) prospectively in patients with impaired glucose tolerance as pioglitazone ( TZD) increases body weight and body fat in diabetic patients and increases the risk of bone fractures. Methods A total of 71 men and 163 women aged 49.3 (10.7) years [mean (s.d.)]; body mass index ( BMI), 34.5 (5.9) kg/m2 were recruited at five sites for measurements of body composition by dual energy X-ray absorptiometry at baseline and at conversion to diabetes or study end, if they had not converted. Results Mean follow-up was 33.6 months in the pioglitazone group and 32.1 months in the placebo group. Body weight increased 4.63 ± 0.60 (m ± s.e.) kg in the pioglitazone group compared to 0.98 ± 0.62 kg in the PIO group (p < 0.0001). Body fat rose 4.89 ± 0.42 kg in the pioglitazone group compared to 1.41 ± 0.44 kg, (p < 0.0001) in placebo-treated subjects. The increase in fat was greater in legs and trunk than in the arms. BMD was higher in all regions in men and significantly so in most. PIO decreased BMD significantly in the pelvis in men and women, decreased BMD in the thoracic spine and ribs of women and the lumbar spine and legs of men. Bone mineral content also decreased significantly in arms, legs, trunk and in the total body. Conclusions Pioglitazone increased peripheral fat more than truncal fat and decreased BMD in several regions of the body. [ABSTRACT FROM AUTHOR]

What is already known about this subject Consumption of high-fructose corn syrup (HFCS) beverages may play a role in the epidemic of obesity., Fructose from sugar (sucrose) is just as bad as from HFCS., Soft Drink consumption related to risk of obesity, diabetes, and CVD in adults and children., What this study adds Non-alcoholic fatty liver increased by consuming fructose in containing beverages., Consumption of sugar sweetened beverages, fruit drinks and probably fruit juice may mimic metabolic syndrome., Reducing intake of calorically sweetened beverages slows weight gain., Background Sugar-sweetened drinks and the fructose they provide are associated with several health problems. Methods Data from the Nielsen Homescan and product content were analysed for sweetener type using the Gladson Nutrition Database. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. Results Over 70% of all foods contain some amounts of added sugar, and consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages is related to the risk of diabetes, the metabolic syndrome and cardiovascular disease in adults and in children. Drinking two sugar-sweetened beverages per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized, controlled trials in children and adults lasting from 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Genetic factors influence the weight gain when drinking soft drinks. Conclusion Consumption of calorie-sweetened beverages and the fructose they contain has continued to increase and may play a role in the epidemic of obesity, the metabolic syndrome and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain and metabolic improvement as well. [ABSTRACT FROM AUTHOR]

MK-0493 is a novel, potent, and selective agonist of the melanocortin receptor 4 (MC4R), one of the best-validated genetic targets and considered one of the most promising for the development of antiobesity therapeutics. An ad libitum energy-intake model was qualified with excellent reproducibility: the geometric mean ratio (GMR) with 95% confidence interval (CI) for total energy intake over a period of 24 h for 30 mg sibutramine/placebo was 0.82 (0.76, 0.88), and for 10 mg sibutramine/placebo it was 0.98 (0.91, 1.05). MK-0493 showed a small and marginally significant effect on 24-h energy intake, whereas 30 mg of sibutramine caused a significant reduction in total 24-h energy intake; specifically, the GMR (95% CI) for 30 mg sibutramine/placebo was 0.79 (0.74, 0.85). MK-0493 was associated with modest weight reduction from baseline but had only small, statistically insignificant effects relative to placebo after 12 weeks in a fixed-dose study and also after 18 weeks of stepped-titration dosing. We conclude that agonism of MC4R is not likely to represent a viable approach to the development of antiobesity therapeutics. [ABSTRACT FROM AUTHOR]

Background: Treatment with thiazolidinediones (TZDs) produces weight gain. Objective: To test whether a portion control diet could prevent weight gain during treatment with pioglitazone in patients with type 2 diabetes mellitus (T2DM). Design: This 16-week randomized, open-label, parallel arm study compared three groups: (i) pioglitazone plus the American Diabetes Association diet (Pio + ADA); (ii) pioglitazone plus a portion control weight loss diet (Pio + PC); (iii) metformin plus the American Diabetes Association diet (Met + ADA). All participants received the same advice about calorie reduction, lifestyle change and exercise. Methods: Fifty-one men and women with T2DM, naive to TZDs, were randomized to a 16-week study. Pioglitazone (Pio) was titrated to a dose of 45 mg/day and metformin (Met) to a dose of 2 g/day. Fasting blood was collected for lipids, insulin and glycosylated haemoglobin A1c (HbA1c) at baseline and 16 weeks. Results: Forty-eight of fifty-one randomized subjects completed the study. Patients treated with Pio + ADA gained 2.15 ± 1.09 kg (mean ± SD) compared with a weight loss of 2.59 ± 1.25 kg (p < 0.05) in the Pio + PC group, and a weight loss of 3.21 ± 0.7 kg (p < 0.05) in the Met + ADA group. Waist circumference and visceral adipose tissue decreased significantly more in the Pio + PC group than in the Pio + ADA group. High-density lipoprotein cholesterol levels were significantly increased in the Pio + PC group compared with the Met + ADA group. Pioglitazone reduced insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) more than metformin. No significant differences between groups were seen for glucose, insulin, HbA1c or low-density lipoprotein cholesterol levels. Conclusions: Pio + PC, prevented weight gain, reduced waist circumference and visceral fat compared with Pio + ADA diet. [ABSTRACT FROM AUTHOR]

Good Calories, Bad Calories has much useful information and is well worth reading. Gary Taubes's tenets related to obesity can be summarized in four statements (i) He believes that you can gain weight and become obese without a positive energy balance; (ii) He also believes that dietary fat is unimportant for the development of obesity; (iii) Carbohydrate, in his view, is what produces obesity and (iv) Insulin secreted by the carbohydrate is the problem in obesity. However, some of the conclusions that the author reaches are not consistent with current concepts about obesity. There are many kinds of obesity, and only some depend on diet composition. Two dietary manipulations produce obesity in susceptible people: eating a high-fat diet and drinking sugar- or high-fructose corn syrup-sweetened beverages. Insulin is necessary but not sufficient in the diet-dependent obesities. When diet is important, it may be the combination of fat and fructose (the deadly duo) that is most important. Regardless of diet, it is a positive energy balance over months to years that is the sine qua non for obesity. Obese people clearly eat more than do lean ones, and food-intake records are notoriously unreliable, as documented by use of doubly labelled water. Underreporting of food intake is greater in obese than in normal-weight people and is worse for fat than for other macronutrient groups. Accepting the concept that obesity results from a positive energy balance does not tell us why energy balance is positive. This depends on a variety of environmental factors interacting with the genetic susceptibility of certain individuals. Weight loss is related to adherence to the diet, not to its macronutrient composition. [ABSTRACT FROM AUTHOR]

Numerous studies have demonstrated that beverages containing sugar, high fructose corn syrup (HFCS) or alcohol are handled differently by the body than when sugar or HFCS are incorporated in solid foods and as a result the overall caloric intake from solid food does not adjust to account for the calories in these beverages. A consideration of our evolutionary history may help to explain our poor compensatory response to calories from fluids. This paper reviews the history of eight important beverages: milk, beer, wine, tea, coffee, distilled alcoholic beverages, juice and soft drinks. We arrive at two hypotheses. First, humans may lack a physiological basis for processing carbohydrate or alcoholic calories in beverage because only breast milk and water were available for the vast majority of our evolutionary history. Alternatives to those two beverages appeared in the human diet no more than 11 000 years ago, but Homo sapiens evolved between 100 000 and 200 000 years ago. Second, carbohydrate and alcohol-containing beverages may produce an incomplete satiation sequence which prevents us from becoming satiated on these beverages. [ABSTRACT FROM AUTHOR]

Crack-tip plasticity in textured aluminium alloys was numerically analysed using an anisotropic yield function and an isotropic hardening law as the material constitutive response. Four real textures obtained from extrusions of rectangular and square shapes as well as five ideal textures typical of rolled products were considered and predicted crack-tip plastic zones were compared with those obtained using the isotropic von Mises yield criterion. The use of the anisotropic yield function revealed important differences in crack-tip plasticity compared with the isotropic case. The plastic zone features obtained for different textures were compared to single crystal results published in the open literature and similar crack-tip plastic strain localization was observed. [ABSTRACT FROM AUTHOR]

The efficacy and safety of an advanced category recombinant antihaemophilic factor produced by a plasma- and albumin-free method (rAHF-PFM) was studied in 111 previously treated subjects with haemophilia A. The study comprised a randomized, double-blinded, crossover pharmacokinetic comparison of rAHF-PFM and RECOMBINATE rAHF (R-FVIII); prophylaxis (three to four times per week with 25–40 IU kg−1 rAHF-PFM) for at least 75 exposure days; and treatment of episodic haemorrhagic events. Median age was 18 years, 96% of subjects had baseline factor VIII<1%, and 108 received study drug. Bioequivalence, based on area under the plasma concentration vs. time curve and adjustedin vivorecovery, was demonstrated for rAHF-PFM and R-FVIII. Mean (±SD) half-life for rAHF-PFM was 12.0 ± 4.3 h. Among 510 bleeding events, 473 (93%) were managed with one or two infusions of rAHF-PFM and 439 (86%) had efficacy ratings of excellent or good. Subjects who were less adherent to the prophylactic regimen had a higher bleeding rate (9.9 episodes subject−1 year−1) than subjects who were more adherent (4.4 episodes subject−1 year−1;P < 0.03). One subject developed a low titre, non-persistent inhibitor (2.0 BU) after 26 exposure days. These data demonstrate that rAHF-PFM is bioequivalent to R-FVIII, and suggest that rAHF-PFM is efficacious and safe, without increased immunogenicity, for the treatment of haemophilia A. [ABSTRACT FROM AUTHOR]

Measurements of factor VIII (FVIII) recovery in previously untreated patients with haemophilia A were done as part of the clinical trial of safety and efficacy of the recombinant FVIII, Recombinate™. In 22 of 72 assessable patients, positive inhibitor titres ≥0.6 Bethesda units mL[sup -1] were detected by the Bethesda assay in one or more plasma samples, and the remaining 50 patients were negative at all timepoints. Of the latter group, 16 individuals without inhibitors unexpectedly had both normal (111) and low (52) recoveries during the study. We investigated the possibility that other antibodies not detectable in the Bethesda assay were responsible for the low recovery, by using a highly sensitive immunopreciptation (IP) assay for detection of all antiFVIII antibodies. Eight of the 16 patients with low and normal recoveries did indeed have antibodies detected by the IP assay, and the remaining eight were negative. Four antibody-positive individuals had insignificantly low titres, and the other four had modest to high titres. In the latter group, antibodies were found with similar frequencies and titre in plasmas from patients with low or normal recovery. Low recovery in haemophilia A patients without inhibitor titres must therefore be attributed to factors other than antiFVIII. [ABSTRACT FROM AUTHOR]

RationaleStudies have shown that risperidone is safe and efficacious in young and middle-aged adults with chronic schizophrenia, but considerably fewer data are availabale on the treatment of elderly patients with schizophrenia or other psychotic disorders, particularly long-term outcomes. ObjectiveA 12-month, open-label study was conducted to assess the effects of risperidone in elderly, chronically ill, psychotic patients. MethodsThis study enrolled 180 elderly, chronically ill, psychotic patients (median age, 72 years [range 54–89]), 97 of whom completed the 12-month study. At endpoint, the mean dose of risperidone was 3.7 mg/day. ResultsClinical improvement (≥20% reduction in Positive and Negative Syndrome Score [PANSS] total score) was achieved by 54% of patients at endpoint. There were significant reductions in PANSS total, subscale (positive, negative, and general psychopathology), and cognition cluster scores at endpoint (p <0.001). Clinical Global Impressions severity of illness scores showed continued improvement through month 12 (p <0.001). In contrast, PANSS data from a historical comparable control group of patients receiving conventional antipsychotic agents showed no symptom improvement over a 12-month treatment period. The severity of preexisting extrapyramidal symptoms (EPS) in patients treated with risperidone decreased significantly from baseline to endpoint (p <0.001), and the use of antiparkinsonian medication decreased from 41.1% of patients before the trial to 25.6% during the trial. There were no spontaneous reports of tardive dyskinesia (TD) and the incidence of assessed TD was 4.3% in contrast to the expected 26% reported in middle-aged and elderly patients receiving conventional antipsychotic agents for 1 year. ConclusionsLong-term treatment with risperidone was associated with continued symptom improvement, a decrease in the severity of preexising EPS, and a low incidence of TD in elderly psychotic patients. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We evaluated weight changes in obese patients at 6-months after they ended participation in a 12-month randomised controlled trial in which they received daily placebo, zonisamide 200 mg or zonisamide 400 mg, in addition to lifestyle counselling. Of the originally randomised 225 patients, 218 completed month-12 when study interventions were discontinued. For the 154 patients who returned for 6-month follow-up off-treatment, weight changes between month-12 and month-18 for placebo (n = 53), zonisamide 200 mg (n = 49) and zonisamide 400 mg groups (n = 52) were 0.5 kg [95% confidence interval ( CI), −0.8 to 1.8; 0.7%], 1.5 kg (0.2-2.8; 1.6%; p = 0.26 vs. placebo) and 2.4 kg (1.1-3.7; 2.6%; p = 0.04 vs. placebo), respectively. Our results suggest that although zonisamide 400 mg daily for 12-months resulted in greater weight loss than with placebo, weight regain after discontinuation of interventions was greater in the zonisamide 400 mg group than placebo group. [ABSTRACT FROM AUTHOR]

This is a case report of an elderly hypertensive patient with mania relatively unresponsive to neuroleptics, whose illness was effectively controlled with verapamil in both the acute and the maintenance phase of treatment. [ABSTRACT FROM AUTHOR]

Twenty-one patients, 14 with haemophilia A and seven with haemophilia B, completed a double-blind crossover study to evaluate the effects of danazol on factor VIII and factor IX levels. Clotting and immunoradiometric assays were used to measure factor levels at baseline, 2 weeks and 8 weeks on both danazol and placebo. Fibrinogen, plasminogen and activated partial thromboplastin time were measured on all patients during placebo and danazol treatment. Although plasminogen levels rose significantly (P less than 0.01) and fibrinogen decreased (P less than 0.01), factor VIII and IX levels did not change. While on danazol, three patients had increased bleeding and shortened euglobulin lysis times compared to their baseline levels. We conclude that danazol does not raise factor VIII or IX levels and increases bleeding in some patients.