Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories.

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.

Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation.

This paper considers the argument for obesity as a chronic relapsing disease process. Obesity is viewed from an epidemiological model, with an agent affecting the host and producing disease. Food is the primary agent, particularly foods that are high in energy density such as fat, or in sugar-sweetened beverages. An abundance of food, low physical activity and several other environmental factors interact with the genetic susceptibility of the host to produce positive energy balance. The majority of this excess energy is stored as fat in enlarged, and often more numerous fat cells, but some lipid may infiltrate other organs such as the liver (ectopic fat). The enlarged fat cells and ectopic fat produce and secrete a variety of metabolic, hormonal and inflammatory products that produce damage in organs such as the arteries, heart, liver, muscle and pancreas. The magnitude of the obesity and its adverse effects in individuals may relate to the virulence or toxicity of the environment and its interaction with the host. Thus, obesity fits the epidemiological model of a disease process except that the toxic or pathological agent is food rather than a microbe. Reversing obesity will prevent most of its detrimental effects.

Markers of dietary protein intake are associated with successful weight loss in the POUNDS Lost trial.

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.

Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial.

BACKGROUND: The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. OBJECTIVES: To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. SUBJECTS/METHODS: Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. RESULTS: Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (Ptrend=0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (Ptrend=0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05). CONCLUSIONS: In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

Two-year changes in circulating adiponectin, ectopic fat distribution and body composition in response to weight-loss diets: the POUNDS Lost Trial.

BACKGROUND/OBJECTIVES: Adiponectin has a pivotal role in linking fat distribution with cardiometabolic disorders. We investigated the associations of long-term changes in circulating adiponectin with body composition and fat distribution at different abdominal depots in response to weight-loss dietary interventions, as well as the modification effect of sex. SUBJECTS/METHODS: In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial, 811 overweight or obese adults were randomly assigned to one of four diets varying in macronutrient intakes. Circulating concentrations of adiponectin were repeatedly measured at baseline, 6 months and 2 years. Body composition and fat distribution were repeatedly measured by dual-energy X-ray absorptiometry scan (n=424) and computed tomography (n=195). RESULTS: Over the 2-year intervention, after adjustment for age, sex, ethnicity, follow-up time, diet group, baseline body mass index and baseline level of respective outcome trait, increase of adiponectin was significantly associated with reduction of total fat mass (FM), total fat-free mass (FFM), whole body total percentage of fat mass (FM%), percentage of trunk fat (TF%), total adipose tissue (TAT), and adipose tissue mass at different depots including visceral (VAT), deep subcutaneous (DSAT) and superficial subcutaneous (SSAT; P<0.03 for each). The relations with FM, FM%, TF%, VAT and DSAT were significantly modified by sex (P for interaction=0.02, 0.005 and <0.001, 0.002, 0.03, respectively) with greater reductions associated with increase of adiponectin in men than in women. CONCLUSIONS: Long-term changes in circulating adiponectin were differentially associated with improvement of body composition and abdominal fat distribution in men and women.

Genetic variation of fasting glucose and changes in glycemia in response to 2-year weight-loss diet intervention: the POUNDS LOST trial.

OBJECTIVE: Weight-loss intervention through diet modification has been widely used to improve obesity-related hyperglycemia; however, little is known about whether genetic variation modifies the intervention effect. We examined the interaction between weight-loss diets and genetic variation of fasting glucose on changes in glycemic traits in a dietary intervention trial. RESEARCH DESIGN AND METHODS: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial is a randomized, controlled 2-year weight-loss trial. We assessed overall genetic variation of fasting glucose by calculating a genetic risk score (GRS) based on 14 fasting glucose-associated single nucleotide polymorphisms, and examined the progression in fasting glucose and insulin levels, and insulin resistance and insulin sensitivity in 733 adults from this trial. RESULTS: The GRS was associated with 6-month changes in fasting glucose (P<0.001), fasting insulin (P=0.042), homeostasis model assessment of insulin resistance (HOMA-IR, P=0.009) and insulin sensitivity (HOMA-S, P=0.043). We observed significant interaction between the GRS and dietary fat on 6-month changes in fasting glucose, HOMA-IR and HOMA-S after multivariable adjustment (P-interaction=0.007, 0.045 and 0.028, respectively). After further adjustment for weight loss, the interaction remained significant on change in fasting glucose (P=0.015). In the high-fat diet group, participants in the highest GRS tertile showed increased fasting glucose, whereas participants in the lowest tertile showed decreased fasting glucose (P-trend <0.001); in contrast, the genetic association was not significant in the low-fat diet group (P-trend=0.087). CONCLUSIONS: Our data suggest that participants with a higher genetic risk may benefit more by eating a low-fat diet to improve glucose metabolism.

Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration.

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.

Weight changes in obese adults 6-months after discontinuation of double-blind zonisamide or placebo treatment.

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.

Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial.

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/m(2) 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.

Calorie-sweetened beverages and fructose: what have we learned 10 years later.

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.

Diet type and changes in food cravings following weight loss: findings from the POUNDS LOST Trial.

Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment. The present study, which was part of the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults. A sample of 811 adults were recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: 1) low fat (20% of energy), average protein (15% of energy); 2) moderate fat (40%), average protein (15%); 3) low fat (20%), high protein (25%); 4) moderate fat (40%), high protein (25%). With few exceptions, the type of diet that participants were assigned did not differentially affect changes in specific food cravings. Participants assigned to the high-fat diets, however, had reduced cravings for carbohydrates at month 12 (p<0.05) and fruits and vegetables at month 24. Also, participants assigned to high-protein diets had increased cravings for sweets at month 6 and month 12 (ps<0.05). Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods (i.e., high fat foods, fast food fats, sweets, and carbohydrates/starches; all ps<0.05). Cravings for fruits and vegetables, however, were increased at month 24 (p<0.05). Calorically restricted diets (regardless of their macronutrient composition) yielded significant reductions in cravings for fats, sweets, and starches whereas cravings for fruits and vegetables were increased.

Effect of diet composition on energy expenditure during weight loss: the POUNDS LOST Study.

BACKGROUND: Weight loss reduces energy expenditure, but the contribution of different macronutrients to this change is unclear. HYPOTHESIS: We tested the hypothesis that macronutrient composition of the diet might affect the partitioning of energy expenditure during weight loss. DESIGN: A substudy of 99 participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial had total energy expenditure (TEE) measured by doubly labeled water, and resting energy expenditure (REE) measured by indirect calorimetry at baseline and repeated at 6 months in 89 participants. Participants were randomly assigned to one of four diets with either 15 or 25% protein and 20 or 40% fat. RESULTS: TEE and REE were positively correlated with each other and with fat-free mass and body fat, at baseline and 6 months. The average weight loss of 8.1 ± 0.65 kg (least-square mean ± s.e.) reduced TEE by 120 ± 56 kcal per day and REE by 136 ± 18 kcal per day. A greater weight loss at 6 months was associated with a greater decrease in TEE and REE. Participants eating the high-fat diet (HF) lost significantly more fat-free mass (1.52 ± 0.55 kg) than the low-fat (LF) diet group (P<0.05). Participants eating the LF diet had significantly higher measures of physical activity than the HF group. CONCLUSION: A greater weight loss was associated with a larger decrease in both TEE and REE. The LF diet was associated with significant changes in fat-free body mass and energy expenditure from physical activity compared with the HF diet.

Sensitivity to the satiating effects of exendin 4 is decreased in obesity-prone Osborne-Mendel rats compared to obesity-resistant S5B/Pl rats.

BACKGROUND: Osborne-Mendel (OM) rats are prone to obesity when fed a high-fat diet, whereas S5B/Pl (S5B) rats are resistant to diet-induced obesity when fed the same diet. OM rats have a decreased satiation response to fatty acids infused in the gastrointestinal tract, compared to S5B rats. One possible explanation is that OM rats are less sensitive to the satiating hormone, glucagon-like peptide 1 (GLP-1). GLP-1 is produced in the small intestine and is released in response to a meal. The current experiments examined the role of GLP-1 in OM and S5B rats. METHODS: Experiment 1 examined preproglucagon mRNA expression in the ileum of OM and S5B rats fed a high-fat (55% kcal) or low-fat (10% kcal) diet. Experiment 2 investigated the effects of a 2 h high-fat meal after a 24 h fast in OM and S5B rats on circulating GLP-1 (active) levels. Experiment 3 examined the effects of exendin-4 (GLP-1 receptor agonist) administration on the intake of a high-fat or a low-fat diet in OM and S5B rats. RESULTS: Preproglucagon mRNA levels were increased in the ileum of OM rats compared to S5B rats and were increased by high-fat diet in OM and S5B rats. OM and S5B rats exhibited a similar meal-initiated increase in circulating GLP-1 (active) levels. Exendin-4 dose dependently decreased food intake to a greater extent in S5B rats compared to OM rats. The intake of low-fat diet, compared to the intake of high-fat diet, was more sensitive to the effects of exendin-4 in these strains. CONCLUSIONS: These results suggest that though OM and S5B rats have similar preproglucagon mRNA expression in the ileum and circulating GLP-1 levels, OM rats are less sensitive to the satiating effects of GLP-1. Therefore, dysregulation of the GLP-1 system may be a mechanism through which OM rats overeat and gain weight.

Effect of a 3-day high-fat feeding period on carbohydrate balance and ad libitum energy intake in humans.

OBJECTIVE: A reduction in glycogen after the switch to an isoenergetic high-fat diet (HFD) might promote a compensatory increase in food intake to reestablish carbohydrate balance. We assessed the effect of an isoenergetic switch from a 49%-carbohydrate to 50%-fat diet on nutrient balance and ad libitum food intake. We hypothesized that carbohydrate balance would be inversely related to ad libitum energy intake. METHODS: In 47 men and 11 women (22.6+/-0.4 years; 26.1+/-0.5 kg m(-2)), fuel balance was measured in a respiration chamber over 4 days. During the first day, an isoenergetic, high-carbohydrate diet was provided followed by a 3-day isoenergetic, HFD. At the end of this period and after 16 h of fasting, three options of foods (cookies, fruit salad and turkey sandwich) were offered ad libitum for 4 h. The relationships between post-chamber ad libitum intake and macronutrient oxidation and balance measured day-to-day and over the 4-day respiration chamber stay were studied. RESULTS: After switching to a HFD, 24-h respiratory quotient decreased from 0.87+/-0.02 to 0.83+/-0.02 (P<0.0001) resulting in a 4-day cumulative carbohydrate, fat and protein balances of -183+/-368, 342+/-480 and 65+/-267 kcal, respectively. Cumulative energy balance (224+/-362 kcal per 4 days) did not influence ad libitum energy intake. However, we detected that 4-day carbohydrate balance was a positive and independent predictor of post-chamber ad libitum energy intake (R (2)=0.10; P=0.01), whereas no significant influence of fat and protein balances was found. CONCLUSION: In response to an isoenergetic change from a high-carbohydrate to HFD, higher carbohydrate balance related to increased energy intake.

Determinants of glucose tolerance in impaired glucose tolerance at baseline in the Actos Now for Prevention of Diabetes (ACT NOW) study.

AIMS/HYPOTHESIS: The aim of the study was to examine the determinants of oral glucose tolerance in 602 persons with impaired glucose tolerance (IGT) who participated in the Actos Now for Prevention of Diabetes (ACT NOW) study. METHODS: In addition to the 602 IGT participants, 115 persons with normal glucose tolerance (NGT) and 50 with impaired fasting glucose (IFG) were identified during screening and included in this analysis. Insulin secretion and insulin sensitivity indices were derived from plasma glucose and insulin during an OGTT. The acute insulin response (AIR) (0-10 min) and insulin sensitivity (S(I)) were measured with the frequently sampled intravenous glucose tolerance test (FSIVGTT) in a subset of participants. RESULTS: At baseline, fasting plasma glucose, 2 h postprandial glucose (OGTT) and HbA(1c) were 5.8 +/- 0.02 mmol/l, 10.5 +/- 0.05 mmol/l and 5.5 +/- 0.04%, respectively, in participants with IGT. Participants with IGT were characterised by defects in early (DeltaI (0-30)/DeltaG (0-30) x Matsuda index, where DeltaI is change in insulin in the first 30 min and DeltaG is change in glucose in the first 30 min) and total (DeltaI(0-120)/DeltaG(0-120) x Matsuda index) insulin secretion and in insulin sensitivity (Matsuda index and S(I)). Participants with IGT in whom 2 h plasma glucose was 7.8-8.3 mmol/l had a 63% decrease in the insulin secretion/insulin resistance (disposition) index vs participants with NGT and this defect worsened progressively as 2 h plasma glucose rose to 8.9-9.94 mmol/l (by 73%) and 10.0-11.05 mmol/l (by 80%). The Matsuda insulin sensitivity index was reduced by 40% in IGT compared with NGT (p < 0.005). In multivariate analysis, beta cell function was the primary determinant of glucose AUC during OGTT, explaining 62% of the variance. CONCLUSION: Our results strongly suggest that progressive beta cell failure is the main determinant of progression of NGT to IGT.

Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not induce weight loss in obese human subjects: energy intake predicts lack of weight loss efficacy.

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.

Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome.

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.

First versus repeat treatment with a lifestyle intervention program: attendance and weight loss outcomes.

OBJECTIVE: Following unblinding of the Diabetes Prevention Program (DPP) results, a 16-session lifestyle intervention program was offered to all study participants, including those who had initially been randomized to lifestyle treatment. This study compares the effects of the lifestyle program between participants who had previous exposure and those who had not. DESIGN: A 16-session behavioral intervention was conducted in groups at each of the 27 DPP sites during a transitional (bridge) period from the DPP trial to the DPP Outcomes Study (DPPOS). Session participation for this 6-month behavioral weight loss program was confirmed by originally randomized treatment groups. SUBJECTS AND MEASUREMENTS: Independently assessed weight measurements were available within a 7-month period before and after the program for 2808 ethnically diverse participants. RESULTS: Participants from the lifestyle group in the DPP were the least likely to attend a repeat offering of a 16-session behavioral weight loss program conducted in groups. Weight loss during the transitional lifestyle program was strongly related to the duration of attendance in the three groups that were participating in the program for the first time (metformin, placebo and troglitazone), but not related to amount of earlier weight loss. CONCLUSION: Individuals who were naive to the behavioral program lost a greater amount of weight and this was strongly related to their degree of participation. A second exposure to a behavioral weight loss program resulted in unsatisfactory low attendance rates and weight loss.

A short history of beverages and how our body treats them.

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.