https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)60283-9.pdf

Prediabetes: a high-risk state for diabetes development

Background Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power. Methods We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. Results A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five...

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Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance

The striking and unexpected relative risk reductions in cardiovascular (CV) mortality (38%), hospitalization for heart failure (35%), and death from any cause (32%) observed in the EMPA-REG OUTCOME trial using an inhibitor of sodium-glucose cotransporter 2 (SGLT2) in patients with type 2 diabetes and high CV risk have raised the possibility that mechanisms other than those observed in the trial-modest improvement in glycemic control, small decrease in body weight, and persistent reductions in blood pressure and uric acid level-may be at play. We hypothesize that under conditions of mild, persistent hyperketonemia, such as those that prevail during treatment with SGLT2 inhibitors, β-hydroxybutyrate is freely taken up by the heart (among other organs) and oxidized in preference to fatty acids. This fuel selection improves the transduction of oxygen consumption into work efficiency at the mitochondrial level. In addition, the hemoconcentration that typically follows SGLT2 inhibition enhances oxygen release to the tissues, thereby establishing a powerful synergy with the metabolic substrate shift. These mechanisms would cooperate with other SGLT2 inhibition-induced changes (chiefly, enhanced diuresis and reduced blood pressure) to achieve the degree of cardioprotection revealed in the EMPA-REG OUTCOME trial. This hypothesis opens up new lines of investigation into the pathogenesis and treatment of diabetic and nondiabetic heart disease.

https://care.diabetesjournals.org/content/diacare/39/7/1108.full.pdf

CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis.

The role of dietary protein in weight loss and weight maintenance encompasses influences on crucial targets for body weight regulation, namely satiety, thermogenesis, energy efficiency, and body composition. Protein-induced satiety may be mainly due to oxidation of amino acids fed in excess, especially in diets with "incomplete" proteins. Protein-induced energy expenditure may be due to protein and urea synthesis and to gluconeogenesis; "complete" proteins having all essential amino acids show larger increases in energy expenditure than do lower-quality proteins. With respect to adverse effects, no protein-induced effects are observed on net bone balance or on calcium balance in young adults and elderly persons. Dietary protein even increases bone mineral mass and reduces incidence of osteoporotic fracture. During weight loss, nitrogen intake positively affects calcium balance and consequent preservation of bone mineral content. Sulphur-containing amino acids cause a blood pressure-raising effect by loss of nephron mass. Subjects with obesity, metabolic syndrome, and type 2 diabetes are particularly susceptible groups. This review provides an overview of how sustaining absolute protein intake affects metabolic targets for weight loss and weight maintenance during negative energy balance, i.e., sustaining satiety and energy expenditure and sparing fat-free mass, resulting in energy inefficiency. However, the long-term relationship between net protein synthesis and sparing fat-free mass remains to be elucidated.

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Dietary Protein, Weight Loss, and Weight Maintenance

The obesity epidemic is among the greatest public health challenges facing the modern world. Regarding dietary causes, most emphasis has been on changing patterns of fat and carbohydrate consumption. In contrast, the role of protein has largely been ignored, because (i) it typically comprises only approximately 15% of dietary energy, and (ii) protein intake has remained near constant within and across populations throughout the development of the obesity epidemic. We show that, paradoxically, these are precisely the two conditions that potentially provide protein with the leverage both to drive the obesity epidemic through its effects on food intake, and perhaps to assuage it. We formalize this hypothesis in a mathematical model. Some supporting epidemiological, experimental and animal data are presented, and predictions are made for future testing.

Obesity: the protein leverage hypothesis

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)16986-9.pdf

Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss?

The rising rate of obesity has been blamed on increased consumption of sugar-sweetened soft drinks, such as carbonated sodas, which fail to satisfy hunger. The objective of the present study was to compare the effect on appetite and energy intake of a sugar-sweetened beverage (cola) and a chocolate milk drink, matched for energy content and volume. It was hypothesised that chocolate milk may be more satiating because of its protein content. Twenty-two healthy young men (age 23 (SD 1 x 8) years) of normal weight (BMI 22 x 2 (SD 1 x 5) kg/m2) were recruited to the randomised cross-over study. Visual analogue scales were used to record subjective appetite ratings every 30 min on each of two test days. A drink of 500 ml cola or chocolate milk (900 kJ) was ingested 30 min before an ad libitum lunch. Satiety and fullness were significantly greater (P=0 x 0007, P=0 x 0004, respectively) 30 min after chocolate milk than after cola. Ratings of prospective consumption and hunger were significantly greater after cola than after chocolate milk, both immediately after preload intake (P=0 x 008, P=0 x 01, respectively) and 30 min afterwards (P=0 x 004, P=0 x 01, respectively). There was no significant difference (P=0 x 42) in ad libitum lunch intake after ingestion of chocolate milk (3145 (SD 1268) kJ) compared with cola (3286 (SD 1346) kJ). The results support the hypothesis that sweetened soft drinks are different from milk products in their impact on short-term hunger and satiety, although differences in subjective appetite scores were not translated into differences in energy intake.

/pdf/increased-satiety-after-intake-of-a-chocolate-milk-drink-2g18wx5vaz.pdf

Increased satiety after intake of a chocolate milk drink compared with a carbonated beverage, but no difference in subsequent ad libitum lunch intake.

Background: The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites. Methodology/Principal Findings: In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p,0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 2764 kg/m 2 ) versus non-carriers (mean BMI: 2865 kg/m 2 )( p.0.05) could be shown. Conclusions/Significance: In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.

/pdf/family-and-population-based-studies-of-variation-within-the-30072pjc81.pdf

A Harper

Papers

Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss?

Increased satiety after intake of a chocolate milk drink compared with a carbonated beverage, but no difference in subsequent ad libitum lunch intake.

Family and Population-Based Studies of Variation within the Ghrelin Receptor Locus in Relation to Measures of Obesity

Can we advise our obese patients to follow the Atkins diet

2003 William J. Stickel Silver Award. Skin temperatures as a one-time screening tool do not predict future diabetic foot complications