OBJECTIVE -To determine the effect of a high-protein (HP) weight loss diet compared with a lower-protein (LP) diet on fat and lean tissue and fasting and postprandial glucose and insulin concentrations.RESEARCH DESIGN AND METHODS -Replacing dietary protein for carbohydrate (CHO) during energy restriction and weight loss has been effective in sparing lean mass and improving insulin sensitivity in obese subjects but has not been tested in subjects with type 2 diabetes. We compared an HP diet (28% protein, 42% CHO, 28% fat [8% saturated fatty acids, 12% monounsaturated fatty acids, 5% polyunsaturated fatty acids]) with an LP diet (16% protein, 55% CHO, 26% fat [8% saturated fatty acids, 11% monounsaturated fatty acids, 5% polyunsaturated fatty acids]) in 54 obese men and women with type 2 diabetes during 8 weeks of energy restriction (1,600 kcal) and 4 weeks of energy balance. Body composition was determined by dual-energy X-ray absorptiometry at weeks 0 and 12.RESULTS -Overall, weight loss of 5.2 Ϯ 1.8 kg was achieved independently of diet composition. However, women on the HP diet lost significantly more total (5.3 vs. 2.8 kg, P ϭ 0.009) and abdominal (1.3 vs. 0.7 kg, P ϭ 0.006) fat compared with the women on the LP diet, whereas, in men, there was no difference in fat loss between diets (3.9 vs. 5.1 kg). Total lean mass decreased in all subjects independently of diet composition. LDL cholesterol reduction was significantly greater on the HP diet (5.7%) than on the LP diet (2.7%) (P Ͻ 0.01).CONCLUSIONS -Both dietary patterns resulted in improvements in the cardiovascular disease (CVD) risk profile as a consequence of weight loss. However, the greater reductions in total and abdominal fat mass in women and greater LDL cholesterol reduction observed in both sexes on the HP diet suggest that it is a valid diet choice for reducing CVD risk in type 2 diabetes. Diabetes Care 25:425-430, 2002T ype 2 diabetes is a major public health problem in the developed world (1). Although there is a strong genetic predisposition to the development of type 2 diabetes, lifestyle and dietary factors, particularly those that promote obesity, are contributors (2). Type 2 diabetes is characterized in most subjects by insulin resistance with inadequate insulin response to maintain normoglycemia (3). Insulin resistance occurs partly as a result of increased concentrations of circulating plasma free fatty acids, released from excess adipocytes in obesity, which compete with glucose for uptake in skeletal muscle (4). In addition, hormones such as resistin (5) and cytokines such as tumor necrosis factor-␣ (6) released from adipocytes may exacerbate insulin resistance. Because ϳ90% of people with type 2 diabetes are obese, weight loss is essential in management. The optimal diet for type 2 diabetes has been the focus of much research, and there remains no consensus on macronutrient composition apart from recommendations that saturated fats be kept low (7). Energy restriction alone significantly improves glucose control and the plasma lipid pro...

Objective: Visual analogue scales are widely used in appetite research, yet the validity of these scales to evaluate appetite and mood has not been assessed in older subjects. The aim of this study was to determine the relations between food intake and visual analogue scale (VAS) ratings of appetite and nonappetite sensations in healthy older and young subjects. Design: Retrospective combined analysis of four single-blind, randomised, controlled appetite studies. Setting: All studies were conducted in the University of Adelaide, Department of Medicine, Adelaide, Australia. Subjects: A total of 45 healthy young men (n ¼ 24) and women (n ¼ 21) aged 18-35 y and 45 healthy older men (n ¼ 24) and women (n ¼ 21) aged 65-85 y were recruited by advertisement. Interventions: Oral, intraduodenal or intravenous administration of treatments which suppressed food intake were compared to control. Up to 90 min after treatment, a test meal was offered and subjects ate freely for between 30 and 60 min. Perceptions were assessed by 100-mm visual analogue scales administered at regular intervals. Results: Food intake at the test meal was positively related to perceptions of hunger, drowsiness, and calmness at both baseline and premeal (r 40.16, Po0.05), and inversely related to premeal ratings of fullness (r4 0.2, Po0.05) in both older and young subjects. Food intake was related to VAS ratings at least as strongly, if not more so, in older as in young subjects. Conclusions: These observations (i) confirm that food intake is related to perceptions of hunger and fullness as assessed by VAS in healthy older and young subjects, and (ii) suggest that sensations, not obviously associated with appetite, including 'drowsiness' and 'calmness', are also associated with food intake.

Aims/hypothesis. This study compared the long-term weight loss and health outcomes at 1-year follow-up, after a 12-week intensive intervention consisting of two low-fat, weight-loss diets, which differed in protein content. Methods. We randomly assigned 66 obese patients (BMI: 27-40 kg/m 2 ) with Type 2 diabetes to either a low-protein (15% protein, 55% carbohydrate) or high-protein diet (30% protein, 40% carbohydrate) for 8 weeks of energy restriction (~6.7 MJ/day) and 4 weeks of energy balance. Subjects were asked to maintain the same dietary pattern for a further 12 months of follow-up. Results. The study was completed by 38 of the subjects, with equal dropouts in each group. At Week 64, weight reductions against baseline were −2.2±1.1 kg (low protein) and −3.7±1.0 kg (high protein), p<0.01, with no diet effect. Fat mass was not different from baseline in either group. At Week 12, both diets reduced systolic and diastolic blood pressure by 6 and 3 mm Hg respectively, but blood pressure increased more with weight regain during follow-up in the lowprotein group (p≤0.04). At Week 64, both diets significantly increased HDL cholesterol and lowered C-reactive protein concentrations. There was no difference in the urinary urea : creatinine ratio at baseline between the two groups, but this ratio increased at Week 12 (in the high-protein group only, p<0.001, diet effect), remaining stable during follow-up in both diets. Conclusions/interpretation. A high-protein weightreduction diet may in the long term have a more favourable cardiovascular risk profile than a lowprotein diet with similar weight reduction in people with Type 2 diabetes.

Aims/hypothesis: Long-term trials in insulintreated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA 1 c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. Methods: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60±9 years, BMI 28.9±4.8 kg/m 2 ) and 15 nondiabetic obese men (age 41±21 years, BMI 34.4±4.5 kg/m 2 ) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 μg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. Results: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Δ−202±64 kcal, −23±8%, p<0.01) and obese (Δ−170±68 kcal, −16±6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. Conclusions/interpretation: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.

Aging is associated with a reduction in appetite and food intake, predisposing to protein-energy malnutrition. The causes of this "anorexia of aging" are largely unknown. To investigate possible contributions of enhanced satiating effects of cholecystokinin (CCK) and reduced stimulation of food intake by ghrelin, eight undernourished older women [age, 80.4 +/- 2.6 yr; body mass index (BMI), 16.9 +/- 0.57 kg/m(2)], eight well-nourished older women (age, 77 +/- 0.9 yr; BMI, 23.7 +/- 0.8 kg/m(2)), and eight well-nourished young women (age, 22 +/- 1.3 yr; BMI, 20.5 +/- 0.4 kg/m(2)), in randomized order, ate on 1 d a 280-kCal preload and on the other no preload, 90 min before an ad libitum meal. At baseline the undernourished, but not the well-nourished, older subjects were less hungry (P < 0.05) than young subjects. Before and after the preload, plasma CCK levels were higher (P < 0.05) in the older than young subjects, with no difference between the older groups. Plasma ghrelin concentrations were higher in the undernourished than both well-nourished groups and decreased similarly after the preload in all groups. The preload suppressed food intake in the well-nourished older and young subjects (P < 0.05), but was without effect in the undernourished old. These observations suggest that reduced basal hunger, rather than increased meal-induced satiety, contributes to the anorexia of aging and that changes in CCK and ghrelin are unlikely to be responsible.

In healthy young and older subjects, the suppression of subsequent energy intake by a liquid preload is nutrient dependent and comparable, and both satiation and satiety are related to antral area and (presumably) antral distension.

OBJECTIVE -To determine the effect of a high-protein (HP) diet compared with a lowprotein (LP) diet on weight loss, resting energy expenditure (REE), and the thermic effect of food (TEF) in subjects with type 2 diabetes during moderate energy restriction.RESEARCH DESIGN AND METHODS -In this study, 26 obese subjects with type 2 diabetes consumed a HP (28% protein, 42% carbohydrate) or LP diet (16% protein, 55% carbohydrate) during 8 weeks of energy restriction (1,600 kcal/day) and 4 weeks of energy balance. Body weight and composition and REE were measured, and the TEF in response to a HP or LP meal was determined for 2 h, at weeks 0 and 12.RESULTS -The mean weight loss was 4.6 Ϯ 0.4 kg (P Ͻ 0.001), of which 4.5 Ϯ 0.4 kg was fat (P Ͻ 0.001), with no effect of diet (P ϭ 0.6). At both weeks 0 and 12, TEF was greater after the HP than after the LP meal (0.064 vs. 0.050 kcal ⅐ kcal Ϫ1 energy consumed ⅐ 2 h Ϫ1 , respectively; overall diet effect, P ϭ 0.003). REE and TEF were reduced similarly with each of the diets (time effects, P ϭ 0.02 and P Ͻ 0.001, respectively).CONCLUSIONS -In patients with type 2 diabetes, a low-fat diet with an increased proteinto-carbohydrate ratio does not significantly increase weight loss or blunt the fall in REE. Diabetes Care 25:652-657, 2002A low-fat, high-carbohydrate diet has traditionally been advocated for type 2 diabetic patients (1); however, there is some evidence that this diet may increase plasma glucose and triacylglycerol concentrations (2,3). Combined with a lowfat (30%) content, replacement of some dietary carbohydrate with protein was shown to enhance weight loss in 65 healthy overweight and obese subjects during a controlled ad libitum diet (4) as well as in 13 obese hyperinsulinemic-normoglycemic male subjects during a hypocaloric diet (5). Although an increase in the ratio of protein to carbohydrate has been shown to lower blood glucose and plasma insulin concentrations in diabetic patients (6,7), to our knowledge, the effects of fixed-intake, energy-restricted diets, with an increased ratio of protein to carbohydrate, on weight loss and energy expenditure in type 2 diabetes have not been reported.A number of mechanisms may explain how greater weight loss can be achieved on such a diet. First, diets with an increase in the ratio of protein to carbohydrate may increase the thermic effect of food (TEF). Acute feeding studies in lean and obese nondiabetic subjects have shown that protein can exert up to three times more TEF compared with isocaloric loads of either carbohydrate or fat (8,9). Numerous studies have examined the thermogenic effect of carbohydrate in type 2 diabetes (10,11), but there is minimal information as to the thermic effect of protein in insulin-resistant states. Tappy et al. (12) showed that the thermic effect of exogenous amino acids was similar in diabetic, obese nondiabetic, and lean control subjects.The blunting of the reduction in resting energy expenditure (REE) after a decrease in weight is a second mechanism through which protein may facilitat...

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