OBJECTIVE -- To determine the effect of a high-protein (HP) diet compared with a low-protein (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 TEE in response to a HP or LP meal was determined for 2 h, at weeks 0 and 12.1
RESULTS -- The mean weight loss was 4.6 [+ or -] 0.4 kg (P < 0.001), of which 4.5 [+ or -] 0.4 kg was fat (P < 0.001), with no effect of diet (P = 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 * [kcal.sup.-1] energy consumed * 2 [h.sup.-1] respectively; overall diet effect, P = 0.003). REE and TEE were reduced similarly with each of the diets (time effects, P = 0.02 and P < 0.001, respectively).
CONCLUSIONS -- In patients with type 2 diabetes, a low-fat diet with an increased protein-to-carbohydrate ratio does not significantly increase weight loss or blunt the fall in REE.
Diabetes Care 25:652-657, 2002
A 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 low-fat (30%) content, replacement of some dietary carbohydrate with protein was shown to enhance weight loss in 65 healthy over-weight 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 facilitate long-term weight loss. In nondiabetic obese and lean populations, weight loss is frequently, but not always (13), associated with a decrease in total and resting energy expenditure after an energy-restrictive diet (14,15). Recently, two small studies showed that 24-h energy expenditure (16) and REE (5) were reduced to a lesser extent in response to hypocaloric, high-protein diets (36-45% protein) than in response to low-protein diets (12-15% protein). The effect of high-protein diets on REE after weight loss in subjects with type 2 diabetes is not yet known.
The aims of this study were to compare the effects of two isocaloric diets, one high and one low in dietary protein (30% and 15% of energy, respectively) on weight loss, REE, respiratory quotient (RQ), and TEF in subjects with type 2 diabetes after energy restriction and subsequent weight maintenance.
RESEARCH DESIGN AND METHODS
Subjects
We recruited 32 Caucasian volunteers with type 2 diabetes by public advertisement. Subjects were excluded if they had proteinuria or a history of liver, unstable cardiovascular, respiratory, or gastrointestinal disease or a malignancy. All subjects gave informed written consent to participate in the study, which was approved by the Human Ethics Committees of the Commonwealth Scientific Industrial Research Organization and the Royal Adelaide Hospital.
Of those 32 subjects, 26 (15 women and 11 men) completed the study. Four subjects withdrew during the course of the study, and two subjects were not included in the analysis (one subject was unable to comply, and data for another subject was incomplete because of a computer crash). Of the remaining 26 subjects, 3 managed their diabetes by diet, 21 required oral hypoglycemics, and 2 required insulin. Subjects on antihypertensive or lipid-lowering medication were asked to maintain their same dosage throughout the study. Most subjects were sedentary at baseline and were requested to maintain their usual physical activity levels and refrain from drinking alcohol throughout the study.
Experimental design
Subjects were matched for fasting plasma glucose, BMI, age, gender, and medication and then randomly assigned to the high-protein (HP) or low-protein (LP) diet. Table 1 shows the physical characteristics of subjects at baseline. The study was conducted on an outpatient basis and consisted of an 8-week energy-restriction component (~1,600 kcal/day or 30% caloric restriction) followed by a 4-week period of the same macronutrient composition, but in an energy-balanced mix.
During weeks 0 and 12, subjects visited the Department of Medicine research clinic after fasting for at least 6 h. On each occasion, the same investigator measured height, weight, REE, and RQ. Thereafter, subjects consumed a test meal and the RQ and TEF were measured for the next 2 h. Before these visits at weeks 0 and 12, subjects were instructed to maintain similar activity and food intake, and a 24-h recall was used to assess compliance. In addition, subjects collected 24-h urine samples for assessment of urea/creatinine ratio at weeks 0, 8, and 12.
Diets
The HP diet consisted of 30% energy from protein (~110g/day) and 40% from carbohydrate, whereas the LP diet consisted of 15% energy from protein (~60 g/day) and 55% from carbohydrate. Diets were matched for fatty acid profile (8% saturated, 12% monounsaturated, and 5% polyunsaturated fatty acids). The diets were prescriptive, fixed-menu plans, and the subjects were supplied with the key foods, which made up 60% of their energy intake, to assist with dietary compliance. These included preweighed portions of beef and chicken suitable for six meals per week, shortbread biscuits, Canola Lite margarine, and Sunola oilplus (MeadowLea Foods, Mascot, Australia), Kraft Free cheese (3% fat; Kraft Foods, Melbourne, Australia), skim milk powder, and diet yogurt for the HP diet and sultanas and rice for the LP diet. Further differences between the two diets are described in detail elsewhere (17).
Every 2 weeks, subjects visited the same research dietitian, who provided detailed dietary instruction and assessment. Energy and macronutrient intakes were analyzed from 3 consecutive days (2 weekdays and 1 weekend day) of checklists from each 2-week period using Diet One Nutritional software, which is based on Australian food composition tables and food manufacturers' data (Xyris Software, Highgate Hill, Australia) (18).
Body weight and body composition measurements
Body weight was recorded in light clothing using an electronic scale. Body composition was measured by whole-body dual X-ray absorptiometry (Norland densitometer XR36; Norland Medical Systems, Fort Atkinson, WI; coefficient of variation [CV]3-4%)
Resting energy expenditure and respiratory quotient
Fasting REE and RQ were measured by indirect calorimetry using a ventilated hood and Deltatrac metabolic monitor (Datex Division Instrumentarium, Helsinki, Finland). Calibration was performed before each measurement.
Subjects lay supine on a bed in a thermoneutral environment with a clear perspex hood over their head and shoulders, and the REE and RQ were recorded for 30 min. The first 10 min of data were discarded to ensure all subjects had reached equilibrium, and the remaining 20 min of data were averaged and represented the values for fasting REE and RQ. In preliminary studies, the intraindividual CV of the Deltatrac system was established to be 2.3% for fasting REE and 5.9% for TEF.
Postprandial respiratory quotient and the thermic effect of food
