Data obtained in our laboratory (1-3) as well as from others (reviewed in 4) indicate that glucose that is absorbed after the digestion of glucose-containing foods is largely responsible for the rise in the circulating glucose concentration after ingestion of mixed meals. Dietary proteins, fats, and absorbed fructose and galactose resulting from the digestion of sucrose and lactose, respectively, have little effect on blood glucose concentration.
We and others also have reported that even short-term starvation (hours) results in a dramatic decrease in the blood glucose concentration in people with type 2 diabetes (5). This seems to be due largely to a rapid, progressive decrease in the rate of glycogenolysis (5,6). Hepatic glycogen stores in turn are dependent on the content of carbohydrate in the diet (6). Thus, a reduced-carbohydrate diet should result in a lower overnight fasting glucose concentration.
To test the hypothesis that a diet that is low in carbohydrate and particularly low in food-derived glucose could lower both the fasting and the postprandial blood glucose in people with type 2 diabetes, we designed a low-carbohydrate diet in which readily digestible starch-containing foods have been de-emphasized. However, the carbohydrate content is sufficient to prevent ketosis. This is in contrast to the low-carbohydrate diets being advocated for weight loss (7). We refer to this as a low-biologically-available-glucose (LoBAG) diet. In our study, we also attempted to ensure weight stability. The effect of 5 weeks of this diet on percentage glycohemoglobin and 24-h glucose, insulin, C-peptide, [beta]-hydroxybutyrate, glucagon, triacylglycerol, and nonesterified fatty acid (NEFA) profiles in eight men with untreated type 2 diabetes is reported. Urea, creatinine, uric acid, and other data related to the metabolism of protein after ingestion of the LoBAG diet will be reported in a subsequent publication.
RESEARCH DESIGN AND METHODS
Men with mild, untreated type 2 diabetes were studied in a special diagnostic and treatment unit (SDTU; similar to a clinical research center). All participants met the National Diabetes Data Group criteria for the diagnosis of type 2 diabetes (8). Participant characteristics are given in Table 1. The study was approved by the Department of Veterans Affairs Medical Center and the University of Minnesota Committees on Human Subjects, and written informed consent was obtained from all participants. The participants did not have hematologic abnormalities, kidney disease, liver disease, macroalbuminuria (>300 mg/24 h), congestive heart failure, or untreated thyroid disease. Before the study, all participants were interviewed to determine their physical activity profile and food aversions and to explain the study process and commitment in detail. Participants confirmed that they had been weight stable for at least 3 months. They were instructed to maintain their current activity level throughout the study. Two weeks before beginning the study, the participants completed a 3-day food frequency questionnaire, with one of the days being a Saturday or a Sunday. This information was used to calculate the total food energy necessary to maintain body weight. None of the participants were being treated with oral hypoglycemic agents or insulin at the time of enrollment in the study. A 5-week randomized, crossover study design was used with a 5-week washout period between diets.
The control (15% protein) diet was designed according to the recommendations of the American Heart Association (9) and the U.S. Department of Agriculture (10,11). The diet consisted of 55% carbohydrate, with an emphasis on starch-containing foods, 15% protein, and 30% fat (10% monounsaturated, 10% polyunsaturated, and 10% saturated fatty acid). A second diet was designed to consist of 20% carbohydrate, 30% protein, and 50% fat. The saturated fatty acid content of the test diet was ~10% of total food energy; thus, the majority of the fat was mono- and polyunsaturated. This diet is referred to in the text as the LoBAG diet. The composition of the diets is given in Table 2.
Participants were randomized to begin the study with either the LoBAG or the control diet by a flip of a coin. Six participants started on the LoBAG diet, and five participants started on the control diet. Unfortunately, three of the participants who started on the control diet did not complete the study for personal reasons (death of spouse, move across country, chose not to finish). Therefore, the data are presented on eight participants who completed both arms of the study. Participants were admitted to the SDTU on the evening before the study. The next day, standardized meals that contained 55% carbohydrate, 30% fat, and 15% protein were given for breakfast, lunch, and dinner at 0800, 1200, and 1800. Participants were asked to remain in the SDTU during the study period with minimal activity.
On the second day in the SDTU, standardized meals again were given. This diet was similar for both baseline studies and is referred to as "control/pre" and "LoBAG/pre" diet in the figures, depending on which study diet followed the inpatient stay. In addition to the meals at 0800, 1200 and 1800, snacks were given at 1600 and 2100. Blood was obtained fasting at 0730, 0745, and 0800, every 15 min for the first hour after meals, every 30 min for the next 2 h, and then hourly until the next meal. Blood was drawn at a total of 46 time points. After this 24-h data accumulation period, the participants were sent home with all of the necessary food for the next 2-3 days as appropriate for the diet to which they were randomized.
Participants returned to the SDTU every 2-3 days to pick up food and meet with the study dietitian. At that time, they provided a urine specimen for analysis of creatinine and urea to determine dietary compliance. They also were weighed and had blood pressure, total glycohemoglobin (tGHb), and blood glucose measured. If their body weight decreased or increased on two successive occasions, then the total food energy of the meals was increased or decreased as appropriate to attempt to maintain weight stability throughout the study. In addition, participants were interviewed regarding dietary compliance, questions or concerns about the study, etc. At the end of the 5-week period, the participants again were admitted to the SDTU and blood was drawn as described above. At this time, the control or LoBAG meals (breakfast, lunch, dinner, and snacks) were given, as appropriate.
The plasma glucose concentration and [beta]-hydroxybutyrate concentration were determined by enzymic methods using an Analox analyzer with an [O.sub.2] electrode (Analox Instruments, London, U.K.). %tGHb was measured by boronate-affinity high-performance liquid chromatography (BioRad Variant; BioRad Labs, Hercules, CA). Serum immunoreactive insulin was measured using a standard double-antibody radioimmunoassay method using kits produced by Incstar (Stillwater, MN). Glucagon and C-peptide were measured by radioimmunoassay using kits from Linco Research (St. Louis, MO) and Diasorin (Stillwater, MN), respectively. NEFAs were measured enzymically using a kit manufactured by Wako Chemicals (Richmond, VA). Weight was determined in street clothes without shoes on a digital scale (Scalitronix, White Plains, NY). Blood pressure was measured using a Dinemap instrument (Critikon/Mediq, Pennsauken, NJ).
The net 24-h incremental area responses were calculated using the overnight fasting value as baseline. Total 24-h area responses were calculated using zero as the baseline. Both area calculations were done using a computer program based on the trapezoid rule. Statistics were determined using Student's t test for paired variates, with the Statview 512+ program (Brain Power, Calabasas, CA) for the Macintosh computer (Apple Computer, Cupertino, CA). P < 0.05 is the criterion for significance. Data are presented as the mean [+ or -] SE.
RESULTS
The average body weight was 219 [+ or -] 10 lb (99 [+ or -] 4.5 kg) and 216 [+ or -] 10 lb (98 [+ or -] 4.5 kg) at the beginning of the control and LoBAG diets, respectively (Fig. 1A). At the end of the 5 weeks on the control diet, the average body weight was 215 [+ or -] 10 lb (98 [+ or -] 4.5 kg). After 5 weeks on the LoBAG diet, the average weight was 212 [+ or -] 9 lb (96 [+ or -] 4.1 kg). Thus, the average body weight decreased by 4 lb (1.8 kg) during the 5-week study period, regardless of diet.
[FIGURE 1 OMITTED]
