Improvement of glucose tolerance in type 2 diabetic patients: traditional vs. modern insulin regimens (results from the Austrian Biaspart Study).

OBJECTIVE: Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet. The aim of the present study was to investigate whether meal-related (breakfast, lunch, dinner) application of biphasic insulin aspart 30 (BIAsp 30) provides better glycaemic control than administration of biphasic human insulin 30 (BHI 30) twice per day. RESEARCH DESIGN AND METHODS: In a multi-centre, randomized, open-label parallel trial, a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks. HbA1c and glycemic exposure parameters were measured at predefined intervals. RESULTS: The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08% (p = 0.6419). Analysing the 7-point blood-glucose (BG) profiles, significant differences in BG levels were observed after lunch (156 vs. 176 mg/dl, p = 0.0289), before dinner (142 vs. 166 mg/dl p = 0.006) and after dinner (154 vs. 182 mg/dl p = 0.002) in favour of BIAsp 30 insulin. Prandial BG increment was lower in the BIAsp 30 group at breakfast (p = 0.057) and lunch (p < 0.0005). No difference was found regarding safety parameters in the two treatment groups. CONCLUSIONS: This study demonstrates that meal-related BIAsp 30-insulin maintains postprandial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients.     

Influence of partial replacement of starch by sucrose in high fat-cholesterol diet on serum lipoprotein responses of cynomolgus monkeys

The influence of partial replacement of starch by sucrose on dietary cholesterol-induced serum lipoprotein responses was examined in 10 male cynomolgus monkeys (Macaca fascicularis). In a crossover design two semipurified diets provided either starch or starch and sucrose (1:1) as carbohydrate (49% by calories) with 0.4 mg cholesterol/kcal. Six weeks of starch + sucrose diet resulted in significantly reduced levels (mean +/- SE, mg/dl) of serum total cholesterol (264 +/- 9 vs 244 +/- 8) and apo B (110 +/- 6 vs 96 +/- 6) when compared with starch diet, whereas serum triglyceride levels remained similar between diets. With respect to changes in lipids and apolipoproteins (A-I or B) of very low (VLDL), low (LDL), intermediate (IDL), and high (HDL) density lipoproteins, starch + sucrose diet significantly increased VLDL-apo B (+34%), and decreased LDL-cholesterol (-18%) and LDL-apo B (-15%) as compared with starch alone; no differences were found in IDL and HDL between diets. The relative proportion of starch to sucrose in a diet appears to influence the magnitude of response of lipoproteins to dietary cholesterol.     

Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man

The aim of this study was to determine if a change in protein/carbohydrate ratio influences plasma steroid hormone concentrations. There is little information about the effects of specific dietary components on steroid hormone metabolism in humans. Testosterone concentrations in seven normal men were consistently higher after ten days on a high carbohydrate diet (468 +/- 34 ng/dl, mean +/- S.E.) than during a high protein diet (371 +/- 23 ng/dl, p less than 0.05) and were accompanied by parallel changes in sex hormone binding globulin (32.5 +/- 2.8 nmol/l vs. 23.4 +/- 1.6 nmol/l respectively, p less than 0.01). By contrast, cortisol concentrations were consistently lower during the high carbohydrate diet than during the high protein diet (7.74 +/- 0.71 micrograms/dl vs. 10.6 +/- 0.4 micrograms/dl respectively, p less than 0.05), and there were parallel changes in corticosteroid binding globulin concentrations (635 +/- 60 nmol/l vs. 754 +/- 31 nmol/l respectively, p less than 0.05). The diets were equal in total calories and fat. These consistent and reciprocal changes suggest that the ratio of protein to carbohydrate in the human diet is an important regulatory factor for steroid hormone plasma levels and for liver-derived hormone binding proteins.     

Effect of twice daily subcutaneous administration of a long-acting somatostatin analog on 24-hour plasma glucose profiles in patients with insulin-dependent diabetes mellitus

To determine the effect of twice daily subcutaneous administration of a long-acting somatostatin analog on diabetic glycemic control, seven insulin-dependent diabetic subjects were treated with mixtures of insulin (regular and lente) given 30 minutes before breakfast and supper alone or along with WY-41, 747, a long-acting somatostatin analog. Postprandial hyperglycemia was markedly reduced after breakfast and supper (peak values 123 +/- 15 vs. 207 +/- 1 mg/dl, P less than 0.01 and 150 +/- 13 vs. 235 +/- 29 mg/dl, P less than 0.02, WY-41,747 + insulin vs. insulin alone, respectively). Although values after lunch and the evening snack were not significantly different, overall mean 24 hr plasma glucose concentrations were significantly less with WY-41,747 plus insulin than with insulin alone (136 +/- 9 vs. 176 +/- 13, P less than 0.05). No serious adverse effects were noted. We conclude that administration of a long-acting somatostatin analog such as WY-41,747 twice daily along with insulin may permit some diabetic patients to achieve satisfactory glycemic control without having to inject insulin 3-4 times daily prior to each meal.     

Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats.

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.     

Glucose and fructose feeding lead to alterations in structure and function of very low density lipoproteins

Young male rats were fed regular lab chow, or a diet containing 66% of total calories as either glucose or fructose. Both experimental diets led to hypertriglyceridemia, with fasting TG concentrations after one week of 195 +/- 20 and 296 +/- 44 mg/dl for rats fed glucose and fructose, respectively, compared to 94 +/- 10 mg/dl in the control rats. Moderate changes in VLDL composition were observed with both test diets, characterized by slight increases in TG: protein ratio, and increased total cholesterol and phospholipid content. In addition, VLDL isolated from rats fed high carbohydrate diets were increased in size, with a mean VLDL particle diameter of 666 A and 720 A in glucose-fed and fructose-fed rats, as compared to 536 A in control rats. The changes in lipid composition and size of VLDL particles isolated from glucose and fructose-fed donor rats were associated with an increase in their rate of removal from the circulation following their injection into normal recipient rats (half-life time 2.4 +/- 0.2 and 3.2 +/- 0.3 min respectively) as compared to VLDL-TG derived from chow fed donors (4.1 +/- 0.2 min). These data indicate that diets high in either glucose or fructose can lead to both structural and functional changes in VLDL, and provide additional evidence that the ability of fructose to induce profound hypertriglyceridemia is not secondary to a defect in VLDL-TG catabolism.     

Metabolic and appetite responses to prolonged walking under three isoenergetic diets.

The effects of three isoenergetic diets on metabolic and appetite responses to prolonged intermittent walking were investigated. Eight men undertook three 450-min walks at intensities varying between 25-30 and 50-55% of maximal O2 uptake. In a balanced design, the subjects were given breakfast, snacks, and lunch containing total carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body mass): mixed diet, 302 CHO, 50 P, 84 F; high-CHO diet, 438 CHO, 46 P, 35 F; high-fat diet, 63 CHO, 44 P, 196 F. Substrate balance was calculated by indirect calorimetry over the 450-min exercise period. Blood samples were taken before exercise and every 45 min during the exercise period. The high-fat diet resulted in a negative total CHO balance (-140 +/- 1 g) and a lower negative fat balance (-110 +/- 33 g) than the other two diets (P < 0.05). Plasma glucagon, nonesterified fatty acids, glycerol, and 3-hydroxybutyrate were higher with the high-fat diet (P < 0.05 vs. high CHO), whereas plasma insulin was lower after high fat (P < 0.05 vs. mixed and high CHO). Subjective ratings of fatigue and appetite showed no differences between the three trials. Although diet influenced the degree of total CHO and fat oxidation, fat was the main source of energy in all trials.     

Effect of lard and corn oil intake on serum lipids in young men

An experimental diet with lard (30 g/day for 7 days) and corn oil (30 g/day for 7 days) on high carbohydrate (basal diet) was given to four healthy Japanese young men and the effect of diets containing different fat on serum lipids was examined. Serum total cholesterol was increased significantly from a basal diet of 106 +/- 23 to 141 +/- 26 mg/dl on lard diet, and then decreased significantly (p less than 0.05) to 111 +/- 22 mg/dl on corn oil diet. Serum triglycerides increased significantly (p less than 0.01) from 66 +/- 38 to 173 +/- 32 mg/dl on basal diet. Serum HDL-cholesterol was decreased significantly (p less than 0.01) from 41.9 +/- 1.6 to 31.2 +/- 3.8 mg/dl on lard diet and increased significantly (p less than 0.05) to 41.9 +/- 4.6 mg/dl on corn oil diet. Serum HDL-cholesterol fraction was decreased significantly (p less than 0.01) from 41.6 +/- 4.9 to 28.1 +/- 3.2% on basal diets, but increased significantly (p less than 0.05) to 44.3 +/- 3.1% on lard diet, and then decreased to 36.3 +/- 2.5% on corn oil diet. Serum HDL phospholipid fraction decreased significantly (p less than 0.05) from 62.5 +/- 6.7 to 50.7 +/- 1.8% on basal diet and increased significantly (p less than 0.05) to 60.4 +/- 1.0% on lard and corn oil diet. Serum phospholipids did not change by experimental diets. It is concluded that lard and corn oil have different and specific roles in lipid metabolism.     

Measurment of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins.

A sensitive and specific double antibody radio-immunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The anti-serum was raised to LDL (d 1.030-1.040 g/ml) and the LDL(2) (d 1.020-1.050 g/ml) was labeled with (125)I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02-0.5 micro g of LDL(2), had an inter-assay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an "average American diet," a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet. The control monkeys (n = 13) had a serum cholesterol of 146 +/- 28 mg/dl and an apoB of 50 +/- 18 mg/dl. In the monkeys maintained on the atherogenic diets the serum apoB was elevated: 103 +/- 28 mg/dl (American), 102 +/- 35 mg/dl (peanut oil), and 312 +/- 88 mg/dl (coconut oil). The values for serum total cholesterol were 333 +/- 65 mg/dl (American), 606 +/- 212 mg/dl (peanut oil), and 864 +/- 233 mg/dl (coconut oil) and were elevated relative to controls (P < 0.001). For each of the diets, total serum cholesterol correlated with serum apoB (P < 0.001). The slopes of the regression lines of serum apoB vs. cholesterol for the monkeys on the PMC, American, and coconut oil diets were similar (m = 0.531, 0.401, and 0.359, respectively), but differed from that of monkeys on the peanut oil diet (m = 0.121). The immunoreactivities of rhesus and human LDL were compared using specific antisera raised against these antigens. In homologous assay systems, monkey and human LDL exhibited unique immunological determinants. The same results were obtained with the delipidated preparations of the two LDLs using antisera raised against either monkey or human apoB. Crossover studies using a heterologous tracer with each anti-serum resulted in the selection of a specific population of antibodies directed against antigenic sites shared by these two LDL species.     

Effect of a high protein diet on glucose tolerance in the rat model

The purpose of this study was to determine the effects of a high protein diet on glucose tolerance. Nine Sprague Dawley rats received a high protein (HP) diet (65% protein, 35% fat) and eight rats consumed a standard chow (SC) diet over eight weeks. Oral glucose tolerance tests (OGTT) were performed at the end of the third and the seventh week. The diet did not effect glucose tolerance in the first (SC=10357+/-294 mg/dl/120 min; HP=9846+/-300 mg/dl/120 min) or the second OGTT (SC=10134+/-395 mg/dl/120 min; HP=10721+/-438 mg/dl/120 min) as reflected by the area under the glucose concentration curve. Similarly, the area under the insulin concentration curve was not effected by the high protein diet during the first (SC=49.21+/-8.46 ng/ml/120 min; HP=41.75+/-10.54 ng/ml/120 min) or the second OGTT (SC=96.63+/-13.68 ng/ml/120 min; HP=92.77+/-17.44 ng/ml/120 min). The high protein diet group experienced a delayed glucose response for the first (SC=30 min at 112+/-7 mg/dl; HP=60 min at 101+/-5 mg/dl) and second OGTT (SC=15 min at 117+/-5 mg/dl; HP=60 min at 95+/-7 mg/dl). Body mass increased to the same extent in each diet group from the initial to final weighing (SC=159+/-2 g to 254+/-7 g; HP=157+/-2 g to 242+/-7 g). Despite a delay in peak glucose response, these findings suggest that glucose tolerance and body mass were neither adversely nor positively affected by a high protein diet.     

Studies on the effect of dietary fish oil on the physical and chemical properties of low density lipoproteins in cynomolgus monkeys

To determine the effect of isocaloric substitution of dietary fish oil for lard on the physical and chemical properties of plasma low density lipoproteins (LDL), ten adult male cynomolgus monkeys were fed diets containing 11% (by weight) fish oil or lard in a crossover study consisting of two 15-week periods with a 6-week washout period in between. The atherogenic diets contained 40% of calories as fat with 0.26 mg cholesterol/kcal. Periodic measurements of plasma lipids were made throughout the study and a large blood sample was taken near the end of each 15-week period for LDL isolation and characterization, and for quantification of plasma apolipoproteins. Values for both studies were combined (mean +/- SE; n = 10) by diet. Significantly lower high density lipoprotein (HDL) cholesterol (28 +/- 2 vs. 57 +/- 8 mg/dl), apoA-I (53 +/- 11 vs. 88 +/- 7 mg/dl), and apoE (4.2 +/- 0.9 vs. 8.2 +/- 1.5 mg/dl) concentrations were found when the animals were consuming the fish oil versus the lard diet, respectively, but total plasma cholesterol (408 +/- 35 vs. 416 +/- 14 mg/dl), LDL cholesterol (356 +/- 34 vs. 331 +/- 17 mg/dl), and apoB (227 +/- 35 vs. 205 +/- 23 mg/dl) levels were not affected. LDL size was smaller during fish oil feeding (4.2 +/- 0.1 vs. 4.9 +/- 0.1 g/mumol) and LDL particle concentration was greater (2.3 +/- 0.2 vs. 1.8 +/- 0.1 microM). During fish oil feeding LDL cholesteryl esters (CE) and phospholipids (PL) were enriched in n-3 fatty acids and were relatively poor in 18:1 and 18:2 LDL CE transition temperature was about 11 degrees C lower during fish oil feeding (32 +/- 1 vs. 44 +/- 0.5 degrees C) and was positively correlated with the number of saturated, monoun-saturated, and n-6 polyunsaturated CE molecules per LDL. The results suggested that the range of transition temperatures among individual animal LDL was primarily determined by the number of monounsaturated CE, and the accumulation of n-3 polyunsaturated CE in LDL during fish oil feeding uniformly lowered the transition temperature of the LDL particle. There was a significant decrease in the percentage of LDL phosphatidylcholine (59 +/- 1 vs. 72 +/- 1%) and an increase in lysophosphatidylcholine (13 +/- 1 vs. 5 +/- 1%) and sphingomyelin (22 +/- 1 vs. 17 +/- 1%) during fish oil feeding relative to that of lard.(ABSTRACT TRUNCATED AT 400 WORDS)     

The influence of high carbohydrate diets on endurance running performance

The purpose of the present study was to examine the influence of high carbohydrate (CHO) diets on recovery of endurance capacity following a treadmill run to exhaustion. Two high CHO diets were used, one in which the normal diet was supplemented with complex carbohydrates and the other in which supplementation was achieved with simple carbohydrates. The thirty recreational runners who took part in this study (fifteen men and fifteen women) completed weighed food intake diaries two to three weeks before the start of the study. From an analysis of this information each subject's 'normal diet' was prescribed before Trial 1 and then a supplemented diet before Trial 2. The aim was to achieve an increase in carbohydrate content to 70% in the diets of the two high CHO groups and an equivalent increase in energy intake by the Control group. The subjects were required to run to exhaustion on a treadmill at a speed equivalent to 70% VO2max on two occasions separated by 3 days. After Trial 1 the subjects were divided into three equal groups. The Complex CHO group (301 +/- 86 mg vs 507 +/- 120 mg) and Simple CHO group (265 +/- 45 mg vs 462 +/- 81 mg) increased their CHO intake by approximately 70% (p less than 0.05) during the 3 days before Trial 2 whereas the Control group increased their energy intake with additional protein and fat so as to match the energy intakes of the two CHO groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of short-term diet and exercise on insulin action in individuals with abnormal glucose tolerance.

The effects of a 10-day low-calorie diet (LCD; n = 8) or exercise training (ET; n = 8) on insulin secretion and action were compared in obese men (n = 9) and women (n = 7), aged 53 +/- 1 yr, with abnormal glucose tolerance by using a hyperglycemic clamp with superimposed arginine infusion and a high-fat drink. Body mass (LCD, 115 +/- 5 vs. 110 +/- 5 kg; ET, 111 +/- 7 vs. 109 +/- 7 kg; P < 0. 01) and fasting plasma glucose (LCD, 115 +/- 10 vs. 99 +/- 4 mg/dl; ET, 112 +/- 4 vs. 101 +/- 5 mg/dl, P < 0.01) and insulin (LCD, 23.9 +/- 5.6 vs. 15.2 +/- 3.9 microU/ml; ET, 17.6 +/- 1.9 vs. 13.9 +/- 2. 4 microU/ml; P < 0.05) decreased in both groups. There was a 40% reduction in plasma insulin during hyperglycemia (0-45 min) after LCD (peak: 118 +/- 18 vs. 71 +/- 14 microU/ml; P < 0.05) and ET (69 +/- 14 vs. 41 +/- 7 microU/ml; P < 0.05) and trends for reductions during arginine infusion and a high-fat drink. The 56% increase in glucose uptake after ET (4.95 +/- 0.90 vs. 7.74 +/- 0.82 mg. min-1. kg fat-free mass-1; P < 0.01) was significantly (P < 0.01) greater than the 19% increase (5.72 +/- 1.12 vs. 6.80 +/- 0.94 mg. min-1. kg fat-free mass-1; P = not significant) that occurred after LCD. The marked increase in glucose disposal after ET, despite lower insulin levels, suggests that short-term exercise is more effective than diet in enhancing insulin action in individuals with abnormal glucose tolerance.     

Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet.

Whole body glucose disposal and skeletal muscle hexokinase, glycogen synthase (GS), pyruvate dehydrogenase (PDH), and PDH kinase (PDK) activities were measured in aerobically trained men after a standardized control diet (Con; 51% carbohydrate, 29% fat, and 20% protein of total energy intake) and a 56-h eucaloric, high-fat, low-carbohydrate diet (HF/LC; 5% carbohydrate, 73% fat, and 22% protein). An oral glucose tolerance test (OGTT; 1 g/kg) was administered after the Con and HF/LC diets with vastus lateralis muscle biopsies sampled pre-OGTT and 75 min after ingestion of the oral glucose load. The 90-min area under the blood glucose and plasma insulin concentration vs. time curves increased by 2-fold and 1.25-fold, respectively, after the HF/LC diet. The pre-OGTT fraction of GS in its active form and the maximal activity of hexokinase were not affected by the HF/LC diet. However, the HF/LC diet increased PDK activity (0.19 +/- 0.05 vs. 0.08 +/- 0.02 min(-1)) and decreased PDH activation (0.38 +/- 0.08 vs. 0.79 +/- 0.10 mmol acetyl-CoA.kg wet muscle(-1).min(-1)) before the OGTT vs. Con. During the OGTT, GS and PDH activation increased by the same magnitude in both diets, such that PDH activation remained lower during the HF/LC OGTT (0.60 +/- 0.11 vs. 1.04 +/- 0.09 mmol acetyl-CoA.kg(-1).min(-1)). These data demonstrate that the decreased glucose disposal during the OGTT after the 56-h HF/LC diet was in part related to decreased oxidative carbohydrate disposal in skeletal muscle and not to decreased glycogen storage. The rapid increase in PDK activity during the HF/LC diet appeared to account for the reduced potential for oxidative carbohydrate disposal.     

High levels of dietary carbohydrate increase glucose transport in poult intestine

The hypothesis was proposed that the carbohydrate in the first diet fed to turkey hatchlings upregulates the glucose transport system. Heavy and light body mass poults were observed to determine differences in glucose transport and carbohydrate digestion. Poults were weighed immediately posthatching. Heavy poults were at least +/-2 S.D. above the mean whereas light poults were at least +/-S.D. below the population mean (62.5 +/- 0.4). Each group was randomly assigned to one of two diets. One diet contained 50% carbohydrate and the remaining diet had 15% carbohydrate. Although the diets were isocaloric, differing carbohydrate (corn starch) and fat (cottonseed oil) content had significant effects on body masses within 3 days. Poults fed low carbohydrate weighed more than those on high carbohydrate perhaps because fat is a preferred energy substrate in the neonatal turkey. Greater carbohydrate in the diet increased glucose uptake and maltase activity compared to diets containing more fat. Heavier poults at hatching remained heavier at 3 days posthatching. No differences between body mass categories were noted in glucose uptake measurements. Thus, differences seen in growth rates may not be attributed to glucose transport in the jejunum. It is concluded that turkeys belong to the class of birds in which the poults respond to more carbohydrate in the diet by increasing plasma T(3) concentrations, upregulating the glucose transport system, and increasing enzymatic activity as with maltase.     

Hyperglycemia compensates for diet-induced insulin resistance in liver and skeletal muscle of rats

High-fat and high-sucrose diets increase the contribution of gluconeogenesis to glucose appearance (glc R(a)) under basal conditions. They also reduce insulin suppression of glc R(a) and insulin-stimulated muscle glycogen synthesis under euglycemic, hyperinsulinemic conditions. The purpose of the present study was to determine whether these impairments influence liver and muscle glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Male rats were fed a high-sucrose, high-fat, or low-fat, starch control diet for either 1 (n = 5-7/group) or 5 wk (n = 5-6/group). Studies involved two 90-min periods. During the first, a basal period (BP), [6-3H]glucose was infused. In the second, a hyperglycemic period (HP), [6-3H]glucose, [6-14C]glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 +/- 1.5 mg/dl; HP: 172.3 +/- 1.5 mg/dl), insulin (BP: 2.5 +/- 0.2 ng/ml; HP: 4.9 +/- 0.3 ng/ml), and glucagon (BP: 81.8 +/- 1.6 ng/l; HP: 74.0 +/- 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among groups in the glucose infusion rate (mg x kg(-1) x min(-1)) necessary to maintain arterial glucose concentrations at approximately 170 mg/dl (pooled average: 6.4 +/- 0.8 at 1 wk; 6.4 +/- 0.7 at 5 wk), percent suppression of glc R(a) (44.4 +/- 7.8% at 1 wk; 63.2 +/- 4.3% at 5 wk), tracer-estimated net liver glycogen synthesis (7.8 +/- 1.3 microg x g liver(-1) x min(-1) at 1 wk; 10.5 +/- 2.2 microg x g liver(-1) x min(-1) at 5 wk), indirect pathway glycogen synthesis (3.7 +/- 0.9 microg x g liver(-1) x min(-1) at 1 wk; 3.4 +/- 0.9 microg x g liver(-1) x min(-1) at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 +/- 0.3 microg x g muscle(-1) x min(-1) at 1 wk; 1.6 +/- 0.3 microg x g muscle(-1) x min(-1) at 5 wk). These data suggest that hyperglycemia compensates for diet-induced insulin resistance in both liver and skeletal muscle.     

Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone and pyruvate

The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on metabolic responses and endurance capacity during leg exercise were determined in eight untrained males (20-30 yr). During the 7 days before exercise, a high-carbohydrate diet was consumed (70% carbohydrate, 18% protein, 12% fat; 35 kcal/kg body weight). One hundred grams of either Polycose (placebo) or dihydroxyacetone and pyruvate (treatment, 3:1) were substituted for a portion of carbohydrate. Dietary conditions were randomized, and subjects consumed each diet separated by 7-14 days. After each diet, cycle ergometer exercise (70% of peak oxygen consumption) was performed to exhaustion. Biopsy of the vastus lateralis muscle was obtained before and after exercise. Blood samples were drawn through radial artery and femoral vein catheters at rest, after 30 min of exercise, and at exercise termination. Leg endurance was 66 +/- 4 and 79 +/- 2 min after placebo and DHAP, respectively (P less than 0.01). Muscle glycogen at rest and exhaustion did not differ between diets. Whole leg arteriovenous glucose difference was greater (P less than 0.05) for DHAP than for placebo at rest (0.36 +/- 0.05 vs. 0.19 +/- 0.07 mM) and after 30 min of exercise (1.06 +/- 0.14 vs. 0.65 +/- 0.10 mM) but did not differ at exhaustion. Plasma free fatty acids, glycerol, and beta-hydroxybutyrate were similar during rest and exercise for both diets. Estimated total glucose oxidation during exercise was 165 +/- 17 and 203 +/- 15 g after placebo and DHAP, respectively (P less than 0.05). It is concluded that feeding of DHAP for 7 days in conjunction with a high carbohydrate diet enhances leg exercise endurance capacity by increasing glucose extraction by muscle.     

Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects

To understand the day-to-day pathophysiology of impaired muscle glycogen storage in type 2 diabetes, glycogen concentrations were measured before and after the consumption of sequential mixed meals (breakfast: 190.5 g carbohydrate, 41.0 g fat, 28.8 g protein, 1253 kcal; lunch: 203.3 g carbohydrate, 48.1 g fat, 44.0 g protein, 1497.5 kcal) by use of natural abundance (13)C magnetic resonance spectroscopy. Subjects with diet-controlled type 2 diabetes (n = 9) and age- and body mass index-matched nondiabetic controls (n = 9) were studied. Mean fasting gastrocnemius glycogen concentration was significantly lower in the diabetic group (57.1 +/- 3.6 vs. 68.9 +/- 4.1 mmol/l; P < 0.05). After the first meal, mean glycogen concentration in the control group rose significantly from basal (97.1 +/- 7.0 mmol/l at 240 min; P = 0.005). After the second meal, the high level of muscle glycogen concentration in the control group was maintained, with a further rise to 108.0 +/- 11.6 mmol/l by 480 min. In the diabetic group, the postprandial rise was markedly lower than that of the control group (65.9 +/- 5.2 mmol/l at 240 min, P < 0.005, and 70.8 +/- 6.7 mmol/l at 480 min, P = 0.01) despite considerably greater serum insulin levels (752.0 +/- 109.0 vs. 372.3 +/- 78.2 pmol/l at 300 min, P = 0.013). This was associated with a significantly greater postprandial hyperglycemia (10.8 +/- 1.3 vs. 5.3 +/- 0.2 mmol/l at 240 min, P < 0.005). Basal muscle glycogen concentration correlated inversely with fasting blood glucose (r = -0.55, P < 0.02) and fasting serum insulin (r = -0.57, P < 0.02). The increment in muscle glycogen correlated with initial increment in serum insulin only in the control group (r = 0.87, P < 0.002). This study quantitates for the first time the subnormal basal muscle glycogen concentration and the inadequate glycogen storage after meals in type 2 diabetes.     

Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice

Two month old C57BL/6 mice were placed on three different diets: 1) normal diet (NC; 0.025% cholesterol), 2) hypercholesterolemic Western-type diet (HC-W; 0.2% cholesterol), and 3) hypercholesterolemic Paigen-type diet (HC-P; 1.25% cholesterol plus 0.5% cholic acid). At 6 months of age, the animals underwent ligation of the left carotid artery and were randomly assigned to vehicle (PBS, subcutaneous) or angiotensin II (Ang II; 1.4 mg/kg/day, subcutaneous) treatment for 4 weeks. Low density lipoprotein-cholesterol levels were similarly increased in both HC diets (NC, 4 +/- 3 mg/dl; HC-W, 123 +/- 17 mg/dl; HC-P, 160 +/- 14 mg/dl). However, the levels of high density lipoprotein-cholesterol (HDL-C) were reduced only in animals fed the HC-P diet (NC, 82 +/- 6 mg/dl; HC-W, 79 +/- 7 mg/dl; HC-P, 58 +/- 7 mg/dl). In Ang II-treated mice, carotid artery ligation induced intimal smooth muscle cell proliferation to a similar extent in NC- and HP-W-fed animals. However, a significantly larger intimal area developed in ligated vessels from Ang II-treated mice fed the HC-P diet (3.6-fold higher than in Ang II-treated NC mice). Together, these results show the accelerating effect of mild hypercholesterolemia, reduced HDL-C levels, and Ang II on intimal hyperplasia after carotid artery ligation in mice.     

Evaluation of the new software program DegifXL4 in the determination of the glycaemic indices of foodstuffs

Aims: There is no standardized protocol for measuring glycemic index (GI) that takes time-of-day effects into account. The software DegifXL2 and Medtronic-Minimed's CGMS and Solutions, makes the GI calculation at breakfast and dinner time possible. The aim of this study was to assess the enhanced data processing software (DegifXL4) enabling the GI calculation at breakfast, lunch, afternoon snack and dinner times. Methods: The glucose levels of 20 healthy volunteers were monitored after they consumed either 50 g of glucose or one of ten alternative foodstuffs either for breakfast and dinner or for lunch or snack. Within the 9-day test period, 10 such meals were monitored in 3 replicates for each volunteer. Specifically, CGMS was used to monitor plasma glucose levels at 5-minute intervals for a period of 120 min following the foodstuff ingestion. Results: Using the enhanced spreadsheed DegifXL 4, a total of 640 profiles were obtained and 491 (77 %) accomplished the criteria for further processing. The percentage of successful tests in each foodstuff varied from 57 to 87 %. Conclusions: The use of the new software DegifXL4 offers accurate GI estimates for foodstuffs eaten for breakfast, lunch, snacks and dinners in three replicates. In combination with the CGMS Solutions Software is DegifXL4 an enhanced efficient and comfortable way to routinely measure GI values.