Deleterious metabolic effects of high-carbohydrate, sucrose-containing diets in patients with non-insulin-dependent diabetes mellitus

The effects of variations in dietary carbohydrate and fat intake on various aspects of carbohydrate and lipid metabolism were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM). Two test diets were utilized, and they were consumed in random order over two 15-day periods. One diet was low in fat and high in carbohydrate, and corresponded closely to recent recommendations made by the American Diabetes Association (ADA), containing (as percent of total calories) 20 percent protein, 20 percent fat, and 60 percent carbohydrate, with 10 percent of total calories as sucrose. The other diet contained 20 percent protein, 40 percent fat, and 40 percent carbohydrate, with sucrose accounting for 3 percent of total calories. Although plasma fasting glucose and insulin concentrations were similar with both diets, incremental glucose and insulin responses from 8 a.m. to 4 p.m. were higher (p less than 0.01), and mean (+/- SEM) 24-hour urine glucose excretion was significantly greater (55 +/- 16 versus 26 +/- 4 g/24 hours p less than 0.02) in response to the low-fat, high-carbohydrate diet. In addition, fasting and postprandial triglyceride levels were increased (p less than 0.001 and p less than 0.05, respectively) and high-density lipoprotein (HDL) cholesterol concentrations were reduced (p less than 0.02) when patients with NIDDM ate the low-fat, high-carbohydrate diet. Finally, since low-density lipoprotein (LDL) concentrations did not change with diet, the HDL/LDL cholesterol ratio fell in response to the low-fat, high-carbohydrate diet. These results document that low-fat, high-carbohydrate diets, containing moderate amounts of sucrose, similar in composition to the recommendations of the ADA, have deleterious metabolic effects when consumed by patients with NIDDM for 15 days. Until it can be shown that these untoward effects are evanescent, and that long-term ingestion of similar diets will result in beneficial metabolic changes, it seems prudent to avoid the use of low-fat, high-carbohydrate diets containing moderate amounts of sucrose in patients with NIDDM.     

Effect of acute variations in dietary fat and carbohydrate intake on retinyl ester content of intestinally derived lipoproteins.

Vitamin A was administered to eight patients with noninsulin-dependent diabetes mellitus in conjunction with the two different test meals containing (as percentage of total calories) either 15% protein, 60% carbohydrate (CHO), and 25% fat or 15% protein, 40% CHO, and 45% fat. The vitamin A and test meals were given at noon (4 h after a standard breakfast), and blood was obtained hourly from noon to midnight for measurement of plasma glucose, insulin, triglyceride (TG), and cholesterol concentrations; concentrations of TG and cholesterol in Sverdberg floatation (Sf) unit above 400 and Sf 20-400 lipoproteins; retinyl ester concentration in plasma; and both Sf more than 400 and Sf 20-400 lipoproteins. The postprandial TG response in plasma, Sf more than 400 lipoproteins, and Sf 20-400 lipoproteins from noon to midnight was only slightly higher than values seen after consumption of the 60% CHO diet, which contained much less fat (25% vs. 45%) and the retinyl ester concentration was actually higher in both lipoprotein fractions after the diet containing the smallest amount of fat (60% CHO). Furthermore, the cholesterol concentration in the plasma and two lipoprotein fractions was identical after the two diets, despite the great difference in fat content. These data indicate that the acute ingestion of high CHO (60%), low fat (25%) diets by patients with noninsulin-dependent diabetes mellitus led to little or no decrease in postprandial plasma or lipoprotein TG or cholesterol concentrations and an actual increase in concentration of potentially atherogenic small chylomicron and/or chylomicron remnants.     

The effect of sucrose content in high and low carbohydrate diets on plasma glucose, insulin, and lipid responses in hypertriglyceridemic humans

To further understand the effect of high carbohydrate (CHO)-low fat diets and the role of variations in dietary sucrose on CHO and lipid metabolism, 10 patients with hypertriglyceridemia were fed 2 isocaloric, typical American diets, containing 40% and 60% CHO, for 15 days in random sequence. Each patient was their own control, and they were divided into 2 groups of 5 patients each. In one group, sucrose was held constant at 13% of total calories (40-13% and 60-13%), whereas the sucrose content was 9% of the total calories on a 40% CHO diet (40-9%), and 15% of total calories on a 60% CHO diet (60-15%) in the other group. Fasting and postprandial blood samples were analyzed for plasma glucose, insulin, cholesterol (Chol), and triglycerides (TG), as well as for Chol and TG in chylomicrons, very low density, low density, and high density lipoproteins (HDL). Fasting plasma TG levels were significantly increased in both groups on the 60% CHO diet, primarily due to increases in very low density-TG concentration. The magnitude of the elevation was attenuated when sucrose content was kept constant. Postprandial TG responses were qualitatively similar. There were no significant changes in plasma Chol concentrations, except for a modest fall in plasma HDL-Chol level after the 60-13% diet period (P less than 0.05). No significant differences were found in fasting plasma glucose or insulin concentration. However, postprandial glucose and insulin responses were increased on both high CHO diets. The results of these studies demonstrate that high CHO-low fat diets, in general, tend to elevate plasma glucose, insulin, and TG concentrations and reduce HDL-Chol concentration in patients with endogenous hypertriglyceridemia. In addition, these data illustrate the important role that small variations in dietary sucrose can play in modulation of CHO and lipid metabolism.     

Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans

Two levels of dietary carbohydrate (40% and 60% of calories) were incorporated into typical U.S. diets and fed for 10 days each to 11 healthy volunteers. Fasting blood samples were drawn on days 8, 9, and 10 of each dietary period and analyzed for glucose, insulin, cholesterol, triglyceride (TG) and high density lipoprotein (HDL)-cholesterol concentrations. In addition, plasma glucose, insulin and TG concentrations were determined before, and for 3 hr after the noon meal on days 8 and 10. No differences were observed in fasting plasma glucose, insulin or cholesterol concentrations. However, fasting plasma TG levels were significantly elevated on the 60% carbohydrate diet, and HDL-cholesterol concentrations were significantly decreased. Furthermore, the plasma insulin and triglyceride responses to the meal tolerance test during the 60% carbohydrate dietary period were significantly elevated. These results indicate that high-carbohydrate diets lead to changes in insulin, TG, and HDL-cholesterol concentrations which have been associated with an increase in incidence of coronary artery disease.     

Comparison of the effects on insulin sensitivity of high carbohydrate and high fat diets in normal subjects.

To examine whether achievable dietary changes influence insulin sensitivity, we performed euglycemic hyperinsulinemic glucose clamps in eight normal subjects who were prescribed high carbohydrate and high fat diets. The high carbohydrate diet was more than 50% (of energy intake) carbohydrate and less than 30% fat; the high fat diet was more than 45% fat (predominantly saturated) and less than 40% carbohydrate. The diets were consumed over consecutive 3-week periods in random sequence. The mean whole body glucose uptake during the glucose clamps was similar after the high carbohydrate (48.3 mumol/kg.min) and high fat diets (47.0 mumol/kg.min; P = 0.5; 95% confidence interval for the difference, -3.4 to 5.9 mumol/kg.min). Fasting blood glucose and serum insulin concentrations were also unchanged. In contrast, there were substantial effects on lipoprotein metabolism. During the high carbohydrate diet, fasting serum cholesterol decreased by 17% (P = 0.06), low density lipoprotein cholesterol decreased by 20% (P = 0.05), high density lipoprotein cholesterol decreased by 24% (P less than 0.005), and triglyceride increased by 33% (P = 0.06) compared with levels during the high fat diet. These results suggest that practically achievable high carbohydrate diets do not enhance insulin sensitivity in nondiabetic subjects and have net effects on lipoprotein metabolism that may be unfavorable.     

Effect of high-carbohydrate-low-fat diets on plasma glucose,insulin and lipid responses in hypertriglyceridemic humans

Two levels of dietary carbohydrate (40% and 60% of calories) were incorporated into typical US diets and fed for 15 days each to eight patients with endogenous hypertriglyceridemia. Fasting blood samples were drawn on days 13, 14, and 15 of each dietary period, and analyzed for glucose, insulin, cholesterol, and triglyceride concentrations, as well as for triglyceride and cholesterol content of the various lipoprotein classes. In addition, these same measurements were made before and for three hours after the noon meal on days 14 and 15. Fasting plasma triglyceride (TG) and very-low-density lipoprotein (VLDL)-TG concentrations were significantly increased (P < 0.005) on the low-fat-high-carbohydrate diet. In addition, integrated postprandial insulin, TG, and VLDL-TG responses to the noon meal were significantly (P < 0.01?0.001) elevated on the low-fat-high-carbohydrate diet. No dietary-induced changes were noted in either the fasting or postprandial values of glucose cholesterol, chylomicron-TG, low-density lipoprotein-cholesterol, high-density lipoprotein (HDL)-cholesterol, HDL₂-cholesterol, or HDL₃-cholesterol. These results indicate that low-fat-high-carbohydrate diets accentuate the metabolic risk factors for coronary artery disease that are already present in patients with endogenous hypertriglyceridemia.     

Carbohydrate-induced hypertriglyceridemia: an insight into the link between plasma insulin and triglyceride concentrations

This study was initiated to test the hypothesis that endogenous hypertriglyceridemia results from a defect in the ability of insulin to inhibit the release of very low-density lipoprotein-triglyceride (TG) from the liver. To accomplish this goal, plasma glucose, insulin, free fatty acid (FFA), and TG concentrations were compared in 12 healthy volunteers, in response to diets containing either 40% or 60% of total calories as carbohydrate (CHO). The protein content of the two diets was similar (15% of calories), and the fat content varied inversely with the amount of CHO (45% or 25%). The diets were consumed in random order, and measurements were made of plasma glucose, insulin, FFA, and TG concentrations at the end of each dietary period, fasting, and at hourly intervals following breakfast and lunch. The results indicated that the 60% CHO diet resulted in higher fasting plasma TG concentrations associated with higher day-long plasma insulin and TG concentrations, and lower FFA concentrations. These results do not support the view that hypertriglyceridemia is secondary to a failure of insulin to inhibit hepatic TG secretion.     

Metabolic effects of added dietary sucrose in individuals with noninsulin-dependent diabetes mellitus (NIDDM)

This study addresses the metabolic effects of sucrose in the diets of 11 individuals with noninsulin-dependent diabetes mellitus (NIDDM). Each of two dietary periods were 15 days in length, and contained 50% of the calories as carbohydrate, 30% as fat, and 20% as protein. The only variable between the two periods was the percentage of total calories as sucrose, 16% v 1%. Fasting blood samples were analyzed for plasma glucose and insulin as well as total plasma VLDL-, LDL- and HDL-cholesterol and triglyceride concentrations. In addition, postprandial blood samples were obtained for the measurement of plasma glucose, insulin and triglyceride concentrations. Fasting plasma glucose, insulin, and day-long insulin concentrations were similar between the two diets. However, the addition of sucrose in amounts comparable to those typically consumed by the general population resulted in significantly elevated day-long glucose (P less than 0.05) and triglyceride (P less than 0.05) responses, as well as elevated fasting total plasma cholesterol (P less than 0.001), triglyceride (P less than 0.05), VLDL-cholesterol (P less than 0.01), and VLDL-triglyceride (P less than 0.05) concentrations. LDL-cholesterol and HDL-cholesterol concentrations were unchanged during the added sucrose diet. It is clear that the consumption of diets containing moderate amounts of sucrose resulted in changes to plasma lipid and postprandial glucose concentrations that have been identified as risk factors for coronary artery disease. Therefore, it seems prudent at this time to advise patients with NIDDM to avoid added dietary sucrose.     

High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk

In this study we compared the effects of variations in dietary fat and carbohydrate (CHO) content on concentrations of triglyceride-rich lipoproteins in 8, healthy, nondiabetic volunteers. The diets contained, as a percentage of total calories, either 60% CHO, 25% fat, and 15% protein, or 40% CHO, 45% fat, and 15% protein. They were consumed in random order for 2 weeks, with a 2-week washout period in between. Measurements were obtained at the end of each dietary period of plasma triglyceride, cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, remnant lipoprotein (RLP) cholesterol, and RLP triglyceride concentrations, both after an overnight fast and throughout an 8-hour period (8 A.M. to 4 P.M.) in response to breakfast and lunch. The 60% CHO diet resulted in higher (mean +/- SEM) fasting plasma triglycerides (206 +/- 50 vs 113 +/- 19 mg/dl, p = 0.03), RLP cholesterol (15 +/- 6 vs 6 +/- 1 mg/dl, p = 0.005), RLP triglyceride (56 +/- 25 vs 16 +/- 3 mg/dl, p = 0.003), and lower HDL cholesterol (39 +/- 3 vs 44 +/- 3 mg/dl, p = 0.003) concentrations, without any change in LDL cholesterol concentration. Furthermore, the changes in plasma triglyceride, RLP cholesterol, and RLP triglyceride persisted throughout the day in response to breakfast and lunch. These results indicate that the effects of lowfat diets on lipoprotein metabolism are not limited to higher fasting plasma triglyceride and lower HDL cholesterol concentrations, but also include a persistent elevation in RLPs. Given the atherogenic potential of these changes in lipoprotein metabolism, it seems appropriate to question the wisdom of recommending that all Americans should replace dietary saturated fat with CHO.     

Induction of hypertriglyceridemia by a low-fat diet.

We have studied the effects of moderate dietary fat restriction on plasma triglyceride, cholesterol, glucose, and insulin response in 27 subjects. Compared with a control diet (45% fat, 40% carbohydrate [CHO], 15% protein) the low fat (higher CHO) diet (30% fat, 55% CHO, 15% protein) produced a 41% increase in fasting triglyceride level (155 +/- 17 to 219 +/- 23 mg%) with no change in fasting plasma cholesterol level. Furthermore, this increase in triglyceride levels; induced by the higher CHO content of the low fat diet, was seen in 26 out of 27 subjects. Postprandial triglyceride, glucose, and insulin levels were also higher on the low fat (higher CHO) diet. Since hypertriglyceridemia is a significant risk factor for the development of coronary heart disease, and since our data indicate that the moderate increase in dietary CHO associated with a low fat diet will elevate plasma triglyceride levels, we believe that more caution is necessary before recommending the wide-spread use of low fat diets for heart disease prevention.     

The long-term effect of low-carbohydrate/high-fat diet on the development of diabetes mellitus in spontaneously diabetic rats

The long-term effect of low-carbohydrate/high-fat diets on the development of diabetes mellitus was studied in Otsuka Long-Evans Tokushima Fatty strain (OLETF) rats. Four groups of spontaneously diabetic (type 2) male rats at 10 weeks of age were pair-fed semi-purified powder diets containing different amounts of carbohydrate (80%, 60%, 40%, 20% of total calories) for 30 weeks. The carbohydrate content was isocalorically substituted for the fat content in the diet. At the onset of experimental feeding (10 weeks of age), an oral glucose tolerance test (OGTT) was normal in each group. After 15 weeks of the test diet feeding there was no significant difference in the glucose tolerance among the 4 groups, although most of the rats were diabetic. The body weight increased with the decrease of the carbohydrate intake and increase of the fat intake (p <0.05), and the difference increased in proportion to age (p<0.05). The severity of diabetes mellitus was also increased along with the lower carbohydrate intake and higher fat intake, when the carbohydrate intake was less than 60% (in energy). On the other hand, there was a significant increase in the 20% group in the postload plasma insulin levels as compared with the other 3 groups at 40 weeks of age. Fasting plasma free fatty acid levels were increased in the lower carbohydrate content groups (20% and 40%) as compared with the higher carbohydrate content groups (60% and 80%) at the end of the experiment. Impairment of insulin secretion may be the cause of glucose intolerance induced by low carbohydrate intake rather than insulin resistance. These findings suggest that low-carbohydrate/high-fat diet aggravates diabetes mellitus in genetically diabetic rats, and that the development of diabetes mellitus is associated with the activation of the glucose-fatty acid cycle.     

Predictors of plasma triglyceride elevation in patients participating in a coronary atherosclerosis treatment program

PURPOSE: Low-fat, high-carbohydrate diets have been used successfully to prevent and treat coronary heart disease, although these diets have been shown to cause elevations in fasting plasma triglyceride concentrations. The present study investigated metabolic factors (glucose, insulin, body weight) associated with changes in plasma triglyceride concentrations in patients participating in a comprehensive, multidisciplinary program, which included the use of a very low-fat diet designed to regress atherosclerotic cardiovascular disease. METHODS: Thirty-six patients were entered into the study and placed on a 10% fat diet. Body mass index and fasting plasma insulin, glucose, lipids, and apolipoproteins were assessed at entrance into and after 3 months of participation in the program. Statistical analysis (discriminant function analysis) was used to identify factors that predicted elevations in plasma triglyceride that occurred during therapy. RESULTS: For the entire group, significant reductions in body weight (-2.4%), fasting glucose (-6%), total cholesterol (-8%), and low-density lipoprotein cholesterol (-11%) were observed, while insulin and triglycerides showed no significant changes. Twenty-one of the patients experienced an increase in fasting triglyceride concentration of 10% or greater. CONCLUSIONS: Three variables (baseline body mass index and fasting triglyceride and insulin concentrations) accurately classified 90% of those who would experience a > or = 10% elevation in triglycerides (P = 0.0002) and 67% of those who experienced no change. The present analysis provides a practical algorithm for clinicians to predict which patients will experience significant elevations in plasma triglyceride concentration when undergoing risk factor reduction that includes the consumption of a very low-fat, high-carbohydrate diet.     

Effect of phenformin on lipid transport in hypertriglyceridemia

The effect of phenformin on lipid metabolism was studied in nine hypertriglyceridemic subjects consuming isocaloric liquid formula diets. On a fat-free, 85% carbohydrate hydrate diet, phenformin reduced plasma triglyceride, cholesterol, and free fatty acid levels, the mean decreases being 14%, 13%, and 16%, respectively. The predominant effect of the drug was on very low density lipoprotein levels, with no change in low density lipoproteins. Plasma triglyceride and cholesterol levels were also reduced in the majority of subjects on a diet containing 40% of calories as fat and 45% as carbohydrate, but phenformin did not have any effect on the carbohydrate induction of triglyceride elevation. Basal insulin levels were reduced by the drug in all subjects (mean change, ?23%) and fasting glucose levels were lowered in the majority. The plasma lipolytic rate measured on endogenous substrate during a prolonged heparin infusion on the fat-free diet was reduced by phenformin (mean change, ?15%), although postheparin lipolytic activity on an artificial substrate was unchanged. Free fatty acid turnover, measured during the same procedure, fell in parallel with the fatty acid levels (mean change, ?27%). It is proposed that phenformin lowers plasma triglyceride levels in most subjects by reducing endogenous triglyceride production, and that the effects of the drug on glucose, insulin, and free fatty acid homeostasis contribute to this action. It is suggested that in some subjects the drug may also impair triglyceride clearance from plasma, and that this may account for the variable therapeutic response, since in three subjects phenformin did not decrease triglyceride levels on both diets.     

Insulin sensitivity after a reduced-fat diet and a monoene-enriched diet in subjects with elevated serum cholesterol and triglyceride concentrations

BACKGROUND AND AIMS: To investigate the effect of a reduced-fat diet and a monoene-enriched diet (MUFA diet) on serum lipids, glucose and insulin metabolism in subjects with elevated cholesterol and triglyceride concentrations. METHODS AND RESULTS: Eighteen subjects with elevated serum cholesterol and triglyceride concentrations consumed the MUFA diet (39% of energy (E%) as fat and 21 E% monoenes) and the reduced-fat diet (34 E% fat, 16 E% monoenes) for 4 weeks according to a randomized cross-over design. Both periods were preceded by consumption of a standardized baseline diet for 2 weeks. Serum lipid and lipoprotein concentrations were determined at the beginning and end of each diet period. A frequently sampled intravenous glucose tolerance test was performed after the MUFA diet and the reduced-fat diet. Insulin sensitivity index (SI) was 40% higher after the reduced-fat diet than after the MUFA diet (2.42 +/- 0.42 vs 1.73 +/- 0.24 10(-4) min-1 U-1 ml-1, p = 0.018). This change in insulin sensitivity was seen in 13 subjects and was most evident in those who began with the MUFA diet. Compared to the baseline diet (high in saturated fat), both experimental diets lowered serum total and LDL cholesterol concentrations (6.6-6.9%, p < 0.05 and 7.4-8.0%, p < 0.05 respectively). CONCLUSIONS: Both diets were equally effective in lowering serum lipid concentrations, but the reduced-fat diet resulted in better insulin sensitivity.     

A high-trans fatty acid diet and insulin sensitivity in young healthy women.

Epidemiological and experimental studies suggest that a diet rich in saturated fat affects insulin sensitivity. Monoenes and dienes that have an usaturated bond with the trans configuration (trans fatty acids) resemble saturated fatty acids with respect to structure, but no published data are available on the effect of trans fatty acids on insulin sensitivity. Therefore, the effects of diets high in trans fatty acids (TFA diet) and oleic acid (monounsaturated fat [MUFA] diet) on glucose and lipid metabolism were studied in 14 healthy women. Subjects consumed both experimental diets for 4 weeks according to a randomized crossover study design. Both experimental diet periods were preceded by consumption of a standardized baseline diet for 2 weeks. The diets provided 36.6% to 37.9% of energy (E%) as fat. In the TFA diet, there was 5.1 E% trans fatty acids, and in the MUFA diet, 5.2 E% oleic acid, substituted for saturated fatty acids in the baseline diet. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of the experimental diet periods. Glucose effectiveness (S(G)) and the insulin sensitivity index (S(I)) did not differ after the two experimental diet periods. There was also no difference in the acute insulin response between the diets. The total cholesterol to high-density lipoprotein (HDL) cholesterol ratio and serum total triglyceride, HDL, and low-density lipoprotein (LDL) triglyceride and apolipoprotein B (apoB) concentrations were higher (P < .05) after the TFA diet. In conclusion, in young healthy women, the TFA diet resulted in a higher total/HDL cholesterol ratio and an elevation in triglyceride and apo B concentrations but had no effect on glucose and insulin metabolism compared with the MUFA diet.     

Effects of calorie-restricted low-carbohydrate diet on glucose and lipid metabolism in Otsuka Long Evans Tokushima Fatty rats

AIM: We investigated the effects of a calorie-restricted low-carbohydrate diet on glucose and lipid metabolism, and body fat distribution, especially on the secretion of leptin and lipoprotein lipase from adipose tissue in Otsuka Long Evans Tokushima Fatty (OLETF) rats. METHODS: Forty-three week-old male OLETF rats were randomized into three groups (n=6 per group): the HC group (HC) was fed a diet with 60% carbohydrate; the LC group (LC) with 30% carbohydrate; and the P-HC group (P-HC) with 60% carbohydrate and pioglitazone (0.1%). The total calorie intake was restricted to 70% of the average intake from each diet (60 kcal/day). The diets were continued for 8 weeks. RESULTS: Similar decreases in body weight and serum glucose were observed in the three groups. Serum insulin concentration was significantly decreased in LC and P-HC compared to HC. Serum total cholesterol and triglycerides decreased significantly (p<0.05) in LC and P-HC compared to HC. The decrease of visceral fat area measured by computed tomography was greatest in LC among the three groups. At the end of the diet, leptin secretion from visceral adipose tissue and lipoprotein lipase (LPL) activity in subcutaneous adipose tissue were significantly higher in LC and P-HC compared to HC (p<0.05). CONCLUSION: These results indicate that under calorie-restricted conditions, low carbohydrates are much more effective than high carbohydrates in improving insulin sensitivity.     

Low-versus high-glycemic index diets in women: effects on caloric requirement, substrate utilization and insulin sensitivity

Background: Lowering dietary glycemic index appears to have positive health effects in obese and/or insulin resistant individuals. However, detailed studies in lean young men show no effect. Methods: This study was designed to test the null hypothesis that a diet rich in low-glycemic carbohydrate has no effect on lipid profile, caloric requirements, fat oxidation, or insulin sensitivity in adult women when compared to one rich in high-glycemic carbohydrate. The metabolic feeding protocol used was conducted in both a free-living and in-patient setting using a randomized crossover design. Seven women were studied on each of 2 diets in which 60% of the calories were from either high- or low-glycemic carbohydrate sources. Each diet lasted 20 days with measurements of caloric requirement, resting metabolic rate, glucose and insulin responses to diet and activity, insulin sensitivity, and lipid profile over the last 7 days. Caloric requirement was determined by bomb calorimetry. Other techniques included indirect calorimetry, hydrodensitometry, stable isotope tracers, and the euglycemic clamp. Results: On the low-glycemic index diet the women's caloric requirements were 11% +/- 1% higher, fat oxidation at fasted rest supplied an average of 45% +/- 4% versus 28% +/- 5% of oxidative requirements, average glucose and insulin levels were approximately 40% lower, low density lipoproteins (LDL) and leptin concentrations were lower, and various indices of insulin sensitivity were > 20% higher. Conclusions: In this group of adult women, a diet that lowered glycemic index well below that typically found in western diets increased both daily caloric requirement and fat oxidation, decreased insulin and glucose concentrations and increased insulin sensitivity.     

Deterioration in carbohydrate metabolism and lipoprotein changes induced by modern, high fat diet in Pima Indians and Caucasians

The transition from a high carbohydrate to a high fat diet may explain in part the dramatic increase in the prevalence of noninsulin-dependent diabetes mellitus among Pima Indians over the last century. In this study, 12 Pimas and 12 caucasians, all nondiabetic, were admitted to a metabolic ward and, in random order, fed 2 14-day weight-maintaining diets: a traditional Pima diet (percentage of calories: carbohydrate, 70% fat, 15%; protein, 15%) and a high fat modern diet (carbohydrate, 30%; fat, 50%; protein, 20%). Carbohydrate metabolism was characterized using the modified iv glucose tolerance test (minimal model), the acute insulin responses to arginine during a 3-step glycemic clamp, and the oral glucose tolerance test. Compared with the traditional diet, the modern diet was associated with a decrease in oral glucose tolerance (P less than 0.01) and higher plasma cholesterol concentrations (P less than 0.02). The decline in glucose tolerance was associated with similar insulin-mediated, but 23% lower glucose-mediated (P less than 0.001), glucose disposal, a 17% lower acute insulin response to glucose (P less than 0.03), a 9% lower beta-cell sensitivity to glucose (P less than 0.02), and similar beta-cell capacities. Pimas and caucasians responded similarly, except for larger changes in plasma lipids among the Pimas. Since glucose-mediated glucose disposal, beta-cell function, and glucose tolerance deteriorated on the modern diet, it is likely that diet composition affects the prevalence of noninsulin-dependent diabetes mellitus in both Pimas and caucasians.     

A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin independent diabetic women

Summary Type 2 (insulin independent) diabetic women were randomly allocated to receive advice for low fat diets or low carbohydrate diets. By 24 h weighed dietary intakes before and after a mean interval of six months, patients in the low fat group had reduced their fat intake from 41% to 31% of total energy, while carbohydrate percentage of total energy intake increased from 38% to 46%. Percentage energy intake from fat and carbohydrate in the control group remained unchanged. Body weight fell in both groups, especially for patients in the low fat group who were obese (weight/height2 28 kg/m²). Mean plasma glucose, HbA₁, and triglycerides were unchanged. Mean plasma total cholesterol fell significantly in the low fat group compared with the controls (p < 0.001), but there was no significant difference in the small reduction of high density lipoprotein cholesterol observed in both groups. Thus, adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol.     

Effects of C358A missense polymorphism of the degrading enzyme fatty acid amide hydrolase on weight loss, adipocytokines, and insulin resistance after 2 hypocaloric diets

It has been demonstrated that the polymorphism 385 C/A of fatty acid amide hydrolase was associated with obesity. We decided to investigate the role of a polymorphism (cDNA 385 C->A) on insulin resistance and weight loss secondary to a low-fat vs a low-carbohydrate diet. A population of 248 patients with obesity was analyzed. Basal measurements were performed, and values were compared to those at the end of a 3-month period in which subjects received either diet I (low fat) or diet II (low carbohydrate). One hundred seventy-eight patients (71.8%) had the genotype C358C (wild-type group), and 70 (28.2%) patients had the genotype C358A (62 patients, 25%) or A358A (8 patients, 3.2%) (mutant-type group). With diet I, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased in the wild-type and mutant-type groups. With diet II, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased in both genotypes. With diet I, leptin, glucose, total cholesterol, triglyceride, insulin, and homeostasis model assessment for insulin sensitivity (HOMA) decreased in the wild-type group. In the mutant-type group, only cholesterol decreased in a significant way. With diet II, leptin, interleukin-6, glucose, total cholesterol, low-density lipoprotein cholesterol, insulin, HOMA, and C-reactive protein decreased in the wild-type genotype. The allele A358 of fatty acid amide hydrolase was associated with a lack of improvement on glucose insulin, HOMA, and leptin levels in both diets after weight loss.