Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals.

BACKGROUND: Clinical studies suggest a role for dietary glycaemic index (GI) in bodyweight regulation and diabetes risk. However, partly because manipulation of GI can produce changes in potentially confounding dietary factors such as fibre content, palatability, and energy density, its relevance to human health remains controversial. This study examined the independent effects of GI in animals. METHODS: Partially pancreatectomised male Sprague-Dawley rats were given diets with identical nutrients, except for the type of starch: high-GI (n=11) or low-GI (n=10). The animals were fed in a controlled way to maintain the same mean bodyweight in the two groups for 18 weeks. Further experiments examined the effects of GI in rats in a cross-over design and C57BL/6J mice in a parallel design. FINDINGS: Despite having similar mean bodyweight (547.9 [SE 13.4] vs 549.2 [15.2] g), rats given high-GI food had more body fat (97.8 [13.6] vs 57.3 [7.2] g; p=0.0152) and less lean body mass (450.1 [9.6] vs 491.9 [11.7] g; p=0.0120) than those given low-GI food. The high-GI group also had greater increases over time in the areas under the curve for blood glucose and plasma insulin after oral glucose, lower plasma adiponectin concentrations, higher plasma triglyceride concentrations, and severe disruption of islet-cell architecture. Mice on the high-GI diet had almost twice the body fat of those on the low-GI diet after 9 weeks. INTERPRETATION: These findings provide a mechanistic basis for interpretation of studies of GI in human beings. RELEVANCE TO PRACTICE: The term GI describes how a food, meal, or diet affects blood sugar during the postprandial period. GI as an independent factor can cause obesity and increase risks of diabetes and heart disease in animals. Use of low-GI diets in prevention and treatment of human disease merits thorough examination.

Glycemic index and obesity.

Although weight loss can be achieved by any means of energy restriction, current dietary guidelines have not prevented weight regain or population-level increases in obesity and overweight. Many high-carbohydrate, low-fat diets may be counterproductive to weight control because they markedly increase postprandial hyperglycemia and hyperinsulinemia. Many high-carbohydrate foods common to Western diets produce a high glycemic response [high-glycemic-index (GI) foods], promoting postprandial carbohydrate oxidation at the expense of fat oxidation, thus altering fuel partitioning in a way that may be conducive to body fat gain. In contrast, diets based on low-fat foods that produce a low glycemic response (low-GI foods) may enhance weight control because they promote satiety, minimize postprandial insulin secretion, and maintain insulin sensitivity. This hypothesis is supported by several intervention studies in humans in which energy-restricted diets based on low-GI foods produced greater weight loss than did equivalent diets based on high-GI foods. Long-term studies in animal models have also shown that diets based on high-GI starches promote weight gain, visceral adiposity, and higher concentrations of lipogenic enzymes than do isoenergetic, macronutrientcontrolled, low-GI-starch diets. In a study of healthy pregnant women, a high-GI diet was associated with greater weight at term than was a nutrient-balanced, low-GI diet. In a study of diet and complications of type 1 diabetes, the GI of the overall diet was an independent predictor of waist circumference in men. These findings provide the scientific rationale to justify randomized, controlled, multicenter intervention studies comparing the effects of conventional and low-GI diets on weight control.

Effects of a low-glycemic load diet in overweight and obese pregnant women: a pilot randomized controlled trial.

BACKGROUND: The optimal diet for pregnancy that is complicated by excessive weight is unknown. OBJECTIVE: We aimed to examine the effects of a low-glycemic load (low-GL) diet in overweight and obese pregnant women. DESIGN: We randomly assigned 46 overweight or obese pregnant women to receive a low-GL or a low-fat diet. Participants received carbohydrate-rich foods, fats, and snack foods through home delivery or study visits. The primary outcome was birth weight z score. Other endpoints included infant anthropometric measurements, gestational duration, maternal weight gain, and maternal metabolic parameters. RESULTS: There were no significant differences in birth weight z score or other measures of infant adiposity between groups. However, in the low-GL compared with the low-fat group, gestational duration was longer (mean ± SD: 39.3 ± 1.1 compared with 37.9 ± 3.1 wk; P = 0.05) and fewer deliveries occurred at ≤ 38.0 wk (13% compared with 48%, P = 0.02; with exclusion of planned cesarean deliveries: 5% compared with 53%; P = 0.002). Adjusted head circumference was greater in the low-GL group (35.0 ± 0.8 compared with 34.2 ± 1.3 cm, P = 0.01). Women in the low-GL group had smaller increases in triglycerides [median (interquartile range): 49 (19, 70) compared with 93 (34, 129) mg/dL; P = 0.03] and total cholesterol [13 (0, 36) compared with 33 (22, 56) mg/dL, P = 0.04] and a greater decrease in C-reactive protein [-2.5 (-5.5, -0.7) compared with -0.4 (-1.4, 1.5) mg/dL, P = 0.007]. CONCLUSIONS: A low-GL diet resulted in longer pregnancy duration, greater infant head circumference, and improved maternal cardiovascular risk factors. Large-scale studies are warranted to evaluate whether dietary intervention during pregnancy aimed at lowering GL may be useful in the prevention of prematurity and other adverse maternal and infant outcomes. This trial is registered at clinicaltrials.gov as NCT00364403.

Long-term effects of dietary glycemic index on adiposity, energy metabolism, and physical activity in mice.

A high-glycemic index (GI) diet has been shown to increase adiposity in rodents; however, the long-term metabolic effects of a low- and high-GI diet have not been examined. In this study, a total of 48 male 129SvPas mice were fed diets high in either rapidly absorbed carbohydrate (RAC; high GI) or slowly absorbed carbohydrate (SAC; low GI) for up to 40 wk. Diets were controlled for macronutrient and micronutrient content, differing only in starch type. Body composition and insulin sensitivity were measured longitudinally by DEXA scan and oral glucose tolerance test, respectively. Food intake, respiratory quotient, physical activity, and energy expenditure were assessed using metabolic cages. Despite having similar mean body weights, mice fed the RAC diet had 40% greater body fat by the end of the study and a mean 2.2-fold greater insulin resistance compared with mice fed the SAC diet. Respiratory quotient was higher in the RAC group, indicating comparatively less fat oxidation. Although no differences in energy expenditure were observed throughout the study, total physical activity was 45% higher for the SAC-fed mice after 38 wk of feeding. We conclude that, in this animal model, 1) the effect of GI on body composition is mediated by changes in substrate oxidation, not energy intake; 2) a high-GI diet causes insulin resistance; and 3) dietary composition can affect physical activity level.

Hepatic steatosis and increased adiposity in mice consuming rapidly vs. slowly absorbed carbohydrate.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is fast becoming a major public health concern, coincident with the increasing prevalence of obesity. Although lifestyle greatly influences development of NAFLD, the specific dietary causes remain largely unknown. The purpose of this study was to determine whether a diet high in rapidly absorbed carbohydrate (RAC) vs. slowly absorbed carbohydrate (SAC), controlled for confounding dietary factors, causes NAFLD in mice with similar body weight. An animal model was chosen because of logistical and ethical challenges to conducting this study in humans. RESEARCH METHODS AND PROCEDURES: Male 129SvPas mice were fed diets high in either RAC (amylopectin; high glycemic index) or SAC (amylose; low glycemic index) for 25 weeks. Diets were controlled for macronutrient and micronutrient content, differing only in starch type. Body weight and composition were measured throughout the study. Hepatic and plasma triacylglycerol concentrations were quantified at the end of the study. RESULTS: Body weight was not significantly different between the two groups. However, total body adiposity increased twice as much, in absolute terms, in the mice fed RAC vs. SAC (12.2 +/- 2.9% vs. 6.1 +/- 4.2%, p < 0.0001). Hepatic triacylglycerol content was 2-fold greater in the RAC group (20.7 +/- 9.4 vs. 9.6 +/- 4.9 mg/g, p = 0.01). In addition, plasma insulin and triacylglycerol concentrations were higher in the RAC group. DISCUSSION: A diet high in RAC causes accumulation of fat in liver, adipose tissue, and plasma in mice. Therefore, a low glycemic index diet may help prevent or treat NAFLD in humans.

Childhood obesity: public-health crisis, common sense cure.

During the past two decades, the prevalence of obesity in children has risen greatly worldwide. Obesity in childhood causes a wide range of serious complications, and increases the risk of premature illness and death later in life, raising public-health concerns. Results of research have provided new insights into the physiological basis of bodyweight regulation. However, treatment for childhood obesity remains largely ineffective. In view of its rapid development in genetically stable populations, the childhood obesity epidemic can be primarily attributed to adverse environmental factors for which straightforward, if politically difficult, solutions exist.

Cardiovascular responses evoked by leptin acting on neurons in the ventromedial and dorsomedial hypothalamus.

Leptin, a circulating hormone produced by adipose tissue, is believed to act on the hypothalamus to increase sympathetic vasomotor activity, in addition to its well-known effects on appetite and energy expenditure. In this study, we determined the cardiovascular effects of direct application of leptin to specific cell groups within the hypothalamus that are known to be activated by circulating leptin. In rats anesthetized with urethane, microinjections of leptin (16 ng in 20 nL solution) were made into the ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, and paraventricular nucleus. Compared with vehicle solution, microinjections of leptin into the ventromedial hypothalamic nucleus evoked significant increases in arterial pressure and renal sympathetic nerve activity, but not heart rate. In contrast, microinjections of leptin into the dorsomedial hypothalamic nucleus evoked significant increases in arterial pressure and heart rate but not renal sympathetic nerve activity, whereas microinjections of leptin into the paraventricular nucleus had no significant effect on any of the measured cardiovascular variables. These results indicate that the ventromedial and dorsomedial hypothalamic regions might be important sites at which leptin activation leads to increases in sympathetic vasomotor activity and heart rate, as occurs in obesity-related hypertension.