Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose-or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle-triglyceride and -cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults. IntroductionStudies investigating the effects of fructose consumption in humans and animals have been comprehensively reviewed (1-4), and while strong evidence exists that consumption of diets high in fructose results in increased de novo lipogenesis (DNL), dyslipidemia, insulin resistance, and obesity in animals, direct experimental evidence that consumption of fructose promotes DNL, dyslipidemia, insulin resistance, glucose intolerance, and obesity in humans is lacking. Thus, we have investigated and compared the biological effects of the 2 major simple sugars in the diet, glucose and fructose, on BW and regional fat deposition and on indices of lipid and carbohydrate metabolism in older, overweight and obese men and women.We sought to answer the following questions: (a) Does consumption of fructose with an ad libitum diet promote greater BW gain and have differential effects on regional adipose deposition and adipose gene expression compared with consumption of glucose with an ad libitum diet? (b) Does consumption of fructose induce dyslipidemia compared with consumption of glucose? (c) Is fructose-induced hypertriglyceridemia the result of increased rates

WHAT'S KNOWN ON THIS SUBJECT: Diabetes during pregnancy has been associated with general development impairments in offspring; however, associations between autism and maternal diabetes have been inconsistent. Few studies have examined related conditions accompanied by underlying increased insulin resistance and their association with developmental outcomes. WHAT THIS STUDY ADDS:This population-based study in young children provides evidence that maternal metabolic conditions are a risk factor for autism, developmental delay without autistic symptoms, and impairments in several domains of development, particularly expressive language, after adjusting for sociodemographic and other characteristics. abstract OBJECTIVE: We examined whether metabolic conditions (MCs) during pregnancy (diabetes, hypertension, and obesity) are associated with autism spectrum disorder (ASD), developmental delays (DD), or impairments in specific domains of development in the offspring. METHODS:Children aged 2 to 5 years (517 ASD, 172 DD, and 315 controls) were enrolled in the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a population-based, case-control investigation between January 2003 and June 2010. Eligible children were born in California, had parents who spoke English or Spanish, and were living with a biological parent in selected regions of California. Children' s diagnoses were confirmed by using standardized assessments. Information regarding maternal conditions was ascertained from medical records or structured interview with the mother.RESULTS: All MCs were more prevalent among case mothers compared with controls. Collectively, these conditions were associated with a higher likelihood of ASD and DD relative to controls (odds ratio: 1.61 [95% confidence interval: 1.10-2.37; odds ratio: 2.35 [95% confidence interval: 1.43-3.88], respectively). Among ASD cases, children of women with diabetes had Mullen Scales of Early Learning (MSEL) expressive language scores 0.4 SD lower than children of mothers without MCs (P , .01). Among children without ASD, those exposed to any MC scored lower on all MSEL and Vineland Adaptive Behavior Scales (VABS) subscales and composites by at least 0.4 SD (P , .01 for each subscale/composite).CONCLUSIONS: Maternal MCs may be broadly associated with neurodevelopmental problems in children. With obesity rising steadily, these results appear to raise serious public health concerns. Pediatrics

Metabolic syndrome comprises a cluster of cardiovascular risk factors (hypertension, altered glucose metabolism, dyslipidemia, and abdominal obesity) that occur in obese children. However, metabolic syndrome can also occur in lean individuals, suggesting that obesity is a marker for the syndrome, not a cause. Metabolic syndrome is difficult to define, due to its nonuniform classification and reliance on hard cutoffs in the evaluation of disorders with non-Gaussian distributions. Defining the syndrome is even more difficult in children, owing to racial and pubertal differences and lack of cardiovascular events. Lipid partitioning among specific fat depots is associated with insulin resistance, which can lead to mitochondrial overload and dysfunctional subcellular energy use and drive the various elements of metabolic syndrome. Multiple environmental factors, in particular a typical Western diet, drive mitochondrial overload, while other changes in Western society, such as stress and sleep deprivation, increase insulin resistance and the propensity for food intake. These culminate in an adverse biochemical phenotype, including development of altered glucose metabolism and early atherogenesis during childhood and early adulthood.

Consuming beverages containing 10%, 17.5%, or 25% Ereq from HFCS produced dose-dependent increases in circulating lipid/lipoprotein risk factors for CVD and uric acid within 2 wk. These results provide mechanistic support for the epidemiologic evidence that the risk of cardiovascular mortality is positively associated with consumption of increasing amounts of added sugars. This trial was registered at clinicaltrials.gov as NCT01103921.