Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs.

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.

Low-protein and methionine, high-starch diets increase energy intake and expenditure, increase FGF21, decrease IGF-1, and have little effect on adiposity in mice.

Low-protein diets most often induce increased energy intake in an attempt to increase protein intake to meet protein needs with a risk of accumulation as fat of the excess energy intake. In female adult BALB/c mice, a decrease in dietary casein from 20% to 6% and 3% increased energy intake and slightly increased adiposity, and this response was exacerbated with soy proteins with low methionine content. The effect on fat mass was however limited because total energy expenditure increased to the same extent as energy intake. Lean body mass was preserved in all 6% fed mice and reduced only in 3% casein-fed animals. Insulin response to an oral glucose tolerance test was reduced in soy-fed mice and in low-protein-fed mice. Low-protein diets did not affect uncoupling protein 1 and increased fibroblast growth factor 21 (FGF21) in brown adipose tissue and increased FGF21, fatty acid synthase, and cluster of differentiation 36 in the liver. In the hypothalamus, neuropeptide Y was increased and proopiomelanocortin was decreased only in 3% casein-fed mice. In plasma, when protein was decreased, insulin-like growth factor-1 decreased and FGF21 increased and plasma FGF21 was best described by using a combination of dietary protein level, protein-to-carbohydrate ratio, and protein-to-methionine ratio in the diet. In conclusion, reducing dietary protein and protein quality increases energy intake but also energy expenditure resulting in an only slight increase in adiposity. In this process, FGF21 is probably an important signal that responds to a complex combination of protein restriction, protein quality, and carbohydrate content of the diet.

An assessment of the influence of macronutrients on growth performance and nutrient utilisation in broiler chickens by nutritional geometry.

The right-angled triangle mixture experiment was designed to include fourteen diets with different concentrations of starch, protein and lipid. Experimental diets were offered to male Ross 308 broiler chickens from 10 to 23 d after hatching, and response curves and surfaces were generated to illustrate the influence of macronutrients on growth performance and nutrient utilisations. Despite the primary function of macronutrients, especially protein, may not be providing energy, macronutrients were expressed as energy derived from starch, protein and fat for statistical purposes in the mixture design. Energy derived from lipid had a greater impact on feed intake than energy derived from starch and protein. When we compared the influence of starch and protein on feed intake, 'equal distance rule' was observed, which means the animal consumes feed to the point on its respective nutritional rails where the shortage of starch exactly equals the surplus of consumed protein. Increasing the protein-derived energy intake increased weight gain in broiler chickens, whereas energy intake derived from starch and lipid had little impact on weight gain. Feed conversion ratio (FCR) may be reduced by either increasing protein energy intake or decreasing starch energy intake. As the slope of the contours was less than 1, the influence of starch energy intakes on FCR exceeded that of protein energy intakes. In conclusion, energy derived from protein is more important than non-protein energy in terms of weight gain, and a balance between protein and energy supplies is required for efficient muscle protein deposition.

Dietary behaviour and nutritional status in underprivileged people using food aid (ABENA study, 2004-2005).

BACKGROUND: Although initiatives are setting up to improve the nutritional status of deprived people, few studies have described the food aid user profile and evaluated their nutritional needs. The contributions of food aid to the food supply, dietary behaviour and nutritional status of food aid users were evaluated in the ABENA study. METHODS: A cross-sectional study was conducted among food aid users in four urban French zones (n = 1664, age ≥18 years). Sociodemographic and economic characteristics, food insufficiency, food supply and diet behaviours were assessed using standardised questionnaires. A subsample of participants underwent clinical and biochemical examinations. Descriptive and comparative analyses were performed taking into account sample weights. RESULTS: Over 70% of participants used food aid as the only source of supply among numerous food groups, and one-quarter of them (27.2%) were using food aid for 3 years or more. The mean food budget was €70.0 per person per month, and 46.0% of subjects were classified as 'food-insufficient'. Half of the subjects fulfilled the French recommendations for starchy foods (48.7%) and 'meat, fish and eggs' (49.4%); 27.3% met the requirements for seafood. Only a very small proportion of participants met the recommendations for fruits and vegetables (1.2%) and dairy products (9.2%). In addition, 16.7% of subjects were obese, 29.4% had high blood pressure, 14.8% were anaemic, 67.9% were at risk of folate deficiency and 85.6% had vitamin D deficiency. CONCLUSIONS: These results provide evidence of an unhealthy diet and poor health profiles in severely disadvantaged persons and highlight the importance of food aid in this population. Thus, this study points to the necessity of improving the nutritional quality of currently distributed food aid.

Associations of socioeconomic factors with inadequate dietary intake in food aid users in France (The ABENA study 2004-2005).

BACKGROUND/OBJECTIVES: Few studies in Europe have examined the relationship of sociodemographic and economic factors with diet in deprived populations. We analysed the association between socioeconomic characteristics and consumption of different food groups in food aid users. SUBJECTS/METHODS: A cross-sectional study was conducted among food aid users in four urban French zones (n=1664). Associations of sociodemographic and economic factors and food aid use with frequency of consumption of the main food groups were tested using multivariate logistic regression models accounting for sampling weights. RESULTS: Both migrant status and consumption of fewer than three daily meals were associated with risk of low frequency of starchy food consumption (<3 times per day). Migrant status was also associated with low frequency of consumption of fruits and vegetables (<3.5 times per day) and dairy products (<2 times per day). Subjects with severe food insufficiency were more likely to be low consumers of fruits and vegetables, meat, seafood and eggs (<1 time per day), and dairy products. A low monthly food budget, temporary housing in a shelter and no source of household income were all associated with risk of low frequency of seafood consumption (<2 times per week). Finally, duration of food aid use, type of food aid distribution and perception of poor health status were associated with low consumption of meat, seafood and eggs. CONCLUSIONS: Economic level and other social characteristics were associated with an unhealthy diet within this deprived French population.

Consumption of the slow-digesting waxy maize starch leads to blunted plasma glucose and insulin response but does not influence energy expenditure or appetite in humans.

Limited research in humans suggests that slowly digestible starch may blunt the postprandial increase and subsequent decline of plasma glucose and insulin concentrations, leading to prolonged energy availability and satiety, compared to more rapidly digestible starch. This study examined the postprandial metabolic and appetitive responses of waxy maize starch (WM), a slow-digestible starch. It was hypothesized that the waxy maize treatment would result in a blunted and more sustained glucose and insulin response, as well as energy expenditure and appetitive responses. Twelve subjects (6 men and 6 women) (age, 23 +/- 1 years; body mass index, 22.2 +/- 0.7 kg/m(2); insulin sensitivity [homeostatic model assessment], 16% +/- 2%; physical activity, 556 +/- 120 min/wk) consumed, on separate days, 50 g of available carbohydrate as WM, a maltodextrin-sucrose mixture (MS), or white bread (control). Postprandial plasma glucose and insulin, energy expenditure, and appetite (hunger, fullness, desire to eat) were measured over 4 hours. Compared to control, the 4-hour glucose response was not different for MS and WM, and the 4-hour insulin response was higher for MS (P < .005) and lower for WM (P < .05). Compared to MS, WM led to lower 4-hour glucose and insulin responses (P < .001). These differences were driven by blunted glucose and insulin responses during the first hour for WM. Postprandial energy expenditure and appetite were not different among treatments. These results support that WM provides sustained glucose availability in young, insulin-sensitive adults.

Evaluation of a dietary targets monitor.

OBJECTIVE: To evaluate a two-page food frequency list for use as a Dietary Targets Monitor in large scale surveys to quantify consumptions of the key foods groups targeted in health promotion. DESIGN: Intakes of fruit and vegetables, starchy foods and fish estimated from a validated food frequency questionnaire (FFQ) were compared with a short food frequency list (the Dietary Targets Monitor) specifically designed to assess habitual frequency of consumption of foods in relation to dietary targets which form the basis of a National (Scottish) Food and Health Policy. SUBJECTS: A total of 1085 adults aged 25-64 y from the Glasgow MONICA Study. RESULTS: : The two questionnaires both collected data on frequencies of food consumption for fruit and vegetables, starchy foods and fish. Comparing the two questionnaires, there were consistent biases, best expressed as ratios (FFQ:Dietary Targets Monitor) between the methods for fruit and vegetables (1.33, 95% CI 1.29, 1.38) and 'starchy foods' (1.08, 95% CI 1.05, 1.12), the DTM showing systematic under-reporting by men. For fish consumption, there was essentially no bias between the methods (0.99, 95% CI 0.94, 1.03). Using calibration factors to adjust for biases, the Dietary Targets Monitor indicated that 16% of the subjects were achieving the Scottish Diet food target (400 g/day) for fruit and vegetable consumption. Nearly one-third (32%) of the subjects were eating the recommended intakes of fish (three portions per week). The Dietary Targets Monitor measure of starchy foods consumption was calibrated using FFQ data to be able to make quantitative estimates: 20% of subjects were eating six or more portions of starchy food daily. A similar estimation of total fat intake and saturated fat intake (g/day) allowed the categorization of subjects as low, moderate or high fat consumers, with broad agreement between the methods. The levels of agreement demonstrated by Bland-Altman analysis, were insufficient to permit use of the adjusted DTM to estimate quantitative consumption in smaller subgroups. CONCLUSIONS: The Dietary Targets Monitor provides a short, easily administered, dietary assessment tool with the capacity to monitor intakes for changes towards national dietary targets for several key foods and nutrients.

Energy expenditure and net substrate utilization in men ingesting usual and high amounts of nonstarch polysaccharide.

BACKGROUND: Diets intrinsically high in nonstarch polysaccharides (NSPs) are frequently advised for body weight regulation and health, but the consequences for energy expenditure and fuel selection are undetermined. OBJECTIVE: We determined whether energy expenditure and fuel selection differ when men consume a diet intrinsically higher in NSP than a usual mixed diet. DESIGN: A randomized crossover design was used in which 12 healthy men were fed a maintenance diet for approximately 3 wk in a metabolic suite. By judicial choice of food exchanges, the usual- and high-NSP diets were similar in protein, fat, and carbohydrate contents. Twenty-four-hour, indirect, open-circuit calorimetry was performed, including measurements of total hydrogen gas and methane. Participants were weight stable (within 2 kg for 3 wk), entered an 11-m3 calorimetry chamber for 36 h with measurements taken in the last 24 h, and underwent a strictly controlled program of moderate physical activity (1.3 x basal metabolic rate). RESULTS: The mean total 24-h energy expenditure and percentages from protein, fat, and carbohydrate metabolism were 10 MJ/d and 16%, 35%, and 48%, respectively. Differences (mean+/-SEM) between the 2 diets were only -0.005+/-0.130 MJ/d, -0.3+/-1.3%, -0.2+/-2.0%, and 0.6+/-2.2%, respectively, and were nonsignificant (P> 0.2). CONCLUSIONS: There was no thermogenic response to the high-NSP diet, which would be advantageous for body weight control, and no short-term influence on body composition, as may be judged from a lack of change in protein, fat, or carbohydrate metabolism.

Replacement of dietary fat by sucrose or starch: effects on 14 d ad libitum energy intake, energy expenditure and body weight in formerly obese and never-obese subjects.

OBJECTIVE: To investigate the impact of a high-sucrose diet vs a high-starch and a high-fat diet on 14 d ad libitum energy intake, body weight, energy expenditure and sympathoadrenal activity. MEASUREMENTS: Food intake; body weight and composition (bioelectrical impedance); 24 h energy expenditure, substrate oxidation rates, spontaneous physical activity, heart rate and appetite sensations in a respiration chamber (VAS scores); plasma catecholamine concentration and blood pressure. SUBJECTS: Twenty normal-weight, healthy women, 9 post-obese (body mass index (BMI): 22.9 +/- 0.7 kg/m2) and 11 closely matched controls (BMI: 22.6 +/- 0.4 kg/m2). RESULTS: Average 14 d ad libitum energy intake was 13% and 12% lower on the starch diet compared with the sucrose and fat diets, respectively (P < 0.05). In both post-obese and normal-weight subjects, body weight and fat mass decreased significantly on the starch diet (by 0.7 +/- 0.2 kg and 0.4 +/- 0.1 kg, respectively, P < 0.05). No changes were observed on the fat or sucrose diets. After 14 d on the sucrose diet, 24 h energy expenditure as well as postprandial plasma adrenaline and noradrenaline concentrations, were significantly increased compared with the other two diets. Overall satisfy and palatability ratings were also highest on the sucrose diet. CONCLUSION: Intake of a 14-d ad libitum high-starch diet decreased energy intake and body weight compared with a high-fat or high-sucrose diet. The increased energy expenditure observed on the sucrose-rich diet can probably be explained both by the increased intake of energy and fructose (mainly from sucrose) on this diet.

Energy balance and expenditure while consuming guar gum at various fat intakes and ambient temperatures.

We devised a new model to evaluate whether dietary composition affects whole-body energy metabolism in rats. Dietary guar gum, but not corn starch, elevates both fecal energy excretion and energy expenditure. Neither ambient temperature (21 vs 28 degrees C) nor fat content of the basal diet (15% vs 33% metabolizable energy) has a marked effect on guar gum's thermogenic stimulus. Starch and guar gum each contribute 17.5 kJ/g to gross energy intake. This energy is fully available from the starch but guar gum contributes only 9-13 kJ/g to digestible energy intake on the low-fat diet (15% of energy), only 6 kJ/g to digestible energy on the higher-fat diet (33% of energy) (because of a fat-gum interaction), decreases urinary energy loss by 1.4-2.7 kJ/g gum, and elevates energy expenditure by 11.6-14.8 kJ/g. The thermogenic effect of the guar gum is highly reproducible. Several potential mechanisms to explain such elevated energy expenditure are considered. The model used to quantify the thermogenic stimulus is highly sensitive and could be applied to the trial of potentially thermogenic drugs as well as dietary ingredients.

[An assessment of therapeutic effects by transcatheter arterial embolization (TAE) with degradable starch microspheres (DSM) for hepatic malignant tumors].

Transcatheter arterial embolization (TAE) by using degradable starch microspheres (DSM) as embolic material, 40 microns in diameter and degraded by serum amylase within one hour, was carried out for thirteen cases with hepatic malignancies including eleven cases with hepatocellular carcinoma (HCC), one case with cholangiocarcinoma and one case with metastatic liver cancer. DSM were mixed with anticancer agents and administered through the catheter, which was introduced by Seldinger's method, via the hepatic artery immediately after hepatic angiography in ten cases and through subcutaneously implanted drug delivery system (Port-A-Cath) in three cases. The dose of DSM was 900 mg/body and adriamycin 30-40 mg/m2 or 12-14 mg/m2 were used. The former was administered through the catheter immediately after angiography and the latter through Port-A-Cath for HCC and cholangiocarcinoma. A same dose of DSM and mitomycin C 15-16 mg/m2 was administered for metastatic liver cancer through the catheter immediately after angiography. The administration was repeated weekly in three cases in which Port-A-Cath was implanted, and at five weeks' interval through the catheter immediately after hepatic angiography in the other ten cases. Therapeutic effects were assessed and pharmacokinetics of adriamycin were studied. Results were as follows; 1) Partial response (PR) was obtained in five cases out of eleven cases with HCC (45.5%) and there were three cases with minor response (MR) in the other six cases. Totally, decrease of tumor size was demonstrated in eight cases out of eleven cases (72.7%). 2) In nine cases in which AFP was positive, the titer of AFP was decreased in seven cases (77.8%). 3) No change (NC) was obtained in cholangiocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

[Assessment of therapeutic effects by transcatheter arterial embolization (TAE) in hepatic malignant tumors with degradable starch microspheres (DSM)].

Transcatheter arterial embolization (TAE) with degradable starch microspheres (DSM) was carried out for fourteen cases with hepatic malignancies including twelve cases with hepatocellular carcinoma (HCC), one case with cholangiocarcinoma and one with metastatic liver cancer. DSM combined with anticancer agents were administered through a catheter introduced by Seldinger's method, in ten cases and through subcutaneously implanted drug delivery system (Port-A-Cath) in four cases. The dose of DSM was 900 mg/body and adriamycin 30-40 mg/m2 through the catheter or 12-14 mg/m2 through Port-A-Cath was used for HCC and cholangiocarcinoma. A same dose of DSM and mitomycin C 15 mg/m2 was administered for metastatic liver cancer through the catheter immediately after angiography. Results were as follows: 1) Partial response (PR) was obtained in six cases (50%) with HCC, and there were two other cases with minor response (MR). PR in cholangiocarcinoma and CR in metastatic liver cancer were obtained. 2) There were no adverse effects in four cases with Port-A-Cath. 3) The concentration of adriamycin in the peripheral venous blood was lower than that of one shot therapy, and decreased rapidly within an hour. These results suggested that good therapeutic effects can be obtained by TAE with DSM combined with anticancer agents for hepatic malignancies.