Campbell H. Thompson

Metabolic abnormalities in developmental dyslexia detected by 1H magnetic resonance spectroscopy

BACKGROUND Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain. METHODS We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age. FINDINGS We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or =0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men. INTERPRETATION We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.

Change in liver size and fat content after treatment with Optifast Very Low Calorie Diet

Background: Laparoscopic adjustable gastric banding (LAGB) requires surgical access to the gastroesophageal junction, which may be compromised by the enlarged, fatty liver that is frequently encountered in the obese. Liver size appears reduced and surgical access improved following preoperative weight loss with Optifast® Very Low Calorie Diet (VLCD). The aim of this study was to assess the effects of 6 weeks Optifast® VLCD on liver volume and fat content. Methods: 18 morbidly obese subjects underwent magnetic resonance imaging and spectroscopy to measure liver size and fat content before and after intensive treatment with Optifast® VLCD for 6 weeks. Results: All subjects completing 6 weeks Optifast® VLCD lost weight. Body weight and BMI (median [interquartile range]) reduced from 119.7 [111.9-131.3] kg and 44 [40-51] kg/m2 respectively, to 110.6 [98.0124.5] kg and 40 [36-47] kg/m2, P<0.001. Median excess weight loss (EWL) was 15.1 [9.6-21.1]%. Baseline liver volume and fat content were related (r=0.633, P=0.005). After 6 weeks Optifast® VLCD, there was a 14.7% reduction in mean liver volume (P<0.001) and a 43% reduction in mean liver fat (P=0.016). The change in liver volume was predicted by the change in the liver fat (r = 0.610, P=0.012). Conclusion: This study has demonstrated that a 6week diet with Optifast® VLCD results in significant related reductions in liver size and liver fat content. This suggests that the reduction in liver volume is due to loss of fat. The reduction in liver fat and volume likely accounts for the perceived improved operability in patients undergoing LAGB.

Noninvasive assessment of hepatic lipid composition: advancing understanding and management of fatty liver disorders

Nonalcoholic fatty liver is frequently observed in obese individuals, yet the factors that predict its development and progression to liver disease are poorly understood. We proposed that proton magnetic resonance spectroscopy (1H‐MRS) might allow noninvasive assessment of hepatic lipid composition. Lipid saturation (SI) and polyunsaturation (PUI) indices measured by 1H‐MRS were in agreement with those expected in oils of known composition. Hepatic triglyceride concentration (HTGC) and composition were then measured in healthy lean (LEAN) men, obese men with normal HTGC (OB), and obese men with hepatic steatosis (OB+HS). The effect of marked changes in dietary fat consumption on hepatic lipids were also compared in lean men after 67 hours of a normal mixed (NM) diet versus a low‐carbohydrate, high‐saturated‐fat (LCHF) diet. SI was significantly higher in OB+HS (0.970 ± 0.004) and OB (0.944 ± 0.008) versus LEAN (0.818 ± 0.025) (P < 0.01 for both). PUI was significantly lower in OB+HS (0.003 ± 0.001) and OB (0.022 ± 0.005) versus LEAN (0.120 ± 0.021) (P < 0.01), and significantly lower in OB+HS versus OB (P < 0.05). LCHF diet did not alter HTGC, SI, or PUI (P > 0.05). The 1H‐MRS method provides for rapid, qualitative assessment of lipid composition. Application of this technique in the liver produces results that are consistent with biopsy‐based approaches demonstrating that relative hepatic lipid saturation increases and polyunsaturation decreases with obesity. Obesity‐related hepatic steatosis is characterized by further depletion of polyunsaturated hepatic lipids. Conclusion: This readily available and noninvasive approach should promote further study into interactions between hepatic and whole‐body lipid metabolism and help to elucidate the pathogenesis of disorders characterized by lipid accumulation within the liver. (HEPATOLOGY 2008.)

A systematic review on animal models of maternal high fat feeding and offspring glycaemic control

The mechanistic link between obese parents and obese offspring and the relative role of genes, and a shared environment is not completely understood. Animal models help us to differentiate between genetic and environmental factors, and the interaction between the two. However, the willingness of researchers to blend results from multiple models makes it difficult for clear mechanisms to be identified for specific hypothesis-driven research. As such we conducted a systematic review of animal models of maternal high fat feeding in an effort to identify the affect on the offspring glycaemic control. Maternal and offspring outcomes are reported in an effort to identify possible relationships to facilitate and focus on future research. We present here data from 11 studies investigating glycaemic control in offspring exposed to a high fat diet (HFD) during maternal gestation only or gestation and lactation. Studies in this review identify a real risk of type 2 diabetes and obesity in male offspring exposed to a maternal HFD. Poor glycaemic control in the offspring appears to be independent of maternal obesity, birth weight or post-weaning macronutrient intake. Inconsistencies between studies however, limit our capacity to identify mechanisms for the developmental origin of these diseases in animal models of overnutrition.

Influence of constant positive airway pressure therapy on lipid storage, muscle metabolism and insulin action in obese patients with severe obstructive sleep apnoea syndrome.

Aim:  To observe the effect of constant positive airway pressure (CPAP) therapy on regional lipid deposition, muscle metabolism and glucose homeostasis in obese patients with obstructive sleep apnoea syndrome (OSAS).

Effect of creatine on aerobic and anaerobic metabolism in skeletal muscle in swimmers.

OBJECTIVE: To examine the effect of a relatively low dose of creatine on skeletal muscle metabolism and oxygen supply in a group of training athletes. METHODS: 31P magnetic resonance and near-infrared spectroscopy were used to study calf muscle metabolism in a group of 10 female members of a university swimming team. Studies were performed before and after a six week period of training during which they took either 2 g creatine daily or placebo. Calf muscle metabolism and creatine/choline ratios were studied in resting muscle, during plantar flexion exercise (10-15 min), and during recovery from exercise. RESULTS: There was no effect of creatine on metabolite ratios at rest or on metabolism during exercise and recovery from exercise. Muscle oxygen supply and exercise performance were not improved by creatine if compared to placebo treated subjects. CONCLUSIONS: Oral creatine supplementation at 2 g daily has no effect on muscle creatine concentration, muscle oxygen supply or muscle aerobic or anaerobic metabolism during endurance exercise.

Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial

BACKGROUND Few well-controlled studies have comprehensively examined the effects of very-low-carbohydrate diets on type 2 diabetes (T2D). OBJECTIVE We compared the effects of a very-low-carbohydrate, high-unsaturated fat, low-saturated fat (LC) diet with a high-carbohydrate, low-fat (HC) diet on glycemic control and cardiovascular disease risk factors in T2D after 52 wk. DESIGN In this randomized controlled trial that was conducted in an outpatient research clinic, 115 obese adults with T2D [mean ± SD age: 58 ± 7 y; body mass index (in kg/m(2)): 34.6 ± 4.3; glycated hemoglobin (HbA1c): 7.3 ± 1.1%; duration of diabetes: 8 ± 6 y] were randomly assigned to consume either a hypocaloric LC diet [14% of energy as carbohydrate (carbohydrate <50 g/d), 28% of energy as protein, and 58% of energy as fat (<10% saturated fat)] or an energy-matched HC diet [53% of energy as carbohydrate, 17% of energy as protein, and 30% of energy as fat (<10% saturated fat)] combined with supervised aerobic and resistance exercise (60 min; 3 d/wk). Outcomes were glycemic control assessed with use of measurements of HbA1c, fasting blood glucose, glycemic variability assessed with use of 48-h continuous glucose monitoring, diabetes medication, weight, blood pressure, and lipids assessed at baseline, 24, and 52 wk. RESULTS Both groups achieved similar completion rates (LC diet: 71%; HC diet: 65%) and mean (95% CI) reductions in weight [LC diet: -9.8 kg (-11.7, -7.9 kg); HC diet: -10.1 kg (-12.0, -8.2 kg)], blood pressure [LC diet: -7.1 (-10.6, -3.7)/-6.2 (-8.2, -4.1) mm Hg; HC diet: -5.8 (-9.4, -2.2)/-6.4 (-8.4, -4.3) mm Hg], HbA1c [LC diet: -1.0% (-1.2%, -0.7%); HC diet: -1.0% (-1.3%, -0.8%)], fasting glucose [LC diet: -0.7 mmol/L (-1.3, -0.1 mmol/L); HC diet: -1.5 mmol/L (-2.1, -0.8 mmol/L)], and LDL cholesterol [LC diet: -0.1 mmol/L (-0.3, 0.1 mmol/L); HC diet: -0.2 mmol/L (-0.4, 0.03 mmol/L)] (P-diet effect ≥ 0.10). Compared with the HC-diet group, the LC-diet group achieved greater mean (95% CI) reductions in the diabetes medication score [LC diet: -0.5 arbitrary units (-0.7, -0.4 arbitrary units); HC diet: -0.2 arbitrary units (-0.4, -0.06 arbitrary units); P = 0.02], glycemic variability assessed by measuring the continuous overall net glycemic action-1 [LC diet: -0.5 mmol/L (-0.6, -0.3 mmol/L); HC diet: -0.05 mmol/L (-0.2, -0.1 mmol/L); P = 0.003], and triglycerides [LC diet: -0.4 mmol/L (-0.5, -0.2 mmol/L); HC diet: -0.01 mmol/L (-0.2, 0.2 mmol/L); P = 0.001] and greater mean (95% CI) increases in HDL cholesterol [LC diet: 0.1 mmol/L (0.1, 0.2 mmol/L); HC diet: 0.06 mmol/L (-0.01, 0.1 mmol/L); P = 0.002]. CONCLUSIONS Both diets achieved substantial weight loss and reduced HbA1c and fasting glucose. The LC diet, which was high in unsaturated fat and low in saturated fat, achieved greater improvements in the lipid profile, blood glucose stability, and reductions in diabetes medication requirements, suggesting an effective strategy for the optimization of T2D management. This trial was registered at www.anzctr.org.au as ACTRN12612000369820.

A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects

BACKGROUND High-fat, low-carbohydrate diets are widely used for weight reduction, but they may also have detrimental effects via increased circulating free fatty acid concentrations. OBJECTIVE We tested whether raising plasma free fatty acids by using a high-fat, low-carbohydrate diet results in alterations in heart and brain in healthy subjects. DESIGN Men (n = 16) aged 22 ± 1 y (mean ± SE) were randomly assigned to 5 d of a high-fat, low-carbohydrate diet containing 75 ± 1% of calorie intake through fat consumption or to an isocaloric standard diet providing 23 ± 1% of calorie intake as fat. In a crossover design, subjects undertook the alternate diet after a 2-wk washout period, with results compared after the diet periods. Cardiac (31)P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, and computerized cognitive tests were used to assess cardiac phosphocreatine (PCr)/ATP, cardiac function, and cognitive function, respectively. RESULTS Compared with the standard diet, subjects who consumed the high-fat, low-carbohydrate diet had 44% higher plasma free fatty acids (P < 0.05), 9% lower cardiac PCr/ATP (P < 0.01), and no change in cardiac function. Cognitive tests showed impaired attention (P < 0.01), speed (P < 0.001), and mood (P < 0.01) after the high-fat, low-carbohydrate diet. CONCLUSION Raising plasma free fatty acids decreased myocardial PCr/ATP and reduced cognition, which suggests that a high-fat diet is detrimental to heart and brain in healthy subjects.

A Very Low Carbohydrate, Low Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial

OBJECTIVE To comprehensively compare the effects of a very low-carbohydrate, high–unsaturated/low–saturated fat diet (LC) with those of a high–unrefined carbohydrate, low-fat diet (HC) on glycemic control and cardiovascular disease (CVD) risk factors in type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Obese adults (n = 115, BMI 34.4 ± 4.2 kg/m2, age 58 ± 7 years) with T2DM were randomized to a hypocaloric LC diet (14% carbohydrate [<50 g/day], 28% protein, and 58% fat [<10% saturated fat]) or an energy-matched HC diet (53% carbohydrate, 17% protein, and 30% fat [<10% saturated fat]) combined with structured exercise for 24 weeks. The outcomes measured were as follows: glycosylated hemoglobin (HbA1c), glycemic variability (GV; assessed by 48-h continuous glucose monitoring), antiglycemic medication changes (antiglycemic medication effects score [MES]), and blood lipids and pressure. RESULTS A total of 93 participants completed 24 weeks. Both groups achieved similar completion rates (LC 79%, HC 82%) and weight loss (LC −12.0 ± 6.3 kg, HC −11.5 ± 5.5 kg); P ≥ 0.50. Blood pressure (−9.8/−7.3 ± 11.6/6.8 mmHg), fasting blood glucose (−1.4 ± 2.3 mmol/L), and LDL cholesterol (−0.3 ± 0.6 mmol/L) decreased, with no diet effect (P ≥ 0.10). LC achieved greater reductions in triglycerides (−0.5 ± 0.5 vs. −0.1 ± 0.5 mmol/L), MES (−0.5 ± 0.5 vs. −0.2 ± 0.5), and GV indices; P ≤ 0.03. LC induced greater HbA1c reductions (−2.6 ± 1.0% [−28.4 ± 10.9 mmol/mol] vs. −1.9 ± 1.2% [−20.8 ± 13.1 mmol/mol]; P = 0.002) and HDL cholesterol (HDL-C) increases (0.2 ± 0.3 vs. 0.05 ± 0.2 mmol/L; P = 0.007) in participants with the respective baseline values HbA1c >7.8% (62 mmol/mol) and HDL-C <1.29 mmol/L. CONCLUSIONS Both diets achieved substantial improvements for several clinical glycemic control and CVD risk markers. These improvements and reductions in GV and antiglycemic medication requirements were greatest with the LC compared with HC. This suggests an LC diet with low saturated fat may be an effective dietary approach for T2DM management if effects are sustained beyond 24 weeks.

Effect of short‐term starvation versus high‐fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men

It is currently believed that intramyocellular triglyceride (IMTG) accumulation and insulin resistance are a consequence of dietary fat ingestion and/or the elevated circulating lipid levels associated with chronic fat surplus. The purpose of this study was to compare the effect of short‐term starvation versus low‐carbohydrate (CHO)/high‐fat diet on IMTG accumulation and the development of insulin resistance in physically fit men. Intramyocellular triglyceride content, measured as intramyocellular lipid (IMCL) by proton magnetic resonance spectroscopy (1H‐MRS), and glucose tolerance/insulin sensitivity, assessed by frequently sampled intravenous glucose tolerance test (IVGTT), were determined after 67 h of: (a) water‐only starvation (S); and (b) very low‐CHO/high‐fat diet (LC). These diets had in common significant restriction of CHO availability but large differences in fat content. All results were compared with those measured after a mixed CHO diet (C). Dietary interventions were administered by cross‐over design. The level of dietary‐induced IMTG accumulation (P= 0.46), insulin resistance (P= 0.27) and glucose intolerance (P= 0.29) was not different between S and LC treatments. Intramyocellular triglyceride content and insulin sensitivity were negatively correlated (r=−0.63, P < 0.01). Therefore, whilst insulin resistance may be due to fat accumulation at a cellular level, in the integrated human organism this outcome is not exclusively a function of dietary fat intake. The comparable level of IMTG accumulation and insulin resistance following S and LC may suggest that these metabolic perturbations are largely a consequence of the increased lipolytic response associated with CHO restriction.