Lean mass modulates glomerular filtration rate in males of normal and extreme body composition.

BACKGROUND: Understanding determinants of glomerular filtration rate (GFR) is important in aiding prediction and interpretation of kidney function. Body composition is known to affect GFR but is not included in current screening of kidney disease. We investigated the association between GFR and body composition in healthy young men with differing body mass but without known diabetes or kidney injury. METHODS: Three groups were recruited: normal BMI (n = 22) with a body mass index (BMI) <25 kg/m(2) , muscular (n = 23) with BMI ≥30 kg/m(2) and bioelectrical impedance body fat ≤20% and obese (n = 22) with BMI ≥30 kg/m(2) and bioelectrical impedance body fat ≥30%. Dietary analyses, GFR clearance by (99m) Tc-DTPA, urine protein and body composition by dual-energy X-ray absorptiometry were measured in all participants. Linear and nonlinear associations of constituents of body composition with GFR were assessed. RESULTS: Muscular men had a higher GFR (mean 186.4 mL/min; 95% CI 171.7-201.1) than normal BMI and obese groups (P = 0.0007). Urine protein and albumin excretion were not elevated in any participants. On multiple regression analysis (r(2) = 0.60), the variables with strong associations with GFR were age (P = 0.0009) and lean mass (P = 0.0001). Fat mass, protein intake and smoking status were not associated. Skeletal muscle mass correlated significantly with GFR in all subgroups. CONCLUSION: Age and lean mass were strong determinants of GFR. Estimates of GFR should therefore be indexed to an estimate of lean mass.

Dietary and supplementary betaine: effects on betaine and homocysteine concentrations in males.

BACKGROUND AND AIMS: Betaine is an osmolyte that when catabolised decreases plasma total homocysteine. A betaine-rich meal has acute effects similar to a supplement, but the effects of a longer-term increase in dietary betaine intake need clarification. We compared the effects of two weeks of dietary and supplementary betaine on plasma betaine and homocysteine concentrations both fasting and after a methionine load. METHODS AND RESULTS: In a randomized crossover study, 8 healthy males (22-36 y) consumed either a betaine-rich diet ( approximately 800 mg/day) or a betaine supplement (0.5 g twice daily) for 14 days. Fasting blood samples were collected on day -5, -1 (pre-treatment) 0, 2, 6, 9, 13 (treatment), 14 and 18 (post-treatment). Post-methionine load blood samples were collected on day -5, 0, 6 and 13, while 24h urine samples were collected on day -5, 0, 6, 13 and 14. Plasma betaine, dimethylglycine, homocysteine and urine betaine, dimethylglycine and creatinine concentrations were measured. Plasma betaine concentrations significantly increased for both treatments compared to pre-treatment values (P<0.001). Fasting homocysteine levels were minimally affected. Both treatments reduced post-methionine load homocysteine and this effect tended to be greater following a betaine-rich diet (P=0.108). Small increases in urinary betaine excretion were observed following both treatments ( approximately 1.5% of supplement; approximately 1.3% of dietary betaine). Most was attributable to increased excretion of betaine as dimethylglycine. CONCLUSIONS: Supplemental or dietary betaine similarly increase circulating betaine concentrations and attenuate the post-methionine load rise in homocysteine concentrations.

Upstream genetic variant near INSIG2, influences response to carnitine supplementation in bipolar patients with valproate-induced weight gain.

BACKGROUND: The protein product of INSIG2 is involved in cholesterol and triglyceride metabolism and homeostasis. Variation at rs7566605 near the gene INSIG2 has been associated with increased BMI. OBJECTIVE: To evaluate the effect of rs7566605/INSIG2 genotype on the ability of valproate-treated bipolar patients (BMI ≥ 25 kg/m2) to lose weight using carnitine supplementation during a 26-week lifestyle intervention study. DESIGN: Forty-eight bipolar patients with clinically significant treatment emergent weight gain were genotyped at the rs7566605 SNP. Participants were randomised to l-carnitine (15 mg/kg/day) or placebo for 26 weeks in conjunction with a moderately energy restricted, low-fat diet. Weight and body fat percent were measured fortnightly. Waist circumference measurements and dual-energy X-ray absorptiometry were used to assess changes in body composition. Obesity-related biomarkers were measured at baseline and 26 weeks. RESULTS: There was a significant interaction between rs7566605/INSIG2 genetic status and treatment with carnitine or placebo. Carnitine had no significant effect on body composition measures in G allele homozygous patients who lost between 0.97 and 2.23 kg of fat. However C allele carriers on average gained 2.28 kg when given a placebo. Carnitine supplementation in this group enabled average weight loss of 2.22 kg of fat (p = 0.01). Approximately half of this mass was in the vital truncal compartment (p = 0.002). Bioinformatic analysis detected that the SNP lies in a highly conserved 336 bp sequence which potentially affects INSIG2 gene expression. CONCLUSIONS: C-carriers at rs7566605, possibly regulating the homeostasis gene INSIG2, lost significantly less weight in this lifestyle intervention study. This effect was reversed by carnitine supplementation.

Determinants of overweight and obesity in patients with bipolar disorder.

OBJECTIVE: To examine lifestyle-related determinants of the excess adiposity observed in patients with bipolar disorder. METHOD: Eighty-nine male and female patients with DSM-IV bipolar disorder who were attending a specialist bipolar clinic or another psychiatric outpatient clinic (19% with body mass index [BMI] > or = 30) and 445 age- and sex-matched reference subjects (12% with BMI > or = 30) participated in a cross-sectional study of nutrient intake and physical activity. Main outcome measures included macronutrient intakes (assessed with 24-hour recall), percentage of energy derived from various food sources, and physical activity levels (assessed with the Life in New Zealand Questionnaire). RESULTS: Mean total energy intake was higher in female patients than in reference subjects: 8468 kJ compared with 6980 kJ (95% confidence interval [CI] = 583 to 2392 kJ). Total daily sucrose and percentage of energy from carbohydrate were higher in patients than in reference subjects; for women, 73 g and 49% (95% CI = 20 to 56 g, 3% to 10) and for men, 89 g and 47% (95% CI = 15 to 59 g, 3% to 9%). Total fluid intake and intake of sweetened drinks were higher in patients than in reference subjects (ratio of geometric means: women, 1.2 and 2.3, respectively [95% CI = 1.1 to 1.4, 1.9 to 2.8]; men, 1.1 and 2.1, respectively [95% CI = 1.0 to 1.23, 1.8 to 2.41). Patients reported fewer episodes of low- to moderate-intensity and high-intensity physical activity as compared with reference subjects (p < or = .05). CONCLUSION: This study confirms that drug-induced changes in food preference can lead to an excessive energy intake largely as a result of a high intake of sucrose. Dietary advice regarding the use of energy-rich beverages along with encouragement to increase levels of physical activity may help prevent weight gain in bipolar patients. The findings also have some bearing on dietary advice aimed at avoiding overweight and obesity in the general population.

Prevalence of overweight and obesity in bipolar patients.

BACKGROUND: Patients who receive pharmacologic treatment for bipolar illness frequently gain weight. This study evaluated the prevalence of overweight and obesity in an unselected group of bipolar patients and matched reference subjects. METHOD: The prevalence of overweight, obesity, and central adiposity was evaluated in 89 euthymic bipolar (DSM-IV) patients and 445 reference subjects, matched for age and sex, using a cross-sectional study design. RESULTS: Female patients were more often overweight and obese than female reference subjects (chi2 = 9.18, df = 2, p = .01). The frequency of overweight was similar in male patients and male reference subjects, but male patients were more likely to be obese. Patients were more centrally obese than the general population in women (chi2 = 32.21, df = 1, p = <.001) and in men (chi2= 8.81, df = 1, p = .003). Patients treated with antipsychotic drugs were more obese than patients not receiving these drugs (chi2= 4.7, df = 1, p = .03). CONCLUSION: Body fat is more centrally distributed in pharmacologically treated bipolar patients than in matched population controls. Obesity is more prevalent in patients than in the general population. Obesity prevalence is clearly related to the administration of antipsychotic drugs.

The response to treatment of subclinical thiamine deficiency in the elderly.

The significance of subclinical thiamine deficiency in the elderly was determined by assessing response to thiamine supplementation in a randomized double-blind, placebo-controlled trial. Thirty-five of 222 people aged > or = 65 y had two concentrations of erythrocyte thiamine pyrophosphate (TPP) < 140 nmol/L 3 mo apart and 41 other people had the first, but not the second, TPP concentration below this value. Both groups were randomly assigned in a double-blind trial to oral thiamine (10 mg/d) or a placebo. All subjects randomly assigned to receive thiamine showed increases in TPP concentrations compared with control subjects. Only the subjects with persistently low TPP concentrations showed subjective benefits from treatment with improvements in quality of life (measured on a visual analogue scale; P = 0.02) and decreases in systolic blood pressure (P = 0.05) and weight (P < 0.01) when compared with subjects given placebo. There was a trend toward benefits in sleep and energy (P = 0.07). We conclude that a low TPP concentration on two occasions is a better predictor of response to treatment than an isolated measurement. Quality of life was enhanced by providing thiamine supplements. Blood pressure and weight were lower after thiamine supplementation.