Long-term psychiatric inpatients' perspectives on weight gain, body satisfaction, diet and physical activity: a mixed methods study.

BACKGROUND: Obesity is a significant problem for people with serious mental illness. We aimed to consider body size from the perspective of long-stay psychiatric inpatients, focussing on: weight gain and its causes and impacts; diet and physical activity; and the perceived ability to make meaningful change in these domains. METHOD: A mixed methods study with 51 long-term psychiatric forensic and rehabilitation inpatients using semi-structured interviews combined with biometric and demographic data. RESULTS: 94% of participants were overweight or obese (mean BMI 35.3, SD 8.1). They were concerned about their weight, with 75% of them attempting to lose weight. Qualitative responses indicated low personal effectiveness and self-stigmatisation. Participants viewed their weight gain as something 'done to them' through medication, hospitalisation and leave restrictions. A prevailing theme was that institutional constraints made it difficult to live a healthy life (just the way the system is). Many had an external locus of control, viewing weight loss as desirable but unachievable, inhibited by environmental factors and requiring a quantum of motivation they found hard to muster. Despite this, participants were thoughtful and interested, had sound ideas for weight loss, and wished to be engaged in a shared endeavour to achieve better health outcomes. Consulting people as experts on their experiences, preferences, and goals may help develop new solutions, remove unidentified barriers, and improve motivation. CONCLUSIONS: The importance of an individualised, multifactorial approach in weight loss programmes for this group was clear. Patient-led ideas and co-design should be key principles in programme and environmental design.

Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period.

BACKGROUND: Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, one-carbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers. METHODS: Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS). RESULTS: Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality = 0.52) and urine (index of individuality = 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and -35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to -80% in plasma). CONCLUSIONS: Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value.

Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study.

BACKGROUND: Betaine is a major osmolyte, also important in methyl group metabolism. Concentrations of betaine, its metabolite dimethylglycine and analog trimethylamine-N-oxide (TMAO) in blood are cardiovascular risk markers. Diabetes disturbs betaine: does diabetes alter associations between betaine-related measures and cardiovascular risk? METHODS: Plasma samples were collected from 475 subjects four months after discharge following an acute coronary admission. Death (n = 81), secondary acute MI (n = 87), admission for heart failure (n = 85), unstable angina (n = 72) and all cardiovascular events (n = 283) were recorded (median follow-up: 1804 days). RESULTS: High and low metabolite concentrations were defined as top or bottom quintile of the total cohort. In subjects with diabetes (n = 79), high plasma betaine was associated with increased frequencies of events; significantly for heart failure, hazard ratio 3.1 (1.2-8.2) and all cardiovascular events, HR 2.8 (1.4-5.5). In subjects without diabetes (n = 396), low plasma betaine was associated with events; significantly for secondary myocardial infarction, HR 2.1 (1.2-3.6), unstable angina, HR 2.3 (1.3-4.0), and all cardiovascular events, HR 1.4 (1.0-1.9). In diabetes, high TMAO was a marker of all outcomes, HR 2.7 (1.1-7.1) for death, 4.0 (1.6-9.8) for myocardial infarction, 4.6 (2.0-10.7) for heart failure, 9.1 (2.8-29.7) for unstable angina and 2.0 (1.1-3.6) for all cardiovascular events. In subjects without diabetes TMAO was only significant for death, HR 2.7 (1.6-4.8) and heart failure, HR 1.9 (1.1-3.4). Adding the estimated glomerular filtration rate to Cox regression models tended to increase the apparent risks associated with low betaine. CONCLUSIONS: Elevated plasma betaine concentration is a marker of cardiovascular risk in diabetes; conversely low plasma betaine concentrations indicate increased risk in the absence of diabetes. We speculate that the difference reflects control of osmolyte retention in tissues. Elevated plasma TMAO is a strong risk marker in diabetes.

Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment are associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes.

PURPOSE: Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes? METHODS: Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants. RESULTS: Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy. CONCLUSIONS: Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial.

The relative effects of fat versus muscle mass on cystatin C and estimates of renal function in healthy young men.

BACKGROUND: It is well known that plasma creatinine concentration is affected by muscle mass, while some studies have suggested cystatin C is affected by body mass index (BMI). Our aim was to assess the effects of lean versus fat mass on cystatin C and creatinine derivative equations in estimating glomerular filtration rate (GFR) in healthy young men. METHODS: Three groups of participants were studied: those classified as normal (BMI 18-25 kg/m(2) with body fat <30%); muscular subjects (BMI >30 kg/m(2) and body fat <20%); and obese subjects (BMI >30 kg/m(2) and body fat >30%). All underwent diethylenetriamine pentaacetic acid GFR, bio-electrical impedance and dual-energy X-ray absorptiometry body composition analysis, measurement of plasma cystatin C, creatinine and high-sensitivity C-reactive protein and completed a diet record. RESULTS: Cystatin C was highest in the obese group (0.77 mg/L; 95% confidence intervals [CI] 0.69-0.77) and creatinine was highest in the muscular group (90.1 µmol/L; 95% CI 84.3-96.0). On multivariate analysis, body fat and GFR (P = 0.003) were significant determinants of cystatin C; muscle mass and age affected creatinine significantly (P = 0.02). Using cystatin C equations, Le Bricon and Hoek showed significantly lower estimated GFR in the obese group but performed reasonably well within 50%, 30% and 20% of GFR. Creatinine equations showed significant underestimations of GFR for the muscular group. CONCLUSIONS: Body fat is a significant determinant of cystatin C while creatinine concentration is highly affected by muscle mass and age. Body composition plays an important role in the interpretation of renal function. Cystatin C equations are still accurate in predicting GFR in our healthy male group without chronic kidney disease.

Betaine and secondary events in an acute coronary syndrome cohort.

BACKGROUND: Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. METHODS: Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. PRINCIPAL FINDINGS: The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). CONCLUSIONS: Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk.

The contrasting relationships between betaine and homocysteine in two clinical cohorts are associated with plasma lipids and drug treatments.

BACKGROUND: Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease. METHODS: The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. PRINCIPAL FINDINGS: In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = -0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = -0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion. CONCLUSIONS: Betaine excretion correlates with homocysteine in subjects with elevated blood lipids.

The NEEDNT Food List: non-essential, energy-dense, nutritionally-deficient foods.

AIM: To provide a list of non-essential, energy-dense, nutritionally-deficient foods in New Zealand (NEEDNT foods) which are usually high in calories and either bereft of nutritional benefits or easily replaced with lower calorie, more nutritious alternatives. METHODS: The List was compiled using the National Heart Foundation and Diabetes New Zealand "Foods to Avoid", "Stop Eating" and "Optional Foods" lists and the Canterbury District Health Board "Supermarket Shopping Guide". Foods and beverages were included if they contained alcohol, saturated fat, added sugar, were prepared using a high fat cooking method or contained a large amount of energy relative to their essential nutrient value. As it has no energy value, salt was not a criterion for inclusion on the List. RESULTS: Over 50 potential foods or groups of foods were identified that contained alcohol, saturated fat, added sugar, were prepared using a high fat cooking method or contained a large amount of energy relative to their essential nutrient value. Fifty foods/groups of foods were included on the final list (Table 1). CONCLUSIONS: The NEEDNT Food List will be a useful tool for medical practitioners and other health professionals working with people wanting to lose weight [corrected].

Plasma lipids and betaine are related in an acute coronary syndrome cohort.

BACKGROUND: Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these. METHODOLOGY: Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment. PRINCIPAL FINDINGS: Plasma betaine negatively correlated with triglyceride (Spearman's r(s) = -0.22, p<0.0001) and non-high-density lipoprotein cholesterol (r(s) = -0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin. CONCLUSION: Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk.

Fibrates plus betaine: a winning combination?

Because most of the cardiac risk remains despite successful statin therapy there has been renewed interest in fibrate therapy for persisting hyperlipidaemia. Fibrate therapy lowers triglycerides but causes the urinary loss of betaine, which is an essential metabolite that is involved in osmoregulation, in methyl group metabolism, and which also affects lipid partitioning in the body. Loss of betaine is associated with an elevation of homocysteine and may compromise the potential benefits of fibrate therapy. However, betaine deficiency could be easily and inexpensively corrected by concurrent betaine supplementation. Clinical trials of combinations of betaine and fibrate, to complement statin therapy, are needed to determine the value of these agents in reducing the residual cardiovascular disease risk.

Fibrates may cause an abnormal urinary betaine loss which is associated with elevations in plasma homocysteine.

PURPOSE: Betaine is an osmolyte, supplies methyl groups, and controls plasma homocysteine. Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations. We suggest there is a connection between fibrate treatment and betaine excretion. METHODS: We identified 32 fibrate-treated patients in several studies (total of 740 subjects) and compared the betaine excretion by these with the excretion by other patients, both in the separate studies and in the combined group. We investigated the correlation of betaine excretion with homocysteine in these groups. RESULTS: Patients taking bezafibrate had higher betaine excretion than patients not taking fibrates, p < 0.00001 in some studies with n < 10. Of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion. Plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate (n = 68, p = 0.043), but the relationship was stronger if patients taking bezafibrate were included (n = 76, p < 0.00001). In elderly (>65 years) subjects with hypertension there was a similar correlation (n = 19, p = 0.047), which was stronger when a subject taking bezafibrate was included (n = 20, p = 0.013). CONCLUSIONS: Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.

Comparison of insulin resistance, metabolic syndrome and adiponectin in overweight bipolar patients taking sodium valproate and controls.

OBJECTIVE: Metabolic abnormalities in patients with bipolar disorder may be secondary to obesity, aspects of the disorder or its treatment. To investigate this further, the purpose the present study was to compare insulin resistance, components of the metabolic syndrome and adiponectin levels in a group of overweight bipolar patients taking sodium valproate and a group of non-psychiatric control subjects. METHODS: Data were collected from 60 overweight bipolar patients who had experienced clinically significant weight gain thought to be related to sodium valproate treatment and from 60 control subjects without psychiatric illness matched for age, gender, body mass index and ethnicity. RESULTS: The frequency of the metabolic syndrome was high in both groups (50% and 32%, respectively), although not significantly different between groups (p = 0.06). Similar frequencies of insulin resistance (HOMA-IR), abdominal obesity, hypertriglyceridaemia, hypertension and fasting hyperglycaemia were found in both groups. High-density lipoprotein cholesterol levels were lower in patients (p = 0.006), while adiponectin was unexpectedly higher than in control subjects (9.6+/-5.9 microg mL(-1) vs 7.4+/-4.3 microg mL(-1), p = 0.03). The frequencies of insulin resistance (HOMA-IR), the metabolic syndrome and its individual components were not significantly different in patients taking atypical antipsychotic medication and patients not on these medications. CONCLUSIONS: Frequencies of insulin resistance and the metabolic syndrome were similar in bipolar patients taking sodium valproate and matched control subjects, but dyslipidaemia was more frequent. Adiponectin levels were higher in patients. Further research is required to clarify the reasons for these findings.

Carnitine does not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted, low-fat diet.

OBJECTIVES: Carnitine deficiency impairs fatty acid beta-oxidation and may partly explain weight gain in valproate-treated patients. The aim of this study was to determine whether l-carnitine supplementation improves weight loss outcomes in bipolar patients taking sodium valproate. METHODS: Sixty bipolar patients with clinically significant weight gain thought to be related to sodium valproate, who had been taking sodium valproate for >or=6 months, were randomized to l-carnitine (15 mg/kg/day) or placebo for 26 weeks, in conjunction with a moderately energy-restricted, low-fat diet. The primary outcome measure was weight change. RESULTS: l-carnitine had no effect on mean weight loss compared with placebo (-1.9 kg versus - 0.9 kg) (F = 0.778, df = 1,58, p = 0.381). The number of people in each group able to lose any weight was identical ( = 0, p = 1.0); more patients in the carnitine group (nine versus five) achieved a clinically significant weight loss (>or=5%) but this was not statistically significant (p = 1.0, Fisher's exact test). CONCLUSIONS: At the dose prescribed in this study carnitine supplementation did not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted, low-fat diet.