Weight loss after laparoscopic adjustable gastric band and resolution of the metabolic syndrome and its components.

BACKGROUND: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution. METHODS: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months. RESULTS: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m-2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss. CONCLUSIONS: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.

A longitudinal study of thyroid autoantibodies in pregnancy: the importance of test timing.

OBJECTIVE: Thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TGAb) are frequently measured to investigate thyroid dysfunction in pregnancy. Despite the recognized fall of these autoantibodies in pregnancy, there is limited guidance on the timing of such testing. We assessed optimal test timing of TPOAb/TGAb for the detection of Hashimoto's thyroiditis and post-partum thyroid dysfunction (PPTD). DESIGN: Prospective longitudinal study with recruitment in Trimester 1. PATIENTS: Healthy women ≤13 weeks' gestation from Mercy Hospital for Women, a tertiary obstetric hospital in Melbourne. MEASUREMENTS: Serum TPOAb, TGAb, TSH and fT4 were measured at Trimester 1 (T1), Trimester 2(T2), Trimester 3(T3) and postpartum (PP) in each participant. Post-partum thyroid dysfunction (PPTD) was defined if TSH deviated from the assay's nonpregnant reference interval. Longitudinal random-effect logistic regression was used to investigate the association between time and positive/negative thyroid autoantibody status. RESULTS: Samples from 140 women at T1 (12·0: 10·3-13·0) (median: IQR weeks' gestation); 95 at T2 (24·3: 23·0-25·9), 79 at T3 (35·9: 34·8-36·7) and 83 at PP (12·4: 10·8-14·6 weeks post-partum) were attained. At T1, 13 (9%) and 15 (11%) women had positive TPOAb and TGAb, respectively. The odds of having a positive TPOAb were 96% lower at T2 [OR = 0·04 (95% CI: 0·02-0·8; P = 0·03)] and 97% lower at T3 [OR = 0·03 (95% CI: 0·001-0·6; P = 0·02)] than at T1. Similarly, the odds of having a positive TGAb were 99·4% lower [OR = 0·006 (95% CI: 0-0·3; P = 0·01)] at T2, and 99·5% lower [OR = 0·005 (95% CI: 0-0·4; P = 0·02)] at T3 than at T1. The ROC analysis diagnostic ORs for a positive TPOAb and/or TGAb to predict PPTD were 7·8 (95% CI: 2·2-27·6), 1·2 (95% CI: 0-8·9), 2·0 (95% CI: 0-16·8), and 12·2 (95% CI: 3·3-44·9) at T1, T2, T3 and post-partum, respectively. CONCLUSIONS: A significant proportion of pregnant women lose their thyroid autoantibody positivity after T1. The gestation-dependent loss of TPOAb/TGAb positivity and reduction in diagnostic accuracy for predicting PPTD limits the value of testing at T2 and T3.

Vitamin B12 and homocysteine status during pregnancy in the metformin in gestational diabetes trial: responses to maternal metformin compared with insulin treatment.

AIM: The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus (GDM) on vitamin B12 and homocysteine (Hcy) status. METHODS: Women with GDM, who met criteria for insulin treatment, were randomly assigned to metformin (n = 89) or insulin (n = 91) in the Adelaide cohort of the metformin in gestational diabetes (MiG) trial. Fasting serum total vitamin B12 (TB12), holotranscobalamin (HoloTC), a marker of functional B12 status and plasma Hcy concentrations were measured at 20-34 weeks (at randomization) and 36 weeks gestation, then at 6-8 weeks postpartum. RESULTS: Circulating TB12, HoloTC and Hcy were similar in both treatment groups at each time point. Women who were taking dietary folate supplements at randomization had higher serum TB12 and HoloTC at randomization than those not taking folate. Overall, serum TB12 fell more between randomization and 36 weeks gestation in the metformin group than in the insulin group (metformin: -19.7 ± 4.7 pmol/l, insulin: -6.4 ± 3.6 pmol/l, p = 0.004). The decrease in serum TB12 during treatment was greater with increasing treatment duration in metformin-treated (p < 0.001), but not in insulin-treated women. CONCLUSIONS: Total, but not bioavailable, vitamin B12 stores were depleted during pregnancy to a greater extent in metformin-treated than in insulin-treated women with GDM, but neither analyte differed between groups at any stage. This adds further evidence supporting metformin as a safe alternative treatment to insulin in GDM. Further investigation is needed to evaluate whether women treated with metformin for longer periods in pregnancy require additional B12 or other supplementation.

Towards appreciating appropriate clinical responses to highly sensitive cardiac troponin assays.

Cardiac troponins (cTn) are structural components of the contractile apparatus of the cardiomyocyte and the recommended biochemical markers for diagnosing myocardial infarction. Although the diagnostic performance of both cTnT and cTnI as biochemical markers are quite similar, it is the analytical sensitivities of these assays that have been found to create the difference. High-sensitivity cTn assays, which are capable of measuring cTn levels 10-folds lower than conventional fourth generation assays, are results of continuous effort to develop more sensitive and accurate tests to detect cardiac injury. While the improvement in the sensitivity of these assays promises improvement in many aspects of patient care, such as earlier myocardial infarction diagnosis and cardiac disease risk assessment, shortcoming of these assays must be considered. Very low measurable levels of cardiac damage biochemical markers can deliver occult yet possible decisive message. Better understanding of the pros and cons of these assays will pledge an appropriate clinical reaction to highly sensitive results.

Sugar restriction: the evidence for a drug-free intervention to reduce cardiovascular disease risk.

BACKGROUND/AIM: Uncertainty exists about what dietary component is most likely to cause coronary heart disease. Over the last thirty years, attention has focused on saturated fat and salt as guilty parties. More recently, evidence suggests that excess sugar intake is more likely than either traditional factor to lead to atherosclerotic disease. Some researchers have also speculated that sugar is addictive, in a similar manner to caffeine and established drugs of abuse. METHODS: Here we review the epidemiological, biochemical and psychological evidence that implicates excess sugar intake as an important cause of ill-health. RESULTS: We found relatively consistent evidence of association between markers of sugar intake and risk factors for cardiovascular disease, or the disease itself. This evidence contrasted with rather weaker evidence which linked either saturated fat or salt with cardiovascular disease endpoints. We also found some evidence of a sugar addiction syndrome. CONCLUSION: We suggest that advice to restrict sugar intake should be a routine part of clinical care, particularly when patients are being counselled about cardiovascular risk.

Validation of an algorithm combining haemoglobin A(1c) and fasting plasma glucose for diagnosis of diabetes mellitus in UK and Australian populations.

AIM: To determine whether glycated haemoglobin (HbA(1c)) can be used in combination with fasting plasma glucose (FPG) for the diagnosis of diabetes in patients with impaired fasting glucose (IFG) and in a broader spectrum of patients. METHODS: An algorithm was derived from oral glucose tolerance test (OGTT) capillary samples in 500 consecutive UK patients with IFG by World Health Organization criteria. It was validated in a further 500 UK patients and, with venous specimens, in 1175 unselected Australian patients. RESULTS: The derivation cohort was aged 61 years (50-69 years) (median IQ range) with 52% male and 12% South Asian. Diabetes Control and Complications Trial-aligned HbA(1c) was 6.2% (5.8-6.6%) (reference interval < 6.0%) and FPG 6.7 mmol/l (6.3-7.2 mmol/l). FPG was in the diabetes range in 36% of patients, with an OGTT identifying a further 12% with diabetes. The derived algorithm, (HbA(1c) >or= 6.0% with FPG < 7.0 mmol/l) identified those patients requiring an OGTT to diagnose diabetes. When applied to the UK validation cohort, sensitivity was 97% and specificity 100%. The algorithm was equally effective in the unselected group, aged 59 years (49-68 years) and 54% male, with sensitivity 93% and specificity 100%. HbA(1c) was 6.0% (5.6-6.6%) and FPG 6.0 mmol/l (5.3-6.8 mmol/l), with 26% having IFG. Use of the algorithm would reduce the number of OGTTs performed in the UK validation cohort by 33% and by 66% in the Australian patients studied. CONCLUSIONS: Use of this algorithm would simplify procedures for diagnosis of diabetes and could also be used for monitoring pre-diabetes. Validation is now required in other populations and patient groups.

Review of a pilot quality-assessment program for interpretative comments.

BACKGROUND: Interpretative commenting constitutes an important aspect of the post-analytical phase in chemical pathology, but has only recently been the subject of quality assessment. The Royal College of Pathologists of Australasia (RCPA)-Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program is currently in its third year, having started in 2000 as a pilot program. We present a review of the pilot program. METHODS: The program is aimed at individuals rather than laboratories. Two cases were circulated to participants of the Chemical Pathology Quality Assurance Program every month over a 6-month period. The case report contained the age and sex of the patient, together with brief clinical notes, the biochemistry results for commenting and other information of relevance. Three lines of space were given for the comment. The comments received from participants were broken down into their components and translated into common key phrases for the purpose of summarization and analysis. A histogram of the frequency of use of the common key phrases was generated. The comments or the key phrases were not given scores or marks, nor was any other indication given as to the appropriateness of their comments. RESULTS: This approach of simple peer-group comparison of comments without any assessment of the appropriateness of the comments was found to be inadequate; thus, when the program continues, key phrases will be classified according to degree of appropriateness and a suggested comment for each case will be proposed by an 'expert' panel. CONCLUSIONS: The program can serve a useful role in continuing education. Clinical biochemists and trainees who add interpretative comments to results produced by their laboratory, or give interpretative advice over the telephone, may potentially benefit from participating in this program.

Differential response of prostate specific antigen to testosterone surge after luteinizing hormone-releasing hormone analogue in prostate cancer and benign prostatic hyperplasia.

OBJECTIVE: To investigate any differences in changes in serum prostate specific antigen (PSA) levels in patients with benign and malignant prostatic disease in response to the testosterone surge after administering a luteinizing hormone-releasing hormone (LHRH) analogue. PATIENTS AND METHODS: The study included 54 patients referred to the urology clinic with intermediate PSA levels (4-10 ng/mL) or an abnormal digital rectal examination. Forty-five patients received a single injection of LHRH analogue depot each at one week before prostate biopsy and nine served as a control group. Changes in PSA levels in response to the testosterone surge from the LHRH analogue were recorded after 5 and 7 days, and were correlated with the biopsy results. The PSA changes were compared with basal PSA levels and the free/total PSA ratio(f/tPSA). RESULTS: Of the 45 patients who underwent prostate biopsy, histopathology showed prostate cancer in 11, benign prostatic hyperplasia in 33 and prostatic intraepithelial neoplasia in one. Patients with cancer had a significantly greater increase in serum PSA levels during the first week after LHRH injection than those in the benign and control groups. Receiver operating characteristic curves showed that the percentage change in PSA level on day 5 was more diagnostic than total PSA and f/tPSA. CONCLUSIONS: There was a marked difference in the PSA response of patients with benign or malignant disease to the testosterone surge produced by the LHRH analogue. Although a larger study would be needed before LHRH-induced provocation could be proposed as a clinical test, in this small series the response was better than that for total PSA or f/tPSA in differentiating benign and malignant disease.

Extreme anxiety/panic disorder.

A 45 year old man is referred to a specialist psychiatric centre. For 3 years he has been experiencing worsening impending fear of death and anxiety which he describes as 'panic attacks'. During these episodes he often experiences palpitations and becomes sweaty. These episodes have not been relieved despite several courses of electroconvulsive therapy. On examination, the man is alert and orientated. He has a normal blood pressure of 125/75 mmHg and electrocardiogram reveals a pulse rate of 102 beats per minute. A psychiatrist orders a number of routine tests to rule out organic disease.

A comparative study of the efficacy of simvastatin and gemfibrozil in combined hyperlipoproteinemia: prediction of response by baseline lipids, apo E genotype, lipoprotein(a) and insulin.

Combined hyperlipoproteinemia (CHL) can be difficult to treat because of the heterogeneous nature of the lipoprotein abnormalities. We compared the relative efficacies of simvastatin and gemfibrozil and sought predictors of responsiveness in terms of the baseline lipids and other potential metabolic determinants (plasma insulin, Lp(a) and apo E genotype). Sixty-six subjects entered a cross-over, randomized trial involving 12 weeks on each drug. Efficacy was assessed after 6 and 12 weeks on each treatment. Simvastatin lowered total cholesterol 24%, triglycerides 12%, LDL cholesterol 33%, raised HDL cholesterol 13% and substantially reduced the cholesterol:triglyceride ratio in VLDL and IDL. Gemfibrozil lowered total cholesterol 5%, triglycerides 44%, raised HDL 26% and reduced VLDL and IDL lipids more than simvastatin did. LDL size increased with both treatments and HDL size increased with simvastatin. Responsiveness (25% fall in cholesterol or 40% fall in triglycerides) was shown by 31/61 subjects when taking simvastatin (cholesterol-lowering) and by 44/60 taking gemfibrozil (triglyceride-lowering). Responsiveness was greatest in those with apo E2 genotype with both drugs (P < 0.05). Unexpectedly, responders to simvastatin tended to have lower baseline total cholesterol but higher triglyceride levels than those whose cholesterol or triglyceride was lowered by gemfibrozil. Nevertheless, more hypercholesterolemic subjects responded to simvastatin and more hypertriglyceridemic subjects to gemfibrozil. Lp(a) (P = 0.04) and plasma insulin concentrations (P = 0.03) were negative predictors of percentage triglyceride-lowering with gemfibrozil. The difference between the two drugs in triglyceride-lowering lessened with rising insulin and falling HDL cholesterol. Thus, the responsiveness to the two major classes of lipid lowering drugs can be partly predicted from baseline lipids and related metabolic parameters.

Low density lipoprotein particle size in hypopituitary adults receiving conventional hormone replacement therapy.

Adults receiving conventional replacement therapy for hypopituitarism are known to have increased cardiovascular mortality. The aim of this study was to assess the lipid profiles of 30 hypopituitary adults compared with 2 case control groups, 1 matched for age, sex, and body mass index (BMI) and the second matched for age and sex only with a BMI representative of the general population. Fasting lipids, lipoproteins, and apoproteins (Apo) were determined by routine methods. Low density lipoprotein (LDL) particle size was determined by nondenaturing gradient gel electrophoresis. LDL size was significantly smaller in the hypopituitary group (25.9 +/- 0.1 nm) than in the BMI-matched (26.2 +/- 0.1 nm; P < 0.05) and standard control (26.3 +/- 0.1 nm; P < 0.01) groups. High density lipoprotein cholesterol levels in the hypopituitary group were significantly lower than those in the BMI-matched control group (1.13 +/- 0.06 vs. 1.34 +/- 0.06 mmol/L; P < 0.05) and the standard control group (1.38 +/- 0.06 mmol/L; P < 0.005). Apo A1 levels were also lower compared with those in the BMI-matched (122 +/- 6 vs. 137 +/- 4 mg/dL; P < 0.05) and the standard (143 +/- 4 mg/dL; P < 0.005) control groups. There was a trend toward higher triglyceride levels when the hypopituitary subjects were compared with the standard control group [1.4 (95% CI, 1.3-2.2) vs. 1.0 (95% CI, 0.9-1.4) mmol/L; P = 0.06]. These differences were more marked in the female subjects studied. No significant differences were noted in total cholesterol, LDL cholesterol, or Apo B levels. We conclude that hypopituitary patients receiving conventional replacement therapy have an atherogenic lipid profile characterized by small dense LDL, decreased high density lipoprotein cholesterol, and increased triglyceride levels, which may contribute to the excess cardiovascular mortality in this group.