Profiling retrospective thyroid function data in complete thyroidectomy patients to investigate the HPT axis set point (PREDICT-IT).

BACKGROUND: The homeostatic euthyroid set point of the hypothalamus-pituitary-thyroid axis of any given individual is unique and oscillates narrowly within substantially broader normal population ranges of circulating free thyroxine (FT4) and thyroid-stimulating hormone (TSH), otherwise termed 'thyroid function test (TFT)'. We developed a mathematical algorithm codenamed Thyroid-SPOT that effectively reconstructs the personalized set point in open-loop situations and evaluated its performance in a retrospective patient sample. METHODS: We computed the set points of 101 patients who underwent total thyroidectomy for non-functioning thyroid disease using Thyroid-SPOT on each patient's own serial post-thyroidectomy TFT. Every predicted set point was compared against its respective healthy pre-operative euthyroid TFT per individual and their separation (i.e. predicted-observed TFT) quantified. RESULTS: Bland-Altman analysis to measure the agreement between each pair of an individual's predicted and actual set points revealed a mean difference in FT4 and TSH of + 3.03 pmol/L (95% CI 2.64, 3.43) and - 0.03 mIU/L (95% CI - 0.25, 0.19), respectively. These differences are small compared to the width of the reference intervals. Thyroid-SPOT can predict the euthyroid set point remarkably well, especially for TSH with a 10-16-fold spread in magnitude between population normal limits. CONCLUSION: Every individual's equilibrium euthyroid set point is unique. Thyroid-SPOT serves as an accurate, precise and reliable targeting system for optimal personalized restoration of euthyroidism. This algorithm can guide clinicians in L-thyroxine dose titrations to resolve persistent dysthyroid symptoms among challenging cases harbouring "normal TFT" within the laboratory ranges but differing significantly from their actual euthyroid set points.

Brown fat activity determined by infrared thermography and thermogenesis measurement using whole body calorimetry (BRIGHT Study).

To assess BAT activity in humans at a population level, infrared thermography (IRT) represents a safe, readily repeatable and affordable alternative to 18F-FDG-PET. Building upon a previously proposed method by our laboratory, we further refined the image computational algorithm to quantify BAT activation in the cervical-supraclavicular (C-SCV) region of healthy young men under thermo-neutral and cold exposure conditions. Additionally, we validated the whole-body calorimeter (WBC) in reliably measuring cold-induced thermogenesis. The temperature gradient between C-SCV-deltoid regions, and the corresponding difference in heat power output, increased upon cold air exposure relative to thermo-neutral conditions (by 74.88 %, p<0.0001; and by 71.34 %, p<0.0001 respectively). Resting and cumulative energy expenditure (EE) rose significantly (by 13.14 % and 9.12 % respectively, p=0.0001) while positive correlations between IRT measures and EE were found with cold air exposure (percentage change in heat power gradient between ROI and deltoid, cold air: r(2)=0.29, p=0.026, Pearson's correlation). IRT and WBC can be used to study BAT activation. The refined algorithm allows for more automation and objectivity in IRT data analysis, especially under cold air exposures.

Associations of physical activity levels and screen time with oral glucose tolerance test profiles in Singaporean women of reproductive age actively trying to conceive: the S-PRESTO study.

AIM: To examine the associations of physical activity and screen time, a proxy for sedentary behaviour, with fasting and post-load glucose levels in Singaporean women enrolled in a multi-ethnic Asian preconception study. METHODS: Moderate and vigorous physical activity and screen time (television and other electronic devices) were self-reported by women enrolled in the S-PRESTO cohort. Fasting, 30-min and 120-min glucose levels before and during a 75-g oral glucose tolerance test were measured. Associations of physical activity and screen time with glucose levels were analysed using multivariable linear marginal regression. RESULTS: A total of 946 women aged 31.4±3.7 years were examined, of whom 72% were of Chinese, 15.5% were of Malay, 9.3% were of Indian and 3.2% were of mixed ethnicity. A total of 32% of women reported being active, 36% watched television ≥2 h/day and 26% used electronic devices ≥3 h/day. In adjusted models, vigorous, but not moderate, physical activity was associated with lower overall glucose levels, and was associated more strongly with post-challenge than fasting glucose levels. Compared to women not engaging in vigorous physical activity, those engaging in physical activity ≥75 min/week had lower mean fasting [-0.14 (95% CI -0.28, -0.01) mmol/l], 30-min [0.35 (95% CI -0.68, -0.02) mmol/l] and 120-min [-0.53 (95% CI -0.16, -0.90) mmol/l] glucose levels (overall P value=0.05). We found no associations of screen time with glucose levels. CONCLUSIONS: Independently of the time spent in non-vigorous physical activity and using screens, engaging in vigorous physical activity may be a modifiable factor to improve glucose regulation in women of Asian ethnicity who are attempting to conceive.

Use of dorsal buttress plate fixation for ulnar carpometacarpal joint fracture dislocations for early mobilization: outcomes of 11 cases.

AIM: This study reviews the surgical outcomes of using dorsal buttress plate for open reduction and internal fixation of ulnar (5th, or 4th and 5th) CMCJ fracture subluxation or dislocations. METHODS: A retrospective review of 11 patients at our center who underwent operative fixation with dorsal buttress plating technique was performed. The surgery was performed between February 2012 and March 2017. Outcome measurements include radiographic evaluation of time to union, grip strength, and range of motion of the wrist. RESULTS: Of 11 patients in our case series, eight had injuries involving both 4th and 5th CMCJs, while three had isolated involvement of 5th CMCJ. Mean time to union on radiographs was 48 days (IQR 17.0; range 30-88). The median palmar flexion and dorsiflexion of the wrist were 56° (IQR 11.3; range 50°-80°) and 65° (IQR 10.0; range 60°-80°) respectively. Patients regained a median of 79% of grip strength (IQR: 36.0, range 43-100). All fingers achieved full range of motion, and no patient had scissoring of the fingers. Two patients had temporary mild numbness over the dorsoulnar aspect of the hand in the region of the 4th webspace. Five patients underwent removal of implants due to plate breakage (n = 2), or mild pain or pain with cold (n = 3). All patients were well after plate removal, and all the patients with pain had resolution of pain after implant removal. CONCLUSION: The dorsal buttress plate is a viable option for fixation of ulnar CMCJ fracture dislocations to allow early mobilization.

Oxytocin in metabolic homeostasis: implications for obesity and diabetes management.

Oxytocin was once understood solely as a neuropeptide with a central role in social bonding, reproduction, parturition, lactation and appetite regulation. Recent evidence indicates that oxytocin enhances glucose uptake and lipid utilization in adipose tissue and skeletal muscle, suggesting that dysfunction of the oxytocin system could underlie the pathogenesis of insulin resistance and dyslipidaemia. Murine studies revealed that deficiencies in oxytocin signalling and oxytocin receptor expression lead to obesity despite normal food intake, motor activity and increased leptin levels. In addition, plasma oxytocin concentration is notably lower in obese individuals with diabetes, which may suggest an involvement of the oxytocin system in the pathogenesis of cardiometabolic disease. More recently, small scale studies demonstrated that intranasal administration of oxytocin was associated with significant weight loss as well as improvements in insulin sensitivity and pancreatic ß-cell responsivity in human subjects. The multi-pronged effects of oxytocin signalling on improving peripheral insulin sensitivity, pancreatic function and lipid homeostasis strongly suggest a role for this system as a therapeutic target in obesity and diabetes management. The complexity of obesity aetiology and the pathogenesis of obesity-related metabolic complications underscore the need for a systems approach to better understand the role of oxytocin in metabolic function.

Low subjective socioeconomic status stimulates orexigenic hormone ghrelin - A randomised trial.

Recent evidence suggests that lower perceived socioeconomic status is linked to increased appetite and intake of greater calories. Yet, whether insecurity of socioeconomic resources directly influences regulatory systems of appetite and energy intake is not known. Considering psychological states, mindsets and beliefs have shown to meaningfully affect physiological responses to food, the present study tested the hypothesis that low subjective socioeconomic status (SSS) will have a direct influence on physiological responses, such as appetite-related hormones (ghrelin, pancreatic polypeptide and insulin). Forty-eight healthy males were randomly (crossover, counterbalanced) assigned, to two experimental conditions where participants were either experimentally induced to feel low SSS or not (control; CON). Feelings of low SSS resulted in an increase in active ghrelin (an orexigenic hormone) following the SSS manipulation compared with baseline, while no change in active ghrelin was observed in CON. Furthermore, participants reported lower fullness and satiety following low SSS compared with CON. Our findings demonstrate that SSS may influence hunger regulation and appetite, and suggest that physiological systems regulating energy balance (i.e. caloric resources) may also be sensitive to perceived deprivation or imbalances in critical non-food resources (socioeconomic resources).

A synopsis of brown adipose tissue imaging modalities for clinical research.

Body weight gain results from a chronic excess of energy intake over energy expenditure. Accentuating endogenous energy expenditure has been accorded considerable attention ever since the presence of brown adipose tissue (BAT) in adult humans was recognized, given that BAT is known to increase energy expenditure via thermogenesis. Besides classic BAT, significant strides in our understanding of inducible brown adipocytes have been made regarding its development and function. While it is ideal to study BAT histologically, its relatively inaccessible anatomical locations and the inherent risks associated with biopsy preclude invasive techniques to evaluate BAT on a routine basis. Thus, there has been a surge in interest to employ non-invasive methods to examine BAT. The gold standard of non-invasive detection of BAT activation is 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography (CT). However, a major limitation of PET/CT as a tool for human BAT studies is the clinically significant doses of ionizing radiation. More recently, several other imaging methods, including single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), infrared thermography (IRT)/thermal imaging and contrast ultrasonography (US) have been developed in hopes that they would allow non-invasive, quantitative measures of BAT mass and activity with lower costs. This review focuses on such methods to detect human BAT activation and white adipose tissue (WAT) browning to prompt the establishment of BAT-centric strategies for augmenting energy expenditure and combatting obesity. Clinical validation of these methods will most likely expand the scope and flexibility of future BAT studies.

Central diabetes insipidus unmasked by corticosteroid therapy for cerebral metastases: beware the case with pituitary involvement and hypopituitarism.

Patients with intra-cerebral metastases often receive glucocorticoids, particularly in the presence of peri-lesional vasogenic cerebral oedema. We present a case of presumptive lung carcinoma with cerebral metastases where central diabetes insipidus was unmasked after glucocorticoid administration and correction of undiagnosed central hypocortisolism.

Allergic reaction to stainless steel sternotomy wires requiring removal: A case report and literature review.

Hypersensitivity to stainless steel sternal sutures are an uncommon occurrence. We present a case of such a patient who developed chronic tissue overgranulation over a sternotomy wound eight weeks post-operatively. Primary suspicion was infection, a more common complication however radiological and laboratory investigation showed otherwise. Conservative management provided limited ephemeral success. After ensuring adequate sternal bone healing, the sutures and granulation tissue were eventually surgically removed without complication and the reoperated wound healed well.

Smaller size of high metabolic rate organs explains lower resting energy expenditure in Asian-Indian Than Chinese men.

BACKGROUND: In Singapore, the obesity prevalence is disproportionately higher in the Asian-Indians and Malays than the Chinese. Lower resting energy expenditure (REE) may be a contributory factor. OBJECTIVE: We explored the association between ethnicity and REE in Chinese, Asian-Indian and Malay men living in Singapore and determined the influence of body composition, mass/volume of high metabolic rate organs, represented by brain volume and trunk fat-free mass (FFM), and physical activity on ethnic differences. DESIGN: Two hundred and forty-four men from Singapore (n=100 Chinese, 70 Asian-Indians and 74 Malays), aged 21-40 years and body mass index of 18.5-30.0 kg m(-2), were recruited in this cross-sectional study. REE was assessed by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. Brain volume was measured by magnetic resonance imaging. Physical activity was assessed by the Singapore Prospective Study Program Physical Activity Questionnaire. RESULTS: REE was significantly lower in Asian-Indians compared with that in Chinese after adjusting for body weight. FFM (total, trunk and limb) and total fat mass were important predictors of REE across all ethnic groups. Brain volume was positively associated with REE only in Malays. Moderate and vigorous physical activity was positively associated with REE only in Asian-Indians and Malays. The difference in REE between Asian-Indians and Chinese was attenuated but remained statistically significant after adjustment for total FFM (59±20 kcal per day), fat mass (67±20 kcal per day) and brain volume (54±22 kcal per day). The association between REE and ethnicity was no longer statistically significant after total FFM was replaced by trunk FFM (which includes heart, liver, kidney and spleen) but not when it was replaced by limb FFM (skeletal muscle). CONCLUSIONS: We have demonstrated a lower REE in Asian-Indians compared with Chinese who may contribute to the higher rates of obesity in the former. This difference could be accounted for by differences in metabolically active organs.

Ethnic differences in insulin sensitivity and beta-cell function among Asian men.

BACKGROUND AND OBJECTIVES: Lean Asian Indians are less insulin sensitive compared with Chinese and Malays, but the pancreatic beta-cell function among these ethnic groups has yet to be studied in depth. We aimed to study beta-cell function in relation to insulin sensitivity among individuals of Chinese, Malay and Asian-Indian ethnicity living in Singapore. SUBJECTS AND METHODS: This is a sub-group analysis of 59 normoglycemic lean (body mass index (BMI) <23 kg m(-)(2)) adult males (14 Chinese, 21 Malays and 24 Asian Indians) from the Singapore Adults Metabolism Study. Insulin sensitivity was determined using fasting state indices (homeostatic model assessment-insulin resistance), the euglycemic-hyperinsulinemic clamp (ISI-clamp) and a liquid mixed-meal tolerance test (LMMTT) (Matsuda insulin sensitivity index (ISI-Mat)). Beta-cell function was assessed using fasting state indices (homeostatic model assessment-beta-cell function) and from the LMMTT (insulinogenic index and insulin secretion index). The oral disposition index (DI), a measure of beta-cell function relative to insulin sensitivity during the LMMTT, was calculated as a product of ISI-Mat and insulin secretion index. RESULTS: Asian Indians had higher waist circumference and percent body fat than Chinese and Malays despite similar BMI. Overall, Asian Indians were the least insulin sensitive whereas the Chinese were most insulin sensitive. Asian Indians had higher beta-cell function compared with Chinese or Malays but these were not statistically different. Malays had the highest incremental area under the curve for glucose during LMMTT compared with Asian Indians and Chinese. However, there were no significant ethnic differences in the incremental insulin area under the curve. The oral DI was the lowest in Malays, followed by Asian Indians and Chinese. CONCLUSION: Among lean Asians, Chinese are the most insulin sensitive whereas Asian Indians are the least insulin sensitive. However, Malays demonstrate higher postprandial glucose excursion with lower beta-cell response compare with Chinese or Asian Indians. The paths leading to type 2 diabetes mellitus might differ between these Asian ethnic groups.

Latent tuberculosis in patients with diabetes mellitus: prevalence, progression and public health implications.

BACKGROUND: Diabetes mellitus (DM) confers a higher risk for tuberculosis (TB). Yet, TB screening and chemoprophylaxis for latent TB infection (LTBI) in DM remains controversial. We conducted a cross-sectional study to elucidate LTBI prevalence and longitudinal follow-up to ascertain LTBI to active TB progression rate in DM. METHODS: 220 DM patients without previous TB from the outpatient diabetes clinic of the hospital were enrolled. T-Spot TB, tuberculin-skin-test (TST) and chest radiography (CXR) were performed. LTBI was defined by negative CXR with reactive T-Spot TB. Progression to active TB was confirmed by cross-checking against the TB registry. RESULTS: The prevalence of LTBI was 28.2% (62/220) by reactive T-Spot. None progressed to active TB from 2007-2013. Multivariate analysis revealed that any co-morbidity (p=0.016) was positively associated while metformin (p=0.008) was negatively associated with LTBI. CONCLUSIONS: Over a quarter of DM patients harbor LTBI. While the lack of demonstrable progression to active TB within the follow-up time frame up to this point does not unequivocally support a routine TB screening policy or anti-TB chemoprophylaxis for LTBI in a diabetic population for now, this preliminary evidence needs re-evaluation with longer follow-up of this enrolled cohort over the next decade.

Mastication effects on the glycaemic index: impact on variability and practical implications.

Glycaemic variability challenges the accuracy and use of the glycaemic index (GI). The purpose of the current study was to determine the role of mastication on GI. Using a randomized, controlled, crossover, non-blind design, 15 healthy young subjects returned on 5 separate days for three glucose and two rice test sessions. At the rice sessions, subjects chewed each mouthful either 15 or 30 times. Rice chewed 15 times produced a total glycaemic response (GR; 155 mmol min/l), peak GR (2.4 mmol/l) and GI (68) significantly lower than when chewed for longer (30 times) (184 mmol min/l, 2.8 mmol/l and 88, respectively). The study shows that the GI of rice is affected by the degree of mastication. Chewing 15 times compared with 30 times significantly attenuates the GI, suggesting that mastication may potentially contribute to the glycaemic variability of rice. While future work must establish the extent and limits to which mastication affects glycaemia, it could also explore the potential of using mastication to reduce the glycaemic load of rice.

Associations between ethnicity, body composition, and bone mineral density in a Southeast Asian population.

CONTEXT AND OBJECTIVE: Chinese men in Singapore have a higher incidence of hip fractures than Malay and Indian men. We investigated whether there were corresponding ethnic differences in peak bone mineral density (BMD) in young men and whether differences in body composition influenced peak BMD. DESIGN AND SETTING: This was a cross-sectional study of healthy volunteers in a tertiary medical center. PARTICIPANTS: A total of 100 Chinese, 82 Malay, and 80 Indian men aged 21 to 40 years, with body mass index between 18 and 30 kg/m(2) underwent dual-energy x-ray absorptiometry to assess BMD, lean mass (LM) and fat mass (FM), and magnetic resonance imaging to quantify abdominal subcutaneous and visceral adipose tissue. Multiple linear regression models, with adjustment for age and height (as a proxy for skeletal size), were used. RESULTS: Malay and Indian men had significantly higher BMD than Chinese men at the lumbar spine (Malay: B, 0.06 ± 0.02, P = .001; Indian: B, 0.03 ± 0.02, P = .049), femoral neck (Malay: B 0.04 ± 0.02, P = .034; Indian: B, 0.04 ± 0.02, P = .041), hip (Malay: B, 0.05 ± 0.02, P = .016; Indian: B, 0.06 ± 0.02, P = .001), and ultradistal radius (Malay: B, 0.03 ± 0.01, P < .001; Indian: B, 0.02 ± 0.01, P = .029), and this difference was retained after adjustment for LM and FM, except in Malay men at the femoral neck and in Indian men at the ultradistal radius. LM was an important independent determinant of BMD at all sites, whereas FM, subcutaneous adipose tissue, and visceral adipose tissue were not significantly associated with BMD at any site. CONCLUSIONS: Lower peak BMD in Chinese men may partly explain the higher fracture incidence in this ethnic group. Further studies are needed to elucidate the reasons for these ethnic differences in bone accumulation.

Associations between complications and health-related quality of life in individuals with diabetes.

OBJECTIVE: Type 2 diabetes and associated complications adversely affect health-related quality of life (HRQoL). However, it is unclear whether different complications have the same or different associations with HRQoL. We examined associations between retinopathy, nephropathy, peripheral neuropathy (microvascular), coronary heart disease, stroke and peripheral arterial disease (macrovascular) in diabetes and HRQoL. DESIGN: This study was a follow-up examination between 2004 and 2007 of participants from four previous cross-sectional population-based studies in Singapore. METHODS: Health-related quality of life was assessed through self-administered SF-36 health survey version 2. Diabetes and complications status were assessed through self-report, clinical and laboratory examinations. About 2601 individuals, 2205 healthy and 396 with diabetes, were studied. RESULTS: Lower physical component scores (PCS) were associated with microvascular (2.96 points, P < 0.001) and both macro- and microvascular complications (4.67 points, P < 0.001), but not diabetes alone. Coronary heart disease (3.86 points, P = 0.007), peripheral neuropathy (11.46 points, P < 0.001) and severe retinopathy (4.46 points, P < 0.001) were associated with lower PCS. The greatest reduction in scores was seen in peripheral neuropathy. CONCLUSIONS: Quality of life in patients with diabetes is affected mainly by presence of complications, and not diabetes per se. Peripheral neuropathy was associated with the greatest reduction in quality of life. Improved management to prevent or delay onset of complications may reduce the effect on quality of life in patients with diabetes.

Neuroglycopenia and adrenergic responses to hypoglycaemia: insights from a local epidemic of serendipitous massive overdose of glibenclamide.

AIMS: Recently, an unlicensed aphrodisiac formulation originating from China known as 'Power 1 Walnut' penetrated the illicit markets of South East Asia including Singapore. Subsequent toxicological analyses revealed that each 'Power 1 Walnut' pill was illegally adulterated with two prescription drugs--sildenafil 1 mg (a PDE5 inhibitor) and glibenclamide 93-98 mg (a long-acting sulphonylurea). As the drug was peddled to numerous people, a local 'hypoglycaemia epidemic' ensued, of which a small cluster presented to our hospital with severe hypoglycaemia. The aim is to characterize the demographics, clinical and labouratory aspects and postulate mechanisms for the relatively atypical presentation. METHODS: A retrospective study of all the patients admitted between 13th January to 15th June 2008 with hypoglycaemia was done with acquisition of all relevant data after ethical approval from our DSRB. RESULTS: 15 patients (25-73 years old) presented with severe hypoglycaemia. All of them presented with neuroglycopenic symptoms (5-confusion, 6-drowsiness to loss of consciousness, 4-seizures and 1-coma) 12-36 h after ingestion of 'Power 1 Walnut'. Liquid chromatography-mass spectrometry (LC/MS) confirmed the presence of glibenclamide in the urine. None experienced a full-blown hypoglycaemia-associated autonomic response defined as sweating, sensation of warmth, anxiety, tremor, nausea, palpitations, tachycardia, and hunger. Only 4/16 patients had symptoms of a partial autonomic response, and 3/16 patients had tachycardia and/or hypertension. CONCLUSIONS: The above suggests an inappropriate autonomic and catecholamine response to severe hypoglycaemia in these cases of serendipitous glibenclamide overdose. Possible reasons for the blunted autonomic responses and apparent autonomic failure are reviewed.