Calcium, Vitamin D, and Bone Derangement in Nephrotic Syndrome.

INTRODUCTION: Derangement in calcium homeostasis is common in nephrotic syndrome (NS). It is postulated that low serum total calcium and vitamin D levels are due to loss of protein-bound calcium and vitamin D. It is unclear if free calcium and free vitamin D levels are truly low. The guideline is lacking with regards to calcium and vitamin D supplementation in NS. This study aims to examine calcium and vitamin D homeostasis and bone turnover in NS to guide practice in calcium and vitamin D levels supplementation. METHODOLOGY: This is a prospective pilot study of ten patients diagnosed with NS, and eight healthy controls. Calcium, vitamin D, and bone turnover-related analytes were assessed at baseline, partial and complete remission in NS patients and in healthy controls. RESULTS: NS patients had low free and total serum calcium, low total 25(OH)D, normal total 1,25(OH)D levels and lack of parathyroid hormone response. With remission of disease, serum calcium and vitamin D metabolites improved. However, nephrotic patients who do not attain complete disease remission continue to have low 25(OH)D level. CONCLUSION: In this study, the vitamin D and calcium derangement observed at nephrotic syndrome presentation trended towards normalisation in remission. This suggested calcium and vitamin D replacement may not be indicated in early-phase nephrotic syndrome but may be considered in prolonged nephrotic syndrome.

Validation of prediction equations for resting energy expenditure in Singaporean Chinese men.

Accurate prediction of resting energy expenditure (REE) is important in establishing adequate dietary intake goals for effective weight management. Previous studies have shown that the validity of an energy prediction equation may depend on the ethnicity of the population. Validation studies are lacking in the Singaporean Chinese population. A total of 96 healthy Singaporean Chinese males of age 21­40 years and body mass index (BMI) 18.5­30.0 kg/m2 participated in this study. REE was measured by indirect calorimetry and compared with REE predicted using existing equations. Validity was evaluated on the basis of mean bias and percentage of subjects predicted within ±10% of REE measured. In addition, Bland and Altman analyses were performed. No significant difference was observed between the mean levels of measured and predicted REE derived from the Owen equation. The Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU), Harris­Benedict and Mifflin equations significantly overestimated the mean measured REE by 7.5%, 6.0% and 2.4% respectively. Percentage of valid predictions for FAO/WHO/UNU, Harris­Benedict, Mifflin and Owen equations were 60%, 67%, 75% and 73% respectively. Bland and Altman analyses demonstrated poor agreement for all equations. The Owen equation provided a valid estimation of REE in Singaporean Chinese men at a group level. However, the individual errors of the equations were unacceptable high and may have limited utility in making clinical decisions on nutritional requirements.

Trends in the incidence and mortality of coronary heart disease in asian pacific region: the Singapore experience.

The rates of coronary heart disease are lower in Asia than in developed countries. Singapore has undergone rapid urbanization over the past several decades. In the several decades between the 1960s and 1980s, a rapid increase in the rates of ischemic heart disease was observed, to the extent that Singapore exhibits one of the highest rates of mortality from cardiovascular disease in the Asia-Pacific region, higher even than the rates in North America. Rates of cardiovascular disease have now stabilized, and are declining. This is, a pattern that has been observed in many developed countries. Increased life expectancy has resulted in an epidemiologic transition that has seen chronic non-communicable diseases replace malnutrition and infections as the major causes of mortality. At the same time, there have been changes in nutrient intake and physical activity as well as rapid increases in the levels of several cardiovascular risk factors including obesity, hypertension, hyperlipidemia, diabetes mellitus and systemic inflammation. Furthermore, when present, there is a lack of awareness and sub-optimal treatment of these risk factors. In addition to the changes in environmental exposures related to socio-economic development, it does appear that specific populations are particularly prone to the development of cardiovascular disease and its risk factors. In particular, Asian Indians experience a high rate of coronary heart disease and diabetes mellitus. Emerging data suggests that Chinese may be particularly prone to the adverse effects of obesity in relation to insulin resistance and inflammation. A concerted effort to change lifestyles to prevent the development of coronary heart disease risk factors, and to improve awareness and treatment of risk factors when then develop, is required to halt the epidemic of coronary heart disease that is occurring in Asia.

Pid1 induces insulin resistance in both human and mouse skeletal muscle during obesity.

Obesity is associated with insulin resistance and abnormal peripheral tissue glucose uptake. However, the mechanisms that interfere with insulin signaling and glucose uptake in human skeletal muscle during obesity are not fully characterized. Using microarray, we have identified that the expression of Pid1 gene, which encodes for a protein that contains a phosphotyrosine-interacting domain, is increased in myoblasts established from overweight insulin-resistant individuals. Molecular analysis further validated that both Pid1 mRNA and protein levels are increased in cell culture models of insulin resistance. Consistent with these results, overexpression of phosphotyrosine interaction domain-containing protein 1 (PID1) in human myoblasts resulted in reduced insulin signaling and glucose uptake, whereas knockdown of PID1 enhanced glucose uptake and insulin signaling in human myoblasts and improved the insulin sensitivity following palmitate-, TNF-α-, or myostatin-induced insulin resistance in human myoblasts. Furthermore, the number of mitochondria in myoblasts that ectopically express PID1 was significantly reduced. In addition to overweight humans, we find that Pid1 levels are also increased in all 3 peripheral tissues (liver, skeletal muscle, and adipose tissue) in mouse models of diet-induced obesity and insulin resistance. An in silico search for regulators of Pid1 expression revealed the presence of nuclear factor-κB (NF-κB) binding sites in the Pid1 promoter. Luciferase reporter assays and chromatin immunoprecipitation studies confirmed that NF-κB is sufficient to transcriptionally up-regulate the Pid1 promoter. Furthermore, we find that myostatin up-regulates Pid1 expression via an NF-κB signaling mechanism. Collectively these results indicate that Pid1 is a potent intracellular inhibitor of insulin signaling pathway during obesity in humans and mice.