The influence of dietary supplementation with cranberry tablets on the urinary risk factors for nephrolithiasis.

PURPOSE: Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n = 5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion. METHODS: Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels. RESULTS: The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p = 0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day). CONCLUSION: Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.

The benefits of utilising geo-mapping for visualising the vitamin D status of Dublin city and the surrounding urban districts.

CONTEXT: There have been few published reports of visualising vitamin D status at a micro level, i.e., within large individual urban centres of countries. OBJECTIVE: To produce a visual map of the vitamin D status [25-hydroxy vitamin D-25(OH)D] of a large urban centre (n > 350,000) incorporating the regions of Dublin city that constitute the general practitioner catchment area of a large academic teaching adult hospital. DESIGN, SETTING AND PARTICIPANTS: An observational investigation of 5287 free living Irish adults (>18 years). RESULTS: Approximately, 15.2 % of those sampled in the winter period (October-February) were vitamin D deficient (<30 nmol/L) compared with 10.8 % of those sampled in the summer period (March-September). Vitamin D tests requested from the most social economically deprived urban locations (Dublin 8 and Lucan postal districts) had the highest rates of deficiency (23.5 and 20.4 %, respectively, both seasons). On average, females had a significantly higher 25(OH)D concentration compared with males (57.9 vs 52.3 nmol/L, respectively), while the younger participants (18-50 years) mean 25(OH)D concentration was 27 % lower in winter and 20.7 % lower in summer in comparison with the older participants (>50 years) (P < 0.0001). CONCLUSIONS: For the first time in Ireland, a visual depiction of data can be used to aid in the rapid identification of vitamin D status trends within a major urban area. These findings provide useful data to help inform public health policy regarding endemic vitamin D insufficiency to help target the population groups and resident location areas most at risk.

Stability and accuracy of total and free PSA values in samples stored at room temperature.

INTRODUCTION: In 2010, an estimated 476,076 total PSA tests were performed in Ireland, at a cost of €3.6 million with the majority ordered by general practitioners. We aimed to replicate storage conditions at room temperature and see if prolonged storage affected total and free PSA values. METHODS: Blood samples were taken from 20 male patients in four VACUETTE® Serum Separator tubes (Greiner-Bio-One, Austria) and stored at room temperature (22 °C) for different time intervals (4, 8, 24, 48 h) before being centrifuged and analyzed. Total PSA (tPSA) and free PSA (fPSA) values were determined using the Tosoh AIA 1800 assay (Tokyo, Japan). RESULTS: Mean tPSA values were measured at 4, 8, 24 and 48 h with values of 7.9, 8.1, 7.8 and 8.0 µg/L, respectively. Values ranged from -1.26 to +2.53 % compared to the initial 4 h interval reading, indicating tPSA remained consistent at room temperature. The tPSA showed no significance between groups (ANOVA, p = 0.283). Mean fPSA values at 4, 8, 24 and 48 h were 2.05, 2.04, 1.83, 1.82 µg/L, respectively. At 24 and 48 h there was 10.73 and 11.22 % reduction, respectively, in fPSA compared to the 4-h time interval, indicating prolonged storage resulted in reduced fPSA values. After 24 h, there was an 8.8 % reduction in the free/total PSA %. The fPSA showed significant differences between groups (ANOVA, p = 0.024). CONCLUSIONS: Our recommendation is that samples that have been stored for prolonged amounts of time (greater than 24 h) should not be used for free PSA testing.

The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population.

AIMS: Environmental and genetic factors contribute to the evolution of type 2 diabetes (T2DM). Presenilin associated rhomboid like protein (PARL) is a mitochondrial protein that has been implicated in T2DM in both the rodent Psammomys obesus and in humans. The SNP variant (Leu262Val) in PARL has been shown to be associated with hyperinsulinaemia in an age-dependent manner in a US non-diabetic, cohort. However, this finding has not been replicated in UK cohorts. We studied Leu262Val associations in an Irish Caucasian T2DM case-control population. METHODS: An RFLP-PCR assay using BstN I was used to assess Leu262Val genotype in a total of 613 subjects, 421 with T2DM and 192 controls. RESULTS: In the control group genotype frequencies were as follows 27.37% (GG), 51.58% (CG) and 21.05% (CC), while in the group with T2DM 30.64% (GG), 47.74% (CG) and 21.62% (CC). We observed no association between Leu262Val variant and T2DM nor was there an association with plasma insulin concentrations or BMI. There was no interaction between age and fasting plasma insulin concentration. However, in the group with T2DM the C allele was associated with higher urinary albumin to creatinine ratio while the GG genotype was associated with an earlier age of onset of T2DM. CONCLUSION: The Leu262Val polymorphism of PARL is not associated with markers of insulin resistance. However, in subjects with T2DM, genetic variation at this locus may indicate earlier onset of T2DM and increased susceptibility to nephropathy and cardiovascular complications.

Adverse metabolic profiles in a cohort of obese Irish children.

BACKGROUND: The metabolic characteristics of obese Irish children are not well defined. We prospectively examined the relationship between the degree of obesity and glucose metabolism, insulin sensitivity and suspected non-alcoholic steatohepatosis (NASH) in a pilot study of obese Irish children. METHODS: We measured height, weight, body mass index (BMI), blood pressure, waist and hip circumference in 18 participants (mean age 15.5 years). Fasting blood glucose, insulin, lipid profile and alanine aminotransferase (ALT) concentrations were also measured. A standard 75 g oral glucose tolerance test was performed and insulin sensitivity was derived from this using a mathematical model--oral glucose insulin sensitivity. RESULTS: There were significant associations between the degree of obesity, insulin sensitivity and markers of liver steatosis. For example, when adjusted for pubertal status, there were significant associations between standardized BMI and insulin sensitivity (regression coefficient, beta = -70.1, P = 0.018) and ALT (beta = 20.7, P = 0.007). CONCLUSION: This study suggests that the degree of obesity is associated with lower insulin sensitivity and possible NASH in obese Irish children.

Depot-related and thiazolidinedione-responsive expression of uncoupling protein 2 (UCP2) in human adipocytes.

OBJECTIVES: Uncoupling protein 2 (UCP2) is a recently described homologue of the uncoupling protein of brown adipocytes (UCP1), which is expressed at high levels in human white adipose tissue. Studies were undertaken (1) to establish whether the expression of UCP2 mRNA varies in a depot-related manner in isolated human adipocytes, (2) to determine whether thiazolidinedione exposure influences the expression of UCP2 mRNA in cultured human pre-adipocytes, and (3) to determine whether human UCP2 is targeted to mitochondria when transfected into mammalian cells. SUBJECTS: Abdominal subcutaneous and omental adipose tissue biopsies were obtained from adult patients undergoing elective intra-abdominal surgical procedures. MEASUREMENTS: A competitive reverse transcriptase-polymerase chain reaction (RT-PCR) was used to quantify UCP2 mRNA expression in human omental and subcutaneous adipocytes, and in cultured human preadipocytes differentiated in vitro using the thiazolidinedione, BRL49653. Chinese hamster ovary cells were transfected with a vector expressing human UCP2, and its cellular localization was determined by confocal immunofluorescence microscopy. RESULTS: Adipocytes isolated from human omentum consistently expressed more UCP2 mRNA than did subcutaneous adipocytes from the same subjects (mean fold difference 2.92+/-0.44 P<0.001, n=11) with no effect of gender or body mass index being seen. BRL49653 treatment of subcutaneously, but not omentally, derived preadipocytes stimulated expression of UCP2 mRNA (5.1+/-1.1 fold). Transfected human UCP2 was detected exclusively in mitochondria of CHO cells. CONCLUSIONS: Increased expression of UCP2 in human omental adipose tissue relative to subcutaneous adipose tissue is related to the expression levels in adipocytes per se, a finding which may relate to the particular functional attributes of this sub-population of adipocytes. Furthermore, BRL 49653 has site-specific effects of on the expression of UCP2 in human preadipocytes, a finding which may be relevant to the therapeutic effects of such compounds. Finally we present evidence for the mitochondrial localisation of human UCP2.

Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension.

Thiazolidinediones are a new class of antidiabetic agent that improve insulin sensitivity and reduce plasma glucose and blood pressure in subjects with type 2 diabetes. Although these agents can bind and activate an orphan nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), there is no direct evidence to conclusively implicate this receptor in the regulation of mammalian glucose homeostasis. Here we report two different heterozygous mutations in the ligand-binding domain of PPARgamma in three subjects with severe insulin resistance. In the PPARgamma crystal structure, the mutations destabilize helix 12 which mediates transactivation. Consistent with this, both receptor mutants are markedly transcriptionally impaired and, moreover, are able to inhibit the action of coexpressed wild-type PPARgamma in a dominant negative manner. In addition to insulin resistance, all three subjects developed type 2 diabetes mellitus and hypertension at an unusually early age. Our findings represent the first germline loss-of-function mutations in PPARgamma and provide compelling genetic evidence that this receptor is important in the control of insulin sensitivity, glucose homeostasis and blood pressure in man.