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The effects of obesity surgery on diabetic nephropathy
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Abstracts / Appetite 58 (2012) 1169–1176
Comparison of the physiological effects of zinc-2-glycoprotein and the 3-adrenoceptor agonist, BRL 35135, in male C57Bl6 ob/ob mice. E.T. WARGENT, M.S. ZAIBI, J.R.S. ARCH, M.A. CAWTHORNE, C. BING, C.J. STOCKER LORE. Laboratory, University of Buckingham, Hunter Street, Buckingham, Bucks MK18 1EG, UK. mike.cawthorne@ buckingham.ac.uk Tisdale and colleagues have shown that the lipid-mobilising factor zinc-2-glycoprotein (ZAG) improves the metabolic state of Aston (ob/ob) mice and this might be mediated via agonism of 3-adrenoceptors. The current study investigated the similarities between the physiological effects of ZAG and the 3-adrenoceptor agonist BRL 35135. Human recombinant ZAG (rhZAG) was obtained from EZBiolab (IN) and its bioactivity assessed by showing that it stimulated lipolysis in murine epididymal adipocytes. Male C57Bl/6-ob/ ob mice were dosed daily for 10 days with either 100 g rhZAG, i.v., or 0.5 mg kg1 BRL 35135, i.p. Food consumption in the ZAG-treated mice was lower than in controls for the first 3 days of dosing only, and in the BRL 35135-dosed mice for the first 24 h only. Likewise, bodyweight was lower in the ZAG-treated mice than in controls only for the first 3 days. Water consumption was reduced in both dosed groups for the whole 10 day dosing period. Fasting blood glucose and glucose tolerance measured after 9 days treatment were improved significantly by both rhZAG and BRL 35135, although plasma insulin concentrations were only lowered by BRL 35135. BRL 35135 significantly increased energy expenditure (after both 1 and 10 days of treatment) and the plasma concentrations of glycerol and NEFA following dosing, whereas rhZAG administration only slightly increased energy expenditure after 10 days and did not increase plasma glycerol or NEFA. We conclude that ZAG does not mimic the effects of BRL 35135, except for improvements in glycaemic control. The improvement in metabolic state is unlikely to be due to ZAG being a typical 3-adrenoceptor agonist, but it could be a consequence of increasing -adrenoceptor signalling. doi:10.1016/j.appet.2012.02.026
The ‘F’ Factor Project. Cardio-respiratory fitness and body mass index of 8–12 year-old children attending schools in Denbighshire, Wales, UK. A serial cross-sectional study from academic years 2008–09 to 2010–11 (A Way of Life Project). R.M. RANSON, A.R. GRIFFIN. Glyndwr University, Plas Coch Campus, Mold Road, Wrexham LL11 2AW, UK. [email protected] The aim of this study was to examine the changes over time in body mass index (BMI) and cardio-respiratory fitness of children under 12 years old. Serial cross-sectional, population-based study. Setting: Primary schools (years 4–6), and secondary schools (year 7) in Denbighshire. Participants: A total of 2950 children, representing 34% of 8–12 year olds in the annual school cohorts between 2008–09 and 2010–11, took part in ‘F’ Factor Fitness Fun Days consisting of Health and Fitness (Eurofit) tests. Weight, height, body mass index (kg/m2 Þ, and obesity using the International Obesity Taskforce definition, cardio-respiratory fitness using the 20m MST.
Mean 20m MST score fell in boys (year 4 and 5) from 48.7 in 1998–99 to 36.3 in 2010–11, and in girls from 36.1 in 1998–99 to 26.9 in 2010–11, showing a 25% decrease over the same period for both boys and girls. Year 6 and 7 boys also experienced an 18% decrease, and years 6 and 7 girls a 28% decrease in 20m MST. Fitness scores fell across all strata of BMI (P < 0.001). Over the 3 year ‘F’ Factor project there was no significant change in BMI 18.75 + 3.21 (2008–09), 18.80 + 3.41 (2009–10), 19.16 + 3.16 (2010–11) (P = 0.688). ‘F’ Factor evidence shows no improvement in high BMI’s across all ages in both genders, whereas cardio-respiratory fitness levels have decreased annually across all ages in both genders. Even among children with an ideal BMI, fitness scores have decreased. doi:10.1016/j.appet.2012.02.027
The effects of obesity surgery on diabetic nephropathy. S. FARUQ, A. MOHITE, P.R. SHAH, A.D. MIRAS, L.-L. CHUAH, T. OLBERS, C. LE ROUX. Imperial Weight Centre, Imperial College London, Charing Cross Hospital, London SW6 8RF, UK. [email protected] Intensive glycaemic control can prevent or delay further progression of diabetic nephropathy in type 2 diabetes (T2DM), thus improving patient morbidity and mortality rates. Obesity surgery successfully achieves intensive glycaemic control in obese T2DM patients, but data regarding its effect on diabetic nephropathy is limited. This study investigated the effect of obesity surgery on diabetic nephropathy. A retrospective study was performed on 70 morbidly obese T2DM patients who underwent obesity surgery between June 2007 and August 2010. Patients underwent either Roux-en-y gastric bypass (RYGB), sleeve gastrectomy or gastric banding. Nephropathy disease was assessed using early morning urine albumin creatinine ratio (ACR). Changes in BMI, HbA1c, systolic and diastolic blood pressure were the secondary endpoints. Baseline data was obtained from within the 6 month pre-operative period and compared with 12 month post-operative data. The cohort of 70 patients experienced significant decreases in median urine ACR from 1.55 (IQR 0.70–6.13) mg/mmol to 1.30 (IQR 0.68–2.73) mg/mmol (p = 0.0078). Of the 27 patients with preoperative microalbuminuria, only 14.1% (n = 4) deteriorated further whereas 85.19% (n = 23) had an improvement and 55.6% (n = 15) underwent complete remission (p = 0.0001). For these 27 patients the median urine ACR reduced from 7.90 mg/mmol (IQR 4.31–48.10) to 2.60 mg/mmol (IQR 1.10–23.50) (p = 0.0022). Forth-eight patients had RYGB surgery; 16 patients had sleeve gastrectomy and 6 patients had gastric banding. The RYGB procedure drove most of the changes with median urine ACR decreasing from 1.35 mg/mmol (IQR 0.63–6.68) to 1.22 mg/mmol (IQR 0.60–3.10) (p = 0.0302). Significant improvements were seen in all secondary endpoints. Within 1 year, obesity surgery can lead to improvements or even complete remission of diabetic nephropathy. Glycaemia dependent and independent mechanisms may facilitate these changes. doi:10.1016/j.appet.2012.02.028
Abstracts / Appetite 58 (2012) 1169–1176
Comparison of the physiological effects of zinc-2-glycoprotein and the 3-adrenoceptor agonist, BRL 35135, in male C57Bl6 ob/ob mice. E.T. WARGENT, M.S. ZAIBI, J.R.S. ARCH, M.A. CAWTHORNE, C. BING, C.J. STOCKER LORE. Laboratory, University of Buckingham, Hunter Street, Buckingham, Bucks MK18 1EG, UK. mike.cawthorne@ buckingham.ac.uk Tisdale and colleagues have shown that the lipid-mobilising factor zinc-2-glycoprotein (ZAG) improves the metabolic state of Aston (ob/ob) mice and this might be mediated via agonism of 3-adrenoceptors. The current study investigated the similarities between the physiological effects of ZAG and the 3-adrenoceptor agonist BRL 35135. Human recombinant ZAG (rhZAG) was obtained from EZBiolab (IN) and its bioactivity assessed by showing that it stimulated lipolysis in murine epididymal adipocytes. Male C57Bl/6-ob/ ob mice were dosed daily for 10 days with either 100 g rhZAG, i.v., or 0.5 mg kg1 BRL 35135, i.p. Food consumption in the ZAG-treated mice was lower than in controls for the first 3 days of dosing only, and in the BRL 35135-dosed mice for the first 24 h only. Likewise, bodyweight was lower in the ZAG-treated mice than in controls only for the first 3 days. Water consumption was reduced in both dosed groups for the whole 10 day dosing period. Fasting blood glucose and glucose tolerance measured after 9 days treatment were improved significantly by both rhZAG and BRL 35135, although plasma insulin concentrations were only lowered by BRL 35135. BRL 35135 significantly increased energy expenditure (after both 1 and 10 days of treatment) and the plasma concentrations of glycerol and NEFA following dosing, whereas rhZAG administration only slightly increased energy expenditure after 10 days and did not increase plasma glycerol or NEFA. We conclude that ZAG does not mimic the effects of BRL 35135, except for improvements in glycaemic control. The improvement in metabolic state is unlikely to be due to ZAG being a typical 3-adrenoceptor agonist, but it could be a consequence of increasing -adrenoceptor signalling. doi:10.1016/j.appet.2012.02.026
The ‘F’ Factor Project. Cardio-respiratory fitness and body mass index of 8–12 year-old children attending schools in Denbighshire, Wales, UK. A serial cross-sectional study from academic years 2008–09 to 2010–11 (A Way of Life Project). R.M. RANSON, A.R. GRIFFIN. Glyndwr University, Plas Coch Campus, Mold Road, Wrexham LL11 2AW, UK. [email protected] The aim of this study was to examine the changes over time in body mass index (BMI) and cardio-respiratory fitness of children under 12 years old. Serial cross-sectional, population-based study. Setting: Primary schools (years 4–6), and secondary schools (year 7) in Denbighshire. Participants: A total of 2950 children, representing 34% of 8–12 year olds in the annual school cohorts between 2008–09 and 2010–11, took part in ‘F’ Factor Fitness Fun Days consisting of Health and Fitness (Eurofit) tests. Weight, height, body mass index (kg/m2 Þ, and obesity using the International Obesity Taskforce definition, cardio-respiratory fitness using the 20m MST.
Mean 20m MST score fell in boys (year 4 and 5) from 48.7 in 1998–99 to 36.3 in 2010–11, and in girls from 36.1 in 1998–99 to 26.9 in 2010–11, showing a 25% decrease over the same period for both boys and girls. Year 6 and 7 boys also experienced an 18% decrease, and years 6 and 7 girls a 28% decrease in 20m MST. Fitness scores fell across all strata of BMI (P < 0.001). Over the 3 year ‘F’ Factor project there was no significant change in BMI 18.75 + 3.21 (2008–09), 18.80 + 3.41 (2009–10), 19.16 + 3.16 (2010–11) (P = 0.688). ‘F’ Factor evidence shows no improvement in high BMI’s across all ages in both genders, whereas cardio-respiratory fitness levels have decreased annually across all ages in both genders. Even among children with an ideal BMI, fitness scores have decreased. doi:10.1016/j.appet.2012.02.027
The effects of obesity surgery on diabetic nephropathy. S. FARUQ, A. MOHITE, P.R. SHAH, A.D. MIRAS, L.-L. CHUAH, T. OLBERS, C. LE ROUX. Imperial Weight Centre, Imperial College London, Charing Cross Hospital, London SW6 8RF, UK. [email protected] Intensive glycaemic control can prevent or delay further progression of diabetic nephropathy in type 2 diabetes (T2DM), thus improving patient morbidity and mortality rates. Obesity surgery successfully achieves intensive glycaemic control in obese T2DM patients, but data regarding its effect on diabetic nephropathy is limited. This study investigated the effect of obesity surgery on diabetic nephropathy. A retrospective study was performed on 70 morbidly obese T2DM patients who underwent obesity surgery between June 2007 and August 2010. Patients underwent either Roux-en-y gastric bypass (RYGB), sleeve gastrectomy or gastric banding. Nephropathy disease was assessed using early morning urine albumin creatinine ratio (ACR). Changes in BMI, HbA1c, systolic and diastolic blood pressure were the secondary endpoints. Baseline data was obtained from within the 6 month pre-operative period and compared with 12 month post-operative data. The cohort of 70 patients experienced significant decreases in median urine ACR from 1.55 (IQR 0.70–6.13) mg/mmol to 1.30 (IQR 0.68–2.73) mg/mmol (p = 0.0078). Of the 27 patients with preoperative microalbuminuria, only 14.1% (n = 4) deteriorated further whereas 85.19% (n = 23) had an improvement and 55.6% (n = 15) underwent complete remission (p = 0.0001). For these 27 patients the median urine ACR reduced from 7.90 mg/mmol (IQR 4.31–48.10) to 2.60 mg/mmol (IQR 1.10–23.50) (p = 0.0022). Forth-eight patients had RYGB surgery; 16 patients had sleeve gastrectomy and 6 patients had gastric banding. The RYGB procedure drove most of the changes with median urine ACR decreasing from 1.35 mg/mmol (IQR 0.63–6.68) to 1.22 mg/mmol (IQR 0.60–3.10) (p = 0.0302). Significant improvements were seen in all secondary endpoints. Within 1 year, obesity surgery can lead to improvements or even complete remission of diabetic nephropathy. Glycaemia dependent and independent mechanisms may facilitate these changes. doi:10.1016/j.appet.2012.02.028