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Metabolic syndrome and renal sodium handling in three ethnic groups living in England

Metabolic syndrome and renal sodium handling in three ethnic groups living in England. A Barbato § † , FP Cappuccio § , EJ Folkerd § , P Strazzullo † , B Sampson # , KGMM Alberti ‡. Published in: Diabetologia 2004; 47: 40-46. Background.

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Metabolic syndrome and renal sodium handling in three ethnic groups living in England

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  1. Metabolic syndrome and renal sodium handling in three ethnic groups living in England A Barbato§†, FP Cappuccio§, EJ Folkerd§, P Strazzullo†, B Sampson#, KGMM Alberti‡ Published in: Diabetologia 2004; 47: 40-46

  2. Background • ↑proximal renal sodium re-absorption associated with ‘metabolic syndrome’ in white men(JAMA 1993;270:354-9 & J Hypertens 1996;14:909-14)

  3. Background • ↑proximal renal sodium re-absorption associated with ‘metabolic syndrome’ in white men(JAMA 1993;270:354-9 & J Hypertens 1996;14:909-14) • ↑proximal renal sodium re-absorption associated with abdominal adiposity in white men (J Hypertens 2001;19:2157-64)

  4. Na + Li + Na+ Na + Uric acid Segmental renal sodium handling studied by the clearance of ‘exogenous’ or ‘endogenous’ lithium

  5. Exogenous Oral load Li+ carbonate 150-900mg Li+ 4-24 mmol Serum & urine Li+ in mM Detectable with A.A.S. Disadvantages natriuretic effect not suitable for serial tests difficult in epidemiology compliance ethics Endogenous No load needed Serum & urine Li+ in mM Detectable with A.A.S. with electrothermal atomisation and tantalum-coated graphite Detection limit 0.05 mM Advantages avoidance of Li+ effect suitable for serial tests applicable to epidemiology Disadvantages special equipment & skill high cost Lithium Clearance: non-invasive assessment of renal tubular sodium handling in vivo in man Clin Sci 1988;74:651-7 JAMA 1993;270:354-9 Am J Physiol 1995;268:F718-22 Diabetologia 2004;47:40-6

  6. Questions • Does the association exist? • Is it consistent in men and women? • Is it present in different ethnic groups with different degrees of metabolic syndrome?

  7. Study design • Population-based cross-sectional survey • Men and women aged 40-59 yrs • Whites, South Asians, African origin • Random selection from GPs age-sex registers after stratification by sex and ethnic group • Fieldwork between March 1994 and July 1996 • Sample size: 1,577 • 1,257 (80%) timed urine collections • 1,190 complete data set available

  8. Measurements • Questionnaire (migration, religion, language, smoking,medical history, therapy) • Physical (height, weight, waist & hip circumferences) • Blood Pressure (by Arteriosonde) • Fasting blood (biochemistry, lipids, glucose, insulin, HOMA index) • Timed Urine after overnight fast (Na, K, Cr, endogenous Li) • Endogenous Li clearance • Between CV%: serum 10.8% (n=100); urine 6.2% (n=185) • Within CV%: serum 6.2% (n=23); urine 4.6% (n=27)

  9. Results 1. Characteristics by ethnic group White African origin South Asian n=426 n=397 n=367 B.M.I. (kg/m2) 25.9 27.9 25.9 W:H ratio 0.861 0.876 0.895 Systolic BP (mmHg) 125.2 133.5 128.7 Diastolic BP (mmHg) 79.5 86.2 82.7 Cholesterol (mM) 6.21 5.61 5.71 Triglycerides§ (mM) 1.21 0.82 1.38 HDL-cholesterol§ (mM) 1.34 1.45 1.15 Fasting glucose§ (mM) 5.13 5.43 5.64 Fasting insulin§ (mU/l) 6.84 8.18 10.70 HOMA index§ 1.54 1.89 2.58 BP Rx (%) 9.6 31.2 14.3 MS ATP III (%) 16.4 16.1 26.7 F.E. sodium (%) 0.81 0.79 0.99 F.E. lithium (%) 18.4 15.6 18.2 All p<0.001 §log-transformed values Adjusted for age and sex

  10. Results 2. F.E.Li vs Metabolic variables White African origin S Asian ^log-transformed values P<0.001 adjusted for age and sex

  11. Results 3. Multiple Regression analyses Adjusted for age and sex

  12. Results 3. Multiple Regression analyses Adjusted for age and sex

  13. Results 4. F.E.Li and Metabolic Syndrome by ATP III criteria* WITH WITHOUT 18.2% 17.9% 15.7% 15.0% 19.0% P=0.003 15.9% Mean (95%CI) * >3 of: waist>102cm (M) >88 (W); Tg >1.7mM; HDL-c <1.04mM (M) <1.3mM (W); BS>6.11mM; BP>130/85mmHg

  14. Summary • An independent association exists between ↑ proximal sodium re-absorption and metabolic indices of vascular risk in white men and women

  15. Summary • An independent association exists between ↑ proximal sodium re-absorption and metabolic indices of vascular risk in white men and women • Insulin levels also relate to renal Na+ handling

  16. Summary • An independent association exists between ↑ proximal sodium re-absorption and metabolic indices of vascular risk in white men and women • Insulin levels also relate to renal Na+ handling • The association is not present in men and women of African or South Asian origin, despite raised insulin levels and more prevalent metabolic syndrome

  17. Summary & Conclusions • An independent association exists between ↑ proximal sodium re-absorption and metabolic indices of vascular risk in white men and women • Insulin levels also relate to renal Na+ handling • The association is not present in men and women of African or South Asian origin, despite raised insulin levels and more prevalent metabolic syndrome • Potential mechanisms (ethnic-specific) to be elucidated • Long-term proximal effect of insulin • ↑ Na+-H+? - ↓ hepatic cAMP - ↑ SNS activity • Possible effects of ↑ glucose • Possible changes in membrane fluidity and ion transport • Role of genetic polymorphisms

  18. Summary & Conclusions • An independent association exists between ↑ proximal sodium re-absorption and metabolic indices of vascular risk in white men and women • Insulin levels also relate to renal Na+ handling • The association is not present in men and women of African or South Asian origin, despite raised insulin levels and more prevalent metabolic syndrome • Potential mechanisms (ethnic-specific) to be elucidated • Long-term proximal effect of insulin • ↑ Na+-H+? - ↓ hepatic cAMP - ↑ SNS activity • Possible effects of ↑ glucose • Possible changes in membrane fluidity and ion transport • Role of genetic polymorphisms • In whites insulin resistance may not involve the kidney!

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