Effect of obesity on insulin secretion in response to a 48-hour Physiological Increase in plasma FFA in Mexican-American subjects genetically predisposed Type 2 Diabetes (Abstract in rivista)

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  • Effect of obesity on insulin secretion in response to a 48-hour Physiological Increase in plasma FFA in Mexican-American subjects genetically predisposed Type 2 Diabetes (Abstract in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • Mathew M.; Darland C.; Gastaldelli A.; Wang S.; Cusi K. (2007)
    Effect of obesity on insulin secretion in response to a 48-hour Physiological Increase in plasma FFA in Mexican-American subjects genetically predisposed Type 2 Diabetes
    (literal)
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  • Mathew M.; Darland C.; Gastaldelli A.; Wang S.; Cusi K. (literal)
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  • Annual Meeting of American Diabetes Association (literal)
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  • 56 (literal)
Rivista
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  • In: Annual Meeting of American Diabetes Association (Chicago, 22-26 giugno 2007). Proceedings, pp. A388 - A388. American Diabetes Association, 2007. (literal)
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  • Results: Background and Aims: A sustained physiologic elevation of plasma FFA induced by lipid infusion impairs insulin secretion in lean normal glucose-tolerant (NGT) subjects genetically predisposed to T2DM (both parents with T2DM; FH+), but the effect in obese pts has not been previously examined in Mexican-American (MxAm) FH+. To this end, we studied the effect of a 48-hour lipid infusion on insulin secretion in 8 obese NGT MxAmFH+ (OBFH+) (42±4yr, BMI=33.5±1.5 kg/m2, FPG=95±3 mg/dl) and 8 obese NGT MxAm matchedcontrols (OB-CON) without a family history of T2DM (40±5yr, BMI=30.0±0.9 kg/m2, FPG=97±3mg/dl). We also compared results with 8 NGT lean MxAmFH+ (L-FH+) (43±5yr, BMI=25±0.9 kg/m2, FPG=94±4 mg/dl) and 8 lean MxAm matched-controls (L-CON) without a family history of T2DM (35±4yr, BMI=25.5±0.9 kg/m2, FPG=93±1mg/dl). Materials and Methods: Pts were admitted twice to the research unit and received either an infusion of saline (SAL-control) or low-dose lipid (LIP; 30 ml/h; target FFA 2-fold elevation). On day 3, a +125 mg/dL hyperglycemic clamp was performed to assess insulin sensitivity (M/I) and secretion rates (ISR) by deconvolution analysis of plasma C-peptide conc. Results: Mean 48-hour plasma FFA were comparable during SAL (NS) in obese subjects and increased similarly by ^70% with LIP (p0.01 vs. SAL; NS between groups).Obese FH+ and CON subjects were insulin resistant (M/I) compared to their respective lean controls (p0.01). During SAL, both OB FH+ and CON groups had a higher increase above baseline (delta) in first (0-10 min; 1stph) and second (10-120 min; 2ndph) phase ISR: L-FH+ vs. OB-FH+ and L-CON vs. OB-CON (both p0.01). When ISR was expressed taking into account insulin sensitivity, 1stph (-19%) and 2nd ph (-16%) ISR was lower in OB-FH+ compared to OB-CON (both p0.05). During LIP, ISR was also lower in L-FH+ and L-CON (1st ph: -60% and -32%, 2nd ph:-31% and -42%, respectively, all p0.01 vs. the respective obese group).Insulin resistance was not further exacerbated by LIP in either OB-FH+ vs. OB-CON. In OB-FH+ vs OB-CON, 1stph (- 30%) and 2ndph (-26%) ISR remained significantly lower when taking into account insulin sensitivity during LIP (both p0.05). LIP infusion caused a greater reduction in both 1stph and 2ndph ISR (both p0.05) in L-FH+ compared to OB-FH+.Conclusion: Obesity is associated with a significant increase in ISR in OB-FH+ vs. OB-CON. ISR in L-FH+ appears to be more susceptible to lipotoxicity than in OB-FH+. (literal)
Note
  • Abstract (literal)
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  • IFC-CNR Pisa UTHSCSA San Antonio Tx USA (literal)
Titolo
  • Effect of obesity on insulin secretion in response to a 48-hour Physiological Increase in plasma FFA in Mexican-American subjects genetically predisposed Type 2 Diabetes (literal)
Abstract
  • Background and Aims: A sustained physiologic elevation of plasma FFA induced by lipid infusion impairs insulin secretion in lean normal glucose-tolerant (NGT) subjects genetically predisposed to T2DM (both parents with T2DM; FH+), but the effect in obese pts has not been previously examined in Mexican-American (MxAm) FH+. To this end, we studied the effect of a 48-hour lipid infusion on insulin secretion in 8 obese NGT MxAmFH+ (OBFH+) (42±4yr, BMI=33.5±1.5 kg/m2, FPG=95±3 mg/dl) and 8 obese NGT MxAm matchedcontrols (OB-CON) without a family history of T2DM (40±5yr, BMI=30.0±0.9 kg/m2, FPG=97±3mg/dl). We also compared results with 8 NGT lean MxAmFH+ (L-FH+) (43±5yr, BMI=25±0.9 kg/m2, FPG=94±4 mg/dl) and 8 lean MxAm matched-controls (L-CON) without a family history of T2DM (35±4yr, BMI=25.5±0.9 kg/m2, FPG=93±1mg/dl). Materials and Methods: Pts were admitted twice to the research unit and received either an infusion of saline (SAL-control) or low-dose lipid (LIP; 30 ml/h; target FFA 2-fold elevation). On day 3, a +125 mg/dL hyperglycemic clamp was performed to assess insulin sensitivity (M/I) and secretion rates (ISR) by deconvolution analysis of plasma C-peptide conc. Results: Mean 48-hour plasma FFA were comparable during SAL (NS) in obese subjects and increased similarly by ^70% with LIP (p0.01 vs. SAL; NS between groups).Obese FH+ and CON subjects were insulin resistant (M/I) compared to their respective lean controls (p0.01). During SAL, both OB FH+ and CON groups had a higher increase above baseline (delta) in first (0-10 min; 1stph) and second (10-120 min; 2ndph) phase ISR: L-FH+ vs. OB-FH+ and L-CON vs. OB-CON (both p0.01). When ISR was expressed taking into account insulin sensitivity, 1stph (-19%) and 2nd ph (-16%) ISR was lower in OB-FH+ compared to OB-CON (both p0.05). During LIP, ISR was also lower in L-FH+ and L-CON (1st ph: -60% and -32%, 2nd ph:-31% and -42%, respectively, all p0.01 vs. the respective obese group).Insulin resistance was not further exacerbated by LIP in either OB-FH+ vs. OB-CON. In OB-FH+ vs OB-CON, 1stph (- 30%) and 2ndph (-26%) ISR remained significantly lower when taking into account insulin sensitivity during LIP (both p0.05). LIP infusion caused a greater reduction in both 1stph and 2ndph ISR (both p0.05) in L-FH+ compared to OB-FH+.Conclusion: Obesity is associated with a significant increase in ISR in OB-FH+ vs. OB-CON. ISR in L-FH+ appears to be more susceptible to lipotoxicity than in OB-FH+. (literal)
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