Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes

Mandeep Bajaj, Thongchai Pratipanawatr, Rachele Berria, Wilailak Pratipanawatr, Sangeeta Kashyap, Kenneth Cusi, Lawrence Mandarine, Ralph A Defronzo

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Abstract

Splanchnic glucose uptake (SGU) plays a major role in the disposal of an oral glucose load (OGL). To investigate the effect of an elevated plasma free fatty acid (FFA) concentration on SGU in patients with type 2 diabetes, we measured SGU in eight diabetic patients (mean age 51 ± 4 years, BMI 29.3 ± 1.4 kg/m2, fasting plasma glucose 9.3 ± 0.7 mmol/l) during an intravenous Intralipid/heparin infusion and 7-10 days later during a saline infusion. SGU was estimated by the OGL insulin clamp method: subjects received a 7-h euglycemic-hyperinsulinemic clamp (insulin infusion rate = 100 mU·m-2·min-1), and a 75-g OGL was ingested 3 h after starting the insulin clamp. After glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4-h period after glucose ingestion from the ingested glucose load (75 g). 3-[3H]glucose was infused during the 3-h insulin clamp before glucose ingestion to determine the rates of endogenous glucose production and glucose disappearance (Rd). Intralipid/heparin or saline infusion was initiated 2 h before the start of the OGL clamp. Plasma FFA concentrations were significantly higher during the OGL clamp with the intralipid/heparin infusion than with the saline infusion (2.5 ± 0.3 vs. 0.11 ± 0.02 mmol/l, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, Intralipid/heparin infusion reduced Rd (4.4 ± 0.3 vs. 5.3 ± 0.3 mg·kg-1·min-1, P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly decreased during the intralipid/heparin versus saline infusion (30 ± 2 vs. 37 ± 2%, P < 0.01). In conclusion, an elevation in plasma FFA concentration impairs both peripheral and SGU in patients with type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)3043-3048
Number of pages6
JournalDiabetes
Volume51
Issue number10
StatePublished - Oct 1 2002

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Viscera
Nonesterified Fatty Acids
Type 2 Diabetes Mellitus
Glucose
Glucose Clamp Technique
Heparin
Insulin
Eating

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Bajaj, M., Pratipanawatr, T., Berria, R., Pratipanawatr, W., Kashyap, S., Cusi, K., ... Defronzo, R. A. (2002). Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes. Diabetes, 51(10), 3043-3048.

Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes. / Bajaj, Mandeep; Pratipanawatr, Thongchai; Berria, Rachele; Pratipanawatr, Wilailak; Kashyap, Sangeeta; Cusi, Kenneth; Mandarine, Lawrence; Defronzo, Ralph A.

In: Diabetes, Vol. 51, No. 10, 01.10.2002, p. 3043-3048.

Research output: Contribution to journalArticle

Bajaj, M, Pratipanawatr, T, Berria, R, Pratipanawatr, W, Kashyap, S, Cusi, K, Mandarine, L & Defronzo, RA 2002, 'Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes', Diabetes, vol. 51, no. 10, pp. 3043-3048.
Bajaj M, Pratipanawatr T, Berria R, Pratipanawatr W, Kashyap S, Cusi K et al. Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes. Diabetes. 2002 Oct 1;51(10):3043-3048.
Bajaj, Mandeep ; Pratipanawatr, Thongchai ; Berria, Rachele ; Pratipanawatr, Wilailak ; Kashyap, Sangeeta ; Cusi, Kenneth ; Mandarine, Lawrence ; Defronzo, Ralph A. / Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes. In: Diabetes. 2002 ; Vol. 51, No. 10. pp. 3043-3048.
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abstract = "Splanchnic glucose uptake (SGU) plays a major role in the disposal of an oral glucose load (OGL). To investigate the effect of an elevated plasma free fatty acid (FFA) concentration on SGU in patients with type 2 diabetes, we measured SGU in eight diabetic patients (mean age 51 ± 4 years, BMI 29.3 ± 1.4 kg/m2, fasting plasma glucose 9.3 ± 0.7 mmol/l) during an intravenous Intralipid/heparin infusion and 7-10 days later during a saline infusion. SGU was estimated by the OGL insulin clamp method: subjects received a 7-h euglycemic-hyperinsulinemic clamp (insulin infusion rate = 100 mU·m-2·min-1), and a 75-g OGL was ingested 3 h after starting the insulin clamp. After glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4-h period after glucose ingestion from the ingested glucose load (75 g). 3-[3H]glucose was infused during the 3-h insulin clamp before glucose ingestion to determine the rates of endogenous glucose production and glucose disappearance (Rd). Intralipid/heparin or saline infusion was initiated 2 h before the start of the OGL clamp. Plasma FFA concentrations were significantly higher during the OGL clamp with the intralipid/heparin infusion than with the saline infusion (2.5 ± 0.3 vs. 0.11 ± 0.02 mmol/l, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, Intralipid/heparin infusion reduced Rd (4.4 ± 0.3 vs. 5.3 ± 0.3 mg·kg-1·min-1, P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly decreased during the intralipid/heparin versus saline infusion (30 ± 2 vs. 37 ± 2{\%}, P < 0.01). In conclusion, an elevation in plasma FFA concentration impairs both peripheral and SGU in patients with type 2 diabetes.",
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AU - Pratipanawatr, Wilailak

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AU - Cusi, Kenneth

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