OBJECTIVE: To quantify the effect of metformin on the metabolism of triglyceride (TG)-rich lipoprotein of intestinal origin in patients with non-insulin-dependent diabetes mellitus (NIDDM) who had responded to sulfonylurea but still had fasting hyperglycemia. RESEARCH DESIGN AND METHODS: Sixteen patients with NIDDM who had demonstrated a fall in fasting plasma glucose concentration > 2.2 mmol/l in response to glipizide treatment but continued to have fasting plasma glucose concentrations > 8.3 mmol/l were studied. Fasting glucose, GHb, lipid and lipoprotein concentrations were determined, and resistance to insulin-mediated glucose disposal was estimated by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of somatostatin, glucose, and insulin. In addition, plasma glucose, insulin, and TG concentrations were measured at frequent intervals from 0800 to 2400, with patients eating breakfast at 0800 and lunch at 1200. Vitamin A was also given at lunch, and the retinyl ester content in plasma and in chylomicron (Svedberg flotation constant [Sf] > 400) and the chylomicron remnant (Sf 20-400) fractions were used to quantify the concentration of postprandial intestinal TG-rich lipoprotein from 1200 to 2400. RESULTS: Fasting plasma glucose concentrations (6.8 +/- 0.4 vs. 10.5 +/- 0.4 mmol/l), GHb levels (7.9 +/- 0.3 vs. 10.8 +/- 0.5%), and day-long plasma glucose concentrations were all significantly lower after metformin treatment (P < 0.001), which was associated with a significant (P < 0.001) fall in SSPG concentration (11.0 +/- 0.9 to 9.6 +/- 0.6 mmol/l). In addition, postprandial concentrations of glucose, insulin, free fatty acids, and TG were lower (P < 0.001) following metformin treatment. Postprandial retinyl ester concentrations were also lower in plasma by 33 +/- 5.7% (P < 0.001) and in both the chylomicron (32 +/- 7.2%, P < 0.001) and chylomicron remnant (26 +/- 7.0%, P < 0.005) fractions. CONCLUSIONS: Addition of metformin to sulfonylurea-treated patients with NIDDM with less than optimal glycemic control was associated with improved glycemic control, lower postprandial insulin and TG concentrations, and a decrease in postprandial concentration of TG-rich lipoproteins of intestinal origin. All of these changes might be expected to decrease risk of coronary heart disease.
OBJECTIVE: To quantify the effect of metformin on the metabolism of triglyceride (TG)-rich lipoprotein of intestinal origin in patients with non-insulin-dependent diabetes mellitus (NIDDM) who had responded to sulfonylurea but still had fasting hyperglycemia. RESEARCH DESIGN AND METHODS: Sixteen patients with NIDDM who had demonstrated a fall in fasting plasma glucose concentration > 2.2 mmol/l in response to glipizide treatment but continued to have fasting plasma glucose concentrations > 8.3 mmol/l were studied. Fasting glucose, GHb, lipid and lipoprotein concentrations were determined, and resistance to insulin-mediated glucose disposal was estimated by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of somatostatin, glucose, and insulin. In addition, plasma glucose, insulin, and TG concentrations were measured at frequent intervals from 0800 to 2400, with patients eating breakfast at 0800 and lunch at 1200. Vitamin A was also given at lunch, and the retinyl ester content in plasma and in chylomicron (Svedberg flotation constant [Sf] > 400) and the chylomicron remnant (Sf 20-400) fractions were used to quantify the concentration of postprandial intestinal TG-rich lipoprotein from 1200 to 2400. RESULTS: Fasting plasma glucose concentrations (6.8 +/- 0.4 vs. 10.5 +/- 0.4 mmol/l), GHb levels (7.9 +/- 0.3 vs. 10.8 +/- 0.5%), and day-long plasma glucose concentrations were all significantly lower after metformin treatment (P < 0.001), which was associated with a significant (P < 0.001) fall in SSPG concentration (11.0 +/- 0.9 to 9.6 +/- 0.6 mmol/l). In addition, postprandial concentrations of glucose, insulin, free fatty acids, and TG were lower (P < 0.001) following metformin treatment. Postprandial retinyl ester concentrations were also lower in plasma by 33 +/- 5.7% (P < 0.001) and in both the chylomicron (32 +/- 7.2%, P < 0.001) and chylomicron remnant (26 +/- 7.0%, P < 0.005) fractions. CONCLUSIONS: Addition of metformin to sulfonylurea-treated patients with NIDDM with less than optimal glycemic control was associated with improved glycemic control, lower postprandial insulin and TG concentrations, and a decrease in postprandial concentration of TG-rich lipoproteins of intestinal origin. All of these changes might be expected to decrease risk of coronary heart disease.
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