Four weeks of near-normalization of blood glucose has no effect on postprandial GLP-1 and GIP secretion, but augments pancreatic B-cell responsiveness to a meal in patients with Type 2 diabetes

被引:50
作者
Hojberg, P. V. [1 ,2 ]
Vilsboll, T. [2 ]
Zander, M. [1 ]
Knop, F. K. [2 ]
Krarup, T. [2 ]
Volund, A. [3 ]
Holst, J. J. [4 ]
Madsbad, S. [1 ]
机构
[1] Univ Copenhagen, Hvidovre Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark
[2] Univ Copenhagen, Gentofte Hosp, Dept Internal Med F, DK-1168 Copenhagen, Denmark
[3] Univ Copenhagen, Novo Nordisk AS, Dept Biostat, DK-1168 Copenhagen, Denmark
[4] Univ Copenhagen, Panum Inst, Dept Med Physiol, DK-1168 Copenhagen, Denmark
关键词
B-cell function; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; meal response; Type 2 diabetes mellitus;
D O I
10.1111/j.1464-5491.2008.02579.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective The aim of the present study was to investigate whether 4 weeks of near-normalization of blood glucose (BG) improves incretin hormone secretion and pancreatic B-cell function during a mixed meal. Research design and methods Nine patients with Type 2 diabetes in poor glycaemic control [glycated haemoglobin (HbA(1c)) 8.0 +/- 0.4%] were investigated before and after 4 weeks of near-normalization of BG (mean BG 6.4 +/- 0.3 mmol/l) using insulin treatment. HbA(1c) after insulin treatment was 6.6 +/- 0.3%. For comparison, nine healthy control subjects were also studied. Postprandial glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) incremental responses were assessed during a mixed meal test. Fasting and postprandial pancreatic B-cell function was determined from calculations of insulin secretion rates in relation to plasma glucose. Results There was no difference in IAUC(totalGLP-1) or in IAUC(totalGIP) between the two experimental days. B-cell sensitivity to glucose (insulinogenic index) did not differ before and after insulin treatment in the fasting state (0.21 +/- 0.17 vs. 0.25 +/- 0.10 pmol kg(-1) min(-1)/mmol l(-1)), but improved significantly during the first 30 min after start of the meal (0.28 +/- 0.07 vs. 0.46 +/- 0.06 pmol kg(-1) min(-1)/mmol l(-1)) and during the following 4 h (0.34 +/- 0.09 vs. 0.56 +/- 0.07 pmol kg-1 min-1/mmol l(-1)). The B-cell responsiveness to changes in plasma glucose, expressed as the slope of the linear relationship between the insulin secretion rate and the concomitant plasma glucose increased from 0.59 +/- 0.16 to 0.94 +/- 0.13 pmol kg-1 min-1/mmol l(-1) ( P < 0.07). Conclusions Four weeks of near-normalization of BG had no effect on postprandial secretion of incretin hormones. Nevertheless, several parameters of meal-induced insulin secretion improved after insulin treatment.
引用
收藏
页码:1268 / 1275
页数:8
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