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
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页码:1268 / 1275
页数:8
相关论文
共 32 条
  • [11] Validation of methods for measurement of insulin secretion in humans in vivo
    Kjems, LL
    Christiansen, E
    Volund, A
    Bergman, RN
    Madsbad, S
    [J]. DIABETES, 2000, 49 (04) : 580 - 588
  • [12] INCREASE IN INSULIN-RESPONSE AFTER TREATMENT OF OVERT MATURITY-ONSET DIABETES IN INDEPENDENT OF THE MODE OF TREATMENT
    KOSAKA, K
    KUZUYA, T
    AKANUMA, Y
    HAGURA, R
    [J]. DIABETOLOGIA, 1980, 18 (01) : 23 - 28
  • [13] THE HETEROGENEITY OF GASTRIC-INHIBITORY POLYPEPTIDE IN PORCINE AND HUMAN GASTROINTESTINAL MUCOSA EVALUATED WITH 5 DIFFERENT ANTISERA
    KRARUP, T
    HOLST, JJ
    [J]. REGULATORY PEPTIDES, 1984, 9 (1-2) : 35 - 46
  • [14] DIMINISHED IMMUNOREACTIVE GASTRIC-INHIBITORY POLYPEPTIDE RESPONSE TO A MEAL IN NEWLY DIAGNOSED TYPE-I (INSULIN DEPENDENT) DIABETICS
    KRARUP, T
    MADSBAD, S
    MOODY, AJ
    REGEUR, L
    FABER, OK
    HOLST, JJ
    SESTOFT, L
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1983, 56 (06) : 1306 - 1312
  • [15] REDUCED INCRETIN EFFECT IN TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES
    NAUCK, M
    STOCKMANN, F
    EBERT, R
    CREUTZFELDT, W
    [J]. DIABETOLOGIA, 1986, 29 (01) : 46 - 52
  • [16] PRESERVED INCRETIN ACTIVITY OF GLUCAGON-LIKE PEPTIDE-1 [7-36 AMIDE] BUT NOT OF SYNTHETIC HUMAN GASTRIC-INHIBITORY POLYPEPTIDE IN PATIENTS WITH TYPE-2 DIABETES-MELLITUS
    NAUCK, MA
    HEIMESAAT, MM
    ORSKOV, C
    HOLST, JJ
    EBERT, R
    CREUTZFELDT, W
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (01) : 301 - 307
  • [17] INCRETIN EFFECTS OF INCREASING GLUCOSE LOADS IN MAN CALCULATED FROM VENOUS INSULIN AND C-PEPTIDE RESPONSES
    NAUCK, MA
    HOMBERGER, E
    SIEGEL, EG
    ALLEN, RC
    EATON, RP
    EBERT, R
    CREUTZFELDT, W
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1986, 63 (02) : 492 - 498
  • [18] Twenty-four-hour insulin secretion rates, circulating concentrations of fuel substrates and gut incretin hormones in healthy offspring of Type II (non-insulin-dependent) diabetic parents: evidence of several aberrations
    Nyholm, B
    Walker, M
    Gravholt, CH
    Shearing, PA
    Sturis, J
    Alberti, KGMM
    Holst, JJ
    Schmitz, O
    [J]. DIABETOLOGIA, 1999, 42 (11) : 1314 - 1323
  • [19] TISSUE AND PLASMA-CONCENTRATIONS OF AMIDATED AND GLYCINE-EXTENDED GLUCAGON-LIKE PEPTIDE-I IN HUMANS
    ORSKOV, C
    RABENHOJ, L
    WETTERGREN, A
    KOFOD, H
    HOLST, JJ
    [J]. DIABETES, 1994, 43 (04) : 535 - 539
  • [20] Minireview:: Secondary β-cell failure in type 2 diabetes -: A convergence of glucotoxicity and lipotoxicity
    Poitout, V
    Robertson, RP
    [J]. ENDOCRINOLOGY, 2002, 143 (02) : 339 - 342