Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes

被引:75
作者
Meneilly, GS
Greig, N
Tildesley, H
Habener, JF
Egan, JM
Elahi, D
机构
[1] Harvard Univ, Geriatr Res Lab, Massachusetts Gen Hosp, Dept Med,Med Sch, Boston, MA 02114 USA
[2] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada
[3] NIA, NIH, Baltimore, MD 21224 USA
[4] Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA
关键词
D O I
10.2337/diacare.26.10.2835
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-Glucagon-like peptide 1 (GLP-1) is an insulinotropic gut hormone that, when given exogenously, may be a useful agent in the treatment of type 2 diabetes. We conducted a 3-month trial to determine the efficacy and safety of GLP-1 in elderly diabetic patients. RESEARCH DESIGN AND METHODS-A total of 16 patients with type 2 diabetes who were being treated with oral hypoglycemic agents were enrolled. Eight patients (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) remained on usual glucose-lowering therapy and eight patients (aged 73 +/- 1 years, BMI 27 +/- 1 kg/m(2)), after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol (.) kg(-1) (.) h(-1). Patients recorded their capillary blood glucose (CBG) levels (four times per day, 3 days per week) and whenever they perceived hypoglycemic symptoms. The primary end points were HbA(1c) and CBG determinations. Additionally, changes in beta-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined. RESULTS-HbA(1c) levels (7.1%) and body weight were equally maintained in both groups. The usual treatment group had a total of 87 CBG measurements of less than or equal to3.6 mmol/l during the study, and only 1 such measurement (3.5 mmol/l) was recorded in the GLP-1 group. Infusion of GLP-1 enhanced glucose-induced insulin secretion (pre: 119 +/- 21; post: 202 +/- 51 pmol/l; P < 0.05) and insulin-mediated glucose disposal (pre: 29.8 +/- 3.3; post: 35.9 +/- 2.3 mumol (.) kg(-1) (.) min(-1) ; P < 0.01). No effect of GLP-1 treatment was seen on the fasting plasma ghrelin levels. Although plasma ghrelin levels decreased during both portions of the clamp, a drug effect was not present. CONCLUSIONS-A GLP-1 compound is a promising therapeutic option for elderly diabetic patients.
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页码:2835 / 2841
页数:7
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共 31 条
  • [1] Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.
    Cummings, DE
    Weigle, DS
    Frayo, RS
    Breen, PA
    Ma, MK
    Dellinger, EP
    Purnell, JQ
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (21) : 1623 - 1630
  • [2] *DIAB PREV PROGR R, 2002, NEW ENGL J MED, V346, P396
  • [3] Minireview: The glucagon-like peptides
    Drucker, DJ
    [J]. ENDOCRINOLOGY, 2001, 142 (02) : 521 - 527
  • [4] Glucagon-like peptides
    Drucker, DJ
    [J]. DIABETES, 1998, 47 (02) : 159 - 169
  • [5] Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state
    Egan, JM
    Meneilly, GS
    Habener, JF
    Elahi, D
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (08) : 3768 - 3773
  • [6] EGAN JM, 2002, AM J PHSYL ENDOCRINO, V284, pE1072
  • [7] THE INSULINOTROPIC ACTIONS OF GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE (GIP) AND GLUCAGON-LIKE PEPTIDE-1(7-37) IN NORMAL AND DIABETIC SUBJECTS
    ELAHI, D
    MCALOONDYKE, M
    FUKAGAWA, NK
    MENEILLY, GS
    SCLATER, AL
    MINAKER, KL
    HABENER, JF
    ANDERSEN, DK
    [J]. REGULATORY PEPTIDES, 1994, 51 (01) : 63 - 74
  • [8] FEEDBACK INHIBITION OF INSULIN-SECRETION BY INSULIN - RELATION TO THE HYPERINSULINEMIA OF OBESITY
    ELAHI, D
    NAGULESPARAN, M
    HERSHCOPF, RJ
    MULLER, DC
    TOBIN, JD
    BLIX, PM
    RUBENSTEIN, AH
    UNGER, RH
    ANDRES, R
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1982, 306 (20) : 1196 - 1202
  • [9] Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans
    Flint, A
    Raben, A
    Astrup, A
    Holst, JJ
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (03) : 515 - 520
  • [10] Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2
    Gutzwiller, JP
    Drewe, J
    Göke, B
    Schmidt, H
    Rohrer, B
    Lareida, J
    Beglinger, C
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1999, 276 (05) : R1541 - R1544