EXAGGERATED EARLY INSULIN RELEASE AND INSULIN RESISTANCE IN A DIABETES-PRONE POPULATION - A METABOLIC COMPARISON OF PIMA-INDIANS AND CAUCASIANS

被引:135
作者
LILLIOJA, S
NYOMBA, BL
SAAD, MF
FERRARO, R
CASTILLO, C
BENNETT, PH
BOGARDUS, C
机构
[1] Geriatrics Research, Education, Clinical Center (GRECC), Seattle Veterans Administration Medical Center, Washington, 98108, Seattle
[2] Department of Psychiatry and Behavioral Sciences, University of Washington, Washington, 98108, Seattle
[3] Bronx Veterans Administration Medical Center, Mt. Sinai School of Medicine, New York, NY
关键词
D O I
10.1210/jcem-73-4-866
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Pima Indians have the highest reported prevalence rate of noninsulin-dependent diabetes mellitus (NIDDM) in the world, so that metabolic comparisons with caucasians, who have a much lower rate, should provide insights into the pathogenesis of NIDDM. We have compared 81 caucasians with 211 Pima Indian nondiabetic subjects similar in age, sex, degree of obesity, and glucose tolerance. During a hyperinsulinemic euglycemic clamp at physiological insulin concentrations, Pima Indians were 17% more insulin resistant than caucasians after accounting for any differences in degree of obesity (P < 0.0001). During oral glucose tolerance testing, mean plasma insulin concentrations were 33% higher in the Pimas (P < 0.0001), but these differences were largely explained by the greater insulin resistance in the Pimas. Insulin clearance did not differ between the races. However, early insulin responses were exaggerated in the Indians and not explained by insulin resistance. After accounting for differences in insulin action, plasma insulin concentrations in Pima Indians were 50% higher than those in caucasians 3-5 min after iv glucose (P < 0.0001), 38% higher 10 min after the end of a meal (P < 0.0001), and 20% higher 30 min after an oral glucose load (P < 0.006). These data suggest that in addition to insulin resistance, Pima Indians have exaggerated early insulin release and either increased beta-cell mass or enhanced beta-cell sensitivity to glucose. The data argue against low or delayed insulin secretion as primary factors leading to NIDDM in Pima Indians and favor insulin resistance as the underlying and initiating cause of the disease.
引用
收藏
页码:866 / 876
页数:11
相关论文
共 64 条
  • [1] IMMUNOREACTIVE GLUCAGON (IRG) RESPONSES TO INTRAVENOUS GLUCOSE IN PREDIABETES AND DIABETES AMONG PIMA INDIANS AND NORMAL CAUCASIANS
    ARONOFF, SL
    BENNETT, PH
    UNGER, RH
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1977, 44 (05) : 968 - 972
  • [2] UNEXPLAINED HYPERINSULINEMIA IN NORMAL AND PREDIABETIC PIMA INDIANS COMPARED WITH NORMAL CAUCASIANS - EXAMPLE OF RACIAL-DIFFERENCES IN INSULIN-SECRETION
    ARONOFF, SL
    BENNETT, PH
    GORDEN, P
    RUSHFORTH, N
    MILLER, M
    [J]. DIABETES, 1977, 26 (09) : 827 - 840
  • [3] ARGININE-STIMULATED HYPERGLUCAGONEMIA IN DIABETIC PIMA INDIANS
    ARONOFF, SL
    BENNETT, PH
    RUSHFORTH, NB
    MILLER, M
    UNGER, RH
    [J]. DIABETES, 1976, 25 (05) : 404 - 407
  • [4] ARONOFF SL, 1976, CLIN ENDOCRINOL META, V43, P279
  • [5] THE DIAGNOSIS OF DIABETES - NEW INTERNATIONAL CLASSIFICATION AND DIAGNOSTIC-CRITERIA
    BENNETT, PH
    [J]. ANNUAL REVIEW OF MEDICINE, 1983, 34 : 295 - 309
  • [6] ASSESSMENT OF INSULIN SENSITIVITY INVIVO - A CRITICAL-REVIEW
    BERGMAN, RN
    HOPE, ID
    YANG, YJ
    WATANABE, RM
    MEADOR, MA
    YOUN, JH
    ADER, M
    [J]. DIABETES-METABOLISM REVIEWS, 1989, 5 (05): : 411 - 429
  • [7] ASSOCIATION OF ELEVATED FASTING C-PEPTIDE LEVEL AND INCREASED INTRA-ABDOMINAL FAT DISTRIBUTION WITH DEVELOPMENT OF NIDDM IN JAPANESE-AMERICAN MEN
    BERGSTROM, RW
    NEWELLMORRIS, LL
    LEONETTI, DL
    SHUMAN, WP
    WAHL, PW
    FUJIMOTO, WY
    [J]. DIABETES, 1990, 39 (01) : 104 - 111
  • [8] GLUCOSE DISPOSAL IS NOT PROPORTIONAL TO PLASMA-GLUCOSE LEVEL IN MAN
    BEST, JD
    TABORSKY, GJ
    HALTER, JB
    PORTE, D
    [J]. DIABETES, 1981, 30 (10) : 847 - 850
  • [9] FAMILIAL DEPENDENCE OF THE RESTING METABOLIC-RATE
    BOGARDUS, C
    LILLIOJA, S
    RAVUSSIN, E
    ABBOTT, W
    ZAWADZKI, JK
    YOUNG, A
    KNOWLER, WC
    JACOBOWITZ, R
    MOLL, PP
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1986, 315 (02) : 96 - 100
  • [10] DISTRIBUTION OF INVIVO INSULIN ACTION IN PIMA-INDIANS AS MIXTURE OF 3 NORMAL-DISTRIBUTIONS
    BOGARDUS, C
    LILLIOJA, S
    NYOMBA, BL
    ZURLO, F
    SWINBURN, B
    ESPOSITODELPUENTE, A
    KNOWLER, WC
    RAVUSSIN, E
    MOTT, DM
    BENNETT, PH
    [J]. DIABETES, 1989, 38 (11) : 1423 - 1432