Research Article| Volume 30, ISSUE 12, P1219-1228, December 15, 1991

Increased insulin levels after OGTT load in peripheral blood and cerebrospinal fluid of patients with dementia of Alzheimer type

      This paper is only available as a PDF. To read, Please Download here.


      An investigation was carried out to determine whether a disturbance of glycometabolism is associated with dementia of Alzheimer type (AD). The first part of the study was carried out on 108 AD patients and 57 normal controls (NCs). Neither the plasma level of insulin nor that of glucose differed significantly between the two groups before the oral glucose tolerance test (OGTT), whereas there was a significantly greater increase of the plasma insulin in the AD group than in the NC group after the OGTT. The second part of the study was carried out on 54 AD patients, 44 patients with vascular dementia (VD), and 26 NCs. Early in the morning after overnight fasting, there was no significant difference in the fasting plasma level of either glucose or insulin, or the cerebrospinal fluid (CSF) level of glucose, among the three groups, However, the CSF level of insulin was significantly higher in the AD group than in the other two groups. These results suggest that an abnormally high level of insulin, not only in the peripheral blood after OGTT load but also in the CSF after fasting, may be associated with the pathology of AD.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Aizenman Y.
        • de Vellis J.
        Brain neurons develop in a serum and glial free environment: Effects of transferrin, insulin, insulin-like growth factor-I and thyroid hormone on neuronal survival, growth, and differentiation.
        Brain Res. 1987; 406: 32-42
        • American Psychiatric Association
        3rd ed. rev. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Press, Washington, DC1987: 54-55
        • Anthony J.C.
        • Le Resche L.
        • Niaz U.
        • et al.
        Limits of the “Mini-Mental State” as a screening test for dementia and delirium among hospital patients.
        Psychol Med. 1982; 12: 397-408
        • Baskin D.G.
        • Figlewicz D.P.
        • Woods S.C.
        • et al.
        Insulin in the brain.
        Annu Rev Physiol. 1987; 49: 335-347
        • Bucht G.
        • Adolfsson R.
        • Lithner F.
        • et al.
        Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type.
        Acta Med Scand. 1983; 213: 387-392
        • Duffy K.R.
        • Pardridge W.M.
        Blood-brain barrier transcytosis of insulin in developing rabbits.
        Brain Res. 1987; 420: 32-38
        • Elovaara I.
        • Icen A.
        • Palo J.
        • et al.
        CSF in Alzheimer's disease studies on blood-brain barrier function and intrathecal protein synthesis.
        J Neurol Sci. 1985; 70: 73-80
        • Eng J.
        • Yalow R.S.
        Evidence against extrapancreatic insulin synthesis.
        in: Proc Natl Acad Sci USA. 78. 1981: 4576-4578
        • Folstein N.F.
        • Folstein S.E.
        • McHugh P.R.
        “Mini-mental state” A practical method for grading the cognitive state of patients for the clinician.
        J Psychiatr Res. 1975; 12: 189-198
        • Garofalo R.S.
        • Rosen O.M.
        Insulin and insulinlike growth factor 1 (IGF-1) receptors during central nervous system development: Expression of two immunologically distinct IGF-1 receptor subunits.
        Mol Cell Biol. 1989; 9: 2806-2817
        • Giddings S.J.
        • Chirgwin J.
        • Permutt M.A.
        Evaluation of rat insulin messenger RNA in pancreatic and extrapancreatic tissues.
        Diabetologia. 1985; 28: 343-347
        • Hachinski V.C.
        • Iliff L.D.
        • Zilhka E.
        • et al.
        Cerebral blood flow in dementia.
        Arch Neurol. 1975; 32: 632-637
        • Havrankova J.
        • Schmechel D.
        • Roth J.
        • et al.
        Identification of insulin in rat brain.
        in: Proc Natl Acad Sci USA. 75. 1978: 5737-5741
        • Havrankova J.
        • Brownstein M.
        • Roth J.
        Insulin and insulin receptors in rodent brain.
        Diabetologia. 1981; 20: 268-273
        • Ihara Y.
        Massive somatodendritic sprouting of cortical neurons in Alzheimer's disease.
        Brain Res. 1988; 459: 138-144
        • Kaneko T.
        • Yaga K.
        Clin All-Round. 1985; 34 (in Japanese): 198-201
        • Manin M.
        • Mizrahi M.
        • Vye P.
        • et al.
        The influence of acute hyperinsulinemia on the insulin-related material in brain, testis, liver, and kidney.
        Metabolism. 1987; 36: 1067-1072
        • McKhann G.
        • Drachman D.
        • Folstein M.
        • et al.
        Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Sciences Task Force on Alzheimer's disease.
        Neurology. 1984; 34: 939-944
        • Ono T.
        • Steffens A.B.
        • Sasaki K.
        Influence of peripheral and intracerebroventricular glucose and insulin infusions on perpheral and cerebrospinal fluid glucose and insulin levels.
        Physiol Behav. 1983; 30: 301-306
        • Pardridge W.M.
        • Eisenberg J.
        • Yang J.
        Human blood-brain barrier insulin receptor.
        J Neurochem. 1985; 44: 1771-1778
        • Peterson C.
        • Ratan R.R.
        • Shlanski M.L.
        • et al.
        Cytosolic free calcium and cell spreading decrease in fibroblasts from aged and Alzheimer donors.
        in: Proc Natl Acad Sci USA. 83. 1986: 7999-8001
        • Probst A.
        • Basler V.
        • Bron B.
        • et al.
        Neuritic plaques in senile dementia of Alzheimer type. A Golgi analysis in the hippocampal region.
        Brain Res. 1983; 268: 249-254
        • Reiser M.
        • Lenz E.
        • Bernstein H.-G.
        • et al.
        Insulin-like immunoreactivity in human cerebrospinal-fluid is independent of insulin blood levels.
        Human Neurobiol. 1985; 4: 53-55
        • Scheibel A.B.
        • Duong T.
        On the possible relationship of cortical microvascular pathology to blood brain barrier changes in Alzheimer's disease.
        Neurobiol Aging. 1988; 9: 41-42
        • Sekimoto H.
        Diagnostic criteria for cerebrovascular disease.
        Jpn J Clin Med. 1986; 44 (in Japanese): 11-22
        • Sims N.
        • Finegan J.M.
        • Blass J.P.
        Altered metabolic properties of cultured skin fibroblasts in Alzheimer's disease.
        Ann Neurol. 1987; 21: 451-457
        • Sulkava R.
        Alzheimer's disease and senile dementia of Alzheimer type.
        Acta Neurol Scand. 1982; 65: 636-650
        • Unger J.
        • McNeill T.H.
        • Moxley III, R.T.
        • et al.
        Distribution of insulin receptor-like immunoreactivity in the rat forebrain.
        Neuroscience. 1989; 31: 143-157
        • Van Houten M.
        • Nance D.M.
        • Gauthier S.
        • et al.
        Origin of insulin-receptive nerve terminals in rat median eminence.
        Endocrinology. 1983; 113: 1393-1399
        • Wallum B.J.
        • Taborsky Jr., G.J.
        • Porte Jr., D.
        • et al.
        Cerebrospinal fluid insulin levels increase during intravenous insulin infusion in man.
        J Clin Endocrinol Metab. 1987; 64: 190-194
        • WHO Expert Committee on Diabetes Mellitus
        Second Report, Technical Report Series 646. WHO, Geneva1980
        • Wisnieski H.M.
        • Kozlowski P.B.
        Evidence of blood-brain barrier changes in senile dementia of the Alzheimer type.
        Ann NY Acad Sci. 1982; 396: 119-129
        • Woods S.C.
        • Porte Jr., D.
        • Bobbioni E.
        • et al.
        Insulin: Its relationship to the central nervous system and to the control of food intake and body weight.
        Am J Clin Nutr. 1985; 42: 1063-1071
        • Young W.S.
        Periventricular hypothalamic cells in the rat brain contain insulin mRNA.
        Neuropeptides. 1986; 8: 93-97