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Loss of cognitive response in type 2 diabetes
- mani.m krishnaswamy (24 February 2004)
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Cognitive functions and T2DM.
- Sergio Stagnaro (5 March 2004)
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common link may be low DHEA
- James M. Howard (5 March 2004)
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Type 2 diabetes and cognitive decline: a question of rectifying potassium?
- Giovanni Gambassi, Giovanni Ghirlanda, Roberto Bernabei (9 March 2004)
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Prevention of cognitive decline in type 2 diabetics: measurement concerns
- Bruce Oddson, JAC Delaney (23 March 2004)
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mani.m krishnaswamy, medical adviser brakes india madrs india 600017
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From the description of loss of cognitive response there are two possibilities frequent episodes of hypoglycemia or diabetes not corrected; these metabolic states can be contributory whereas in strict control such a phenomenon may not be seen Competing interests: None declared |
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Researcher inBiophysical Semeiotics. Via Erasmo Piaggio 23/8 16037 Riva Trigoso (Genova) Italy.
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Sirs, In this exciting paper - although studying cognitive function and cognitive decline over two years of follow up, in women (and what happens in diabetic men?,) is really to short time - there is something I can't understand. Cerebral cells do not need insulin in order to take up glucose from blood. In addition, results of the "insulin secretion acute pick test", I described earlier (See HONCode web site 233736, www.semeioticabiofisica.it), are always normal in diabetic patients, even a lot of years after disease onset, showing that microcirculatory events in the brains of diabetic patients are not particularly compromised. Competing interests: None declared |
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James M. Howard, independent biologist 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
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A case may be made that low DHEA, or high background DHEAS, the inactive source of DHEA, may produce type 2 diabetes. Also, a case may be made that low DHEA reduces cognitive function. I suggest the common link here is loss of DHEA. These are coincidental symptoms of loss of DHEA. Competing interests: None declared |
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Giovanni Gambassi, Associate Professor Università Cattolica, 00168 Rome, Italy, Giovanni Ghirlanda, Roberto Bernabei
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While the study by Logroscino et al. did confirm the a priori hypothesis that among women aged 70-81 years type 2 diabetes is associated with substantial cognitive decline, an additional finding came out somewhat unexpected. In contrast to diabetic women using insulin treatment, those who were on oral hypoglycaemic agents performed similarly to women without diabetes. Although the manuscript does not provide additional information on the specific oral agents used, we speculate that this paradoxically “protective” effect be exerted by sulphonylureas by virtue of their action on ATP-sensitive potassium channels (KATP channels).(1,2) Several structural classes of the six-transmembrane domain, voltage- gated K+ channel are now known.(3) Among others, the KATP channels are heteromeric complexes of pore-forming inwardly rectifying potassium channel subunits and regulatory sulfonylurea receptor subunits. KATP channels are widely distributed throughout the nervous system including the brain and the highest levels of binding are found in the substantia nigra and in the hippocampus.(4) Sulfonylureas like glibenclamide block KATP channels; they are commonly used in the therapy of type 2 diabetes. Functionally, KATP channels provide a means of linking the electrical activity of a cell to its metabolic state, and neurotransmitter release are mediated via KATP channels. For example, the large basal forebrain neurones that provide the principal ascending cholinergic input to both the hippocampus and cerebral cortex and whose integrity is vital to learning and memory processes are modulated by KATP channels.(5) K channels may be a possible site of Alzheimer’s disease (AD) pathology. Indeed, changes in Cp20, a specific memory-associated protein that is a potent regulator of K channels, have been proposed as a possible pathophysiologic mechanism for the memory loss of AD.(6) In the same way, tacrine, the prototype of acetylcholinesterase inhibitors, contains a 4- aminopyridine moiety that resembles that of a K channel blocking agent,(7) and do behave so in hippocampal neurons preparations.(8) Similar effect has also been demonstrated for two additional acetylcholinesterase inhibitors like donepezil,(9) and galantamine.(10) 1. Landi F, Bernabei R, Gambassi G. Non-insulin-dependent diabetes mellitus and Alzheimer’s disease. J Am Geriatr Soc 1997;45:654-5 2. Bingham E, Hopkins D, Pernet A, Reid H, Macdonald IA, Amiel SA. The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study. Diabet Med 2003;20:231-7 3. Gutman GA, Chandy KG, Adelman JP, Aiyar J, Bayliss DA, Clapham DE, Covarriubias M, Desir GV, Furuichi K, Ganetzky B, Garcia ML, Grissmer S, Jan LY, Karschin A, Kim D, Kuperschmidt S, Kurachi Y, Lazdunski M, Lesage F, Lester HA, McKinnon D, Nichols CG, O'Kelly I, Robbins J, Robertson GA, Rudy B, Sanguinetti M, Seino S, Stuehmer W, Tamkun MM, Vandenberg CA, Wei A, Wulff H, Wymore RS; International Union of Pharmacology.International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels. Pharmacol Rev. 2003;55(4):583-6. 4. Treherne JM, Ashford ML. The regional distribution of sulphonylurea binding sites in rat brain. Neuroscience 1991;40:523-31 5. Allen TGJ, Brown DA. Modulation of the excitability of cholinergic basal forebrain neurones by KATP channels. J Physiol 554.2:353-70 6. Kim CS, Han YF, Etcheberrigaray R. Alzheimer and beta-amyloid treated fibroblasts demonstrate a decrease in a memory associated GTP- binding protein, Cp20. Proc Natl Acad Sci USA 1995;92:3060-4 7 Wagstaff AJ, McTavish D. Tacrine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in Alzheimer disease. Drugs Aging 1994;4:510-40 8. Li Y, Hu GY. Huperzine A, a nootropic agent, inhibits fast transient potassium current in rat dissociated hippocampal neurons. Neurosci Lett 2002;324:25-8 9. Zhong CB, Zhang W, Wang XL. Effect of donepezil on the delayed rectifier-like potassium current in pyramidal neurons of rat hippocampus and neocortex. Yao Xue Xue Bao 2002;37:415-8 10. Pan YP, Xu XH, Wang XL. Galantamine blocks delayed rectifier, but not transient outward potassium current in rat dissociated hippocampal pyramidal neurons. Neurosci Lett 2003;336:37-40 Competing interests: None declared |
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Bruce Oddson, Post-Doctoral Fellow Department of Psychology, University of Toronto, 100 St. George St.,Toronto, Ont., Canada, M4G 1R8, JAC Delaney
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In a recent study Logroscino et al looked at cognitive decline in older women with type 2 diabetes (1). One of the interesting results found is that hypoglycaemic medications seemed to provide partial protection against an otherwise high rate of cognitive decline. It is a shame, however, that the authors did not assess overall exposure to the hypoglycaemic medication by the participants. This is important as studies have shown that intensive drug therapy markedly reduces the rate of diabetic complications (2). Instead they relied on participant self report of hypoglycaemic medication use. Because no attempt was made to assess the degree of compliance it is not possible to assess the actual impact of oral hypoglycaemic medications in this population. If the participants, being health care professionals, were highly compliant then we might be seeing the maximum effective protection of these drugs. However, if the participants were not highly compliant then the degree of protection might be underestimated. There are further concerns with the method because of the way cognitive performance was assessed. There is some evidence that blood glucose level can affect cognitive performance (3). Ordinarily it is possible to accept measures of cognitive function as a proxy for general cognitive ability. In this case the concern must be raised that measures of immediate performance would be subject to relatively temporary fluctuations in performance due to uncontrolled variations in blood sugar. We would expect that successful control of blood sugar would have an effect on both immediate performance and long term cognitive ability. In the reverse case the present study cannot be assumed to describe limitations in real world participation in the absence of measures geared to their measurement or of indications of the amount to which glucose control is poor across the day. For these reasons it is difficult to interpret the effect proposed despite the fact that we agree with their confidence in its statistical reliability due to the large sample size in this study. Further work needs to be done in order to properly interpret the results of this interesting finding. Bruce Oddson, PhD, Post Doctoral Fellow (Department of Psychology, University of Toronto, Toronto, Ontario, Canada), Research Associate (Research Department, Bloorview MacMillan Children's Centre, Toronto, Ontario, Canada) JAC Delaney, MA, MSc, Statistician (Department of Clincial Epidemiology, Royal Victoria Hospital, Montreal, Quebec, Canada) 1. Logroscino G, Kang JH and Grodstein F. Prospective study of type 2 diabetes and cognitive decline in women aged 70-81 years. BMJ. 2004;328(7439):548. 2. UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet1998; 352:837–54 3. Benton D, Ruffin MP, Lassel T, Nabb S, Messaoudi M, Vinoy S, Desor D and Lang V. The delivery rate of dietary carbohydrates affects cognitive performance in both rats and humans. Psychopharmacology (Berl). 2003 Feb;166(1):86-90 Competing interests: None declared |
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