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Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions

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DOI: 10.4236/nm.2011.21005    4,691 Downloads   9,862 Views   Citations

ABSTRACT

The rates of type 2 diabetes (T2DM) continue to parallel the rising rates of obesity in the United States, increasingly affecting adolescents as well as adults. Hippocampal and frontal lobe reductions have been found in older adults with type 2 diabetes, and we sought to ascertain if these brain alterations were also present in obese adolescents with T2DM. In a cross-sectional study we compared MRI-based regional brain volumes of 18 obese adolescents with T2DM and 18 obese controls without evidence of marked insulin resistance. Groups were matched on age, sex, school grade, ethnicity, socioeconomic status, body mass index, and waist circumference. Relative to obese controls, adolescents with T2DM had significantly reduced hippocampal and prefrontal volumes, and higher rates of global cerebral atrophy. Hemoglo-bin A1c, an index of long-term glycemic control, was inversely associated with prefrontal volume and positively associ-ated with global cerebral atrophy (both p < 0.05). Brain integrity is negatively impacted by T2DM already during ado-lescence, long before the onset of overt macrovascular disease. Paralleling the findings of greater vascular and renal complications among obese adolescents with severe insulin resistance and T2DM relative to their age-matched peers with type 1 diabetes, we find clear evidence of possible brain complications. Our findings call for aggressive and early intervention to limit the negative impact of obesity-associated insulin resistance leading to T2DM on the developing brains of adolescents.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

H. Bruehl, V. Sweat, A. Tirsi, B. Shah and A. Convit, "Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions," Neuroscience and Medicine, Vol. 2 No. 1, 2011, pp. 34-42. doi: 10.4236/nm.2011.21005.

References

[1] D. Jolliffe, “Extent of Overweight among US Children and Adolescents from 1971 to 2000,” International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, Vol. 28, 2004, pp. 4-9. doi:10.1038/sj.ijo.0802421
[2] E. Ferrannini, A. Natali, P. Bell, P. Cavallo-Perin, N. Lalic and G. Mingrone, “Insulin Resistance and Hypersecretion in Obesity,” Journal of Clinical Investigation, Vol. 100, No. 5, 1997, pp. 1166-1173. doi:10.1172/JCI119628
[3] J. M. Lee, M. J. Okumura, M. M. Davis, W. H. Herman and J. G. Gurney, “Prevalence and Determinants of Insulin Resistance among U.S. Adolescents: A Population-Based Study,” Diabetes Care, Vol. 29, No. 11, 2006, pp. 2427-2432. doi:10.2337/dc06-0709
[4] D. O. Smith and D. LeRoith, “Insulin Resistance Syndrome, Pre-Diabetes, and the Prevention of Type 2 Diabetes Mellitus,” Clinical Cornerstone, Vol. 6, No. 2, 2004, pp. 7-13. doi:10.1016/S1098-3597(04)80050-4
[5] American Diabetes Association, “Type 2 Diabetes in Children and Adolescents,” Diabetes Care, Vol. 23, No. 3, 2000, pp. 381-389. doi:10.2337/diacare.23.3.381
[6] T. Aye and L. L. Levitsky, “Type 2 Diabetes: An Epidemic Disease in Childhood,” Current Opinion in Pediatrics, Vol. 15, No. 4, 2003, pp. 411-415.
[7] N. Gungor, T. Thompson, K. Sutton-Tyrrell, J. Janosky and S. Arslanian, “Early Signs of Cardiovascular Disease in Youth with Obesity and Type 2 Diabetes,” Diabetes Care, Vol. 28, No. 5, 2005, pp. 1219-1221. doi:10.2337/diacare.28.5.1219
[8] S. McQuaid, D. J. O’Gorman, O. Yousif, T. P. Yeow, Y. Rahman, D. Gasparro, G. Pacini and J. J. Nolan, “Early- Onset Insulin-Resistant Diabetes in Obese Caucasians has Features of Typical Type 2 Diabetes, but 3 Decades Earlier,” Diabetes Care, Vol. 28, No. 5, 2005, pp. 1216- 1218. doi:10.2337/diacare.28.5.1216
[9] M. C. Eppens, M. E. Craig, J. Cusumano, S. Hing, A. K. F. Chan, N. J. Howard, M. Silink and K. C. Donaghue, “Prevalence of Diabetes Complications in Adolescents with Type 2 Compared with Type 1 Diabetes,” Diabetes Care, Vol. 29, No. 6, 2006, pp. 1300-1306.
[10] D. M. Maahs, B. M. Snively, R. A. Bell, L. Dolan, I. Hirsch, G. Imperatore, B. Linder, S. M. Marcovina, E. J. Mayer-Davis, D. J. Pettitt, B. L. Rodriguez and D. Dabelea, “Higher Prevalence of Elevated Albumin Excretion in Youth with Type 2 than Type 1 Diabetes: The SEARCH for Diabetes in Youth Study,” Diabetes Care, Vol. 30, No. 10, 2007, pp. 2593-2598. doi:10.2337/dc07-0450
[11] S. Gold, I. Dziobek, V. Sweat, A. Tirsi, K. Rogers, H. Bruehl, W. Tsui, S. Richardson, E. Javier and A. Convit, “Hippocampal Damage and Memory Impairments as Possible Early Brain Complications of Type 2 Diabetes,” Diabetologia, Vol. 50, No. 4, 2007, pp. 711-719.
[12] H. Bruehl, O. T. Wolf, V. Sweat, A. Tirsi, S. Richardson and A. Convit, “Modifiers of Cognitive Function and Brain Structure in Middle-Aged and Elderly Individuals with Type 2 Diabetes Mellitus,” Brain Research, Vol. 1280, 2009, pp. 186-194. doi:10.1016/j.brainres.2009.05.032
[13] G. M. Reaven, L. W. Thompson, D. Nahum and E. Haskins, “Relationship between Hyperglycemia and Cognitive Function in Older NIDDM Patients,” Diabetes Care, Vol. 13, 1990, pp. 16-21.
[14] N. Awad, M. Gagnon and C. Messier, “The Relationship between Impaired Glucose Tolerance, Type 2 Diabetes, and Cognitive Function,” Journal of Clinical and Experimental Neuropsychology: Official Journal of the International Neuropsychological Society, Vol. 26, 2004, pp. 1044-1080.
[15] T. den Heijer, S. E. Vermeer, E. J. van Dijk, N. D. Prins, P. J. Koudstaal, A. Hofman and M. M. Breteler, “Type 2 Diabetes and Atrophy of the Medial Temporal Lobe Structures on Brain MRI,” Diabetologia, Vol. 46, 2003, pp. 1604-1610. doi:10.1007/s00125-003-1235-0
[16] E. S. C. Korf, L. R. White, P. Scheltens and L. J. Launer, “Brain Aging in Very Old Men with Type 2 Diabetes: The Honolulu-Asia Aging Study,” Diabetes Care, Vol. 29, No. 10, 2006, pp. 2268-2274.
[17] A. Kumar, E. Haroon, C. Darwin, D. Pham, O. Ajilore, G. Rodriguez and J. Mintz, “Gray Matter Prefrontal Changes in Type 2 Diabetes Detected Using MRI,” Journal of Magnetic Resonance Imaging, Vol. 27, No. 1, 2008, pp. 14-19. doi:10.1002/jmri.21224
[18] C. M. Ryan and M. Geckle, “Why is Learning and Memory Dysfunction in Type 2 Diabetes Limited to Older Adults?” Diabetes/Metabolism Research and Reviews, Vol. 16, No. 5, 2000, pp. 308-315.
[19] P. L. Yau, D. C. Javier, C. M. Ryan, W. H. Tsui, B. A. Ardekani, S. Ten and A. Convit, “Preliminary Evidence for Brain Complications in Obese Adolescents with Type 2 Diabetes Mellitus,” Diabetologia, Vol. 53, No. 11, 2010, pp. 2298-2306. doi:10.1007/s00125-010-1857-y
[20] J. Gunstad, R. H. Paul, R. A. Cohen, D. F. Tate, M. B. Spitznagel, S. Grieve and E. Gordon, “Relationship between Body Mass Index and Brain Volume in Healthy Adults,” International Journal of Neuroscience, Vol. 118, No. 11, 2008, pp. 1582-1593.
[21] J. Gunstad, R. H. Paul, R. A. Cohen, D. F. Tate and E. Gordon, “Obesity is Associated with Memory Deficits in Young and Middle-Aged Adults,” Eating and Weight Disorders, Vol. 11, No. 1, 2006, pp. e15-e19.
[22] H. Bruehl, V. Sweat, J. Hassenstab, V. Polyakov and A. Convit, “Cognitive Impairment in Nondiabetic Middle- Aged and Older Adults is Associated with Insulin Resistance,” Journal of Clinical and Experimental Neuropsychology, Vol. 32, No. 5, 2010, pp. 487-493. doi:10.1080/13803390903224928
[23] J. Gunstad, M. B. Spitznagel, R. H. Paul, R. A. Cohen, M. Kohn, F. S. Luyster, R. Clark, L. M. Williams and E. Gordon, “Body Mass Index and Neuropsychological Function in Healthy Children and Adolescents,” Appetite, Vol. 50, No. 2-3, 2008, pp. 246-251.
[24] K. J. Mather, A. E. Hunt, H. O. Steinberg, G. Paradisi, G. Hook, A. Katz, M. J. Quon and A. D. Baron, “Repeatability Characteristics of Simple Indices of Insulin Resistance: Implications for Research Applications,” Journal of Clinical Endocrinology Metabolism, Vol. 86, No. 11, 2001, pp. 5457-5464.
[25] D. R. Matthews, J. P. Hosker, A. S. Rudenski, B. A. Naylor, D. F. Treacher and R. C. Turner, “Homeostasis Model Assessment: Insulin Resistance and á-Cell Function from Fasting Plasma Glucose and Insulin Concentrations in Man,” Diabetologia, Vol. 28, 2004, pp. 412- 419. doi:10.1007/BF00280883
[26] J. Radziuk, “Insulin Sensitivity and its Measurement: Structural Commonalities among the Methods,” Journal of Clinical Endocrinology & Metabolism, Vol. 85, No. 12, 2004, pp. 4426-4433. doi:10.1210/jc.85.12.4426
[27] P. Expert, “Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III),” Journal of the American Medical Association, Vol. 285, 2001, pp. 2486-2497.
[28] A. Convit, M. J. de Leon, C. Tarshish, S. De Santi, A. Kluger, H. Rusinek and A. George, “Hippocampal Volume Losses in Minimally Impaired Elderly,” Lancet, Vol. 345, 1995, p. 266. doi:10.1016/S0140-6736(95)90265-1
[29] A. Convit, P. R. McHugh, O. T. Wolf, M. J. de Leon, M. Bobinski, S. De Santi, A. Roche and W. Tsui, “MRI Volume of the Amygdala: A Reliable Method Allowing Separation from the Hippocampal Formation,” Psychiatry Research: Neuroimaging, Vol. 90, No. 2, 1999, pp. 113-123. doi:10.1016/S0925-4927(99)00007-4
[30] A. Convit, O. T. Wolf, M. J. de Leon, M. Patalinjug, E. Kandil, D. Cardebat, A. Scherer, L. A. Saint Louis and R. Cancro, “Volumetric Analysis of the Pre-Frontal Regions: Findings in Aging and Schizophrenia,” Psychiatry Research: Neuroimaging, Vol. 107, No. 2, 2001, pp. 61- 73. doi:10.1016/S0925-4927(01)00097-X
[31] P. Scheltens, F. Barkhof, D. Leys, J. P. Pruvo, J. J. Nauta, P. Vermersch, M. Steinling and J. Valk, “A Semiquantative Rating Scale for the Assessment of Signal Hyperintensities on Magnetic Resonance Imaging,” Journal of the Neurological Sciences, Vol. 114, No. 1, 1993, pp. 7- 12. doi:10.1016/0022-510X(93)90041-V
[32] J. A. Mindell and J. A. Owens, “A Clinical Guide to Pediatric Sleep: Diagnosis and Management of Sleep Problems,” Lippincott Williams & Wilkins, Philadelphia, 2003.
[33] E. Dayyat, L. Kheirandish-Gozal, O. Sans Capdevila, M. M. A. Maarafeya and D. Gozal, “Obstructive Sleep Apnea in Children: Relative Contributions of Body Mass Index and Adenotonsillar Hypertrophy,” Chest, Vol. 136, No. 1, 2009, pp. 137-144.
[34] P. M. Macey, R. Kumar, M. A. Woo, E. M. Valladares, F. L. Yan-Go and R. M. Harper, “Brain Structural Changes in Obstructive Sleep Apnea,” Sleep, Vol. 31, No. 7, 2008, pp. 967-977.
[35] A. B. Hollingshead, “Two Factor Index of Social Position: New Haven,” Yale University, 1957.
[36] H. Bruehl, O. T. Wolf and A. Convit, “A Blunted Cortisol Awakening Response and Hippocampal Atrophy in Type 2 Diabetes Mellitus,” Psychoneuroendocrinology, Vol. 34, No. 6, 2009, pp. 815-821. doi:10.1016/j.psyneuen.2008.12.010
[37] B. M. Lobnig, O. Kroemeke, C. Optenhostert-Porst and O. T. Wolf, “Hippocampal Volume and Cognitive Performance in Long-Standing Type 1 Diabetic Patients without Macrovascular Complications,” Diabetic Medicine, Vol. 23, No. 1, 2006, pp. 32-39.
[38] M. Vanhanen, K. Koivisto, L. Karjalainen, E. L. Helkala, M. Laakso, H. Soininen and P. Riekkinen, Sr., “Risk for Non-Insulin-Dependent Diabetes in the Normoglycaemic Elderly is Associated with Impaired Cognitive Function,” NeuroReport, Vol. 8, 1997, pp. 1527-1530.
[39] S. Kalmijn, E. J. M. Feskens, L. J. Launer, T. Stijnen and D. Kromhout, “Glucose Intolerance, Hyperinsulinaemia and Cognitive Function in a General Population of Elderly Men,” Diabetologia, Vol. 38, 1995, pp. 1096-1102. doi:10.1007/BF00402181
[40] J. E. Tooke and M. M. Hannemann, “Adverse Endothelial Function and the Insulin Resistance Syndrome,” Journal of Internal Medicine, Vol. 247, No. 4, 2000, pp. 425-431.
[41] J. E. Tooke and K. L. Goh, “Endotheliopathy Precedes Type 2 Diabetes,” Diabetes Care, Vol. 21, 1998, pp. 2047-2049. doi:10.2337/diacare.21.12.2047
[42] K. B. Stansberry, S. A. Shapiro, M. A. Hill, P. M. McNitt, M. D. Meyer and A. I. Vinik, “Impaired Peripheral Vasomotion in Diabetes,” Diabetes Care, Vol. 19, 1996, pp. 715-721. doi:10.2337/diacare.19.7.715
[43] A. I. Vinik, T. Erbas, T. S. Park, K. B. Stansberry, J. A. Scanelli and G. L. Pittenger, “Dermal Neurovascular Dysfunction in Type 2 Diabetes,” Diabetes Care, Vol. 24, No. 8, 2001, pp. 1468-1475.
[44] V. Novak, D. Last, D. C. Alsop, A. M. Abduljalil, K. Hu, L. Lepicovsky, J. Cavallerano and L. A. Lipsitz, “Cerebral Blood Flow Velocity and Periventricular White Matter Hyperintensities in Type 2 Diabetes,” Diabetes Care, Vol. 29, No. 7, 2006, pp. 1529-1534.
[45] L. Petrica, M. Petrica, A. Vlad, F. Bob, C. Gluhovschi, G. Gluhovschi, C. D. Jianu, S. Ursoniu, A. Schiller, S. Velciov, V. Trandafirescu and G. Bozdog, “Cerebrovascular Reactivity is Impaired in Patients with Non-Insulin-Dependent Diabetes Mellitus and Microangiopathy,” Wien Klin Wochenschr, Vol. 119, No. 11-12, 2007, pp. 365- 371. doi:10.1007/s00508-007-0809-0
[46] D. Last, C. de Bazelaire, D. C. Alsop, K. Hu, A. M. Abduljalil, J. Cavallerano, R. P. Marquis and V. Novak, “Global and Regional Effects of Type 2 Diabetes on Brain Tissue Volumes and Cerebral Vasoreactivity,” Diabetes Care, Vol. 30, No. 5, 2007, pp. 1193-1199.
[47] M. P. Mattson, P. B. Gurthrie and S. B. Kater, “Intrinsic Factors in the Selective Vulnerability of Hippocampal Pyramidal Neurons,” Progress in Clinical & Biological Research, Vol. 317, 1989, pp. 333-351.
[48] S. Manschot, G. Biessels, H. de Valk, A. Algra, G. Rutten, J. van der Grond, L. Kappelle and on behalf of the Utrecht Diabetic Encephalopathy Study, “Metabolic and Vascular Determinants of Impaired Cognitive Performance and Abnormalities on Brain Magnetic Resonance Imaging in Patients with Type 2 Diabetes,” Diabetologia, Vol. 50, No. 11, 2007, pp. 2388-2397. doi:10.1007/s00125-007-0792-z
[49] N. Raz, K. M. Rodrigue, and J. D. Acker, “Hypertension and the Brain: Vulnerability of the Prefrontal Regions and Executive Functions,” Behavioral Neuroscience, Vol. 117, No. 6, 2003, pp. 1169-1180.
[50] T. Paus, D. L. Collins, A. C. Evans, G. Leonard, B. Pike and A. Zijdenbos, “Maturation of White Matter in the Human Brain: A Review of Magnetic Resonance Studies,” Brain Research Bulletin, Vol. 54, No. 3, 2001, pp. 255-266. doi:10.1016/S0361-9230(00)00434-2
[51] T. Paus, “Mapping Brain Maturation and Cognitive Development during Adolescence,” Trends in Cognitive, Vol. 9, No. 2, 2005, pp. 60-68.
[52] H. J. Woerle, C. Neumann, S. Zschau, S. Tenner, A. Irsigler, J. Schirra, J. E. Gerich and B. Goke, “Impact of Fasting and Postprandial Glycemia on Overall Glycemic Control in Type 2 Diabetes Importance of Postprandial Glycemia to Achieve Target HbA1c Levels,” Diabetes Research and Clinical Practice, Vol. 77, 2007, pp. 280- 285. doi:10.1016/j.diabres.2006.11.011
[53] A. Ceriello, K. Esposito, L. Piconi, M. Ihnat, J. Thorpe, R. Testa, A. R. Bonfigli and D. Giugliano, “Glucose “Peak” and Glucose “Spike”: Impact on Endothelial Function and Oxidative Stress,” Diabetes Research and Clinical Practice, Vol. 82, No. 2, 2008, pp. 262-267. doi:10.1016/j.diabres.2008.07.015
[54] K. J. Smith, R. Kapoor and P. A. Felts, “Demyelination: The Role of Reactive Oxygen and Nitrogen Species,” Brain Pathology, Vol. 9, No. 1, 2009, pp. 62-92.

  
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