Near Normalization of Metabolic and Functional Features of the Central Nervous System in Type 1 Diabetic Patients With End-Stage Renal Disease After Kidney-Pancreas Transplantation

  1. Antonio Secchi, MD2,9
  1. 1Nephrology Division, Transplantation Research Center, Children's Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  2. 2Department of Medicine, San Raffaele Scientific Institute, Milan, Italy
  3. 3Department of Neuroradiology, San Raffaele Scientific Institute, Milan, Italy
  4. 4Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (DiSTeBA), Università del Salento, Lecce, Italy
  5. 5Neurology Psychological Service, San Raffaele Scientific Institute, Milan
  6. 6Department of Anesthesiology, San Raffaele Scientific Institute, Milan, Italy
  7. 7Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy
  8. 8Department of Neurology, San Raffaele Scientific Institute, Milan, Italy
  9. 9Università Vita-Salute, Milan, Italy
  1. Corresponding author: Paolo Fiorina, paolo.fiorina{at}


OBJECTIVE The pathogenesis of brain disorders in type 1 diabetes (T1D) is multifactorial and involves the adverse effects of chronic hyperglycemia and of recurrent hypoglycemia. Kidney-pancreas (KP), but not kidney alone (KD), transplantation is associated with sustained normoglycemia, improvement in quality of life, and reduction of morbidity/mortality in diabetic patients with end-stage renal disease (ESRD).

RESEARCH DESIGN AND METHODS The aim of our study was to evaluate with magnetic resonance imaging and nuclear magnetic resonance spectroscopy (1H MRS) the cerebral morphology and metabolism of 15 ESRD plus T1D patients, 23 patients with ESRD plus T1D after KD (n = 9) and KP (n = 14) transplantation, and 8 age-matched control subjects.

RESULTS Magnetic resonance imaging showed a higher prevalence of cerebrovascular disease in ESRD plus T1D patients (53% [95% CI 36–69]) compared with healthy subjects (25% [3–6], P = 0.04). Brain 1H MRS showed lower levels of N-acetyl aspartate (NAA)-to-choline ratio in ESRD plus T1D, KD, and KP patients compared with control subjects (control subjects vs. all, P < 0.05) and of NAA-to-creatine ratio in ESRD plus T1D compared with KP and control subjects (ESRD plus T1D vs. control and KP subjects, P ≤ 0.01). The evaluation of the most common scores of psychological and neuropsychological function showed a generally better intellectual profile in control and KP subjects compared with ESRD plus T1D and KD patients.

CONCLUSIONS Diabetes and ESRD are associated with a precocious form of brain impairment, chronic cerebrovascular disease, and cognitive decline. In KP-transplanted patients, most of these features appeared to be near normalized after a 5-year follow-up period of sustained normoglycemia.

  • Received September 1, 2011.
  • Accepted November 10, 2011.

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