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

Abstract

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 ((1)H 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 (1)H 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.

Figure 1

Axial fluid-attenuated inversion recovery acquisitions showing hyperintense lesions suggestive of chronic cerebrovascular disease in a control subject (A), an ESRD plus T1D patient (B), and a KP-transplanted patient (C). Single-voxel ¹H MRS brain examination shows Cho, total creatine (Cr), and NAA spectra in a control subject (D), in an ESRD plus T1D patient (E), and in a KP patient (F). (A high-quality color representation of this figure is available in the online issue.)

Figure 2

MRI and ¹H MRS evaluation were performed in the four groups of patients. No differences between groups were evident for brain volume (A), WB_NAA (B), and [NAA] (C). NAA/Cho (D) and NAA/creatinine (Cr) (E) were significantly lower in ESRD plus T1D patients compared with control (CTRL) subjects and were near normalized in KP- but not KD-transplanted patients. The Cho-to-creatinine ratio is shown as well (F).