Why Alzheimer’s disease is now referred to as Type III Diabetes

Alzheimer’s, a neurodegenerative disease whose diagnosis was once only indicated by the presence of neurofribrillary tangles and beta-amyloid plaque build up in the brain, is continuing to be investigated as a metabolic disease characterized by similar metabolic pathogenesis as type-2 diabetes, or insulin resistance. Type-2 diabetes is a disease defined by insulin resistance, that is, when insulin, the hormone responsible for taking blood sugar out of our blood and into our muscles, “resists” to do its job, leaving blood sugar elevated to exert harmful inflammatory effects systemically throughout the body.

Epidemiological researchers are more and more convinced by the astounding evidence for the association between T2D and dementia or other mild cognitive impairment that T2D is a significant risk factor for developing Alzheimer’s. 2 In this context, the potentiating effects of insulin resistance on microvascular disease is of great interest since cerebral microvascular disease has been recognized as an accelerating component of AD for years.3 The data presented in this review presents significant evidence that “AD is intrinsically a neuroendocrine disease caused by selective impairments in insulin and IGF signaling” and production locally in the brain.1

Ground breaking studies examining postmortem (deceased individuals’) brain tissue of AD subjects provides definitive evidence that AD is correlated with fundamental abnormalities in insulin/IGF signaling that are strongly associated with “the development and progression of structural, molecular, and biochemical lesions that correlate with dementia.”1 Diminished levels of insulin and IGF-1 in the brain were found to be associated with AD, as well as receptor genes and “all the signaling pathways that mediate insulin and IGF-1 stimulated neuronal survival.”1

The key finding, according to my understanding from what is explained in this review, is that T2D was not present in the individuals with AD and dementia-associated neurodegeneration whose brain tissue was histologically analyzed, although the abnormalities described here are quite similar to what we would find in individuals with type 1 and 2 diabetes. These abnormalities are primarily characterized by decreased IGF and their corresponding receptors, which are important for proper islet cell function, cells in the pancreas that produce insulin. However, these abnormalities were only found local to the brain in these AD subjects. It is important to highlight that the researchers here demonstrated that T2D with obesity causes brain insulin resistance with some AD-features, but the effects are relatively modest and lack most of the prime abnormalities that define AD. Therefore, T2D itself was deemed as “not sufficient in itself” to cause AD. Hence, a new term, “Type-3 Diabetes”, was coined in order to represent this brain-specific form of diabetes like symptoms.1 Referring to AD as type-3 diabetes “is justified, because the fundamental molecular and biochemical abnormalities overlap with T1DM and T2DM rather than mimic the effects of either one.”1

1.         de la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol. 2008;2(6):1101-1113. doi:10.1177/193229680800200619

2.         Pasquier F, Boulogne A, Leys D, Fontaine P Diabetes mellitus and dementia. Diabetes Metab. 2006 November; 32(5 Pt 1):403-14.

3.         Etiene D, Kraft J, Ganju N, Gomez-Isla T, Gemelli B, Hyman BT, Hedley-Whyte ET, Wands JR, De La Monte SM Cerebrovascular Pathology Contributes to the Heterogeneity of Alzheimer's Disease. J Alzheimers Dis. 1998 Dec; 1(2):119-134.