Type 3 Diabetes and Its Role Implications in Alzheimer’s Disease

Nguyen, Thuy Trang; Ta, Qui Thanh Hoai; Nguyen, Thi Kim Oanh; Nguyen, Thi Thuy Dung; Giau, Vo Van

doi:10.3390/ijms21093165

Cited by 221 publications

(169 citation statements)

References 103 publications

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“…19 Patients with DM are at increased risk for dementia and both diseases have similar risk factors and biologic mechanisms. 9,10,18,19 Indeed, AD is twice as frequent in diabetic patients compared to patients without DM and shared pathophysiologic features include IR, amyloid aggregations, inflammatory stress, and cognitive disturbances. 10,20 Approximately 8 million people in the US are diagnosed with psoriasis, a chronic, systemic inflammatory condition of the skin condition.…”

Section: Epidemiologymentioning

confidence: 99%

“… 9 , 10 , 18 Indeed, a phenotypic consequence of IR or deficiency can result in AD, sometimes referred to as “type 3” diabetes or diabetes of the brain. 19 Patients with DM are at increased risk for dementia and both diseases have similar risk factors and biologic mechanisms. 9 , 10 , 18 , 19 Indeed, AD is twice as frequent in diabetic patients compared to patients without DM and shared pathophysiologic features include IR, amyloid aggregations, inflammatory stress, and cognitive disturbances.…”

Section: The Diabetes Syndrome As a Conceptual Frameworkmentioning

confidence: 99%

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The Diabetes Syndrome – A Collection of Conditions with Common, Interrelated Pathophysiologic Mechanisms

Rachfal¹,

Grant²,

Schwartz³

2021

IJGM

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The four basic pathophysiologic mechanisms which damage the β-cell within diabetes (ie, genetic and epigenetic changes, inflammation, an abnormal environment, and insulin resistance [IR]) also contribute to cell and tissue damage and elevate the risk of developing all typical diabetes-related complications. Genetic susceptibility to damage from abnormal external and internal environmental factors has been described including inflammation and IR. All these mechanisms can promote epigenetic changes, and in total, these pathophysiologic mechanisms interact and react with each other to cause damage to cells and tissues ultimately leading to disease. Importantly, these pathophysiologic mechanisms also serve to link other common conditions including cancer, dementia, psoriasis, atherosclerotic cardiovascular disease (ASCVD), nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). The "Diabetes Syndrome", an overarching group of interrelated conditions linked by these overlapping mechanisms, can be viewed as a conceptual framework that can facilitate understanding of the interrelationships of superficially disparate conditions. Recognizing the association of the conditions within the Diabetes Syndrome due to common pathophysiologies has the potential to provide both benefit to the patient (eg, prevention, early detection, precision medicine) and to the advancement of medicine (eg, driving education, research, and dynamic decision-based medical practice).

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Section: Epidemiologymentioning

confidence: 99%

Section: The Diabetes Syndrome As a Conceptual Frameworkmentioning

confidence: 99%

The Diabetes Syndrome – A Collection of Conditions with Common, Interrelated Pathophysiologic Mechanisms

Rachfal¹,

Grant²,

Schwartz³

2021

IJGM

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“…Type 1 diabetes mellitus, or insulin deficiency due to autoimmune ß-cell destruction, and type 2 diabetes, due to a progressive loss of ß-cell secretion sufficient to overcome insulin resistance [ 10 ], have not, however, been related to AD [ 9 ]. The relationship between T3D and AD has been based on the fact that both the processing and clearance of amyloid-β (Aβ) are attributed to impaired insulin signaling, and that IR mediates the dysregulation of bioenergetics and progress to AD [ 11 , 12 ]. Determining progression of T3D neurodegeneration towards early AD is challenging, and chronic stress might provide more insight as a potential risk factor in this process.…”

Section: Introductionmentioning

confidence: 99%

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study

Malan

Hamer

Känel

et al. 2021

Biology

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Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer’s disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer’s and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 ± 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitiveexe-func); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitiveexe-func control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitiveexe-func control and neuronal glia injury (Adjusted R2 0.30; p ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitiveexe-func, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; p ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke.

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“…According to the results of previous studies, it is highly likely that patients who suffer from diabetes mellitus (DM) will also develop AD and it is even called type III diabetes [11,12]. The relationship between DM and AD is being widely investigated using animal models, including a model of DM induction as a result of STZ injection [2,4,8].…”

Section: Introductionmentioning

confidence: 99%

Insulin receptors in the CA1 field of hippocampus and selected blood parameters in diabetic rats fed with bilberry fruit

Matysek¹,

Borowiec²,

Szwajgier³

et al. 2021

Ann Agric Environ Med.

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Introduction. Bilberry fruit is believed to be a promising factor in the treatment of diabetes mellitus. Chronic hyperglycaemia affects the function of the central nervous system, which may be manifested as changes in hypothalamic insulin signalling. Materials and method. Using DPPH and ABTS assays, total phenolic content in bilberry fruit and its antioxidant activities were examined. The selected biochemical parameters of blood (glucose, fructosamine, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), as well as the expression of insulin receptors, were studied in the hippocampal CA1 field of healthy and diabetic (streptozotocin-induced; 60 mg kg-1 body weight) Wistar rats fed with bilberry fruit (16 g kg-1 body weight per day; 6 weeks), as well as of the corresponding control groups. Results. Biochemical analyses revealed ambiguous results, but a significantly (P<0.05) decrease in the level of LDL-cholesterol was observed in the group of healthy rats supplemented with bilberry pulp after 6 weeks of the treatment. There was also a difference (P<0.05) in the level of LDL-cholesterol in the mentioned healthy animals fed with bilberry, versus the healthy control group. An increased number of insulin receptors-immunoreactive neurons as well as nerve fibres in the CA1 field of diabetic rats fed with bilberry fruit was also found. Conclusions. An inclusion of bilberry fruit in the daily diet during the course of diabetes can lead to plasticity of hippocampal neurons/nerve fibres, manifested by changes in insulin receptors expression. Whether or not the observed changes had protective effects (by reducing damages caused by diabetes mellitus) on the function of the central nervous system neurons needs further study.

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Type 3 Diabetes and Its Role Implications in Alzheimer’s Disease

Cited by 221 publications

References 103 publications

The Diabetes Syndrome – A Collection of Conditions with Common, Interrelated Pathophysiologic Mechanisms

The Diabetes Syndrome – A Collection of Conditions with Common, Interrelated Pathophysiologic Mechanisms

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study

Insulin receptors in the CA1 field of hippocampus and selected blood parameters in diabetic rats fed with bilberry fruit

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