Higher Inflammatory Markers Can Predict Severe Cognitive Impairment for Patients with T2D

There is strong evidence that circulating markers of systemic inflammation can predict long-term cognitive decline among older people with type 2 diabetes.

Diabetes Mellitus has been one of the top leading causes of disability worldwide and is predicted to be the seventh leading cause of mortality by 2040. Also, people with diabetes mellitus are at risk of developing cardiovascular and renal complications and a 50% increased risk of experiencing dementia compared with the general population. 826,000 incidences of Alzheimer’s disease have been associated with diabetes globally. Diabetes has been reported to have a strong relationship with age-related cognitive decline, causing an early stage of age onset of medically mental decline by two and half years. Cognitive changes due to diabetes might be related to the development of vascular lesions, cerebral degeneration, and loss of white matter, but the underlying mechanism is not well understood. Clinically, it has been proven people with dementia-related diabetes are prone to having dementia pathology. Some vascular risk factors as been noted, as well as insulin, fasting glucose impairments, high blood pressure, and coronary artery diseases. Systemic Inflammation has been identified to play a role because people with diabetes have an increased level of system inflammatory mediators compared to the general population.

Furthermore, evidence shows that type 2 diabetes incidence can be predicted by low-grade Inflammation, With the IL-6 inflammatory marker driving this association. There has been strong proof that inflammatory markers can predict changes in cognition in cross-sectional analyses and among the general population. In a previous study, higher circulating levels of inflammatory mediators were related to a decrease in cognitive function among older adults with type 2 diabetes; however, there has been little evidence about the longitudinal relationship between systemic inflammation and long-term diabetes-related cognitive changes. This ten-year follow-up Edinburgh Type 2 Diabetes Study (ET2DS) aimed to determine the longitudinal relationship between baseline measurement of specific circulating markers of systemic Inflammation and long-term cognitive decline among older people with type 2 diabetes.

 Edinburgh Type 2 Diabetes Study is a prospective cohort study that includes 1066 adult participants aged 60 to 75 years with type 2 diabetes. The researchers measured baseline data of C-reactive protein, IL-6, TNF-α fibrinogen, and neuropsychological testing on the cognitive domain was carried out on the participants. They repeated cognitive testing after ten years among 581 participants. Principal component analysis was used to derive a cognitive ability score from the battery of seven individual cognitive tests. The relationship between baseline inflammatory markers and cognitive outcomes at follow-up was determined using Linear regression. Participants included in this study are those using insulin or oral glucose-lowering medications, those whose HbA_1c is>48 mmol/mol (6.5%) at the baseline clinic, or if their diabetes was managed through diet control.

After adjusting for age, sex, and general cognitive ability, the researchers observed an association of (P = .032) and (P = .018) for higher baseline fibrinogen levels and a more significant decline in general cognitive ability. However, the association was not statistically significant after adjusting for diabetes-related covariables and baseline vascular risk factors. Furthermore, after data analysis was carried out, it was observed that there was an association between higher IL-6 with a more significant decrease in the test of executive functioning (P = .006) and abstract reasoning (P = .001), while increases in the level of C-reactive protein (P = .001) and fibrinogen  (P = .001) were related with a more significant reduction in processing speed. According to the researchers, the statistical significance remained after adjusting for diabetes and vascular-related risks.  

In conclusion, this study shows that at ten years, higher baseline levels of systemic inflammatory markers, including plasma interleukin-6 and fibrinogen, have an association with an increase in cognitive impairment among older adults with type 2 diabetes, as reported by the data. Suppose future research proves the relationship between the pathophysiological and causal. In that case, the attempt taken to alleviate the overall systemic Inflammation may be helpful in the prevention of occurrence and severe cognitive impairment among older adults with type 2 diabetes.

Practice Pearls:

• Higher baseline levels of inflammatory markers, including plasma IL-6, fibrinogen, and C-reactive protein, were associated with a decrease in cognitive function among older people with type 2 diabetes.
• This study helps to address the previous insufficient evidence of a future relationship between systemic inflammation markers and a decrease in cognitive function in people with type 2 diabetes.
• If future evidence shows the association between pathophysiological and casual, the attempt to decrease overall systemic inflammation may aid in preventing incidence and severity of cognitive impairment among older adults diagnosed with type 2 diabetes.

Suliman, Anniek J., et al. “Higher Baseline Inflammatory Marker Levels Predict Greater Cognitive Decline in Older People with Type 2 Diabetes: Year 10 Follow-up of the Edinburgh Type 2 Diabetes Study – Diabetologia.” SpringerLink, Springer Berlin Heidelberg, 21 Dec. 2021, https://link.springer.com/article/10.1007/s00125-021-05634-w.

“Baseline Inflammatory Markers Predict 10-Year Cognitive Decline in Type 2 Diabetes.” Healio, https://www.healio.com/news/endocrinology/20220310/baseline-inflammatory-markers-predict-10year-cognitive-decline-in-type-2-diabetes.

          Janet Falade, PharmD Candidate, South College School of Pharmacy