The association between serum DPP4 levels and cognitive decline in prenatal pregnant women with Gestational diabetes mellitus

Serum DPP4 levels may be associated with cognitive dysfunction in perinatal pregnant women with gestational diabetes mellitus 

Gestational diabetes mellitus (GDM) occurs in about 7% of all pregnancies, ranging from 1% to 14%, depending on the specific population studied, and the diagnostic test used to assess the presence of gestational diabetes. The ADA defines gestational diabetes as diabetes diagnosed in the first place. during the second or third trimester of pregnancy, the person does not have pre-existing type 1 or type 2 diabetes. (Diabetes detected for the first time in the first trimester is considered pre-existing diabetes.) Women at higher risk of gestational diabetes include obese and non-white women and people with glucose intolerance, a family history of diabetes, or a history of gestational diabetes. Hormonal changes of placental origin occur in the last trimester of pregnancy causes varying levels of glucose intolerance. Normal physiological reactions in the mother need to increase insulin (three times the non-pregnant state). High blood sugar in the first two trimesters is associated with higher birth defects and miscarriage rates, in addition to the consequences of hyperglycemia for the mother. In the second trimester of pregnancy, high blood sugar leads to too much nutrition for the fetus and makes the newborn baby weigh too much. To compensate, the fetal pancreas secretes too much insulin. At birth, babies with hyperinsulinemia can have severe hypoglycemia and are more likely to become obese or develop diabetes in adulthood. Among its other adverse effects, studies have shown that diabetes is associated with decrements in several domains of cognitive function. Cognitive decline can occur in the early stages of type 1 and type 2 diabetes and can manifest as mild to moderate reductions in cognitive function as measured by neuropsychological testing compared to non-diabetic controls. Although the etiology of cognitive impairment in people with T2DM is unclear, some studies have suggested that defects may cause cognitive decline in patients with diabetes in insulin signaling, autonomic function, and neuroinflammatory pathways. 

Dipeptidyl peptidase-4 (DPP-44) inhibitors are a class of antihyperglycemic drugs that work on the incretin system and are commonly referred to as the ‘gliptins’ – sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin. In addition to their antihypertensive effect, this class of drugs also has anti-inflammatory, anti-apoptotic, and immunomodulatory effects on the heart, kidneys, and blood vessels independent of the incretin pathway. Some studies have shown that this class of drugs can also be used for kidney and liver transplant patients with post-organ diabetes mellitus (NODAT) because of all these benefits. Although some studies have demonstrated that administration of DPP-4 in older patients with type 2 diabetes suffer from mild cognitive impairment, may improve glucose control, and protects against worsening in cognitive functioning, several recent studies have suggested a possible relationship between serum DPP4 and cognitive dysfunction in perinatal pregnant women with gestational diabetes mellitus (GDM). A recent case-control study examined data obtained from 217 participants divided into three groups: [(GDM group (n = 81), healthy pregnant (HP) group (n = 85), and control group (n = 51)], blood lipids, glycated hemoglobin, and glucose levels were measured, and ELISA was used to detect. DPP4, interleukin-6 (IL-6), and 8-iso-prostaglandin F2α (8-iso-PGF2α), and brain-derived neurotrophic factor (BDNF). The cognitive status of each group was assessed using the Montreal Cognitive Assessment (MoCA). The study key findings were as follow:

  • Visuospatial/executive function and attention were significantly different (P < 0.05) in the GDM, and HP groups compared to the control group, but no significant difference was noted between the GDM and HP groups.
  • Language has a significantly different score in the GDM group (P < 0.05).
  • Memory score was significantly different between the HP and control groups (P < 0.05) and between the GDM and HP groups.
  • The levels of DPP4, IL-6, and 8-iso-PGF2α in the GDM group were significantly higher than those in the HP and control groups (P < 0.05)
  • BDNF levels in the GDM group were significantly lower than those in the HP and control groups (P < 0.05). 

Based on these findings, the study concluded that there is a relationship between elevated serum DPP4 levels and cognitive dysfunction, mainly manifested as memory loss, in perinatal pregnant women with gestational diabetes mellitus (GDM) 

Practice pearls:

  • Both type 1 and type 2 diabetes are associated with cognitive decline. 
  • DPP-4 may improve glucose control and protect against worsening in cognitive functioning in older patients with type 2 diabetes but may worsen cognitive dysfunction in women with GDM.
  • In women with GDM, DPP4 elevated levels may lead to cognitive dysfunction manifested as memory loss.

References:

Sana SRGL, Li EY, Deng XJ, Guo L. Association between plasma dipeptidyl peptidase-4 levels and cognitive function in perinatal pregnant women with gestational diabetes mellitus. World J Clin Cases 2021; 9(33): 10161-10171 [PMID: 34904086 DOI: 10.12998/wjcc.v9.i33.10161]

Kasina SVSK, Baradhi KM. Dipeptidyl Peptidase IV (DPP IV) Inhibitors. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542331/

Moheet, Amir et al. “Impact of diabetes on cognitive function and brain structure.” Annals of the New York Academy of Sciences vol. 1353 (2015): 60-71. doi:10.1111/nyas.12807

Zilliox, Lindsay A et al. “Diabetes and Cognitive Impairment.” Current diabetes reports vol. 16,9 (2016): 87. doi:10.1007/s11892-016-0775-x

Elmoataz Elmamoun

PharmD Candidate, 2022, South College School of Pharmacy

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