| Background With the change of lifestyle, the improvement in the living standard and the acceleration of aging process, the incidence of diabetes, obesity, metabolic syndrome and other metabolic diseases become higher and higher. At the same time, neurodegenerative diseases, such as Alzheimer’s disease has risen to be the serious public health problem. Moreover, a large number of studies have shown that metabolic diseases, such as diabetes, obesity will increase the risk of developing Alzheimer’s disease. Therefore, early identification of mild cognitive impairment in patients with diabetes or obesity and other metabolic diseases, looking for biomarkers in the early stage of Alzheimer’s disease and preventing further deterioration in cognitive function are of great significance. Ghrelin, a kind of brain-gut peptide, is related with insulin resistance, glucose metabolism disorder, obesity and other endocrine disorders. In recent years, with the further study of ghrelin and its receptor in the central nervous system, it is found that ghrelin has an important role in improving cognitive function and modulating learning, memory, emotion and so on. Besides, a few studies have found that serum ghrelin is associated with executive function which impaired in the early stage of cognitive impairment, suggesting that the level of serum ghrelin may be a biomarker of mild cognitive dysfunction in patients with diabetes, obesity and other metabolic diseases, and may become a pre-clinical sign of Alzheimer’s disease. However, at present, research on the relationship between serum ghrelin level and executive function is still in the primary stage, and few in population-based study. Association between them remains controversial, so further studies are urgently needed.Objective To understand the correlation between serum ghrelin and cognitive function, especially executive function in patients with diabetes, obesity, metabolic syndrome and other metabolic diseases. It is expected to provide theoretical basis for the early identification of mild cognitive impairment in these patients and the further study on therapeutic target for cognitive dysfunction.Methods Cross-sectional study was adopted among patients with diabetes, metabolically healthy obesity and metabolic syndrome recruited from inpatient or outpatient in the first affiliated hospital of Anhui Medical University from March to August in 2015. Each group has thirty patients aged twenty to fifty-five. At the same time, thirty age-matched controls were recruited in the community. Years of education, height, weight, waist circumference, waist hip ratio, blood pressure and other general information were collected among all groups. Biochemical indexes, such as fasting blood glucose(FBG), glycosylated hemoglobin(GHb or Hb A1c), triglyceride(TG), total cholesterol(TCH), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), very low-density lipoprotein cholesterol(VLDL-C) and ghrelin were also tested. Montreal Cognitive Assessment was adopted to assess global cognition of the subjects and then we used Stroop Test and Wisconsin Card Sorting Test to assess executive function of them. SPSS 20.0 software was used to analyze the data. Quantitative data were compared using one-way-ANOVA or rank sum test and qualitative data were compared using Chi-square test. The correlation between serum ghrelin, other factors and executive function was analyzed using multiple linear regression.Results(1) Compared with the normal group, diabetes and metabolic syndrome group had lower level of serum ghrelin and the difference was statistically significant(P< 0.01). Although serum ghrelin level in metabolically healthy obesity group was a little lower than the normal group, the difference was not statistically significant(P> 0.05).(2) There were significant difference in total Mo CA score, visual spatial executive function and attention among diabetes, metabolic syndrome and normal group(P< 0.01). However, the total Mo CA score and the scores of sub items of Mo CA had no significant difference between metabolically healthy obesity and normal group(P> 0.05). No significant difference was found in naming, calculation, language and orientation ability among four groups(P> 0.05).(3) Compared with the normal group, the Stroop interference effect of diabetes and metabolic syndrome group were stronger and the difference was statistically significant(P< 0.05, P< 0.01, respectively). The difference of Stroop interference effect was not statistically significant between metabolically healthy obesity and normal group(P> 0.05).(4) Compared with the normal group, the number of categories completed was fewer and percentage of correct responses was lower in WCST in diabetes and metabolic syndrome group(P< 0.01). Besides, total trials, error responses, perseverative responses, perseverative errors, non-perseverative errors and trials to compete first category in WCST were more than the normal group. The percentage of error responses, perseverative responses, perseverative and non-perseverative errors were higher and the differences were statistically significant(P< 0.01, the percentage of non-perseverative errors, P< 0.05). There was no significant difference in any indexes of WCST betweenmetabolically healthy obesity and normal group(P> 0.05). The difference of correct responses among four groups was not statistically significant(P> 0.05).(5) It was found by multiple linear regression analysis that total Mo CA score was positively correlated with years of education, while negatively correlated with age, waist hip ratio and Hb A1 c. Associations between total Mo CA score and serum ghrelin, BMI, SBP, DBP, FBG, serum lipid were not found.Besides, Stroop interference effect was positively related with age and waist hip ratio, negatively related with serum ghrelin. There were significant correlations between indexes of WCST and serum ghrelin, Hb A1 c, years of education and other factors.Conclusions(1) The level of serum ghrelin and years of education are positively correlated with executive function, including response inhibition, working memory, attention, mental flexibility among patients with metabolic syndrome and other metabolic diseases. However, Hb A1 c and age are negatively correlated with executive function.(2) The level of serum ghrelin may be a biomarker of mild cognitive dysfunction in patients with diabetes, metabolic syndrome and other metabolic diseases, and may become a pre-clinical sign of Alzheimer’s disease. |
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