Reduced Serum Levels of Klotho are Associated with Mild Cognitive Impairment in Patients with Type 2 Diabetes Mellitus

Figures & data

Table 1 Clinical Characteristics and Biochemical Parameters of Type 2 Diabetic Elderly Patients with and without MCI

Variables	MCI	Non-MCI	T or χ^2	P value
Number of patients	91	201
Age (year)*	60.54 ± 7.22	59.07 ± 6.85	3.935	<0.001
Gender (male/female)^†	50/41	108/93	0.037	0.847
Education (years)*	10.16 ± 2.19	11.35 ± 2.31	4.118	<0.001
BMI*	27.41 ± 1.49	26.76 ± 1.75	3.100	0.002
Smoking^†	31 (34.1%)	55 (27.4%)	1.354	0.245
Hypertension^†	46 (50.5%)	86 (42.8%)	1.524	0.217
Duration of T2DM (years)*	9.07 ± 0.96	8.14 ± 0.95	7.709	<0.001
FBG (mmol/L)*	8.89 ± 0.44	8.82 ± 0.49	1.183	0.238
PBG (mmol/L)*	14.42 ± 0.46	14.26 ± 0.52	2.533	0.012
HbA1c (%)*	9.59 ± 0.40	9.36 ± 0.42	4.536	<0.001
TG (mmol/L)*	2.78 ± 0.45	2.53 ± 0.52	3.945	<0.001
TC (mmol/L)*	6.18 ± 0.44	6.08 ± 0.46	1.873	0.062
LDL-C (mmol/L)*	3.71 ± 0.49	3.56 ± 0.39	2.772	0.006
HDL-C (mmol/L)*	1.57 ± 0.31	1.77 ± 0.34	4.806	<0.001
Creatinine (μmol/L)*	84.61 ± 6.89	77.03 ± 9.63	6.762	<0.001
CRP (mg/L)*	6.36 ± 1.11	5.18 ± 1.12	8.389	<0.001
MoCA	23.08 ± 1.38	28.15 ± 1.30	30.223	<0.001
Klotho (pg/mL)*	260.9 ± 33.9	296.6 ± 33.5	8.414	<0.001

Notes: *Significance, P<0.05; comparing patients with MCI and those without MCI (controls), ^†Indicate categorical data, Data are mean - SD values. Mann–Whitney U-test (Z), or χ² test was used to test for significant differences.

Abbreviations: MCI, mild cognitive impairment; BMI, body mass index; T2DM, diabetes type 2; FBG, fasting blood glucose; PBG, postprandial blood glucose; HbA1c, glycosylated hemoglobin; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; CRP, C-reactive protein; MoCA, Montreal Cognitive Assessment.

Figure 1 Serum levels of Klotho in T2DM and control cases. All data are medians and inter-quartile range (IQR); P values refer to Mann–Whitney U-tests for differences between groups. ***P<0.001 vs healthy control group (without MCI) and ^###P<0.001 vs healthy control group (with MCI).

Abbreviations: MCI, mild cognitive impairment; T2DM, type 2 diabetes mellitus.

Table 2 Relationship of Serum Level of Klotho with Other Clinical Indicators in Group of Diabetic Elderly Patients

Variables	r	P value
Age (year)*	−0.184	0.002
Education (years)*	0.319	<0.001
BMI*	−0.151	0.010
Duration of T2DM (years)*	−0.193	0.001
FBG (mmol/L)*	−0.073	0.216
PBG (mmol/L)*	−0.082	0.161
HbA1c (%)*	−0.197	0.001
TG (mmol/L)*	−0.065	0.271
TC (mmol/L)*	−0.039	0.511
LDL-C (mmol/L)*	−0.111	0.058
HDL-C (mmol/L)*	0.272	<0.001
Creatinine (μmol/L)*	−0.178	0.002
CRP (mg/L)*	−0.319	<0.001

Notes: *Significance, p < 0.05; r, correlation coefficient.

Abbreviations: BMI, body mass index; T2DM, diabetes type 2; FBG, fasting blood glucose; PBG, postprandial blood glucose; HbA1c, glycosylated hemoglobin; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; CRP, C-reactive protein.

Table 3 Assessment Results of the Risk of Having MCI in a Multivariable Logistic Regression Model in Elderly Patients with Type 2 Diabetes

Variables	β	SE of β	P value	OR	95% CI
Education (years)*	−0.218	0.096	0.022	0.804	0.667–0.969
Duration of T2DM (years)*	0.889	0.205	<0.001	2.433	1.628–3.638
HbA1c (%)*	1.210	0.548	0.027	3.355	1.146–9.821
HDL-C (mmol/L)*	−1.594	0.649	0.014	0.203	0.057–0.725
Creatinine (μmol/L)*	0.127	0.028	<0.001	1.136	1.075–1.200
CRP (mg/L)*	0.837	0.196	<0.001	2.309	1.574–3.388
Klotho (pg/mL)*	−0.013	0.004	<0.001	0.987	0.980–0.994

Notes: *Significance, p < 0.05. β, regression coefficient.

Abbreviations: CI, confidence interval for odds ratio; OR, odds ratio; SE, standard error; T2DM, diabetes type 2; HbA1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; CRP, C-reactive Protein.