Vitamin D Level as a Predictor of Dysmobility Syndrome in Middle-aged and older adults with Type 2 Diabetes

doi:10.21203/rs.3.rs-3300434/v1

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Vitamin D Level as a Predictor of Dysmobility Syndrome in Middle-aged and older adults with Type 2 Diabetes

https://doi.org/10.21203/rs.3.rs-3300434/v1

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This cross-sectional study aimed to explore the effect of 25-(OH) Vit D on Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients, including 330 patients (66.96±8.78 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. The 25-(OH) Vit D is grouped at the 25th percentile into two groups (group A <36.2nmol/L, group B ≥ 36.2nmol/L). Data on grip strength, six meters grip strength, and level of 25-(OH) vitamin D were collected and measure bone mineral density (BMD) by Dual-energy X-ray (DXA). The incidence of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. Compared with patients without DMS, the level of 25-(OH)Vit D in patients with DMS was lower (41.74±14.60 vs 47.19±13.01, P＜0.05). With DMS as the dependent variable, Gender, age, vitamin D level, HbA1c, ALB, HDLC, eGFR, Diabetic retinopathy, diabetes nephropathy, and diabetes peripheral neuropathy were taken as independent variables, and logistic regression analysis was performed to find the independent factors, which include age (OR value=1.175，95%CI：1.110-1.243, P=0.000), low levels of 25-(OH) Vit D (OR value=2.910，95%CI：1.357-6.242, P=0.006), and higher levels of HbA1c(OR value=1.288, 95%CI: 1.085-1.529, P=0.004), they are associated with the risk of DMS’s prevalence in T2DM patients. But males reduce the risk of DMS by 51.3% (OR value=0.487, 95%CI: 0.238-0.998, P=0.05).

Vitamin D

Dysmobility Syndrome

Type 2 Diabetes Mellitus

Sarcopenia Osteoporosis

Dysmotility Syndrome(DMS), which was first proposed by the Japanese Orthopaedic Society in 2007¹, includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, history of falls, and obesity, having three or more of these conditions were diagnosed with DMS. Its hazards are an increased risk of falls, fractures, and disability², there is a study showing that DMS increases mortality in adults aged 50 and above³. China is becoming an aging nation, which will lead to more and more people suffering from Type 2 Diabetes mellitus(T2DM). Therefore, more attention needs to be paid to this disease. The literature shows that the probability of DMS in patients with type 2 diabetes is significantly higher than that in patients without T2DM⁴. Patients with T2DM are prone to vitamin D deficiency⁵, and some studies show that vitamin D is closely related to obesity⁶,osteoporosis⁷, and Sarcopenia⁸. At present, the diagnosis of DMS is complex, and requires the use of multiple instruments and equipment for measurement, so the diagnosis of DMS requires a higher cost. Therefore we aim to predict the risk of DMS in patients with type 2 diabetes through simple laboratory indicators, such as vitamin D levels, and serum 25-(OH) Vit D can stably and effectively express the level of vitamin D in the body⁹, which can simplify the diagnostic process and reduce the diagnostic cost of DMS.

A cross-sectional analysis was performed on patients with T2DM who were hospitalized in Qinhuangdao First Hospital from October 2020 to February 2022. The inclusion criteria included the following: 1) diagnosed with T2DM;2) over the age of 50;3) with basic communication, comprehension, and full behavioral skills;4)without vitamin D supplementation. The exclusion criteria included the following: 1) uncorrected acute complications of diabetes such as diabetic ketoacidosis, hyperosmolar hyperglycemic state; 2) acute cerebrovascular disease, gastrointestinal bleeding, acute and chronic renal failure decompensated, severe liver dysfunction, and other patients with a history of severe physical damage;3) patients with severe osteoarthritis or neuromuscular disease affecting daily activities;4) acute infectious disease patients; 5) malignant tumor patients;6) patients who received vitamin D supplementation. All patients who met the inclusion criteria signed the informed consent form approved by the Ethics Committee of Qinhuangdao First Hospital. The ethical approval number is 2020B004. A total of 330 patients with T2DM were included in this study, 153 males (46.4%) and 177 females (53.6%), According to the 25th percentile of 25-(OH)Vit D, they were divided into two groups, group A with < 36.2 nmol/L, group B with ≥ 36.2 nmol/L.

Collect the gender, age, history of diabetes and complications, history of falls and fractures in the past 1 year, history of hypertension, history of cerebral infarction, history of smoking, and history of drinking from each patient in chronological order. Anthropometric measurements include height, weight, waist circumference (WC), blood pressure, Speed of six meters, and grip strength. Body mass index (BMI) was calculated by dividing weight (kg) by height squared (m²), and BMI ≥ 27 kg/m² is defined as obesity. Blood pressure was measured twice with a mercury sphygmomanometer after 10 min of rest while the subjects were seated, and the average of the two measurements was used for analysis. Subjects perform a 6m walking test at a natural pace, record the time (s), and then calculate that the pace is equal to 6m/time (s), with ≤ 0.8 m/s as the diagnosis of a slow pace¹⁰. Grip Strength measurement with JAMAR Electronic Grip Dynamometer, The grip strength of the subjects' left and right hands was measured, and the average was taken after three measurements, the average grip strength of both hands is less than 26kg for men and less than 18kg for women which is diagnosed as low grip strength¹⁰. The French MEDILINK bone density instrument was used to measure BMC, lumbar spine L1-4BMD, femoral neck BMD, whole-body muscle content, whole-body fat content, and calculate the skeletal muscle mass index (SMI) = skeletal muscle mass/height 2 (Kg/m2), low muscle mass was diagnosed by SMI ≤ 5.40 kg/m² in women and ≤ 7.0 kg/m² in men, which is the diagnostic criteria developed by the Asian sarcopenia working group (ASWG) in 2014¹⁰. The measured with DXA T value of the Lumbar spine or femoral neck ≤-2.5 was defined as Osteoporosis. Laboratory Examinations: Blood tests were performed after at least 9 hours of fasting, and serum 25-(OH)Vit D was measured by using the Abbott Automatic Chemiluminescence Meter. HbA1C, blood uric acid, Serum creatinine, Lipids [total cholesterol (TC), triglyceride (TG), HDL-C, and low-density lipoprotein-cholesterol (LDL-C)], ALB, and Fasting blood glucose (FBG) concentration were measured by direct methods on an automated biochemical analyzer (Hitachi LST008 Tokyo, Japan), and then we calculated the eGFR by using the CKD study equation. Hemoglobin (HGB) was measured by an automatic blood analyzer (XE-2100, Japan).

The statistical analysis was performed with SPSS version 23.0 (SPSS Inc., Chicago, IL, USA). Measurement data were expressed as mean ± standard deviation, Differences in serum 25(OH)Vit D between Non-DSM with T2DM and DSM with T2DM subjects were evaluated by using a Student’s t-test for continuous measures and a chi-square test for categorical measures. Spearman correlation coefficients were determined for bivariate associations of 25(OH)Vit D and other covariates. Multivariate logistic regression analysis was done to identify independent factors affecting the risk of T2DM with DMS. We expressed the results of this analysis as odds ratios (ORs) and 95% confidence intervals (CI) for VitD deficiency. p < 0.05 was accepted as statistically significant.

3.1 Subsection

3.1.1 Clinical characteristics of the study subjects

The clinical characteristics of the study subjects are shown in Table 1–2. The mean age of the DMS group was 73.24 years and 67.9% were women. The mean age of the Non-DMS group was 64.82 years and 48.8% were women. Compared with the Non-DMS group (n = 246), patients of DMS in T2DM had lower serum 25-(OH) Vit D level (47.19 ± 13.01 nmol/L vs. 41.74 ± 14.60 nmol/L, p = 0.003), and in male patients (43.38 ± 12.98 vs 49.59 ± 13.70 P < 0.05), while in female patients (40.96 ± 15.38 vs 44.78 ± 11.85 P > 0.05); and had higher age (73.24 ± 7.47 VS 64.82 ± 8.16 P < 0.05), thicker WC（94.05 ± 8.33 VS 91.17 ± 10.15 P < 0.05）, HDL-C（1.14 ± 0.26 VS 1.07 ± 0.25 P < 0.05）, and longer history of diabetes, and lower DBP, eGFR, ALB, and HGB. There is currently no statistical difference in BMI, SBP, diabetes complications, FBG, HbA1c, TG, TC, and LDL-C between the two groups.

3.1.2. Factors associated with serum 25-(OH)Vit D levels in patients of DMS with T2DM

We evaluated correlations between serum 25-(OH)Vit D and other factors in patients of DMS with T2DM. The result shows that the serum 25- (OH) Vit D levels in T2DM patients with DMS were positively correlated with grip strength (r = 0.226, P < 0.001), Six meters Speed (r = 0.146, P = 0.001), HbA1c (r = 0.206, P < 0.001), ALB (r = 0.166, P = 0.005), SMI (r = 0.254, P < 0.001), and overall muscle mass (r = 0.219, P = 0.002), whereas Age(r=-0.150, P = 0.009) was a negative correlation(Table 3).

3.1.3. The proportion of different vitamin D levels in DMS and its branches

The incidence of DMS in patients with T2DM was 25.5% in this study. The proportion of vitamin deficiency is 67.9% in patients with T2DM. We performed a chi-square test and the results showed that group A with lower vitamin D levels had a higher proportion of low grip strength, Osteoporosis, low Six meters Speed, and DMS than the group B with higher vitamin D levels, and the difference was statistically significant(p＜0.05) (Table 4), but low SMI accounts for a relatively high proportion of low levels of vitamin D, but P = 0.231, which is not statistically significant.

3.1.4 Logistic regression analysis of risk factors for DMS in a patient with T2DM

A logistic regression analysis was performed to find the independent factors associated with the risk of DMS in T2DM patients. The dependent variable is group DMS (0 = Non-DMS group,1 = DMS group), The independent variables are respectively gender(0 = female,1 = male), age, diabetic retinopathy(0 = without,1 = with), diabetic neuropathy(0 = without,1 = with), diabetic nephropathy(0 = without,1 = with) and 25-(OH)Vit D (1 = group A = the level of 25-hydroxyvitamin D < 36.2 nmol/L,0 = group B = the level of 25-hydroxyvitamin D ≥ 36.2nmol/L), HbA1c, ALB, HDLC, eGFR were taken as independent variables. The result showed that the age (OR value = 1.175, 95%CI: 1.110–1.243, P = 0.000), low levels of 25-(OH) Vit D (OR value = 2.910, 95%CI༚1.357–6.242, P = 0.006), and higher levels of HbA1c(OR value = 1.288, 95%CI: 1.085–1.529, P = 0.004), they are associated with the risk of DMS’s prevalence in T2DM patients. But males reduce the risk of DMS by 51.3% (OR value = 0.487, 95%CI: 0.238–0.998, P = 0.05) (Table 5).

3.2 Tables

Table 1

Clinical laboratory characteristics of the subjects in different groups.
variable	Non-DMS group (n = 246)	DMS Group (n = 84)	t or χ²	P
Age(years) mean(SD)	64.82(8.16)	73.24(7.47)	-8.71	＜0.001*
Gender (male/female)	(126/120)	(27/57)	9.16	0.002*
BMI(kg/m²) mean(SD)	25.30(3.30)	25.54(3.35)	-0.57	0.571
WC (cm) mean (SD)	91.17(10.15)	94.05(8.33)	-2.12	0.035*
SBP(mmHg)mean(SD)	144.13(20.16)	142.69(19.50)	0.57	0.570
DBP(mmHg)mean(SD)	84.05(11.26)	80.11(12.19)	2.71	0.007*
history of diabetes	10.08(8.63)	12.07(9.20)	-1.80	0.073*
diabetic retinopathy	(202/39)	(71/13)	0.023	0.879
diabetic neuropathy	(147/94)	(54/30)	0.286	0.593
diabetic nephropathy	(211/32)	(72/12)	0.067	0.796

* means that it is statistically significant. Baseline laboratory values represent the mean ± SD. BMI: body mass index (calculated as weight in kilograms divided by height in meters squared), WC: waist circumference; SBP: systolic blood pressure, DBP: diastolic blood pressure.

Table 2

Laboratory characteristics of the subjects in different groups
variable		Non-DMS group (n = 246)	DMS Group (n = 84)	t or χ²	P
HbA1c(%)mean(SD)		8.83(4.55)	8.98(2.26)	-0.28	0.778
FPG(mmol/L)mean(SD)		8.27(3.18)	8.45(3.54)	-0.418	0.676
25-(OH)Vit D mean(SD)	Total population	47.19(13.01)	41.74(14.60)	3.00	0.003*
	male	49.59(13.70)	43.38(12.98)	2.00	0.047*
	female	44.78(11.85)	40.96(15.38)	1.71	0.089
TG(mmol/L)mean(SD)		1.90(1.29)	1.94(1.18)	-0.27	0.785
TC(mmol/L) mean (SD)		5.11(1.48)	5.28(1.38)	-0.90	0.370
HDL-C(mmol/L)mean (SD)		1.07(0.25)	1.14(0.26)	-2.17	0.031*
LDL-C(mmol/L) mean (SD)		3.95(18.51)	2.93(1.02)	0.50	0.616
eGFR(ml/min) mean(SD)		95.41(18.71)	84.09(23.76)	3.80	＜0.001*
uACR(mg/mmol)mean(SD)		8.62(31.64)	11.08(21.62)	-0.612	0.541
ALB(g/L) mean(SD)		43.30(4.95)	41.14(14.60)	3.45	0.001*
HGB(g/L) mean(SD)		140.92(15.66)	132.47(15.15)	4.28	＜0.001*

* means that it is statistically significant. FPG: fasting plasma glucose, HbA1C: hemoglobin A1C, 25(OH)D: 25-hydroxyvitamin D, TG: triglycerides, TC: cholesterol, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol, eGFR: estimated glomerular filtration rate, UACR: urine albumin creatinine ratio, ALB: albumin, HGB༚ hemoglobin.

Table 3

Correlations between the 25-(OH)Vit D and other variables
variable	r	P
Age(years)	-0.150	0.009*
BMI(kg/m²)	0.029	0.621
WC(cm)	-0.026	0.663
SBP(mmHg)	-0.03	0.603
DBP(mmHg)	0.045	0.434
Grip Strength (Kg)	0.226	＜0.001*
Speed of six meters(m/s)	0.146	0.011*
SMI(Kg/m²)	0.254	＜0.001*
body muscles(g)	0.219	0.002*
body fat(g)	0.045	0.436
FPG(mmol/L)	-0.041	0.487
TG(mmol/L)	-0.031	0.592
TC(mmol/L)	-0.020	0.727
HDL-C(mmol/L)	-0.064	0.269
LDL-C(mmol/L)	-0.014	0.809
HbA1c(%)	0.206	＜0.001*
uACR (mg/mmol)	-0.064	0.281
ALB(g/L)	0.166	0.005*
eGFR(ml/min)	0.110	0.075
Creatinine(umol/L)	-0.015	0.790

* means that it is statistically significant. BMI: body mass index (calculated as weight in kilograms divided by height in meters squared), WC: waist circumference; SBP: systolic blood pressure, DBP: diastolic blood pressure, FPG: fasting plasma glucose, HbA1C: hemoglobin A1C, 25(OH)D: 25-hydroxyvitamin D, TG: triglycerides, TC: cholesterol, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol, eGFR: estimated glomerular filtration rate, UACR: urine albumin creatinine ratio, ALB: albumin, SMI: skeletal lean mass index.

Table 4

The proportion of different vitamin D levels in DMS and its branches
	Group A	Group B	X²	p
Lower SMI (%)	68.5	60.7	1.436	0.231
Lower Grip (%)	43.8	23.1	11.718	0.001*
Higher BMI (%)	26.0	31.0	0.655	0.418
Fall (%)	11.0	13.1	0.231	0.631
Osteoporosis (%)	41.1	20.5	12.332	＜0.001*
Lower Six meters Speed (%)	32.9	18.3	6.849	0.001*
DMS (%)	38.4	18.8	11.80	0.001*

* means that it is statistically significant. group A <36.2nmol/L, group B ≥ 36.2nmol/L; SMI: skeletal lean mass index, BMI: body mass index (calculated as weight in kilograms divided by height in meters squared).DMS: Dysmobility Syndrome, X²: Chi-square value

Table 5

Logistic regression analysis of risk factors for DMS in a patient with T2DM
Variables	B	Odds Ratio	95% CI	p
Gender(male)	-0.720	0.487	0.238–0.998	0.05
Age	0.161	1.175	1.110–1.243	0.000*
25-(OH) Vit D (group A)	1.068	2.910	1.357–6.242	0.006*
HbA1C	0.253	1.288	1.085–1.529	0.004*

The dependent Variable is group DMS (0 = Non-DMS group,1 = DMS group), The independent variables are gender(0 = female,1 = male), age, diabetic retinopathy(0 = without,1 = with), diabetic neuropathy(0 = without,1 = with), diabetic nephropathy(0 = without,1 = with) and 25-(OH)Vit D (group A = the level of 25-hydroxyvitamin D < 36.2 nmol/L, group B = the level of 25-hydroxyvitamin D ≥ 36.2nmol/L), HbA1c, ALB, HDLC, eGFR.

As China gradually enters an aging society, the quality of life of the elderly has attracted people's attention, and T2DM and DMS are common chronic diseases. Studies have shown that vitamin D levels decline with being older¹¹ and are associated with diabetes¹². At present, there are relevant research reports on each branch of DMS, mainly focusing on the research of bone and muscle as exercise organs, energy metabolism, and endocrine hormone action target organs. Kim et al. found that older adults with diabetes lost approximately 26 percent of muscle mass and approximately 33 percent less muscle strength per year compared with older adults without diabetes¹³. Some literature pointed out that patients with T2DM are prone to combined obesity and increased body fat rate¹⁴, increased incidence of osteoporosis¹⁵, increased incidence of fractures¹⁶, and are prone to problems such as slow gait and balance. However, a new concept, covering multiple factors such as osteoporosis, sarcopenia, balance ability, and obesity, was rarely studied.

This study found that the proportion of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM, and the research results show that grip strength, Speed of six meters, and SMI are a positive correlation with serum 25-(OH)Vit D in patients with T2DM, which indicates that vitamin D is related to various branches of DMS. The detection rate of DMS in the group with low levels of 25-(OH)Vit D (< 36.2nmol/L)was higher, and the Detection rate of low levels of 25-(OH)Vit D in grip strength, osteoporosis, and six meters speed facet was higher, which further proves that vitamin D is related to muscle function and osteoporosis. logistic regression analysis showed that aging and low 25-(OH)Vit D increased the risk of DMS by 1.153 and 1.961 times in patients with T2DM, but age is an uncontrollable factor. And some foreign studies have pointed out that the lack of vitamin D levels can lead to decreased muscle function¹⁷, and also increase the risk of decreased bone density, osteoporosis, falls, and fractures⁷. Meta-analysis showed that long-term calcium and vitamin D supplementation significantly reduced total fracture risk by 15% and hip fracture risk by 30%¹⁸, and foreign reports show that timely supplementation of vitamin D can reduce muscle damage¹⁹. So relatively low vitamin D levels may help identify DMS in T2DM patients. In addition, the study also found that males are a protective factor against T2DM with DMS, and reduce the risk of their occurrence by 54.6%, which consider that is related to the testosterone levels in the body, and females are in menopause after the age of 50, they relatively lack sex hormones. Previous studies have shown that testosterone reduces the occurrence of sarcopenia by stimulating cellular metabolism and survival pathways and inhibiting death pathways²⁰. This study did not see the effect of diabetic complications on DMS, but studies have shown that muscle strength in type 2 diabetes is associated with the severity of diabetic peripheral neuropathy²¹.

There are still some deficiencies in this study. First, it is a single-center study. Second, the level of 25-(OH)Vit D in the T2DM population is generally low. Last but not least, due to the small sample size, a more suitable cut-off point value of vitamin D could not be found.

In summary, the results of this study suggest that older T2DM patients with relatively low 25-(OH)Vit D levels have an increased risk of DMS, and male is the protective factor against DMS in T2DM patients. It is hoped that middle-aged and elderly patients with type 2 diabetes, especially female patients will pay attention to 25-(OH)Vit D levels. Call on more people to know about DMS early, and reduce the occurrence of DMS T2DM patients by supplementing vitamin D, which can improve the quality of life of the elderly.

abbreviations	full name
25（OH）Vit D	25-hydroxyvitamin D
1，25( OH) ₂D	1，25-hydroxyvitamin D
ALB	albumin
BMD	bone mineral density
BMI	body mass index
DBP	diastolic pressure
DMS	Dysmobility Syndrome
DXA	Dual-energy X-ray
eGFR	estimated glomerular filtration rate
ER	estrogen receptor
FBG	Fasting blood glucose
HbA1c	glycosylated hemoglobin
HDL-C	High density lipoprotein cholesterol
LDL-C	Low density lipoprotein cholesterol
HGB	hemoglobin
OP	osteoporosis
PTH	parathyroid hormone
SDP	systolic pressure
T2DM	Type 2 diabetes mellitus
TC	cholesterol
TG	triglyceride
SMI	Skeletal muscle mass index of limbs
uACR	Urine microalbumin/creatinine ratio
VD	vitamin D
VDR	Vitamin D receptor
WC	waistline

Ethics approval and consent to participate：

This study had been performed in accordance with the Declaration of Helsinki and had been approved by the Ethics Committee of Qinhuangdao First Hospital.

Consent for publication

Informed consent was obtained from all subjects involved in the study.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

We declare that we have no known competing financial or personal relationship with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service, or company.

Funding

The research of 25-(OH) Vit D and dysmobility syndrome in older patients with type 2 diabetes（GZ2023044）

Authors' contributions

Name	contribution
Yongfang Ma	data collection and drafting and editing of the paper
Bowei Liu	data analysis and revision of the paper
Fuzai Yin	revision of the paper
Junru Liu	data collection
Xing Wang	data collection
Dongmei Fan	data collection
Lina Sun	data collection
Lanyu Lu	data collection

Acknowledgements

This work was supported by the People's Livelihood Program Special Project of the Hebei Provincial Department of Science and Technology（2037708D）

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Vitamin D Level as a Predictor of Dysmobility Syndrome in Middle-aged and older adults with Type 2 Diabetes

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Abstract

1. INTRODUCTION

2. MATERIALS AND METHODS

3. RESULTS

3.1 Subsection

3.1.1 Clinical characteristics of the study subjects

3.1.2. Factors associated with serum 25-(OH)Vit D levels in patients of DMS with T2DM

3.1.3. The proportion of different vitamin D levels in DMS and its branches

3.1.4 Logistic regression analysis of risk factors for DMS in a patient with T2DM

3.2 Tables

4. DISCUSSION

Abbreviations

Declarations

References

Additional Declarations

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