Association between hemoglobin and low muscle mass in patients with type 2 diabetes mellitus

doi:10.21203/rs.3.rs-2213874/v1

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Association between hemoglobin and low muscle mass in patients with type 2 diabetes mellitus

https://doi.org/10.21203/rs.3.rs-2213874/v1

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Objective

Low hemoglobin (Hb) levels are related to malnutrition and can lead to dysfunction and physical disability. T2DM is more likely to develop low muscle mass. This study is performed to evaluate the association between hemoglobin and low muscle mass in T2DM patients.

Method

This cross-sectional study recruited 1054 inpatients in Qilu Hospital (Qingdao). Skeletal muscle index (SMI) was measured using dual energy X-ray absorptiometry. Hb was detected by automatic blood cell analyzer. Logistic regression analysis was utilized to determine the risk factors for low muscle mass.

Result

119 male subjects (20.3%) and 60 female subjects (12.6%) had low muscle mass in T2DM patients. Hb was correlated with a decreased risk of low muscle mass in both genders. Multiple linear regression analysis showed that SMI was associated with age, HbA1c, and Hb in male subjects. While in female subjects, SMI was associated with age, SBP, and Hb. In male participants, Hb was positively correlated with SMI after multivariate adjustment. Hb was positively correlated with SMI when Hb was ≤ 136. However, the correlation was not statistically significant when Hb was > 136. In addition, Hb was correlated with SMI after multivariate analysis in female subjects. When Hb was > 122, Hb was positively correlated with SMI. Hb was negatively correlated with SMI when Hb was ≤ 122, however, the association was not statistically significant.

Conclusion

Hb is inversely correlated with the presence of low muscle mass in T2DM patients.

hemoglobin

low muscle mass

skeletal muscle index

Sarcopenia is a syndrome featured with age-related loss of muscle mass, muscle strength and/or physical function [1]. Sarcopenia is prone to result in adverse health events such as falls, fractures, fatigue, mobility disorders, disabilities, metabolic disorders, and mortality, greatly reducing the quality of life of the elderly [2]. As a common metabolic disease, type 2 diabetes mellitus (T2DM) is spread all over the world. T2DM is more likely to develop sarcopenia or low muscle mass [3]. Recent studies have shown that sarcopenia is closely related to T2DM [4–6]. With the progress of T2DM, the skeletal muscle function and muscle mass of patients will gradually decrease, and the prevalence of sarcopenia is much higher than that of normal people [7]. To reduce the adverse effect of sarcopenia or low muscle mass on the health, it’s important to find early biomarkers of sarcopenia in T2DM patients.

Low hemoglobin (Hb) levels or anemia affects almost a third of the world’s population, which is particularly common among older persons [8]. Anemia occured in 20% T2DM patients and is associated with diabetic complications and poor prognosis [9]. Sarcopenia and anemia are both related to malnutrition and can lead to dysfunction and physical disability. Most studies of sarcopenia have focused on its association with infections, falls, and frailty [10–12]. However few studies have evaluated the relationship between sarcopenia and hemoglobin, especially in patients with T2DM. Hence, our study aimed to evaluate the roles of hemoglobin in low muscle mass in T2DM patients.

Participants

This study was a cross-sectional study which was conducted in the Department of Endocrinology of Qilu hospital (Qingdao). 1054 participants diagnosed with T2DM were recruited from patients hospitalized between September of 2017 and September of 2019. T2DM was diagnosed according to the American Diabetic Association criteria, fasting blood glucose ≥ 7.0 mmol/L or blood glucose ≥ 11.1 mmol/L at 2 hours postprandial. All participants were ≥ 20 years old. The participants were excluded as follows: pregnancy, tumor, sever osteoarthritis of the hip or knee, severe cardiovascular diseases, and stroke. The Ethics Committee of Qilu hospital (Qingdao) approved the study, and all participants signed written consent.

The Definition Of Low Muscle Mass

Skeletal muscle index (SMI) was detected by DXA (Hologic Discovery A, Waltham, MA, USA). SMI was computed according to the formula of the skeletal muscle mass of limbs in kg divided by height in meters squared (kg/m²). The criteria for low muscle mass was according to the consensus of Asian Working Group for Sarcopenia, with SMI less than 7.0 kg/m² for men or 5.4 kg/m² for women [13].

Measurements

The information of height, weight, blood pressures, duration of diabetes, clinical, and laboratory analyses were collected. Body mass index (BMI) was determined using the formula of the weight in kg divided by height in meters squared (kg/m²). Fasting blood was taken from all the participants after all overnight fasting. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), fasting blood glucose (FPG), and glycosylated hemoglobin (HbA1c) were measured by biochemistry automatic analyzer (Hitachi 7170, Tokyo, Japan). Hemoglobin (Hb) was detected by automatic blood cell analyzer (XN-9000, SYSMEX, Japan).

Statistical analysis

All statistical analyses were carried out using Statistical Products and Service Solutions (SPSS for Windows, version 22; Chicago, IL). Data were described as means ± SD for continuous variables. To compare differences of characteristics between T2DM patients with and without low muscle mass, unpaired t-test and chi-square test were employed. To ascertain the risk factors for low muscle mass, logistic regression analysis was carried out. Multiple linear regression analysis adjusted for potential influencing factors was utilized to further analyze the independent association between Hb and SMI. To evaluate the relationship between Hb and SMI, a smooth curve fitting was employed. Then, according to the smooth curve fit, a multivariate piecewise linear regression was utilized to survey the threshold correlation of Hb and SMI. Statistical significance was set as P < 0.05.

General characteristics of the participants

This present study included 1054 patients with T2DM. General clinical characteristics and laboratory test result were shown in Table 1. Among all T2DM patients, 119 male subjects (20.6%) had low muscle mass, while 60 female subjects (12.6%) presented low muscle mass. In male subjects, low muscle mass group showed higher age, HDL, and HbA1c as well as lower SMI, BMI, TG, RBC, Hb and diastolic blood pressure (DBP) compared with normal muscle mass group. In female subjects, T2DM patients with low muscle mass showed higher age, as well as lower SMI, BMI, TG, FPG, RBC, and Hb compared with those with normal low muscle mass.

Table 1

The characteristic differences between T2DM patients with and without low muscle mass
Characteristics	Male (n = 578)			Female (n = 476)
	Normal muscle mass (n = 459)	Low muscle mass (n = 119)	P value	Normal muscle mass (n = 416)	Low muscle mass (n = 60)	P value
Age (years)	54.46 ± 11.91	60.67 ± 13.45	< 0.001	61.3 ± 10.8	65.63 ± 11.22	0.004
Duration (years)	8.04 ± 6.69	9.03 ± 5.83	0.144	8.62 ± 5.82	8.85 ± 6.46	0.77
BMI (kg/m²)	27.61 ± 4.11	23.65 ± 4.83	< 0.001	27.21 ± 4.26	22.53 ± 2.89	< 0.001
SMI	8.19 ± 1.51	6.45 ± 0.48	< 0.001	6.49 ± 0.88	5.08 ± 0.32	< 0.001
SBP (mmHg)	140.31 ± 19.45	137.5 ± 21.43	0.197	143.36 ± 20.8	142.88 ± 22.26	0.871
DBP (mmHg)	82.76 ± 12.74	78.66 ± 13.02	0.002	76.74 ± 12.87	76.9 ± 11.14	0.925
TG (mmol/L)	2.31 ± 2.27	1.41 ± 0.81	< 0.001	1.83 ± 1.33	1.4 ± 0.79	0.001
TC (mmol/L)	4.52 ± 1.15	4.47 ± 1.09	0.691	4.72 ± 1.35	4.67 ± 0.97	0.767
LDL (mmol/L)	2.98 ± 0.90	2.97 ± 0.94	0.937	3.02 ± 0.92	2.85 ± 0.85	0.611
HDL (mmol/L)	1.14 ± 0.27	1.23 ± 0.35	0.007	1.3 ± 0.37	1.39 ± 0.35	0.094
FPG (mmol/L)	8.14 ± 2.73	7.97 ± 3.17	0.587	7.77 ± 2.83	6.6 ± 2.24	< 0.001
HbA1c (%)	8.44 ± 2.08	8.91 ± 2.18	0.039	8.31 ± 2.01	7.98 ± 2.11	0.252
RBC	4.86 ± 0.46	4.58 ± 0.50	< 0.001	4.38 ± 0.42	4.2 ± 0.4	0.002
Hb	147.19 ± 12.53	139.36 ± 13.41	< 0.001	129.87 ± 11.49	124.95 ± 9.57	0.002
MCV	90.14 ± 4.19	90.91 ± 5.46	0.15	90.04 ± 4.35	90.65 ± 4.08	0.309
MCHC	336.91 ± 10.46	335.65 ± 11.92	0.292	330.2 ± 10.69	329.53 ± 13.98	0.725
RDW-CV	12.31 ± 0.68	12.47 ± 1.23	0.179	12.52 ± 0.77	12.57 ± 1.24	0.309

The Correlation Between Hb And Low Muscle Mass

As shown in Table 2, Hb was associated with a decreased risk of low muscle mass in both male and female T2DM groups. Hb was inversely correlated with low muscle mass in both male and female T2DM patients, after adjusting for age. Furthermore, Hb was still inversely associated with low muscle mass after adjusting for age, DBP, SBP, and duration of diabetes.

Table 2

The association between Hb and low muscle mass
Model	Male			Female
	Model 1	Model 2	Model 3	Model 1	Model 2	Model 3
OR(95CI)	0.955(0.939–0.970)	0.965(0.948–0.982)	0.965(0.948–0.982)	0.962(0.938–0.970)	0.967(0.943–0.991)	0.962(0.937–0.987)
P value	< 0.001	< 0.001	< 0.001	0.02	0.009	0.004
Model 1 was not adjusted; Model 2 was adjusted for age; Model 3 was adjusted for age, SBP, DBP, duration of diabetes

The Association Between Smi And Other Characteristics

The correlation between SMI and other characteristics was shown in Table 3. SMI was associated with age, HbA1c, and Hb in male subjects. In female subjects, SMI was associated with age, SBP, and Hb.

Table 3

The association between Hb and SMI
	Male		Female
	β (95% CI)	P value	β (95% CI)	P value
Age (years)	-0.22 (-0.035, -0.009)	< 0.001	-0.023 (-0.033, -0.014)	< 0.001
Duration (years)	-0.006 (-0.027, 0.015)	0.57	0.01 (-0.006, 0.025)	0.216
SBP (mmHg)	0.004 (-0.003, 0.011)	0.302	0.007 (0.001, 0.012)	0.013
DBP (mmHg)	0.007 (-0.005, 0.019)	0.241	-0.002 (-0.011, 0.007)	0.696
TG (mmol/L)	0.027 (-0.072, 0.125)	0.594	0.011 (-0.077, 0.100)	0.804
TC (mmol/L)	0.002 (-0.441, 0.445)	0.993	0.064 (-0.151, 0.279)	0.557
LDL (mmol/L)	-0.036(-0.479, 0.406)	0.871	-0.06 (-0.291, 0.172)	0.612
HDL (mmol/L)	-0.433 (-1.127, 0.261)	0.221	-0.303 (-0.728, -0.123)	0.163
FPG (mmol/L)	0.015 (-0.04, 0.069)	0.597	-0.009 (-0.049, 0.03)	0.644
HbA1c (%)	-0.099 (-0.169, -0.029)	0.006	-0.012 (-0.064, 0.04)	0.657
Hb	0.015 (0.004, 0.026)	< 0.001	0.01 (0.002, 0.018)	0.019

Non-linear Association Between Hb And Smi

As shown in Fig. 1, Hb might have some non-linear relationship with SMI in male participants. A two-piecewise linear regression model was shown in Table 4. After adjusting for age, DBP, SBP, and duration of diabetes, Hb was non-linearly correlated with SMI. Hb was positively correlated with SMI, when Hb was ≤ 136. However, the correlation was not statistically significant when Hb was > 136.

Table 4

The correlation between Hb and SMI in male subjects
Models	β (95% CI)	P value
Model I
One line slope	0.015 (0.005, 0.025)	0.004
Model II
Turning point	136
< 136 slope 1	0.035 (0.007, 0.063)	0.016
> 136 slope 2	0.008 (-0.006, 0.022)	0.273
The independent association between the Hb and SMI.
Model I, linear analysis; Model II, non-linear analysis. Adjustment variables: age, SBP, DBP, duration of diabetes.

As shown in Fig. 2, Hb might have some non-linear relationship with SMI in female participants. A two-piecewise linear regression model was shown in Table 5. After adjusting for age, DBP, SBP, and duration of diabetes, Hb was correlated with SMI. However Hb was positively correlated with SMI when Hb was > 122. When Hb was ≤ 122, Hb was negatively correlated with SMI, however, the association was not statistically significant.

Table 5

The correlation between Hb and SMI in female subjects
Models	β (95% CI)	P value
Model I
One line slope	0.010 (0.003, 0.017)	0.009
Model II
Turning point	122
< 122 slope 1	-0.014 (-0.037, 0.008)	0.215
> 122 slope 2	0.019 (0.008, 0.030)	< 0.001
The independent association between the Hb and SMI.
Model I, linear analysis; Model II, non-linear analysis. Adjustment variables: age, SBP, DBP, duration of diabetes.

Our research suggested that Hb was inversely correlated with low muscle mass in T2DM patients. Hb was positively correlated with SMI in male T2DM patients. Hb was positively correlated with SMI, when Hb was > 122 in female T2DM patients. A Chinese longitudinal study of 730 community-dwelling people aged ≥ 65 years showed that low hemoglobin was a risk factor for sarcopenia [14]. This is similar to our study. Multiple mechanisms may be involved between low muscle mass and low Hb: (1) One of the most common symptoms of low hemoglobin is fatigue, which is an important factor limiting physical function [15]. (2) Low hemoglobin levels may lead to local hypoxia of skeletal muscle, thereby compromising muscle strength and (or) performance [16–17]. (3) Hb carries more than 2/3 of the human body’s iron, which is a good indicator of tissue perfusion and iron level, so it may affect the iron utilization of myoglobin [18]. (4) Low Hb and iron deficiency affect the structure and quality of bone and muscle by participating in collagen synthesis and remodeling as well as vitamin D metabolism [19]. Therefore it may be possible to use Hb as a marker of sarcopenia to actively intervene in T2DM patients.

Age, weight, malnutrition, physical inactivity, immnue system defects, and chronic diseases all contribute to the development of sarcopenia [20]. In this present study, compared with subjects with normal muscle mass, those with low muscle mass had higher age, which was in line with our expectation. Meanwhile, low muscle mass group showed lower BMI, TG than normal muscle mass group in T2DM patients, which was contrary to traditional view. Previous study suggested that BMI as a metabolic risk factor was significantly related to loss of skeletal muscle and sarcopenia. In Japan, a study on 183 T2DM patients also showed that the muscle mass of patients with large visceral fat accumulation was significantly lower than that of patients without visceral fat accumulation [21]. However, other studies have found that T2DM patients with low BMI showed an increased risk of sarcopenia [22, 23]. A cross-sectional analysis of 132 T2DM patients aged ≥ 65 years showed that a higher BMI was a protective factor for sarcopenia in elderly T2DM patients [24]. The prevalence of low muscle mass or sarcopenia significantly decreases as BMI increases in T2DM patients [25]. This was similar to our study.

Poor control of blood glucose fluctuation in T2DM may increase the risk of low muscle mass. This present study showed that low muscle mass group had higher HbA1c than normal muscle mass group in T2DM patients; however, the difference was not statistically significant in female T2DM patients. Other investigators also got the similar results. Sugimoto’s study showed that the muscle mass of T2DM with HbA1c ≥ 8% was significantly reduced, and the risk of falls and fractures was increased in future [26]. This may be related to the inflammatory response caused by high blood glucose.

This study has several limitations. First, this study was limited by relatively small sample size, which might limit the generalizability of our outcomes. Secondly, the cross-sectional nature of the data limited the strength of conclusion. Future research should account for longitudinal studies.

To sum up, hemogolobin is inversely correlated with the presence of low muscle mass in T2DM patients.

Author contributions

All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by Sujun Ge, Wenchao Hu. Sujun Ge and Wenchao Hu prepared table 1-5. Fengxia Zhan prepared figures1, 2. The first draft of the manuscript was written by Sujun Ge and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding Statement

No funding.

Conflict of Interest Statement

The authors declare that there is no conflict of interest regarding the publication of this article.

Ethics approval

This study was approved by the ethics board of Qilu Hospital of Shandong University (Qingdao).

Data availability statement

Data are available upon reasonable request.

Acknowledgments

No acknowledgments.

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No competing interests reported.

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Version 1

posted

You are reading this latest preprint version

Association between hemoglobin and low muscle mass in patients with type 2 diabetes mellitus

Status:

Version 1

Abstract

Objective

Method

Result

Conclusion

Figures

Introduction

Materials And Methods

Participants

The Definition Of Low Muscle Mass

Measurements

Statistical analysis

Results

General characteristics of the participants

The Correlation Between Hb And Low Muscle Mass

The Association Between Smi And Other Characteristics

Non-linear Association Between Hb And Smi

Discussion

Declarations

References

Additional Declarations

Status:

Version 1