Clinical characteristics of adolescents and young adults with type 2 diabetes and Traditional Chinese Medicine therapies: a single-center experience in China from 2011 to 2023

Abstract

OBJECTIVE:

To clarify the clinical characteristics of type 2 diabetes in adolescents and young adults (T2DMY) patients, and their treatment strategies involving Traditional Chinese Medicine (TCM) and Western Medicine.

METHODS:

This study was conducted at Dongfang Hospital of Beijing University of TCM. Clinical data of outpatients and inpatients from 2011 to 2023 were retrieved from the electronic medical record database with type 2 diabetes mellitus (T2DM) as the first diagnosis.

RESULTS:

A total of 405 outpatients and 570 inpatients with T2DMY were included in the analysis. Compared with middle aged and elderly T2DM patients (T2DME), T2DMY patients have a higher proportion of diabetes family history and higher body mass index, poorer control of blood glucose, blood lipid, liver and kidney function, and a higher incidence of non-alcoholic fatty liver disease and gout. In terms of anti-diabetes treatment, T2DMY patients are more likely to receive metformin and insulin drugs. In terms of TCM diagnosis and treatment, compared with T2DME patients, T2DMY patients are more frequently diagnosed with the syndrome of phlegm damp trapped spleen, and more herbs such as Fuling (Poria) and Chenpi (Pericarpium Citri Reticulatae) are more frequently used to invigorate the spleen and dispel dampness.

CONCLUSION:

Compared with T2DME patients, T2DMY patients have worse metabolism. In the treatment of TCM, more attention can be paid to the function of the spleen, and the herbal medicine can be used to enhance the function of the spleen and dispell dampness when it is compatible with Qitonifying drugs.

1. INTRODUCTION

In the past decades, diabetes has become a global public health problem. The global prevalence rate of adult diabetes is about 8% (over 90% of them have type 2 diabetes mellitus (T2DM), which is expected to increase to more than 10% by 2040.¹ Although T2DM is an age-related disease, the prevalence of diabetes among young people is increasing. According to a national survey, the total prevalence of diabetes among people under 40 years old in China reached 3.9%.² A Global Burden of Disease Study 2019 from 204 countries and regions showed that the age-standardized incidence rate (per 100 000 population) of T2DM among adolescents and young adults under 40 years of age increased from 117.22 in 1990 to 183.36 in 2019. The age-standardized disability adjusted life years increased from 106.34 in 1990 to 149.61 in 2019, and the age-standardized mortality rate increased from 0.74 in 1990 to 0.77 in 2019.³

Pathological processes related to diabetes, including the development of insulin resistance and the deterioration of β cell function is faster in type 2 diabetes in adolescents and young adults (T2DMY) patients than in middle aged and elderly T2DM patients (T2DME).⁴ Early onset leads to longer lifetime exposure to hyperglycemia, making it more prone to long-term complications.

Traditional Chinese Medicine (TCM) is a valuable scientific and technological resource for treating diseases and promoting human health. In general, the application of Chinese herbal formulas is fundamental to TCM practice, and TCM adopts a holistic approach that often involves choosing a combination of several herbal remedies and other treatments based on a patient's specific characteristics or symptoms. Diabetes is called "Xiaoke" (meaning consumptive thirst) in Chinese medicine. TCM has the characteristics of multi-link, multi-pathway and multi-target in the prevention and treatment of diabetes.⁵

Many studies on the treatment of T2DM and its complications with TCM have been published. Prediabetic patients often prefer TCM interventions, as Chinese herbs exhibit fewer side effects than antidiabetic drugs during this stage. TCM in improving insulin sensitivity, protecting pancreatic β-cells, and promoting insulin secretion,⁶ correcting glucolipid metabolism disorders,⁷ modulating the intestinal flora composition of T2DM patients.⁸

The current goal of clinical precision medicine is to find individual hierarchies with common characteristics, which can be used to optimize disease prediction, prevention, diagnosis, and treatment. Understanding the clinical characteristics and treatment strategies for T2DM in adolescents and young adults will bring us closer to this goal. The World Health Organization defines the age group below 45 years old as young adults, and the Youth Federation defines 18-40 years old as young adults. Many high-impact articles mentioned that the incidence of T2DM in individuals under 40 years is relatively high, with a poor prognosis.^9,10 Therefore, we take 40 years old as a critical point. In this study, we define T2DMY as type 2 diabetes in adolescents and young people under 40 years of age. The purpose is to compare the clinical characteristics and differences between TCM and modern medicine of T2DMY and T2DME patients who visited the Dongfang Hospital of Beijing University of TCM from January 2011 to December 2023, with the aim of providing clinical evidence for the prevention and treatment of T2DMY.

2. MATERIALS AND METHODS

2.1. Study population

Sample Size Calculation: Based on the primary outcome of glycemic control [measured by hemoglobin A1c (HbA1c) levels], we conducted a power analysis to determine the required sample size. Assuming a mean difference of 1.0% in HbA1c between T2DMY and T2DME groups with a standard deviation of 1.5%, and aiming for a power of 80% (β = 0.2) at a significance level of 0.05 (α = 0.05),^3,9 the calculated sample size per group was approximately 384 patients. Considering potential dropouts and data loss, we increased the sample size by 10%, resulting in a target sample size of 422 patients per group.

The data comes from the electronic medical record analysis database of Dongfang Hospital of Beijing University of TCM. The inclusion criteria were: patients with a primary diagnosis of T2DM and age ≤ 40 years. Outpatient and inpatient patients from January 1, 2011, to December 31, 2023, were included. The diagnosis of T2DM is based on the diagnostic and classification criteria of the World Health Organization. Finally, 405 outpatients and 570 inpatients with T2DM were included in the analysis.

To compare the clinical characteristics of T2DM patients under 40 years old, we also included outpatients and inpatients who were over 40 years old and visited Dongfang Hospital of Beijing University of Chinese Medicine at the same time, and compared the clinical characteristics and TCM/Western Medicine treatment strategies of T2DM patients across different age groups. This sample size ensures sufficient statistical power to detect significant differences between the groups while providing reliable and generalizable results.

Personal identifying information (e.g., patient names) was de-identified and replaced with unique codes. Throughout and after the study, individual participants could not be identified or linked to their data.

2.2. Data collection and ethics statement

Through retrospective analysis of the clinical data of patients, the following information was collected: age, gender, course of diabetes, family history of diabetes, laboratory test results, TCM syndromes and drug treatment schemes. For patients who visited multiple times during the study period, we used data from their first visit.

The main hypoglycemic drugs used in this study included metformin, sulfonylureas, α-glucosidase inhibitors (AGis), dipeptidyl peptidase-4 inhibitors (DPP-4is), and insulin.

This study was approved by the Ethics Committee of Dongfang Hospital of Beijing University of Chinese Medicine, with the ethics number of JDF-IRB-2022051002. This study is a retrospective clinical study, which only uses the existing medical records or data, and does not involve the identity or privacy of the subjects, nor does it cause any risk or harm to the subjects. Therefore, the consent of the ethics committee was obtained, and the informed consent of the patient was exempted. Clinical trial number, Consent to Participate, and Consent to Publish declarations: not applicable. Patient and Public Involvement: It was not appropriate to involve patients or the public in the design, conduct, reporting, or dissemination plans of our research.

2.3. Data entry and software analysis

In this study, the software "TCM Inheritance Computing Platform (V3.0)" (Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, China) was used to analyze the data of Chinese herbals used by patients. First, one researcher entered patient information into the software; after data entry, two independent researchers verified the entered data to ensure accuracy. Through the "statistical analysis" module in the software, the frequency of the use of Chinese herb use was calculated, and the data statistics of the four properties, five flavors and meridian tropism of Chinese herbals were carried out. The association rule module was used to analyze the rules of formulation, and the core herbals and herbal combinations were discovered.

2.4. Statistical analysis

Qualitative data are described by frequency and percentage, quantitative data conforming to a normal distribution are described as mean ± standard deviation ($\overline{x}$± s), while those not conforming to a normal distribution are described by median and interquartile range (IQR). The χ ² test or Fisher’s exact test was used for comparison between data sets, and t-test or Wilcoxon rank sum test was used for measurement data. The correlation between risk factors and outcome events was analyzed by logistic regression. The significance level of statistical tests was set at 0.05.

3. RESULTS

3.1. Characteristics of the patients

A total of 975 patients with T2DMY were included in this study, with the youngest age being 15 years. Among them, there were 405 outpatient patients, of whom 64.20% were male; 570 inpatients, 75.09% of whom were male. Outpatient and inpatient T2DME patients over 40 years of age were matched and included in the same period and gender ratio. Compared with T2DME patients, the duration of diabetes in T2DMY patients is shorter (Table 1).

Table 1.

Basic information of patients with T2DMY vs T2DME

Variable	Outpatient					Inpatient
	T2DMY (n = 405)	T2DME (n = 405)	Z value	P value		T2DMY (n = 570)	T2DME (n = 570)	Z value	P value
Male sex (n)	260	260	-	-		428	428	-	-
Age (years)	36 (33, 39)	62 (54, 69)	－24.651	< 0.001		35 (32, 38)	63 (56, 72)	－29.243	< 0.001
Duration of diabetes (months)	36 (8.5, 60)	84 (24, 120)	－4.164	< 0.001		24 (3, 60)	132 (60, 240)	－18.342	< 0.001

Notes: T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients. Qualitative data are described by median and interquartile range.

The patients' family history of diabetes, smoking history, drinking history, and body mass index (BMI) were statistically compared. Because the medical history records of outpatients are not comprehensive, only 1140 inpatients are counted in this part. Compared with T2DME patients, T2DMY patients had a higher proportion of family history of diabetes and a higher BMI, while there was no significant difference in the history of smoking and alcohol consumption (Table 2).

Table 2.

Clinical characteristics of patients with T2DMY vs T2DME

Variable	T2DMY (n = 570)	T2DME (n = 570)	Z/χ 2 value	P value
Family history [positive, n (%)]	150 (26.32)	89 (15.61)	19.699	< 0.001
Smoking history [positive, n (%)]	293 (51.40)	292 (51.23)	0.004	0.953
Drinking history [positive, n (%)]	190 (33.33)	216 (37.89)	2.586	0.108
BMI	28.00 (25.10, 30.79)	25.30 (23.41, 27.75)	-0.6782	<0.001

Notes: T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients; BMI: body mass index. Qualitative data are described by median and interquartile range.

3.2. Multivariate analysis of T2DMY risk

The following risk factors were included in the final calculations: smoking and drinking history, family history of diabetes, and BMI. The results showed that family history of diabetes and BMI were risk factors for T2DMY (Table 3).

Table 3.

Risk factors of T2DMY

Risk factor	P value	OR (95% CI)
Family history	0.002	0.423 (0.247, 0.724)
Smoking	0.967	0.989 (0.593, 1.650)
Drinking	0.398	1.258 (0.739, 2.144)
BMI	< 0.001	0.880 (0.832, 0.931)

Notes: T2DMY: type 2 diabetes in adolescents and young adults patients; OR: odds ratio; CI: confidence interval; BMI: body mass index. The correlation between risk factors was analyzed by logistic regression.

3.3. Patients' glycemic control, lipid profile, and liver and kidney function levels

The statistical results showed that compared with T2DME patients, T2DMY patients had significantly worse glycemic control and HbA1c, as well as higher fasting insulin (FINS) levels (Table 4). The levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in T2DMY patients, and high-density lipoprotein cholesterol (HDL-C) was low. Alanine transaminase (ALT) and uric acid (UA) levels were higher in T2DMY patients than in T2DME patients, whereas urea and cystatin C levels were lower. There was no significant difference in Urine microalbumin (mAlb) between the two groups. After adjusting for the effect of duration of disease, no significant difference in FINS levels was observed between the two groups, while all other indicators remained significantly different.

Table 4.

Laboratory examination indicators for T2DMY and T2DME patients

Clinical index	T2DMY (n = 975)	T2DME (n = 975)	Unadjusted P value	Adjusted P valuea
HbA1c (%)	9.9 (8.1, 11.4)	8.2 (7.1, 9.8)	<0.001	<0.001
FINS (uIU/mL)	9.76 (4.90, 15.98)	7.97 (4.40, 13.09)	0.004	0.057
TC (mmol/L)	4.72 (3.93, 5.42)	3.90 (3.21, 4.80)	<0.001	<0.001
TG (mmol/L)	2.01 (1.41, 3.37)	1.43 (1.00, 1.96)	<0.001	<0.001
HDL-C (mmol/L)	0.97 (0.82, 1.16)	1.11 (0.92, 1.33)	<0.001	<0.001
LDL-C (mmol/L)	3.10 (2.43, 3.82)	2.57 (1.86, 3.18)	<0.001	<0.001
ALT (U/L)	25.5 (16.2, 49.38)	16.45 (11.4, 22.60)	<0.001	<0.001
Urea (mmol/L)	4.50 (3.63, 5.43)	5.60 (4.30, 7.56)	<0.001	<0.001
cystatin C (mg/L)	0.82 (0.70, 0.94)	1.10 (0.93, 1.51)	<0.001	0.002
mAlb (mg/L)	15.37 (7.79, 35.36)	17.13 (6.95, 60.97)	0.154	0.895
UA (μmol/L)	354.6 (289.73, 420.70)	320.65 (259.15, 382.30)	<0.001	<0.001

Notes: T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients; HbA1c: hemoglobin A1c; FINS: fasting insulin; TC: total cholesterol; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; ALT: alanine transaminase; mAlb: microalbumin; UA: uric acid. ^aAdjusted for disease duration. Qualitative data are described by median and interquartile range.

3.4. Occurrence of diabetes comorbidities and complications

In the statistics of diabetic complications (Table 5), the incidence of diabetic nephropathy was higher in T2DME, and after adjusting for the influencing factors of the course of the disease, the incidence of diabetic retinopathy was statistically different. In the diagnosis of comorbidities, after adjusting for the impact of disease duration, T2DME patients had a higher incidence of hypertension and hyperlipidemia, and T2DMY patients had a higher incidence of non-alcoholic fatty liver and gout.

Table 5.

Occurrence of diabetes comorbidities and complications in patients with T2DMY and T2DME (n)

Variable		T2DMY (n = 975)	T2DME (n = 975)	Unadjusted P value	Adjusted P valuea
Complication	Diabetic nephropathy	16	36	0.005	0.452
	Diabetic retinopathy	41	43	0.823	0.018
	Diabetic neuropathy	45	63	0.075	0.113
Comorbidity	Hypertension	131	409	<0.001	<0.001
	Hyperlipidemia	177	321	<0.001	<0.001
	Non-alcoholic fatty liver	132	116	0.277	0.004
	Gout	36	14	0.002	0.031

Notes: T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients. ^aAdjusted for disease duration. Qualitative data are described by median and interquartile range. The correlation between outcome events was analyzed by logistic regression.

3.5. Use of antidiabetic medications

In the use of hypoglycemic drugs. The highest proportion of patients with T2DMY who visited the outpatient clinic used metformin and insulin, and more than patients with T2DME. Among the inpatient patients, T2DME patients had a higher proportion of insulin and AGis treatment, and more than T2DMY patients. For the use of sulfonylureas, the use rate of T2DME patients was higher than that of T2DMY patients in both outpatient and inpatient settings. For the use of Dpp-4is, there was no difference in the frequency of use among patients of different ages (Table 6).

Table 6.

Glucose-lowering medications used in patients with T2DMY and T2DME (n)

Item	Outpatient					Inpatient
	T2DMY (n = 405)	T2DME (n = 405)	χ 2 value	P value		T2DMY (n = 570)	T2DME (n = 570)	χ 2 value	P value
Metformin	154	92	22.442	<0.001		307	284	1.859	0.173
AGis	53	43	1.182	0.277		219	305	26.121	<0.001
Sulfonylureas	11	27	7.068	0.008		29	83	28.872	<0.001
DPP-4is	39	46	0.644	0.422		151	179	3.344	0.067
Insulin	64	30	13.912	<0.001		370	430	15.088	<0.001

Notes: T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients; DPP-4is: dipeptidyl peptidase-4 inhibitors. The χ² test or Fisher’s exact test was used for comparison between data sets.

3.6. Frequency of use of Chinese herbal medicine

A total of 370 Chinese herbs were used in the Chinese medicine prescriptions of the included patients, and the top 10 herbs with the highest frequency of use (Freq) are shown in supplementary Table 1. Huangqi (Radix Astragali Mongolici), Fuling (Poria), Danshen (Radix Salviae Miltiorrhizae), and Gegen (Radix Puerariae Lobatae) were the most frequently used herbs among outpatients. Among inpatients, Baizhu (Rhizoma Atractylodis Macrocephalae), Huangqi (Radix Astragali Mongolici), and Gancao (Radix Glycyrrhizae) were the most frequently used herbs. There was no significant difference in herb use frequency between different age groups.

3.7. The meridians of herbal medicine

According to the statistics of the meridians tropism of 370 herbs involved, the drugs were classified into 12 meridians, and the frequency of occurrence of meridians was counted. The results showed that the spleen meridian was the most common meridian of the drugs used frequently in T2DMY outpatients and inpatients, while the liver meridian was the most common meridian of the drugs used frequently in T2DME outpatients and inpatients. In addition, the lung meridian and the stomach meridian were also the high-frequency meridian items of medication in each group (Figure 1).

Figure 1. Radar map of the meridians of herbs.

The radar map of the distribution frequency of herbs belonging to the twelve meridians. T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients.

3.8. Four properties and five flavors characteristics of herbal medicine

The properties and flavors of 370 herbs involved in this study were classified. Among outpatients of different ages, cold drugs were the most common, followed by warm drugs. In inpatient patients, warm drugs were the most common, followed by cold drugs. These results indicated that cold and warm herbs were the main types used for all T2DM patients (Figure 2A).

Figure 2. Radar map of the frequency of herbal medicine belonging to the four properties and five flavors attributes.

A: four properties radar map of herbal medicine; B: five flavors radar map of herbal medicine. T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients.

In the distribution of the five flavors of herbal medicine, sweet herbs were the most commonly used in outpatients at different ages, followed by bitter herbs. In inpatient patients, bitter medicine was the most, followed by sweet medicine. The results showed that sweet and bitter taste drugs were the main herbs for all T2DM patients (Figure 2B).

3.9. Analysis of efficacy categories of herbal medicine

According to the efficacy category statistics of herbal medicines for the treatment of T2DM, the top five efficacy categories of herbs with the highest use frequency in each group are shown in supplementary Figure 1. For patients of all ages (both outpatients and inpatients), the high-frequency efficacy categories were highly similar, mainly including deficiency-tonifying herbs, heat-clearing herbs, and blood-activating and stasis-resolving herbs.

3.10. High frequency herbal combinations

Based on the association rules, with the support level of 20% and the confidence level of 60%, the top 5 high-frequency herbal combinations were identified by sorting the combination frequencies in descending order (supplementary Table 2). Among outpatients, the most frequently used combinations were Fuling (Poria), Gegen (Radix Puerariae Lobatae), and Danshen (Radix Salviae Miltiorrhizae), each combined with Huangqi (Radix Astragali Mongolici). Among inpatients, the most frequently used combination was Fuling (Poria) and Huangqi (Radix Astragali Mongolici) combined with Baizhu (Rhizoma Atractylodis Macrocephalae). The common herbal combinations were similar between T2DM patients of different ages, but significantly different between outpatients and inpatients.

The most commonly used herbs, [e.g., Baizhu (Rhizoma Atractylodis Macrocephalae) and Fuling (Poria)] are known for their spleen-invigorating and dampness-dispelling effects and are often combined to enhance the efficacy of spleen strengthening and dampness drying. For instance, the combination of Huangqi (Radix Astragali Mongolici) and Danshen (Radix Salviae Miltiorrhizae) is frequently used to tonify Qi and activate blood circulation, which can enhance the therapeutic effects of improving microcirculation and preventing diabetic complications.¹¹ These compatibility schemes are consistent with the TCM principles of syndrome differentiation and treatment, and their efficacy has been verified by both traditional clinical practice and modern pharmacological studies.

3.11. High frequency TCM syndromes

A TCM syndrome is an abstract summary of the pathological changes of a disease at a specific stage, which can reveal the essence of the disease more deeply and comprehensively. The TCM syndrome characteristics of patients were statistically analyzed. Among outpatients and inpatients, the characteristics and frequencies of the top five high-frequency syndromes are shown in supplementary Figure 2. Among the included patients (both outpatients and inpatients of different ages), the syndrome of dual deficiency of Qi and Yin was the most common. Second, outpatients with T2DMY were more likely to present with dampness encumbrance, and T2DME patients were more likely to present with liver-kidney depletion syndrome. In contrast, inpatiens were more likely to present with phlegm and blood stasis blocking collaterals.

3.12. Comparison of TCM syndrome distribution between different genders

Select the top 7 syndrome types with high frequency, and gender-based differences in syndrome proportions were analyzed. As shown in Table 7, the proportion of phlegm damp trapped spleen syndrome in T2DMY patients was higher than that in T2DME patients (P < 0.001); The proportion of T2DME patients was higher than that of T2DMY patients with phlegm and blood stasis blocking collaterals (P < 0.001) and blood stasis blocking collaterals (P < 0.001). Dampness heat internal retention (P = 0.001) and Yin deficiency and hyperactivity of fire (P = 0.002) syndrome types, the proportions were higher in male patients than in female patients.

Table 7.

Proportion of syndrome distribution in different genders (%)

Syndrome type	T2DMY (n = 975)			T2DME (n = 975)
	Male	Female		Male	Female
Dual deficiency of Qi and Yin	45.93	42.16		40.41	40.42
Phlegm Damp trapped Spleen	8.28	6.97		1.16	0.70
Phlegm and blood stasis blocking collaterals	8.87	7.32		14.24	14.63
Dampness-heat internal retention	5.96	3.14		7.27	2.44
Spleen deficiency with dampness encumbrance	4.51	5.23		2.47	2.44
Blood stasis blocking collaterals	4.36	4.18		11.63	7.67
Yin deficiency and hyperactivity of fire	5.38	1.74		3.49	1.39

Notes: T2DMY: type 2 diabetes in adolescents and young adults patients; T2DME: type 2 diabetes in middle aged and elderly patients.

4. DISCUSSION

It has been shown that T2DM patients with onset in adolescents and young adults under the age of 40 years represent a unique pathological entity, characterized by a more aggressive phenotype than T2DM in later life. According to this retrospective study, family history of diabetes and high BMI are risk factors for T2DMY. Previous studies have also shown that the concordance of T2DM in monozygotic twins is high,¹² and the increased risk of T2DM associated with family history reflects the common genetic burden and environmental exposure. Regarding the relationship between BMI and T2DMY, on the one hand, although high BMI is a risk factor for T2DMY, some children and adolescents with T2DM have relatively low BMI, highlighting the etiological complexity of T2DM. On the other hand, the location of obesity is critical, and fatty liver degeneration and visceral fat are important risk factors for T2DM,¹³ which is consistent with the results of the present study, in which the prevalence of non-alcoholic fatty liver disease was higher in T2DMY patients than in T2DME patients.

The disease course of T2DMY is more rapid and destructive than that of T2DME, and the high incidence of comorbidities and complications impairs patients’ quality of life in the long term.¹ The renal and neurological complications of T2DMY patients began to appear within 5 years after the diagnosis of T2DM,¹⁴ and the risk of non-fatal cardiovascular disease in T2DMY patients was also higher than that in T2DME patients,¹⁰ and recent studies have shown that nearly 60% of T2DMY patients have at least one microvascular complication.⁴ The results of this study also showed that compared with T2DME patients, T2DMY patients had worse blood glucose, blood lipid levels, and liver and kidney function control. In terms of comorbidities and complications, T2DME patients had a higher prevalence of hypertension, hyperlipidemia, and diabetic retinopathy, while T2DMY patients had a higher prevalence of nonalcoholic fatty liver disease and gout. Notably, despite worse lipid profiles in T2DMY patients, the prevalence of hyperlipidemia was lower in T2DMY than in T2DME patients. This may be explained by two factors: first, although TC, HDL-C, and LDL-C levels were less favorable in T2DMY patients, their quartile ranges remained within the normal reference range; second, T2DME patients with hyperlipidemia were more likely to receive drug interventions to control lipid levels.

Despite increasing attention being paid to the epidemiological investigation of T2DMY, young-onset T2DM is characterized by poor response to currently approved drugs.¹⁵ Additionally, age-related and socioeconomic factors pose significant challenges to treatment adherence and disease management. Western Medicine primarily relies on symptoms and laboratory tests to classify diseases and often applies standardized treatments for the same disease type. In contrast, TCM emphasizes syndrome differentiation and treatment, allowing for individualized interventions even for the same disease.¹⁶

In the clinical practice of TCM, different syndromes with different metabolic characteristics and susceptibility to treatment. The results of this study show that for the distribution of TCM Syndromes of different ages, the most prevalent syndrome is "dual deficiency of Qi and Yin ". Qi deficiency is characterized by symptoms such as mental fatigue, lassitude, palpitations, and spontaneous sweating; Yin deficiency is associated with internal heat, manifested as polydipsia, polyphagia, preference for cold drinks, irritability, and insomnia. Excessive internal heat causes fluid consumption, so therapeutic strategies for such patients focus on nourishing Yin and clearing heat, using herbs such as Gegen (Radix Puerariae Lobatae), Huanglian (Rhizoma Coptidis), and Dihuang (Radix Rehmanniae).

Second, patients with T2DMY are prone to spleen-deficiency and phum-dampness, and the spleen meridian is the most common target meridian for drug selection. According to the theory of TCM, insufficient spleen Qi leads to transportation and chemical dysfunction, affecting the transport of nutrients and water metabolism. The patients with T2DME are prone to the syndrome of phlegm and blood stasis obstructing collaterals, and the liver meridian is the most frequently used drugs. The blood stasis syndrome is mainly manifested as microcirculation changes and vascular endothelial damage, resulting in slow blood flow in patients, thus causing microvascular lesions and even cardiovascular and cerebrovascular diseases.

According to the types of high-frequency syndromes, T2DM is a mixture of deficiency syndrome and excess syndrome. Correspondingly, the high-frequency herbs are mainly classified into three efficacy categories: deficiency-tonifying, heat-clearing, and blood-activating and stasis-resolving. In our statistics, the most commonly used herbal medicine for T2DMY is Baizhu (Rhizoma Atractylodis Macrocephalae), which functions to invigorate the spleen, tonify Qi, dry dampness, and promote diuresis. Most often combined with Fuling (Poria) to enhance the effects of spleen strengthening and dampness drying. Modern pharmacological studies have shown that atractylenolide I and atractylenolide II, the extracts of atractylenolide, have a significant stimulatory effect on glucose uptake in C2C12 cells of mouse skeletal muscle and can improve TNF-α induced insulin resistance in these cells.¹⁷

The most commonly used herbal medicine for T2DME is Huangqi (Radix Astragali Mongolici), which is the most commonly used representative of the category of invigorating Qi. It can invigorate Qi and generate blood, promote body fluid circulation, and treat spleen deficiency. Most commonly used with Fuling (Poria), it can replenish Qi and strengthen the spleen. It is most frequently combined with Fuling (Poria) to enhance Qi-tonifying and spleen-strengthening effects; when combined with Danshen (Radix Salviae Miltiorrhizae), it can enhance the latter’s efficacy in activating blood circulation and resolving stasis. Modern pharmacological studies have shown that Huangqi (Radix Astragali Mongolici) has antioxidant and anti-inflammatory effects,¹⁸ astragaloside IV can alleviate insulin resistance, reduce blood glucose and triglyceride levels, astragalus polysaccharide can promote islet cell proliferation, inhibit islet β cell death,¹⁹ and Huangqi (Radix Astragali Mongolici) can effectively prevent kidney injury caused by T2DM.²⁰

In addition to drugs for invigorating Qi and promoting blood circulation and removing blood stasis, the second most common type of prescription for T2DM is heat-clearing drugs, such as Huanglian (Rhizoma Coptidis) and Jinyinhua (Flos Lonicerae). Since ancient times, Huanglian (Rhizoma Coptidis) has been known as "the holy medicine of lowering blood glucose".²¹ Modern pharmacology shows that Huanglian (Rhizoma Coptidis) can improve glucose metabolism, insulin resistance, pancreatic islets β Cells, regulating intestinal flora and other ways to exert antidiabetic effects.²² The high-frequency use of these Chinese herbs in T2DMY patients can be attributed to their multi-target effects on improving metabolic abnormalities. These herbs not only enhance glucose and lipid metabolism but also reduce inflammation and improve microcirculation, which are critical for managing the complex pathophysiology of T2DMY. The combination of these herbs in TCM formulas provides a holistic approach to treating T2DMY, addressing both deficiency and excess syndromes. Future research should focus on elucidating the specific molecular mechanisms and optimizing the use of these herbs in clinical practice.

To control blood glucose, Chinese patients often adopt the method of integrated traditional Chinese and Western Medicine for holistic intervention. The results of this study highlight the importance of such integration in T2DMY treatment. The high-frequency use of certain Chinese herbs, such as Baizhu (Rhizoma Atractylodis Macrocephalae) and Fuling (Poria) suggests that invigorating the spleen and dispelling dampness are core TCM strategies for T2DMY. These herbs can complement Western Medicine by improving overall metabolic status and reducing complication risks. For example, the high-frequency combination of Baizhu (Rhizoma Atractylodis Macrocephalae) and Fuling (Poria) reflects their synergistic effects in improving insulin resistance, as demonstrated in prior studies.¹⁶ Combining these herbs with metformin may enhance glycemic control, suggesting a potential integrative therapy for T2DMY. Among T2DMY patients using metformin (76%), 62% were concurrently prescribed Huangqi (Radix Astragali Mongolici), which may mitigate metformin-induced gastrointestinal side effects.¹⁸

The strategy, concept, and practice of integrated traditional Chinese and western medicine are forming a perfect medical and health system. Due to the strong complementarity of the two medical systems, patients can be provided with more accurate disease descriptions, new diagnostic methods and individualized diagnosis and treatment plans. Further research is needed to explore the optimal integration of Traditional Chinese and Western Medicine in the management of T2DMY, including randomized controlled trials to evaluate the efficacy and safety of combined treatment regimens. The results of this study further clarify the clinical characteristics and treatment of patients with T2DMY, and provide a reference for clinical diagnosis and treatment of Traditional Chinese and Western Medicine.

Although this retrospective study provides valuable insights into T2DMY characteristics and TCM treatment patterns, prospective cohort studies are needed to validate these findings. Future work could include: (a) A 12-month follow-up of T2DMY patients receiving TCM/ Western integrated therapy to assess long-term outcomes. (b) Randomized controlled trials comparing TCM herb combinations [e.g., Huangqi (Radix Astragali Mongolici) + Fuling (Poria)] with standard Western Medicine care.

In conclusion, this study indicates that compared to T2DME patients, T2DMY patients have poorer metabolic conditions, and the TCM syndrome of phlegm damp trapped spleen is more significant. After T2DM diagnosis, timely combined TCM-Western Medicine intervention for complications is necessary; additionally, herbs for invigorating the spleen and dispelling dampness should be administered appropriately to improve patients’ overall health status and prevent complications.

5. SUPPORTING INFORMATION

Supporting data to this article can be found online at http://www.journaltcm.com.

Funding Statement

Supported by the Fundamental Research Funds for the Central Universities: Study on the Mechanism of Chaibei Zhixian Decoction in Treating Refractory Epilepsy through the Nitric Oxide Synthase- Reactive Oxygen Species-Ferroptosis Pathway (No. 2025-JYB-XJSJJ041)