Biochemical markers to detect protein malnutrition in type 2 diabetes and liver cirrhosis patients

Abstract

The study aimed to evaluate blood biochemical markers in individuals with type 2 diabetes (T2D) and liver cirrhosis (LC) to discover if they may be utilized to assess their nutritional status, specifically protein malnutrition (PM). A retrospective examination of 500 T2D patients referred to the hospital from January 2022 to December 2023 was performed. After that, participants were split into 2 groups: LC and non-LC. The research comprised T2D individuals with LC. We used their medical data and referring physician reports. Two hundred thirty-five (47%) individuals diagnosed with both T2D and LC were included in the study out of a total of 500 patients referred to Madinah Hospital. The LC group had greater average age, body mass index (BMI), fasting blood glucose, hemoglobin A1c, insulin resistance, and triglycerides as compared to other T2D patient groups without LC. Two hundred thirty-five people with LC were evaluated nutritionally using biomarkers including total protein, albumin, urea, creatinine, and transferrin, which can be a useful evaluation method. A 53.2% of individuals with LC and T2D had PM. A 47% of 500 individuals with T2D and LC. LC had elevated levels of BMI, lipids, liver enzymes, and total bilirubin. A 53.2% had PM as shown by biochemical markers, which might be useful in evaluating patients’ nutritional status. PM correlated with older age, decreased hemoglobin levels, reduced total protein, albumin, and transferrin but high ALP with high BMI index (obese). These findings can assist T2D with LC specialists develop better nutritional management and quality of life methods.

1. Introduction

Chronic liver disease constitutes a major health problem in the Kingdom of Saudi Arabia (KSA).^[1,2] Liver diseases, especially liver cirrhosis (LC) have reached dangerous levels among Saudi adults and are impacting the expenses of health care. Based on the latest World Health Organization data issued in 2018, liver disease deaths in KSA reached 3209 or 3.08% of total deaths. The age-adjusted death rate of 20.24 per 100,000 population ranks Saudi Arabia #71 in the world. Studies demonstrated that LC constituted the major cause of chronic liver diseases diagnosed by liver biopsy.^[3] This was comparable with reports from Western and Eastern regions and Riyadh.^[4–6]

Diabetes mellitus (DM) is a persistent illness that has exhibited a rise in both frequency and occurrence globally in recent decades. Type 2 diabetes mellitus (T2D) accounts for a majority of diabetes cases, ranging from 90% to 95%.^[7,8] Research indicates that certain populations, such as those residing in KSA, exhibit a greater susceptibility to the development of this condition. The pathophysiological underpinnings of T2D are rooted in insulin resistance (IR), a condition characterized by an augmented demand for insulin in the peripheral tissues (namely, muscle and adipose) to attain euglycemia and to curtail hepatic glucose production. This has been well documented in the literature.^[9] Recent research has established a strong correlation between IR and various other liver illnesses. Chronic hepatitis, which can be attributed to various factors such as hepatitis B virus, hepatitis C virus, hemochromatosis, and cirrhosis, has been found to correlate with IR. Certain authors have documented the occurrence of “hepatogenous diabetes,” a condition that has been acknowledged by the World Health Organization as a distinct entity that pertains to the emergence of T2D as a result of cirrhosis.^[10] According to research, a significant proportion of individuals diagnosed with cirrhosis, up to 96%, may exhibit glucose intolerance, while approximately 30% may present with clinical diabetes.^[11] The present discourse revolves around the potential of T2D to act as a risk factor for the advancement and onset of liver disease, in the absence of other metabolic syndrome-related risk factors such as obesity and hypertriglyceridemia.^[12,13] Conversely, diabetes that arises as a complication of cirrhosis is referred to as “hepatogenous diabetes” and is not acknowledged by the American Diabetes Association and the World Health Organization as a distinct autonomous condition.^[14] Prior studies have documented a notable incidence of hepatic disorders among individuals with diabetes and a significant occurrence of diabetes among those with liver disease.^[13,14]

Previous studies have indicated that individuals diagnosed with LC commonly experience protein malnutrition (PM).^[15] The incidence of malnutrition is widespread across all forms of LC, ranging from 20% in compensated liver disease to over 80% in decompensated liver disease.^[16] This condition is linked to a heightened risk of complications and elevated short- and long-term mortality rates.^[16] Additionally, a research study was conducted to examine the frequency of malnutrition among elderly individuals with diabetes and its impact on their prognosis. The study revealed that 39.1% of patients were at risk of malnutrition, while 21.2% of patients were diagnosed with malnutrition. According to the findings of a multivariate analysis, malnutrition was found to be significantly associated with female gender, age, and the presence of diabetic complications.^[17] The prevalence of T2D and LC in Saudi Arabia is estimated to be 16.4% and 45.5%, respectively among the population.^[18,19] However, there is limited knowledge regarding the nutritional status and biochemical markers among these patients, particularly in the Madinah region. One purpose of this study was to understand if some biochemical markers may help assess PM in individuals with type 2 diabetes (T2D) and LC.

2. Materials and methods

We conducted a retrospective analysis of the medical records of 500 patients diagnosed with T2D, who were referred to our hospital between January 2022 and December 2023 (Fig. 1). These patients were categorized into 2 distinct cohorts based on the presence or absence of LC, as documented in their medical records:

Figure 1.

The study flow chart.

1. Patients with LC: this group comprised individuals who had a confirmed diagnosis of LC in addition to T2D. The diagnosis of cirrhosis was verified through clinical records, which included medical history, laboratory results, imaging studies (such as ultrasound or CT scans), and reports from referring physicians. This ensured that only patients with a well-documented cirrhosis diagnosis were included in the LC cohort.

2. Patients without LC: the second group included patients with T2D who had no documented diagnosis of LC. Their medical records were reviewed to confirm the absence of cirrhosis, ensuring that no signs or diagnostic findings suggestive of liver disease were present. Patients with any indication of liver disease were excluded from this cohort to maintain clear group distinctions.

2.1. Group assignment and exclusion criteria

To maintain consistency and avoid confounding factors, we applied several exclusion criteria during the group assignment process:

• Nationality: non-Saudi patients were excluded to reduce potential variability due to different healthcare access or genetic backgrounds.

• Age: patients under 18 years of age were excluded, as pediatric cases of T2D and LC present different clinical considerations compared to adults.

• Mental health: patients with severe mental disorders, such as psychosis or major depression, were excluded due to potential issues with adherence to treatment or complications that could skew outcomes.

• Advanced liver complications: individuals with severe encephalopathy or hepatomegaly were excluded, as these conditions could confound the analysis of the cirrhosis cohort by representing more advanced disease stages.

• ICU admissions and nutrition support: patients admitted to the ICU who were receiving nutritional support were excluded to prevent bias, as critical illness and artificial nutrition could significantly influence the metabolic and clinical outcomes being studied.

2.2. Data collection

In addition to assigning patients to the appropriate cohort, we collected comprehensive demographic and clinical data from patient records. This included:

• Demographic information: age, gender, and nationality.

• Medical history: data on comorbidities such as hypertension, dyslipidemia, renal disease, cardiovascular disease, and family history of T2D and dyslipidemia were extracted from the patient files. This information was used to control for potential confounders and to better understand the baseline characteristics of each group.

The clear assignment criteria and strict exclusion process were implemented to ensure robust comparisons between the 2 groups, minimizing bias and maximizing the reliability of our findings.

PM is clinically diagnosed based on the patient’s medical history and anthropometric measurements, which include height, weight, and body mass index (BMI) measurements. Typically, blood tests revealed anemia (anemia is defined by the World Health Organization as hemoglobin (HB) levels of <7.7 mmol/L (13 g/dL) in men and 7.4 mmol/L (12 g/dL) in women^[20]), low serum protein and albumin levels, and aberrant liver function.^[21] Nutrition status was assessed based on evaluating the biomarker levels related to PM in LC patients.

2.2.1. Rationale for biochemical markers to evaluate PM

The biochemical markers used in this study, such as serum protein, albumin, and HB, were selected because they are widely recognized indicators of PM, especially in patients with LC. These markers were chosen based on their clinical relevance, as LC often leads to reduced protein synthesis and impaired liver function, which directly affects serum protein and albumin levels. Additionally, anemia is a common complication in cirrhotic patients, making HB a crucial marker for evaluating nutritional status in this context.

2.2.2. Biochemical markers reflect PM

Biochemical markers provide a valuable objective measure of nutritional status. For instance:

• Serum protein and albumin levels reflect the liver’s ability to synthesize proteins, which is often diminished in cirrhotic patients due to impaired liver function.

• Low HB levels (anemia) are another common feature in patients with PM, as protein deficiency can lead to reduced production of HB, affecting oxygen transport and overall metabolic function.

By evaluating these markers, we were able to assess the degree of malnutrition objectively, offering a practical and clinically applicable method of assessing PM in cirrhotic patients.

BMI was calculated as weight (kg) divided by height in meters square (m²). Classification of BMI was based on the World Health Organization criteria. BMI was classified as underweight (<18.5 kg/m²), normal (18.5–25.0 kg/m²), overweight (25.0–29.9 kg/m²), or obese (>30.0 kg/m²).^[22]

2.3. Laboratory investigations

From laboratory records for LC patients, we evaluated the levels of hemoglobin (Hb), C-reactive protein, fasting blood sugar (FBG), insulin, total cholesterol, triglyceride (TG), hemoglobin A1c (HbA1c), liver enzymes; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin (direct and indirect), total proteins, albumin, total bilirubin, urea, creatinine, transferrin, and lipid profile that were analyzed previously by using Automated Immunoassay Analyzer according to the manufacturer’s instructions.

The Homeostasis Model Estimation of Insulin Resistance index, which involves the multiplication of fasting insulin levels in Uµ/mL by fasting glucose levels in mg/dL and dividing the result by 405, was employed to assess the extent of IR. The healthy range is considered to be within the values of 0.5 to 1.4. If the patient’s readings are below 1.0, it can be inferred that they exhibit insulin sensitivity, a favorable physiological condition. According to the source,^[23] an IR value exceeding 1.9 is indicative of early stages, while a value >2.9 suggests high levels of IR (Fig. 1).

2.4. Disclosure of ethical statements

Approval of the research protocol: the study was conducted with ethical clearance obtained from the Ethical Committee at the College of Applied Medical Sciences, Taibah University, Madinah. Additionally, ethical approval was granted by the Institutional Review Board (IRB), General Directorate of Health Affairs in Madinah, with approval number IRB022-22.

2.5. Informed consent

The ethics committee excluded the retrospective analysis of medical records from informed consent, which involved anonymization of all data.

2.6. Statistical analysis

Data analysis was conducted using SPSS, version 26 (Chicago, United States). To test the normality of the data, we applied the Kolmogorov–Smirnov test. The results indicated that the data showed a reasonably good fit with the normal distribution, supporting the use of parametric tests in our analysis. Additionally, we visually inspected Q–Q plots, which further confirmed that the distribution of the data was appropriate for parametric testing (data not shown). Quantitative variables were summarized as frequencies, percentages, means, and standard deviations. The independent Student t test was used to assess mean differences between study groups. To mitigate the risk of type I errors due to multiple comparisons, we applied the Bonferroni correction to adjust P-values for the biochemical markers evaluated (data not shown).

To evaluate associations between predictor variables (both categorical and continuous) and PM in hepatic cirrhosis patients with T2D, we employed logistic regression analysis. Adjusted odds ratios and 95% confidence intervals were provided. A P-value threshold of ≤.05 or ≤.001 was considered statistically significant.

3. Results

The present study involved the analysis of a total of 500 patients with T2D, comprising 249 males and 251 females. The cohort exhibited a 47% prevalence of LC, with a sample size of 235 patients with T2D. Table 1 presents the fundamental clinical characteristics of the study cohort, categorized based on the presence or absence of LC. In comparison to the non-LC cohort, the LC cohort exhibited a higher mean age (P < .05) and statistically significant elevations in FBG, HbA1c, IR, BMI, TGs, ALT, AST, ALP, De Ritis ratio (AST/ALT ratio > 1) and total bilirubin, while concurrently displaying lower levels of HB, albumin, transferrin, and total protein (all P < .001). The LC group showed a significant increase in serum high-sensitivity C-reactive protein levels compared to the non-LC group (22.9 ± 4.26 g/dL vs 9.3 ± 3.32 g/dL, P < .001) along with a higher BMI in the overweight category within the LC group (29.5 ± 6.55 kg/m² vs 24.5 ± 5.55 kg/m², P < .001) (Table 1).

Table 1.

Clinical and biochemical characteristics of patients with and without liver cirrhosis (n = 500).

Parameter	Patients without liver cirrhosis, n = 265 (53%)	Patients with liver cirrhosis, n = 235 (47%)	P-value
Age (years)	47.45 ± 10.23	55.55 ± 11.18	<.05 *
Gender (male/female)	132/133	117/118	–
FBG (mmol/L)	10.91 ± 2.41	13.61 ± 2.22	.001 **
HbA1c (%)	8.5 ± 2.37	10.2 ± 2.41	.002 **
Insulin Uµ/mL	35.11 ± 2.51	36.91 ± 2.12	.01 *
IR	17.2 ± 4.51	22.2 ± 5.81	<.001 **
Hemoglobin (mmol/L)	12.54 ± 3.21	6.1 ± 1.10	.001 **
LDL-C (mmol/L)	2.21 ± 0.31	2.41 ± 0.42	>.05
HDL-C (mmol/L)	3.54 ± 1.32	3.64 ± 1.21	>.05
Total cholesterol (mmol/L)	5.17 ± 1.29	5.20 ± 1.41	>.05
Triglycerides (TG) (mmol/L)	1.64 ± 1.11	2.9 ± 1.12	.001 **
BMI (kg/m2)	24.5 ± 5.55	29.5 ± 6.55 †	<.001 **
hs-CRP (mg/L)	9.3 ± 3.32	22.9 ± 4.26	.001 **
Albumin (g/dL)	5.54 ± 1.99	3.2 ± 1.3	.002 **
Total Protein (g/dL)	6.5 ± 1.87	5.3 ± 1.4	.001 **
AST (IU/L)	33.4 ± 6.55	72.21 ± 13.24	<.001 **
ALT (IU/L)	40.3 ± 10.26	66.89 ± 12.54	<.001 **
ALP (IU/L)	55.5 ± 11.16	133 ± 10.36	<.001 **
AST/ALT ratio	0.8 ± 0.4	1.1 ± 0.9 ††	<.05 *
Total bilirubin (mg/dL)	0.13 ± 0.11	1.5 ± 0.51	.001 **
Urea (mmol/L)	3.5 ± 1.16	3.4 ± 1.12	>.05
Creatinine (mg/dL)	0.9 ± 0.6	1.4 ± 0.9	.001 **
Transferrin (mg/dL)	300 ± 10.14	200 ± 9.46	<.001 **

Values are mean ± standard deviation, and P-value obtained from Independent Student t test. Bold values are statistically significant.

ALP = alkaline phosphatase, ALT = alanine transaminase, AST = aspartate transaminase, BMI = body mass index, FBG = fasting blood glucose, HbA1c = hemoglobin A1c, HDL-C = high density lipoprotein, hs-CRP = high-sensitivity C-reactive protein, IR = insulin resistance, LDL-C = low-density lipoprotein.

^* P < .05.

^** P < .001.

^† BMI indicated as overweight (25.0–29.9 kg/m²).

^†† AST/ALT ratio = too high indicative of cirrhosis.

In addition, an investigation was conducted on the nutritional status of 235 individuals diagnosed with LC. This was achieved by analyzing biomarkers associated with PM, including low HB levels, abnormal liver function, and reduced serum protein, albumin levels, and transferrin. The study revealed that 53.2% of the participants were affected by PM, while 46.8% exhibited normal levels, as presented in Table 2.

Table 2.

Protein-malnutrition (PM) prevalence in LC patients with T2D (n = 235).

PM category	Frequency	Percentage
Malnourished (%)	125	53.2
Normal (%)	110	46.8

The frequency (percentage) of variables, bold values were considered the highest frequency (percentage).

LC = liver cirrhosis, T2D = type 2 diabetes.

The study conducted a comparison of baseline characteristics between LC patients (n = 235) with and without PM. The study determined that the presence of PM significantly impacted specific blood biomarkers in patients, resulting in decreased levels of HB, total protein, albumin, and transferrin (all P < .001), especially when combined with a high BMI (P < .001) compared to patients without PM. On the other hand, there was a notable rise in FBG and ALP levels (P < .001) in the PM group as illustrated in Table 3.

Table 3.

Comparison of baseline characteristics between patients with protein malnutrition (PM) and without PM (n = 235).

Parameter	Patients without PM n = 110	Patients with PM n = 125	P-value
Age (years)	48.45 ± 11.13	55.45 ± 12.12	<.05 *
Gender (male/female)	66/44	51/74	–
FBG (mmol/L)	8.91 ± 2.81	11.31 ± 2.42	<.001 **
HbA1c (%)	7.2 ± 2.37	8.7 ± 2.51	.001 **
Hemoglobin (mmol/L)	6.2 ± 1.10	5.2 ± 1.11	.001 **
Triglycerides (TG) (mmol/L)	2.8 ± 1.11	2.9 ± 1.10	>.05
BMI (kg/m2)	25.4 ± 6.52	31.5 ± 7.15 †	<.001 **
hs-CRP (mg/L)	21.6 ± 4.16	21.9 ± 4.26	>.05
Albumin (g/dL)	3.5 ± 1.3	2.2 ± 1.1	.001 **
Total protein (g/dL)	5.63 ± 1.2	3.2 ± 1.2	<.001 **
AST (IU/L)	72.31 ± 14.21	72.21 ± 11.24	>.05
ALT (IU/L)	66.79 ± 11.44	66.78 ± 12.44	>.05
ALP (IU/L)	132 ± 10.26	145 ± 11.26	.003 **
Creatinine (mg/dL)	1.4 ± 0.9	1.3 ± 0.8	>.05
Transferrin (mg/dL)	200 ± 8.46	180 ± 7.26	<.001 **

Values are mean ± standard deviation. P-value obtained from Independent Student t test. Bold values are statistically significant.

ALP = alkaline phosphatase, ALT = alanine transaminase, AST = aspartate transaminase, BMI = body mass index, FBG = fasting blood glucose, HbA1c = hemoglobin A1c, HDL-C = high density lipoprotein, hs-CRP = high-sensitivity C-reactive protein, IR = insulin resistance, LDL-C = low-density lipoprotein.

^* P < .05.

^** P < .001.

^† BMI indicated obese (>30.0 kg/m²).

Table 4 presents the multivariate analysis-derived OR and 95% confidence intervals for factors with a P-value of <.05 in the logistic regression analysis. The study revealed that older age (P = .03), lower levels of HB, total protein, and albumin (P < .05), and increased levels of ALP (P = .04) were statistically significant prognostic indicators associated with the occurrence of PM in individuals with LC.

Table 4.

Logistic regression analysis of factors contributing to the presence of protein malnutrition (PM) in liver cirrhosis (LC) patients.

Variables	Odd ratio (OR)	(95% CI)	P-value
Age (years)	8.33	(5.10–10.34)	.03*
Hemoglobin (mmol/L)	9.69	(4.11–11.37)	.02*
Total cholesterol (mmol/L)	1.12	(0.10–1.31)	>.05
Triglycerides (TG) (mmol/L)	5.22	(2.22–6.23)	.04*
BMI (kg/m2)	4.21	(1.21–5.14)	.05*
Albumin (g/dL)	9.27	(3.19–11.21)	.01*
Total Protein (g/dL)	9.49	(4.33–11.34)	.01*
ALP (IU/L)	5.39	(2.19–7.36)	.04*
Total bilirubin (mg/dL)	1.32	(1.01–2.11)	>.05
Creatinine (mg/dL)	1.77	(1.01–2.54)	>.05
Transferrin (mg/dL)	5.89	(2.79–8.66)	.04*

ALP = alkaline phosphatase, BMI = body mass index, CI = confidence interval.

^* P < .05, logistic regression analysis.

4. Discussion and conclusion

The current investigation consisted of the examination of a cohort of 500 individuals diagnosed with T2D. The cohort consisted of 249 male participants and 251 female individuals. In the cohort, the observed prevalence of LC was 47% among 235 people, with an average age of 55.55 years. The LC cohort demonstrated a higher average age (P ≤ .05) and statistically significant increases in FBG, HbA1c, IR, BMI, TGs, ALT, AST, ALP, and total bilirubin. At the same time, they exhibited lower levels of HB, albumin, transferrin, and total protein, all of which were statistically significant (all P < .05).

Both DM and cirrhosis exhibit a protracted, asymptomatic progression, posing challenges in establishing the chronological order of these conditions. The relationship between diabetes and LC is reciprocal, as individuals with T2DM have the potential to develop nonalcoholic fatty liver disease, which can subsequently advance to cirrhosis.^[24] According to our data, a significant proportion of the study population, specifically 47%, exhibited LC. This finding aligns with numerous prior studies that have also reported a substantial prevalence of LC. The occurrence of various forms of LC in individuals diagnosed with T2D has been documented to vary between 20% and 70% according to previous studies.^[25] Prospective investigations have provided evidence indicating that DM is correlated with an elevated susceptibility to hepatic complications and mortality among individuals diagnosed with LC. The potential role of DM in the development of liver damage is believed to involve the promotion of inflammation and fibrosis. This process is thought to be facilitated by an elevation in mitochondrial oxidative stress, which is mediated by adipokines. DM has the potential to cause liver damage by stimulating inflammation and fibrosis. This is achieved through an elevation in mitochondrial oxidative stress, which is primarily mediated by the actions of leptin, adiponectin, interleukin-6, and TNF-α. These molecules are produced within chronically inflamed adipose tissue, also known as adipositis. The synthesis of these chemical mediators is prompted by the presence of RI, which exhibited an elevated level in our patient population (3.7 ± 0.81). The potential association between T2DM and the heightened occurrence of LC necessitates additional research to provide a more comprehensive understanding of this relationship. Moreover, obesity, which is characterized by a BMI equal to or >30 in various populations, represents a significant determinant for noncommunicable diseases. According to national statistics from 2013, the prevalence of obesity in Saudi Arabia was reported to be 24.1% among men and 33.5% among women.^[26] The presence of obesity is a contributing factor in the onset of various chronic illnesses, such as T2DM and liver disease.^[27,28] In the present investigation, it was observed that individuals diagnosed with T2DM and exhibiting a high BMI had an increased likelihood of developing liver disease (LC). These findings suggest that the combination of obesity and T2DM may contribute to the development of advanced liver disease, potentially increasing the risk by more than 2-fold.^[29]

Changes in nutritional status are frequently correlated with LC, which can result in serious complications and a shortening of life expectancy. Malnutrition is widely regarded as the most prevalent complication associated with LC. Malnutrition is characterized as the persistent and insufficient consumption of food, leading to a modified nutritional condition accompanied by substantial reductions in weight and muscle mass.^[30] The most appropriate terminology to characterize malnutrition in individuals with cirrhosis is PM, wherein there is a simultaneous depletion of both muscle and adipose tissue. Nevertheless, it is evident that the prevailing and subsequent decline in muscle mass among individuals with cirrhosis indicates that sarcopenia is the primary manifestation of PM.^[29,30] Protein malnutrition has been observed to impact a substantial proportion of individuals diagnosed with LC, ranging from 25% to 56% of patients. Consistent with prior research, our findings revealed that 53.2% of the participants experienced PM, whereas 46.8% demonstrated normal protein levels as determined through the evaluation of biomarkers levels associated with PM. These markers consisted of low HB levels, abnormal liver function, diminished serum protein and albumin levels, low transferrin and an elevated BMI. Hepatic changes result in the development of nutritional deficiencies. Liver disease is commonly linked to both malnutrition and obesity. The strong correlation between the liver and nutrition implies that any changes or abnormalities in the liver can lead to deficiencies in nutritional intake. Consequently, various conditions of malnutrition or obesity have been found to be linked with liver diseases. The significance of metabolic hepatic steatosis is growing due to the global rise in the prevalence of obesity, T2D, and dyslipidemia. Given that the majority of patients in our study group are diagnosed with T2D and are obese, it is imperative to implement suitable nutritional interventions and lifestyle modifications in order to facilitate weight reduction. The effectiveness of weight loss in the regression of liver fibrosis, which is a critical determinant of patient survival, has been demonstrated.^[30] Additionally, it is worth noting that individuals with T2D and LC commonly experience several metabolic disruptions. These include fluctuations in energy expenditure, modifications in glucose metabolism, shifts in protein metabolism, and impairments in lipid metabolism. The presence of changes in glucose metabolism leads to a reduction in glycogen reserves, hyperinsulinemia resulting from insulin receptor blockade, diminished glucose oxidation in the liver, impaired glucose tolerance, and heightened complications associated with T2D. The modification of protein metabolism results in heightened protein catabolism and expedited conversion of amino acids into glucose through gluconeogenesis. In relation to proteins, a reduction in the synthesis of albumin occurs within the hepatic system. The presence of hypoalbuminemia results in the occurrence of edema in the intestinal mucosa, subsequently causing a decline in the ability to absorb nutrients. Moreover, taking into account the necessity of proteins for energy production, there is a decrease in skeletal muscle mass. Sarcopenia is a commonly observed phenomenon in individuals afflicted with chronic liver disease.

Biochemical markers such as serum protein, albumin, and HB play crucial roles in evaluating PM, especially in patients with LC and T2D. These markers provide valuable insights into the nutritional status of patients and are directly linked to the underlying pathophysiology of both LC and T2D, which often co-exist and exacerbate malnutrition. While biochemical markers such as albumin and HB are valuable tools for objectively assessing PM, it is important to consider them in conjunction with other clinical assessments, such as anthropometric measurements (e.g., BMI, weight loss) and subjective assessments (e.g., Subjective Global Assessment). These biochemical markers provide a snapshot of the patient’s metabolic and nutritional health, which, when combined with broader clinical assessments, offers a comprehensive evaluation of malnutrition. Hence, it is advisable to evaluate the nutritional status and detect malnutrition in individuals with T2D and LC. Biochemical markers like serum protein, albumin, and HB are integral to assessing PM in patients with LC and T2D. These markers reflect both the direct impact of liver dysfunction on protein synthesis and the systemic effects of malnutrition, providing a reliable and objective means of evaluating nutritional status. When interpreted alongside clinical assessments, they offer a powerful tool for diagnosing malnutrition and guiding treatment decisions, ultimately improving patient care and outcomes. By doing so, it is possible to enhance IR and mitigate protein-calorie malnutrition, thereby offering potential advantages to these patient populations.

4.1. Study limitations

The study exhibits several limitations. First, this is a retrospective observational study, which inherently restricts our ability to establish causality between biochemical markers and PM. Additionally, the value of the biochemical markers used to assess PM may be subject to individual variability, influenced by factors such as dietary characteristics, medications, or recent physical activity in patients. Therefore, it is prudent to exercise caution when interpreting our current findings, as these factors were not controlled in this study.

Furthermore, the study population was drawn from a predominantly ethnically homogeneous group, consisting primarily of Saudi patients. While this allowed us to maintain consistency within our cohort, it may limit the generalizability of the findings to more diverse populations, where genetic, lifestyle, and healthcare access differences might lead to different clinical outcomes. The relationship between PM, LC, and T2D could vary significantly in populations with different ethnic or cultural backgrounds. As a result, the applicability of our findings to broader global populations is uncertain, and caution is advised when extrapolating these results to patients with different ethnicities, nationalities, or healthcare environments. Future studies should aim to include more diverse patient populations and broaden selection criteria to better capture the complexity of PM across different demographic and clinical contexts. The present study revealed that age, ALP, TG, albumin levels, low HB levels, and transferrin are significant predictors of the occurrence of PM. During the initial phases of LC, these factors can be valuable in distinguishing patients with PM from those without, potentially aiding in the prevention of cirrhosis complications. However, the aforementioned limitations should be taken into account when interpreting these findings, and further research is necessary to validate these predictors in more heterogeneous populations.

5. Conclusion

A total of 47% of the 500 participants diagnosed with T2D exhibited the presence of LC. The LC group exhibited higher mean values for age, BMI, TGs, AST, ALT, ALP, and total bilirubin. The increasing prevalence of T2DM on a global scale has led to a concomitant rise in the incidence of liver disease among affected individuals. It is imperative for endocrinologists to recognize liver disease as a potential outcome of T2D along with the medical consequences of obesity and IR, and aim to optimize the therapeutic outcomes for these individuals. Additionally, LC displayed indications of PM, as demonstrated by decreased levels of HB, transferrin, serum protein, and albumin. The research revealed a significant association between PM and various factors, including older age, higher BMI, reduced levels of HB, total protein, and albumin, as well as elevated levels of ALP. Evaluating the levels of protein, albumin, transferrin, and HB in the blood is beneficial in managing malnutrition linked to obesity in individuals with T2D and LC. The body’s nutritional status significantly impacts both health and the efficacy of illness therapy and its repercussions. Saudi health care should enhance the system for frequently monitoring these indicators to decrease the risk of PM in these patients and its repercussions. Also, these indications can help identify persons with PM and prevent consequences associated with LC in patients with T2D.

Acknowledgments

The authors extend their appreciation to Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2025R155), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Author contributions

Conceptualization: Walaa M. Mohammedsaeed, Dalal Binjawhar, Amal M. Surrati.

Data curation: Walaa M. Mohammedsaeed, Dalal Binjawhar.

Formal analysis: Walaa M. Mohammedsaeed.

Funding acquisition: Dalal Binjawhar.

Investigation: Dalal Binjawhar.

Methodology: Walaa M. Mohammedsaeed, Amal M. Surrati.

Validation: Walaa M. Mohammedsaeed.

Visualization: Walaa M. Mohammedsaeed.

Writing – original draft: Walaa M. Mohammedsaeed.

Writing – review & editing: Dalal Binjawhar, Amal M. Surrati.