Type 2 diabetes mellitus (T2DM), chronic metabolic disease and is a global health problem. It consists of an array of dysfunctions, characterized by hyperglycemia due to insulin resistance, inadequate secretion of insulin, and excessive or inappropriate glucagon secretion. In recent years, T2DM has been on the rise among chronic non-communicable diseases worldwide. In the year 2021, it is estimated that 537 million people affected with diabetes, and this number is projected to increase 783 million by 2045. In India, prevalence of T2DM 77 million in 2019, and is projected to increase 134 million by 2045.1,2

T2DM is associated with micro, macro-vascular, and neuropathic complications. Diabetic patients have 2 to 4 times and 1.5 to 3.6 fold increases in risks of cardiovascular disease (CVD) and mortality, respectively. Therefore, early diagnosis of T2DM is very much essential for the timely management and also helps to reduce or prevent diabetic vascular complications.3 Obesity, especially abdominal obesity is well known risk factor for development of T2DM and insulin resistance.Metabolic changes in adipose tissue directlyaffect the glucose homeostasis and lipid levels in blood. It is proposed that T2DM may stem from complex metabolic disturbancescaused by excessive abnormal lipid or liver fat accumulation.4

Research studies show that waist circumference (WC), a common measure of abdominal obesity, and increased triglyceride (TG) levels are associated with increased risk of developing T2DM. 5,6 For the early detection of metabolic disorders, new markers that combine anthropometric measurements with blood lipid levels have been developed.7,8

The LAP index is one of those indicators which assess visceral fat. In 2005, Kahn introduced this LAP index which is a combination of waist circumference and fasting plasma triglyceride levels for determining lipid buildup and predicting excessive visceral obesity in adults. 9 However, LAP index has gained further attention due to its links to liver disease, chronic kidney disease and insulin resistance conditions. 10-11 According to the Korea National Health and Nutrition Examination Survey, the LAP index may represent insulin resistance and β-cell function even in non-diabetic individuals. 12

A study conducted by P Vijayalakshmi et al., to determine the association between LAP index and insulin resistance (IR) in T2DM. They reported that elevated LAP index levels are associated with IR in T2DM and they suggested that LAP index may be a useful marker for cardio-metabolic risk in early-stage T2DM. 13 A study conducted by Sadafi S et al., reported that a strong association between elevated LAP index levels and T2DM in the adult population of western Iran and suggested that LAP index is a potential tool for screening diabetes susceptibility.4

Another study by Tang M, et al., conducted a study to determine the relationship between LAP index and diabetic kidney disease (DKD) in patients with T2DM. They reported that LAP index was higher in the DKD group than in the non-DKD group, and LAP index is positively correlated with DKD, suggested that LAP index may have potential value to diagnose DKD in clinical practice.14

Similarly, the triglyceride glucose (TyG) index, first proposed by Simental-Mendia et al in 2008, and is calculated by the formula Ln[fasting triglyceride (mg/dL) x fasting glucose (mg/dL)/2].15

T2DM patients often display an atherogenic dyslipidemia and obesity, which greatly increases their risk for coronary artery disease (CAD). Research studies have shown that elevated triglyceride, low density lipoprotein cholesterol (LDL-C) and TG/HDL ratio, a marker of small dense LDL particle, augmented the development of cardiovascular disease in diabetes. This increased prevalence of lipid abnormalities/dyslipidemia in diabetes mellitus has been attributed to insulin resistance and its associated complications.3

In the recent years, studies have reported that TyG index can accurately identify IR, which may be related to its integrated consideration of both blood glucose and lipid factors, making it a more comprehensive reflection of the metabolic status of the body. 16

A study conducted by Selvi NMK et al., reported that TyG index is a useful tool for assessing glycemic control in T2DM patients and positively correlated with HbA1c and HOMA-IR. TyG may be useful as an alternative marker toassess glycemic control in diabetic patients.3  In 2022, a study conducted by Lopez-Jaramillo P et al., reported that increased levels of TyG index is associated with future cardiovascular mortality, myocardial infarction (MI), stroke, and T2DM, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. 17 A study by Jin JL, et al., in 2018 reported, TyG index was positively associated with future cardiovascular events (CVEs), suggesting that TyG may be a useful marker for predicting clinical outcomes in patients with CAD. 18 Despite of their role in various diseases, a limited data was available in Karnataka diabetic subjects.

AIM

This study aimed to assess lipid accumulation product (LAP) index and triglyceride to glucose (TyG) index in patients with Type 2 Diabetes Mellitus.

A cross-sectional study design was conducted in Department of Biochemistry in association with Department of General Medicine, Akash Institute of Medical Sciences and Research Centre, Devanahalli, Bengaluru, Karnataka, India. After obtaining the Institutional Ethics Committee and informed consent from all the study subjects, a total of 252 subjects were recruited into the study by using simple random sampling method. Out of 252, T2DM subjects were 126 and non-diabetic subjects were 126. Sample size was calculated with a power of 80% and with Type I error of 5% by using the formula: [Z1-α/2]2 [b] [1-b]/d2.

Inclusion Criteria

Diabetic and non-diabetic subjects willing to participate in the study, age of 20 - 60 years, both male and females, newly diagnosed and known T2DM subjects were included as cases. T2DM was diagnosed based on American Diabetes Association (ADA) criteria. Age and sex matched non-diabetics were recruited as controls.

Exclusion criteria

Patients refused to participate in the study, diabetes other than T2DM, co-morbidities other than T2DM, autoimmune diseases, malignancy and pregnant women were excluded from the study.

Sample collection

Fasting blood samples were collected using proper aseptic precautions. Fluoride tubes were used for glucose estimation, and a clot activator tubes were used for urea, creatinine and lipid profile. Samples were allowed to stand for 30 minutes at room temperature, followed by centrifugation at 2000 rpm for 10 minutes to obtain plasma/sera. The obtained plasma/sera sample was used for the estimation of fasting and post-prandial glucose by (GOD-POD method), urea (urease), creatinine (jaffe’s), total cholesterol (cholesterol oxidase/peroxidase), triglycerides (glycerol phosphate oxidase/peroxidase), HDLC (HDLC- Direct) were estimated by using Biochemistry fully auto analyzer. LDLC and VLDLC were calculated by Frieldwald’s formula. Anthropometric measurements, such as height and weight for calculating BMI, were recorded. WC was measured in the horizontal plane at the level of the umbilicus during minimal respiration. Blood pressure was measured in addition to family history and lifestyle parameters. The LAPI was calculated as follows: for men, {WC (cm)-65} x {TG concentration (mmol/L)} and for women, {WC (cm)-58}x{TG concentration (mmol/L)} and TyG index.9,15 A detailed history and clinical examination was done for all the study subjects.

Statistical Analysis

The data was analyzed descriptive statistical analysis, and the results were expressed as mean±SD. Categorical variables were presented as percentages. The difference observed if any in quantitative measurement were tested by applying Mann Whitney U test. Spearman’s rho correlation was applied to correlate LAP & TyG index with BMI, blood pressure and blood sugar. The p value (p <0.05) was considered as statistically significant.

The present study results showed that, significant increase in the mean age of cases 56.2±10.2 years, BMI in cases 28.5±3.5 (kg/m²),waist circumference in cases 100.5±8.3 cm, blood pressure in cases [systolic 126.1±8.9 mmHg, diastolic 86.2±3.6 mmHg] were observed in T2DM cases compared to non-diabetic subjects. Fasting blood sugar 144.1±30.8 mg/dl, Post-prandial blood sugar215.2±50.6 mg/dl, blood urea 29.1±5.4, creatinine 1.1±0.2 mg/dl, total cholesterol 199±40.8 mg/dl, Triglycerides 178.5±33.5 mg/dl, Low density lipoprotein cholesterol129.5±26.8 mg/dl, very low density lipoprotein cholesterol 35.9±4.6mg/dl were significantly increased in T2DM cases than non-diabetic subjects.  Lipid accumulation product index 75.8±40.9 and Triglyceride to glucose (TyG) index 4.2±1.1 were also significantly increased in T2DM cases compared with non-diabetic subjects as shown in Table 1.

 Table: 1 Comparison of demographic details, biochemical parameters, LAPI and TyG index in T2DM patients and non-diabetic subjects

In the present study, significant positive correlation was observed between LAPI with BMI (r=0.166), and fasting blood sugar (r=0.189). Similarly, TyG index also showed positive correlation with BMI (r=0.275) and fasting blood sugar (r=0.191) as shown in table 2. 

Table 2. Correlation of LAPI, TyG index with BMI, blood pressure, and blood sugar

Type 2 diabetes mellitus is a major global health problem. Dyslipidemia and insulin resistance plays a major role in development of micro- and macro-vascular complications. In the present study, it was found that LAPI and TyG index were significantly increased in T2DM cases compared to non-diabetic subjects. Significant positive correlation was observed for LAPI and TyG index with BMI and fasting blood sugar. Dyslipidemia, hyper triglyceridemia, and low HDL cholesterol levels are associated with T2DM and insulin resistance (IR). 19

The LAP a composite index of WC and TG, a new indicator of accumulated visceral adipose tissue. LAP index is mainly associated with dysfunctional and lipolytic adipose tissue, a key factor in the development of diabetes and metabolic syndrome. Waist circumference, a parameter of LAP index, represents abdominal subcutaneous adipose tissue and visceral adipose tissue. 20 In accordance with our study findings, a study conducted by Mirmiran P et al., reported that higher LAPI in T2DM patients associated with increased oxidative stress, insulin resistance, and inflammation. 21

Insulin resistance (IR), associated with development and progression of T2DM, and chronic inflammation, along with dysfunctional mitochondrial due to obesity, can accelerate IR in T2DM patients. Even, prolonged exposure to fatty acids can decrease insulin secretion, disrupt the expression of insulin gene, and increase β-cell death. 22,23 Similarly another study by Wakabayashi I and Daimon T also reported a strong association between LAP and hyperglycaemia and diabetes. 24

Yet another study by Ioachimescu AG et al., concluded that LAPI was a predictor of mortality in non diabetic individuals with CVD. 25 In a cross-sectional study by Xia C et al., it was demonstrated

that LAP had a greater impact on IR compared to BMI and WC. 11 In a study conducted by Ray L et al., in Indian subjects reported that LAPI is a better predictor of metabolic syndrome (MetS) compared to BMI and WC. 26 In a study by Anoop SS et al., in southern Indian population reported that LAP index showed higher predictive accuracy for the risk of insulin resistance as compared with HOMA-IR, QUICKI and FG-IR in non-obese, normoglycemic Asian Indian males from Southern India. 27 In a study by Yu J et al., reported that elevated LAP levels and the transition patterns of maintained-high LAP and low-to-high LAP are significant risk factors for T2DM in women. 28

The TyG index is more associated with insulin resistance than HOMA-IR and insulin resistance is the underlying mechanism of metabolic syndrome and T2DM. 29 A study conducted on middle-aged and elderly Chinese individuals by Li R et al. also showed a significant association between the LAP and TyG index with metabolic syndrome. 30

In a study conducted by Selvi NMK et al., concluded that TyG index is a useful tool for assessing glycemic control in T2DM patients and positively correlated with HbA1c and HOMA-IR and suggested that TyG can be used as a simple and inexpensive alternative to assess glycemic control in patients with diabetes. 3 In a prospective cohort study by Lopez-Jaramillo P et al., reported that TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. 17

In a study conducted by Gao YM et al., reported that in individuals with T2DM and CKD, a significant and positive association was shown between an elevated TyG index and the risk of ESRD. This conclusion provides evidence for the clinical importance of the TyG index for evaluating renal function decline in individuals with T2DM and CKD. 31 In a study conducted by Tu Z et al., reported that elevated TyG was significantly associated with an increased risk of diabetic kidney disease (DKD) in T2D, but no significant relationship was shown with diabetic peripheral neuropathy (DPN). This finding provided further evidence for the clinical significance of integrating TyG into the initial assessment of diabetic microvascular complications. 32

The study results may concludes that significant increase in LAPI and TyG index and their significant positive correlation with BMI, blood pressure and fasting blood sugar. Further studies with large sample size are recommended.

Limitations:

The major limitation of the current study is a lack of a population-based study design, small sample size and a cross-sectional design and causal inferences could not be made.

Funding: Nil

Conflict of Interest: Nil

Acknowledgement

We would like to thank the authorities of Akash Institute of Medical Sciences and Research Centre (AIMSRC), Devanahalli, Bengaluru, Karnataka, India.

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