The impact of high intensity interval training on serum omentin-1 levels,lipid profile,and insulin resistance in obese men with type 2 diabetes mellitus

Abstract

BACKGROUND:

High-intensity interval training (HIIT) is an effective exercise method that could lead to favorable changes in obese and diabetic subjects.

OBJECTIVE:

To investigate the effects of HIIT on serum omentin-1 levels, lipid profile, and insulin resistance in diabetic obese men.

METHODS:

Fifty obese men suffering from T2DM with ages between 40 and 60 years were enrolled. Subjects were divided into two groups: the HIIT ( $n=$ 26) and control group ( $n=$ 24). The HIIT group subjects underwent 12 weeks (3 sessions per week) of HIIT program, while the control group subjects kept to their normal daily activities. Fasting blood glucose levels, serum omentin-1 levels, lipid profile, and insulin resistance were evaluated at baseline and after the experiment.

RESULTS:

HIIT resulted in significant improvements in the subjects’ body composition, serum omentin-1 levels, lipid profiles, fasting insulin, HOMA-IR ( $p<$ 0.05). Further, highly significant negative correlations were observed between serum omentin levels, on the one hand, and body mass index, body weight, and waist circumference, on the other.

CONCLUSIONS:

Twelve weeks of HIIT may be an effective training strategy to improve serum omentin-1 levels, body composition, lipid profile, and insulin sensitivity in diabetic obese men.

Keywords

Diabetes mellitus obese exercise plasma omentin-1 insulin resistance

1. Introduction

Type 2 diabetes mellitus (T2DM) is a serious, highly prevalent global health concern; T2DM patients are expected to double by 2045. Both obesity and T2DM are leading causes of cardiovascular disease and premature mortality, raising the burden on healthcare systems worldwide [1]. Commonly, patients with T2DM have dyslipidemia – a lipid metabolism abnormality characterized by an increase or decrease in plasma lipids. The main changes in the lipid profile may include an increase in triglycerides, increased total cholesterol together with low-density lipoprotein (LDL), and decreased high-density lipoprotein (HDL) [2].

Moreover, obesity is associated with increased adipose tissue and visceral fat. Over time, the accumulation of visceral fat causes low-grade systemic inflammation. Various adipokines are secreted by the adipose tissue [3]. One of the most important functions of adipokines is its ability to regulate the functions of the pancreas and skeletal muscles [4, 5]. Defects in the production and action of adipokines can affect insulin function and glucose homeostasis [6].

Adipokines can be either pro-inflammatory or anti-inflammatory. Proinflammatory adipokines serve a primary role in developing and advancing insulin resistance and inflammatory processes. In contrast, anti-inflammatory adipokines play important protective and beneficial roles. Typically, patients with obesity and T2DM have an imbalance between proinflammatory and anti-inflammatory adipokines, leading to increased insulin resistance and altered metabolic functions [7]. Moreover, the progressive decrease in muscle mass with aging in turn increases the circulating proinflammatory adipokines, aggravating glucose intolerance and metabolic dysfunction. Adiponectin, omentin, and nitric oxide are examples of anti-inflammatory adipokines that fulfill an important protective role against insulin resistance [8].

Omentin is a recently discovered anti-inflammatory adipokine. Omentin-1, the most common type of omentin in the body, is a 38 kDa adipokine produced and secreted within the adipose tissue by stromal vascular adipocytes [9]. Normally, the plasma level of omentin-1 is about 20 ng/ml; however, this value is lower in overweight and obese subjects and is unfortunately progressively reduced in obese diabetic patients [10]. In the human body, omentin-1 serves an important function in the metabolism of glucose by stimulating adipocytes to use more glucose and increasing insulin action. Omentin-1 levels were found to be low in both obesity and T2DM patients [11]. Insulin resistance may be a result of reduced omentin-1 in blood in T2DM patients [12]. Moreover, plasma levels of omentin-1 have been found to be increased by weight loss in individuals with obesity [13, 14, 15, 16]. Regular exercise is one of the effective and safe strategies to deal with dyslipidemia and improve the balance between proinflammatory and anti-inflammatory adipokines [17].

Of various exercise maneuvers, the high intensity interval training (HIIT) is a regimen achieving an increase in popularity in improving cardiorespiratory fitness, insulin sensitivity, and reducing cardio-metabolic risks [18, 19]. It is a time-efficient modality that involves short bouts of a vigorous intensity exercise alternated with passive intervals or brief low intensity active recovery periods. HIIT is considered an excellent alternative to traditional moderate-intensity programs as it leads to higher adherence rates in the diabetic and obese population [18, 19]. Additionally, HIIT has been reported to improve the inflammatory profile through weight loss, which in turn leads to an increase in anti-inflammatory adipokines [20].

Few studies have investigated the impact of interval training, particularly HIIT, on adipokines in patients with obesity and diabetes. Some studies have reported significant improvements in omentin-1 levels, while others have not [21]. A six-week aerobic training program has been found to increase circulating omentin-1 by 10.4% in obese women [13]. Further, 12 weeks of aerobic exercise has been observed to significantly increase plasma omentin-1 levels in overweight and obese men [15]. In T2DM patients, a twelve-week program involving both resistance and aerobic training decreased insulin resistance and improved omentin-1 concentrations in blood [22]. However, 12 weeks of traditional aerobic exercise failed to change omentin-1 levels in obese women [23], while decreased omentin-1 levels were reported after two months of HIIT in overweight and obese men [24]. In fact, the effect of HIIT on plasma adipokines and insulin sensitivity is still ambiguous. Therefore, this study aimed to evaluate the effects of HIIT on plasma omentin-1 levels, lipid profile, and insulin resistance in obese men with T2DM.

2. Methods

2.1 Participants

Seventy obese men with T2DM volunteered to participate in this study. Potential participants were recruited from nearby hospitals and healthcare facilities and through the researcher’s personal contacts in Alkharj city. Before commencing the study, all participants were screened by a licensed physician by using medical history and personal health questionnaires. All participants in the sample were informed about the purpose, nature, and risks of the study. Informed consent was obtained from all participants before starting the study. The study procedures were carried out in accordance with the Declaration of Helsinki, and the experimental protocols were approved by the Research Ethics Committee in the Department of Physical Therapy and Health Rehabilitation, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Saudi Arabia (No: RHPT 021/018). All study outcomes were evaluated before and after the 12 weeks of post-test by the same researcher to minimize individual variations in techniques.

2.1.1 Inclusion criteria

•
Men with ages ranging from 40 to 60 years.
•
T2DM for at least two years but with controlled blood glucose.
•
Obesity with body mass index more than 30 kg/m ${}^{2}$ .
•
All subjects were sedentary performing less than 150 min/week of moderate-intensity exercise for at least the last six months.

2.1.2 Exclusion criteria

•
Use of exogenous insulin.
•
Subjects with acute or chronic cardiovascular or metabolic diseases who may, therefore, have limitations concerning their participation in HIIT.
•
Acute or chronic inflammatory disease.
•
Severe dyslipidemia.
•
Cerebrovascular disease.
•
Cancer.

2.2 Study design

This study was a randomized, controlled trial that was conducted in the Department of Physical Therapy and Health Rehabilitation, Prince Sattam Bin Abdulaziz University, over 12 weeks between February 2022 and October 2023. The subjects were divided into two groups (the HIIT group and the control group).

2.3 Study plan and randomization

The subjects were recruited and randomly allocated into two age and socioeconomic matched groups. The randomization codes were created using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA). Subsequently, the allocation data was hidden in sealed non-transparent envelopes with serial numbers. Eligible participants were referred to a researcher who randomly assigned them to either the exercise group or the control group. A researcher who was not involved in the sample recruitment performed the randomization process, and the authors of the study were blinded to the study groups. The HIIT group subjects underwent 12 weeks (3 sessions per week) of this training, while the control group subjects kept to their normal daily activities.

2.4 Outcome measures

Fasting blood glucose levels, serum omentin-1 levels, lipid profile, and insulin resistance(measured using the homeostasis model assessment for insulin resistance [HOMA-IR] method) were evaluated at baseline and after the experimental period.

2.5 Assessment procedures

2.5.1 Body composition assessments

The body weight and height of all subjects were measured using a weight and height scale (Detecto, made in the USA). The subjects were weighed wearing light clothes and no footwear. The weights of the subjects were recorded to the nearest 0.1 kg and heights to the nearest 0.1 cm. Obese subjects (BMI $\geqslant$ 30 kg/m ${}^{2})$ were selected by dividing the body weight (kg) by height in square meters (m ${}^{2}$ ). Other measurements included measuring the waist circumference of all subjects, done after gentle exhalation using a metallic tape placed between the lower rib margin and the top of the iliac crest. The average value of two measurements was recorded.

The fat mass percentage was evaluated using the InBody 770 multi-frequency bioelectrical impedance analysis (BIA) scale (Biospace, Cerritos, California, USA). The researcher manually recorded all subjects’ age, gender, and height in the apparatus. All subjects were scanned using criterion imaging and positioning procedures according to the manufacturer’s instructions. Each subject had to stand barefoot on the podium of the apparatus, and the soles of their feet had to be placed directly on the electrodes. The subject had to keep direct contact with the electrodes in the handgrips of the device and had to maintain this erect posture for about one minute with 30 ${}^{\circ}$ shoulder abduction and elbow extension [25].

2.5.2 Blood sampling and analysis

Figure 1.

Flow chart diagram.

Blood samples were collected from all subjects pre- and post-intervention (48–72 hours after the last training session) from the antecubital vein at around 8:00 am after 12 hours of overnight fast. Serum samples were separated and centrifuged. Insulin, lipid profile, and fasting blood glucose were assessed immediately (Clinical Analyzer, Hitachi, Tokyo, Japan). To measure the plasma level of omentin-1, samples were frozen at $-$ 70 to $-$ 80 degrees centigrade. The TC, TG, and HDL-C levels in plasma were measured using a clinical chemistry analyzer (Siemens Healthcare Diagnostics, Germany). The formula LDL-C $=$ TC $-$ [HDL-C $+$ (TG/5)] was used to calculate LDL-C. The plasma fasting insulin levels were measured using the ELISA method (Monobind, California, USA). The HOMA-IR method was used to calculate insulin resistance according to the following formula: HOMA-IR $=$ [fasting insulin (mU/L) $\times$ FBG (mg/dL)]/405 [26].

2.6 Treatment procedures

2.6.1 Exercise group

The HIIT group subjects underwent HIIT on a motorized treadmill (h/p/cosmos, Pulsar 4.0, Nussdorf-Traunstein, Germany), three sessions per week for twelve successive weeks. A trained physical therapist was assigned the supervision of the exercise sessions. The exercise intensity was determined according to the subjects’ maximum heart rate (HRmax). For each subject, the HRmax was estimated using the following formula: HRmax $=$ 208 $-$ 0.7 $\times$ age [27]. Each session started with a warming-up period and finished with a cooling-down period for 5–10 minutes. After warming up, the subjects were asked to perform the exercise for the effort time that included five two-minute high-intensity intervals (at 85–95% of the HR ${}_{\text{max}})$ . The exercise intensity was increased by 5% every four weeks, starting with 85% of the HR ${}_{\text{max}}$ in the first four weeks, 90% in the following four weeks, and then 95% of the HR ${}_{\text{max}}$ in the last four weeks. The high-intensity intervals were interspersed with two-minute active recovery intervals (at 50–60% of the HR ${}_{\text{max}})$ .

A polar heart rate monitor (Polar, FS1c, Polar Oy, Kempele, Finland) was used to monitor the subjects’ heart rate throughout the HIIT sessions.

2.6.2 Control group

Table 1
Participants’ characteristics and measures of body composition

	HIIT group ( $n=$ 26) Mean $\pm$ SD (CI 95%)		Control group ( $n=$ 24) Mean $\pm$ SD (CI 95%)		Group $\times$ time interaction
Variable	Pre	Post	Pre	Post	$p$	$\eta^{2}_{\text{Partial}}$
Age, years	46.76 $\pm$ 3.68		47.87 $\pm$ 2.6		0.23 ${}^{\ddagger}$	–
	(45.03–48.21)		(46.77–48.97)
Duration of disease, years	6.03 $\pm$ 1.21		5.66 $\pm$ 1.27		0.29 ${}^{\ddagger}$	–
	(5.47–6.52)		(5.12–6.2)
Body weight, kg	98.23 $\pm$ 3.14	92.42 $\pm$ 3.08 ${}^{\dagger}$	97.6 $\pm$ 2.89	97.5 $\pm$ 2.63	$P<$ 0.001 ${}^{*}$	0.462
	(96.96–99.49)	(91.17–93.67)	(96.48–98.93)	(96.38–98.61)
BMI, kg/m ${}^{2}$	37.78 $\pm$ 1.66	34.01 $\pm$ 1.96 ${}^{\dagger}$	37.82 $\pm$ 1.6	37.17 $\pm$ 1.36	$P<$ 0.001 ${}^{*}$	0.433
	(37.11–38.45)	(33.22–34.81)	(37.15–38.5)	(36.59–37.75)
Waist circumference, cm	109.03 $\pm$ 2.69	103.69 $\pm$ 3.86 ${}^{\dagger}$	110.58 $\pm$ 2.71	109.83 $\pm$ 2.58	$P<$ 0.001 ${}^{*}$	0.410
	(107.95–110.12)	(102.13–105.25)	(109.43–111.73)	(108.74–110.92)
Body fat, %	44.07 $\pm$ 1.32	41.53 $\pm$ 1.06 ${}^{\dagger}$	45.16 $\pm$ 1.92	44.54 $\pm$ 1.61	$P<$ 0.001 ${}^{*}$	0.375
	(43.54–44.61)	(41.10–41.96)	(44.35–45.98)	(43.85–45.22)

HbA ${}_{\text{1c}}$ : Glycated hemoglobin; BMI: Body mass index; HIIT: High-intensity interval training; CI: Confidence interval; $\eta^{2}_{\text{Partial}}$ : Effect size of the difference; ${}^{\ddagger}$ Non-significant changes between two groups; ${}^{*}$ Changes from pre- to post-intervention among HIIT and control groups are significant at $p<$ 0.05; ${}^{\dagger}$ Significant changes of post-tests between the two groups at $p<$ 0.05.

The control group included 29 subjects, but only 24 subjects completed the study. Subjects in the control group were instructed not to participate in any exercise program during the experimental period and to maintain their normal daily activity.

2.7 Sample size calculation

The sample size was calculated using effect size ( $d=$ 0.40) and a probability of 0.05 using the G*Power 3.0.10 software (University of Dusseldorf, Dusseldorf, Germany). For the null hypothesis to be rejected, the power of analysis was set at 80%, and 48 patients were recruited. The sample size was raised to 58 patients, anticipating withdrawals or dropouts of about 20% of the patients. A flowchart diagram is shown in Fig. 1.

2.8 Statistical analysis

Statistical tests were conducted using IBM SPSS Statistics 23.0 (Chicago, IL, USA). All data were expressed as mean $\pm$ SD. The Shapiro-Wilk test was used to check if the continuous variables followed a normal distribution. An independent $t$ -test was performed to confirm the homogeneity of basic characteristics of parametric data between the two groups. A two-way mixed analysis of variance (ANOVA) (2 $\times$ 2, group $\times$ time) was used to explore the differences before and after treatment in the variables of interest between the HIIT and control groups. The $p$ -value was set at $p<$ 0.05.

3. Results

3.1 Participants’ characteristics

The results of the statistical analyses revealed no significant differences in the baseline values of all measured variables between the study groups. The mean age ( $\pm$ SD) of the HIIT group subjects was 46.7 ( $\pm$ 3.6 years), while the mean age ( $\pm$ SD) of the control group subjects was 47.8 ( $\pm$ 2.6 years). The mean duration of disease ( $\pm$ SD) in the HIIT group was 6 ( $\pm$ 1.2 years), whereas it was 5.6 ( $\pm$ 1.2 years) in the control group. Further, the mean percentage of HbA ${}_{\text{1C}}$ ( $\pm$ SD) in the control group was 8.1 ( $\pm$ 0.66). The mean percentage of HbA ${}_{\text{1C}}$ ( $\pm$ SD) in the HIIT group was 7.63 ( $\pm$ 0.84), which significantly decreased at the end of the intervention, $F$ (1, 48) $=$ 14.91, $p<$ 0.001, 0.237, and significantly decreased compared with the control group, $F$ (1, 48) $=$ 36.1, $p<$ 0.001, 0.429.

3.2 Anthropometry and body composition

Table 2
Serum omentin-1 at baseline and end of the intervention in the study groups

Serum omentin-1, ng/ml	18.13 $\pm$ 1.72	26.17 $\pm$ 1.82 ${}^{\dagger}$	19.15 $\pm$ 1.86	19.46 $\pm$ 1.87	$P<$ 0.001*	0.979
	HIIT group ( $n=$ 26) Mean $\pm$ SD (CI 95%)		Control group ( $n=$ 24) Mean $\pm$ SD (CI 95%)		Group $\times$ time interaction
Variable	Pre	Post	Pre	Post	$p$	$\eta^{2}_{\text{Partial}}$
	(17.46–18.96)	(25.49–27.04)	(18.37–19.94)	(18.67–20.25)

CI: Confidence interval; $\eta^{2}_{\text{Partial}}$ : Effect size of the difference; ${}^{*}$ Changes from pre- to post-intervention among HIIT and control groups are significant at $p<$ 0.05; ${}^{\dagger}$ Significant changes of post-tests between the two groups at $p<$ 0.05.

Table 3

Lipid profile at baseline and end of the intervention in the study groups

Variable	Pre	Post	Pre	Post	$p$	$\eta^{2}_{\text{Partial}}$
	HIIT group ( $n=$ 26) Mean $\pm$ SD (CI 95%)		Control group ( $n=$ 24) Mean $\pm$ SD (CI 95%)		Group $\times$ time interaction
TC, mg/dl	222.96 $\pm$ 10.59	208.61 $\pm$ 11.58 ${}^{\dagger}$	223.75 $\pm$ 11.13	222.04 $\pm$ 8.49	$P<$ 0.001 ${}^{*}$	0.294
	(218.68–227.24)	(203.93–213.29)	(219.04–228.45)	(218.45–225.63)
TG, mg/dl	169.57 $\pm$ 11.07	157.34 $\pm$ 10.68 ${}^{\dagger}$	170.75 $\pm$ 6.8	168.95 $\pm$ 6.34	$P<$ 0.001 ${}^{*}$	0.243
	(165.10–174.05)	(153.03–161.66)	(167.87–173.62)	(166.27–171.63)
HDL-C, mg/dl	49.92 $\pm$ 5.01	59.76 $\pm$ 7.5 ${}^{\dagger}$	50.12 $\pm$ 5.61	48.62 $\pm$ 5.04	$P<$ 0.001 ${}^{*}$	0.520
	(47.89–51.95)	(56.72–62.80)	(47.75–52.49)	(46.49–50.75)
LDL-C, mg/dl	136.03 $\pm$ 2.64	118.61 $\pm$ 2.07 ${}^{\dagger}$	135.62 $\pm$ 2.07	134.54 $\pm$ 3.06	$P<$ 0.001 ${}^{*}$	0.850
	(134.86–137.05)	(117.82–119.59)	(134.41–136.83)	(133.24–135.83)

TC: Total cholesterol; TG: Triglycerides; HDL-C: High-density lipoprotein-cholesterol; LDL-C: Low-density lipoprotein-cholesterol; CI: Confidence interval; $\eta^{2}_{\text{Partial}}$ : Effect size of the difference; ${}^{*}$ Changes from pre- to post-intervention among HIIT and control groups are significant at $p<$ 0.05; ${}^{\dagger}$ Significant changes of post-tests between the two groups at $p<$ 0.05.

The anthropometrical and body composition measures of the subjects at baseline and the end of the study period are presented in Table 1. A significant interaction was observed between the effects on the groups pre- to post-intervention on all anthropometrical and body composition measures ( $p<$ 0.001). In comparison with those at baseline, body weight measures were significantly reduced in the HIIT group in response to the HIIT training program, $F$ (1, 48) $=$ 47.54, $p<$ 0.001, $\eta$ 2 $=$ 0.498. Further, body weight reduction within the HIIT group was statistically significant when compared with the control group, $F$ (1, 48) $=$ 10,18, $p=$ 0.002, $\eta$ 2 $=$ 0.175. Consequently, the BMI in the HIIT group was significantly decreased after the intervention when compared with baseline measures, $F$ (1, 48) $=$ 73.85, $p<$ 0.001, $\eta$ 2 $=$ 0.606. It was also noted that these BMI changes were statistically significant when the HIIT group was compared with the control group, $F$ (1, 48) $=$ 16.29, $p<$ 0.001, $\eta$ 2 $=$ 0.253. Moreover, the waist circumference was significantly reduced in the HIIT group compared with the control group, $F$ (1, 48) $=$ 33.29, $p<$ 0.001, $\eta$ 2 $=$ 0.410, with the waist circumference being 109.03 $\pm$ 2.69 cm before the HIIT intervention compared with 103.69 $\pm$ 3.86 cm after ( $p<$ 0.001). Similar changes were noted for the body fat percentage as it was significantly lower after the HIIT intervention than that before, $F$ (1, 48) $=$ 69.63, $p<$ 0.001, $\eta$ 2 $=$ 0.592, and it was also lower in the HIIT group compared with the control group, $F$ (1, 48) $=$ 28.74, $p<$ 0.001, $\eta$ 2 $=$ 0.375.

3.3 Serum omentin-1

The changes in serum omentin-1 levels between the two groups pre- to post-intervention are presented in Table 2. The results of the study show that serum omentin-1 levels in the HIIT group were significantly higher after the intervention compared with the baseline values, $F$ (1, 48) $=$ 2556.2, $p<$ 0.001, $\eta$ 2 $=$ 0.982. Moreover, this was endorsed by a significant interaction between the type of intervention and pre- to post-intervention ( $p<$ 0.001). Furthermore, serum omentin-1 levels were significantly higher in the HIIT group in comparison with the control group, $F$ (1, 48) $=$ 31.23, $p<$ 0.001, $\eta$ 2 $=$ 0.394.

3.4 Lipid profile

Table 4
Insulin resistance at baseline and end of the intervention in the study groups

Variable	Pre	Post	Pre	Post	$p$	$\eta^{2}_{\text{Partial}}$
	HIIT group ( $n=$ 26) Mean $\pm$ SD (CI 95%)		Control group ( $n=$ 24) Mean $\pm$ SD (CI 95%)		Group $\times$ time interaction
Fasting insulin, $\mu$ U/ml	12.89 $\pm$ 2.82	9.36 $\pm$ 1.62 ${}^{\dagger}$	12.43 $\pm$ 2.24	12.28 $\pm$ 1.92	$P<$ 0.001 ${}^{*}$	0.581
	(11.85–14.26)	(8.63–9.99)	(11.48–13.38)	(11.47–13.10)
Fasting glucose, (mg/dl)	161.73 $\pm$ 10.66	141.26 $\pm$ 9.89 ${}^{\dagger}$	159.66 $\pm$ 12.45	160.45 $\pm$ 10.65	$P<$ 0.001 ${}^{*}$	0.610
	(156.91–166.25)	(136.41–144.83)	(154.40–164.92)	(155.96–164.95)
HOMA-IR	4.39 $\pm$ 1.22	2.63 $\pm$ 0.91 ${}^{\dagger}$	4.12 $\pm$ 1.04	4.07 $\pm$ 1.06	$P<$ 0.001 ${}^{*}$	0.433
	(3.93–4.96)	(2.26–3.05)	(3.68–4.56)	(3.62–4.52)

HOMA-IR: Homeostatic model assessment of insulin resistance; CI: Confidence interval; $\eta^{2}_{\text{Partial}}$ : Effect size of the difference; ${}^{*}$ Changes from pre- to post-intervention among HIIT and control groups are significant at $p<$ 0.05; ${}^{\dagger}$ Significant changes of post-tests between the two groups at $p<$ 0.05.

Figure 2.

The correlations between serum omentin and: (A) BMI; (B) Body weight; (C) Waist circumference; (D) Homeostatic Model Assessment for Insulin Resistance (HOMA-IR); Significant was set at $p<$ 0.01.

The changes in the lipid profile between the two groups pre- and post-intervention are outlined in Table 3. Significant interaction effects were observed between the type of interventions and pre- to post-intervention scores on the lipid profile ( $p<$ 0.001). The HIIT group underwent a significant reduction in TC significantly compared with the control group, $F$ (1, 48) $=$ 7.30, $p=$ 0.009, $\eta$ 2 $=$ 0.132, as the TC score differed significantly pre- to post-treatment, $F$ (1, 48) $=$ 32.21, $p<$ 0.001, $\eta$ 2 $=$ 0.402. Additionally, the TG level was significantly decreased within the HIIT group when compared with the control group, $F$ (1, 48) $=$ 8.45, $p=$ 0.006, $\eta$ 2 $=$ 0.150, and when the scores pre- and post-intervention were compared, $F$ (1, 48) $=$ 27,77, $p<$ 0.001, $\eta$ 2 $=$ 0.367. HDL was increased significantly after the intervention, $F$ (1, 48) $=$ 28.09, $p<$ 0.001, $\eta$ 2 $=$ 0.369, and when the HIIT group was compared with the control group, $F$ (1, 48) $=$ 13.71, $p=$ 0.001, $\eta$ 2 $=$ 0.22. Further, LDL was decreased in the HIIT group in comparison with the control group, $F$ (1, 48) $=$ 182.19, $p<$ 0.001, $\eta$ 2 $=$ 0.791, as the LDL scores in the HIIT group changed significantly pre- to post-intervention, $F$ (1, 48) $=$ 350, $p<$ 0.001, $\eta$ 2 $=$ 0.879.

3.5 Insulin resistance

The influence of HIIT on the insulin resistance profile pre- to post-treatment in comparison with the control group is shown in Table 4. The effects of HIIT on all insulin resistance parameters were dependent on the treatment duration, and this was influenced by a significant interaction between the type of treatment and treatment duration ( $p<$ 0.001). The HIIT program barely enhanced the fasting insulin levels in the HIIT group compared with the control group, $F$ (1, 48) $=$ 4.37, $p=$ 0.42, 0.084. However, fasting insulin levels were highly significantly increased pre- to post-treatment in the HIIT group compared with the control group, $F$ (1, 48) $=$ 67.85, $p<$ 0.001, 0.622. The fasting glucose levels were, however, significantly reduced in the HIIT group compared with the control group, $F$ (1, 48) $=$ 9.08, $p=$ 0.004, 0.159, as the scores after the intervention was better than those before, especially in the HIIT group, $F$ (1, 48) $=$ 64.33, $p<$ 0.001, 0.573. Finally, the HOMA-IR score improved due to HIIT intervention compared with the control group, $F$ (1, 48) $=$ 4.78, $p=$ 0.034, 0.091, as the HOMA-IR score after the intervention (2.63 $\pm$ 0.91) was reduced significantly than before (4.39 $\pm$ 1.22) in the HIIT group, $F$ (1, 48) $=$ 41.36, $p<$ 0.001, 0.463.

3.6 Correlations between serum omentin and variables of interest

The relationship between serum omentin and body compositions and insulin resistance is outlined in Fig. 2. Highly significant correlations were noted between serum omentin and BMI, body weight, and waist circumference ( $r=$ $-$ 0.82, $-$ 0.90, $-$ 0.80 respectively, $p<$ 0.001). The insulin resistance was moderately correlated with serum omentin ( $r=$ $-$ 0.74, $p<$ 0.001).

4. Discussion

The effects of HIIT in improving insulin sensitivity and glycemic control emphasize the growing evidence concerning the benefits of this type of exercise in the management of diabetes mellitus. To this end, the present study aimed to investigate the effects of HIIT on plasma omentin-1 levels, lipid profile,and insulin resistance in obese men with T2DM. The data gathered in the present study showed that twelve weeks of HIIT resulted in significant improvements in plasma omentin-1 levels, body composition, lipid profile, and insulin resistance in obese men with T2DM. Moreover, highly significant correlations were observed between serum omentin and BMI, body weight, and waist circumference ( $r=$ $-$ 0.82, $-$ 0.90, $-$ 0.80 respectively, $p<$ 0.001). Insulin resistance was moderately correlated with serum omentin ( $r=$ $-$ 0.74, $p<$ 0.001).

In the present study, plasma omentin-1 levels increased in the HIIT group by 44%. Similar findings were reported in previous studies. It has been found that eight weeks of strenuous bicycle exercise significantly increased plasma omentin-1 concentrations by nearly 51% in inactive patients with T2DM [28]. More recently, HIIT was shown to result in significant increases in plasma omentin-1 levels in obese males [29, 30] and females [31]. Furthermore, plasma omentin-1 levels in male children with obesity were found to increase in response to 16 weeks of combined aerobic and resistance exercise associated with weight loss and improved insulin sensitivity [32].

The increase in plasma omentin-1 levels following exercise training may be explained by two mechanisms: first, exercise-induced weight loss and improvement in body composition [33] and second, exercise-induced physiological adaptation in skeletal muscles [13]. The first mechanism is supported in the present study based on the significant weight loss and improved body composition found in the HIIT group as well as the negative correlation observed between plasma omentin-1 levels and BMI, body weight, and waist circumference [34]. However, previous studies reported no changes in plasma omentin-1 levels in response to exercise training despite significant weight loss [23, 35]. The second mechanism suggests that plasma omentin-1 levels may increase in response to the physiological adaptation of skeletal muscle to exercise training. Skeletal muscle fibers adapt to chronic exercise by releasing myokines that act on adipose tissue to promote omentin-1 secretion [13]. Whether the increase in the plasma levels of omentin due to exercise is caused by weight loss, muscle-derived myokines, or both still needs further investigation.

In contrast with the results of the present study, 12 weeks of interval training failed to increase plasma omentin-1 concentrations in obese middle-aged males [35]. In addition, three months of aerobic exercise was found to be inadequate to improve serum omentin-1 levels in obese subjects [22]. Further, 10 weeks of HIIT reportedly slowed down weight gain in obese rats but induced no improvement in omentin levels [17]. This discrepancy between the results of the present study and those of previous studies may be due to different sample populations, exercise protocols, or intensities.

Regarding lipid profile, the results of the present study showed significant improvements in all measured parameters in the HIIT group. TC, TG, and LDL-C decreased by 6.4%, 7.2%, and 12.8% respectively while HDL-C increased by 19.7%. The mechanisms explaining exercise-induced improvement in lipid profile are still uncertain. However, plasma lipid levels may be decreased due to improvement in the ability of skeletal muscle fibers to consume lipids. Moreover, exercise-induced increases in lecithin-cholesterol acyltrans and lipoprotein lipase activity may be involved in the promotion of triglyceride hydrolysis [36].

Significant weight loss reported in the HIIT group subjects in the present study appears to have a role in improving lipid profile parameters [37]. Meanwhile, increased plasma omentin-1 levels could have a role in improving lipid profile through the activation of AMPK pathways leading to improved regulation of lipid metabolism [38]. Similar improvements in the circulating levels of LDL-C and total cholesterol have been reported following HIIT in individuals with T2DM [39]. Additionally, HDL-C improved significantly in overweight adolescents following three months of aerobic interval training [40]. On the other hand, four weeks of HIIT were shown to cause no significant improvement in TC, TG, HDL, and LDL-C in overweight and obese females [31]. Moreover, the lipid profile showed no significant changes after 12 weeks of low-volume HIIT in obese patients with metabolic syndrome [41].

Subjects in the HIIT group showed significant improvement in both fasting insulin and insulin resistance measured by the HOMA-IR method. Improvements in insulin sensitivity have been found to be associated with caloric restriction-induced weight loss with an average weight loss of about 15% of the initial weight [42]. However, a previous meta-analysis found no association between insulin resistance and body weight loss in T2DM in response to HIIT [43]. In the same meta-analysis, it was suggested that improvement in insulin sensitivity could be due to exercise-induced reduction in abdominal adiposity rather than overall weight loss [43]. In the present study, both body weight and waist circumference as indirect parameters of visceral fat mass significantly improved following the HIIT program, and this could be one of the factors contributing to the exercise-induced improvement in the HOMA-IR score. Moreover, it has been suggested that increases in circulating omentin levels may improve insulin sensitivity [44], and this may be evidenced by the negative correlation between the omentin levels and insulin resistance measured by the HOMA-IR method for the present study.

Several mechanisms have been postulated to explain how omentin-1 can improve insulin resistance. For instance, increases in plasma omentin-1 levels can enhance insulin-mediated glucose uptake by adipocytes in vitro via Akt signaling [44]. Increased omentin-1 may also restrain rapamycin, causing the stimulation of insulin receptor substrate [45]. Furthermore, it has been shown that omentin-1 can up-regulate adiponectin gene expression [46]. Significant improvements in insulin resistance (measured by using the HOMA-IR method) and glycemic control found in the present study agree with other studies reporting similar improvements in T2DM patients after 12 weeks of HIIT [28] and following 6 months of aerobic exercise [29]. Further, 12 weeks of low-volume sprint interval training caused significant reductions in HOMA-IR scores in overweight females [47]. Exercise-induced improvements in insulin sensitivity and glycemic control appear to be dependent on exercise intensity [28] and related to changes in body fat mass [48].

This study has some limitations. First, we recruited only men from a specific age range, and this may influence the generalizability of the study results to the whole population. In addition, there was no long-term follow-up to track improvements. Furthermore, we did not control the dietary intake in the study group, which could affect the measured outcomes.

5. Conclusion

Twelve weeks of HIIT induced a significant increase in serum omentin-1 levels in diabetic obese men. Moreover, significant improvements were observed in insulin sensitivity with improvements in both body composition and lipid profile. Furthermore, highly significant correlations existed between serum omentin and BMI, body weight, and waist circumference ( $r=$ $-$ 0.82, $-$ 0.90, and $-$ 0.80 respectively, $p<$ 0.001). Meanwhile, insulin resistance was moderately correlated with serum omentin ( $r=$ $-$ 0.74, $p<$ 0.001).

Author contributions

CONCEPTION: Ahmed S. Ahmed.

PERFORMANCE OF WORK: Ahmed S. Ahmed and Marwan S. Ahmed.

DATA COLLECTION: Ahmed S. Ahmed and Marwan S. Ahmed.

DATA ANALYSIS: Ahmed S. Ahmed.

DATA INTERPRETATION: Ahmed S. Ahmed.

PREPARATION OF THE MANUSCRIPT: Ahmed S. Ahmed and Marwan S. Ahmed.

REVISION FOR IMPORTANT INTELLECTUAL CONTENT: Ahmed S. Ahmed and Marwan S. Ahmed.

Ethical considerations

All patients signed a consent form by fulfilling the information sheets provided to each patient. Research Ethics Committee (No: RHPT 021/018) in Physical Therapy and Health Rehabilitation department, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Saudi Arabia granted ethical approval for this study. All procedures followed guidelines described by the (Declaration of Helsinki, 1964).

Funding

This project was supported by the deanship of scientific research at Prince Sattam bin Abdulaziz University under the research project (PSAU-2022/03/20350).

Footnotes

Acknowledgments

The authors are grateful to the Deanship of scientific research at Prince Sattam bin Abdualziz University, Saudi Arabia, for accomplishing this work.

Conflict of interest

The authors have no conflicts of interest to report.

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