Insulin Resistance Risk Factors Research Articles

Is type 1 diabetes a risk factor for insulin resistance in young adults?

Is type 1 diabetes a risk factor for insulin resistance in young adults?

Correlation Between Serum Vitamin E and HOMA-IR in Patients with T2DM.

Peroxidation is one of the important causes of insulin resistance (IR), and vitamin E is a natural antioxidant, and there may be some correlation between serum vitamin E levels and insulin resistance. The correlation between serum vitamin E and insulin resistance in type 2 diabetes mellitus (T2DM) population. Two hundred and forty-two people (119 with T2DM) were included. One hundred and nineteen patients with T2DM were selected as the case group, and 123 people with non-T2DM were selected as the control group. People insulin resistance was detected by the homeostasis model assessment method (HOMA-IR) greater than 2.69 were included in the diabetic insulin resistance group, and those with HOMA-IR less than 2.69 were included in the diabetic non-insulin resistance group. Record the general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Correlation analysis, logistic regression, trend analysis, and restricted cubic spline (RCS) were performed using SPSS 25.0 and R 4.1.1 software. Correlation analysis, logistic regression, trend analysis, restricted cubic spline (RCS) analysis were conducted on general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. The logistic regression results showed that after adjusting for confounding factors, vitamin E was an independent influencing factor for insulin resistance in T2DM patients (P < 0.001). The trend analysis results show that with the decrease of serum vitamin E levels, the risk of insulin resistance in T2DM patients gradually increases. The RCS results showed that the risk of insulin resistance was significantly increased when the serum vitamin E level was lower than 10,575.23 ng/mL. Serum vitamin E levels are lower in T2DM patients than in healthy populations; Vitamin E is an independent influencing factor for HOMA-IR in T2DM patients. The risk of insulin resistance gradually increases in T2DM patients as serum vitamin E levels decrease. Vitamin E is a risk factor for insulin resistance at serum vitamin E levels below 10,575.23 ng/mL. At higher serum vitamin E levels than 10,575.23 ng/mL, vitamin E is a protective factor for insulin resistance.

Effects of vitamin family members on insulin resistance and diabetes complications.

The following letter to the editor highlights the article "Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance" in World J Diabetes 2023 Oct 15; 14 (10): 1514-1523. It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Isoleucine‐restricted diets improve high‐fat diet‐induced nonalcoholic fatty liver disease via regulating insulin resistance and gut microbiota

AbstractObesity, caused by a long‐term high‐fat diet, is a risk factor for insulin resistance and nonalcoholic fatty liver disease (NAFLD). The gut microbiota plays an important role in NAFLD development by producing lipopolysaccharides (LPS). Isoleucine (ILE), as one of the branched‐chain amino acids (BCAAs), has a negative effect on glucose and lipid metabolism in obese mice. Therefore, we speculated that isoleucine‐restricted diets could prevent high‐fat diet‐induced insulin resistance and NAFLD. For this purpose, 30 C57BL/6J mice received a control check diet (CK), a high‐fat diet (HFD), and a isoleucine‐restricted diet (IR) for 12 weeks, respectively. The current study revealed that IR diets reversed HFD‐induced weight gain, increased fasting glucose levels, and lipid metabolism disorder. Furthermore, IR diets attenuated HFD‐induced hepatic inflammation by regulating the LPS/TLR4/NF‐κB signaling pathway. Moreover, hepatic insulin resistance and gluconeogenesis disorder were significantly improved by IR diets. In addition, IR diets reshaped HFD‐induced gut microbiota imbalance, reflected in decreasing the proportion of Proteobacteria phylum and LPS contents. Taken together, our studies support that restricting isoleucine in high‐fat diets was a novel means of preventing obesity‐induced NAFLD and insulin resistance.

TyG index is positively associated with HOMA-IR in cholelithiasis patients with insulin resistance: Based on a retrospective observational study

Background/objectiveCholelithiasis is a common disease but pose significant global health and financial burdens. Mechanisms of the disease are associated with insulin resistance (IR), obesity, metabolic syndrome, and type 2 diabetes. Insulin resistance is commonly observed in cholelithiasis patients. More recently, the triglyceride-glucose (TyG) index has been proposed as an alternative marker of insulin resistance. In our study we aimed to understand whether the TyG index is correlated with HOMA-IR in cholelithiasis patients. And also we aimed the predict a cutoff value for determining insulin resistance in cholelithiasis patients. MethodsA total of 184 cholelithiasis patients were matched in terms of age, gender, and BMI. They were divided into two groups based on their Homa IR levels (IR and Non-IR group). This study was a retrospective, observational study and clinical data was obtained from electronic medical records. Cutoff value for Tyg index was established through ROC Analysis. Binary Logistic Regression was used to identify factors affecting insulin resistance. ResultsA significant cutoff value was found for the TyG index in determining the presence of insulin resistance. Having a TyG index of ≥8.71 indicates the presence of insulin resistance. The sensitivity was 68.48%, the specificity was 58.70%. Binary Logistic Regression analyses showed that an increase in Tyg Index, waist circumference and waist-to-height ratio values increases the risk of insulin resistance by 2.705 (p = 0.001), 1.032 (p = 0.029), and 334.057 (p = 0.012) times respectively. ConclusionOur study indicated that TyG index is positively correlated with HOMA-IR. TyG index was found as a risk factor for insulin resistance.

Anti-Inflammatory and Anti-Adipocyte Dysfunction Effects of Ficus lindsayana Latex and Root Extracts.

Low-grade chronic inflammation and adipocyte dysfunction are prominent risk factors of insulin resistance and type 2 diabetes mellitus (T2DM) in obesity. Thus, prevention of inflammation and adipocyte dysfunction could be one possible approach to mitigate T2DM development. Several Ficus species have been used in traditional medicine for ameliorating inflammation and T2DM. Our previous studies reported biological effects of Ficus lindsayana including antioxidant, anti-cancer, and anti-α-glucosidase activities. Further, this study therefore investigated whether F. lindsayana latex (FLLE) and root (FLRE) extracts inhibit inflammation-stimulated insulin resistance in adipocytes and inflammation in macrophages. FLLE and FLRE (200 µg/mL) had no significant cytotoxicity for macrophages, adipocytes, and blood cells (PBMCs and RBCs). FLRE had a total flavonoid content about three times higher than FLLE, while both had similar levels of total phenolic content. FLRE showed higher abilities than FLLE in suppressing inflammation in both macrophages and adipocytes and reversing the inflammation-induced insulin resistance in adipocytes. In TNF-α-induced adipocytes, FLRE significantly improved insulin-induced glucose uptake and insulin-suppressed lipolysis, while FLLE only significantly improved glucose uptake. Moreover, FLRE and FLLE remarkably reduced chemoattractant (MCP-1) but improved adipogenic (PPARγ and CEBPα) gene expression, leading to the promotion of adipogenesis and the suppression of insulin resistance. In LPS-induced macrophages, FLRE, but not FLLE, significantly inhibited LPS-induced NO production. Moreover, FLRE significantly reduced LPS-stimulated iNOS, COX-2, IL-1β, IL-6, and TNF-α gene expression. These results may provide the potential data for the development of this plant, especially the root part, as an alternative medicine, functional ingredient, or food supplement for the prevention of inflammation and obesity-associated insulin resistance, as well as T2DM.

Aprepitant boasted a protective effect against olanzapine-induced metabolic syndrome and its subsequent hepatic, renal, and ovarian dysfunction; Role of IGF1/p-AKT/FOXO1 and NFκB/IL-1β/TNF-α signaling pathways in female Wistar albino rats

Olanzapine-induced metabolic syndrome (MS) is a primary risk factor for insulin resistance, hepatorenal damage, and polycystic ovarian syndrome. The objective of the current study was to assess the protective effects of aprepitant (AP) against MS caused by olanzapine and the associated ovarian, renal, and liver dysfunction via modulation of IGF1/p-AKT/FOXO1 and NFκB/IL-1β/TNF-α signaling pathways. AP mitigated all biochemical and histopathological abnormalities induced by olanzapine and resulted in a significant reduction of serum HOMA-IR, lipid profile parameters, and a substantial decrease in hepatic, renal, and ovarian MDA, IL-6, IL-1β, TNF-α, NFκB, and caspase 3. Serum AST, ALT, urea, creatinine, FSH, LH, and testosterone also decreased significantly by AP administration. The FOXO 1 signaling pathway was downregulated in the AP-treated group, while GSH, SOD, and HDL cholesterol levels were elevated.

Are we closer to better understanding risk factors for insulin resistance among children and adolescents with perinatally acquired HIV?

Are we closer to better understanding risk factors for insulin resistance among children and adolescents with perinatally acquired HIV?

Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease featured by insulin resistance (IR) and decreased insulin secretion. Currently, vitamin D deficiency is found in most patients with T2DM, but the relationship between vitamin D and IR in T2DM patients requires further investigation. To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM. Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed. Based on the diagnostic criteria of IR, the patients were divided into a resistance group (n = 100) and a non-resistance group (n = 62). Subsequently, patients in the resistance group were subdivided to a conventional group (n = 44) or a joint group (n = 56) according to the treatment regimens. Logistic regression was carried out to analyze the risk factors of IR in T2DM patients. The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment. Notable differences were observed in age and body mass index (BMI) between the resistance group and the non-resistance group (both P < 0.05). The resistance group exhibited a lower 25-hydroxyvitamin D3 (25(OH)D3) level, as well as notably higher levels of 2-h postprandial blood glucose (2hPG), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) than the non-resistance group (all P < 0.0001). Additionally, the resistance group demonstrated a higher triglyceride (TG) level but a lower high-density lipoprotein-cholesterol (HDL-C) level than the non-resistance group (all P < 0.0001). The BMI, TG, HDL-C, 25(OH)D3, 2hPG, and HbA1c were found to be risk factors of IR. Moreover, the post-treatment changes in levels of 25(OH)D3, 2hPG, FBG and HbA1c, as well as TG, total cholesterol, and HDL-C in the joint group were more significant than those in the conventional group (all P < 0.05). Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the non-insulin resistant group. Logistic regression analysis revealed that 25(OH)D3 is an independent risk factor influencing IR. Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.

Study to determine between HbA1C and C-reactive protein in Diabetes mellitus

Background: Studies have shown that C-reactive protein, as an inflammatory marker, is an important risk factor for insulin resistance and type 2 DM. Measurement of inflammatory markers like CRP will improve the prediction of the risk of these events. The aim of this study was to investigate the relationship between hemoglobin A1c, one of the indicators of diabetes, and the highly sensitive C-reactive protein, one of the indicators of inflammation. Materials and Methods: This prospective observational study was carried out in the Department of Pathology, Patan Hospital. This study included each 154 subjects of Type 2 diabetic patients and healthy control. Statistical analysis was done using Pearson’s correlation test and data was expressed as mean ±SD for each parameter. A p-value of &lt; 0.05 was considered to be significant. Results: Most (57.7%) of the patients were between 40 to 60 years with a female preponderance of (0.5:1). The HbA1c and CRP values were high in the case group compared to the control group and analysis shows statistical significance. There was a statistically significant association between CRP level in the diabetic group (patient with HbA1C greater than 5.7%) than in the control group (patient with HbA1C equal to or less than 5.7%) (p- Value=0.005). Conclusions: Higher HbA1c levels are associated with increased CRP, demonstrating that poorly controlled diabetes mellitus is associated with increased systemic inflammation. Timely screening and early detection of elevated CRP in diabetes mellitus patients can prevent further complications and consequences.

Non-linear association of atherogenic index of plasma with insulin resistance and type 2 diabetes: a cross-sectional study

BackgroundAlthough there is numerous evidence on the epidemiological risk factors for insulin resistance (IR)-related metabolic diseases, there is still insufficient evidence to explore the non-linear association of Atherogenic Index of Plasma (AIP) with IR. Therefore, we aimed to elucidate the non-linear relationship between AIP and IR and type 2 diabetes (T2D).MethodsThis cross-sectional study was conducted in the National Health and Nutrition Survey (NHANES) from 2009 to 2018. A total of 9,245 participants were included in the study. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included IR and T2D defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, subgroup analysis, generalized additive model, smooth fitting curve and two-part logistic regression were adopted to reveal the relationship of AIP with IR and T2D.ResultsAfter adjustment for age, gender, race, education level, smoking status, alcohol consumption, vigorous/moderate physical activity, body mass index, waist circumference and hypertension, we found that AIP was positively associated with fasting blood glucose (β = 0.08, 95% CI: 0.06, 0.10), glycosylated hemoglobin (β = 0.04, 95% CI: 0.39, 0.58), fasting serum insulin (β = 4.26, 95% CI: 3.73, 4.79), and homeostasis model assessment of insulin resistance (β = 0.22, 95% CI: 0.18, 0.25). Further studies found that AIP was associated with increased risk of IR (OR = 1.29, 95% CI: 1.26–1.32) and T2D (OR = 1.18, 95% CI: 1.15–1.22). However, the positive association between AIP and IR or T2D was more significant in female than in male (IR: P for interaction = 0.0135; T2D: P for interaction = 0.0024). A non-linear and inverse L-shaped association was found between AIP and IR, while a J-shaped association was found between AIP and T2D. In patients with − 0.47 < AIP < 0.45, increased AIP was significantly associated with increased risk of IR and T2D.ConclusionsAIP showed an inverse L-shaped association with IR and a J-shaped association with T2D, indicating that AIP should be reduced to a certain level to prevent IR and T2D.

Habitual intake of advanced glycation endproducts is not associated with worse insulin sensitivity, worse beta cell function, or presence of prediabetes or type 2 diabetes: The Maastricht Study

A diet high in advanced glycation endproducts (AGEs) is a potential risk factor for insulin resistance, beta cell dysfunction, and ultimately type 2 diabetes. We investigated associations between habitual intake of dietary AGEs and glucose metabolism in a population-based setting. In 6275 participants of The Maastricht Study (mean±SD age: 60±9, 15.1% prediabetes and 23.2% type 2 diabetes), we estimated habitual intake of dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) by combining a validated food frequency questionnaire (FFQ) with our mass-spectrometry dietary AGE database. We determined insulin sensitivity (Matsuda- and HOMA-IR index), beta cell function (C-peptidogenic index, glucose sensitivity, potentiation factor, and rate sensitivity), glucose metabolism status, fasting glucose, HbA1c, post-OGTT glucose, and OGTT glucose incremental area under the curve. Cross-sectional associations between habitual AGE intake and these outcomes were investigated using a combination of multiple linear regression and multinomial logistic regression adjusting for several potential confounders (demographic, cardiovascular, and lifestyle factors). Generally, higher habitual intake of AGEs was not associated with worse indices of glucose metabolism, nor with increased presence of prediabetes or type 2 diabetes. Higher dietary MG-H1 was associated with better beta cell glucose sensitivity. The present study does not support an association of dietary AGEs with impaired glucose metabolism. Whether higher intake of dietary AGEs translates to increased incidence of prediabetes or type 2 diabetes on the long term should be investigated in large prospective cohort studies.

Allopurinol

Allopurinol

Aerobic and resistance exercises affect the BDNF/TrkB signaling pathway, and hippocampal neuron density of high-fat diet-induced obese elderly rats.

Obesity, caused by a high-fat diet (HFD) in elderly, is a risk factor for insulin resistance and a precursor to diabetes and can lead to impaired cognitive function. Physical exercise has positive effects on decrease obesity and improvement brain function. We investigated which type of aerobic (AE) or resistance (RE) exercise can be more effective in reducing HFD-induced cognitive dysfunction in obese elderly rats. 48 male Wistar rats (19-monthold) were divided into six groups: Healthy control (CON), CON+AE, CON+RE, HFD, HFD+AE, and HFD+RE. Obesity was induced by 5 months of HFD feeding in older rats. After obesity confirmation, RT (with a range of 50% to 100%1RM/3 days/week) and AE (running at 8-m/min for 15-min to 26-m/min for 60-min /5 days/week) was performed for 12-weeks. Morris water maze Test was used to evaluate cognitive performance. All data were analyzed using two-way statistical test of variance. The results showed that obesity had a negative effect on glycemic index, increased inflammation, decreased antioxidant levels, decreased BDNF/TrkB and decreased nerve density in hippocampal tissue. The Morris water maze results clearly showed cognitive impairment in the obesity group. But 12 weeks after AE and RE, all the measured variables were on the improvement path, and in general, no difference was observed between the two exercise methods. Two mods of exercise (AE and RE) may be having same effects on nerve cell density, inflammatory, antioxidant and functional status of hippocampus of obese rats. Each of the AE and RE can create beneficial effects on the cognitive function of the elderly.

Review of Inflammatory Markers in Metabolic Syndrome

The conditions included in the definition of metabolic syndrome typically include central obesity (excessive fat accumulation around the waist), insulin resistance, hyperglycemia (elevated blood sugar levels), dyslipidemia (abnormal levels of lipids in the blood), and hypertension (high blood pressure). Having any three or more of these conditions is considered to be indicative of metabolic syndrome. Metabolic syndrome (MetS) is emerging as a major public health problem with pro-inflammatory changes leading to Insulin Resistance and Cardiovascular Disease (CVD) at a very young age. Metabolic syndrome (MetS) is a global health concern; metabolic syndrome is becoming more common in our country. It is found to be a risk factor for insulin resistance and abnormal adipose tissue . Clinical symptoms of the syndrome could include abdominal obesity, hypertension, diabetes, hypertriglyceridemia, and low HDL cholesterol. So far various studies have been conducted on the effect of inflammatory markers like Serum Uric acid (UA), serum homocysteine, Leptin, Lp(a) etc. Most of them have reported a positive correlation between these inflammatory markers and the various components of (MetS) like abdominal obesity, elevated Blood pressure, Fasting blood Glucose and Lipid profile abnormalities like elevated Triglycerides (TAG) and low High Density Lipoprotein-Cholesterol (HDL-C). Various studies have reported a positive correlation between serum uric acid and Serum Homocysteine and Lp(a) in causing endothelial dysfunction and premature Cardiovascular events. Hence a review of the studies pertaining to the various inflammatory markers was done. There was an association of various inflammatory markers like uric acid, homocysteine, MDA, lipoprotein and others. More awareness must be created even at the high school level regarding the ill effects of sedentary lifestyle the likely hood of metabolic syndrome. An early identification of surging biomarker levels in high-risk children may find new cases at an earlier stage to prevent upcoming diabetes mellitus and its complications.

Sleep duration and timing are prospectively linked with insulin resistance during late adolescence.

The aim of this study was to evaluate whether short sleep duration or later sleep timing isa risk factor for insulin resistance (IR) in late adolescence. Mexico City adolescents enrolled in a longitudinal birth cohort (ELEMENT) took part in two study visits during peri-puberty that occurred approximately 2 years apart. IR was assessed with serum glucose and insulin. Four groups were defined using puberty-specific cutpoints: no IR over the follow-up period, transition from normal to IR, transition from IR to normal, and IR at both timepoints. Baseline sleep assessments were measured with 7-day wrist actigraphy. Multinomial logistic regression models were used to evaluate associations between sleep duration and timing with homeostatic model assessment of insulin resistance categories, adjusting for age, sex, and baseline pubertal status. Adolescents who were ≥ 1hour below the sleep duration recommendations-for-age were 2.74 times more likely to develop IR (95% CI: 1.0-7.4). Similarly, adolescents who were in the latest category of sleep midpoint (>4:33 a.m.) were more likely than those with earliest midpoints (1 a.m.-3a.m.) to develop IR (oddsratio=2.63, 95% CI: 1.0-6.7). Changes in adiposity over follow-up did not mediate sleep and IR. Insufficient sleep duration and late sleep timing were associated with development of IR over a 2-year period in late adolescence.

β-(1,3)-D-glucan from &lt;em&gt;Pleurotus ostreatus&lt;/em&gt; correlates with lower plasma IL-6, IL-1β, HOMA-IR, and higher pancreatic beta cell count in High-Fat and High-Fructose Diet (HFFD) rats

Introduction: The increasing consumption of high-fat and high-fructose foods contributes to the increasing prevalence of global obesity. Low-grade chronic inflammation in obesity is a significant risk factor for insulin resistance and type 2 diabetes. Therefore, this study aimed to determine the effect of β-(1,3)-D-glucan from oyster mushroom (Pleurotus ostreatus) extract on rats fed with a high-fat and high-fructose diet. Design and Methods: This experimental study was conducted on 35 male Sprague-Dawley rats aged eight weeks. The rats were divided into groups given a normal (N) diet, a high-fat and high-fructose diet (HFFD), D1 (HFFD+125 mg/kg BW β-glucan), D2 (HFFD+250 mg/kg BW β glucan), and D3 (HFFD+375 mg/kg BW β-glucan) with an intervention of 14 weeks. IL-6 and IL-1β levels were measured by the ELISA method, while HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) was calculated by the fasting insulin (ng/mL) x fasting blood glucose (mg/dL)/405 formula. Pancreatic beta-cell counts were measured by hematoxylin and eosin (H&amp;E) staining. Results: The results showed no differences in IL-6 and IL-1β between the treatment groups. However, there were significant differences in HOMA-IR and pancreatic beta-cell counts between groups. There were negative correlations between the dose of β-glucan and IL-6, IL-1β, and HOMA-IR levels. Also, there was a positive correlation between the dose of β-glucan and the number of pancreatic beta cells. Conclusions: Administration of β-(1,3)-D-glucan from oyster mushroom (Pleurotus ostreatus) extract prevented hyperglycemia and insulin resistance, also reduced inflammation in rats fed with HFFD regardless of weight gain.

Mechanistic insights of soluble uric acid-induced insulin resistance: Insulin signaling and beyond.

Hyperuricemia is a metabolic disease caused by purine nucleotide metabolism disorder. The prevalence of hyperuricemia is increasing worldwide, with a growing trend in the younger populations. Although numerous studies have indicated that hyperuricemia may be an independent risk factor for insulin resistance, the causal relationship between the two is controversial. There are few reviews, however, focusing on the relationship between uric acid (UA) and insulin resistance from experimental studies. In this review, we summarized the experimental models related to soluble UA-induced insulin resistance in pancreas and peripheral tissues, including skeletal muscles, adipose tissue, liver, heart/cardiomyocytes, vascular endothelial cells and macrophages. In addition, we summarized the research advances about the key mechanism of UA-induced insulin resistance. Moreover, we attempt to identify novel targets for the treatment of hyperuricemia-related insulin resistance. Lastly, we hope that the present review will encourage further researches to solve the chicken-and-egg dilemma between UA and insulin resistance, and provide strategies for the pathogenesis and treatment of hyperuricemia related metabolic diseases.

Combination of a Glucagon-Like Peptide 1 Analog and a Sodium-Glucose Cotransporter 2 Inhibitor Improves Lipid Metabolism Compared to the Monotherapies in Experimental Metabolic Syndrome

Background: Obesity is a risk factor for insulin resistance, dyslipidemia, fatty liver disease, and all disorders associated with metabolic syndrome. Here we evaluated the association of the glucagon-like peptide 1 (GLP-1) analog, liraglutide, and the sodium-glucose cotransporter-2 (SGLT-2) inhibitor, canagliflozin, on the improvement of metabolic syndrome symptoms in a high-fat diet (HFD)-induced obesity rat model. Methods: Male Wistar rats received either a control diet or HFD ad libitum for 5 months. After 4 months of diet, HFD rats were randomly divided into four experimental groups (HFD, HFD + liraglutide, HFD + canagliflozin, and HFD + liraglutide + canagliflozin). Treatment groups received liraglutide (100 µg/kg) and/or canagliflozin (10 mg/kg) once daily for one month. Body mass and food intake were monitored throughout the experiment. An oral glucose tolerance test, biochemical parameters, epididymal and liver fat, and adipocyte morphology were assessed after the treatment period. Results: Rats on the HFD developed obesity, glucose intolerance, dyslipidemia, and fatty liver. Liraglutide reduced food intake and body weight, normalized the lipid profile, and reduced abdominal and liver fat. Canagliflozin slightly reduced body mass and improved glucose tolerance and dyslipidemia. The combination therapy was more effective than the monotherapies in normalizing the lipid profile. Conclusions: The combination of liraglutide and canagliflozin was more effective than the monotherapies in improving dyslipidemia and liver fat. These results indicate that the combination of GLP-1 receptor agonists and SGLT-2 inhibitors is a promising therapeutic strategy to treat dyslipidemia, and possibly prevent fatty liver disease in metabolic syndrome and obese patients. J Endocrinol Metab. 2022;12(6):168-177 doi: https://doi.org/10.14740/jem843

Effect of Intermittent Fasting on Muscle Glycogen Stores in Rats with High-Calorie Diet

Insulin resistance in skeletal muscle is important since it is normally responsible for most of the insulin-mediated glucose disposal and contains the largest glycogen storage regulated by insulin sensitivity. A high-calorie diet is known to be a risk factor for insulin resistance. Lifestyle modification by regulating caloric intake through intermittent fasting (IF) is recommended to prevent insulin resistance. This study aims to analyze the effect of eight weeks of intermittent fasting on skeletal muscle glycogen stores in rats with a four-week high-calorie diet. A total 24 healthy male Wistar rats were divided into four groups, Ad-libitum with a standard diet (AL-SD) Ad-libitum with a high-calorie diet (AL-HCD) IF with a standard diet (IF-SD) IF with a high-calorie diet (IF-HCD). Muscles were obtained and stained with PAS stain to evaluate glycogen expression based on color intensity. The results of the glycogen expression score were obtained as follows, AL-SD=2.113±0.589 AL-HCD=1.827±0.375 IF-SD=2.109±0.499 IF-HCD=1.979±0.334. Although there was no significant difference between groups (p> 0.05), IF can prevent excessive reduction of glycogen stores in subjects with a HCD compared to the AL-HCD group. In conclusion, this study suggests that IF might improve the reduction of glycogen stores in muscles due to a high-calorie diet.