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Background: Diabetic dyslipidemia poses a significant risk factor for cardiovascular complications in patients with diabetes mellitus. Empagliflozin and liraglutide are two commonly used medications in diabetes management, yet their comparative efficacy and safety in treating diabetic dyslipidemia remain under-explored. Aims and Objectives: This study aimed to assess the effectiveness and safety of Empagliflozin versus liraglutide in managing diabetic dyslipidemia. Materials and Methods: The study enrolled 100 participants with diabetes and dyslipidemia, divided equally into empagliflozin and liraglutide treatment groups. Baseline characteristics, including age, gender distribution, ethnicity, and duration of diabetes, were assessed and compared between the groups. Lipid profiles, encompassing total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were evaluated at baseline and after 6 months of treatment. Safety outcomes, such as the occurrence of mild gastrointestinal symptoms, hypoglycemia, and serious adverse events, were also monitored. Results: Both treatment groups exhibited comparable baseline characteristics. Following 6 months of treatment, both empagliflozin and liraglutide demonstrated significant improvements in lipid profiles. Reductions in total cholesterol, LDL cholesterol, and triglycerides, along with increases in HDL cholesterol, were observed in both groups. Moreover, there were no significant differences in the occurrence of adverse events between the two treatment groups, indicating similar safety profiles. Conclusion: This study provides evidence supporting the effectiveness and safety of empagliflozin and liraglutide in managing diabetic dyslipidemia. These findings highlight the potential of both medications as viable therapeutic options for patients with diabetes and dyslipidemia.

Background: Diabetic dyslipidemia poses a significant risk factor for cardiovascular complications in patients with diabetes mellitus. Empagliflozin and liraglutide are two commonly used medications in diabetes management, yet their comparative efficacy and safety in treating diabetic dyslipidemia remain under-explored. Aims and Objectives: This study aimed to assess the effectiveness and safety of Empagliflozin versus liraglutide in managing diabetic dyslipidemia. Materials and Methods: The study enrolled 100 participants with diabetes and dyslipidemia, divided equally into empagliflozin and liraglutide treatment groups. Baseline characteristics, including age, gender distribution, ethnicity, and duration of diabetes, were assessed and compared between the groups. Lipid profiles, encompassing total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were evaluated at baseline and after 6 months of treatment. Safety outcomes, such as the occurrence of mild gastrointestinal symptoms, hypoglycemia, and serious adverse events, were also monitored. Results: Both treatment groups exhibited comparable baseline characteristics. Following 6 months of treatment, both empagliflozin and liraglutide demonstrated significant improvements in lipid profiles. Reductions in total cholesterol, LDL cholesterol, and triglycerides, along with increases in HDL cholesterol, were observed in both groups. Moreover, there were no significant differences in the occurrence of adverse events between the two treatment groups, indicating similar safety profiles. Conclusion: This study provides evidence supporting the effectiveness and safety of empagliflozin and liraglutide in managing diabetic dyslipidemia. These findings highlight the potential of both medications as viable therapeutic options for patients with diabetes and dyslipidemia. [ABSTRACT FROM AUTHOR]

Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/β) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type-9 (PCSK-9) is a serine protease with profound effects on plasma LDL-C, the major risk factor for cardiovascular diseases (CVDs). However, plasma PCSK-9 level and its association with the biomarkers of CVDs, diabetes, and associated complications have not yet been reported in the northeastern population of India. Methods: Of the total cohort (n = 233), we analyzed healthy controls (HC; n = 50), freshly diagnosed type-2-diabetes mellitus (T2DM-FD; n = 46), T2DM treated (T2DM-T; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemia (T2DM-DL; n = 45) subjects. Plasma PCSK-9 and other biological determinants associated with T2DM, CVD, and nephrotic dysfunction were assessed. Results: The level of plasma PCSK-9 in HC, T2DM-FD, T2DM-T, T2DM-N, and T2DM-DL groups was found to be 184.1 ± 13.83, 183.1 ± 24.4.3, 241.8 ± 75.42, 403.7 ± 85.94, and 641.3 ± 135.5 ng/mL, respectively, indicating its role in the severity of the here-mentioned complications. Moreover, plasma PCSK-9 levels further showed a significant correlation with the biomarkers of hyperglycemia, particularly HbA1c, as well as LDL-C in T2DM-FD, T2DM-N, and T2DM-DL subjects of the Indian population, while moderate association in T2DM-T subjects. Conclusions: Our first-of-its-kind clinical study aiming to quantify the circulatory PCSK-9 level in the Indian population concluded that elevated PCSK-9 was significantly associated with the severity of diabetes and associated complications. Moreover, such elevation in PCSK-9 might be attributed to the lipid- and glucose-lowering medication-induced SREBP-2-dependent mechanisms. Since our conclusion is based on a pilot study, further cohort studies in larger populations of India are required to get a generalization regarding the role of PCSK-9 in DM and associated complications. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcer is a serious disabling consequence of Diabetes Mellitus. They are characterized by the breakdown of skin and underlying tissues in the feet, and are a major cause of lower limb amputations. Various risk factors have been identified for the development of diabetic foot ulcers, including poor glycemic control, peripheral neuropathy, peripheral arterial disease, and impaired wound healing. it is considered that the lipid profile is one of many factors that contribute to the formation and progression of diabetic foot ulcers. To stratify the incidence of diabetic foot ulcers (DFUs), biomarkers are required. The aim of this review is to assess the relationship between the risk of DFU and lipid profile in diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Peroxisome proliferator-activated receptors (PPARs) play crucial roles in regulating glucolipid metabolism. Previous studies showed that E17241 could ameliorate atherosclerosis and lower fasting blood glucose levels in ApoE−/− mice. In this work, we investigated the role of E17241 in glycolipid metabolism in diabetic KKAy mice. Approach and results: We confirmed that E17241 is a powerful pan-PPAR agonist with a potent agonistic activity on PPARγ, a high activity on PPARα, and a moderate activity on PPARδ. E17241 also significantly increased the protein expression of ATP-binding cassette transporter 1 (ABCA1), a crucial downstream target gene for PPARs. E17241 clearly lowered plasma glucose levels, improved OGTT and ITT, decreased islet cholesterol content, improved β-cell function, and promoted insulin secretion in KKAy mice. Moreover, E17241 could significantly lower plasma total cholesterol and triglyceride levels, reduce liver lipid deposition, and improve the adipocyte hypertrophy and the inflammatory response in epididymal white adipose tissue. Further mechanistic studies indicated that E17241 boosts cholesterol efflux and insulin secretion in an ABCA1 dependent manner. RNA-seq and qRT-PCR analysis demonstrated that E17241 induced different expression of PPAR target genes in liver and adipose tissue differently from the PPARγ agonist rosiglitazone. In addition, E17241 treatment was also demonstrated to have an exhilarating cardiorenal benefits. Conclusions: Our results demonstrate that E17241 regulates glucolipid metabolism in KKAy diabetic mice while having cardiorenal benefits without inducing weight gain. It is a promising drug candidate for the treatment of T2DM.

Abstract Background Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions by post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes and dyslipidemia. We aimed to identify new common miRNAs both in MVs and plasma that could be predictive biomarkers for diabetic dyslipidemia evolution. Methods For this purpose, plasma from 63 participants in the study (17 type 2 diabetic patients, 17 patients with type 2 diabetes and dyslipidemia, 14 patients with dyslipidemia alone and 15 clinically healthy persons without diabetes or dyslipidemia) was used for the analysis of circulating cytokines, MVs, miRNAs and MV-associated miRNAs. Results The results uncovered three miRNAs, miR-218, miR-132 and miR-143, whose expression was found to be significantly up-regulated in both circulating MVs and plasma from diabetic patients with dyslipidemia. These miRNAs showed significant correlations with important plasma markers, representative of this pathology. Thus, MV/plasma miR-218 was negatively correlated with the levels of erythrocyte MVs, plasma miR-132 was positively connected with MV miR-132 and negatively with uric acid and erythrocyte plasma levels, and plasma miR-143 was negatively related with creatinine levels and diastolic blood pressure. Also, three miRNAs common to MV and plasma, namely miR-21, miR-122, and miR-155, were identified to be down-regulated and up-regulated, respectively, in diabetic dyslipidemia. In addition, MV miR-21 was positively linked with cholesterol plasma levels and plasma miR-21 with TNFα plasma levels, MV miR-122 was negatively correlated with LDL-c levels and plasma miR-122 with creatinine and diastolic blood pressure and positively with MV miR-126 levels, MV miR-155 was positively associated with cholesterol and total MV levels and negatively with HDL-c levels, whereas plasma miR-155 was positively correlated with Il-1β plasma levels and total MV levels and negatively with MV miR-223 levels. Conclusions In conclusion, miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 show potential as biomarkers for diabetic dyslipidemia, but there is a need for more in-depth studies. These findings bring new information regarding the molecular biomarkers specific to diabetic dyslipidemia and could have important implications for the treatment of patients affected by this pathology.

Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/β) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management.

Background: Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions by post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes and dyslipidemia. We aimed to identify new common miRNAs both in MVs and plasma that could be predictive biomarkers for diabetic dyslipidemia evolution. Methods: For this purpose, plasma from 63 participants in the study (17 type 2 diabetic patients, 17 patients with type 2 diabetes and dyslipidemia, 14 patients with dyslipidemia alone and 15 clinically healthy persons without diabetes or dyslipidemia) was used for the analysis of circulating cytokines, MVs, miRNAs and MV-associated miRNAs. Results: The results uncovered three miRNAs, miR-218, miR-132 and miR-143, whose expression was found to be significantly up-regulated in both circulating MVs and plasma from diabetic patients with dyslipidemia. These miRNAs showed significant correlations with important plasma markers, representative of this pathology. Thus, MV/plasma miR-218 was negatively correlated with the levels of erythrocyte MVs, plasma miR-132 was positively connected with MV miR-132 and negatively with uric acid and erythrocyte plasma levels, and plasma miR-143 was negatively related with creatinine levels and diastolic blood pressure. Also, three miRNAs common to MV and plasma, namely miR-21, miR-122, and miR-155, were identified to be down-regulated and up-regulated, respectively, in diabetic dyslipidemia. In addition, MV miR-21 was positively linked with cholesterol plasma levels and plasma miR-21 with TNFα plasma levels, MV miR-122 was negatively correlated with LDL-c levels and plasma miR-122 with creatinine and diastolic blood pressure and positively with MV miR-126 levels, MV miR-155 was positively associated with cholesterol and total MV levels and negatively with HDL-c levels, whereas plasma miR-155 was positively correlated with Il-1β plasma levels and total MV levels and negatively with MV miR-223 levels. Conclusions: In conclusion, miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 show potential as biomarkers for diabetic dyslipidemia, but there is a need for more in-depth studies. These findings bring new information regarding the molecular biomarkers specific to diabetic dyslipidemia and could have important implications for the treatment of patients affected by this pathology. [ABSTRACT FROM AUTHOR]

Background: Small dense low-density lipoprotein cholesterol (sdLDL-C) is the lipoprotein marker among the various lipoproteins that is most strongly related to atherosclerosis. Insulin resistance (IR) can alter lipid metabolism, and sdLDL-C is characteristic of diabetic dyslipidemia. Therefore, this study sought to inspect the relationship between the triglyceride-glucose (TyG) index and mean low-density lipoprotein (LDL) particle size. Methods: In this study, a total of 128 adults participated. The correlation coefficients between various lipoproteins and the TyG index were compared using Steiger's Z test and the Spearman correlation. The independent link between the TyG index and mean LDL particle size was demonstrated by multiple linear regression analysis. To identify the TyG index cutoff value for the predominance of sdLDL particles, receiver operating characteristic curves were plotted. Results: Mean LDL particle size correlated more strongly with the TyG index than did very low-density lipoprotein, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Regression analysis demonstrated that mean LDL particle size had a strong association with the TyG index (β coefficient = -0.038, P-value < 0.001). The TyG index optimal cutoff value for sdLDL particle predominance and the corresponding area under the curve (standard error: 0.028, 95% confidence interval: 0.842–0.952) were 8.72 and 0.897, respectively, which were close to the cutoff value of diabetes risk in Koreans. Conclusions: Mean LDL particle size is more strongly correlated with the TyG index than do other lipid parameters. After correcting for confounding variables, mean LDL particle size is independently linked with the TyG index. The study indicates that the TyG index is strongly related to atherogenic sdLDL particles predominance. [ABSTRACT FROM AUTHOR]

Background: The height from sea levels, environmental factors, human-environment interactions, and lifestyle significantly influence the lipid profile and glycemic control of a population. Objective: This study aims to explore the influence of altitude on lipid profiles and glycemic control among the Saudi population at sea level and high altitude. Methods: In this retrospective cross-sectional study, a large dataset of patients of both gender and over 30 years old attending internal medicine clinics from two different regions at different heights from sea level, Jeddah (sea level) and Asir region (high altitudes) and referred to commercial laboratories for glycated haemoglobin (HbA1c) and lipids profile. Results: Compared to the Asir region, the Jeddah region had significantly higher mean values for fasting blood sugar (FBG), total cholesterol (TC), low-density lipoprotein (LDL-C), and triglycerides (TG) (P < 0.05). Every 1 mg/dL increase in FBG results in a 0.662 mg/dL increase in TG from the Jeddah region. However, it was a 0.318 mg/dL increase in TG from the Asir region. HbA1c demonstrated a significant (P < 0.05) strong positive correlation with TC, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and lipid ratio. FBG levels were also associated with a high level of TC/HDL-C (β = 0.137 95% confidence interval [CI]: 0.11-0.21; P < 0.05), LDL-C/high-density lipoprotein cholesterol (HDL-C) (β = 0.50; 95% CI: 0.31-1.49; P < 0.05), and TG/HDL-C (β = 0.14; 95% CI = 0.12-0.15; P < 0.05) in Jeddah region. However, significantly high blood pressure was observed in the population from high altitudes. Conclusion: Our results demonstrated a significant positive correlation between lipid profile and glycemic control with high prevalence at sea level. [ABSTRACT FROM AUTHOR]

Background: The height from sea levels, environmental factors, human–environment interactions, and lifestyle significantly influence the lipid profile and glycemic control of a population. Objective: This study aims to explore the influence of altitude on lipid profiles and glycemic control among the Saudi population at sea level and high altitude. Methods: In this retrospective cross-sectional study, a large dataset of patients of both gender and over 30 years old attending internal medicine clinics from two different regions at different heights from sea level, Jeddah (sea level) and Asir region (high altitudes) and referred to commercial laboratories for glycated haemoglobin (HbA1c) and lipids profile. Results: Compared to the Asir region, the Jeddah region had significantly higher mean values for fasting blood sugar (FBG), total cholesterol (TC), low-density lipoprotein (LDL-C), and triglycerides (TG) (P < 0.05). Every 1 mg/dL increase in FBG results in a 0.662 mg/dL increase in TG from the Jeddah region. However, it was a 0.318 mg/dL increase in TG from the Asir region. HbA1c demonstrated a significant (P < 0.05) strong positive correlation with TC, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and lipid ratio. FBG levels were also associated with a high level of TC/HDL-C (β = 0.137 95% confidence interval [CI]: 0.11–0.21; P < 0.05), LDL-C/high-density lipoprotein cholesterol (HDL-C) (β = 0.50; 95% CI: 0.31–1.49; P < 0.05), and TG/HDL-C (β = 0.14; 95% CI = 0.12–0.15; P < 0.05) in Jeddah region. However, significantly high blood pressure was observed in the population from high altitudes. Conclusion: Our results demonstrated a significant positive correlation between lipid profile and glycemic control with high prevalence at sea level.

• 74 million adults in India had diabetes in 2021 (1 in 12), more than half undiagnosed. • Diabetes in India is associated with earlier age of onset compared to Western groups. • More than 90% of Indian patients with diabetes are estimated to have dyslipidemia. • Indian patients with diabetes have an aggressive course of atherosclerosis. • Aggressive treatment of diabetic dyslipidemia is needed to prevent ASCVD events. In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians. [ABSTRACT FROM AUTHOR]

Thyroid dysfunction, diabetes, and dyslipidemia are significant health problems worldwide. They affect each other, and clinicians must be aware of the association between diabetic dyslipidemia and thyroid dysfunction to provide effective treatment and sound management for both. This study investigates the prevalence of thyroid disorder and its association with glycated hemoglobin and lipid profile in Najran city of Saudi Arabia. In this investigation, 2,741 (1,610 females and 1,131 males) laboratory findings of the commercial laboratories were screened over 2 years in Najran city of Saudi Arabia. The thyroid dysfunction associated with diabetes and dyslipidemia was a common laboratory finding, with a prevalence of 12.1% primary hypothyroidism, 34.5% subclinical hypothyroidism, 8.6% primary hyperthyroidism, and 4.2% subclinical hyperthyroidism. The prevalence of subclinical hypothyroidism, primary hyperthyroidism, and subclinical hyperthyroidism was considerably higher in females (P < 0.05). The overall prevalence of prediabetes and diabetes was 19.9% and 26%, respectively. The biochemical investigation of the study population showed that the prediabetic and diabetic group of the people with thyroid dysfunction had a significantly high prevalence (P < 0.05) of total cholesterol low-density lipoprotein, and triglycerides than the nondiabetic subject in the euthyroid group. However, the nondiabetic study subject had a significantly higher serum high-density lipoprotein. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a set of metabolic disorders that result in persistent diseases characterised by excessive blood sugar because of the lack of manufacturing of insulin, a hormone responsible for regulating sugar levels. This study became carried out on 42 (24 female, 18 male) noninsulin-dependent diabetics without a control group for comparison. The information had been obtained from November 2021 to February 2022 from the clinical data of the Diabetes Center in the Nasiriyah city. The exclusion criteria had been patients with type 1 diabetes who have been already taking lipid-decreasing drugs. Patients had been categorized into two groups based on glycated hemoglobin, the good glycemic control group having less than 7.0% and the poor glycemic control group having more than 7.0%. Data have been analyzed in the use of the (SPSS) program (p-value =0.05) and the superiority of dyslipidemia in diabetic patients was 43% amongst men and 57% amongst females. This study evaluated the relationship amongst glycemic control and lipid profile amongst diabetic patients. Evaluation of data by kind shows gender that there may be no significant difference in blood sugar parameters in addition to lipid level amongst males and females except for HDL values that are higher in females. [ABSTRACT FROM AUTHOR]

Poor glycemic control and dyslipidemia are hallmarks of type 2 diabetes mellitus (T2DM), which predispose to cardiovascular diseases. Peroxisome proliferator-activated receptor-α (PPARα) has been associated with atherosclerosis, but its role in T2DM is less clear. Previously, we studied PPARα expression levels in diabetics with and without dyslipidemia (DD). In this study we described the association with fasting blood glucose, HbA1c levels and lipid levels of the study population. Patient demography and biochemical data were collected from hospitals in Islamabad, Pakistan, and RT-PCR data of PPARα expression were retrieved from our previous study from the same cohort. We performed t-tests and regression analysis to evaluate the relationships between PPARα expression and demographic and clinical variables. As expected, body mass index and HbA1c were elevated in T2DM and DD patients compared to controls. Blood lipids (total cholesterol, triglycerides, LDL and HDL) were significantly higher in the DD group compared to the other two groups. In the T2DM and DD groups, the PPARα expression was not associated with any of the physical and biochemical parameters measured in this study. Expression of the PPARα gene was independent of blood lipids and glycemic control in this study. Further research is necessary to better understand the biological parameters of PPARα expression. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder, and cardiovascular disease (CVD) is a significant cause of mortality and morbidity in diabetic individuals. In addition to hyperglycemia, lipid abnormalities associated with T2DM play a crucial role in the development of CVD complications. Diabetic dyslipidemia is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL) particles, reduced high-density lipoprotein (HDL) cholesterol, and impaired HDL function. Angiopoietin protein-like 3 (ANGPTL3) is a liver-derived protein that plays a crucial role in regulating plasma lipoprotein metabolism by inhibiting lipoprotein lipase and influencing lipid levels. Inhibiting ANGPTL3 has shown promising effects in promoting HDL-mediated cholesterol reverse transport and reducing the levels of TG-rich lipoproteins and LDL cholesterol. Here, we explore the potential of ANGPTL3 as a therapeutic target for lipid management in T2DM patients., (© 2024. The Author(s).)

Dyslipidemia is a common feature of type 2 diabetes mellitus and is characterised by elevated triglyceride, decreased HDL cholesterol, and increased small dense LDL cholesterol levels. The underlying causes appears to be associated with insulin resistance, increased free fatty acid reflux, and low-grade inflammation, resulting in increased hepatic lipogenesis, and altered lipoprotein metabolism. Improved glycaemic control has been shown to have a positive effect on lipoprotein levels in diabetics. This can be achieved through medications/therapeutics and life style changes. Several classes of pharmacologic agents are currently in use to treat dyslipidemia. However, they may have dangerous long-term side effects, including an increased risk of liver dysfunction, weight gain, and cardiovascular diseases. Therefore, stronger alternatives with fewer side effects are required to reduce the diabetes associated complications. Many secondary plant metabolites have been shown to improve glucose homeostasis and lower lipid levels. Aloe vera and its constituents have long been used in a traditional medicine system for a diverse range of biological activities, including hypoglycaemic, antioxidant, anticarcinogenic, anti-inflammatory, and wound healing effects through various mechanisms and they have been covered well in literature. However, studies on the potential role of Aloe vera in the treatment of diabetic dyslipidemia are scanty. Therefore, in this systematic review, we focussed on the potential effect of Aloe vera and its active components in alleviating diabetic dyslipidemia, as well as their mechanism of action in pre-clinical and clinical studies.

Diabetic dyslipidemia is a significant contributor in the pathogenesis of type 2 diabetes (T2D). The study aimed at comparing the effect of dapagliflozin, liraglutide, and atorvastatin alone or their combinations on lipids and inflammatory markers and their vascular impact in T2D rats. There were 56 male albino rats included in the study and divided into two main groups. Group A (8 rats) served as normal control. Group B (48 rats) were streptozotocin–nicotinamide‐induced diabetic rats. Subgroups (B‐1, B‐2, B‐3, B‐4, B‐5, and B‐6) received (no medications, dapagliflozin, liraglutide, atorvastatin, dapagliflozin + atorvastatin, and liraglutide + atorvastatin), respectively. Urine albumin/creatinine ratio (UACR), glycosylated hemoglobin (HBA1c), fasting serum glucose (FSG), serum low‐density lipoprotein‐cholesterol (LDL‐C), high‐density lipoprotein‐cholesterol (HDL‐C), TGs, lipoprotein(a) Lp (a), serum thyrotropin (TSH), highly sensitive C‐reactive protein (hs‐CRP) and advanced glycation end products (AGEs), were assessed. Qualitative and quantitative histological examination of kidneys focused on renal corpuscles. Dapagliflozin improved the studied parameters but with statistically insignificant increase in LDL‐C, Lp (a) and significant increase in UACR. Atorvastatin improved the studied parameters but with statistically insignificant increase in FSG and HbA1C. Liraglutide and the combination groups significantly improved all studied parameters. Histologically, liraglutide and atorvastatin produced therapeutic effect, while dapagliflozin depicted nephrotoxic effect. Combination groups resulted in better effects with normalization of most of renal corpuscles. There were positive correlations between LDL‐C and hs‐CRP, AGEs, TSH and mesangial expansion. Combination of atorvastatin with liraglutide can improve its vasculoprotective effect. Moreover, combination of atorvastatin with dapagliflozin can ameliorate its possible nephrotoxic effect. [ABSTRACT FROM AUTHOR]

Ashok Kumar Das,1 Banshi Saboo,2 Ambika G Unnikrishnan3 1Department of Endocrinology, Pondicherry Institute of Medical Sciences, Pondicherry, India; 2Department of Endocrinology, Dia Care, Ahmedabad, Gujarat, India; 3Department of Endocrinology, Chellaram Diabetes Institute, Pune, Maharashtra, IndiaCorrespondence: Ambika G UnnikrishnanDepartment of Endocrinology, Chellaram Diabetes Institute, Pune, 411021, Maharashtra, IndiaTel +91 8605011934Email info@mediception.comBackground: Diabetic dyslipidemia is a risk factor for coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). American Diabetes Association (ADA) provides internationally accepted guidelines to manage dyslipidemia in T2DM.Objective: To assess if ADA guidelines are followed for managing dyslipidemia in patients with T2DM in India.Methods: This was a subset analysis of a prospective, cross sectional, observational study (LEADD Study) conducted at 199 sites across India to evaluate dyslipidemia management practices in T2DM patients (N=4002), in a real-world setting. The data was stratified based on age and atherosclerotic cardiovascular disease (ASCVD) and ASCVD risk factors to record the percentages of T2DM patients achieving LDL-C target and treated optimally with the Guideline directed intensity of statin. Analysis was conducted using descriptive statistics.Results: As per ADA 2018 targets: LDL-C levels (< 100mg/dL) were seen in 30.6% of participants. High intensity statins were prescribed to 13.4% of the participants with LDL levels ≥ 100 mg/dL. ASCVD risk assessment details were available for 89.2% of participants. Data was not available for smoking and albuminuria. In participants < 40 years of age, 80% and 64.2% with ASCVD and ASCVD risk factors, respectively, did not achieve target LDL-C levels. In this age group, 15.6% and 83.3% of participants with ASCVD risk factors and ASCVD group, respectively, were not receiving statins in the recommended dose. In participants ≥ 40 years of age, 88.0% and 91.5% with ASCVD and ASCVD risk factors, respectively, did not have LDL-C levels as per ADA 2018 targets. In this age group, 87.2% and 77.9% of participants with ASCVD risk factors and ASCVD, respectively, were not receiving statins in the recommended dose.Conclusion: The sub-analysis of LEADD study shows sub-optimal adherence to ADA 2018 guidelines for management of diabetic dyslipidemia.Keywords: diabetic dyslipidemia, hyperlipidemia in diabetes, abnormal lipid profile in diabetes, dyslipidemia in diabetes, hypercholesteremia in diabetes

Diabetics are liable to fatal atherosclerotic cardiovascular diseases. It is clinically attributed to their imbalanced plasma lipoproteins. Fixed‐dose combination "polypill" of simvastatin (10 mg) and sitagliptin phosphate (100 mg) is mainly indicated for the treatment of diabetic dyslipidemia. Novel green micellar electrokinetic capillary chromatographic method has been developed for simultaneous determination of simvastatin and sitagliptin phosphate in binary synthetic mixtures and their pharmaceutical formulation. Separation was achieved using a deactivated fused silica capillary (50 cm effective length × 50 μm id) through a background running electrolyte of 100 mM borate buffer (pH 9.1) and 100 mM sodium dodecyl sulfate. Diode array detection was set at 238 and 210 nm for simvastatin and sitagliptin phosphate, respectively. All experimental parameters were closely varied and optimized. Both drugs declared good linearities over the range of 10–100 μg/mL. Proposed study was validated according to International Council for Harmonization guidelines. It was applied to the assay of laboratory‐made binary mixtures and marketed tablets. Electrophoretic assay was compared with a reported spectrophotometric one. Satisfactory t‐test and F‐ratio indicated insignificant differences between both methods. Moreover, it is the first capillary electrophoretic simultaneous assay for simvastatin and sitagliptin phosphate, and fits a linear correlation with the green analytical attributes. [ABSTRACT FROM AUTHOR]

Diabetic dyslipidemia is characterised by low HDL-C and high triglyceride levels. Unlike the Caucasian population, though LDL-C levels are not very high, there is a preponderance of more atherogenic small, dense LDL particles among Indians. Furthermore, apo B levels are elevated. This, unique 'atherogenic dyslipidemia', is frequently encountered in South Asians with diabetes. People with type 2 diabetes are considered to be at high risk for vascular events. Hence, irrespective of other risk factors such as age, male gender, hypertension, family history, smoking, obesity, and polycystic ovary syndrome in women, they must be screened for dyslipidemia. Other major ASCVD risk factors include family history of hyperlipidemia, low levels of HDL-C, hypertriglyceridemia, and increased levels of total serum cholesterol level, non-HDL-C, LDL-C, apo B, Lp(a), triglyceride-rich remnants, and small, dense LDL-C. In patients with diabetes, dyslipidemia should be assessed at diagnosis and annually thereafter. In patients with type 1 diabetes, screening for dyslipidemia should be initiated from the age of 12 years. Periodical screening for dyslipidemia is recommended in overweight or obese children with a family history of type 2 diabetes, or those from a predisposed race/ethnicity like Asian, American Indian, etc. Both fasting and non-fasting lipid profiles are important for managing Indian patients with dyslipidemia. For routine screening, a fasting lipid profile is not mandatory; the decision to acquire fasting or non-fasting lipid values must be individually tailored. Apolipoprotein B level is considered an enhanced estimate of an individual's exposure to atherosclerotic lipoproteins, and may be predominantly valuable for assessment of risk in individuals where LDL-C measurement underestimates this burden (those with diabetes mellitus, high triglycerides, obesity, or low LDL-C). The QRISK3 assessment tool algorithm calculates an individual's risk of developing a heart attack or stroke over 10 years, and takes into account ethnicity as a risk factor. Considering the possible genetic influence of Indian ethnicity on CVD, the QRISK3 score exemplifies as the current most accurate CVD screening tool available for the Indian population. Stratification of ASCVD risk in Indian diabetic patients: • High risk: diabetes with 0–1 other major ASCVD risk factors and no evidence of target organ damage. • Very high risk: diabetes with ≥2 other major ASCVD risk factors or evidence of target organ damage. High-risk patients necessitate management comparable to that for secondary prevention of CVD. The most important step in defining treatment goals for dyslipidemia in diabetic patients is an extensive assessment of their cardiovascular risk, with LDL-C as the primary target, and non HDL-C, HDL-C, and apo B as secondary targets. A comprehensive strategy is essential in the management of dyslipidemia so as to regulate lipid levels and tackle related metabolic deviations and modifiable risk factors. Essential considerations to improve lipid profile and glycemic control, and reduce CVD risk: • Accomplish healthy weight and aerobic activity level, • Implement an energy-restricted, well-balanced diet, • No or at most moderate alcohol consumption, and • Smoking (or any other tobacco use) cessation. Medical nutrition therapy plays a central part in diabetes management; every individual with diabetes must be actively engaged in self-management, education, and treatment planning with their healthcare team, together with the collective development of an individualised eating plan. Statins are beneficial as a primary or secondary prevention strategy, to reduce the risk of cardiovascular events, in patients with ASCVD or multiple cardiovascular risk factors especially in those with diabetes. Unless contraindicated, first-line cholesterol-lowering therapy includes the use of moderate- to high-intensity statin. Ezetimibe, when combined with statins, provides additive and complementary therapeutic lipid effects, resulting in considerable reductions in LDL-C and significant achievement of target cholesterol levels. It also permits the use of lower dosage of statins without compromising efficacy, reducing the odds of dose-dependent statin adverse effects. Bempedoic acid seems to provide a safe and effective oral therapeutic option for lipid lowering in patients intolerant to statins. PCSK9 inhibitor therapy, in diabetes, induces analogous relative reductions in cardiovascular risk, and is recommended to further reduce LDL-C in patients aged 40–79 years with LDL-C ≥190 mg/dL, with ASCVD risk factors, or other significant additional-high risk markers (including diabetes) and LDL-C ≥100 mg/dL or non-HDL-C ≥130 mg/dL on maximally tolerated statin therapy and/or ezetimibe. Fenofibrate has shown to reduce CVD in diabetic patients with elevated triglycerides and low HDL-C levels. Saroglitazar has well-documented positive effects in the management of diabetic dyslipidemia; not only does it improve lipid parameters (triglycerides, apo B, non-HDL-C), it has a significant impact on glycemic parameters (HbA1c and fasting blood glucose) in dyslipidemic patients. It, hence, appears as a novel therapy for decreasing cardiovascular risk in patients with type 2 diabetes. Omega-3 fatty acids offer additional benefits when administered as an add-on to statins, and could be attributed to the lowering of detrimental chronic inflammatory markers in people with diabetes and high-risk cardiovascular patients. Icosapent ethyl may provide additional risk reduction benefit, beyond a statin, in individuals with ASCVD or diabetes and multiple risk factors and triglyceride ≥150 mg/dL. Considering the evidence in patients with diabetic dyslipidemia combined with the experience and consensus of the experts, we recommend a step-wise approach for the management for diabetic dyslipidemia in the Indian population (Table 7). [ABSTRACT FROM AUTHOR]

Saroglitazar—a unique dual peroxisome proliferator-activated receptor agonist was approved marketing authorization in India in 2013 for diabetic dyslipidemia. Postmarketing studies have additionally shown improvement in liver parameters in diabetic dyslipidemia patients with nonalcoholic fatty liver disease (NAFLD) who received saroglitazar. The aim of this study was to evaluate the effect of saroglitazar on liver function test, liver fibrosis score by FibroScan, lipid profiles, HbA1c in NAFLD patients with diabetic dyslipidemia in southern India. A prospective, interventional, pilot study was performed to study the safety and efficacy of saroglitazar in NAFLD patients having type 2 diabetes mellitus. About 97 patients were screened, of which 85 patients were involved in the study based on the inclusion criteria. The clinical parameters and liver stiffness were measured at the baseline and also after 12 weeks of treatment with administration of saroglitazar 4 mg once daily. The change in the parameters at the baseline and after the end of the treatment was measured and was subjected to statistical analysis using SPSS software. The recruited patients received saroglitazar and were followed up for a period of 12 weeks. The clinical parameters such as fasting blood sugar, postprandial blood sugar, HbA1c, total cholesterol, triglycerides, SGPT, and liver stiffness showed significant difference after 12 weeks of treatment when compared with the baseline values. No adverse drug reaction was reported in patients receiving saroglitazar during the study. Saroglitazar was found to show significant improvement in liver parameters in NAFLD patients with a significant reduction in liver fibrosis and triglycerides level. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the adverse effects of HMG CoA reductase inhibitor (statin) and garlic (Allium sativum) on renal function in diabetic dyslipidemic patients. Methods: This clinical trial was conducted at Surgeon Munawar Memorial Hospital, Karachi from 1st March 2019 to 30th August 2019. Total of 60 patients of 30-70 years of age with abnormal lipid profile were enrolled for this study after a written consent. The study was conducted to assess the side effects of statin (20 mg/day) and garlic (300 mg/day) in diabetic dyslipidemia patients. The study period consisted of six months. Blood pressure, body weight and height of subjects were assessed. The patient answered the questionnaire on health complaints, smoking, social role, drug usage, family history and dietary pattern. The initial inclusion criteria of the patient were 1) Age between 30-70 years old of either sex, 2) Patients with diabetic dyslipidemia. The exclusion criteria were 1) Pregnancy or lactation, 2) Patients with liver diseases, 3) Patients with renal diseases. Detailed medical history and physical examination of all patients were carried out. Results: This study included 60 patients with an abnormal lipid profile of age 30-70 years. Internationalstatin product (20 mg/day) and local garlic product (300 mg/day) for 08 weeks were used for oral administration in patients. Urea and creatinine levels in the serum of diabetic dyslipidemic patients were measured before and after treatment with an international statin (20 mg/day) and a local garlic product (300 mg/day). Conclusion: According to the findings of this study, statins increase the serum level of urea and creatinine while garlic has no effect on urea and creatinine serum level.

Poor glycemic control and dyslipidemia are hallmarks of type 2 diabetes mellitus (T2DM), which predispose to cardiovascular diseases. Peroxisome proliferator-activated receptor-α (PPARα) has been associated with atherosclerosis, but its role in T2DM is less clear. Previously, we studied PPARα expression levels in diabetics with and without dyslipidemia (DD). In this study we described the association with fasting blood glucose, HbA1c levels and lipid levels of the study population. Patient demography and biochemical data were collected from hospitals in Islamabad, Pakistan, and RT-PCR data of PPARα expression were retrieved from our previous study from the same cohort. We performed t-tests and regression analysis to evaluate the relationships between PPARα expression and demographic and clinical variables. As expected, body mass index and HbA1c were elevated in T2DM and DD patients compared to controls. Blood lipids (total cholesterol, triglycerides, LDL and HDL) were significantly higher in the DD group compared to the other two groups. In the T2DM and DD groups, the PPARα expression was not associated with any of the physical and biochemical parameters measured in this study. Expression of the PPARα gene was independent of blood lipids and glycemic control in this study. Further research is necessary to better understand the biological parameters of PPARα expression.

Diabetic dyslipidemia, a common pattern of lipid abnormalities associated with diabetes, is characterized by hyperglycemia, elevated serum levels of triglycerides and low-density lipoprotein (LDL)-cholesterol, and reduced serum levels of high-density lipoprotein (HDL)-cholesterol. These lipid abnormalities make diabetes an independent risk-factor for the development of cardiovascular disease. Two mouse models of diabetes were used in the present study: 1) streptozotocin (STZ)-induced insulin-deficient male Swiss Webster mice (a model of T1DM), and 2) male diet-induced obese (DIO) mice rendered insulin-resistant by maintenance on a high-fat diet for 30 weeks (a model of T2DM). Both models were then treated with MA-[D-Leu-4]-OB3 by oral gavage for 14 or 17 days. At the end of the test period, the mice were exsanguinated by cardiac puncture; serum was prepared from the whole blood and analyzed by ELISA for total-, HDL-, LDL/VLDL-cholesterol, and triglyceride content. In mouse models of both T1DM and T2DM, MA-[D-Leu-4]-OB3 significantly (P < 0.05) reduced serum levels of triglycerides and LDL/VLDL-cholesterol, and elevated serum HDL-cholesterol to levels approaching or equivalent to those seen in normal non-diabetic mice of the same age and sex. Our results suggest that in addition to its effects on energy balance, glycemic control, and cognitive function, MA-[D-Leu-4]-OB3, by modulating serum lipid levels, may also be beneficial in reducing the risk of adverse cardiovascular events associated with both T1DM and T2DM. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the adverse effects of HMG CoA reductase inhibitor (statin) and garlic (Allium sativum) on renal function in diabetic dyslipidemic patients. Methods: This clinical trial was conducted at Surgeon Munawar Memorial Hospital, Karachi from 1st March 2019 to 30th August 2019. Total of 60 patients of 30-70 years of age with abnormal lipid profile were enrolled for this study after a written consent. The study was conducted to assess the side effects of statin (20 mg/day) and garlic (300 mg/day) in diabetic dyslipidemia patients. The study period consisted of six months. Blood pressure, body weight and height of subjects were assessed. The patient answered the questionnaire on health complaints, smoking, social role, drug usage, family history and dietary pattern. The initial inclusion criteria of the patient were 1) Age between 30-70 years old of either sex, 2) Patients with diabetic dyslipidemia. The exclusion criteria were 1) Pregnancy or lactation, 2) Patients with liver diseases, 3) Patients with renal diseases. Detailed medical history and physical examination of all patients were carried out. Results: This study included 60 patients with an abnormal lipid profile of age 30-70 years. International statin product (20 mg/day) and local garlic product (300 mg/day) for 08 weeks were used for oral administration in patients. Urea and creatinine levels in the serum of diabetic dyslipidemic patients were measured before and after treatment with an international statin (20 mg/day) and a local garlic product (300 mg/day). Conclusion: According to the findings of this study, statins increase the serum level of urea and creatinine while garlic has no effect on urea and creatinine serum level. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Peroxisome proliferator-activated receptors (PPARs) play crucial roles in regulating glucolipid metabolism. Previous studies showed that E17241 could ameliorate atherosclerosis and lower fasting blood glucose levels in ApoE −/− mice. In this work, we investigated the role of E17241 in glycolipid metabolism in diabetic KKAy mice. We confirmed that E17241 is a powerful pan-PPAR agonist with a potent agonistic activity on PPARγ, a high activity on PPARα, and a moderate activity on PPARδ. E17241 also significantly increased the protein expression of ATP-binding cassette transporter 1 (ABCA1), a crucial downstream target gene for PPARs. E17241 clearly lowered plasma glucose levels, improved OGTT and ITT, decreased islet cholesterol content, improved β-cell function, and promoted insulin secretion in KKAy mice. Moreover, E17241 could significantly lower plasma total cholesterol and triglyceride levels, reduce liver lipid deposition, and improve the adipocyte hypertrophy and the inflammatory response in epididymal white adipose tissue. Further mechanistic studies indicated that E17241 boosts cholesterol efflux and insulin secretion in an ABCA1 dependent manner. RNA-seq and qRT-PCR analysis demonstrated that E17241 induced different expression of PPAR target genes in liver and adipose tissue differently from the PPARγ agonist rosiglitazone. In addition, E17241 treatment was also demonstrated to have an exhilarating cardiorenal benefits. Our results demonstrate that E17241 regulates glucolipid metabolism in KKAy diabetic mice while having cardiorenal benefits without inducing weight gain. It is a promising drug candidate for the treatment of T2DM. [Display omitted] • E17241, a unique pan-PPAR agonist and an ABCA1 upregulator, effectively ameliorates diabetic dyslipidemia in KKAy mice. • E17241 significantly lowers plasma fasting glucose levels and improves OGTT and ITT in KKAy mice. • E17241 improves islet function by promoting islet cholesterol efflux in an ABCA1-dependent way. • E17241 decreases liver lipid accumulation and eWAT mass by regulating PPAR target genes differently from rosiglitazone. • E17241 has cardiorenal benefits in KKAy mice. [ABSTRACT FROM AUTHOR]

Abstract Background Saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) agonist, in clinical trials, has shown an improvement in lipid and glycemic parameters through the PPAR-α and γ agonist actions, respectively. It was granted marketing authorization in India in 2013 for diabetic dyslipidemia. This review was conducted to summarize the effects of Saroglitazar in patients with diabetic dyslipidemia in real world clinical studies conducted after marketing authorization in India. Methods In this review, we selected real world clinical studies of Saroglitazar published as manuscripts and abstracts presented at scientific conferences. In all these studies, patients with diabetic dyslipidemia were treated with Saroglitazar 4 mg once daily for at least 12 weeks and different lipid and glycemic parameters were measured at the baseline and end of the study. Results In 18 selected studies (5 published manuscripts and 13 abstracts), a total of 5824 patients with diabetic dyslipidemia were prescribed Saroglitazar 4 mg for a duration ranging from 12 to 58 weeks. Across all the studies, mean age of patients ranged from 49.6 to 59.1 years and the proportion of female patients ranged from 22% to 42%. Across all the studies, there was a consistent mean reduction in triglyceride levels (~ 45% to 62%), total cholesterol levels (~ 17% to 26%), non-high-density lipoprotein cholesterol levels (~ 21% to 36%), low-density lipoprotein cholesterol levels (~ 11% to 27%), and glycosylated hemoglobin levels (~ 0.7% to 1.6%) with an increase in mean high-density lipoprotein cholesterol levels (up to 9%) from baseline to end of the study. Saroglitazar also improved alanine aminotransferase levels and fatty liver (evaluated by FibroScan™) in non-alcoholic fatty liver disease patients with diabetic dyslipidemia. Body weight remained unchanged and no significant adverse events (AEs) were reported in the studies. Conclusion Saroglitazar effectively improved lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia in real-world clinical studies of up to 58 weeks duration.

Introduction: Worldwide, Diabetes mellitus is the most common chronic disorder and risk factor for Coronary Artery Disease (CAD). The atherogenic indices including atherogenic index of plasma is a novel indicator of diabetic dyslipidemia, which is equivalent to the risk predictor of CAD. Aim: To compare the atherogenic indices including atherogenic index of plasma, cardiac risk ratio and atherogenic coefficient in individuals with Type 2 diabetes mellitus and in control group. Materials and Methods: The present study included 280 participants; of which 70 were healthy age and sex matched controls and 210 were known cases of Type 2 diabetes mellitus (30-60 years). Lipid profile was assessed by enzymatic assay and atherogenic indices including, atherogenic index of plasma, cardiac risk ratio and atherogenic coefficient were calculated. Patients with chronic liver/kidney disease and on lipid lowering drugs were excluded. Statistical analysis was done with SPSS version 20.0 and chi-square and one sample t-test was applied, p

Diabetes mellitus is associated with increased risk for atherosclerotic cardiovascular disease (CVD). Recent prospective studies in healthy individuals suggest that the postprandial triglyceride (TG) level is a better independent predictor for assessing future CVD events than fasting TG levels. In contrast, results have been more controversial among diabetic patients, as some studies report a positive association between postprandial TG and CVD. This raises the issue of to what extent postprandial TG levels may be of predictive value in the diabetic population. One possibility impacting on the predictive power of postprandial TG in identifying CVD risk may be the presence of other risk factors, including alterations in lipid and lipoprotein metabolism, which could make it more difficult to identify the impact of postprandial lipemia on cardiovascular risk. The findings provide a challenge to develop a better approach to assess the impact of postprandial lipemia on CVD risk under diabetic conditions.

• What is Insig-1. • Insig-1 in lipid metabolism. • Mechanisms of Insig-1 in lipid metabolism. • Insig-1 in lipid disorders. Growing evidence has demonstrated that Insig-1 is intricately involved in lipid metabolism regulation and the progression of lipid disorders. Our review summarizes updated information on the role and underlying mechanisms of Insig-1 in lipid metabolism dyshomeostasis and lipid disorders. As a member of the insulin-induced gene family, insulin-induced gene 1 (Insig-1) is a six-span transmembrane protein embedded in the endoplasmic reticulum (ER) membrane. Insig-1 is widely involved in the maintenance of intracellular lipid metabolism homeostasis by controlling the activation of sterol regulatory element-binding proteins (SREBPs) and the degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). Growing experimental and clinical data have identified that Insig-1 reduces lipid accumulation in hepatocytes to relieve the development of nonalcoholic fatty liver disease (NAFLD), downregulates the plasma level of free cholesterol and protects β cells against lipotoxicity to alleviate diabetic dyslipidemia. In addition, Insig-1 suppresses adipogenesis and inhibits the differentiation of preadipocytes to prevent the occurrence of obesity. Insig-1 is a key regulatory factor that maintains intracellular lipid metabolism homeostasis and is a promising therapeutic target for lipid disorders. [ABSTRACT FROM AUTHOR]

The incidence of diabetes mellitus in Indonesia continues to increase. Diabetic dyslipidemia, as one of the complications, significantly increase the risk of developing cardiovascular disease causing 65% of death in diabetes patients. This study evaluated the statin therapy and comorbidity factors on lipid profile of diabetic dyslipidemia patients. A cross-sectional study consisted of patients who received and did not received statin therapy. The achievement of LDL cholesterol target was determined according to the ATP III guidelines. Related comorbidity factors were also evaluated. There were 36 patients (12%) who received statin therapy and 86 patients (28.7%) who did not receive statin therapy, achieving the LDL cholesterol target. The achievement of LDL cholesterol target was associated with the presence of statin therapy (p = 0.000). Stroke, hypertension, and peripheral arterial disease (PAD) as the comorbidity factors were not associated with these variables, while coronary heart disease (CHD) was associated with the presence of statin therapy (p = 0.008), the achievement of LDL cholesterol target (p = 0.007), and the duration of statin therapy (p = 0.022). The achievement of LDL cholesterol target was associated with the presence of statin therapy. CHD as the comorbidity factors was associated with the presence of statin therapy, the achievement of LDL cholesterol target, and the duration of statin therapy. [ABSTRACT FROM AUTHOR]

Introduction: Worldwide, Diabetes mellitus is the most common chronic disorder and risk factor for Coronary Artery Disease (CAD). The atherogenic indices including atherogenic index of plasma is a novel indicator of diabetic dyslipidemia, which is equivalent to the risk predictor of CAD. Aim: To compare the atherogenic indices including atherogenic index of plasma, cardiac risk ratio and atherogenic coefficient in individuals with Type 2 diabetes mellitus and in control group. Materials and Methods: The present study included 280 participants; of which 70 were healthy age and sex matched controls and 210 were known cases of Type 2 diabetes mellitus (30-60 years). Lipid profile was assessed by enzymatic assay and atherogenic indices including, atherogenic index of plasma, cardiac risk ratio and atherogenic coefficient were calculated. Patients with chronic liver/kidney disease and on lipid lowering drugs were excluded. Statistical analysis was done with SPSS version 20.0 and chi-square and one sample t-test was applied, p<0.05 were considered as statistically significant. Results: Duration of diabetes was 6 to 10 years, the average BMI was 26.09 kg/m2. Among 210 diabetic patients 73 (34.76%) were of normal weight, 128 (60.95%) overweight and 09 (4.29%) obese; 87% had diabetic dyslipidemia. High level of HbA1c (8.8±1.5%) was associated with increase in duration of diabetes, the average duration of Type 2 diabetes in study population was 9.8±4.4 years. Significantly increased levels of cholesterol (188.3±31.9), triglyceride (161.3±19.4) and LDL-C (114.9±30.9) and decreased HDL-C (41.17±3.19) in diabetic patients as compared to control (165.5±35.5, 114.5±9.28, 94.4±34.4 and 48.17±3.4 respectively) (p<0.001) was noted. The atherogenic indices showed significantly increased levels of Atherogenic Index of Plasma (AIP) {(0.22±0.07) vs (0.04±0.01)} (p<0.001); Cardiac Risk Ratio (CRR) {(4.60±0.81) vs (2.44±0.71)} and Atherogenic Coefficient (AC) {(3.60±0.81) vs (2.44±0.71)} (p<0.001) in Type 2 diabetic patients vs control group. Conclusion: All diabetic patients having at least one kind of dyslipidemia, assessment of atherogenic indices, especially atherogenic index of plasma gives valuable information about future risk of abnormal cardiac event. Thus, it could be a better marker and predictor for increased risk of CAD in Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains as the first cause of death among infectious diseases worldwide. Global incidence of tuberculosis is in part coincident with incidence of type 2 diabetes (T2D). Incidence of T2D is recognized as a high-risk factor that may contribute to tuberculosis dissemination. However, mechanisms which favor infection under T2D are just starting to emerge. Here, we first discuss the evidences that are available to support a metabolic connection between TB and T2D. Then, we analyze the evidences of metabolic changes which occur during T2D gathered thus far for its influence on susceptibility to M. tuberculosis infection and TB progression, such as hyperglycemia, increase of 1AC levels, increase of triglycerides levels, reduction of HDL-cholesterol levels, increased concentration of lipoproteins, and modification of the activity of some hormones related to the control of metabolic homeostasis. Finally, we recognize possible advantages of metabolic management of immunity to develop new strategies for treatment, diagnosis, and prevention of tuberculosis.

Tuberculosis (TB) remains as the first cause of death among infectious diseases worldwide. Global incidence of tuberculosis is in part coincident with incidence of type 2 diabetes (T2D). Incidence of T2D is recognized as a high-risk factor that may contribute to tuberculosis dissemination. However, mechanisms which favor infection under T2D are just starting to emerge. Here, we first discuss the evidences that are available to support a metabolic connection between TB and T2D. Then, we analyze the evidences of metabolic changes which occur during T2D gathered thus far for its influence on susceptibility to M. tuberculosis infection and TB progression, such as hyperglycemia, increase of 1AC levels, increase of triglycerides levels, reduction of HDL-cholesterol levels, increased concentration of lipoproteins, and modification of the activity of some hormones related to the control of metabolic homeostasis. Finally, we recognize possible advantages of metabolic management of immunity to develop new strategies for treatment, diagnosis, and prevention of tuberculosis. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes self-management education (DSME) and medical nutrition therapy (MNT) improve glycemic control and reduce risk of chronic comorbid disease. Objective Document outcomes for patients with type 2 diabetes (T2D) completing DSME and MNT through American Diabetes Association–recognized programs. Design Descriptive, retrospective chart review. Participants/setting Four random samples of 100 records of patients with T2D completing DSME and MNT at each of four regional centers in Alabama, June 2013 to 2014, were chosen for review; after exclusions, 392 records were retained. Outcome measures Weight, body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein, high-density lipoproteins (HDL), triglycerides (TG), and TG-to-HDL ratio. Analysis Mixed-model analysis of variance was used to determine differences between continuous variables. McNemar test was used to assess frequency of patients reaching glycemic targets. Paired t tests were used to determine significance of lipid parameters. Results Significant reductions were observed at end of program and 1 year in weight (2.67±5.54 kg, P <0.001; 2.25±5.45 kg, P =0.001), BMI (0.93±1.91, P <0.001; 0.76±1.93, P =0.001), and HbA1c (1.82%±2.23%, P <0.001; 1.22%±2.15%, P <0.001). Patients managed by diet alone had a mean baseline HbA1c of 6.95% and exhibited a 0.8% reduction in HbA1c (P <0.001) at end of program. Those managed with diet plus drug therapy had a baseline HbA1c of 9% and exhibited a 2.09% reduction in HbA1c (P <0.001). Following DSME and MNT, 62% of patients reached glycemic targets (HcA1c≤7%), as compared with 32% at baseline (P <0.001). Significant reductions in TG were observed from baseline (162±74 mg/dL [4.19±1.91 mmol/L]) to follow-up (109±36 mg/dL [2.82±0.92 mmol/L]) (P <0.001). HDL increased from baseline (45±13 mg/dL [1.16±0.34 mmol/L]) to follow-up (48±11 mg/dL [1.24±0.28 mmol/L]) (P =0.05). The TG-to-HDL ratio improved from a baseline of 4.07±2.41 to 2.48±1.26 at follow-up (P <0.001). Conclusions Reductions were observed in weight, BMI, HbA1c, TG, and TG-to-HDL ratio. Improved patient outcomes were achieved in the clinical setting and support universal coverage to increase patient access to DSME and MNT. [ABSTRACT FROM AUTHOR]

Talinum triangulare leaf flavonoid extract (TTFE) was evaluated for its effects on streptozotocin‐hyperglycemia and associated complications especially as it relates to dyslipidemia, lipid peroxidation, and renal dysfunction in rats. Two normoglycemic rat groups designated: control (administered distilled water) and control + TTFE (administered 10 mg/kg b.w. TTFE) and two streptozotocin‐induced (STZ) diabetic rat groups designated: STZ‐control (administered distilled water) and STZ + TTFE (administered 10 mg/kg TTFE). The treatment was given orally once daily for 21 consecutive days. Body weight and insulin concentration showed significant improvement while blood glucose, uric acid, creatinine, and total bilirubin concentrations were significantly reduced in diabetic rats administered TTFE compared to diabetic untreated rats. Furthermore, triglycerides, total cholesterol, LDL‐cholesterol, and malondialdehyde concentrations were significantly lowered in diabetic rats administered TTFE compared with diabetic untreated rats. Key enzymes involved in carbohydrate breakdown and cholesterol synthesis, α‐amylase and 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) reductase, respectively, were significantly inhibited in TTFE‐treated diabetic rats compared to diabetic control. Results presented in this study suggest that administration of TTFE for 21 days normalized STZ‐induced hyperglycemia and its associated dyslipidemia by a mechanism involving inhibition of α‐amylase and HMG‐CoA reductase activities, respectively, in rats. The study describes the potential antihyperglycemic effect of Talinum triangulare leaf flavonoid extract in streptozotocin‐induced diabetic rats. In addition to restoring blood glucose level in diabetic rats, significant improvement in blood lipid profile, as well as upregulation of antioxidant enzyme activities, was also observed. The extract was also observed to inhibit alpha‐amylase and 3‐hydroxy‐3‐methylglutaryl‐CoA reductase activities thus providing possible mechanistic justification for its observed antihyperglycemic and antilipidemic activities, respectively. [ABSTRACT FROM AUTHOR]

1. Saroglitazar, a novel peroxisome proliferator-activated receptor (PPAR) agonist, regulates lipid and glucose metabolism. The objective of this report is to provide a preclinical evaluation (in vitro/in vivo) of ADME properties of saroglitazar. In vitro studies included determination of permeability, metabolic stability, plasma protein binding, CYP reaction phenotyping and CYP inhibitory liability. In vivo studies included oral bioavailability and pharmacokinetic assessment in mouse, rat and dog. The excretion of saroglitazar was determined in rats. Exploratory metabolism of saroglitazar was evaluated using in vitro and in vivo samples. 2. Saroglitazar was metabolically more stable in human liver microsomes as compared to rat and dog liver microsomes, highly protein bound (98-99.6%) with high Caco2 permeability (104 nm/s) with <2 efflux ratio. In vitro metabolism in rat, dog and human liver microsomes revealed three putative metabolites corresponding to di-hydroxylation, mono-oxygenation and dehydrogenation moieties. 3. Oral bioavailability was 100%, 72% and 47% in mouse, rat and dog, respectively. The intravenous clearance and volume of distribution of saroglitazar were 3.6, 8.5 and 6.9 mL/min/kg and 1.3, 4.8 and 1.8 L/kg for mouse, rat and dog, respectively. The elimination half-life of saroglitazar ranged between 6 and 15 h. Saroglitazar appeared to be eliminated via hepatobiliary route with negligible renal excretion. [ABSTRACT FROM AUTHOR]

Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2 diabetes, causing diabetic dyslipidemia. Cyclocarya paliurus (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in lipid loaded mice (Kurihara et al., 2003), although the detailed mechanisms and active ingredients for this hypolipidemic effect have not yet been answered. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches. Our results revealed that serum and hepatic levels of total triglyceride (TG), total cholesterol (T-CHO), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), as well as 30 lipids including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were improved in comparison with untreated diabetic mice. In parallel, 14 phytochemical compounds of CP were determined in mice serum after CP administration. Mechanistically, the network pharmacology analysis revealed the predicted targets of CP’s active ingredients ALOX12, APP, BCL2, CYP2C9, PTPN1 and linked lipidome targets PLD2, PLA2G(s), and PI3K(s) families could be responsible for the CP effects on diabetic dyslipidemia. In conclusion, this study revealed the beneficial effects of CP on diabetic dyslipidemia are achieved by reducing accumulation of hepatic lipid droplets and regulating circulatory lipids in diabetic mice, possibly through PI3K signaling and MAPK signaling pathways. GRAPHICAL ABSTRACTWork flow of the evaluation of the effects and mechanisms of Cyclocarya paliurus leaves tea on dyslipidemia in diabetic mice.

Glucose and lipid metabolism are linked to each other in many ways. The most important clinical manifestation of this interaction is diabetic dyslipidemia, characterized by elevated triglycerides, low high density lipoprotein cholesterol (HDL-C), and predominance of small-dense LDL particles. However, in the last decade we have learned that the interaction is much more complex. Hypertriglyceridemia and low HDL-C cannot only be the consequence but also the cause of a disturbed glucose metabolism. Furthermore, it is now well established that statins are associated with a small but significant increase in the risk for new onset diabetes. The underlying mechanisms are not completely understood but modulation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA)-reductase may play a central role as genetic data indicate that mutations resulting in lower HMG CoA-reductase activity are also associated with obesity, higher glucose concentrations and diabetes. Very interestingly, this statin induced increased risk for new onset type 2 diabetes is not detectable in subjects with familial hypercholesterolemia. Furthermore, patients with familial hypercholesterolemia seem to have a lower risk for type 2 diabetes, a phenomenon which seems to be dose-dependent (the higher the low density lipoprotein cholesterol, the lower the risk). Whether there is also an interaction between lipoprotein(a) and diabetes is still a matter of debate.

Saroglitazar is a dual PPAR α/γ agonist approved in India for the management of diabetic dyslipidemia. Aims: The objective of this study was to evaluate the safety and efficacy of saroglitazar 4 mg once daily in clinical practice. Methods: This was an observational, multicenter, single-arm study. Patients with type 2 diabetes (with on-going antidiabetic medication), age above 18 years, and triglycerides ≥200 mg/dL were included. Results: A total 2804 patients with a mean duration of diabetes 6.29 yrs were included in this analysis. The baseline demographic profile was: mean age of 53 yrs, mean body weight 72.3 kg and mean BMI of 27 kg/m2. 62.5% patients were male and 57.8% were reported to be on statin therapy at baseline. All 2804 patients were on antidiabetic medications with 15.4% patients on monotherapy and rest were on two or more than two antidiabetic medications at baseline. The baseline triglycerides and HbA1C values were 312.3 mg/dL and 8.3% respectively. At 3 months follow-up, use of saroglitazar 4 mg led to significant reduction in TG (35.8%), LDL-C (16.4%), total cholesterol (19%) and non-HDL-C (23.4%). Addition of saroglitazar to baseline antidiabetic medications showed a significant 0.9% absolute reduction in HbA1c with significant improvement in fasting and post prandial plasma glucose. No serious adverse events, alteration in liver or renal enzymes and edema or weight gain were reported. Conclusion: Saroglitazar is a potential therapeutic option in type 2 diabetic patients with high TG levels, not controlled by statins, for comprehensive control of lipid and glycemic parameters with acceptable safety profile.

Background: Dyslipidemia is an important comorbid factor of type 2 diabetes mellitus (T2DM) that increases the risk of cardiovascular diseases. This study aimed to assess the pattern of dyslipidemia and atherogenic indices and determine its relation with glycemic control., Methods: A cross-sectional study enrolled 382 patients with diabetic dyslipidemia. The socio-demographics data, clinical features, and laboratory parameters were collected. The baseline lipid parameters such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1C) were measured. Atherogenic indices such as TC/HDL-C ratio, TG/HDL-C ratio, LDL-C/HDL-C ratio, non-HDL-C/HDL-C and atherogenic index of plasma (AIP) [log10 (TG/HDL-C)] were calculated. T2DM patients were classified into three groups based on the degree of glycemic control: Good glycemic control (HbA1C<7%), fair control (HbA1C 7-8%), and poor control (HbA1C>8%)., Results: The population's mean age was 48.60±6.15 years, with 145 (38%) males. We found mixed dyslipidemia as the most prevalent (36.1%) form of dyslipidemia in our patients. The most common pattern in atherogenic indices was AIP (94.2%). HbA1c was positively correlated with duration of diabetes (r = 0.253, p<0.001). In multivariate logistic regression analysis, duration of diabetes (>10 years) was significantly associated with poor glycemic control with an odds ratio (OR) of 2.31(95% CI; 1.25-4.24, p=0.007)., Conclusion: The present study indicated that neither the pattern of dyslipidemia nor the atherogenic indices were markers of poor glycemic control among South Indian patients attending our tertiary care institute. However, duration of diabetes was significantly associated with poor glycemic control., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bage et al.)

Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2 diabetes, causing diabetic dyslipidemia. Cyclocarya paliurus (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in lipid loaded mice (Kurihara et al., 2003), although the detailed mechanisms and active ingredients for this hypolipidemic effect have not yet been answered. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches. Our results revealed that serum and hepatic levels of total triglyceride (TG), total cholesterol (T-CHO), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), as well as 30 lipids including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were improved in comparison with untreated diabetic mice. In parallel, 14 phytochemical compounds of CP were determined in mice serum after CP administration. Mechanistically, the network pharmacology analysis revealed the predicted targets of CP’s active ingredients ALOX12, APP, BCL2, CYP2C9, PTPN1 and linked lipidome targets PLD2, PLA2G(s), and PI3K(s) families could be responsible for the CP effects on diabetic dyslipidemia. In conclusion, this study revealed the beneficial effects of CP on diabetic dyslipidemia are achieved by reducing accumulation of hepatic lipid droplets and regulating circulatory lipids in diabetic mice, possibly through PI3K signaling and MAPK signaling pathways. GRAPHICAL ABSTRACT Work flow of the evaluation of the effects and mechanisms of Cyclocarya paliurus leaves tea on dyslipidemia in diabetic mice. [ABSTRACT FROM AUTHOR]

In 2015, the US Food and Drug Administration (FDA) approved the anti-proprotein convertase subtilsin/kexin type 9 (PCSK9) monoclonal antibodies, alirocumab and evolocumab, to treat patients with hypercholesterolemia and mixed dyslipidemia. Since then, considerable attention has been paid to the use of these monoclonal antibodies for the treatment of diabetic dyslipidemia with a goal of reducing the risk for cardiovascular disease. Recently, consensus statements on the clinical use of PCSK9 inhibitors in patients with type 2 diabetes mellitus, who are unable to achieve the goal of low-density lipoprotein cholesterol (<70 mg/dL or <1.8 mmol/L), have been published by panels of experts in Greece, Europe (European Society of Cardiology and European Atherosclerosis Society Task Force), and the United States (American College of Cardiology Consensus Committee). On December 1, 2017, the FDA approved evolocumab to prevent heart attack, stroke, and coronary revascularization. In this article, we review recent advances concerning the pathophysiology of diabetic dyslipidemia, the physiology of PCSK9, the mechanisms of action of PCSK9 inhibitors, clinical trials examining PCSK9 inhibitors in type 2 diabetes, and perspectives of nonstatin therapy in the treatment of diabetic dyslipidemia. [ABSTRACT FROM AUTHOR]

Diabetic dyslipidemia in type 2 diabetes (T2DM) is characterized by elevated levels of triglycerides (TG), decreased levels of high density lipoprotein-cholesterol (HDL-C), elevated levels of low density lipoprotein-cholesterol (LDLC), and the predominance of small and dense LDL particles (sdLDL). The mechanism underlying diabetic dyslipidemia remains unclear. Insulin resistance is believed to be an important determinant. Mechanisms underlying insulin resistance-induced diabetic dyslipidemia seem to be related to apolipoprotein CIII (ApoCIII), a known inhibitor of lipoprotein lipase. The concentration of very low density lipoprotein1 (VLDL1) with a higher TG content and abundant ApoCIII was found to be significantly elevated in patients with T2DM. Recently, volanesorsen as a promising ApoIII inhibitor was shown to improve the lipid profile in patients with diabetic dyslipidemia. Herein, this paper will review recent advance in pathophysiology of diabetic dyslipidemia and the role of ApoCIII in this condition, with focus on describing a novel drug volanesorsen as potential treatment strategy. [ABSTRACT FROM AUTHOR]