Statins exacerbate glucose intolerance and hyperglycemia in a high sucrose fed rodent model

Seshadri, Sriram; Rapaka, Naimisha; Prajapati, Bhumika; Mandaliya, Dipeeka; Patel, Sweta; Muggalla, Christopher Shamir; Kapadia, Bandish; Babu, Phanithi Prakash; Misra, Parimal; Uday, Suma

doi:10.1038/s41598-019-45369-8

Cited by 20 publications

(19 citation statements)

References 41 publications

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“…However, when a longer duration of simvastatin treatment (i.e up to 80 days) was applied, significant weight loss was observed. (4) The main finding of the present study (Figure 1) revealed a significantly lower level of skeletal muscle PGC-1α in the simvastatin group compared to the control group (p = .026). This is similar to the study by Goodman et al(2015) which found a decrease in PGC-1α levels in the soleus muscles of mice given simvastatin 60 mg kg -1 day -1 and simvastatin 80 mg kg -1 day -1 for 2 weeks.…”

Section: Resultssupporting

confidence: 52%

Simvastatin Toxicity Induces Mitochondrial Dysfunction in Rat Skeletal Muscle

Zulfahmidah¹,

Hardjo²,

Kadir³

2021

Indian Journal of Forensic Medicine & Toxicology

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Background: Statins are the class of drugs that are widely used for lowering LDL cholesterol and as primary and secondary prevention to cardiovascular disease. However, the widespread use of statins is constrained by the presence of toxicity or intolerance, which affects drug control rates. The toxicity or intolerance of statins ranges from 10-15%. The most common statin toxicity is statin-associated muscle symptoms (SAMS). The underlying mechanisms of SAMS involve the disruption of mitochondrial biogenesis, potential membrane changes, reduced number of mitochondria, and changes in protein oxidative activity due to the accumulation of ROS in cells and tissues. The disruption of mitochondrial biogenesis can be marked by a decrease of peroxisome proliferator-activated receptor co-activator gamma (PGC-1a). This study aimed to determine the effect of simvastatin on skeletal muscle PGC-1a.Methods: Sixteen female Wistar rats (8-10 weeks of age) were randomized into 2 groups: (1) control group (n=8), and (2) simvastatin group(n=8). For 30 days, the simvastatin group was exposed to simvastatin at a dose of 10 mg/kg/day. Meanwhile, the control group animals only received 0.5% methyl cellulose. Gastrocnemius muscles were collected and PGC-1a levels were evaluated by using ELISA Kit.Results: Following 30 days of treatment, a significantly lower level of skeletal muscle PGC-1awas observed in the simvastatin group compared to the control group (p = .026). Conclusion:Our finding indicates that administration of simvastatin at a dose of 10 mg/kg/day for 30 days may decrease skeletal muscle PGC-1a leading to mitochondrial dysfunction in rat skeletal muscle.

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Section: Resultssupporting

confidence: 52%

Simvastatin Toxicity Induces Mitochondrial Dysfunction in Rat Skeletal Muscle

Zulfahmidah¹,

Hardjo²,

Kadir³

2021

Indian Journal of Forensic Medicine & Toxicology

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“…We found no overlap in statistically significant endpoints for DEA and statins except for decreased LDL/HDL ratios for DEA (9.8%; our 3-week study) versus statins [26.7%; 18-24month study (64)]. However, statins may increase hyperglycemia and risk for T2D (65) especially on a high carbohydrate diet (66) and their adverse effects include severe muscle condition; rhabdomyolysis, further exacerbated by metabolic syndrome (67). Thus, the population that cannot tolerate statins may benefit from DEA treatment that may lower the risk of progressive diseases initiated and driven by dyslipidemia.…”

Section: Discussionmentioning

confidence: 62%

Oral Azelaic Acid Ester Decreases Markers of Insulin Resistance in Overweight Human Male Subjects

Streeper

Louden²,

Izbicka

2020

In Vivo

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Background/Aim: Insulin resistance (IR) is linked to increased risk of cardiovascular disease and cancer. We examined safety and efficacy of the natural product diethyl azelate (DEA) in overweight males with a varying degree of IR. Patients and Methods: Seventeen subjects [age 18-42, hemoglobin A1c (A1c) of 5.2-6.2%] received orally 1 mg/kg DEA daily for 21 days. Blood plasma glucose, insulin and lipid levels were assessed before and after treatment. Results: DEA was well tolerated without hypoglycemia or adverse effects except transient diarrhea (n=1). DEA significantly reduced fasting glucose by 6.06 mg/dl (n=8) and insulin by 37.8% (n=8) in subjects with IR and/or A1c ≥5.6%. Furthermore, it improved cholesterol/HDL, LDL/HDL, and non-cholesterol HDL/HDL by 5.4, 6.5, and 6.6%, respectively in all subjects, and by 8.0, 9.8, and 9.8%, respectively in 9 subjects with A1c ≥5.6%. Conclusion: DEA efficacy correlates with the degree of IR. DEA holds promise as a novel treatment for the management of IR.Azelaic acid and its esters, azelates, occur naturally in plants, animals, and humans. We discovered that the naturally occurring fatty acid ester, diethyl azelate (DEA) (1), can be used for the treatment of diet-and ethanol-induced insulin resistance (IR), the hallmark of metabolic syndrome, prediabetes and Type 2 diabetes (T2D). A number of studies (2-4) have shown a correlation of metabolic diseases with increased risk of cancer, especially liver, pancreatic and endometrial (5-7).The Western diet combined with a sedentary lifestyle results in chronic metabolic inflammation (8,9). A diet 1173 This article is freely accessible online.

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“…Patients not treated with statins were more likely to improve HbA1c levels after transitioning to therapy with insulin pump. While several studies have shown an association of treatment with statins and increased HbA1c levels and risk of diabetes in the general population and in type 2 diabetes, [34][35][36] few studies assessed this association in T1D. In the Thousand & 1 Study, use of statins was independently associated with increased HbA1c in patients T1D.…”

Section: Discussionmentioning

confidence: 99%

Predictors of the effectiveness of insulin pumps in patients with type 1 diabetes mellitus

Neves

Carvalho

2021

Endocrine

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Insulin pump therapy has become the preferential treatment for type 1 diabetes (T1D) as it mimics the physiological secretion of insulin better than multiple daily injections. However, not all patients improve with insulin pump therapy. This study aims to determine the predictors of the effectiveness of insulin pumps in T1D. MethodsWe conducted a retrospective observational study of patients who started insulin pumps. Data from four timepoints (before, at 6, 12 and 36 months) were evaluated for outcomes of glycemic control and safety.The association of baseline predictors with outcomes was analyzed using linear and logistic regression models. ResultsWe evaluated 136 patients (57.4% females, age 36 ± 12 years, duration of T1D 14 ± 9 years). During the follow-up, there was a mean decrease of HbA1c of 0.9 ± 1.2%. The improvement in HbA1c was independent of sex, age and duration of T1D. Higher baseline HbA1c, family history of diabetes and not being treated with statins were predictors of improvement in HbA1c. Not being treated with statins and higher baseline HbA1c predicted improvement in HbA1c without worsening hypoglycemia. History of hypoglycemia was a predictor of severe hypoglycemia. Family history, higher baseline HbA1c and psychological/psychiatric disorders were predictors of ketoacidosis. ConclusionBene ts of insulin pump were independent of sex, age, and duration of T1D. Baseline HbA1c, family history of diabetes, treatment with statins, history of hypoglycemia and psychological/psychiatric disorders were predictors of outcomes and may allow the identi cation of patients who bene t most from insulin pump therapy or who are at increased risk of complications.

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Statins exacerbate glucose intolerance and hyperglycemia in a high sucrose fed rodent model

Cited by 20 publications

References 41 publications

Simvastatin Toxicity Induces Mitochondrial Dysfunction in Rat Skeletal Muscle

Simvastatin Toxicity Induces Mitochondrial Dysfunction in Rat Skeletal Muscle

Oral Azelaic Acid Ester Decreases Markers of Insulin Resistance in Overweight Human Male Subjects

Predictors of the effectiveness of insulin pumps in patients with type 1 diabetes mellitus

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