Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study

Duvnjak, Lea; Blaslov, Kristina

doi:10.1016/j.jacl.2016.04.012

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…Given information gleaned from previous work as well as this investigation, it is hypothesized that Fluvastatin is inhibiting myoblast fusion in vitro via a mechanism independent of extracellular matrix remodeling. Although further investigation into this mechanism are warranted, the current investigation complements previous reports of the negative effects of statins on skeletal muscle health, which include changes in the adaptive response to stressors (current work), storage, and transport of lipids (Rebalka et al, 2016 ), and metabolic capacity/glucose handling (Ridker et al, 2008 ; Duvnjak and Blaslov, 2016 ).…”

Section: Discussionsupporting

confidence: 69%

Statin Therapy Negatively Impacts Skeletal Muscle Regeneration and Cutaneous Wound Repair in Type 1 Diabetic Mice

et al. 2017

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Those with diabetes invariably develop complications including cardiovascular disease (CVD). To reduce their CVD risk, diabetics are generally prescribed cholesterol-lowering 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors (i.e., statins). Statins inhibit cholesterol biosynthesis, but also reduce the synthesis of a number of mevalonate pathway intermediates, leading to several cholesterol-independent effects. One of the pleiotropic effects of statins is the reduction of the anti-fibrinolytic hormone plasminogen activator inhibitor-1 (PAI-1). We have previously demonstrated that a PAI-1 specific inhibitor alleviated diabetes-induced delays in skin and muscle repair. Here we tested if statin administration, through its pleiotropic effects on PAI-1, could improve skin and muscle repair in a diabetic rodent model. Six weeks after diabetes onset, adult male streptozotocin-induced diabetic (STZ), and WT mice were assigned to receive control chow or a diet enriched with 600 mg/kg Fluvastatin. Tibialis anterior muscles were injured via Cardiotoxin injection to induce skeletal muscle injury. Punch biopsies were administered on the dorsal scapular region to induce injury of skin. Twenty-four days after the onset of statin therapy (10 days post-injury), tissues were harvested and analyzed. PAI-1 levels were attenuated in statin-treated diabetic tissue when compared to control-treated tissue, however no differences were observed in non-diabetic tissue as a result of treatment. Muscle and skin repair were significantly attenuated in Fluvastatin-treated STZ-diabetic mice as demonstrated by larger wound areas, less mature granulation tissue, and an increased presence of smaller regenerating muscle fibers. Despite attenuating PAI-1 levels in diabetic tissue, Fluvastatin treatment impaired cutaneous healing and skeletal muscle repair in STZ-diabetic mice.

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Section: Discussionsupporting

confidence: 69%

Statin Therapy Negatively Impacts Skeletal Muscle Regeneration and Cutaneous Wound Repair in Type 1 Diabetic Mice

et al. 2017

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“…With regards to insulin resistance it was reported in the metabolic syndrome in men (METSIM) cohort that statin treatment was associated with decreased insulin sensitivity [62]. Along the same lines it was recently reported that type-1 diabetics on statin treatment showed decreased insulin sensitivity [66]. There are however reports of increased insulin sensitivity with statins, especially with pravastatin [67,68].…”

Section: Statins and Insulin Sensitivitymentioning

confidence: 95%

Lessons from basic pancreatic beta cell research in type-2 diabetes and vascular complications

2017

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The changes in lifestyle with increased access of food and reduced physical activity have resulted in the global epidemic of obesity. Consequently, individuals with type 2 diabetes and cardiovascular disease have also escalated. A central organ in the development of diabetes is the pancreas, and more specifically the pancreatic beta cells within the islets of Langerhans. Beta cells have been assigned the important task of secreting insulin when blood glucose is increased to lower the glucose level. An early sign of diabetes pathogenesis is lack of first phase insulin response and reduced second phase secretion. In this review, which is based on the foreign investigator award lecture given at the JSDC meeting in Sendai in October 2016, we discuss a possible cellular explanation for the reduced first phase insulin response and how this can be influenced by lipids. Moreover, since patients with cardiovascular disease and high levels of cholesterol are often treated with statins, we summarize recent data regarding effects on statins on glucose homeostasis and insulin secretion. Finally, we suggest microRNAs (miRNAs) as central players in the adjustment of beta cell function during the development of diabetes. We specifically discuss miRNAs regarding their involvement in insulin secretion regulation, differential expression in type 2 diabetes, and potential as biomarkers for prediction of diabetes and cardiovascular complications. Keywords Insulin secretion Á Exocytosis Á Beta cell Á Obesity Á Statin Á MicroRNA/miRNA The original version of this article was revised: The text including the subheading ''Statins and insulin sensitivity'' was transposed incorrectly and it has been updated in this article.

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“…Capozzi and Svendsen et al recently investigated the intra-islet paracrine relationship and demonstrated an essential role for alpha cell in the regulation of beta cell function in different models, raising the possibility that abnormal paracrine signaling contributes to alteration in glucose homeostasis during diabetes and emphasizing a role for paracrine intra-islet α-cell actions to maintain appropriate β-cell function (45,46). Although there is still a lack of a clear molecular explanation for the adverse effects of statin therapy on insulin sensitivity, this association has been reported in other studies: Duvniak et al showed that statin therapy introduction was associated with 36% increased risk of reduced insulin sensitivity after adjustment for confounding risk factors in subjects with type 1 diabetes; these findings were observed after 56 months of statin exposure (47). Furthermore, Cederberg et al reported a reduction in insulin sensitivity and secretion in non-diabetic Finnish men on statin therapy; decreases in insulin sensitivity and insulin secretion were dose dependent for simvastatin and atorvastatin (7).…”

Section: Discussionmentioning

confidence: 90%

Impaired glucagon suppression and reduced insulin sensitivity in subjects with prediabetes undergoing atorvastatin therapy

Urbano

Pino

Purrello

et al. 2019

European Journal of Endocrinology

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Objective Statin therapy has been linked to an increased risk of type 2 diabetes in high-risk populations; however, the pathophysiology of this association remains to be clarified. We investigated glucagon suppression and its relationship with insulin resistance in prediabetic subjects undergoing atorvastatin therapy; in addition, we studied molecular insulin signaling in pancreatic α-cells exposed to atorvastatin in vitro. Design and methods Fifty subjects with prediabetes were divided into two groups based on atorvastatin therapy. All subjects underwent an oral glucose tolerance test. Early (0–30 min), late (30–120 min) and overall (0–120 min) glucagon suppression were evaluated. Insulin sensitivity was estimated by the insulin sensitivity index (ISI0–120). Insulin signaling pathway and insulin-mediated glucagon suppression were investigated in pancreatic αTC1-6 cells chronically exposed (24 or 48 h) to atorvastatin (100 ng/mL). Results Individuals on statin therapy (n = 26) showed a significantly reduced early (0–30 min) (P = 0.003) and overall (0–120 min) (P = 0.01) glucagon suppression compared with controls (n = 24). In multivariate regression analysis, early glucagon suppression (0–30 min) exhibited a significant correlation with statin therapy. Regression analysis showed a significant association between ISI 0-120 and early0-30 (r = 0.33, P < 0.05) and overall0-120 (r = 0.38, P < 0.05) glucagon suppression. Moreover, in αTC1-6 cells atorvastatin treatment affected insulin-mediated glucagon suppression, insulin receptor phosphorylation and IRS-1-AKT pathway signaling. Conclusions Prediabetic patients undergoing statin therapy exhibit impaired glucagon suppression associated with lower insulin sensitivity. Our data revealed a new molecular aspect behind the deregulation of insulin sensitivity secondary to statin exposure.

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Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study

Cited by 9 publications

References 38 publications

Statin Therapy Negatively Impacts Skeletal Muscle Regeneration and Cutaneous Wound Repair in Type 1 Diabetic Mice

Statin Therapy Negatively Impacts Skeletal Muscle Regeneration and Cutaneous Wound Repair in Type 1 Diabetic Mice

Lessons from basic pancreatic beta cell research in type-2 diabetes and vascular complications

Impaired glucagon suppression and reduced insulin sensitivity in subjects with prediabetes undergoing atorvastatin therapy

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