Insulin Therapy Improves Endothelial Function in Type 2 Diabetes

Vehkavaara, Satu; Mäkimattila, Sari; Schlenzka, A; Vakkilainen, Juha; Westerbacka, Jukka; Yki‐Järvinen, Hannele

doi:10.1161/01.atv.20.2.545

Cited by 108 publications

(70 citation statements)

References 60 publications

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“…Recently, Riddle et al [4] demonstrated that even a simple insulin regimen lowers HbA 1 c levels to 6.9% in type 2 diabetic patients. However, due to peripheral insulin resistance, most of the patients needed rather high insulin dosages [4,5]. In this and other trials, the insulin analogue glargine was shown to improve glycaemic control with significantly less nocturnal hypoglycaemia than NPH insulin [2][3][4]6].…”

Section: Introductionmentioning

confidence: 70%

“…Currently, evidence is accumulating that insulin therapy in diabetic patients has rather beneficial effects on the cardiovascular system. It has been shown to normalise lipid abnormalities by reducing total plasma triglycerides and increasing plasma HDL-cholesterol, and also to improve endothelial function, determined by measuring forearm blood flow responses to endothelium-dependent vasodilators [5,6,9,10]. Furthermore, insulin exerts anti-inflammatory effects, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells

Staiger

Schweitzer³

et al. 2005

Diabetologia

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Aims/hypothesis: Present guidelines for the treatment of type 2 diabetes recommend HbA 1 c values of less than 7%. As beta cell function worsens during progress of the disease, insulin therapy is often necessary to achieve this ambitious goal. However, due to peripheral insulin resistance, many patients need rather high insulin dosages. In the light of the extremely high cardiovascular risk of diabetic patients, it is important to determine whether high concentrations of insulin or its frequently used analogues are harmful to the cardiovascular system. We therefore investigated the modulatory effects of regular human insulin and its analogue glargine on proliferation and apoptosis of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). Methods: Cells were treated with regular human insulin or insulin glargine. Proliferation was determined by [ 3 H]thymidine incorporation and by flow cytometric analysis of Ki-67 expression. Apoptosis was assessed by flow cytometry (cell cycle analysis and annexin V staining) and determination of caspase-3 activity. Results: HCAECs and HCASMCs treated with regular human insulin or insulin glargine did not show significant increases in DNA synthesis or Ki-67 expression. Administration of regular human insulin or insulin glargine did not modulate the extent of apoptotic events. No influence of insulin on lipoapoptotic vascular cell death could be detected.Conclusions/interpretation: Taken together, neither regular human insulin nor insulin glargine influences growth and apoptosis of human coronary artery cells in vitro. Our data do not suggest that regular human insulin or insulin glargine promote atherosclerosis through mechanisms affecting the cellularity of human coronary arteries.

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Section: Introductionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells

Staiger

Schweitzer³

et al. 2005

Diabetologia

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“…Insulin therapy has been shown to improve fasting and postprandial brachial artery FMD [164,165] and FABF [166][167][168], possibly through reduced glycaemia and a direct increase in endothelial NO production through 1-phosphatidylinositol 3-kinase signaling [166,169]. Studies investigating the effects of sulphonylureas on ED have demonstrated inconsistent results in T2D patients [170][171][172].…”

Section: Antiglycemic Agents and Insulin Sensitizersmentioning

confidence: 99%

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

2013

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■ AbstractType 2 diabetes (T2D) markedly increases the risk of cardiovascular disease. Endothelial dysfunction (ED), an early indicator of diabetic vascular disease, is common in T2D and independently predicts cardiovascular risk. Although the precise pathogenic mechanisms for ED in T2D remain unclear, at inception they probably involve uncoupling of both endothelial nitric oxide synthase activity and mitochondrial oxidative phosphorylation, as well as the activation of vascular nicotinamide adenine dinucleotide phosphate oxidase. The major contributing factors include dyslipoproteinemia, oxidative stress, and inflammation. Therapeutic interventions are designed to target these pathophysiological factors that underlie ED. Therapeutic interventions, including lifestyle changes, antiglycemic agents and lipid-regulating therapies, aim to correct hyperglycemia and atherogenic dyslipidemia and to improve ED. However, high residual cardiovascular risk is seen in both research and clinical practice settings. Well-designed studies of endothelial function in appropriately selected volunteers afford a good opportunity to test new therapeutic interventions, paving the way for clinical trials and utilization in the care of the diabetic patient. However, based on the results from a recent clinical trial, niacin should not be added to a statin in individuals with low high-density lipoprotein cholesterol and very well controlled low-density lipoprotein cholesterol.

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“…Besides the well-known benefit of insulin in the metabolic control of diabetic patients, some researchers also propose the existence of a cardioprotective action. Recent studies have shown that insulin exerts anti-inflammatory and anti-atherogenic effects and improves endothelial function (18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Impact of previous insulin therapy on the prognosis of diabetic patients with acute coronary syndromes

António

Soares²,

Lourenco

et al. 2010

Arq Bras Endocrinol Metab

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Objective: To determine whether previous insulin treatment independently influences subsequent outcomes in diabetic patients with ACS (acute coronary syndromes). Subjects and methods: 375 diabetic patients with ACS, divided in 2 groups: Group A (n = 69) -previous insulin and Group B (n = 306) -without previous insulin. Predictors of 1-year mortality and major adverse cardiac events (MACE) were analyzed by Cox regression analysis. Results: Group A had more previous stroke (17.4% vs. 9.2%, p = 0.047) and peripheral artery disease (13.0% vs. 3.6%, p = 0.005). They had significantly higher admission glycemia and lower LDL cholesterol. There were no significant differences in the type of ACS, in 1-year mortality (18.2% vs. 10.4%, p = 0.103) or MACE (32.1% vs. 23.0%, p = 0.146) between groups. In multivariate analysis, insulin treatment was neither an independent predictor of 1-year mortality nor of MACE. Conclusion: Despite the more advanced atherosclerotic disease, diabetics under insulin had similar outcomes to those without insulin. Insulin may protect diabetics from the expected poor adverse outcome of an advanced atherosclerotic disease. Arq Bras Endocrinol Metab. 2010;54(7):612-9 Keywords Insulin; diabetes; acute coronary syndromes; outcomes RESUMO Objectivo: Avaliar se a insulinoterapia prévia influencia de forma independente o prognóstico de diabéticos após uma síndrome coronária aguda (SCA). Sujeitos e métodos: 375 doentes diabéti-cos com SCA, divididos em 2 grupos: Grupo A (n = 69) -sob insulinoterapia prévia e Grupo B (n = 306) -sem insulinoterapia prévia. Os preditores de mortalidade a um ano e de eventos cardíacos adversos maiores (MACE) foram determinados pela regressão de Cox. Resultados: Verificou-se maior proporção de acidente vascular cerebral prévio (17,4% vs. 9,2%, p = 0,047) e doença arterial periférica (13,0% vs. 3,6%, p = 0,005) no Grupo A. Esses doentes apresentaram glicemia na admissão significativamente mais elevada e LDL inferior. Não houve diferenças estatisticamente significativas no tipo de SCA, na mortalidade (18,2% vs. 10,4%, p = 0,103) e MACE (32,1% vs. 23,0%, p = 0,146) em um ano entre os 2 grupos. Na análise multivariada, a insulinoterapia prévia não foi preditor independente nem de mortalidade, nem de MACE em 1 ano. Conclusão: Apesar da doença aterosclerótica mais avançada, os diabéticos previamente insulino-tratados têm um prognóstico semelhante aos não insulino-tratados. A insulinoterapia crônica poderá proteger os diabéticos da evolução desfavorável própria da doença aterosclerótica avançada. Arq Bras Endocrinol Metab. 2010;54(7):612-9 Descritores Insulina; diabetes; síndromes coronárias agudas; prognóstico Copyright © ABE&M todos os direitos reservados. 613Arq Bras Endocrinol Metab. 2010;54/7Insulin and acute coronary syndromes

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Insulin Therapy Improves Endothelial Function in Type 2 Diabetes

Cited by 108 publications

References 60 publications

Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells

Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

Impact of previous insulin therapy on the prognosis of diabetic patients with acute coronary syndromes

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