Glycemic Control and Complications in Type 2 Diabetes Mellitus

Stolar, Mark W.

doi:10.1016/j.amjmed.2009.12.004

Cited by 282 publications

(209 citation statements)

References 48 publications

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“…Controlling blood glucose is the primary clinical intervention for diabetes; however, glycemic control only manages the risk of complications: it does not restore normal metabolic activity. Consequently, patients with good glycemic control simply slow the progression of microvascular complications, rather than prevent them (7). Understanding the underlying molecular mechanisms that alter microvascular function in diabetes, therefore, is crucial to developing new strategies to prevent debilitating vascular complications.…”

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confidence: 99%

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

et al. 2016

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Diabetes strongly associates with microvascular complications that ultimately promote multiorgan failure. Altered myogenic responsiveness compromises tissue perfusion, aggravates hypertension, and sets the stage for later permanent structural changes to the microcirculation. We demonstrate that skeletal muscle resistance arteries isolated from patients with diabetes have augmented myogenic tone, despite reasonable blood glucose control. To understand the mechanisms, we titrated a standard diabetes mouse model (high-fat diet plus streptozotocin [HFD/STZ]) to induce a mild increase in blood glucose levels. HFD/STZ treatment induced a progressive myogenic tone augmentation in mesenteric and olfactory cerebral arteries; neither HFD nor STZ alone had an effect on blood glucose or resistance artery myogenic tone. Using gene deletion models that eliminate tumor necrosis factor (TNF) or sphingosine kinase 1, we demonstrate that vascular smooth muscle cell TNF drives the elevation of myogenic tone via enhanced sphingosine-1-phosphate (S1P) signaling. Therapeutically antagonizing TNF (etanercept) or S1P (JTE013) signaling corrects this defect. Our investigation concludes that vascular smooth muscle cell TNF augments resistance artery myogenic vasoconstriction in a diabetes model that induces a small elevation of blood glucose. Our data demonstrate that microvascular reactivity is an early disease marker and advocate establishing therapies that strategically target the microcirculation.

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confidence: 99%

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

et al. 2016

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“…[1,2], which is characterised by progressive albuminuria and a gradual decline in GFR, in association with progressive renal fibrosis or sclerosis, leading to ultimate chronic renal failure [3]. Although many therapeutic remedies focusing on hyperglycaemia and high blood pressure have been used, many patients still suffer progressive and severe renal injury [4], making the investigation of other pathogenic pathways and relevant therapeutic strategies worthwhile. Importantly, immune-mediated inflammatory processes [5], apoptosis [6,7] and reactive oxygen species (ROS) [5,8] in the kidney are involved in the developmental and progressive stages of DN.…”

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confidence: 99%

Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-κB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis

Yang¹,

Ka²,

et al. 2013

Diabetologia

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Aims/hypothesis Chronic inflammatory processes have been increasingly shown to be involved in the pathogenesis of diabetes and diabetic nephropathy. Recently, we demonstrated that a lectin-like domain of thrombomodulin (THBD), which is known as THBD domain 1 (THBDD1) and which acts independently of protein C activation, neutralised an inflammatory response in a mouse model of sepsis. Here, therapeutic effects of gene therapy with adeno-associated virus (AAV)-carried THBDD1 (AAV-THBDD1 ) were tested in a mouse model of type 2 diabetic nephropathy.Electronic supplementary material The online version of this article

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“…19) Undiagnosed DM or postprandial hyperglycemia has a progressive impact on vascular complications. 4,[20][21][22][23] Microvascular DM complications are strongly associated with HbA1c levels. 3,4) In contrast, macrovascular complications develop in the early stages of glycometabolic disorders and do not linearly correlate with HbA1c values.…”

Section: Discussionmentioning

confidence: 99%

“…4,[20][21][22][23] Microvascular DM complications are strongly associated with HbA1c levels. 3,4) In contrast, macrovascular complications develop in the early stages of glycometabolic disorders and do not linearly correlate with HbA1c values. 6,24) In the 1990s, intensive glucose lowering treatments for patients with DM demonstrated protective effects on microvascular complications but did not decrease macro-vascular complications (the Diabetes Control and Complications Trial; DCCT, Kumamoto study, UK Prospective Diabetes Study; UKPDS33).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, elevated HbA1c values are associated with increased prevalence and complexity of coronary artery disease (CAD), polyvascular disease, future microvascular and macro-vascular complications, and mortality. [3][4][5][6] However, in patients with established DM, intensive intervention for glycemic control guided by HbA1c values did not improve the risk of macro-vascular complications and survival prognosis. [7][8][9] To obtain favorable effects for protection from macro-vascular complications, early diagnosis and early intervention to correct glycemic abnormalities are essential.…”

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confidence: 99%

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Ability of 1,5-Anhydro-d-glucitol Values to Predict Coronary Artery Disease in a Non-Diabetic Population

2015

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SummaryIncreasing evidence has indicated that postprandial hyperglycemia affects coronary artery disease (CAD). The serum 1,5-anhydro-d-glucitol (1,5-AG) value is a useful clinical marker to evaluate short-term glycemic status and reflects glycemic excursions with greater sensitivity when compared with hemoglobinA1c (HbA1c), especially for patients in the postprandial state. The aim of this study was to evaluate the predictive value of 1,5-AG for CAD in patients without diabetes mellitus.This study included 729 consecutive patients who had undergone their first coronary angiography. A total of 284 patients (246 diabetic In multivariable logistic regression analysis, the HbA1c values did not indicate a predictive value for the prevalence of CAD. In contrast, the 1,5-AG levels were still an independent predictor of CAD (adjusted odds ratio 0.96, 95% confidence interval 0.93-0.99, P = 0.0097).Serum 1,5-AG is superior to HbA1c for predicting CAD prevalence in patients without diabetes mellitus. (Int Heart J 2015; 56: 587-591)

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Glycemic Control and Complications in Type 2 Diabetes Mellitus

Cited by 282 publications

References 48 publications

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-κB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis

Ability of 1,5-Anhydro-d-glucitol Values to Predict Coronary Artery Disease in a Non-Diabetic Population

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