Mannose-Binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

Gedebjerg, Anne; Bjerre, Mette; Kjærgaard, Alisa D; Steffensen, Rudi; Nielsen, Jens Steen; Rungby, Jørgen; Friborg, Søren; Brandslund, Ivan; Thiel, Steffen; Beck‐Nielsen, Henning; Sørensen, Henrik Toft; Hansen, Troels Krarup; Thomsen, Reimar Wernich

doi:10.2337/dc20-0345

Cited by 27 publications

(23 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differences between these study populations and their characterization might partially explain such contradictions. Moreover, the baseline cardiovascular risk has to be considered: all GAMI patients had a recent AMI, whereas only 10% of the patients studied by Hansen et al [ 9 ] had a previous cardiovascular event and the cohort from the Danish study [ 10 ] included a more unselected population with type 2 diabetes. Nevertheless, the hypothesis from the latter study [ 10 ], i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the baseline cardiovascular risk has to be considered: all GAMI patients had a recent AMI, whereas only 10% of the patients studied by Hansen et al [ 9 ] had a previous cardiovascular event and the cohort from the Danish study [ 10 ] included a more unselected population with type 2 diabetes. Nevertheless, the hypothesis from the latter study [ 10 ], i.e. that MBL levels and cardiovascular risk have a U-shaped relationship, could not be tested in the present study because of the limited sample size.…”

Section: Discussionmentioning

confidence: 99%

“…In accordance, a meta-analysis by Zhao et al [ 6 ] collecting data from 12 independent case–control studies, suggested that high expression of MBL may be correlated with a significantly increased risk of vascular complications in diabetes. More recently, a Danish cohort study reported a U-shaped association of MBL with cardiovascular outcomes in patients with type 2 diabetes [ 10 ]. Nevertheless, the role of MBL remains to be investigated in controlled settings and possibly related to acute stress.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mannose-binding lectin does not explain the dismal prognosis after an acute coronary event in dysglycaemic patients. A report from the GAMI cohort

Meziani

Ferrannini

Bjerre

et al. 2022

Cardiovasc Diabetol

Self Cite

View full text Add to dashboard Cite

Background Mannose binding lectin (MBL) has been suggested to be associated with an impaired cardiovascular prognosis in dysglycaemic conditions, but results are still contrasting. Our aims are (i) to examine whether MBL levels differ between patients with an acute myocardial infarction (MI) and healthy controls and between subgroups with different glucose tolerance status, and (ii) to investigate the relation between MBL and future cardiovascular events. Methods MBL levels were assessed at discharge and after 3 months in 161 AMI patients without any previously known glucose perturbations and in 183 age- and gender-matched controls from the Glucose metabolism in patients with Acute Myocardial Infarction (GAMI) study. Participants were classified as having dysglycaemia, i.e. type 2 diabetes or impaired glucose tolerance, or not by an oral glucose tolerance test. The primary outcome was a composite of cardiovascular events comprising cardiovascular death, AMI, stroke or severe heart failure during 11 years of follow-up. Total and cardiovascular mortality served as secondary outcomes. Results At hospital discharge patients had higher MBL levels (median 1246 μg/L) than three months later (median 575 μg/L; p < 0.01), the latter did not significantly differ from those in the controls (801 μg/L; p = 0.47). MBL levels were not affected by dysglycaemia either in patients or controls. Independent of glycaemic state, increasing MBL levels did not predict any of the studied outcomes in patients. In unadjusted analyses increasing MBL levels predicted cardiovascular events (hazard ratio HR: 1.67, 95% confidence interval CI 1.06–2.64) and total mortality (HR 1.53, 95% CI 1.12–2.10) in the control group. However, this did not remain in adjusted analyses. Conclusions Patients had higher MBL levels than controls during the hospital phase of AMI, supporting the assumption that elevated MBL reflects acute stress. MBL was not found to be independently associated with cardiovascular prognosis in patients with AMI regardless of glucose state.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mannose-binding lectin does not explain the dismal prognosis after an acute coronary event in dysglycaemic patients. A report from the GAMI cohort

Meziani

Ferrannini

Bjerre

et al. 2022

Cardiovasc Diabetol

Self Cite

View full text Add to dashboard Cite

show abstract

“…MBL plays a role in the immune system as it activates the complement system and has been linked to diabetic nephropathy and the risk of cardiovascular disease in diabetes ( 8 , 9 ). MBL levels increase up to 140% during pregnancy with a sharp decrease after delivery ( 10 ) and is speculated to contribute to a normal placentation and pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Extreme insulin resistance during pregnancy: a therapeutic challenge

Kampmann

Ovesen

Møller

et al. 2021

Endocrinology, Diabetes &Amp; Metabolism Case Reports

View full text Add to dashboard Cite

Summary During pregnancy, maternal tissues become increasingly insensitive to insulin in order to liberate nutritional supply to the growing fetus, but occasionally insulin resistance in pregnancy becomes severe and the treatment challenging. We report a rare and clinically difficult case of extreme insulin resistance with daily insulin requirements of 1420 IU/day during pregnancy in an obese 36-year-old woman with type 2 diabetes (T2D) and polycystic ovary syndrome (PCOS). The woman was referred to the outpatient clinic at gestational week 12 + 2 with a hemoglobin A1c (HbA1c) at 59 mmol/mol. Insulin treatment was initiated immediately using Novomix 30, and the doses were progressively increased, peaking at 1420 units/day at week 34 + 4. At week 35 + 0, there was an abrupt fall in insulin requirements, but with no signs of placental insufficiency. At week 36 + 1 a, healthy baby with no hypoglycemia was delivered by cesarean section. Blood samples were taken late in pregnancy to search for causes of extreme insulin resistance and showed high levels of C-peptide, proinsulin, insulin-like growth factor (IGF-1), mannan-binding-lectin (MBL) and leptin. CRP was mildly elevated, but otherwise, levels of inflammatory markers were normal. Insulin antibodies were undetectable, and no mutations in the insulin receptor (INSR) gene were found. The explanation for the severe insulin resistance, in this case, can be ascribed to PCOS, obesity, profound weight gain, hyperleptinemia and inactivity. This is the first case of extreme insulin resistance during pregnancy, with insulin requirements close to 1500 IU/day with a successful outcome, illustrating the importance of a close interdisciplinary collaboration between patient, obstetricians and endocrinologists. Learning points This is the first case of extreme insulin resistance during pregnancy, with insulin requirements of up to 1420 IU/day with a successful outcome without significant fetal macrosomia and hypoglycemia. Obesity, PCOS, T2D and high levels of leptin and IGF-1 are predictors of severe insulin resistance in pregnancy. A close collaboration between patient, obstetricians and endocrinologists is crucial for tailoring the best possible treatment for pregnant women with diabetes, beneficial for both the mother and her child.

show abstract

“…The association between MBL and cardiovascular events and mortality in T2D has recently been reassessed in a large cohort study, which indicates a U-shaped association in T2D ( 48 ). Earlier studies suggested that MBL levels were significantly greater in T1D patients with DKD when compared with those with normoalbuminuria ( 57 ).…”

Section: Clinical Evidence For Altered Complement In Dkdmentioning

confidence: 99%

The Complement Pathway: New Insights into Immunometabolic Signaling in Diabetic Kidney Disease

Tan

Snelson

Østergaard

et al. 2022

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: The metabolic disorder, diabetes mellitus, results in microvascular complications, including diabetic kidney disease (DKD), which is partly believe to involve disrupted energy generation in the kidney, leading to injury that is characterized by inflammation and fibrosis. An increasing body of evidence indicates that the innate immune complement system is involved in the pathogenesis of DKD; however, the precise mechanisms remain unclear. Recent Advances: Complement, traditionally thought of as the prime line of defense against microbial intrusion, has recently been recognized to regulate immunometabolism. Studies have shown that the complement activation products, Complement C5a and C3a, which are potent pro-inflammatory mediators, can mediate an array of metabolic responses in the kidney in the diabetic setting, including altered fuel utilization, disrupted mitochondrial respiratory function, and reactive oxygen species generation. In diabetes, the lectin pathway is activated via autoreactivity toward altered self-surfaces known as danger-associated molecular patterns, or via sensing altered carbohydrate and acetylation signatures. In addition, endogenous complement inhibitors can be glycated, whereas diet-derived glycated proteins can themselves promote complement activation, worsening DKD, and lending support for environmental influences as an additional avenue for propagating complement-induced inflammation and kidney injury. Critical Issues: Recent evidence indicates that conventional renoprotective agents used in DKD do not target the complement, leaving this web of inflammatory stimuli intact. Future Directions: Future studies should focus on the development of novel pharmacological agents that target the complement pathway to alleviate inflammation, oxidative stress, and kidney fibrosis, thereby reducing the burden of microvascular diseases in diabetes. Antioxid. Redox Signal . 37, 781–801.

show abstract

Mannose-Binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

Cited by 27 publications

References 42 publications

Mannose-binding lectin does not explain the dismal prognosis after an acute coronary event in dysglycaemic patients. A report from the GAMI cohort

Mannose-binding lectin does not explain the dismal prognosis after an acute coronary event in dysglycaemic patients. A report from the GAMI cohort

Extreme insulin resistance during pregnancy: a therapeutic challenge

The Complement Pathway: New Insights into Immunometabolic Signaling in Diabetic Kidney Disease

Contact Info

Product

Resources

About