Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy

Saraheimo, Markku; Forsblom, Carol; Hansen, Troels Krarup; Teppo, Anna‐Maija; Fagerudd, Johan; Pettersson-Fernholm, Kim; Thiel, Steffen; Tarnow, Lise; Ebeling, Pertti; Flyvbjerg, Allan; Groop, Per‐Henrik

doi:10.1007/s00125-004-1594-1

Cited by 87 publications

(84 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The association between MBL and diabetic nephropathy has been observed in several clinical studies (2)(3)(4)(5)(6)(7)(8). Also, the MBL2 genotype in the present cohort was marginally unequally distributed between patients with or without diabetic nephropathy.…”

Section: Discussionsupporting

confidence: 78%

“…Several studies have demonstrated the close association between the lectin pathway of complement activation and diabetic nephropathy. In particular, high concentrations of the carbohydrate pattern-recognition molecule mannan-binding lectin (MBL), which initiates complement activation, are linked to diabetic nephropathy defined by urinary albumin excretion rate (2)(3)(4)(5)(6)(7)(8). In the present cohort, we previously showed the cross-sectional association between MBL2 genotype and diabetic nephropathy (2).…”

mentioning

confidence: 56%

See 1 more Smart Citation

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

et al. 2015

View full text Add to dashboard Cite

OBJECTIVEMannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this. RESEARCH DESIGN AND METHODSWe studied an existing 12-year prospective cohort with RESULTSNinety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002). CONCLUSIONSHigh MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.Late diabetes complications contribute to excess morbidity and mortality in diabetes. The complement cascade of the immune system is most likely implicated in the development of these complications (1). Diabetes may induce the formation of complement-activating ligands by two mechanisms: altered enzymatic protein glycosylation and increased nonenzymatic advanced glycation end product formation. Both products are hypothesized to be adversely recognized by complement-activating

show abstract

Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 56%

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

et al. 2015

View full text Add to dashboard Cite

show abstract

“…These observations seem to contradict recent articles describing increased MBL concentrations in patients with type 1 diabetes with microvascular complications [29][30][31][32][33]. However, MBL plays a dual role in modifying inflammatory responses to injury [34].…”

Section: Discussionmentioning

confidence: 70%

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

Fernández-Real¹,

Strączkowski

Vendrell

et al. 2006

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance. Materials and methods We performed a cross-sectional study of MBL protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in association with obesity, markers of inflammation and insulin action (euglycaemic clamp, n=113), and a longitudinal study of MBL protein before and after weight loss in obese patients (n=10). We also studied the effects of MBL in vitro in muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse model. Results Among 434 consecutive non-diabetic men, the ageadjusted serum MBL concentration was lower in obese subjects than in lean subjects (median: 959 μg/ml [interquartile range: 116.8-2,044 μg/ml] vs 1,365 [467-2,513] μg/ml; p=0.01) and was accompanied by increased serum inflammatory markers. Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum MBL concentration increased by a median of 110.2% after weight loss. The change in serum concentration of MBL was positively associated with the increase in insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma concentration of MBL-A was lower in insulinresistant obese ob/ob mice, as was the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL markedly increased fatty acid oxidation. Conclusions/interpretation These findings suggest that MBL, previously thought only to be involved in inflammation and immune system function, affects metabolic pathways.

show abstract

“…In these studies, MBL levels correlated with UAE within the normal range, but not with metabolic control. The serum MBL levels were increased in microalbuminuric type 1 diabetic patients when compared with normoalbuminuric patients [6]. Diabetic nephropathy was more prevalent among type 1 diabetic patients with a high MBL expression genotype and high circulating MBL levels than among patients with a low MBL genotype and low serum MBL levels [5].…”

Section: Discussionmentioning

confidence: 89%

“…Under normal conditions MBL does not bind to the body's own structures, but it does possess potential self-reactive properties. A significant association between serum MBL levels and renal function has been reported in normoalbuminuric, microalbuminuric and macroalbuminuric type 1 diabetic patients [4][5][6]. Furthermore, in a cohort study of type 1 diabetic patients followed for 18 years from diagnosis, serum MBL was a significant predictor of later renal impairment.…”

mentioning

confidence: 90%

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

et al. 2007

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis An increasing amount of evidence indicates that mannose-binding lectin (MBL) plays a role in the development of diabetic nephropathy. The main objective of the study was to analyse whether MBL influences the effects of diabetes on the kidneys. Materials and methods In one group of wild-type mice and in one group of MBL double knockout mice we induced diabetes by the use of streptozotocin as a model of type 1 diabetes. Two groups of non-diabetic mice, wild-type and MBL knockout, were also included. By two-way ANOVA we evaluated if MBL modulated the effects of diabetes by testing the interaction between diabetes and MBL. Results MBL interacted with the effects of diabetes on three outcome measures: kidney weight (p<0.001), urinary albumin excretion (p=0.001) and the expression of collagen IVα1 (Col4a1) mRNA (p=0.002). This means that the effects that diabetes normally has on these parameters were significantly modified by MBL. MBL showed a tendency to interact with the effects of diabetes on glomerular basement membrane thickness and total mesangial volume (p=0.065 and p=0.063, respectively). Glomerular volume and total mesangial volume were significantly smaller in animals lacking MBL than in wild-type animals (p=0.006 and p=0.047, respectively). Conclusions/interpretation These findings, for the first time, show that the degree of kidney alteration as a consequence of diabetes is modified by MBL. These findings support a pivotal role of MBL in the development of diabetic kidney disease.

show abstract

Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy

Cited by 87 publications

References 18 publications

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

Contact Info

Product

Resources

About