Depression in type 1 diabetes was associated with high levels of circulating galectin-3

Objective Neuroinflammatory responses are implicated in depression. The aim was to explore whether depression in patients with type 1 diabetes (T1D) was associated with high circulating galectin-3, controlling for metabolic variables, s-creatinine, life style factors, medication and cardiovascular complications. Design Cross-sectional. Methods Participants were T1D patients (n = 283, 56% men, age 18–59 years, diabetes duration ≥1 year). Depression was assessed by Hospital Anxiety and Depression Scale-depression subscale. Blood samples, anthropometrics and blood pressure were collected, and supplemented with data from medical records and the Swedish National Diabetes Registry. Galectin-3 ≥2.562 µg/l, corresponding to the 85th percentile, was defined as high galectin-3. Results Median (quartile1, quartile3) galectin-3 (µg/l) was 1.3 (0.8, 2.9) for the 30 depressed patients, and 0.9 (0.5, 1.6) for the 253 non-depressed, P = 0.009. Depression was associated with high galectin-3 in all the 283 patients (adjusted odds ratio (AOR) 3.5), in the 161 men (AOR 3.4), and in the 122 women (AOR 3.9). HbA1c, s-lipids, s-creatinine, blood pressure, obesity, smoking, physical inactivity, cardiovascular complications and drugs (antihypertensive, lipid lowering, oral antidiabetic drugs and antidepressants) were not associated with high galectin-3. Conclusions This is the first study to show an association between depression and galectin-3. Depression was the only explored parameter associated with high circulating galectin-3 levels in 283 T1D patients. High galectin-3 levels might contribute to the increased risk for Alzheimer’s disease, cardiovascular and all-cause mortality observed in persons with depression. Potentially, in the future, treatment targeting galactin-3 might improve the prognosis for patients with high galectin-3 levels.

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Soluble CD163 was linked to galectin-3, diabetic retinopathy and antidepressants in type 1 diabetes

Endocrine Connections ◽

10.1530/ec-18-0336 ◽

2018 ◽

Vol 7 (12) ◽

pp. 1343-1353 ◽

Cited By ~ 5

Author(s):

Eva O Melin ◽

Jonatan Dereke ◽

Maria Thunander ◽

Magnus Hillman

Keyword(s):

Blood Pressure ◽

Type 1 Diabetes ◽

Diabetic Retinopathy ◽

Depression Scale ◽

High Plasma ◽

Soluble Form ◽

Diabetes Clinic ◽

Cross Sectional ◽

Galectin 3

Objective Depression has been associated with diabetic retinopathy and increased plasma levels of galectin-3, a lectin expressed in activated macrophages. Increased levels of sCD163, the soluble form of a macrophage expressed scavenger receptor involved in several inflammatory processes, have been demonstrated in the vitreous of the eye in type 1 diabetes (T1D) patients with severe diabetic retinopathy. The aim was to explore whether circulating sCD163 was associated with diabetic retinopathy, depression and/or galectin-3 in T1D patients, controlling for gender, metabolic factors, other diabetes complications, life style and medication. Design Cross sectional. Methods Two hundred eighty-seven T1D patients, men 56%, age 18–59 years, diabetes duration ≥1 year, were consecutively recruited from one specialist diabetes clinic. Depression was assessed by Hospital Anxiety and Depression Scale-Depression subscale. Blood samples, anthropometrics and blood pressure values were collected, supplemented with data from electronic medical records and the Swedish National Diabetes Registry. High plasma sCD163 was defined as ≥0.575 mg/L (corresponding to the 80th percentile) and high plasma galectin-3 as ≥4.659 µg/L (corresponding to the 95th percentile). Results The prevalence of depression was 10%, antidepressant medication 8%, diabetic retinopathy 72%, high sCD163 20% and high galectin 3 5%. High galectin-3 (AOR 9.7), antidepressants (AOR 3.8), diabetic retinopathy (AOR 2.4) and systolic blood pressure (per mmHg) (AOR 1.03) were associated with high sCD163. Conclusions This is the first study to show that circulating sCD163 was independently associated with galectin-3, the use of antidepressants and diabetic retinopathy, in patients with T1D. Depression was not associated with sCD163.

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Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

BMC Psychiatry ◽

10.1186/s12888-020-02977-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Eva O. Melin ◽

Jonatan Dereke ◽

Magnus Hillman

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Goodness Of Fit ◽

Hdl Cholesterol ◽

Cross Sectional ◽

Cholesterol Levels ◽

Increased Risk ◽

Galectin 3 ◽

Low Levels

Abstract Background Low levels of the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and depression are linked to cardiovascular disease. Galectin-3, inadequate glycemic control and low high-density lipoprotein (HDL)-cholesterol levels were previously linked to depression in these patients with type 1 diabetes mellitus (T1DM). The main aim was to explore whether sTWEAK was associated with depression. A secondary aim was to explore diabetes related variables associated with low sTWEAK. Methods Cross-sectional design. T1DM patients (n = 283, men 56%, age18–59 years) were consecutively recruited from one specialist diabetes clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. Enzyme linked immunosorbent assays were used to measure sTWEAK and galectin-3. Low sTWEAK was defined as < 7.2 ng/ml and high galectin-3 as ≥2.6 ng/ml. Multiple logistic regression analyses were performed, calibrated and validated for goodness of fit. We adjusted for age, sex, diabetes duration, galectin-3, metabolic variables, serum-creatinine, smoking, physical inactivity, medication, and cardiovascular complications. Results For 29 depressed versus 254 non-depressed patients the prevalence rates were for low sTWEAK: 93 and 68% (p = 0.003) and for high galectin-3: 34 and 13% (p = 0.005) respectively. HDL-cholesterol levels were lower for the depressed (p = 0.015). Patients with low sTWEAK versus high sTWEAK had lower usage of continuous subcutaneous insulin infusion (CSII) (6% versus 17%, p = 0.005). Low sTWEAK (adjusted odds ratio (AOR) 9.0, p = 0.006), high galectin-3 (AOR 6.3, p = 0.001), HDL-cholesterol (per mmol/l) (AOR 0.1, p = 0.006), use of antidepressants (AOR 8.4, p < 0.001), and age (per year) (AOR 1.05, p = 0.027) were associated with depression. CSII (AOR 0.3, p = 0.003) and depression (AOR 7.1, p = 0.009) were associated with low sTWEAK. Conclusions Lower levels of sTWEAK and HDL-cholesterol and higher levels of galectin-3 were independently associated with depression in T1DM. These factors might all contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. CSII (inversely) and depression were independently associated with low sTWEAK levels.

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Depression, obesity, and smoking were independently associated with inadequate glycemic control in patients with type 1 diabetes

Acta Endocrinologica ◽

10.1530/eje-13-0137 ◽

2013 ◽

Vol 168 (6) ◽

pp. 861-869 ◽

Cited By ~ 35

Author(s):

Eva O Melin ◽

Maria Thunander ◽

Ralph Svensson ◽

Mona Landin-Olsson ◽

Hans O Thulesius

Keyword(s):

Type 1 Diabetes ◽

Glycemic Control ◽

Physical Inactivity ◽

Depression Scale ◽

Self Report ◽

Cross Sectional ◽

Diabetes Registry ◽

Control Of Diabetes ◽

Inadequate Glycemic Control

ObjectiveThe aim of this study was to explore the associations between inadequate glycemic control of diabetes and psychological, anthropometric, and lifestyle variables in a population-based cohort of type 1 diabetes patients.DesignCross-sectional study.MethodsIn this study, 292 patients with type 1 diabetes, aged 18–59 years, participated. Psychological data were assessed by self-report instruments: Hospital Anxiety and Depression Scale and Toronto Alexithymia Scale-20. Anthropometrics, blood analyses, data from medical records, and data from the Swedish National Diabetes Registry were collected.ResultsSelf-reported depression (adjusted odds ratio (AOR) 4.8), obesity (AOR 4.3), and smoking (AOR 3.0) were independently associated with inadequate glycemic control of diabetes (HbA1c>8.6%). Gender-stratified analyses showed that self-reported depression (AOR 19.8) and obesity (AOR 7.0) in women and smoking in men (AOR 4.2) were associated with HbA1c>8.6%. Alexithymia, antidepressant medication, and physical inactivity were associated with HbA1c>8.6% only in bivariate analyses. Alexithymia, self-rated anxiety, physical inactivity, and absence of abdominal obesity were associated with self-reported depression.ConclusionsDepression was the only psychological factor independently associated with HbA1c>8.6%. The association was of comparable importance as obesity and smoking, well-known risk factors for inadequate glycemic control and diabetes complications. The association between depression and HbA1c>8.6% was particularly strong for women. Alexithymia, which is a relatively stable personality trait, was associated with depression. In the future care of patients with diabetes, psychological aspects should be considered alongside anthropometrics and lifestyle factors in order to achieve the goals for HbA1c.

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Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

10.21203/rs.2.19662/v2 ◽

2020 ◽

Author(s):

Eva.O. Melin ◽

Jonatan Dereke ◽

Magnus Hillman

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Goodness Of Fit ◽

Hdl Cholesterol ◽

Cross Sectional ◽

Cholesterol Levels ◽

Increased Risk ◽

Galectin 3 ◽

Low Levels

Abstract BackgroundLow levels of the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and depression are linked to cardiovascular disease. Galectin-3, inadequate glycemic control and low high-density lipoprotein (HDL)-cholesterol levels were previously linked to depression in these patients with type 1 diabetes mellitus (T1DM). The main aim was to explore whether sTWEAK was associated with depression. A secondary aim was to explore diabetes related variables associated with low sTWEAK.MethodsCross-sectional design. T1DM patients (n = 283, men 56%, age18-59 years) were consecutively recruited from one specialist diabetes clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥ 8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. Enzyme linked immunosorbent assays were used to measure sTWEAK and galectin-3. Low sTWEAK was defined as < 7.2 ng/ml and high galectin-3 as ≥ 2.6 ng/ml. Multiple logistic regression analyses were performed, calibrated and validated for goodness of fit. We adjusted for age, sex, diabetes duration, galectin-3, metabolic variables, serum-creatinine, smoking, physical inactivity, medication, and cardiovascular complications. Results For 29 depressed versus 254 non-depressed patients the prevalence rates were for low sTWEAK: 93% and 68% (p = 0.003) and for high galectin-3: 34% and 13% (p = 0.005) respectively. HDL-cholesterol levels were lower for the depressed (p = 0.015). Patients with low sTWEAK versus high sTWEAK had lower usage of continuous subcutaneous insulin infusion (CSII) (6% versus 17%, p = 0.005). Low sTWEAK (adjusted odds ratio (AOR) 9.0, p = 0.006), high galectin-3 (AOR 6.3, p = 0.001), HDL-cholesterol (per mmol/l) (AOR 0.1, p = 0.006), use of antidepressants (AOR 8.4, p < 0.001), and age (per year) (AOR 1.05, p = 0.027) were associated with depression. CSII (AOR 0.3, p = 0.003) and depression (AOR 7.1, p = 0.009) were associated with low sTWEAK.ConclusionsLower levels of sTWEAK and HDL-cholesterol and higher levels of galectin-3 were independently associated with depression in T1DM. These factors might all contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. CSII (inversely) and depression were independently associated with low sTWEAK levels.

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Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

10.21203/rs.2.19662/v1 ◽

2019 ◽

Author(s):

Eva O Melin ◽

Jonatan Dereke ◽

Magnus Hillman

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Hdl Cholesterol ◽

Cross Sectional ◽

Depressed Patients ◽

Increased Risk ◽

Galectin 3 ◽

Low Levels ◽

Diabetes Patients

Abstract BackgroundLow levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) have previously been linked to cardiovascular disease, which is also the case for depression. High levels of galectin-3 and HbA1c, and low levels of HDL-cholesterol, have previously been linked to depression in these patients. The aim was to explore whether low levels of sTWEAK were associated with depression in type 1 diabetes patients. We adjusted for age, sex, galectin-3, HbA1c, HDL-cholesterol, antidepressants, and cardiovascular complications. MethodsCross-sectional design. Type 1 diabetes patients (n=287, men 56%, age18-59 years) were consecutively recruited from one specialist diabetes out-patient clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic medical records. ELISA was used to measure sTWEAK and galectin-3. Low sTWEAK was defined as <7.1 ng/ml (<70th percentile), high galectin-3 as ≥2.562 µg/l (≥85th percentile) and high HbA1c as >70 mmol/mol (>8.6%). Non-parametric tests were used. Multiple logistic regression analyses (Backward: Wald) were performed, and calibrated and validated for goodness of fit with the data variables. Results Median (q1, q3) (ng/ml) sTWEAK were for 30 depressed and 257 non-depressed patients 1.5 (1.2, 2.9) and 2.7 (1.3, 13.0) respectively (p =0.021); median (q1, q3) (µg/l) galectin-3 were 1.348 (0.827, 2.850) and 0.916 (0.533, 1.637) respectively (p = 0.005). Four-teen percent of patients with low sTWEAK were depressed, and 2% of patients with high sTWEAK were depressed (p = 0.003). Low sTWEAK (adjusted odds ratio (AOR) (CI)) 9.5 (2.0-46) ), high galectin-3 (AOR (CI) 6.5 (2.3-18.7)), use of antidepressants (AOR (CI) 10.3 (3.3-30.4)), HDL-cholesterol (per mmol/l) (inversely) (AOR (CI) 0.1 (0.03-0.5)), and age (per year) (AOR (CI) 1.05 (1.00-1.09)) were associated with depression. ConclusionsThe depressed patients with type 1 diabetes had lower levels of sTWEAK than the non-depressed, which might contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. Low levels of sTWEAK and HDL-cholesterol and high levels of galectin-3 were independently associated with depression.

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Coeliac disease is associated with depression in children and young adults with type 1 diabetes: results from a multicentre diabetes registry

Acta Diabetologica ◽

10.1007/s00592-020-01649-8 ◽

2021 ◽

Author(s):

Sascha René Tittel ◽

◽

Désirée Dunstheimer ◽

Dörte Hilgard ◽

Burkhild Knauth ◽

...

Keyword(s):

Type 1 Diabetes ◽

Young Adults ◽

Coeliac Disease ◽

Diabetes Patient ◽

Routine Care ◽

Diabetes Registry ◽

Increased Risk ◽

Treatment Data ◽

Children And Young Adults

Abstract Aims To analyse the association between coeliac disease (CD) and depression in children, adolescents, and young adults with type 1 diabetes (T1D). Methods We included 79,067 T1D patients aged 6–20 years, with at least six months of diabetes duration, and treatment data between 1995 and 2019 were documented in the diabetes patient follow-up registry. We categorized patients into four groups: T1D only (n = 73,699), T1 + CD (n = 3379), T1D + depression (n = 1877), or T1D + CD + depression (n = 112). Results CD and depression were significantly associated (adjusted OR: 1.25 [1.03–1.53]). Females were more frequent in both the depression and the CD group compared with the T1D only group. Insulin pumps were used more frequently in T1D + CD and T1D + depression compared with T1D only (both p < .001). HbA1c was higher in T1D + depression (9.0% [8.9–9.0]), T1D + CD + depression (8.9% [8.6–9.2]), both compared with T1D only (8.2% [8.2–8.2], all p < .001). We found comorbid autism, attention deficit hyperactivity disorder, anxiety, schizophrenia, and eating disorders more frequently in the T1D + CD + depression group compared with T1D only (all p < .001). Conclusions CD and depression are associated in young T1D patients. The double load of T1D and CD may lead to an increased risk for depression. Depression was associated with additional psychological and neurological comorbidities. Aside from imperative CD screening after T1D diagnosis and regular intervals, depression screening might be helpful in routine care, especially in patients with diagnosed CD.

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Association between central non-dipping pattern and platelet morphology in adults with type 1 diabetes without cardiovascular disease: a cross-sectional study

Scientific Reports ◽

10.1038/s41598-021-94414-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michal Kulecki ◽

Dariusz Naskret ◽

Mikolaj Kaminski ◽

Dominika Kasprzak ◽

Pawel Lachowski ◽

...

Keyword(s):

Blood Pressure ◽

Type 1 Diabetes ◽

Smoking Status ◽

Cross Sectional Study ◽

Cross Sectional ◽

Distribution Width ◽

Non Invasive ◽

Platelet Morphology ◽

Oscillometric Device

AbstractThe non-dipping pattern is nighttime systolic blood pressure (SBP) fall of less than 10%. Several studies showed that the non-dipping pattern, increased mean platelet volume (MPV), and platelet distribution width (PDW) are associated with elevated cardiovascular risk. Hypertensives with the non-dipping pattern have higher MPV than the dippers but this relationship was never investigated among people with type 1 diabetes mellitus (T1DM). This study aimed to investigate the association between the central dipping pattern and platelet morphology in T1DM subjects. We measured the central and brachial blood pressure with a validated non-invasive brachial oscillometric device—Arteriograph 24—during twenty-four-hour analysis in T1DM subjects without diagnosed hypertension. The group was divided based on the central dipping pattern for the dippers and the non-dippers. From a total of 62 subjects (32 males) aged 30.1 (25.7–37) years with T1DM duration 15.0 (9.0–20) years, 36 were non-dippers. The non-dipper group had significantly higher MPV (MPV (10.8 [10.3–11.5] vs 10.4 [10.0–10.7] fl; p = 0.041) and PDW (13.2 [11.7–14.9] vs 12.3 [11.7–12.8] fl; p = 0.029) than dipper group. Multivariable logistic regression revealed that MPV (OR 3.74; 95% CI 1.48–9.45; p = 0.005) and PDW (OR 1.91; 95% CI 1.22–3.00; p = 0.005) were positively associated with central non-dipping pattern adjusting for age, sex, smoking status, daily insulin intake, and height. MPV and PDW are positively associated with the central non-dipping pattern among people with T1DM.

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Association of glycemic variability and hypoglycemia with distal symmetrical polyneuropathy in adults with type 1 diabetes

Scientific Reports ◽

10.1038/s41598-021-02258-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ziyang Shen ◽

Hemin Jiang ◽

Rong Huang ◽

Yunting Zhou ◽

Qian Li ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glycemic Variability ◽

Mean Amplitude ◽

Cross Sectional Study ◽

Cross Sectional ◽

C Peptide ◽

Nocturnal Hypoglycemia ◽

Increased Risk ◽

Distal Symmetrical Polyneuropathy

AbstractPrevious studies exploring the influence of glycemic variability (GV) on the pathogenesis of distal symmetrical polyneuropathy (DSPN) in type 1 diabetes (T1DM) produced conflicting results. The aim of this study was to assess the relationship between GV and DSPN in T1DM. Adults with T1DM were included in this cross-sectional study and asked to undergo 3-day CGM. GV quantified by coefficient of variation (CV) and mean amplitude of glucose excursions (MAGE) were obtained from CGM. Clinical characteristics and biochemical assessments were collected for analysis. The study comprised 152 T1DM patients (53.9% males) with mean age of 44.2 year. Higher levels of age and duration of diabetes and lower levels of total cholesterol, LDL, fasting C-peptide and postprandial C-peptide were observed in DSPN subjects. DSPN groups displayed a higher blood glucose between 00:00 and 12:59 according to the CGM profile. Higher MAGE and CV were associated with increased risk of DSPN in the fully adjusted model. Meanwhile, a significant association between measurements of hypoglycemia, especially nocturnal hypoglycemia, and DSPN was found after multiple tests. CGM parameters describing the glycemic variability and hypoglycemia were potential risk factors for DSPN in adults with T1DM.

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Abstract 569: Albuminuria, the HDL Proteome, and Prevalent Coronary Artery Calcium in Type 1 Diabetes

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.569 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Baohai Shao ◽

Leila Zelnick ◽

Jake Wimberger ◽

John Brunzell ◽

Jonathan Himmelfarb ◽

...

Keyword(s):

Type 1 Diabetes ◽

Coronary Artery ◽

Coronary Artery Calcium ◽

Renin Angiotensin System ◽

Cross Sectional Study ◽

Lipid Lowering ◽

Atherosclerotic Cardiovascular Disease ◽

Cvd Risk ◽

Cross Sectional

Patients with type 1 diabetes (T1D) are at high risk of atherosclerotic cardiovascular disease (CVD). Albuminuria is strongly associated with CVD risk and fully accounts for the excess overall mortality risk in some T1D cohorts. One important contributor might be alterations of the HDL proteome. In the current study, we tested the hypotheses that albuminuria is associated with alterations in the HDL proteome in T1D, and that these alterations are associated with prevalent CVD. We performed a cross-sectional study of 191 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) participants selected according to levels of urine albumin excretion (67 persistent normoalbuminuria, 64 persistent microalbuminuria, and 60 persistent macroalbuminuria). We used targeted proteomics and isotope dilution tandem-mass spectrometry to quantify the concentration of 47 proteins in HDL. Adjusting for age, sex, DCCT treatment group, duration of diabetes, lipid-lowering medications, renin-angiotensin system inhibitors, smoking, BMI, and HbA1c, and after accounting for multiple comparisons, six proteins in HDL were significantly associated with albuminuria (2 increased and 4 decreased). For example, compared to normoalbuminuria, macroalbuminuria was associated with 57% and 177% higher AMBP ( P =0.0003) and PTGDS ( P =0.0006), respectively, and 28% and 27% lower PON1 ( P =0.002) and PON3 ( P =0.008), respectively. Furthermore, PON1 and PON3 in HDL were strongly and negatively associated with the presence of coronary artery calcium, with odds ratios per 1-SD difference of 0.63 (0.43-0.92, 95% CI, P =0.02) for PON1 and 0.59 (0.40-0.87, 95% CI, P =0.008) for PON3. Our observations indicate that the HDL proteome is remodeled in albuminuric patients with T1D, and that these alterations in HDL’s protein cargo may mediate, in part, the relationship of albuminuria with CVD. Because PON1 and PON3 are anti-atherogenic in hypercholesterolemic mice, our data suggest that low levels of PON1 and PON3 in HDL increase the risk of atherosclerosis in diabetic humans. In future studies, it will be important to determine whether reductions of PON1 and PON3 in HDL predict the risk of future CVD in subjects with T1D.

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Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes: a comparative cross-sectional study

Lipids in Health and Disease ◽

10.1186/s12944-020-01397-2 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Eva O. Melin ◽

Jonatan Dereke ◽

Magnus Hillman

Keyword(s):

Type 1 Diabetes ◽

Advanced Glycation End Products ◽

Inflammatory Responses ◽

Lipid Lowering ◽

Advanced Glycation ◽

Cross Sectional ◽

Lipid Lowering Drugs ◽

Glycation End Products ◽

End Products

Abstract Background The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed. Results In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P < 0.001), and triglycerides (P < 0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD. Conclusions Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.

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