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

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.

Galectin-3 Binding Protein, Depression, and Younger Age Were Independently Associated With Alexithymia in Adult Patients With Type 1 Diabetes

“…Blood pressure was measured in the sitting position by a nurse. The antihypertensive drugs which were used by the patients were previously described ( 41 ). The use of antihypertensive drugs was dichotomized into users and non-users ( 41 ).…”

“…The antihypertensive drugs which were used by the patients were previously described ( 41 ). The use of antihypertensive drugs was dichotomized into users and non-users ( 41 ). Indications for antihypertensive drugs were systolic blood pressure >130 mm Hg and/or diastolic blood pressure >80 mm Hg ( 41 ).…”

“…Serum-lipids were collected after an overnight fast. Lipid lowering drugs were HMG CoA-reductase inhibitors, and the use of lipid lowering drugs was dichotomized into users and non-users ( 41 ). Indications for lipid lowering drugs were total cholesterol (TC) >4.5 mmol/l (>1.74 mg/dl) and/or LDL-cholesterol >2.5 mmol/l (>97 mg/dl) ( 41 ).…”

“…Self-report questionnaires were used to assess alexithymia, depression and anxiety. Blood samples, anthropometrics, and blood pressure were collected, supplemented with data from electronic health records (12,15,31,(40)(41)(42)(47)(48)(49). The study was performed in accordance with the Declaration of Helsinki, and was approved by the Regional Ethical Review Board of Linköping University, Linköping (Registration no.…”

“…Other factors previously linked to cardiovascular disease and mortality are metabolic disturbances (13,33,34), T1D (35), physical inactivity (36), smoking (37), depression (38), and anxiety (39). Depression has also been linked to several inflammatory, metabolic and HPA-axis disturbances (15,31,32,(40)(41)(42)(43)(44), which is also the case for obesity, smoking and physical inactivity (15,36,37,42,45). T1D is an auto-immune disorder characterized by insulindeficiency (46), which is accompanied by several metabolic disturbances (33,34).…”