Depression was associated with younger age, female sex, obesity, smoking, and physical inactivity, in 1027 patients with newly diagnosed type 2 diabetes: a Swedish multicentre cross-sectional study.

BACKGROUND: Depression is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The aims were to explore the prevalence of depression, anxiety, antidepressant use, obesity, Hemoglobin A1c > 64 mmol/mol, life-style factors, pre-existing CVD, in patients with newly diagnosed T2D; to explore associations with depression; and to compare with Swedish general population data. METHODS: Multicentre, cross-sectional study. INCLUSION CRITERIA: adults with serologically verified newly diagnosed T2D. Included variables: age, sex, current depression and anxiety (Hospital Anxiety and Depression Scale), previous depression, antidepressant use, obesity (BMI ≥ 30 and ≥ 40 kg/m2), Hemoglobin A1c, pre-existing CVD. Logistic regression analyses were performed. RESULTS: In 1027 T2D patients, aged 18-94 years, depression was associated with age (per year) (inversely) (odds ratio (OR) 0.97), anxiety (OR 12.2), previous depression (OR 7.1), antidepressant use (OR 4.2), BMI ≥ 30 kg/m2 (OR 1.7), BMI ≥ 40 kg/m2 (OR 2.3), smoking (OR 1.9), physical inactivity (OR 1.8), and women (OR 1.6) (all p ≤ 0.013). Younger women (n = 113), ≤ 59 years, compared to younger men (n = 217) had higher prevalence of current depression (31% vs 12%), previous depression (43 vs 19%), anxiety (42% vs 25%), antidepressant use (37% vs 12%), BMI ≥ 30 kg/m2 (73% vs 60%) and BMI ≥ 40 kg/m2) (18% vs 9%), and smoking (26% vs 16%) (all p ≤ 0.029). Older women (n = 297), ≥ 60 years, compared to older men (n = 400) had higher prevalence of previous depression (45% vs 12%), anxiety (18% vs 10%), antidepressant use (20% vs 8%), BMI ≥ 30 kg/m2 (55% vs 47%), BMI ≥ 40 kg/m2 (7% vs 3%) (all p ≤ 0.048), but not of current depression (both 9%). Compared to the Swedish general population (depression (women 11.2%, men 12.3%) and antidepressant use (women 9.8%, men 5.3%)), the younger women had higher prevalence of current depression, and all patients had higher prevalence of antidepressant use. CONCLUSIONS: In patients with newly diagnosed T2D, the younger women had the highest prevalence of depression, anxiety, and obesity. The prevalence of depression in young women and antidepressant use in all patients were higher than in the Swedish general population. Three risk factors for CVD, obesity, smoking, and physical inactivity, were associated with depression.

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

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.

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.

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.

Lower HDL-cholesterol, a known marker of cardiovascular risk, was associated with depression in type 1 diabetes: a cross sectional study.

BACKGROUND: Depression, metabolic disturbances and inflammation have been linked to cardiovascular disease and mortality. Low levels of high-density lipoprotein cholesterol (HDL-cholesterol), a known marker of cardiovascular risk, have been observed in patients with major depression in psychiatric populations. Our main aim was to explore associations between depression, antidepressants, and metabolic and inflammatory variables in patients with type 1 diabetes (T1D). A secondary aim was to explore variables associated with HDL-cholesterol. METHODS: Cross-sectional design. T1D patients (n = 292, men 55%, age18-59 years, diabetes duration ≥1 year) were consecutively recruited from one specialist diabetes clinic. Depression was defined as ≥8 points for Hospital Anxiety and Depression Scale-Depression sub scale. Blood samples, anthropometrics, blood pressure, and data regarding medication and life style were collected from electronic health records. Non-parametric tests, multiple logistic and linear regression analyses were performed. RESULTS: The depression prevalence was 10 and 8% used antidepressants. Median (q1, q3) HDL-cholesterol (mmol/l) was for the depressed 1.3 (1.2, 1.5) and for the non-depressed 1.6 (1.3, 1.8), p = 0.001. HDL-cholesterol levels (per mmol/l) were negatively associated with depression (Adjusted odds ratio (AOR) 0.2, p = 0.007), and the use of antidepressants was positively associated with depression (AOR 8.1, p <  0.001). No other metabolic or inflammatory variables, or life style factors, were associated with depression when adjusted for antidepressants. Abdominal obesity was associated with antidepressants in women (AOR 4.6, p = 0.029). Decreasing HDL-cholesterol levels were associated with increasing triglyceride levels (p <  0.001), increasing high-sensitive C-reactive protein (hs-CRP) levels (p = 0.021), younger age (p <  0.001), male sex (p <  0.001), and depression (p = 0.045). CONCLUSIONS: Lower HDL-cholesterol levels, known predictors of cardiovascular disease, were associated with depression in patients with T1D. The use of antidepressants was associated with abdominal obesity in women. Depression, low-grade inflammation measured as hs-CRP, higher triglycerides, male sex, and lower age were independently associated with lower HDL-cholesterol levels.

Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation.

Dendritic cells (DCs) involved in proinflammatory immune responses derive mainly from peripheral monocytes, and the cells subsequently mature and migrate into the inflammatory micromilieu. Here we report that suppressing of 15-lipoxygenase-1 led to a substantial reduction in DC spreading and podosome formation in vitro. The surface expression of CD83 was significantly lower in both sh-15-lipoxygenase-1 (15-LOX-1)-transduced cells and DCs cultivated in the presence of a novel specific 15-LOX-1 inhibitor. The T-cell response against tetanus-pulsed DCs was only affected to a minor extent on inhibition of 15-LOX-1. In contrast, endocytosis and migration ability of DCs were significantly suppressed on 15-LOX-1 inhibition. The expression of 15-LOX-1 in DCs was also demonstrated in affected human skin in atopic and contact dermatitis, showing that the enzyme is indeed expressed in inflammatory diseases in vivo. This study demonstrated that inhibiting 15-LOX-1 led to an impaired podosome formation in DCs, and consequently suppressed antigen uptake and migration capacity. These results indicated that 15-LOX-1 is a potential target for inhibiting the trafficking of DCs to lymphoid organs and inflamed tissues and decreasing the inflammatory response attenuating symptoms of certain immunologic and inflammatory disorders such as dermatitis.-Han, H., Liang, X., Ekberg, M., Kritikou, J. S., Brunnström, Å., Pelcman, B., Matl, M., Miao, X., Andersson, M., Yuan, X., Schain, F., Parvin, S., Melin, E., Sjöberg, J., Xu, D., Westerberg, L. S., Björkholm, M., Claesson, H.-E. Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation.

Psychoeducation against depression, anxiety, alexithymia and fibromyalgia: a pilot study in primary care for patients on sick leave.

OBJECTIVES: Feasibility testing of a psychoeducational method -The Affect School and Script Analyses (ASSA) - in a Swedish primary care setting. Exploring associations between psychological, and medically unexplained physical symptoms (MUPS). DESIGN: Pilot study. SETTING: Three Swedish primary care centers serving 20,000 people. INTERVENTION: 8 weekly 2-hour sessions with a 5-7 participant group led by two instructors - followed by 10 individual hour-long sessions. SUBJECTS: Thirty-six patients, 29 women (81%), on sick-leave due to depression, anxiety, or fibromyalgia. OUTCOME MEASURES: Feasibility in terms of participation rates and expected improvements of psychological symptoms and MUPS, assessed by self-report instruments pre-, one-week post-, and 18 months post-intervention. Regression coefficients between psychological symptoms and MUPS. RESULTS: The entire 26-hour psychoeducational intervention was completed by 30 patients (83%), and 33 patients (92%) completed the 16-hour Affect School. One-week post-intervention median test score changes were significantly favorable for 27 respondents, with p < .05 after correction for multiple testing for 9 of 11 measures (depression, anxiety, alexithymia, MUPS, general health, self-affirmation, self-love, self-blame, and self-hate); 18 months post intervention the results remained significantly favorable for 15 respondents for 7 of 11 measures (depression, alexithymia, MUPS, general health, self-affirmation, self-love, and self-hate). CONCLUSIONS: A psychoeducational method previously untested in primary care for mostly women patients on sick-leave due to depression, anxiety, or fibromyalgia had >80% participation rates, and clear improvements of self-assessed psychological symptoms and MUPS. The ASSA intervention thus showed adequate feasibility in a Swedish primary care setting. Key Points A pilot study of a psychoeducational intervention - The Affect School and Script Analyses (ASSA) - was performed in primary care • The intervention showed feasibility for patients on sick-leave due to depression, anxiety, or fibromyalgia • 92% completed the 8 weeks/16 hours Affect School and 83% completed the entire 26-hour ASSA intervention • 9 of 11 self-reported measures improved significantly one-week post intervention • 7 of 11 self-reported measures improved significantly 18 months post-intervention.

Depression differed by midnight cortisol secretion, alexithymia and anxiety between diabetes types: a cross sectional comparison.

BACKGROUND: Increased prevalence of depression is found in both type 2 diabetes (T2D) and type 1 diabetes (T1D). Melancholia and atypical depression differ by cortisol secretion and clinical features. The aim was to compare the clinical presentation of T1D and T2D patients in relation to self-reported depression, self-reported anxiety, alexithymia, obesity, and midnight salivary cortisol (MSC). METHODS: Comparative cross-sectional design. The participants were consecutively recruited from one hospital diabetes outpatient clinic: 24 T2D patients (31-59 years) and 148 T1D patients (32-59 years). Self-reported depression, anxiety and alexithymia were assessed by Hospital Anxiety and Depression scale and Toronto Alexithymia Scale-20. MSC, HbA1c, anthropometrics and data from medical records were collected. Multiple logistic regression analyses were performed. RESULTS: Comparisons of prevalence between diabetes types showed for T2D/T1D: depression 25%/12% (P = 0.10); high MSC (≥9.3 nmol/L) 38%/22% (P = 0.13); alexithymia 25%/13% (P = 0.12); anxiety 38%/35% (P = 0.82). The prevalence of high MSC did not differ between depressed and non-depressed T2D patients (17% vs. 44%, P = 0.35), but differed between depressed and non-depressed T1D patients (53% vs. 18%, P = 0.003). The alexithymia prevalence differed between depressed and non-depressed T2D patients (67% vs.11%, P = 0.018), and between depressed and non-depressed T1D patients (47% vs. 11%, P < 0.001). The anxiety prevalence did not differ between depressed and non-depressed T2D patients (67% vs. 28%, P = 0.15), but differed between depressed and non-depressed T1D patients (76% vs. 30%, P < 0.001). The obesity prevalence (BMI ≥30 kg/m2) was 83% for depressed T2D patients and 6% for depressed T1D patients. In the T2D patients, depression was associated with alexithymia (Adjusted odds ratio (AOR) 15.0). In the T1D patients, depression was associated with anxiety (AOR 11.0), foot complications (AOR 8.5), HbA1C >70 mmol/mol (AOR 6.4), and high MSC (≥9.3 nmol/L) (AOR 4.8). CONCLUSIONS: The depressed T2D patients had traits of atypical depression, without associated high MSC (≥9.3 nmol/L) and anxiety, but the association with alexithymia was strong. The depressed T1D patients had traits of melancholia with associated high MSC and anxiety. The obesity prevalence was high in depressed T2D patients and low in depressed T1D patients.

Elevated blood lipids are uncommon in patients with post-polio syndrome--a cross sectional study.

BACKGROUND: The post-polio syndrome occurs in people who previously have had poliomyelitis. After the initial recovery, new or increasing neurologic symptoms occur. Inflammation and dyslipidaemia may play an important role in the development of atherosclerotic complications, for example myocardial infarction and angina pectoris. Previous studies on cardiovascular risk factors in the post-polio syndrome have found a higher prevalence of hypertension, ischemic heart disease, hyperlipidaemia, and stroke in these patients. The present study was undertaken in order to evaluate whether post-polio patients have elevated lipid values, and if blood lipid abnormalities could be correlated to signs of inflammation. METHODS: Cross-sectional study of 89 consecutive post-polio patients, (53 women, mean age 65 years) from the Post-Polio Outpatient Clinic, Danderyd University Hospital, Stockholm, Sweden. The lipid profiles of post-polio patients were compared to age and sex matched reference values from two earlier studies. Statistical analyses were performed by the Student's t-test, and linear regression analyses were assessed by Pearson's correlation coefficient. RESULTS: Mean total cholesterol levels (5.7 mmol/L) were low or normal in post-polio patients, whereas low density lipoprotein levels (3.6 mmol/L) were normal, and high density lipoprotein (1.5 mmol/L) and triglycerides (1.4 mmol/L) lower than reference values. The prevalence of diabetes (7%), hypertension (38%), concomitant cardiovascular disease, (including angina pectoris, myocardial infarction, heart failure, atrial fibrillation and stroke) (7%), and calculated 10 year risk of coronary heart disease according to Framingham risk score algorithm (8%) was not increased in post-polio patients. CONCLUSIONS: Compared to reference populations, post-polio patients in Sweden appear to have low or normal total cholesterol and low density lipoprotein levels, whereas high density lipoprotein and triglyceride levels are low. Hence, a possible persisting inflammatory process in post-polio syndrome does not seem to be associated with increased lipids and an increased risk for coronary heart disease events.

Depression, smoking, physical inactivity and season independently associated with midnight salivary cortisol in type 1 diabetes.

BACKGROUND: Disturbances of the circadian rhythm of cortisol secretion are associated with depression, coronary calcification, and higher all-cause and cardiovascular mortality.The primary aim of this study was to test the associations between midnight salivary cortisol (MSC), depression and HbA1c, and control for behavioural, environmental and intra individual factors with possible impact on cortisol secretion, like smoking, physical inactivity, season, medication, diabetes duration, severe hypoglycemia episodes, age and gender in patients with type 1 diabetes. Secondary aims were to present MSC levels for a reference group of non-depressed type 1 diabetes patients with a healthy life style (physically active and non-smoking), and to explore seasonal variations. METHODS: A cross-sectional population based study of 196 patients (54% men and 46% women) aged 18-59 years that participated in a randomized controlled trial targeting depression in type 1 diabetes. Depression was assessed by the Hospital Anxiety and Depression Scale-depression subscale. MSC, HbA1c, serum-lipids, blood pressure, waist circumference and data from medical records and the Swedish National Diabetes Registry were collected. RESULTS: Thirty four patients (17%) had MSC ≥9.3 nmol/L, which was associated with smoking (AOR 5.5), spring season (AOR 4.3), physical inactivity (AOR 3.9), self-reported depression (AOR 3.1), and older age (per year) (AOR 1.08). HbA1c >70 mmol/mol (>8.6%) (AOR 4.2) and MSC ≥9.3 nmol/L (AOR 4.4) were independently linked to self-reported depression. Season was strongly associated with MSC levels and no other variables studied showed seasonal variations. In a reference group of 137 non-depressed patients with a healthy life style (physically active, non-smoking) the median MSC level was 4.6 nmol/L (range 1.9-23.0). CONCLUSIONS: In this study of patients with type 1 diabetes high MSC was linked to smoking, physical inactivity, depression, season and older age. Thus a high cortisol value identified three major targets for treatment in type 1 diabetes.

Post-polio syndrome - somatosensory dysfunction and its relation to pain: a pilot study with quantitative sensory testing.

OBJECTIVE: To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing. DESIGN: A cross-sectional, descriptive, pilot study conducted during 1 month. SUBJECTS/PATIENTS: Six patients with previously established post-polio syndrome and related chronic pain. METHODS: All subjects underwent a neurological examination including neuromuscular function, bedside sensory testing, a thorough pain anamnesis, and pain drawing. Screening for neuropathic pain was done with 2 questionnaires. A comprehensive Quantitative Sensory Testing battery was conducted with z-score transformation of obtained data, enabling comparison with published reference values and the creation of sensory profiles, as well as comparison between the study site (more polio affected extremity) and internal control site (less affected extremity) for each patient. RESULTS: Derived sensory profiles showed signs of increased prevalence of sensory aberrations compared with reference values, especially Mechanical Pain Thresholds, with significant deviation from reference data in 5 out of 6 patients. No obvious differences in sensory functions were seen between study sites and internal control sites. CONCLUSION: Post-polio syndrome may be correlated with a mechanical hyperalgesia/allodynia and might be correlated to a somatosensory dysfunction. With lack of evident side-to-side differences, the possibility of a generalized dysfunction in the somatosensory system might be considered.

Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinases explored in relation to the severity and progression of diabetic retinopathy in patients with type 1 diabetes: baseline and prospective analyses.

AIMS: To explore whether circulating matrix metalloproteinase-2 (MMP-2), MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin, MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-14, TIMP-2 and TIMP-3 were associated with the severity and progression of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D). METHODS: Baseline and prospective analyses were conducted over a period of 10.5 person-years. In 2009, recruitment and biochemical analyses (MMPs, TIMPs, glycated haemoglobin (HbA1c), serum creatinine, macroalbuminuria) were performed. Fundus photography, performed at baseline and at follow-up in accordance with the regional screening programme, was compared after being categorised according to the International Clinical Diabetic Retinopathy Disease Severity Scale. 'DR progression at least one leve' was calculated. High MMP-2 was defined as ≥178 ng/mL (≥75th percentile) and high TIMP-2 as ≥205 ng/mL (≥75th percentile). DR was dichotomised as 'at least moderate DR' or 'no/mild DR'. RESULTS: The study included 267 participants, 57% of whom were men. At baseline, the prevalence of high MMP-2 (p=0.001) and high TIMP-2 (p=0.008) increased with the severity of DR. 'At least moderate DR' (adjusted OR (AOR) 2.4, p=0.008) and macroalbuminuria (AOR 3.6, p=0.025) were independently associated with high MMP-2. 'At least moderate DR' (AOR 2.3, p=0.009) and macroalbuminuria (3.4, p=0.031) were independently associated with high TIMP-2. DR progression occurred in 101 (46%) patients (p<0.001). HbA1c≥53 mmol/mol was associated with the progression of DR (crude OR 3.8, p=0.001). No other MMPs or TIMPs were linked to the severity or the progression of DR. CONCLUSIONS: High levels of MMP-2 and TIMP-2 indicated more severe DR or diabetic nephropathy. Only HbA1c was associated with the progression of DR in 267 patients with T1D.

Soluble CD163 and glycated haemoglobin were independently associated with the progression of diabetic retinopathy in adult patients with type 1 diabetes.

OBJECTIVE: High vitreous levels of soluble (s)CD163 have been demonstrated in severe diabetic retinopathy (DR). The aim of this study was to explore the predictive values of plasma sCD163 and glycated haemoglobin (HbA1c) for DR progression in adults with type 1 diabetes. METHODS AND ANALYSES: The study design was prospective. Fundus photography performed in 2009 and at follow-up (≤12 years later) were compared after being categorised according to the International Clinical Diabetic Retinopathy Disease Severity Scale. 'DR progression at least one level' was calculated. In 2009, data collection (sex, age, diabetes duration, metabolic variables, serum creatinine, macroalbuminuria and lifestyle factors) and biochemical analyses were performed. Plasma sCD163 and HbA1c were divided into quartiles. Logistic regression analyses were performed. RESULTS: The prevalence of DR in 2009 versus at follow-up in 270 participants (57% male) were: no apparent 28% vs 18%; mild 20% vs 13%; moderate 24% vs 26%; severe 11% vs 13%; and proliferative DR 17% vs 30% (p<0.001). DR progression occurred in 101 (45%) patients. HbA1c ≥54 mmol/mol (≥7.1%) (>1st quartile) (adjusted odds ratio (AOR) 3.8, p<0.001) and sCD163 ≥343 ng/mL (>1st quartile) (AOR 2.6, p=0.004) were independently associated with DR progression. The associations with DR progression increased significantly from the first to the fourth quartile for HbA1c (AORs: 1; 2.5; 3.6; 7.4), but not for sCD163 (AORs: 1; 2.9; 2.4; 2.4). CONCLUSION: Plasma sCD163 may constitute a valuable biomarker for DR progression in addition to and independent of the well-established biomarker HbA1c.

A comparison in women with newly diagnosed diabetes between those with and without a history of gestational diabetes: a new perspective.

AIMS: Previous gestational diabetes mellitus (GDM) entails increased risk of future diabetes. We describe the characteristics of women with previous GDM and compare with no previous GDM from the cohort Diabetes in Kalmar and Kronoberg (DKK) of 1248 adults, 40% women, with new diabetes, and factors affecting age and C-peptide levels at diagnosis of diabetes. METHODS: Age-at-diagnosis of diabetes, BMI, hypertension, hyperlipidemia, smoking, physical activity, and pre-existing myocardial infarction, stroke, or peripheral arterial insufficiency were registered at ordinary care visits close to diagnosis of diabetes, for the 43 women (9.4% of 456 from DKK with complete data for this analysis) with self-reported previous GDM (yes/no) and 86 controls without it, matched for date of diagnosis of diabetes. Blood samples were centrally analyzed for GADA and C-peptide for classification of diabetes. RESULTS: Women with previous GDM had lower mean age-at-diagnosis of diabetes, 53.4 vs 65.0 years, lower systolic blood pressure (SBP), 131.2 vs 137.5 mmHg, and fewer had pre-existing hypertension than without previous GDM (p < 0.001-0.05). Among antibody negative women with previous GDM, BMI (p = 0.024), hypertension (p = 0.023) and hyperlipidemia (p < 0.001) were associated with higher levels of C-peptide, while physical activity was inversely associated (p = 0.035), and SBP (p = 0.02) and hypertension (p = 0.016) were associated with age-at-diagnosis of diabetes. CONCLUSIONS: Women with previous GDM were a decade younger and had lower prevalence of hypertension at diagnosis of diabetes; C-peptide levels were associated with BMI, hypertension, and hyperlipidemia and showed a tendency to be lower, possibly indicating a phenotype with higher risk of overt cardiovascular disease later in life.

PAIN IN POST-POLIO SYNDROME: A SEPARATE PAIN ENTITY?

BACKGROUND: Most patients with polio recover from the initial infection, but develop muscle weakness, pain and fatigue after 15-40 years, a condition called post-polio syndrome. Although poliovirus has been almost eliminated, 12-20 million people worldwide still have polio sequelae. The pain is described mainly as nociceptive, but some patients experience neuropathic pain. The aim of this study was to further characterize post-polio pain. PATIENTS AND METHODS: A total of 20 patients with post-polio syndrome participated in the study. Physical examination was performed, and questionnaires containing pain drawing and visual analogue scales (VAS) for pain intensity during rest and motion and VAS for fatigue were completed. A walk test was performed to evaluate physical performance. RESULTS: Pain intensity was high (42/100 on the VAS at rest and 62/100 while moving). The pain was localized in both joints and muscles. Pain in the muscles was of "deep aching" character, included "muscle cramps" and was located mainly in polio-weakened limbs. CONCLUSION: Muscle pain in patients with post-polio syndrome does not fulfil the criteria for either nociceptive or neuropathic pain; thus, it is suggested that the pain is termed "post-polio muscular pain". The intensity of post-polio muscular pain is higher while moving, but does not influence physical function, and is separate from fatigue.

Galectin-3, metalloproteinase-2 and cardiovascular disease were independently associated with metalloproteinase-14 in patients with type 1 diabetes: a cross sectional study.

BACKGROUND: Type 1 diabetes (T1D) is a major risk factor for cardiovascular disease (CVD). Matrix metalloproteinase-14 (MMP-14) is involved in the development of atherosclerosis and CVD. The main aim was to explore the associations between MMP-14 and selected inflammatory and metabolic variables, CVD, depression, physical activity, smoking and medication in patients with T1D. The secondary aim was to explore associations with CVD. METHODS: Cross-sectional design. The participants were consecutively recruited from one specialist diabetes out-patient clinic. Depression was assessed by a self-report instrument. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. High MMP-14 was defined as ≥ 5.81 ng/mL. Non-parametric tests, Chi2 tests and multiple logistic regression analyses were performed. RESULTS: Two hundred and sixty-eighth T1D patients aged 18-59 years participated (men 58%, high MMP-14 25%, CVD 3%). Sixty-seven patients with high MMP-14, compared to 201 patients with lower MMP-14, had higher prevalence of CVD (8% versus 1%, p = 0.012), and had higher levels of galectin-3 (p < 0.001) and MMP-2 (p = 0.018). Seven patients with CVD, compared to 261 without, were older (p = 0.003), had longer diabetes duration (p = 0.027), and had higher prevalence of high MMP-14 (71% versus 24%, p = 0.012), abdominal obesity (p = 0.014), depression (p = 0.022), usage of antidepressants (p = 0.008), antihypertensive drugs (p = 0.037) and statins (p = 0.049). Galectin-3 (per ng/mL) [adjusted odds ratio (AOR) 2.19, p < 0.001], CVD (AOR 8.1, p = 0.027), and MMP-2 (per ng/mL) (AOR 1.01, p = 0.044) were associated with high MMP-14. Depression (AOR 17.4, p = 0.006), abdominal obesity (15.8, p = 0.006), high MMP-14 (AOR 14.2, p = 0.008), and diabetes duration (AOR 1.10, p = 0.012) were associated with CVD. CONCLUSIONS: The main findings of this study were that galecin-3, MMP-2, and CVD were independently associated with high levels of MMP-14 in T1D patients. The association between MMP-14 and galectin-3 is a new finding. No traditional risk factors for CVD were associated with MMP-14. Depression, abdominal obesity and MMP-14 were independently associated with CVD.

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

Aims: Alexithymia has been linked to cardiovascular disease. The aim was to explore whether the immuno-inflammatory variables galectin-3 binding protein (Gal3BP), soluble (s)CD163 and galectin-3 were independently associated with alexithymia, while controlling for known risk factors for cardiovascular disease, such as depression, anxiety, impaired glycemic control, obesity, smoking, and physical inactivity in patients with type 1 diabetes (T1D). Methods: Cross-sectional design. The participants were consecutively recruited from one diabetes out-patient clinic. Alexithymia, depression and anxiety were assessed by self-report instruments. Blood samples, anthropometrics, and blood pressure were collected, supplemented with data from electronic health records. High Gal3BP was defined as ≥3.3 µg/ml, high sCD163 as ≥0.6 µg/ml, high galectin-3 as ≥2.6 ng/ml, impaired glycemic control as HbA1c >70 mmol/mol (>8.6%) and abdominal obesity as waist circumference ≥ 1.02 m for men and ≥ 0.88 m for women. Results: Two hundred and ninety two patients participated (men 56%, aged 18-59 years, alexithymia prevalence 15%). Patients with alexithymia had higher prevalence of depression (34 vs. 6%, p < 0.001), anxiety (61 vs. 30%, p < 0.001), high Gal3BP levels (39 vs. 17%, p = 0.004), high HbA1c levels (46 vs. 24%, p = 0.006), and abdominal obesity (29 vs. 15%, p = 0.045). Depression [adjusted odds ratio (AOR) 6.5, p < 0.001], high Gal3BP levels (AOR 2.4, p = 0.035), and age (AOR 0.96, p = 0.027) were independently associated with alexithymia. Abdominal obesity (AOR 4.0, p < 0.001), high Gal3BP levels (AOR 2.8, p = 0.002), and depression (AOR 2.9, p = 0.014) were associated with high HbA1c. Abdominal obesity and anxiety were associated [Crude odds ratio (COR) 2.4, p = 0.006]. Conclusions: T1D patients with alexithymia had higher prevalence of high Gal3BP levels, depression, impaired glycemic control, anxiety, and abdominal obesity, which are known risk factors for cardiovascular disease. Only high Gal3BP levels, depression, and younger age were independently associated with alexithymia in adult patients with T1D.

Admission glucose level was associated with increased short-term mortality and length-of-stay irrespective of diagnosis, treating medical specialty or concomitant laboratory values.

BACKGROUND: Glucose is a routine emergency sample. General guidelines for inpatient hyperglycemia are scarce, except in myocardial infarction, stroke, and perioperative/ICU. Previous studies found admission glucose associated with increased mortality in specific conditions. Scandinavian data, and for general patients, are scarcer. We investigated admission glucose levels, 30-day mortality, and length-of-stay (LoS), in a Swedish hospital. METHODS: From 8146 emergency visits data regarding age, gender, dates of admission, discharge and death, diagnoses, admission p-glucose, s-sodium, s-potassium, b-hemoglobin, b-WBC and s-CRP, was collected, and for 6283 information regarding diagnosis of diabetes the previous 5 years. Visits were grouped in hypoglycemia (≤4.0), normoglycemia (>4.0-≤7.0), modest (>7.0-≤11.1) and severe hyperglycemia (>11.1) mmol/l. RESULTS: Short-term mortality was 1.5% in the normoglycemic, 2.6% in the hypoglycemic, 4.0-4.5% in modest and severe hyperglycemia, p < 0.001; Cox proportional hazard ratios (HR) for groups of patients without/with diabetes were 6.8; 1; 3.4; 4.4/7.3; 3.9; 4.0; 2.1 compared to the normoglycemic without diabetes (p 0.0001-0.05); adjusted for age, and concurrent levels of sodium, potassium, Hb, WBC and CRP 1.51 (1.07-2.1, p 0.02) with modest hyperglycemia, and 1.08 (0.60-1.95, p 0.80) in severe hyperglycemia. Mean LoS was 1.2 and 1.7 days longer with modest and severe hyperglycemia. CONCLUSIONS: Short-term mortality increased substantially with admission hypo- and hyperglycemia for patients both with and without diabetes, irrespective of treating medical specialty, main discharge diagnosis, or concurrent laboratory values. Patients with diabetes (16%) were older, with higher glucose levels at admission, and with a different pattern of the association of admission glucose and mortality.

Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H.

In 2005 the commonality of sarcotubular myopathy (STM) and limb girdle muscular dystrophy type 2H (LGMD2H) was demonstrated, as both are caused by the p D487N missense mutation in TRIM32 originally found in the Manitoba Hutterite population. Recently, three novel homozygous TRIM32 mutations have been described in LGMD patients. Here we describe a three generation Swedish family clinically presenting with limb girdle muscular weakness and histological features of a microvacuolar myopathy. The two index patients were compound heterozygotes for a frameshift mutation in TRIM32 (c.1560delC ) and a 30 kb intragenic deletion, encompassing parts of intron 1 and the entire exon 2 of TRIM32. In these patients, no full-length or truncated TRIM32 could be detected. Interestingly, heterozygous family members carrying only one mutation showed mild clinical symptoms and vacuolar changes in muscle. In our family, the phenotype encompasses additionally a mild demyelinating polyneuropathic syndrome. Thus STM and LGMD2H are the result of loss of function mutations that can be either deletions or missense mutations.

Female sex, high soluble CD163, and low HDL-cholesterol were associated with high galectin-3 binding protein in type 1 diabetes.

BACKGROUND: Galectin-3 binding protein (Gal3BP), sCD163, galectin-3, and depression have been linked to cardiovascular disease and mortality. In patients with type 1 diabetes, female sex has also been linked to cardiovascular disease and mortality. The aim was to explore whether female sex, sCD163, galectin-3, and depression were associated with Gal3BP in patients with type 1 diabetes. We adjusted for metabolic variables, creatinine, smoking, physical inactivity, and cardiovascular disease. METHODS: Cross-sectional design. Patients with type 1 diabetes (n = 285, women 44%, age18-59 years, diabetes duration 1-55 years) were consecutively recruited from one diabetes outpatient clinic. Blood samples, anthropometrics, and blood pressure were collected, supplemented with data from electronic medical records. High Gal3BP was defined as ≥3.3 mg/l (≥80th percentile). Depression was assessed by a self-report instrument. Linear and logistic regression models were elaborated for the associations and calibrated and validated for goodness of fit with the data variables. RESULTS: Median (q1, q3) Gal3BP was 2.3 (1.8, 3.1) mg/l. The prevalence of high Gal3BP for women was 30% and 14% for men (p = 0.001). Female sex (adjusted odds ratio (AOR) 3.0), sCD163 (per µg/l) (AOR 6.6), and total cholesterol (per mmol/l) (AOR 1.6) were positively associated with high Gal3BP, and HDL-cholesterol (per mmol/l) (AOR 0.2) was negatively associated with high Gal3BP. CONCLUSIONS: High Gal3BP levels were associated with female sex, increasing sCD163 and total cholesterol levels, and decreasing HDL-cholesterol levels in patients with type 1 diabetes. The prevalence of high Gal3BP was more than twice as high in the women as in the men.

Midnight salivary cortisol secretion associated with high systolic blood pressure in type 1 diabetes.

OBJECTIVE: To explore associations between high midnight salivary cortisol (MSC) secretion and high blood pressure (BP) in type 1 diabetes (T1D). METHODS: Cross-sectional study of 196 adult patients with T1D (54% men). Associations between high MSC (≥9.3 nmol/L) and high systolic BP (>130 mmHg), and high diastolic BP (>80 mmHg) were explored for all patients, users and non-users of antihypertensive drugs (AHD). Adjustments were performed for age, sex, diabetes-related variables, p-creatinine, smoking, physical inactivity, depression and medication. RESULTS: The prevalence of high MSC differed between patients with high and low systolic BP in all 196 patients: 39 vs 13% (P = 0.001); in 60 users of AHD: 37 vs 12% (P = 0.039), and in 136 non-users of AHD: 43 vs 13% (P = 0.012). Significant associations with high systolic BP were for all patients: physical inactivity (adjusted odds ratio (AOR) 6.5), high MSC (AOR 3.9), abdominal obesity (AOR 3.7), AHD (AOR 2.9), age (per year) (AOR 1.07), and p-creatinine (per µmol/L) (AOR 1.03); for 60 users of AHD: high MSC (AOR 4.1) and age (per year) (AOR 1.11); for 136 non-users of AHD: abdominal obesity (AOR 27.4), physical inactivity (AOR 14.7), male sex (AOR 9.0), smoking (AOR 7.9), and age (per year) (AOR 1.08). High MSC was not associated with high DBP. CONCLUSIONS: In adult patients with T1D, high systolic BP was associated with physical inactivity, high MSC secretion, abdominal obesity, p-creatinine, age, and AHD, the latter indicating treatment failure.