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.

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.

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 Prevalence of Mild Alpha-1-Antitrypsin Deficiency in Hospitalized COVID-19-Patients.

Introduction: Alpha-1-antitrypsin (AAT) has been shown to inhibit SARS-CoV-2 cell entry and suggested as a therapeutic agent for COVID-19. Furthermore, epidemiological association of high prevalence of Alpha-1-antitrypsin deficiency (AATD) and regional severity of COVID-19-impact has been hypothesized. In our study setting, the estimated prevalence rates of mild (PI*MZ, PI*SS or PI*MS) and moderate-to-severe AATD (PI*ZZ or PI*SZ) are high, 9% and 0.2%, respectively. Our primary aim was to examine the prevalence rate of AATD among hospitalized COVID-19-patients. Methods: In this prospective observational study, enrollment occurred from December 2020 to January 2021 in two COVID-19-units at Skåne University Hospital, Lund, Sweden. Case definition was a patient hospitalized due to COVID-19. Patients were screened for AATD with PI-typing and if results were inconclusive, PCR for the S- and Z-genes were performed. Patients were categorized as severe or moderate COVID-19 and 30-day-mortality data were collected. The primary outcome was prevalence rate of AATD. The secondary outcome investigated association between presence of mild AATD and severe COVID-19. Results: We enrolled 61 patients with COVID-19. Two patients out of 61 (3%) had mild AATD (PI*MZ) and none had moderate-to-severe AATD. 30/61 (49%) had severe COVID-19. Both patients with mild AATD developed severe COVID-19. Yet, presence of AATD was not significantly associated with severe COVID-19 (p=0.24). Conclusion: Mild AATD (PI*MS or PI*MZ) was rare in a small cohort of hospitalized patients with COVID-19 in a study setting with a high background prevalence of AATD.

Real-world cost-effectiveness of insulin degludec in type 1 and type 2 diabetes mellitus from a Swedish 1-year and long-term perspective.

BACKGROUND AND AIMS: The ReFLeCT study demonstrated that switching to insulin degludec from other basal insulins was associated with reductions in glycated hemoglobin and hypoglycemic events in type 1 (T1D) and type 2 diabetes (T2D), and reductions in insulin doses in T1D. The aim of the present analysis was to assess the short- and long-term cost-effectiveness of switching to insulin degludec in Sweden. METHODS: Short-term outcomes were evaluated over 1 year in a Microsoft Excel model, while long-term outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Cohort characteristics and treatment effects were sourced from the ReFLeCT study. Costs (in 2018 Swedish krona [SEK]) encompassed direct medical expenditure and indirect costs from loss of workplace productivity. In the long-term analyses, patients were assumed to receive insulin degludec or continue prior insulin therapy (primarily insulin glargine U100) for 5 years, before all patients intensified to once-daily degludec and mealtime aspart. RESULTS: Switching to insulin degludec was associated with improved quality-adjusted life expectancy of 0.04 and 0.02 quality-adjusted life years (QALYs) over 1 year, and 0.16 and 0.08 QALYs over patient lifetimes, in T1D and T2D. Combined costs in T1D and T2D were estimated to be SEK 1,249 lower and SEK 1,181 higher over the short-term, and SEK 157,258 and SEK 2,114 lower over the long-term. Benefits were due to lower insulin doses in T1D, reduced rates of hypoglycemia, and lower incidences of diabetes-related complications. Insulin degludec was associated with an incremental cost-effectiveness ratio of SEK 64,298 per QALY gained for T2D over 1 year and considered dominant for T1D and T2D in all other comparisons. CONCLUSIONS: Insulin degludec was projected to be cost-effective or dominant versus other basal insulins for the treatment of T1D and T2D in Sweden.

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.

Standard mortality rates and years of life lost for serologically defined adult-onset type 1 and type 2 diabetes - A fifteen year follow-up.

AIMS: The Diabetes Incidence in Kronoberg (DIK) study of adult-onset diabetes used serological classification. Standard Mortality Rates (SMR) and Years of Life Lost (YLL) 15 years after adult-onset (18-100 years) of diabetes were compared to the population of Kronoberg. METHODS: Of 1609/1660 (97%) patients, 112 (7%) had type 1 (T1D) (GADA+ and/or ICA+, and/or C-peptide < 0.25 nmol/l), and 1497 (93%) had type 2 diabetes (T2D) (antibody- and C-peptide ≥ 0.25 nmol/l). The National Swedish Mortality Register provided time of death. RESULTS: For T1D SMR did not differ from the Kronoberg population in any age group. In T2D SMR was 1.20 (1.12-1.29). After 15 years 26% (29/112) T1D and 52% (785/1497) T2D patients had died, p < 0.0001. In T2D SMR was 5.6 (30-39 years), 2 (40-59 years), 1.4 (60-69 years), and thereafter no difference. There were no significant sex differences in mortality, and no YLL to adult-onset T1D, but five YLL to T2D for onset at ages 20-60 years. CONCLUSIONS: For adult-onset T1D SMR did not differ from the general population, in contrast to previous findings in childhood-onset (< 30 years of age) T1D. The difference in mortality between persons with diabetes and the general population was due to higher mortality in T2D.

Midnight salivary cortisol secretion and the use of antidepressants were associated with abdominal obesity in women with type 1 diabetes: a cross sectional study.

BACKGROUND: Abdominal obesity is a risk factor for cardiovascular disease. The aim was to explore the influence of midnight salivary cortisol (MSC), antidepressants and sex on abdominal obesity in type 1 diabetes (T1D). We controlled for physical inactivity, smoking, depression and alexithymia. METHODS: Cross sectional study of 190 T1D patients (86 women/104 men, 18-59 years, diabetes duration 1-55 years), consecutively recruited from one specialist diabetes outpatient clinic. Anthropometrics, blood pressure, saliva and blood samples were collected, supplemented with data from electronic medical records. Depression and alexithymia were assessed by self-report instruments. MSC (nmol/l) was categorised into 3 levels: high MSC: (≥ 6.7) (n = 64); intermediate MSC: ≥ 3.7- < 6.7) (n = 64); low MSC (< 3.7) (n = 62). Abdominal obesity was defined as waist circumference (meters) ≥ 0.88 for women and as ≥ 1.02 for men. Multiple logistic regression analyses (Backward: Wald) were performed. The Hosmer and Lemeshow test for goodness-of-fit and Nagelkerke R2 were used to evaluate each multiple logistic regression analysis model. RESULTS: The prevalence of abdominal obesity was three times higher in the women than in the men (24% versus 8%) (p = 0.002). Antidepressants were used by 10% of the women and by 4% of the men (p = 0.09). The prevalence of high MSC was 1.7 times higher in the women (43% versus 26%); the prevalence of both intermediate MSC (28% versus 38%) and low MSC (29% versus 36%) were lower in the women (p = 0.048). Significant associations with abdominal obesity were for all 190 patients: female sex (adjusted odds ratio (AOR) 3.4 (confidence interval (CI) 1.4-8.2)) and the use of antidepressants (AOR 4.3 (CI 1.2-14.8)); for the 86 women: high MSC (AOR 18.4 (CI 1.9-181)) and use of antidepressants (AOR 12.2 (CI 2.0-73.6)); and for the 104 men: alexithymia (AOR 5.2 (CI 1.1-24.9)). CONCLUSIONS: Clear sex differences were demonstrated with a distinct higher prevalence of abdominal obesity, as well as a distinct higher prevalence of high midnight salivary cortisol in the women with type 1 diabetes. High midnight salivary cortisol secretion and the use of antidepressants were independent risk factors for abdominal obesity in the women.

Obstetric and perinatal outcomes in pregnancies complicated by diabetes, and control pregnancies, in Kronoberg, Sweden.

BACKGROUND: Diabetes during pregnancy is an increasingly common metabolic disorder, associated with significantly increased risks for both mother and child. Aim of this study was to compare maternal and perinatal outcomes in women with pregestational (PDM) type 1 (T1DM), type 2 diabetes (T2DM), gestational diabetes mellitus (GDM) and compare these to pregnancies not complicated with diabetes. This study also evaluated a specifically organized care-model mostly involving specialist diabetes nurses. METHODS: Retrospective population-based records review 2009-2012. Rates of maternal (preeclampsia, pre-term delivery, cesarean section (CS)) and fetal outcomes (large for gestational age (LGA), macrosomia, congenital malformations/intrauterine death) were assessed and potential predisposing or contributing factors as maternal age, ethnicity, obesity, weight gain, parity, HbA1c levels, insulin types and doses. RESULTS: Among 280 pregnancies 48 were PDM, 97 GDM and 135 without diabetes. Within the group with diabetes, early-pregnancy BMI was higher (p = 0.0001), pregnancy weight gain lower (11.1 ± 6.7 kg vs 13.1 ± 7.1 kg, p = 0.005), more delivered preterm (p = 0.0001), by CS (p = 0.05), and had more LGA neonates (p = 0.06) than the group without diabetes. Among pregnancies with diabetes, GDM mothers gained less weight (9.9 kg vs 13.5 kg) (p = 0.006), and rates of CS (p = 0.03), preterm deliveries (p = 0.001) and LGA (p = 0.0001) were not increased compared to PDM; More T1DM infants were LGA, 60% vs. 27% in T2DM. In pregnancies with diabetes obesity, excessive weight gain and multiparity were associated with increased risk of LGA neonates, and mother's type of diabetes and gestational week were associated with higher rates of CS. CONCLUSION: Weight gain during pregnancy was lower in pregnancies with diabetes and prevalence of LGA, CS and preterm deliveries in GDM was not elevated, also for T2DM, except increased prevalence of LGA in T1DM that warrants increased clinical attention, indicating that this model of antenatal diabetes care may have contributed to improved maternal and fetal outcomes.

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.

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

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.

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.

Abdominal obesity in type 1 diabetes associated with gender, cardiovascular risk factors and complications, and difficulties achieving treatment targets: a cross sectional study at a secondary care diabetes clinic.

BACKGROUND: Abdominal obesity is linked to cardiovascular diseases in type 1 diabetes (T1D). The primary aim was to explore associations between abdominal obesity and cardiovascular complications, metabolic and inflammatory factors. The secondary aim was to explore whether achieved recommended treatment targets differed between the obese and non-obese participants. METHODS: Cross sectional study of 284 T1D patients (age 18-59 years, men 56%), consecutively recruited from one secondary care specialist diabetes clinic in Sweden. Anthropometrics, blood pressure, serum-lipids and high-sensitivity C-reactive protein (hs-CRP) were collected and supplemented with data from the patients' medical records and from the Swedish National Diabetes Registry. Abdominal obesity was defined as waist circumference men/women (meters): ≥1.02/≥0.88. Hs-CRP was divided into low-, moderate-, and high-risk groups for future cardiovascular events (< 1, 1 to 3, and > 3 to ≤8.9 mg/l). Treatment targets were blood pressure ≤ 130/≤ 80, total cholesterol ≤4.5 mmol/l, LDL: ≤ 2.5 mmol/l, and HbA1c: ≤5 2 mmol/mol (≤ 6.9%). Different explanatory linear, logistic and ordinal regression models were elaborated for the associations, and calibrated and validated for goodness of fit with the data variables. RESULTS: The prevalence of abdominal obesity was 49/284 (17%), men/women: 8%/29% (P < 0.001). Women (adjusted odds ratio (AOR) 6.5), cardiovascular complications (AOR 5.7), HbA1c > 70 mmol/mol (> 8.6%) (AOR 2.7), systolic blood pressure (per mm Hg) (AOR 1.05), and triglycerides (per mmol/l) (AOR 1.7), were associated with abdominal obesity. Sub analyses (n = 171), showed that abdominal obesity (AOR 5.3) and triglycerides (per mmol/l) (AOR 2.8) were associated with increasing risk levels of hs-CRP. Treatment targets were obtained for fewer patients with abdominal obesity for HbA1c (8% vs 21%, P = 0.044) and systolic blood pressure (51% vs 68%, P = 0.033). No patients with abdominal obesity reached all treatment targets compared to 8% in patients without abdominal obesity. CONCLUSIONS: Significant associations between abdominal obesity and gender, cardiovascular disease, and the cardiovascular risk factors low-grade inflammation, systolic blood pressure, high HbA1c, and triglycerides, were found in 284 T1D patients. Fewer patients with abdominal obesity reached the treatment targets for HbA1c and systolic blood pressure compared to the non-obese.

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.

Gender, alexithymia and physical inactivity associated with abdominal obesity in type 1 diabetes mellitus: a cross sectional study at a secondary care hospital diabetes clinic.

BACKGROUND: Obesity is linked to cardiovascular diseases and increasingly common in type 1 diabetes mellitus (T1DM) since the introduction of intensified insulin therapy. Our main aim was to explore associations between obesity and depression, anxiety, alexithymia and self-image measures and to control for lifestyle variables in a sample of persons with T1DM. Secondary aims were to explore associations between abdominal and general obesity and cardiovascular complications in T1DM. METHODS: Cross sectional study of 284 persons with T1DM (age 18-59 years, men 56%), consecutively recruited from one secondary care hospital diabetes clinic in Sweden. Assessments were performed with self-report instruments (Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale-20 items and Structural Analysis of Social Behavior). Anthropometrics and blood samples were collected for this study and supplemented with data from the patients' medical records. Abdominal obesity was defined as waist circumference men/women (meters): ≥1.02/≥0.88, and general obesity as BMI ≥30 kg/m2 for both genders. Abdominal obesity was chosen in the analyses due to the high association with cardiovascular complications. Different explanatory logistic regression models were elaborated for the associations and calibrated and validated for goodness of fit with the data variables. RESULTS: The prevalence of abdominal obesity was 49/284 (17%), men/women: 8%/29% (P < 0.001). Abdominal obesity was associated with women (AOR 4.9), physical inactivity (AOR 3.1), alexithymia (AOR 2.6) and age (per year) (AOR 1.04). One of the three alexithymia sub factors, "difficulty identifying feelings" (AOR 3.1), was associated with abdominal obesity. Gender analyses showed that abdominal obesity in men was associated with "difficulty identifying feelings" (AOR 7.7), and in women with use of antidepressants (AOR 4.3) and physical inactivity (AOR 3.6). Cardiovascular complications were associated with abdominal obesity (AOR 5.2). CONCLUSIONS: Alexithymia, particularly the alexithymia subfactor "difficulty identifying feelings", physical inactivity, and women, as well as cardiovascular complications were associated with abdominal obesity. As abdominal obesity is detrimental in diabetes due to its association with cardiovascular complications, our results suggest two risk factor treatment targets: increased emotional awareness and increased physical activity.

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.

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

OBJECTIVE: The 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. DESIGN: Cross-sectional study. METHODS: In this study, 292 patients with type 1 diabetes, aged 1859 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. RESULTS: Self-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. CONCLUSIONS: Depression 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.

Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis.

OBJECTIVE: GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients. DESIGN AND METHODS: Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values <0.05 were considered statistically significant. RESULTS: PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04-1.23), which was significantly increased in females (1.23; 95% CI, 1.09-1.38%) but not in males (SPR 1.04; 95% CI, 0.92-1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference. CONCLUSIONS: GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures.

Levels of C-peptide, body mass index and age, and their usefulness in classification of diabetes in relation to autoimmunity, in adults with newly diagnosed diabetes in Kronoberg, Sweden.

OBJECTIVE: C-peptide is a main outcome measure in treatment trials of diabetes. C-peptide also has a role in the classification of diabetes, which is often difficult in adults and this is also increasingly recognised in adolescents and elders. AIM: We aimed to describe the levels of C-peptide in relation to age and body mass index (BMI) in a large population-based cohort of adults with newly diagnosed diabetes and compare the capabilities of C-peptide, age and BMI to discriminate between autoimmune and non-autoimmune diabetes. SUBJECTS AND METHODS: Blood samples from 1180 patients were analysed regarding islet cell antibody, glutamic acid decarboxylase antibody and fasting C-peptide (FCP). Receiver operating characteristics (ROC) curves were analysed to check the ability of age, BMI and C-peptide to discriminate between autoantibody-positive (Ab(+)) and -negative (Ab(-)) diabetes. RESULTS: Mean FCP was 0.73±0.5 (range 0.13-1.80) nmol/l in the Ab(+) and 1.42±0.9 (range 0.13-8.30) nmol/l in the Ab(-). FCP was 0.02 nmol/l higher per year increase in age at diagnosis of diabetes. Mean BMI was 26.0±4.8 (range 18.0-39.0) kg/m(2) in the Ab(+) and 28.9±5.3 (range 15.5-62.6) kg/m(2) in the Ab(-). FCP increased with age also within each BMI group. The highest area under the curve (AUC) in the ROC analysis was found for C-peptide, followed by age and BMI (0.78, 0.68 and 0.66 respectively). CONCLUSIONS: At diagnosis of diabetes, C-peptide was superior to age and BMI in discriminating between autoimmune and non-autoimmune diabetes. C-peptide increased significantly with BMI and age, latter also within each BMI group. Most of the adults had normal or high levels of C-peptide at presentation of diabetes among the autoimmune patients.

Incidence of diabetes mellitus and evolution of glucose parameters in growth hormone-deficient subjects during growth hormone replacement therapy: a long-term observational study.

OBJECTIVE: Growth hormone (GH) deficiency is associated with insulin resistance and diabetes. The aim of the current study was to determine incidence of diabetes during GH replacement therapy (GHRT) and the effect of GHRT on fasting plasma glucose concentrations and HbA(1c) in adult patients with GH deficiency. RESEARCH DESIGN AND METHODS: A total of 5,143 GH-deficient patients (male 49.9%; mean age ± SD, 49 ± 13 years; BMI 29.1 ± 5.9 kg/m(2)) were analyzed. Mean observation period was 3.9 years (range 0.01-13). Total number of patient-years was 20,106. Observed number of cases (O) was compared with expected number of cases (E). Reference rates were from Sweden, three additional European regions, and one U.S. region. RESULTS: Patients who developed diabetes (n = 523) were older; had higher BMI, waist circumference, triglyceride concentrations, and blood pressure; and had lower HDL-cholesterol concentrations (P < 0.0001) than those who did not develop diabetes. Diabetes incidence was 2.6 per 100 patient-years, equal in both sexes, and significantly increased compared with the Swedish reference (O/E = 6.02; P < 0.0001) as well as with the four other populations (O/E = 2.11-5.22). O/E increased with BMI and decreased with duration of GHRT (P < 0.0001). There was no significant association with GH dose (P = 0.74) or IGF-I SDS (P = 0.47). In subjects not developing diabetes, plasma glucose concentrations increased from 84.4 ± 0.9 mg/dL to 89.5 ± 0.8 mg/dL (0.70 mg/dL/year) and HbA(1c) increased from 4.74 ± 0.04% to 5.09 ± 0.13% (0.036%/year) after 6 years of GHRT. CONCLUSIONS: Diabetes incidence appears to be increased in GH-deficient patients receiving GHRT and exhibiting an adverse risk profile at baseline. Therefore, glucose homeostasis parameters should be monitored carefully in these patients.