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Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (amp;lt; 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event. Funding Agencies|European Union Horizon 2020 project [634869]; Swedish Research Council [2012-2215, 2015-03477]; Landstinget Dalarna (Falun, Sweden); Dalarna University (Falun, Sweden); Sparbanksstiftelsen Nya [552, 693, 932, 2297]; Region Vastmanland (Vasteras, Sweden); Swedish Medical Association; Swedish Heart-Lung Foundation [20150429]

Aims: To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. Methods: Patients newly initiated on insulin (n = 2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. Results: The total mean annual healthcare cost increased from 1656 per patient 2 years before insulin initiation to 3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was 13,823 in the insulin group compared to 9989 in the NIAD group. Conclusions: Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. This is an open access article under the CC BY-NC-ND license. Funding Agencies|AstraZeneca

Aims/Hypothesis The aim of this study was to identify risk factors associated with confirmed fatal hyperglycaemia, which could predispose potentially preventable deaths in individuals on glucose lowering drugs. Methods A retrospective register-based case-control study conducted on a nationwide cohort with individuals who died due to hyperglycaemia as determined by forensic postmortem examination, in Sweden August 2006 to December 2012. Vitreous glucose was used to diagnose hyperglycaemia postmortem. The forensic findings stored in the National Forensic Medicine Database were linked to nationwide registers. Cases that died due to confirmed hyperglycemia with dispensed glucose lowering drugs were identified and living controls with dispensed glucose lowering drugs were randomly selected in the Swedish prescribed drug register and matched on age and sex. Information on comorbidities, dispensed pharmaceuticals, clinical data and socioeconomic factors were obtained for cases and controls. Adjusted multiple logistic regression models were used to identify risk factors associated with fatal hyperglycaemia. Results During the study period 322 individuals, mostly males (79%) with the mean age of 53.9 years (SD. +/- 14) died due to confirmed hyperglycaemia. Risk factors for fatal hyperglycaemia included; insulin treatment (OR = 4.40; 95% CI, 1.96, 9.85), poor glycaemic control (OR = 2.00 95% CI, 1.23, 3.27), inadequate refill-adherence before death (OR = 3.87; 95% CI, 1.99, 7.53), microvascular disease (OR = 3.26; 95% CI, 1.84, 5.79), psychiatric illness (OR = 2.30; 95% CI, 1.32, 4.01), substance abuse (OR = 8.85; 95% CI, 2.34, 35.0) and/or living alone (OR = 2.25; 95% CI, 1.21, 4.18). Conclusions/ Interpretation Our results demonstrate the importance of clinical attention to poor glycaemic control in subjects with psychosocial problems since it may indicate serious non-adherence, which consequently could lead to fatal hyperglycaemia.

Background: Anemia is common in elderly people and especially in nursing home residents. Few studies have been performed on the consequences of anemia in a nursing home population. This study explored the prevalence of anemia in nursing homes in Sweden, including risk factors and mortality associated with anemia or hemoglobin (Hb) decline. Methods: Three hundred ninety patients from 12 nursing homes were included during 2008-2011. Information about medication, blood samples, questionnaire responses and information about physical and social activities was recorded. The baseline characteristics of the patients were compared for subjects with and without anemia. Vital status was ascertained during the following 7 years from baseline to compare the survival. Hb levels amp;lt;120 g/L in women and amp;lt;130 g/L in men were used to define anemia. For 220 of the subjects Hb change during one year was registered and the quartiles in Hb change were compared in terms of baseline characteristics and mortality. Results: The prevalence of anemia at baseline was 52% among men and 32% among women. The men with anemia had a two-year mortality significantly higher (61%) than the men without anemia (29%, p = 0.001) but there was no statistical difference in two- year survival in women. In anemic men there was a higher mortality (Hazard Ratio = 1.58) during a total follow-up period of up to 7 years after adjustment for age, increased B-type natriuretic peptide (BNP) and decreased estimated Glomerular Filtration Rate (eGFR). Among men, but not women, we found baseline correlations between anemia and elevated BNP (amp;gt;100 ng/L) and severely reduced eGFR (amp;lt;30 ml/min). When the lowest quartile of Hb change (decline amp;gt;9 g/L) was compared with the highest (improvement amp;gt;6 g/L) the mortality was higher in the lowest quartile (p = 0.03). Conclusions: Anemia is common in nursing home residents in Sweden, especially among men for whom it is related to higher mortality. A rapid Hb drop is associated with higher mortality. Regardless of earlier Hb values, monitoring Hb regularly in a nursing home population seems important for catching rapid Hb decline correlated with higher mortality. Funding Agencies|Medical Research Council of Southeast Sweden (FORSS); Futurum - academy of health and care, Region Jonkoping county; Swedish Society of Medicine; Fromma Foundation; ALF funding from Region Skane