Changes in HbA_1cduring the first six years after the diagnosis of Type 2 diabetes mellitus predict long-term microvascular outcomes

To analyze the association between change in HbA1c during the first 6 years after diagnosis of Type 2 diabetes mellitus (Type 2 DM) and incident micro- and macrovascular morbidity and mortality during 13 years thereafter. This is an observational study of the participants in the intervention arm of the randomized controlled trial Diabetes Care in General Practice (DCGP) in Denmark. 494 newly diagnosed persons with Type 2 DM aged 40 years and over with three or more measurements of HbA1c during six years of intervention were included in the analyses. Based on a regression line, fitted through the HbA1c-measurements from 1 to 6 years after diabetes diagnosis, glycaemic control was characterized by the one-year level of HbA1c after diagnosis, and the slope of the regression line. Outcomes were incident diabetes-related morbidity and mortality from 6 to 19 years after diabetes diagnosis. The association between change in HbA1c (the slope of the regression line) and clinical outcomes were assessed in adjusted Cox regression models. The median HbA1c level at year one was 60 (IQR: 52-71) mmol/mol or (7.65 (IQR: 6.91-8.62) %). Higher HbA1c levels one year after diagnosis were associated with a higher risk of later diabetes-related morbidity and mortality. An increase in HbA1c during the first 6 years after diabetes diagnosis was associated with later microvascular complications (HR per 1.1 mmol/mol or 0.1% point increase in HbA1c per year; 95% CI) = 1.14; 1.05-1.24). Change in HbA1c did not predict the aggregate outcome 'any diabetes-related endpoint, all-cause mortality, diabetes-related mortality, myocardial infarction, stroke, or peripheral vascular diseases. We conclude that suboptimal development of glycaemic control during the first 6 years after diabetes diagnosis was an independent risk factor for microvascular complications during the succeeding 13-year follow-up, but not for mortality or macrovascular complications

Urinary albumin and 8-oxo-7,8-dihydroguanosine as markers of mortality and cardiovascular disease during 19 years after diagnosis of type 2 diabetes:A comparative study of two markers to identify high risk patients

Urinary albumin is an important biomarker used to identify high risk patients with diabetes, but there is a need for new biomarkers that alone or in combination with urinary albumin could give an even better prediction of clinical patient outcomes. One promising biomarker is 8-oxo-7,8-dihydroguanosine (8-oxoGuo) that represents intracellular oxidative stress. We investigated the ability of microalbuminuria (MA) and urinary 8-oxoGuo, alone and in combination, to predict mortality and cardiovascular disease (CVD) in patients with type 2 diabetes. We used data from 1381 newly diagnosed diabetes patients, and urinary albumin and 8-oxoGuo were assessed in morning urine collected at the time of diabetes diagnosis and at a follow-up visit 6 years later. Associations between the urinary markers and mortality and CVD were assessed in Cox proportional hazards regression models. Test performance was assessed using sensitivity, specificity, positive predictive value and negative predictive value for 10-year mortality and 10-year incidence of CVD. Both 8-oxoGuo and urinary albumin were statistically significantly associated with all-cause mortality at diagnosis as well as at 6-year follow-up. At diagnosis only urinary albumin was associated with CVD. In contrast, only 8-oxoGuo was associated with CVD at 6-year follow-up. When investigating test performance, we found that by combining information from MA and 8-oxoGuo the ability to correctly identify patients at risk could be improved. The findings suggest that measurement of urinary 8-oxoGuo provides additional information about risk to that obtained from urinary albumin, and that the combined use of 8-oxoGuo and urinary albumin could be useful for a better identification of patients at risk of CVD and death

Intentional Weight Loss and Longevity in Overweight Patients with Type 2 Diabetes:A Population-Based Cohort Study

OBJECTIVE:This study examined the influence of weight loss on long-term morbidity and mortality in overweight (BMI≥25 kg/m2) patients with type 2 diabetes, and tested the hypothesis that therapeutic intentional weight loss supervised by a medical doctor prolongs life and reduces the risk for cardiovascular disease in these patients. METHODS:This is a 19 year cohort study of patients in the intervention arm of the randomized clinical trial Diabetes Care in General Practice. Weight and prospective intentions for weight loss were monitored every third month for six years in 761 consecutive patients (≥40 years) newly diagnosed with diabetes in general practices throughout Denmark in 1989-92. Multivariable Cox regression was used to estimate the association between weight change during the monitoring period (year 0 to 6) and the outcomes during the succeeding 13 years (year 6 to 19) in 444 patients who were overweight at diagnosis and alive at the end of the monitoring period (year 6). The analysis was adjusted for age, sex, education, BMI at diagnosis, change in smoking, change in physical activity, change in medication, and the Charlson comorbidity 6-year score. Outcomes were from national registers. RESULTS:Overall, weight loss regardless of intention was an independent risk factor for increased all-cause mortality (P<0.01). The adjusted hazard ratio for all-cause mortality, cardiovascular mortality, and cardiovascular morbidity attributable to an intentional weight loss of 1 kg/year was 1.20 (95%CI 0.97-1.50, P = 0.10), 1.26 (0.93-1.72, P = 0.14), and 1.06 (0.79-1.42, P = 0.71), respectively. Limiting the analysis to include only those patients who survived the first 2 years after the monitoring period did not substantially change these estimates. A non-linear spline estimate indicated a V-like association between weight change and all-cause mortality, suggesting the best prognosis for those who maintained their weight. CONCLUSIONS:In this population-based cohort of overweight patients with type 2 diabetes, successful therapeutic intentional weight loss, supervised by a doctor over six years, was not associated with reduced all-cause mortality or cardiovascular morbidity/mortality during the succeeding 13 years

The role of diseases, risk factors and symptoms in the definition of multimorbidity:a systematic review

<p>Objective is to explore how multimorbidity is defined in the scientific literature, with a focus on the roles of diseases, risk factors, and symptoms in the definitions. Design: Systematic review. Methods: MEDLINE (PubMed), Embase, and The Cochrane Library were searched for relevant publications up until October 2013. One author extracted the information. Ambiguities were resolved, and consensus reached with one co-author. Outcome measures were: cut-off point for the number of conditions included in the definitions of multimorbidity; setting; data sources; number, kind, duration, and severity of diagnoses, risk factors, and symptoms. We reviewed 163 articles. In 61 articles (37%), the cut-off point for multimorbidity was two or more conditions (diseases, risk factors, or symptoms). The most frequently used setting was the general population (68 articles, 42%), and primary care (41 articles, 25%). Sources of data were primarily self-reports (56 articles, 42%). Out of the 163 articles selected, 115 had individually constructed multimorbidity definitions, and in these articles diseases occurred in all definitions, with diabetes as the most frequent. Risk factors occurred in 98 (85%) and symptoms in 71 (62%) of the definitions. The severity of conditions was used in 26 (23%) of the definitions, but in different ways. The definition of multimorbidity is heterogeneous and risk factors are more often included than symptoms. The severity of conditions is seldom included. Since the number of people living with multimorbidity is increasing there is a need to develop a concept of multimorbidity that is more useful in daily clinical work. Key Points</p><p>The increasing number of multimorbidity patients challenges the healthcare system. The concept of multimorbidity needs further discussion in order to be implemented in daily clinical practice.</p><p>Many definitions of multimorbidity exist and most often a cut-off point of two or more is applied to a range of 4–147 different conditions.</p><p>Diseases are included in all definitions of multimorbidity.</p><p>Risk factors are often included in existing definitions, whereas symptoms and the severity of the conditions are less frequently included.</p><p></p> <p>The increasing number of multimorbidity patients challenges the healthcare system. The concept of multimorbidity needs further discussion in order to be implemented in daily clinical practice.</p> <p>Many definitions of multimorbidity exist and most often a cut-off point of two or more is applied to a range of 4–147 different conditions.</p> <p>Diseases are included in all definitions of multimorbidity.</p> <p>Risk factors are often included in existing definitions, whereas symptoms and the severity of the conditions are less frequently included.</p

Multimorbidity and mortality:A 15-year longitudinal registry-based nationwide Danish population study

Supplementary_material_5_JoC for Multimorbidity and mortality: A 15-year longitudinal registry-based nationwide Danish population study by TG Willadsen, V Siersma, DR Nicolaisdóttir, R Køster-Rasmussen, DE Jarbøl, S Reventlow, SW Mercer, and N de Fine Olivarius in Journal of Comorbidity</p