Overweight, hyperglycemia and tobacco use are modifiable risk factors for onset of retinopathy 9 and 17years after the diagnosis of diabetes - A retrospective observational nation-wide cohort study.

BACKGROUND: The aims of this study were to estimate the risk for diabetic retinopathy (DR) and to identify risk factors. We investigated a nationwide population-based cohort with diabetes diagnosed at age 15-34years. PATIENTS AND METHODS: Of 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) 444 (56%) patients with retinal photos available for classification of retinopathy participated in a follow-up study 15-19 (median 17) years after diagnosis. Mean age was 42.3±5.7years, BMI 26.1±4.1kg/m2, 62% were male and 91% had type 1 diabetes. A sub-study was performed in 367 patients with retinal photos from both the 9 and 17year follow up and the risk for development of retinopathy between 9 and 17years of follow up was calculated. RESULTS: After median 17years 324/444 (73%, 67% of T1D and 71% of T2D), had developed any DR but only 5.4% proliferative DR. Male sex increased the risk of developing retinopathy (OR 1.9, 95% CI 1.2-2.9). In the sub-study obesity (OR 1.2, 95% CI 1.04-1.4), hyperglycemia (OR 2.5, 95% CI 1.6-3.8) and tobacco use (OR 2.9, 95% CI 1.1-7.3) predicted onset of retinopathy between 9 and 17years after diagnosis of diabetes. CONCLUSION: The number of patients with severe retinopathy after 17years of diabetes disease was small. The risk of developing retinopathy with onset between 9 and 17years after diagnosis of diabetes was strongly associated to modifiable risk factors such as glycemic control, obesity and tobacco use.

Glycaemic control and excess risk of ischaemic and haemorrhagic stroke in patients with type 1 diabetes: a cohort study of 33 453 patients.

OBJECTIVE: To estimate the excess risk of stroke in relation to glycaemic control in patients with type 1 diabetes. METHODS: In this prospective, matched cohort study, we identified patients with type 1 diabetes, aged ≥18 years, who were registered in the Swedish National Diabetes Register from 1998-2011 and five control subjects for each case from the general population, matched for age, sex and county of residence. The risks of all strokes, ischaemic stroke and haemorrhagic stroke were estimated using Cox hazard regression. RESULTS: Of 33 453 type 1 diabetes patients [mean age, 35.5 (SD 14.4) years; mean follow-up, 7.9 (SD 4.3) years; and mean diabetes duration, 20.2 years (SD 14.6)], 762 (2.3%) were diagnosed with stroke compared with 1122 (0.7%) of 159 924 control subjects [mean follow-up, 8.2 (SD 4.3) years]. The overall multiple-adjusted hazard ratios (HRs) for type 1 diabetes patients versus control subjects were 3.29 (95% CI: 2.96-3.66) and 2.49 (95% CI: 1.96-3.16) for ischaemic and haemorrhagic stroke, respectively. The risk of ischaemic and haemorrhagic stroke incrementally increased with increasing HbA1c; the risk of ischaemic stroke was significantly increased with HbA1c within target [≤6.9% (≤52 mmol mol-1 )] [multiple-adjusted HR 1.89 (95% CI: 1.44-2.47)]. For HbA1c ≥9.7% (≥83 mmol mol-1 ), there was a markedly increased risk of both ischaemic and haemorrhagic stroke, with multiple-adjusted HRs of 7.94 (95% CI: 6.29-10.03) and 8.17 (95% CI 5.00-13.35), respectively. CONCLUSIONS: Individuals with type 1 diabetes have an increased risk of ischaemic and haemorrhagic stroke, increasing markedly with poor glycaemic control.

Long-term excess risk of stroke in people with Type 2 diabetes in Sweden according to blood pressure level: a population-based case-control study.

AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden. METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals (CIs) were estimated at six different blood pressure levels. RESULTS: During a median follow-up of 4 years, 19 548 (4.8%) people with Type 2 diabetes and 61 690 (3.2%) without diabetes were diagnosed with stroke, corresponding to an adjusted hazard ratio of 1.43 (95% CI 1.41-1.46) for people with Type 2 diabetes as a group. Compared with people without diabetes, the risk of stroke for people with Type 2 diabetes with different blood pressure levels was significantly higher, starting at blood pressure levels > 130/80 mmHg. Hazard ratios for stroke were 1.20 (95% CI 1.16-1.24), 1.47 (95% CI 1.43-1.50), and 1.97 (95% CI 1.90-2.03) for blood pressure categories of 130-139/80-89 mmHg, 140-159/90-99 mmHg and ≥ 160/≥ 100 mmHg, respectively, after adjustment for age, sex, diabetes duration, being born in Sweden, maximum education level and baseline comorbidities. CONCLUSIONS: People with Type 2 diabetes and blood pressure < 130/80 mmHg had a risk of stroke similar to that of the general population.

Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10-year follow-up.

AIMS: To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications. METHODS: We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline. RESULTS: Among people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c , BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration. CONCLUSIONS: People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.

LDL cholesterol is not a good marker of cardiovascular risk in Type 1 diabetes.

AIM: LDL cholesterol (LDL-C) is considered an important cardiovascular disease (CVD) risk factor. Less is known in Type 1 diabetes. We assessed LDL-C and total cholesterol to HDL cholesterol ratio (TC/HDL-C) as predictors of CVD in Type 1 diabetes. METHODS: The study monitored 30 778 people with Type 1 diabetes, baseline 2003-2006, to 31 December 2011. Cox regression analyses were performed with LDL-C and TC/HDL-C as predictors of fatal/non-fatal CVD. Models were adjusted for traditional CVD risk factors. RESULTS: Hazard ratios (HR) (with 95% CI) per 1 mmol/l increase in LDL-C for CVD were 1.09 (1.01-1.18) in people without lipid-lowering medication and 1.02 (0.95-1.09) in people with lipid-lowering medication (P = 0.02 and 0.65). In people aged 40 years or older having a CVD risk factor, and in people with a history of CVD, HR was 1.07 (0.99-1.16) and 1.02 (0.92-1.13) (P = 0.07 and 0.66). HR per 1 unit increase in TC/HDL-C was 1.12 (1.05-1.20) in people without lipid-lowering medication and 1.08 (1.02-1.15) in people with lipid-lowering medication (P < 0.001 and 0.01). For people aged 40 or older and people with a history of CVD, HR was 1.16 (1.09-1.24) and 1.04 (0.95-1.14) (P < 0.001 and 0.43). Broken down into octiles, LDL-C was not a significant predictor of CVD in any group. Higher octiles of TC/HDL-C were significant predictors for CVD in people without lipid-lowering medication and in those aged 40 years or older. CONCLUSION: In this study of people with Type 1 diabetes in clinical practice, LDL-C was not a good predictor of CVD. We found no support for an LDL-C cut-off point < 2.6 mmol/l. TC/HDL-C seems more reliable as a marker for CVD risk when considering primary prevention.

Short-term effects of a pay-for-performance programme for diabetes in a primary care setting: an observational study.

OBJECTIVE: A pay-for-performance (P4P) programme for primary care was introduced in 2011 by a Swedish county (with 1.6 million inhabitants). Effects on register entry practice and comparability of data for patients with diabetes mellitus were assessed. DESIGN AND SETTING: Observational study analysing short-term outcomes before and after introduction of a P4P programme in the study county as compared with a reference county. SUBJECTS: A total of 84 053 patients reported to the National Diabetes Register by 349 primary care units. MAIN OUTCOME MEASURES: Completeness of data, level and target achievement of glycated haemoglobin (HbA1c), blood pressure (BP), and LDL cholesterol (LDL). RESULTS: In the study county, newly recruited patients who were entered during the incentive programme were less well controlled than existing patients in the register - they had higher HbA1c (54.9 [54.5-55.4] vs. 53.7 [53.6-53.9] mmol/mol), BP, and LDL. The percentage of patients with entry of BP, HbA1c, LDL, albuminuria, and smoking increased in the study county but not in the reference county (+26.3% vs -1.5%). In the study county, with an incentive for BP < 130/80 mmHg, BP data entry behaviour was altered with an increased preference for sub-target BP values and a decline in zero end-digit readings (38.3% vs. 33.7%, p < 0.001). CONCLUSION: P4P led to increased register entry, increased completeness of data, and altered BP entry behaviour. Analysis of newly added patients and data shows that missing patients and data can cause performance to be overestimated. Potential effects on reporting quality should be considered when designing payment programmes. Key points A pay-for-performance programme, with a focus on data entry, was introduced in a primary care region in Sweden. Register data entry in the National Diabetes Register increased and registration behaviour was altered, especially for blood pressure. Newly entered patients and data during the incentive programme were less well controlled. Missing data in a quality register can cause performance to be overestimated.

The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors.

AIMS: The main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34 years). METHODS: All 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19 years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. RESULTS: After median 17 years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1 kg/m²), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p = 0.041), BMI (p = 0.012) and HbA1c (p < 0.001) were significant predictors of developing diabetic nephropathy between 9 and 17 years of diabetes. At 17 years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1 mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.05 1.12 per 1 mmHg increase) were associated with DN. CONCLUSIONS: Patients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9 years of follow-up was a risk marker for later development of diabetic nephropathy.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison.

AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Predicting mortality in people with type 2 diabetes mellitus after major complications: a study using Swedish National Diabetes Register data.

AIM: To predict mortality risk and life expectancy for patients with type 2 diabetes after a major diabetes-related complication. METHODS: The study sample, taken from the Swedish National Diabetes Register, consisted of 20 836 people with type 2 diabetes who had their first major complication (myocardial infarction, stroke, heart failure, amputation or renal failure) between January 2001 and December 2007. A Gompertz proportional hazards model was derived which determined significant risk factors associated with mortality and was used to estimate life expectancies. RESULTS: Risk of death changed over time according to type of complication, with myocardial infarction initally having the highest initial risk of death, but after the first month, the risk was higher for heart failure, renal failure and amputation. Other factors that increased the risk of death were male gender (hazard ratio 1.06, 95% CI 1.02-1.12), longer duration of diabetes (hazard ratio 1.07 per 10 years, 95% CI 1.04-1.10), smoking (hazard ratio 1.51, 95% CI 1.40-1.63) and macroalbuminuria (hazard ratio 1.14, 95% CI 1.06-1.22). Low BMI, low systolic blood pressure and low estimated GFR also increased mortality risk. Life expectancy was highest after a stroke, myocardial infarction or heart failure, lower after amputation and lowest after renal failure. Smoking and poor renal function were the risk factors which had the largest impact on reducing life expectancy. CONCLUSIONS: Risk of death and life expectancy differs substantially among the major complications of diabetes, and factors significantly increasing risk included smoking, low estimated GFR and albuminuria.

Assessment of beta-cell function in young patients with type 2 diabetes: arginine-stimulated insulin secretion may reflect beta-cell reserve.

OBJECTIVE: Simple methods for the evaluation of dynamic b-cell function in epidemiological and clinical studies of patients with type 2 diabetes (T2D) are needed. The aim of this study was to evaluate the dynamic beta-cell function in young patients with T2D with different disease durations and treatments. METHODS: Overall, 54 subjects with T2D from the Diabetes Incidence Study in Sweden (DISS) and 23 healthy control participants were included in this cross-sectional study. Beta-cell function was assessed by intravenous (i.v.) administration of arginine followed by i.v. glucose. The acute insulin and C-peptide responses to arginine (AIRarg and Ac-pepRarg, respectively) and to glucose (AIRglu and Ac-pepRglu, respectively)were estimated.Homeostasis model assessment of b-cell function(HOMA-b) andCpeptide assessments were also used for comparisons between patients with T2D and control participants. RESULTS: AIRarg and Ac-pepRarg, but not AIRglu and Ac-pepRglu, could differentiate between patients with different disease durations. AIRglu values were 89% (P < 0.001) lower and AIRarg values were 29% (P < 0.01) lower in patients with T2D compared with control participants. HOMA-b and fasting plasma C-peptide levels did not differ between the T2D and control groups. CONCLUSION: In young patients with T2D, the insulin secretory response to i.v. glucose is markedly attenuated, whereas i.v. arginine-stimulated insulin release is better preserved and can distinguish between patients with different disease duration and antidiabetic therapies. This suggests that the i.v. arginine stimulation test may provide an estimate of functional beta-cell reserve.

Level of physical activity associated with risk of cardiovascular diseases and mortality in patients with type-2 diabetes: report from the Swedish National Diabetes Register.

AIMS: To estimate risks of coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality with low or higher levels of physical activity (PA) assessed with questionnaire, in an observational study of patients with type-2 diabetes from the Swedish National Diabetes Register. SUBJECTS AND METHODS: A total of 15,462 patients (60 years), were followed for 5 years from baseline in 2004 until 2009, with 760 CVD events and 427 total mortality events based on 54,344 person-years. RESULTS: Comparing 6963 patients with low baseline PA (never or 1-2 times/week for 30 min) and 8499 patients with higher baseline PA (regular 3 times/week or more), hazard ratios for fatal/nonfatal CHD, fatal/nonfatal CVD, fatal CVD, and total mortality were 1.25 (95% CI 1.05-1.48; p = 0.01), 1.26 (95% CI 1.09-1.45; p = 0.002), 1.69 (95% CI 1.18-2.41; p = 0.004), and 1.48 (95% CI 1.22-1.79; p < 0.001), adjusting for age, sex, diabetes duration, diabetes treatment, and smoking (model 1). Adjusting also for HbA1c, systolic blood pressure, low- and high-density lipoprotein cholesterol, triglycerides, body mass index, and albuminuria (model 2), HRs were 1.19 (95% CI 1.00-1.42; p = 0.049), 1.18 (95% CI 1.02-1.36; p = 0.04), 1.54 (95% CI 1.07-2.22; p = 0.02), and 1.41 (95% CI 1.16-1.72; p < 0.001), respectively. Corresponding results (model 2), comparing 4166 patients having low PA both baseline and at follow up with all other 11,296 patients were 1.68 (95% CI 1.41-2.01), 1.68 (95% CI 1.45-1.96), 2.12 (95% CI 1.48-3.03), and 2.03 (95% CI 1.66-2.48) (all p < 0.001) and compared to 2797 patients with low baseline PA and higher PA at follow up were 2.51 (95% CI 1.87-3.38), 2.54 (95% CI 1.98-3.27), 3.26 (95% CI 1.74-6.10), and 2.91 (95% CI 2.08-4.07) (all p < 0.001). CONCLUSIONS: This large observational study of patients with type-2 diabetes showed considerably increased risks for CVD and mortality with low PA.

The association between BMI and hospitalization for heart failure in 83,021 persons with Type 2 diabetes: a population-based study from the Swedish National Diabetes Registry.

AIM'S: The aim was to To study the relationship between BMI and hospitalization for heart failure in people with Type 2 diabetes. METHODS: We identified 83 021 individuals with Type 2 diabetes from the Swedish National Diabetes Registry during 1998-2003, who were followed until hospitalization for heart failure, death or end of follow-up on 31 December 2009. Cox regression analyses were performed, adjusting for age, sex, HbA(1c), blood pressure, diabetes duration, smoking, microalbuminuria, cardiac co-morbidities, glucose-lowering and anti-hypertensive medications. RESULTS: During a median follow-up of 7.2 years, 10 969 patients (13.2%) were hospitalized with heart failure. By categories of BMI, with BMI 20 to < 25 kg/m(2) as the reference, hazard ratios for patients during follow-up were 1.07 (95% CI 0.91-1.26) for a mean BMI of < 20 kg/m(2), 1.04 (95% CI 0.98-1.11) for BMI 25 to < 27.5 kg/m(2), 1.22 (95% CI 1.15-1.30) for BMI 27.5 to < 30 kg/m(2), 1.54 (95% CI 1.45-1.63) for BMI 30 to < 35 kg/m(2), 2.16 (95% CI 2.00-2.33) for BMI 35 to < 40 kg/m(2) and 3.22 (95% CI 2.88-3.60) for BMI 40 kg/m(2) or higher. There was a significant interaction between BMI and sex (P = 0.0006), with numerically higher hazard ratios for hospitalization for heart failure within each BMI category for men than for women. CONCLUSIONS: Obesity is strongly related to hospitalization for heart failure in people with Type 2 diabetes, and the relationship is somewhat stronger for men than for women. Preventing weight gain and promoting weight loss may be crucial in reducing the incidence of future hospitalizations for heart failure in this population.

LDL-cholesterol versus non-HDL-to-HDL-cholesterol ratio and risk for coronary heart disease in type 2 diabetes.

AIMS: We assessed the association between different blood lipid measures and risk of fatal/nonfatal coronary heart disease (CHD), which has been less analysed previously in type 2 diabetes. DESIGN, METHODS: Observational study of 46,786 patients with type 2 diabetes, aged 30-70 years, from the Swedish National Diabetes Register, followed for a mean of 5.8 years until 2009. Baseline and updated mean low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-, non-HDL-cholesterol, and non-HDL-to-HDL-cholesterol ratio were measured. RESULTS: Hazard ratios (HR) for CHD with quartiles 2-4 of baseline lipid measures, with lowest quartile 1 as reference: 1.03-1.29-1.63 for LDL; 1.23-1.41-1.95 for non-HDL; 1.29-1.39-1.57 for HDL; and 1.31-1.67-2.01 for non-HDL:HDL, all p < 0.001 except for quartile 2 of LDL, when adjusted for clinical characteristics and nonlipid risk factors. A similar picture was seen with updated mean values. Splines with absolute 6-year CHD rates in a Cox model showed decreasing rates only down to around 3 mmol/l for LDL, with linearly decreasing rates to the lowest level of non-HDL:HDL. Non-HDL and HDL were independent additive risk factors for CHD risk. HRs per 1 SD continuous decrease in baseline or updated mean HDL were 1.14-1.17 when fully adjusted as above, and 1.08-1.13 when also adjusted for non-HDL (p < 0.001). HRs were 1.13-1.16 adjusted for LDL, and 1.22-1.26 adjusted for total cholesterol and triglycerides (p < 0.001). Splines showed progressively increasing 6-year CHD rates with lower HDL down to 0.5 mmol/l. CONCLUSIONS: This study suggests that lower levels of non-HDL:HDL are a better risk marker for CHD than LDL-cholesterol below 3 mmol/l.

The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the relationship between glycaemic control and hospitalisation for heart failure in patients with type 2 diabetes. METHODS: Patients included in the Swedish National Diabetes Register (NDR) during 1998-2003 were followed until hospitalisation for heart failure, death or 31 December 2009. Unadjusted and adjusted incidence rates for heart failure were estimated by Poisson regression and relative risk was estimated by Cox regression. RESULTS: In 83,021 patients with type 2 diabetes, 10,969 (13.2%) were hospitalised with a primary or secondary diagnosis of heart failure during a mean follow-up of 7.2 years. The incidence increased by male sex (p < 0.001), older age (p < 0.001) and longer diabetes duration (p < 0.001). In Cox regression adjusting for risk factors of heart failure the HR per each percentage unit higher HbA(1c) (10 mmol/mol) for heart-failure hospitalisation was 1.12 (95% CI 1.10, 1.14). By category of HbA(1c) the HR for heart failure hospitalisation was: HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol), 0.91 (95% CI 0.84, 0.98); HbA(1c) 7.0 to <8.0% (53 to <64 mmol/mol), 0.99 (95% CI 0.91, 1.07); HbA(1c) 8.0 to <9.0% (64 to < 75 mmol/mol), 1.10 (95% CI 1.01, 1.20); HbA(1c) 9.0 to <10.0% (75 to <86 mmol/mol), 1.27 (95% CI 1.15, 1.41); HbA(1c) ≥ 10.0 % (≥ 86 mmol/mol), 1.71 (1.51, 1.93) (reference HbA(1c) <6% [42 mmol/mol]). The HR for patients with HbA(1c) 7.0 to <8.0% (53 to < 64 mmol/mol) compared with patients with HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol) was 1.09 (95% CI 1.03, 1.14). CONCLUSIONS/INTERPRETATION: Poor glycaemic control (HbA(1c) >7% [53 mmol/mol]) is associated with an increased risk of hospitalisation for heart failure in patients with type 2 diabetes.

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment.

AIMS/HYPOTHESIS: The aim of this study was to analyse whether the increased mortality rates observed in insulin-treated patients with type 2 diabetes and coronary artery disease are explained by comorbidities and complications. METHODS: A retrospective analysis of data from two Swedish registries of type 2 diabetic patients (n = 12,515) undergoing coronary angiography between the years 2001 and 2009 was conducted. The association between glucose-lowering treatment and long-term mortality was studied after extensive adjustment for cardiovascular- and diabetes-related confounders. Patients were classified into four groups, according to glucose-lowering treatment: diet alone; oral therapy alone; insulin in combination with oral therapy; and insulin alone. RESULTS: After a mean follow-up time of 4.14 years, absolute mortality rates for patients treated with diet alone, oral therapy alone, insulin in combination with oral therapy and insulin alone were 19.2%, 17.4%, 22.9% and 28.1%, respectively. Compared with diet alone, insulin in combination with oral therapy (HR 1.27; 95% CI 1.12, 1.43) and insulin alone (HR 1.62; 95% CI 1.44, 1.83) were associated with higher mortality rates. After adjustment for baseline differences, insulin in combination with oral glucose-lowering treatment (HR 1.22; 95% CI 1.06, 1.40; p < 0.005) and treatment with insulin only (HR 1.17; 95% CI 1.02, 1.35; p < 0.01) remained independent predictors for long-term mortality. CONCLUSIONS/INTERPRETATION: Type 2 diabetes patients treated with insulin and undergoing coronary angiography have a higher long-term mortality risk after adjustment for measured confounders. Further research is needed to evaluate the optimal glucose-lowering treatment for these high-risk patients.

Glucose-lowering treatment and clinical results in 163 121 patients with type 2 diabetes: an observational study from the Swedish national diabetes register.

AIMS: To analyse clinical characteristics and treatment results in unselected type 2 diabetes mellitus (T2DM) patients, with non-pharmacological treatment as well as the most commonly used pharmacological glucose-lowering treatment regimens, in everyday clinical practice. METHODS: In this population-based cross-sectional study, information was linked from the Swedish National Diabetes Register, Prescribed Drug Register and Patient Register. T2DM patients with non-pharmacological treatment and T2DM patients continuously using the 12 most common pharmacological treatment regimens were included in the study (n = 163121). RESULTS: There were statistically significant differences in clinical characteristics between the groups. Patients with insulin-based treatment regimens had the longest duration of diabetes and more cardiovascular risk factors than the T2DM-population in general. The proportion of patients reaching HbA1c ≤ 7% varied between 70.1% (metformin) and 25.0% [premixed insulin (PMI) + SU) in patients with pharmacological treatment. 84.8% of the patients with non-pharmacological treatment reached target. Compared to patients on metformin, patients on other pharmacological treatments had a lower likelihood, with hazard ratios ranging from 0.58; 95% confidence interval (CI), 0.54-0.63 to 0.97;0.94-0.99, of having HbA1c ≤ 7% (adjusted for covariates). Patients on insulin-based treatments had the lowest likelihood, while non-pharmacological treatment was associated with an increased likelihood of having HbA1c ≤ 7%. CONCLUSION: This nation-wide study shows insufficiently reached treatment goals for haemoglobin A1c (HbA1c) in all treatment groups. Patients on insulin-based treatment regimens had the longest duration of diabetes, more cardiovascular risk factors and the highest proportions of patients not reaching HbA1c target.

Time trends in absolute and modifiable coronary heart disease risk in patients with Type 2 diabetes in the Swedish National Diabetes Register (NDR) 2003-2008.

AIMS: The aim was to evaluate treatment goal achievements early in the course of Type 2 diabetes, and their effect on 10-year risk of coronary heart disease in patients receiving usual care. METHODS: Assessment of risk factor control 3 years after diagnosis in patients with Type 2 diabetes with no previous coronary heart disease included from the Swedish National Diabetes Register; a total of 19,382 patients (mean age 58 years) in cross-sectional surveys from 2003 to 2008, and a subgroup of 4293 patients followed individually from year of diagnosis to follow-up after a mean 2.6 years. Estimation of absolute 10-year risk of coronary heart disease using the U.K. Prospective Diabetes Study risk engine, and modifiable 10-year risk defined as percentage excess risk above patients with 'normal' risk factor values. RESULTS: Treatment goals for HbA1c , blood pressure, total and LDL cholesterol were achieved in 78.4, 65.5, 55.6% and 61.0%, respectively, in the cross-sectional survey in 2008, following a trend of generally improved control. In the individually followed patients in the subgroup, mean absolute 10-year coronary heart disease risk increased from 13.7% (men/women 16.9/9.5%) to 14.2 (men/women 17.6/9.6%) (P < 0.001) from year of diagnosis to follow-up after 2.6 years, while mean modifiable risk decreased from 37.7% (men/women 28.6/49.9%) to 19.1% (13.2/26.9%) (P < 0.001 in all). CONCLUSIONS: A high achievement of treatment goals and a low mean modifiable 10-year coronary heart disease risk was found at the 3-year follow-up, both in the cross-sectional survey in 2008 and in patients individually followed since diagnosis. This indicates the feasibility and significance of early multifactorial risk factor treatment.

Additive effects of glycaemia and dyslipidaemia on risk of cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register.

AIMS/HYPOTHESIS: The study aimed to assess the relative importance of the control of HbA(1c) and total cholesterol/HDL-cholesterol ratio (TC/HDL) on risk of cardiovascular disease (CVD). METHODS: In 22,135 participants with type 2 diabetes (age 30-75 years, 15% with previous CVD) followed for 5 years, baseline and annually updated mean HbA(1c) and TC/HDL were analysed and also categorised in combinations of quartiles. Outcomes were fatal/non-fatal CHD, stroke, CVD and total mortality. RESULTS: In all participants, HRs per 1 SD increase in updated mean HbA(1c) or TC/HDL using Cox regression analysis were 1.13 (95% CI 1.07, 1.19) and 1.31 (1.25, 1.37) for CHD, 1.15 (1.06, 1.24) and 1.25 (1.17, 1.34) for stroke, 1.13 (1.08, 1.18) and 1.29 (1.24, 1.34) for CVD (all p < 0.001), and 1.07 (1.02, 1-13; p = 0.01) and 1.18 (1.12, 1.24; p < 0.001) for total mortality, respectively, adjusted for clinical characteristics and traditional risk factors. The p value for the interaction between HbA(1c) and TC/HDL was 0.02 for CHD, 0.6 for stroke and 0.1 for CVD. Adjusted mean 5-year event rates in a Cox model, in combinations of quartiles of updated mean TC/HDL and HbA(1c) (lowest <3.1 mmol/l and 5.0-6.4% [31-46 mmol/mol]; <3.1 mmol/l and ≥7.8% [≥62 mmol/mol]; ≥4.6 mmol/l and 5.0-6.4% 31-46 mmol/mol; and highest ≥4.6 mmol/l and ≥7.8% [≥62 mmol/mol]), were 4.8%, 7.0%, 9.1% and 14.5% for CHD, and 7.1%, 9.9%, 12.8% and 19.4% for CVD, respectively. Adjusted HRs for highest vs lowest combinations were 2.24 (1.58-3.18) for CHD and 2.43 (1.79-3.29) for CVD (p < 0.001). CONCLUSIONS/INTERPRETATION: Hyperglycaemia and hyperlipidaemia were less than additive for CHD and additive for other endpoints, with the lowest risk at lowest combination levels and a considerable increase in absolute risk at high combination levels.

A new model for 5-year risk of cardiovascular disease in Type 1 diabetes; from the Swedish National Diabetes Register (NDR).

AIMS: We assessed the association between risk factors and cardiovascular disease in an observational study of patients with Type 1 diabetes from the Swedish National Diabetes Register. METHODS: A derivation sample of 3661 patients, aged 30-65 years, 6.1% with previous cardiovascular disease, baseline 2002, and 197 cardiovascular disease events when followed for 5 years until 2007. A separate validation data set of 4484 patients, baseline 2003, 201 cardiovascular disease events when followed for 4 years. RESULTS: Adjusted hazard ratios at Cox regression for fatal/non-fatal cardiovascular disease were: diabetes duration 2.76 (2.21-3.44); onset age 1.47 (1.21-1.78); log ratio total cholesterol:HDL cholesterol 1.26 (1.09-1.45); log HbA(1c) 1.19 (1.03-1.38); log systolic blood pressure 1.17 (1.01-1.34) (1 SD increase in continuous variables); smoker 1.76 (1.27-2.46); macroalbuminuria (> 200 µg/min) 1.52 (1.10-2.10); previous cardiovascular disease 3.51 (2.54-4.84). All eight variables were used to elaborate a risk equation for 5-year cardiovascular disease risk. Regarding calibration in the derivation data set, ratio predicted 5-year risk (mean 5.4 ± 7.9%) to observed event rate was 1.0. Discrimination was sufficient, with C-statistic 0.83, sensitivity and specificity 72 and 77%, respectively, for the top quartile of predicted risk. Similarly, calibration and discrimination were adequate in the validation data set: ratio of predicted 4-year risk/observed rate 0.94, C-statistic 0.80, sensitivity and specificity 62 and 77%, respectively, for the top quartile. CONCLUSIONS: This 5-year cardiovascular disease risk model from a large observational study of patients with Type 1 diabetes in routine care showed adequate calibration and discrimination and can be useful for clinical practice. It should also be tested in patients with Type 1 diabetes from other countries.

New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR).

AIMS: To analyse the association between glycosylated haemoglobin A1c (HbA1c) and cardiovascular disease (CVD) in patients with type 2 diabetes in the Swedish National Diabetes Register (NDR). METHODS: An observational study of 18 334 patients (age 30-79 years, previous CVD in 18%, baseline HbA1c 5.0-10.9%) who were followed for 6 years (mean 5.6 years) from 1997/1998 until 2003. RESULTS: Hazard ratios per 1% unit increase in baseline or updated mean HbA1c for fatal/nonfatal coronary heart disease (CHD), CVD and total mortality were 1.11-1.13, 1.10-1.11 and 1.09-1.10, respectively (all P < 0.001), adjusted for several risk factors and clinical characteristics in Cox regression. Adjusted 6-year event rates increased with higher baseline or updated mean HbA1c with no J-shaped risk curves, in all patients and also when subgrouping by shorter (mean 3 years) or longer (mean 14 years) diabetes duration, by presence or absence of previous CVD, or by treatment with oral hypoglycaemic agents (OHAs) or insulin. Risk reductions of 20% for CHD and 16% for CVD (P < 0.001) were found in patients with a baseline mean HbA1c of 6.5%, compared to those with a mean level of 7.5%. Compared to OHA-treated patients, insulin-treated patients had an increased risk of total mortality, due almost exclusively to an increased risk of non-CVD mortality, and due less to a weakly significant increased risk of fatal CVD. HbA1c was not associated with non-CVD mortality. CONCLUSIONS: This observational study showed progressively increasing risks of CHD, CVD and total mortality with higher HbA1c, and no risk increase at low HbA1c levels even with longer diabetes duration, previous CVD or treatment with either insulin or OHAs. Patients achieving HbA1c <7% showed benefits for risk reduction.