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.

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.

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.

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.

Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study.

AIMS/HYPOTHESIS: Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. METHODS: Seventy-one patients (age 18-70 years), who did not reach HbA(1c) 6.5% (48 mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16 week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0 mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16 weeks after randomisation (allocation by central office) to Alo (n = 25), Alo/Pio (n = 22) or Pbo (n = 24). Blood was sampled at pre-specified intervals, starting at 15 min before and ending 8 h after meal ingestion. RESULTS: At week 16, Alo (n = 25) and Alo/Pio (n = 21) vs Pbo (n = 24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p < 0.001), as well as in chylomicron TG (p < 0.001) and VLDL1 TG iAUCs (p < 0.001 and p = 0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p = 0.028), and a non-significant trend towards a decrease with Alo/Pio (p = 0.213). The incidence of adverse events was low and consistent with previous studies. CONCLUSIONS/INTERPRETATION: Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TG-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00655863.

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.

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.

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.

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.

Pulse pressure strongly predicts cardiovascular disease risk in patients with type 2 diabetes from the Swedish National Diabetes Register (NDR).

OBJECTIVES: To analyze pulse pressure (PP) as a risk predictor for coronary heart disease (CHD), stroke and cardiovascular disease (CVD; CHD and/or stroke) in type 2 diabetic patients. METHODS: A total of 11,128 female and male type 2 diabetic patients with known baseline PP values and no CVD, aged 50-74 years, were followed for a mean duration of 5.6 years (1998-2003). A subgroup of 5521 patients with known mean PP values (mean values at baseline and at the end of the study) was also included. RESULTS: Hazard ratios (HRs) with 95% CI for fatal/nonfatal CHD with baseline or mean PP>or=75mmHg, compared to <75mmHg, were 1.23 (1.07-1.40; P=0.003) and 1.32 (1.07-1.62; P=0.009), respectively, after adjusting for mean blood pressure (MBP), age, gender, diabetes duration, HbA(1c), body mass index (BMI), lipid-reducing drugs, microalbuminuria > 20microg/min, antihypertensive drugs and hypoglycaemic treatment, using Cox regression analyses. Fully-adjusted respective HRs for stroke were 1.17 (0.98-1.39) and 1.21 (0.90-1.61) and, for CVD, 1.23 (1.10-1.37; P<0.001) and 1.28 (1.07-1.52; P=0.007). Fully-adjusted HRs for baseline PP increased per quartile and, CHD, stroke or CVD, were 1.09 (1.03-1.16; P=0.004), 1.14 (1.05-1.23; P=0.002) and 1.11 (1.05-1.17; P<0.001), respectively. The data suggest that, if a mean PP>or=75mmHg were to be avoided, then 15% and 17% of CHD and or CVD, cases, respectively, in such a cohort might be prevented after multivariable adjustments, with a further 10% of cases avoided if also adjusted for MBP and age. Increasing baseline MBP, age and microalbuminuria were independently and significantly associated (P<0.001) with increasing baseline or mean PP. CONCLUSION: Increased PP is a powerful independent risk predictor of CVD in type 2 diabetic patients, and lowering PP can lead to a marked reduction in risk.

Risk factor control in patients with Type 2 diabetes and coronary heart disease: findings from the Swedish National Diabetes Register (NDR).

AIMS: Patients with Type 2 diabetes and coronary heart disease (CHD) are infrequently treated to risk factor targets in current guidelines. We aimed to examine risk factor management and control levels in a large sample of patients with Type 2 diabetes with CHD. METHODS: This was an observational study of 1612 patients with first incidence of CHD before 2002, and of 4570 patients with first incidence of CHD before 2005, from the Swedish National Diabetes Register (NDR). RESULTS: In patients with CHD 1-2 years before follow-up, the achievement of cardiovascular risk factor targets (follow-up 2002/follow-up 2005) was: HbA(1c) < 7%, 47%/54% (P < 0.01); blood pressure < or = 130/80 mmHg, 31%/40% (P < 0.001); total cholesterol < 4.5 mmol/l, 47%/60% (P < 0.001); and low-density lipoprotein-cholesterol < 2.5 mmol/l, 49%/65% (P < 0.001). Use of medication: antihypertensives, 90%/94% (P < 0.01); lipid-lowering drugs, 75%/86% (P < 0.001); and aspirin, 85%/89% (P < 0.05). A high prevalence of adverse lifestyle characteristics prevailed (2002/2005): overweight [body mass index (BMI) > or = 25 kg/m(2)], 86%/85%; obesity (BMI > or = 30 kg/m(2)), 41%/42%; smokers in age group < 65 years, 16-23%/18-19%; as well as waist circumference > or = 102 cm (men) or > or = 88 cm (women), 68% in 2005. CONCLUSIONS: Patients with a combination of Type 2 diabetes and CHD showed an increased use of lipid-lowering drugs over time, corresponding to improving blood lipid levels. A discrepancy existed between the prevalent use of antihypertensive drugs and the low proportion reaching blood pressure targets. Regretfully, a high prevalence of adverse lifestyle characteristics prevailed. Evidence-based therapy with professional lifestyle intervention and drugs seems urgent for improved quality of secondary prevention in these patients.

Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients.

AIMS/HYPOTHESIS: The aim of this study of type 2 diabetic patients in the Swedish National Diabetes Register was to study the associations of BMI, overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI >or= 30 kg/m(2)) with cardiovascular disease in type 2 diabetes, as these associations have not previously been clarified. METHODS: Patients aged 30-74 years with no previous CHD or stroke (N = 13,087) were followed for a mean of 5.6 years until 2003 for fatal or non-fatal CHD, stroke, cardiovascular disease (CHD or stroke) and total mortality. In total, 1,922 cardiovascular-disease events occurred, based on 64,864 person-years. RESULTS: The relative risks of CHD, stroke, cardiovascular disease and total mortality for a 5 unit increase in BMI at baseline were 15%, 11%, 13% and 27%, respectively, using Cox regression analysis, after adjusting for age, sex, diabetes duration, hypoglycaemic treatment and smoking (model 1), and were 9%, 4% (not significant), 7% and 20%, respectively, when adjusting also for HbA(1c), blood pressure, antihypertensive drugs, lipid-reducing drugs and microalbuminuria (model 2). Adjusted hazard ratios (model 1) for CHD, cardiovascular disease and total mortality with overweight were 1.27 (95% CI 1.09-1.48), 1.24 (1.09-1.41) and 1.16 (0.94-1.45), respectively, and 1.49 (1.27-1.76), 1.44 (1.26-1.64) and 1.71 (1.36-2.14) with obesity, as compared with normal weight. Significant hazard ratios were attenuated when adjusted according to model 2. For a 1 unit increase in BMI during follow-up, the relative risk of CHD (model 2) was 1.13 (1.04-1.23; p = 0.005). CONCLUSIONS/INTERPRETATION: Both overweight and obesity independently increased the risk of CHD and cardiovascular disease in patients with type 2 diabetes. The CHD risk was higher with increasing BMI than with stable or decreasing BMI during the study.

Antihyperglycaemic treatment of type 2 diabetes: results from a national diabetes register.

AIM: To describe clinical characteristics and antihyperglycemic treatment patterns in patients with varying duration of diabetes. METHODS: We performed a cross-sectional survey of 61890 type 2 diabetic (DM2) patients from the Swedish National Diabetes Register (NDR) in 2004. We also analysed the effect of types of treatment and risk factors on glycaemic control in a longitudinal cohort study from 1996 to 2004. HbA(1c), risk factors and treatments were determined locally in primary care as well as hospital outpatient clinics. RESULTS: Insulin was frequently used in DM2 patients with long duration of diabetes, although the mean HbA(1c) increased and only a few in this group reached HbA(1c) <7.0%. Patients showing long-term improvement in HbA(1c) (>1%) from 1996 to 2004 were more often treated with insulin than with oral hypoglycaemic agents (OHA). During this period, the HbA(1c) levels leading to additional treatment decreased. A low BMI, decreasing BMI and not smoking were predictors of good long-term metabolic control. Hypertension and hyperlipidaemia were frequent in both newly diagnosed DM2 patients and in patients with a long duration of diabetes. CONCLUSIONS: Insulin treatment was frequently used, particularly in patients with a long duration of DM2. The glycaemic control, which usually deteriorates over time, did not reach the recommended goal, despite the fact that complementary treatment was added at lower HbA(1c) levels in 2003 than in 1996. High frequencies of hypertension, hyperlipidaemia and high 10-year risks of coronary heart disease necessitate intensified risk factor control in the future.

Weight loss and metabolic effects of topiramate in overweight and obese type 2 diabetic patients: randomized double-blind placebo-controlled trial.

OBJECTIVE: To examine the metabolic effects and body composition changes after topiramate treatment of obese type 2 diabetic patients (DM2) for 11 months. DESIGN AND SUBJECTS: Thirty-eight DM2 on diet or sulfonylurea treatment participated in this randomized double-blind placebo-controlled trial. Thirteen placebo-treated and nine topiramate-treated patients completed the trial. Patients were randomized to treatment with topiramate 96 mg b.i.d. or placebo (6-week run-in phase, 2-months titration phase, 9-months maintenance phase). MEASUREMENTS: Insulin sensitivity was measured with euglycaemic hyperinsulinemic clamps. Weight, HbA1c, fasting glucose, blood lipids and safety variables were measured at regular intervals. Body composition was determined with computerized tomography. Meal tests were performed to evaluate postprandial glucose and insulin levels. Three-day diet recalls were carried out to evaluate energy ingestion. RESULTS: The mean age was 58.6+/-7.1 years, body weight 98.1+/-16.1 kg, BMI 33.0+/-4.5 kg/m(2), and glycosylated hemoglobin (HbA1c) 7.3+/-0.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.1+/-0.9%), fasting plasma glucose, body weight (-6.6+/-3.3%), as well as body fat, lean body mass, postprandial glucose and free fatty acid levels but there were no significant changes in insulin sensitivity. The daily average energy intake decreased more in the topiramate group than in the placebo group. Paresthesia and central nervous system-related side effects were the main causes for the dropout rate. CONCLUSIONS: Topiramate treatment of overweight DM2 reduced body weight and body fat, and was associated with a marked improvement in glycaemic control whereas no significant improvement in insulin-stimulated glucose uptake was demonstrated. Further studies are required to clarify whether this effect might occur through changes in insulin sensitivity in the liver and/or pancreatic insulin secretion.

Obesity and cardiovascular risk factors in type 2 diabetes: results from the Swedish National Diabetes Register.

OBJECTIVES: To compare obese with normal and overweight type 2 diabetic patients regarding body mass index (BMI) and cardiovascular risk factors, and to analyse changes in weight versus risk factors. DESIGN AND SETTING: A cross-sectional study of 44 042 type 2 patients, and a 6-year prospective study of 4468 type 2 patients. RESULTS: Obese patients (BMI > or = 30 kg m(-2)), 37% of all patients, had high frequencies of hypertension (88%), hyperlipidaemia (81%) and microalbuminuria (29%). Only 11% had blood pressure <130/80 mmHg. Their ratio of triglycerides to HDL cholesterol was considerably elevated, whilst the mean total and LDL cholesterol were similar as in normal weight subjects. Obese patients had elevated odds ratios for hypertension, hyperlipidaemia and microalbuminuria: 2.1, 1.8 and 1.4 in the cross-sectional study, similarly confirmed in the prospective 6-year study. BMI was an independent predictor of these risk factors (P < 0.001), although only slightly associated with HbA1c and not with total or LDL cholesterol. A change in BMI during the prospective study was related to a change in HbA1c in patients treated with diet and oral hypoglycaemic agents (OHAs) but not with insulin. In all patients, an increase in BMI was related to the development of hypertension, and a change in BMI to change in blood pressure, also mostly confirmed when treated with diet, OHAs or insulin. CONCLUSIONS: The high frequencies of risk factors in obese type 2 patients implies an increased risk of cardiovascular disease and the need for therapeutic measures. The paradox that hypoglycaemic treatment accompanied by weight gain may increase cardiovascular risk factors seems to be verified here concerning hypertension but not concerning microalbuminuria.

The gap between guidelines and reality: Type 2 diabetes in a National Diabetes Register 1996-2003.

Guidelines for the treatment of risk factors in diabetes care have been updated recently, due to indisputable results from clinical end-point trials. This study evaluates risk factor control compared with current national and international targets during the period 1996-2003 in Type 2 diabetes (DM2). Patients were registered in primary-care and hospital outpatient clinics using computer software, or via the Internet. The clinical characteristics of the patients, treatment, HbA(1c), and risk factors were reported after screening by local methods. The numbers of cases of DM2 reported were 17547 in 1996 and 57119 in 2003. The mean HbA(1c) decreased from 7.8 to 7.2%, while blood pressure decreased from 150/82 to 143/78 mmHg during the same period. Longitudinal analysis of results was performed in 5356 patients repeatedly reported, showing slightly lower effects. The new European treatment targets of HbA(1c)< or = 6.1%, blood pressure < 130/80 mmHg and total cholesterol < 4.5 mmol/l were attained by 16, 13 and 28% of the patients in 2003, respectively. The prevalence of the metabolic syndrome in 2003 was 77%. Aspirin was prescribed in 36% of cases. Lipid-lowering, anti-hypertensive drugs, and treatment with oral hypoglycaemic agents in combination with insulin were increasingly employed during the period studied. Risk factor control in DM2 reported to the National Diabetes Register (NDR) is slowly improving, although multiple risk factors and the metabolic syndrome are found in most patients. The majority of subjects do not achieve current target levels for HbA(1c), blood pressure and blood lipids. Thus, giving up smoking and increased use of aspirin are called for, as well as more aggressive treatment of hyperglycaemia, elevated blood pressure and blood lipid levels, in accordance with updated international guidelines.

Microalbuminuria and risk factors in type 1 and type 2 diabetic patients.

A prospective study of normoalbuminuric diabetic patients was performed between 1997 and 2002 on 4097 type 1 and 6513 type 2 diabetic patients from the Swedish National Diabetes Register (NDR); mean study period, 4.6 years. The strongest independent baseline risk factors for the development of microalbuminuria (20-200 microg/min) were elevated HbA(1c) and diabetes duration in both types 1 and 2 diabetic patients. Other risk factors were high BMI, elevated systolic and diastolic BP in type 2 patients, and antihypertensive therapy in type 1 patients. A subsequent larger cross-sectional study in 2002 showed that established microalbuminuria was independently associated with HbA(1c), diabetes duration, systolic BP, BMI, smoking and triglycerides in types 1 and 2 diabetic patients, and also with HDL-cholesterol in type 2 patients. Relatively few types 1 and 2 patients with microalbuminuria achieved treatment targets of HbA(1c) < 6.5% (21-48%), BP < 130/85 mmHg (33-13%), cholesterol < 5 mmol/l (48-46%), triglycerides < 1.7 mmol/l (83-48%) and BMI < 25 kg/m(2) (50-18%), respectively. In conclusion, high HbA(1c), BP and BMI were independent risk factors for the development of microalbuminuria in types 1 and 2 diabetic patients. These risk factors as well as triglycerides, HDL-cholesterol and smoking were independently associated with established microalbuminuria. Treatment targets were achieved by a relatively few patients with microalbuminuria.

Smoking is associated with increased HbA1c values and microalbuminuria in patients with diabetes--data from the National Diabetes Register in Sweden.

OBJECTIVES: The aim was to examine trends in the proportion of smoking in diabetes patients, and to study associations between smoking, glycaemic control, and microalbuminuria. METHODS: Smoking habits were reported to the Swedish National Diabetes Register (NDR), with data from hospitals and primary health care. Patient characteristics included were age, gender, type of treatment, diabetes duration, HbA1c, BMI, blood pressure, antihypertensive and lipid-lowering drugs, and microalbuminuria. RESULTS: The proportion of smokers in type 1 diabetes was 12-15% during 1996-2001, it was high in females<30 years (12-16%), and was higher in the age group 30-59 years (13-17%) than in older (6-9%) patients. The corresponding proportion of smoking in type 2 diabetes was 10-12%, higher in those less than 60 years of age (17-22%) than in older (7-9%) patients. Smoking type 1 and type 2 patients in 2001 had higher mean HbA1c but lower mean BMI values than non-smokers. Smokers also had higher frequencies of microalbuminuria, in both type 1 (18 vs 14%) and type 2 (20% vs 13%) diabetes. Multiple logistic regression analyses disclosed that smoking was independently associated with elevated HbA1c levels (p<0.001) and microalbuminuria (p<0.001), but negatively with BMI (p<0.001), in both type 1 and type 2 diabetes. CONCLUSIONS: Smoking in patients with diabetes was widespread, especially in young female type 1, and in middle-aged type 1 and type 2 diabetes patients, and should be the target for smoking cessation campaigns. Smoking was associated with both poor glycaemic control and microalbuminuria, independently of other study characteristics.

Hypertension in diabetes: trends in clinical control in repeated large-scale national surveys from Sweden.

Hypertension in diabetes is an important and treatable cardiovascular risk factor. Treatment targets from guidelines cannot always be achieved in everyday clinical practice. It is therefore of great importance to monitor trends in hypertension control in defined populations. Patients with type I diabetes (range 6685-10,100; treated hypertension 21-29%) or with type II diabetes (range 15,935-22,605; treated hypertension 47-56%) were included in four national samples between 1996 and 1999. This screening was part of the procedures for the National Diabetes Register in Sweden, which monitors trends in clinical practice and risk factors for patients with diabetes, recruited both in primary health care and at the hospital level. A favourable trend in mean and median blood pressure levels was noticed during the 4-year study period, based either on data from repeated surveys or on repeated measures in the same individual, both for type I diabetes (mean: -2/-2 mmHg; P < 0.01) and for type II diabetes (mean: -5/-3 mmHg; P < 0.001). Correspondingly, the proportion of hypertensive patients in acceptable control of blood pressure (< or =140/85 mmHg) increased (P < 0.001) both in type I diabetes (52.0-57.9%) and in type II diabetes (22.4-33.3%). It was concluded that hypertension is a widespread cardiovascular risk factor in patients with diabetes, especially systolic hypertension. A trend for a better systolic blood pressure control during the late 1990s in hypertensive patients with type II diabetes in Sweden could translate into substantial (estimated) clinical benefits in cardiovascular and diabetes-related morbidity. The National Diabetes Register makes a quality assessment of the hypertension treatment possible.

What causes impaired glucose tolerance to deteriorate or normalize?

Twenty-five middle-aged subjects with impaired glucose tolerance (IGT) were analysed 5 years later, showing normal glucose tolerance in 28% and persistent glucose deterioration in 72%. Body mass index (strongly) and 2-h glucose levels were clinically useful predictors, in the newly detected IGT-subjects, of persistent glucose deterioration (IGT or NIDDM) 5 years later. The frequency of hypertension was 36% in the newly-detected IGT subjects. Five years later this frequency increased to 54% in the persistently hyperglycaemic group, and decreased to none in the normalized group. Predictors of hypertension at the follow-up were baseline blood pressure and parts of the hyperinsulinaemic syndrome, such as serum triglyceride at baseline, BMI and 2-h glucose at the follow-up. Microalbuminuria (greater than 20 mg day-1) was not found at the 5-years follow-up, either if the subjects then had NIDDM, IGT or normal glucose tolerance. ECG abnormalities (ST segment and T wave changes) were two-fold more prevalent in the group with IGT or NIDDM than in the normalized group at the follow-up. Predictors were baseline BMI and incremental BMI. In conclusion, obesity and high 2-h glucose in newly-detected IGT-subjects seemed to predict the persistence of IGT 5 years later. Hypertension, but not microalbuminuria, was frequent when glucose deterioration persisted.