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.

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.

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.

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.

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.

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.

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.

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.

Insulin release and peripheral sensitivity at the oral glucose tolerance test.

With the use of a 75 g oral glucose tolerance test, both insulin release (IRG) and the degree of peripheral sensitivity (SI) were evaluated simultaneously in groups with normal (NGT) and impaired (IGT) glucose tolerance as well as NIDDM. IRG was expressed as the ratio of the area under the insulin curve to that of the glucose curve above fasting levels. The peripheral glucose uptake rate (M) during the OGTT was measured as the difference between the glucose load and the increase in the amount of glucose in the glucose space during the oral glucose tolerance test (OGTT). SI was expressed as the ratio of the metabolic clearance rate (M/mean blood glucose) to log mean serum insulin. In the non-obese groups, both mean IRG and mean SI values were decreased with an increasing degree of hyperglycemia from NGT to NIDDM. Decreased mean SI values were also found in obese subjects. IGT-subjects given 3 months of diet and exercise achieved improved SI values. A non-obese NIDDM-group had higher mean IRG and mean SI values after 6 months of treatment with glipizide. The results were comparable to data obtained with more complicated techniques, such as the insulin clamp and suppression tests, and should be easy to apply on a large scale in epidemiological studies.

Findings in a health survey of middle-aged subjects in Uppsala 1981-82. Risk factors for diabetes mellitus and cardiovascular disease.

In a health survey in 1981-82 in the city of Uppsala 819 subjects (443 females and 376 males), 47-54 years old, were examined. A 75 g oral glucose tolerance test OGTT was performed in each subject, and fasting and 2-h venous whole blood glucose values were determined. The 2-h value was somewhat higher in females, 4.7 mmol X l-1, than in males, 4.4 mmol X l-1 (p less than 0.01). Known or probable manifest diabetes was present in 1.9% of all subjects. Glucose values within the limits for WHO criteria of glucose intolerance were found in another 7.1% of all subjects after one OGTT. The rates were similar in both sexes. A history of diabetes in first-degree relatives was noted in 13.2% of all subjects. According to a questionnaire, 1.1% of all subjects had had hospital care for myocardial infarction, 4.7% had angina pectoris and 2.4% had intermittent claudication. The rate of subjects on antihypertensive treatment or with untreated high blood pressure greater than or equal to 170/105 mm Hg was 11.2%; of these only 1.8% had untreated high blood pressure. Of the treated subjects, the treatment was adequate in 82.9%. Obesity, defined as relative body mass index greater than or equal to 120%, was found in 34.0% of all subjects, more frequently in females than in males. The rate of smokers was 28.5%. A comparison was made with the results of a similar health survey of about 2 300 middle-aged men in Uppsala in 1970-73. The prevalence of angina pectoris was higher among the men of the present survey than among those of the 1970-73 survey, which may at least partly be due to differences in methodology. Relative body weight was higher, and fewer men were regularly active during leisure for at least 2-3 h per week in the present study. The rates of hypertension were similar, but fewer men had untreated high blood pressure and more men were on antihypertensive treatment in the present study. There was a lower frequency of smokers in this study.

Short-term treatment of glucose intolerance in middle-aged subjects by diet, exercise and sulfonylurea.

In a screening survey of women and men 47-54 years old for detection of glucose intolerance (GI), with 75 g oral glucose tolerance tests (OGTT), 25 subjects with GI were randomly selected for a therapeutic trial for normalization of the GI. A control group of 18 GI subjects was chosen randomly from the same health survey and given no treatment for 5-10 months; no significant changes in OGTT variables, body mass index, blood pressure or blood lipids were found in this group during follow-up. The treatment group was given advice concerning a low-sucrose, low-fat, high-fiber and energy-restricted (when overweight) diet and also concerning exercise - single-handed (16 subjects) or in an exercise group (9 subjects). The GI improved in the 25 treated subjects after 6 months of this therapy. Thus the total area under the glucose curve and the 1-h and the 2-h glucose values had decreased, the mean 2-h glucose value was restored to normal (less than 7.0 mmol X l-1) and 48% of the treated subjects had a normal 2-h glucose value. Body mass index, systolic blood pressure, serum cholesterol and serum triglycerides were also reduced at the follow-up. The 6-month result was similar in the subgroup of nine GI subjects who followed the dietary advice and exercised in a group for at least one hour per week during at least three months. Physical working capacity was increased, although non-significantly. Glipizide, 1.25 mg daily, was added at breakfast to ten GI-subjects who still had pathological 2-h glucose values after 6 months of dietary and exercise treatment. After a further 6 months of treatment of these 10 subjects, the total glucose area and the 2-h glucose value were reduced, while the mean 2-h glucose value had not required the normal level. Body mass index was unchanged. Another four subjects in this subgroup now showed a normal 2-h glucose value. In conclusion, the 2-h glucose value was restored to normal in totally 64% of all treated GI subjects after short-term treatment with a diet, exercise and, in some cases, added glipizide.

Pulse pressure, mean blood pressure and impaired glucose tolerance--a study in middle-aged subjects.

In a study of 695 middle-aged subjects, without antihypertensive agents, and without more pronounced obesity, both pulse pressure (PP) and mean blood pressure (MBP) were strongly related to 2-h blood glucose in 75 g OGTTs (p < 0.001). All hypertensives (DBP > or = 90 mm Hg) were separated into 39 with higher PP (> or = 60 mm Hg) and 137 with lower PP (< 60 mm Hg). The high PP hypertensives, compared with the low PP hypertensives and all 519 normotensives, had higher frequency of impaired glucose tolerance (IGT; WHO-criteria), 33%, 6%, and 4%, respectively (p < 0.001), and also higher mean 2-h blood glucose, 5.9, 4.5, and 4.2 mmol.l-1, respectively (p < 0.001). These differences were independent of MBP levels. Similarly, all 54 hypertensives with higher MBP (> or = 110 mm Hg) had more IGT and higher 2-h glucose than the 122 hypertensives with lower MBP (< 110 mm Hg) or the normotensives, 30%, 5% and 4%, respectively (p < 0.001), and 5.8, 4.4, 4.2 mmol.l-1, respectively (p < 0.001), independently of PP. Thus, both high PP and high MBP were related to IGT, independently of each other.

Influences of familial and environmental factors on hypertension.

A group of 293 middle-aged subjects with a parental history of hypertension was compared with 210 middle-aged subjects without this history. The adjusted odds ratio for hypertension (WHO-criteria) was 2.0 with parental hypertension - independent of obesity, physical leisure time activity, age and sex. Comparatively in all 503 participants, the independent odds ratio for hypertension was 3.3 with obesity. Analysis of variance in all participants disclosed that blood pressure was independently related to three predictors, parental hypertension (p less than 0.05), body mass index (p less than 0.001), and 2-h blood glucose (p less than 0.001). Additional analysis of variance in all subjects, to estimate if these three predictors were interrelated, disclosed that parental hypertension was not related to either 2-h glucose or body mass index. A clear association was seen between 2-h glucose and body mass index (p less than 0.001). This was underlined in a separate analysis of the 88 hypertensives, among which 25% had impaired glucose tolerance (WHO-criteria). In conclusion, own obesity (environment) had about 1.5 times stronger influence on hypertension than parental hypertension (heredity). Parental hypertension seemed to have a separate influence on the blood pressure. Body mass index and 2-h glucose seemed to have partly separate, and partly interrelated, influences on the blood pressure.

Prevalences of risk factors and angiopathy in diabetic patients in Uppsala.

The prevalences of risk factors and angiopathy were studied in 260 diabetic patients, 100 females and 160 males, 35-54 years old, in Uppsala. The prevalence, in females and males separately, of hypertension (WHO-criteria) was 46-34%, of hypercholesterolaemia (greater than or equal to 6.7 mmol.l-1) 32-29%, and of obesity (relative BMI greater than or equal to 120%) 25-20%. Those smoking greater than 15 cigarettes/day were 11-20%. Mean HbA1 was 10.6-10.5%. The prevalence of angina pectoris was 11-6%, of possible infarction 4-6%, and of major ECG abnormalities 6-4%. Large vessel (cardiovascular) disease was independently related to HbA1 (strongly), hypertension, cholesterol, age and familial NIDDM. The prevalence of severe retinopathy (blindness, new vessels or large hemorrhage) was 0% with 7-13 years of diabetes duration, and 26% with greater than or equal to 14 years of duration. The prevalence of severe proteinuria was 4% with 7-13 years of diabetes duration, and 15% with greater than or equal to 14 years of duration. Small vessel (retinopathy and nephropathy) disease was independently related to diabetes duration (strongly), HbA1 and hypertension. The data were discussed related to data from the London, Berlin and Tokyo centres of the WHO Multinational Study of Vascular Disease in Diabetics, using the same study protocol in the present study.

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.