LDL cholesterol level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes mellitus: A nationwide cohort study.

BACKGROUND: Microvascular complications are common in people with diabetes, where poor glycaemic control is the major contributor. The aim of this study was to explore the association between elevated LDL cholesterol levels and the risk of retinopathy or nephropathy in young individuals with type 1 diabetes. METHODS: This was a nationwide observational population-based cohort study, including all children and adults with a duration of type 1 diabetes of ≤ 10 years, identified in the Swedish National Diabetes Register between 1998 and 2017. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) of retinopathy or nephropathy in four LDL cholesterol categories: <2.6 (Reference), 2.6-3.4, 3.4-4.1 and > 4.1 mmol L-1 . RESULTS: In total, 11 024/12 350 (retinopathy/nephropathy, both cohorts, respectively) children and adults (median age 21 years, female 42%) were followed up to 28 years from diagnosis until end of study. Median duration of diabetes when entering the study was 6 and 7 years in the retinopathy and nephropathy cohort, respectively. Median LDL cholesterol was 2.4 mmol L-1 , and median HbA1c level was 61 mmol mol-1 (7.7 %). After multivariable adjustment, the HRs (95% CI) for retinopathy in individuals with LDL cholesterol levels of 2.6-3.4, 3.4-4.1 or > 4.1 mmol L-1 were as follows: 1.13 (1.03-1.23), 1.16 (1.02-1.32) and 1.18 (0.99-1.41), compared with the reference. The corresponding numbers for nephropathy were as follows: 1.15 (0.96-1.32), 1.30 (1.03-1.65) and 1.41 (1.06-1.89). CONCLUSIONS: Young individuals with type 1 diabetes exposed to high LDL cholesterol levels have an increased risk of retinopathy and nephropathy independent of glycaemia and other identified risk factors for vascular complications.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Mercury vapour lamps interfere with the bat defence of tympanate moths (Operophtera spp.; Geometridae)

Bats often forage near streetlamps, where they catch moths in particular. At least two hypotheses may explain the apparent increase in the availability of moths to bats feeding around streetlamps: (1) the moths become concentrated near the light and therefore more profitable to exploit; and (2) the light interferes with the moths' evasive flight behaviour. We tested the second of these hypotheses by exposing flying male winter moths, Operophtera spp., to bursts of ultrasound (26 kHz, 110 dB sound pressure level) from an electronic source. The light from a 125 W mercury vapour lamp had a quantitative effect on the moths' evasive flight response at close range (within ca 4 m), inhibiting it totally in nearly half (43%, N=125) of the cases. By contrast, moths flying in the surrounding woodland and without interference from the lamp always responded to the sound. Streetlamps of the mercury vapour type (white lamps) thus interfere with the defensive behaviour of moths and presumably increase their vulnerability to echolocating bats. This may have implications for the conservation of both moths and bats. Copyright 1998 The Association for the Study of Animal Behaviour.