Burkhard Haastert

High prevalence of undiagnosed diabetes mellitus in Southern Germany: Target populations for efficient screening. The KORA survey 2000

Aims/hypothesisTo estimate the prevalence of undiagnosed diabetes mellitus, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), and their relations with cardiovascular risk factors in the general population aged 55 to 74 years in Southern Germany.MethodsOral glucose tolerance tests were carried out in a random sample of 1353 subjects aged 55 to 74 years participating in the KORA (Cooperative Health Research in the Region of Augsburg) Survey 2000. Prevalences of glucose tolerance categories (1999 WHO criteria) were adjusted for sample probabilities. The numbers needed to screen (NNTS) to identify one person with undiagnosed diabetes were estimated from age-adjusted logistic regression models.ResultsSample design-based prevalences of known and unknown diabetes, IGT, and IFG were 9.0%, 9.7%, 16.8%, 9.8% in men, and 7.9%, 6.9%, 16.0%, 4.5% in women, respectively. In both sexes, participants with undiagnosed diabetes had higher BMI, waist circumference, systolic blood pressure, triglycerides, uric acid, and lower HDL-cholesterol than normoglycaemic subjects. A combination of abdominal adiposity, hypertension, and parental diabetes in men resulted in a NNTS of 2.9 (95%CI: 2.0–4.6). In women, the combination of increased triglycerides, hypertension and parental diabetes history yielded a NNTS of 3.2 (95%CI: 2.2–5.1).Conclusion/interpretationAbout 40% of the population aged 55 to 74 years in the Augsburg region have disturbed glucose tolerance or diabetes. Half of the total cases with diabetes are undiagnosed. Cardiovascular risk factors worsen among glucose tolerance categories, indicating the need for screening and prevention. Screening for undiagnosed diabetes could be most efficient in individuals with abdominal adiposity (men), hypertriglyceridaemia (women), hypertension, and parental diabetes history.

Mortality in Diabetic Patients with Cardiovascular Autonomic Neuropathy

Cardiovascular autonomic diabetic neuropathy (CADN) may carry an increased risk of mortality. However, in previous studies the prognosis of patients with CADN seemed to be influenced by life‐threatening macro‐ and microvascular complications which had already been present at the start of the study period. Between 1981 and 1983, 1015 diabetic patients have been examined for CADN (abnormal heart rate variation at rest and during deep respiration) at the Diabetes Research Institute, Düsseldorf. Thirty‐five patients (28 with Type 1 diabetes, 7 with Type 2 diabetes) with CADN have been retrospectively recruited and reviewed 8 years later and compared with 35 patients without CADN who were matched for sex, age, and duration of diabetes. Exclusion criteria for entry into the study included severe micro‐ or macrovascular complications, such as proliferative retinopathy, proteinuria or symptomatic coronary artery disease. During the 8‐year observation period, 8 patients with CADN and 1 patient without CADN died. The survival rate estimates steadily declined in patients with CADN over the whole period studied. The 8‐year survival rate estimate in patients with CADN was 77 % compared with 97 % in those with normal autonomic function (p < 0.05). Deaths were mainly due to macrovascular diseases (n = 3) and sudden unexpected deaths (n = 3). One patient with CADN died after an episode of severe hypoglycaemia. Among the deceased patients, coefficient of variation of R‐R intervals during deep breathing was significantly reduced when compared with those who survived (1.04 ± 0.5 % vs 1.87 ± 1.0 %; p < 0.05), and symptoms of autonomic neuropathy (orthostatic hypotension, gastroparesis, gustatory sweating) were more frequent (7/8 vs 10/27 patients). The mean QTc interval was not different between the groups. These results suggest a relatively poor prognosis of patients with CADN in the absence of clinically detectable micro‐ and macrovascular complications.

Incidence of Lower Limb Amputations and Diabetes

OBJECTIVE We collected data on the incidence rates of amputations and their relative risk in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS From all three hospitals in a city of ∼ 160,000 inhabitants, we obtained complete lists of nontraumatic lower limb amputations. From each patient record, diabetic status was determined. We estimated age-specific and standardized incidence rates of amputations in the diabetic and nondiabetic populations and in the entire population, as well as the relative and attributable risks due to diabetes. RESULTS Nontraumatic lower limb amputations were performed on 106 residents of Leverkusen (Germany) in 1990 and 1991. Of them, 82 (77.4%) had diabetes. Mean age was 72.0 years. In the case of multiple amputations, only the highest level was counted for the analysis. The following results were standardized to the German population. Incidence rates (100,000−1 · year−1) were determined to be as follows: for all amputations per total population, 33.8; for amputations in diabetic individuals per diabetic population, 209.2; for amputations in nondiabetic individuals per nondiabetic population, 9.4. Relative risk was 22.2; attributable risk among exposed, 0.96; population attributable risk, 0.72. When the study is repeated to monitor the St. Vincent targets (50% reduction), a reduction in the amputation rate in the diabetic population by 46% will be detected with 90% power. CONCLUSIONS We found incidence rates similar to those in the non-Indian population of the U.S. Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.

Prediction of Mortality Using Measures of Cardiac Autonomic Dysfunction in the Diabetic and Nondiabetic Population The MONICA/KORA Augsburg Cohort Study

OBJECTIVES—To evaluate whether reduced heart rate variability (HRV), prolonged corrected QT (QTc) interval, or increased QT dispersion (QTD) are predictors of mortality in the general diabetic and nondiabetic population. RESEARCH DESIGN AND METHODS—Nondiabetic (n = 1,560) and diabetic (n = 160) subjects aged 55–74 years were assessed to determine whether reduced HRV, prolonged QTc interval, and increased QTD may predict all-cause mortality. Lowest quartiles for the maximum-minimum R-R interval difference (max-min, as measured at baseline from a 20-s standard 12-lead resting electrocardiogram without controlling for depth and rate of respiration), QTc >440 ms and QTD >60 ms, were used as cutpoints. RESULTS—During a 9-year follow-up, 10.5% of the nondiabetic and 30.6% of the diabetic population deceased. In the nondiabetic individuals, multivariate Cox proportional hazard models adjusted for cardiovascular risk factors and demographic variables showed that prolonged QTc interval (hazard ratio 2.02 [95% CI 1.29–3.17]; P = 0.002) but not low max-min (0.93 [0.65–1.34]; P = 0.700), and increased QTD (0.98 [0.60–1.60]; P = 0.939) were associated with increased mortality. In the diabetic subjects, prolonged QTc was also a predictor of mortality (3.00 [1.34–6.71]; P = 0.007), while a trend for an increased risk was noted in those with low max-min (1.74 [0.95–3.18]; P = 0.075), whereas increased QTD did not predict mortality (0.42 [0.06–3.16]; P = 0.402). CONCLUSIONS—Prolonged QTc interval, but not increased QTD, is an independent predictor of a twofold and threefold increased risk of mortality in the nondiabetic and diabetic elderly general population, respectively. Low HRV during spontaneous breathing tends to be associated with excess mortality in the diabetic but not nondiabetic population.

Long-Term Prognosis of Diabetic Foot Patients and Their Limbs Amputation and death over the course of a decade

OBJECTIVE There is a dearth of long-term data regarding patient and limb survival in patients with diabetic foot ulcers (DFUs). The purpose of our study was therefore to prospectively investigate the limb and person survival of DFU patients during a follow-up period of more than 10 years. RESEARCH DESIGN AND METHODS Two hundred forty-seven patients with DFUs and without previous major amputation consecutively presenting to a single diabetes center between June 1998 and December 1999 were included in this study and followed up until May 2011. Mean patient age was 68.8 ± 10.9 years, 58.7% were male, and 55.5% had peripheral arterial disease (PAD). Times to first major amputation and to death were analyzed with Kaplan-Meier curves and Cox multiple regression. RESULTS A first major amputation occurred in 38 patients (15.4%) during follow-up. All but one of these patients had evidence of PAD at inclusion in the study, and 51.4% had severe PAD [ankle-brachial pressure index ≤0.4]). Age (hazard ratio [HR] per year, 1.05 [95% CI, 1.01–1.10]), being on dialysis (3.51 [1.02–12.07]), and PAD (35.34 [4.81–259.79]) were significant predictors for first major amputation. Cumulative mortalities at years 1, 3, 5, and 10 were 15.4, 33.1, 45.8, and 70.4%, respectively. Significant predictors for death were age (HR per year, 1.08 [95% CI, 1.06–1.10]), male sex ([1.18–2.32]), chronic renal insufficiency (1.83 [1.25–2.66]), dialysis (6.43 [3.14–13.16]), and PAD (1.44 [1.05–1.98]). CONCLUSIONS Although long-term limb salvage in this modern series of diabetic foot patients is favorable, long-term survival remains poor, especially among patients with PAD or renal insufficiency.

Reduced Incidence of Lower-Limb Amputations in the Diabetic Population of a German City, 1990–2005 Results of the Leverkusen Amputation Reduction Study (LARS)

OBJECTIVE—We evaluated whether the incidence of amputations in one German city (Leverkusen, population ∼160,000) had decreased between 1990 and 2005. RESEARCH DESIGN AND METHODS—From all three hospitals in the city, we obtained complete lists of nontraumatic lower-limb amputations in 1990–1991 and 1994–2005. Only the first observed amputation in residents of Leverkusen was counted. A total of 692 patients met the inclusion criteria. Data about the population stucture, separately for each year of the observation period, were received from the city administration and the Federal Office of Statistics. To test for time trend, we fitted Poisson regression models. RESULTS—Of all subjects, 72% had known diabetes and 58% were male. Mean age was 71.7 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population per 100,000 person-years) varied considerably between years (maximum 549 in 1990, minimum 281 in 2004). In the diabetic population, the estimated relative risk (RR) per year was 0.976 (95% CI 0.958–0.996, P = 0.0164). The same trend was observed when only amputations above the ankle (n = 352) (RR 0.970 [95% CI 0.943–0.997], P = 0.0318) were considered. Over 15 years, an estimated reduction of amputations above the toe level by 37.1% (95% CI 12.3–54.8) results. There was no significant change of incident amputations in the nondiabetic population (RR 1.022 [0.989–1.056], P = 0.1981). CONCLUSIONS—This finding is likely to be due to improved management of the diabetic foot syndrome after a network of specialized physicians and defined clinical pathways for wound treatment and metabolic control were introduced.

Incidence of lower-limb amputations in the diabetic compared to the non-diabetic population. Findings from nationwide insurance data, Germany, 2005-2007.

INTRODUCTION One major objective is to reduce the risk of lower limb amputation in diabetes mellitus. Nationwide data to incidences of amputations in the diabetic and non-diabetic populations in Germany as well as relative and attributable risks due to diabetes are lacking so far. MATERIAL AND METHODS Using data of a nationwide statutory health insurance (1.6 million members), we assessed all first non-traumatic lower-limb amputations between 2005 and 2007. We estimated sex-age-specific and standardized incidences of amputations in the diabetic and non-diabetic populations, and relative and attributable risks due to diabetes. RESULTS Of all subjects with a first amputation in the study period 2005-2007 (n=994), 66% had diabetes, 76% were male, mean age (SD) was 67 (13) years. Incidences per 100 000 person years (standardized to the 2004 German population) in the diabetic and the non-diabetic populations: 176.5 (95% confidence interval 156.0-196.9) and 20.0 (17.0-23.1) in men, and 76.9 (61.9-91.8) and 13.4 (10.7-16.2) in women. Standardized relative risks: 8.8 (7.3-10.7) in men and 5.7 (4.3-7.6) in women. Attributable risks among exposed: 0.89 and 0.83 and population attributable risks 0.59 and 0.40, each in men and women, respectively. DISCUSSION In our first German nationwide study, we found the relative risk of lower limb amputation in the diabetic compared to the non-diabetic to be lower than in earlier regional studies in Germany, supporting results of regional reductions of the excess amputation risk due to diabetes. A repetition of the study is warranted to further evaluate trends according to the St. Vincent goals.

Incidence of Blindness in Relation to Diabetes: A population-based study

OBJECTIVE A reduction of diabetes-related blindness was declared a primary objective for Europe (St. Vincent Declaration). We collected data about incidence rates of blindness in the diabetic population compared with the nondiabetic population. Up to now, such data are scarce—even worldwide. RESEARCH DESIGN AND METHODS A complete list of newly registered blindness allowance recipients was drawn up in the district of Württemberg-Hohenzollern, Germany, between 1990 and 1993. From these data, we estimated age-specific and standardized incidence rates of blindness in the entire, the diabetic, and the nondiabetic population, as well as relative and attributable risks due to diabetes. RESULTS There were 2,714 people meeting the inclusion criteria; 1,823 (67.2%) were female and 781 (28.8%) had diabetes. In 318 subjects, diabetes was likely to be the only cause of blindness; in 192 subjects, it was one of several contributory causes. Age of women was 73.9 ± 19.4 years (mean ± SD) and of men 63.3 ± 25.5 years. Results standardized to the (West) German population are as follows: incidence rates (per 100,000 person-years): total population: 13.5; diabetic population: 60.6; nondiabetic population: 11.6; relative risk: 5.2; attributable risk among exposed: 0.81; and population attributable risk: 0.14. The relative risks decreased considerably with increasing age. When the study is repeated to monitor the St. Vincent targets, a reduction in the incidence rate of blindness in the diabetic population by 17% will be detected with 95% power. CONCLUSIONS Great relative and attributable risks, especially in younger age-groups, indicate the need for increased attention to preventive measures for microvascular complications.

Effect of evidence based risk information on “informed choice” in colorectal cancer screening: randomised controlled trial

Objective To compare the effect of evidence based information on risk with that of standard information on informed choice in screening for colorectal cancer. Design Randomised controlled trial with 6 months’ follow-up. Setting German statutory health insurance scheme. Participants 1577 insured people who were members of the target group for colorectal cancer screening (age 50-75, no history of colorectal cancer). Interventions Brochure with evidence based risk information on colorectal cancer screening and two optional interactive internet modules on risk and diagnostic tests; official information leaflet of the German colorectal cancer screening programme (control). Main outcome measure The primary end point was “informed choice,” comprising “knowledge,” “attitude,” and “combination of actual and planned uptake.” Secondary outcomes were “knowledge” and “combination of actual and planned uptake.” Knowledge and attitude were assessed after 6 weeks and combination of actual and planned uptake of screening after 6 months. Results The response rate for return of both questionnaires was 92.4% (n=1457). 345/785 (44.0%) participants in the intervention group made an informed choice, compared with 101/792 (12.8%) in the control group (difference 31.2%, 99% confidence interval 25.7% to 36.7%; P<0.001). More intervention group participants had “good knowledge” (59.6% (n=468) v 16.2% (128); difference 43.5%, 37.8% to 49.1%; P<0.001). A “positive attitude” towards colorectal screening prevailed in both groups but was significantly lower in the intervention group (93.4% (733) v 96.5% (764); difference −3.1%, −5.9% to −0.3%; P<0.01). The intervention had no effect on the combination of actual and planned uptake (72.4% (568) v 72.9% (577); P=0.87). Conclusions Evidence based risk information on colorectal cancer screening increased informed choices and improved knowledge, with little change in attitudes. The intervention did not affect the combination of actual and planned uptake of screening. Trial registration Current Controlled Trials ISRCTN47105521.

Hip fracture incidence in the elderly in Austria: An epidemiological study covering the years 1994 to 2006

BackgroundHip fractures in the elderly are a major public health burden. Data concerning secular trends of hip fracture incidence show divergent results for age, sex and regions. In Austria, the hip fracture incidence in the elderly population and trends have not been analysed yet.MethodsHip fractures in the population of 50 years and above were identified from 1994 to 2006 using the national hospital discharge register. Crude incidences (IR) per 100,000 person years and standardised incidences related to the European population 2006 were analysed. Estimate of age-sex-adjusted changes was determined using Poisson regression (incidence rate ratios, IRRs).ResultsThe number of hospital admissions due to hip fracture increased from a total number of 11,694 in 1994 to 15,987 in 2006. Crude incidences rates (IR) per 100.000 for men increased from 244.3 (95% confidence interval (CI) 234.8 to 253.7) in 1994 to IR 330.8 (95% CI 320.8 to 340.9) in 2006 and for women from 637.3 (95% CI 624.2 to 650.4) in 1994 to IR 758.7 (95% CI 745.0 to 772.4) in 2006. After adjustment for age and sex the annual hip fracture incidence increase was only small but statistically significant (IRR per year 1.01, 95% CI 1.01 to 1.01, p < 0.01). Change of IRR over the 12 years study period was 13%. It was significantly higher for men (IRR over 12 years 1.21, 95% CI 1.16 to 1.27) than for women (IRR over 12 years 1.10, 95% CI 1.06 to 1.14) (interaction: p = 0.03).ConclusionIn contrast to findings in other countries there is no levelling-off or downward trend of hip fracture incidence from 1994 to 2006 in the Austrian elderly population. Further investigations should aim to evaluate the underlying causes in order to plan effective hip fracture reduction programmes.