Guido Giani

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.

Novel biomarkers for pre-diabetes identified by metabolomics

Type 2 diabetes (T2D) can be prevented in pre‐diabetic individuals with impaired glucose tolerance (IGT). Here, we have used a metabolomics approach to identify candidate biomarkers of pre‐diabetes. We quantified 140 metabolites for 4297 fasting serum samples in the population‐based Cooperative Health Research in the Region of Augsburg (KORA) cohort. Our study revealed significant metabolic variation in pre‐diabetic individuals that are distinct from known diabetes risk indicators, such as glycosylated hemoglobin levels, fasting glucose and insulin. We identified three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2) and acetylcarnitine) that had significantly altered levels in IGT individuals as compared to those with normal glucose tolerance, with P‐values ranging from 2.4 × 10−4 to 2.1 × 10−13. Lower levels of glycine and LPC were found to be predictors not only for IGT but also for T2D, and were independently confirmed in the European Prospective Investigation into Cancer and Nutrition (EPIC)‐Potsdam cohort. Using metabolite–protein network analysis, we identified seven T2D‐related genes that are associated with these three IGT‐specific metabolites by multiple interactions with four enzymes. The expression levels of these enzymes correlate with changes in the metabolite concentrations linked to diabetes. Our results may help developing novel strategies to prevent T2D.

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.

Incidence of Type 2 diabetes in the elderly German population and the effect of clinical and lifestyle risk factors: KORA S4/F4 cohort study

Aims  To determine the incidence of Type 2 diabetes in an elderly population in Germany and its association with clinical and lifestyle factors.

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.

Assessing health-related quality of life in patients with restless legs syndrome

BACKGROUND Restless Legs Syndrome (RLS) has a substantial impact on normal daily activities. Because of the high prevalence it is necessary to evaluate the impact on the health-related quality of life (HRQoL). OBJECTIVE To assess health-related quality of life in patients with RLS. METHODS A total of 519 patients (327 female patients; mean age: 64.2 y) were recruited in five different German centers according to the diagnostic criteria of the International RLS Study Group. Patients were either interviewed or completed a mailed questionnaire. The questionnaire consisted of an evaluation of the sociodemographic, clinical and health-related status. HRQoL was evaluated with the EuroQoL (EQ-5D). In addition, the IRLS scale, the MOS Sleep Scale, the Epworth Sleepiness Scale, and the BDI were applied as clinical rating scales. RESULTS HRQoL is substantially affected by RLS. The mean EQ-5D-VAS was 55.6 and considerably lower compared to the general population. It was found to be as low as in other chronic neurological disorders such as Parkinsons disease and stroke. From different factors investigated by uni- and multivariate analyses, severity of RLS and depressive symptoms had the most significant impact on HRQoL. Additionally, sleep deficits, the duration of the disease and net household income were identified as predictors for different EQ-5D outcome scores. CONCLUSIONS RLS considerably affects HRQoL. Further comparative studies are necessary to evaluate the effect of disease symptoms on HRQoL and their change due to medication.

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.

APOA5 variants and metabolic syndrome in Caucasians

Apolipoprotein A5 (APOA5) gene variants were reported to be associated with two components of metabolic syndrome (MetS): higher TG levels and lower HDL levels. Moreover, a recent Japanese case-control study found variant −1131T>C associated with MetS itself. Thus, our study systematically analyzed the APOA5 gene for association with lipid parameters, any other features of MetS, including waist circumference, glucose-related parameters, blood pressure, uric acid, and MetS itself in Caucasians. Ten polymorphisms were analyzed in a large fasting sample of the population-based Cooperative Health Research in the Region of Augsburg (KORA) survey S4 (n = 1,354; southern Germany) and in a second fasting sample, the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1,770; Austria). Minor alleles of variants −1131T>C, −3A>G, c.56C>G, 476G>A, and 1259T>C were significantly associated with higher TG levels in single polymorphism (P < 0.001) and haplotype (P ⩽ 6.6 × 10−6) analysis. Besides associations with lower HDL levels in SAPHIR (P ⩽ 0.001), there were no significant findings with any other features of MetS. Variant c.56C>G was associated with higher risk for MetS [odds ratio (95% confidence interval) = 1.43 (1.04, 1.99), P = 0.03 for KORA and 1.48 (1.10, 1.99), P = 0.009 for SAPHIR). Our study confirms the association of the APOA5 locus with TG and HDL levels in humans. Furthermore, the data suggest a different mechanism of APOA5 impact on MetS in Caucasians, as variant c.56C>G (not analyzed in the Japanese study) and not −1131T>C, as in the Japanese subjects, was associated with MetS.

Early infant feeding and risk of type 1 diabetes mellitus—a nationwide population-based case–control study in pre-school children

The evidence on the role of environmental factors in the development of type 1 diabetes is conflicting. Reducing potential bias and the variety of exposures, we investigated the association between type 1 diabetes risk and nutritional and environmental exposures in pre‐school children.

Prevalence of undiagnosed diabetes and impaired glucose regulation in 35-59-year-old individuals in Southern Germany: the KORA F4 Study.

Diabet. Med. 27, 360–362 (2010)