Association of the habitual dietary intake with the fatty liver index and effect modification by metabotypes in the population-based KORA-Fit study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging threat for public health with diet being a major risk factor in disease development and progression. However, the effects of habitual food consumption on fatty liver are still inconclusive as well as the proposed role of the individuals' metabolic profiles. Therefore, the aim of our study is to examine the associations between diet and NAFLD with an emphasis on the influence of specific metabotypes in the general population. METHODS: A total of 689 participants (304 men and 385 women) of the KORA-Fit (S4) survey, a follow-up study of the population-based KORA cohort study running in the Region of Augsburg, Germany, were included in this analysis. Dietary information was derived from repeated 24-h food lists and a food frequency questionnaire. The intake of energy and energy-providing nutrients were calculated using the national food composition database. The presence of fatty liver was quantified by the fatty liver index (FLI), and metabotypes were calculated using K-means clustering. Multivariable linear regression models were used for the analysis of habitual food groups and FLI; for the evaluation of macronutrients, energy substitution models were applied. RESULTS: A higher consumption of nuts and whole grains, and a better diet quality (according to Alternate Healthy Eating Index and Mediterranean Diet Score) were associated with lower FLI values, while the intake of soft drinks, meat, fish and eggs were associated with a higher FLI. The isocaloric substitution of carbohydrates with polyunsaturated fatty acids was associated with a decreased FLI, while substitution with monounsaturated fatty acids and protein showed increased FLI. Statistically significant interactions with the metabotype were observed for most food groups. CONCLUSION: The consumption of plant-based food groups, including nuts and whole grains, and diet quality, were associated with lower FLI values, whereas the intake of soft drinks and products of animal origin (meat, fish, eggs) were associated with a higher FLI. The observed statistically significant interactions with the metabotype for most food groups could help to develop targeted prevention strategies on a population-based level if confirmed in independent prospective studies.

Sex-specific associations between systolic, diastolic and pulse pressure and hemostatic parameters in the population-based KORA-Fit study: a cross-sectional study.

BACKGROUND: Several prior studies postulated an effect of hypertension on coagulation factors. However, population-based studies investigating the sex-specific associations between hypertension and hemostatic parameters are scarce. Therefore, we investigated the relationship between blood pressure and parameters of coagulation, namely activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen, factor VIII, antithrombin III, protein C, protein S, and D-dimer in men and women from the general population. METHODS: Based on 803 participants (376 men, 427 women) from the KORA-Fit Study the sex-specific relationship between systolic, diastolic, and pulse pressure and commonly measured coagulation factors were investigated using multivariable-adjusted linear regression models. RESULTS: Hypertensive males had significantly higher median fibrinogen levels and factor VIII activity in comparison to normotensive males. There was a statistically significant difference between females with and without hypertension regarding the parameter fibrinogen, D-dimers, Protein S activity, and factor VIII activity. In multivariable linear regression analyses no significant association between systolic blood pressure, diastolic blood pressure, as well as pulse pressure and the investigated hemostatic parameters was found in men. In women, a significant positive association could be observed between systolic blood pressure and D-dimer level [ß-estimate per mmHg increase 3.37 (95% CI 0.935-5.804; p = 0.007)] and between pulse pressure and D-dimer level [ß-estimate per mmHg increase 5.351 (95% CI 1.772-8.930; p = 0.003)]. CONCLUSIONS: It appears that sex differences exist in the association between blood pressure parameters and commonly measured coagulation markers in the general population. Further studies are needed to identify the underlying causes.

Anterior-wall and non-anterior-wall STEMIs do not differ in long-term mortality: results from the augsburg myocardial infarction registry.

Background: Different ST-segment elevation myocardial infarction (STEMI) localizations go along with dissimilarities in the size of the affected myocardium, the causing coronary vessel occlusion, and the right ventricular participation. Therefore, this study aims to clarify if there is any difference in long-term survival between anterior- and non-anterior-wall STEMI. Methods: This study included 2,195 incident STEMI cases that occurred between 2009 and 2017, recorded by the population-based Augsburg Myocardial Infarction Registry, Germany. The study population comprised 1.570 men and 625 women aged 25-84 years at acute myocardial infarction. The patients were observed from the day of their first acute event with an average follow-up period of 4.3 years, (standard deviation: 3.0). Survival analyses and multivariable Cox regression analyses were performed to examine the association between infarction localizations and long-term all-cause mortality. Results: Of the 2,195 patients, 1,118 had an anterior (AWS)- and 1,077 a non-anterior-wall-STEMI (NAWS). No significant associations of the STEMI localization with long-term mortality were found. When comparing AWS with NAWS, a hazard ratio of 0.91 [95% confidence interval: 0.75-1.10] could be calculated after multivariable adjustment. In contrast to NAWS, AWS was associated with a greater <28 day mortality, less current or former smoking and higher creatine kinase-myocardial band levels (CK-MB) and went along with a higher frequency of impaired left ventricular ejection fraction (<30%). Conclusions: Despite pathophysiological differences between AWS and NAWS, and identified differences in multiple clinical characteristics, no significant differences in long-term mortality between both groups were observed.

Inflammatory plasma proteins predict short-term mortality in patients with an acute myocardial infarction.

BACKGROUND: The aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: In 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score. RESULTS: The markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735-0.89], GRACE score AUC: 0.7961 [CI: 0.6965-0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269-0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192-0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016-0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score. CONCLUSIONS: Inflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.

Prognostic value of stress hyperglycemia ratio on short- and long-term mortality after acute myocardial infarction.

AIMS: Prior studies demonstrated an association between hospital admission blood glucose and mortality in acute myocardial infarction (AMI). Because stress hyperglycemia ratio (SHR) has been suggested as a more reliable marker of stress hyperglycemia this study investigated to what extent SHR in comparison with admission blood glucose is associated with short- and long-term mortality in diabetic and non-diabetic AMI patients. METHODS: The analysis was based on 2,311 AMI patients aged 25-84 years from the population-based Myocardial Infarction Registry Augsburg (median follow-up time 6.5 years [IQR: 4.9-8.1]). The SHR was calculated as admission glucose (mg/dl)/(28.7 × HbA1c (%)-46.7). Using logistic and COX regression analyses the associations between SHR and admission glucose and mortality were investigated. RESULT: Higher admission glucose and higher SHR were significantly and nonlinearly associated with higher 28-day mortality in AMI patients with and without diabetes. In patients without diabetes, the AUC for SHR was significantly lower than for admission glucose (SHR: 0.6912 [95%CI 0.6317-0.7496], admission glucose: 0.716 [95%CI 0.6572-0.7736], p-value: 0.0351). In patients with diabetes the AUCs were similar for SHR and admission glucose. Increasing admission glucose and SHR were significantly nonlinearly associated with higher 5-year all-cause mortality in AMI patients with diabetes but not in non-diabetic patients. AUC values indicated a comparable prediction of 5-year mortality for both measures in diabetic and non-diabetic patients. CONCLUSIONS: Stress hyperglycemia in AMI patients plays a significant role mainly with regard to short-term prognosis, but barely so for long-term prognosis, underlining the assumption that it is a transient dynamic disorder that occurs to varying degrees during the acute event, thereby affecting prognosis.

Physical activity, muscular strength, and polypharmacy among older multimorbid persons: Results from the KORA-Age study.

The purpose of this study was to examine whether physical activity (PA) and muscular strength (MS) are related to polypharmacy. Our cross-sectional analysis was based on 711 patients with multimorbidity (MMB), aged 65-94 years, who participated in the KORA-Age study. Participants underwent a face-to-face interview and extensive physical examinations including anthropometric measurements, registration of chronic diseases, determination of health-related behaviors (smoking, alcohol intake, physical activity, etc.), collection of blood samples and measurement of hand-grip strength. PPha was defined as the use of >4 drugs and MMB as having ≥2 of 13 chronic diseases. Prevalence of PPha was 44.6% (n=317), and a significant difference was found in the number of drugs used between participants with and without PPha (7.2±2.1 vs 2.5±1.2, P<.001). Patients in the lower compared to the upper tertile of physical activity had a significantly increased odds to be on PPha (OR: 1.64, 95% CI: 1.05-2.56, P=.031) after controlling for age, gender, BMI, family status, education, alcohol intake, smoking habits, number of diseases, hs-CRP, and telomere length. On the contrary, no significant association between muscular strength and PPha was found (OR: 1.04, 95% CI: 0.66-1.63, P=.873) after multivariable adjustment. Among older persons with MMB, lower levels of physical activity, but not low muscular strength, are associated with higher odds of PPha. Increasing the levels of physical activity appears to be highly recommended in order to potentially reduce the risk of PPha among multimorbid persons aged 65 and older.

Low serum omentin levels in the elderly population with Type 2 diabetes and polyneuropathy.

AIMS: To investigate the hypothesis that high serum levels of omentin, an adipokine with anti-inflammatory, insulin-sensitizing and cardioprotective properties, may be related to a lower risk of diabetic sensorimotor polyneuropathy. METHODS: The association between serum omentin level and polyneuropathy was estimated in people aged 61-82 years with Type 2 diabetes (47 with and 168 without polyneuropathy) from the population-based KORA F4 study. The presence of clinical diabetic sensorimotor polyneuropathy was defined as bilateral impairment of foot vibration perception and/or foot pressure sensation. Omentin levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum omentin level was inversely associated with polyneuropathy after adjustment for age, sex, height, waist circumference, hypertension, total cholesterol, smoking, alcohol intake and physical activity [odds ratio 0.45 (95% CI 0.21-0.98); P = 0.043]. Although omentin was positively correlated with adiponectin (r = 0.55, P < 0.0001) and inversely with tumour necrosis factor-α (r = -0.30, P = 0.019), additional adjustment for adiponectin and tumour necrosis factor-α had little impact on the association. CONCLUSIONS: Serum levels of omentin are reduced in people with Type 2 diabetes and diabetic sensorimotor polyneuropathy, independently of established risk factors of polyneuropathy. This association is only partially explained by biomarkers of subclinical inflammation.

Association between muscular strength and inflammatory markers among elderly persons with cardiac disease: results from the KORA-Age study.

Little is known about the association between muscle strength and inflammation in diseased individuals and particularly in cardiac patients. Thus, our purpose was to examine the association of muscular strength with the inflammatory status in older adults with and without cardiac disease. The cross-sectional analysis was based on 1079 adults aged 65-94 years, who participated in the KORA-Age study. Participants underwent an interview and extensive physical examinations including anthropometric measurements, registration of diseases and drug intake, determination of health-related behaviors, collection of blood samples for measurements of interleukin-6 and hs-CRP and muscle strength measurement using hand-grip dynamometry. Cardiac patients (n = 323) had higher levels of IL-6 and poorer muscle strength compared with older adults without cardiac disease. Among persons with cardiac diseases, muscle strength in the lower tertile compared to the upper tertile was significantly associated with increased odds of having elevated IL-6 levels (OR 3.53, 95 % CI 1.18-10.50, p = 0.024) after controlling for age, gender, body fat, alcohol intake, smoking status, diseases, medications and physical activity, whereas the association between muscle strength and hs-CRP remained borderline significant (OR 2.80, 95 % CI 0.85-9.24, p = 0.092). The same trends, with slightly lower odds ratios, were also observed in older adults without cardiac disease. Lower levels of muscular strength are associated with higher concentrations of IL-6 and hs-CRP in elderly individuals with and without cardiac disease suggesting a significant contribution of the muscular system in reducing low-grade inflammation that accompanies cardiac disease and aging.

A clinical screening score for diabetic polyneuropathy: KORA F4 and AusDiab studies.

AIMS: Since screening for distal sensorimotor polyneuropathy (DSPN) in individuals with diabetes is being underused, our aim was to develop a clinical screening score for identifying individuals with DSPN. METHODS: All participants with type 2 diabetes and aged 61-82 years from the German population-based KORA F4 Study (n=177) and the Australian population-based AusDiab Study (n=244) were combined into one study sample. Risk indicators of DSPN were identified and entered into a stepwise model-selection procedure, constructing two consecutive scores with increasing complexity (a base and clinical model). RESULTS: The prevalence of DSPN was 18.2% (95% confidence interval (CI): 14.7-22.3). The base model comprised age (years), height (cm), weight (kg), pain or discomfort in the feet and/or legs (yes/no), and duration of diabetes (years), yielding an area under the receiver operating characteristics curve (AUC) of 0.80 (95% CI: 0.76-0.85). The clinical model additionally included diastolic blood pressure (mmHg) and serum creatinine levels (mmol/l). The AUC increased only marginally to 0.82 (0.77-0.87) (p for AUC comparison=0.188). The internal validation of the scores produced similar AUCs. CONCLUSIONS: The screening scores developed in this study are a simple tool to differentiate between a high and low likelihood of having DSPN among individuals with type 2 diabetes.

The use of dietary supplements among older persons in southern Germany - results from the KORA-age study.

OBJECTIVES: Current population-based surveys in Europe on the prevalence of dietary supplement (DS) use in older individuals are scarce. The aim of the present study was to investigate patterns, prevalence and determinants of non-herbal DS use in aged subjects. Furthermore, the intake amounts of vitamins and minerals from supplements were assessed. DESIGN: Cross-sectional. SETTING: Data on supplement use were available from an age- and sex-stratified random sample of the German population-based KORA (Cooperative Health Research in the Region of Augsburg)-Age study. PARTICIPANTS: 1,079 persons who were born in or before the year 1943. MEASUREMENTS: Use of dietary supplements and medications during the last seven days was recorded in a face-to-face interview in 2009. Participants were asked to bring all packages of ingested preparations to the study center. Not only vitamin/mineral supplements, but also non-vitamin non-mineral non-herbal supplements and drugs containing vitamins and minerals were coded as DS. RESULTS: The age-standardized prevalence of DS intake was 54.3% in women and 33.8% in men, respectively. The most commonly supplemented mineral and vitamin, respectively, was magnesium (31.9%) and vitamin D (21.5%) in women and magnesium (18.0%) and vitamin E (12.0%) in men. The highest intakes, compared to the German Dietary Reference Intakes, were reported for biotin, vitamin B6 and B1. Excessive intakes (equal or above the European Tolerable Upper Intake Levels (UL)) were observed especially for magnesium and vitamin E. 20.2% of the women and 32.5% of the men who took magnesium supplements regularly exceeded the UL for magnesium. In case of vitamin E this was true for 8.0% of the women and 13.6% of the men. Determinants of DS use were sex, education, smoking, physical activity, neurological diseases, and stroke. CONCLUSION: A high proportion of the general population aged 65 years and older in Southern Germany uses DS, especially supplements containing vitamins/minerals. The supplementation of vitamin D can be regarded as favorable in this age group, whereas the excessive intakes of vitamin E might be a cause of concern.

Increased cerebrospinal fluid levels of nerve cell biomarkers in narcolepsy with cataplexy.

BACKGROUND: The association between narcolepsy with cataplexy and the hypocretinergic system in the central nervous system is strong since up to 75-90% of all patients have cerebrospinal fluid (CSF) hypocretin-1 deficiency. The predominant occurrence of HLADQB1*0602 tissue type in narcolepsy patients and recent results from genome-wide association studies suggest an underlying immunological mechanism. The present study was initiated to clarify whether measurement of nerve cell biomarkers in CSF could give additional knowledge of the pathophysiological mechanisms causing narcolepsy with cataplexy. METHODS: Two patient groups with narcolepsy, comprising 18 patients with low CSF hypocretin-1 concentrations and typical cataplexy, and 18 patients with normal CSF hypocretin-1 levels and mild cataplexy-like symptoms, were compared to 17 controls. We measured the nerve cell biomarkers beta-amyloid (Aß42), total tau protein (T-tau), phosphorylated tau (P-tau) and neuron-specific enolase (NSE) in CSF. RESULTS: The concentrations of all biomarkers were significantly elevated in both patient groups compared to the controls. The concentration of beta-amyloid was significantly higher in the patient group with normal CSF hypocretin-1 concentration than in those with low concentrations, whereas the other biomarkers showed no difference between the patient groups. CONCLUSION: The findings of elevated levels of CSF biomarkers independent of CSF hypocretin-1 reduction may reflect alterations in cell metabolism. The results suggest a more extensive affection of the sleep regulating cellular network, affecting other neuronal sites important in the regulation of sleep, in addition to the hypocretin-producing neurons.

[TSH-reference range of adults: results from the population-based study KORA F4]. / TSH-Referenzbereich bei süddeutschen Erwachsenen: Ergebnisse aus der bevölkerungsbasierten KORA F4-Studie.

INTRODUCTION: There is no valid nationwide reference value for Thyroid-stimulating hormone (TSH) for German adults because of different iodine supply and different laboratory equipment, however, reference values for single regions of Germany have been defined. The aim of this study was to find a reference value for South Germany and to compare this with results of other population-based studies. METHODS: 3080 individuals from the KORA-F4 study (Cooperative Health Research in the Region of Augsburg) at the age range of 32 to 81 years were examined regarding their thyroid characteristics (anamnesis, sonography and clinical chemistry). After excluding individuals with known as well as unknown thyroid disorders revealed by the KORA study, there were 710 thyroid-healthy individuals left to evaluate TSH-, fT3- and fT4-reference ranges. RESULTS: For thyroid-healthy men and women we evaluated a TSH-reference range of 0.52-3.60 mIU/l on Siemens Vista Analysers with a median of 1.49 mIU/l. We could not find any statistically significant influence of age or sex. Median iodine excretion in urine was 118.6 µg/g creatinine in our healthy population which is above the recommended target value of 100 µg/g. DISCUSSION: The TSH-reference value of the South German population is higher than the one assessed in the Northeast-German SHIP-study 10 years ago. For the definition of a TSH-reference value, population-based and apparatus-specific examinations are necessary.

Plasma MR-proANP levels are associated with carotid intima-media thickness in the general community: the KORA F4 study.

OBJECTIVE: Subjects with metabolic syndrome (MetS) and individuals with type 2 diabetes are at high risk for vascular complications. Hormones acting on vascular endothelium may be involved in the atherogenic process associated with metabolic disorders. The objective of this study was to determine the correlation of pro-atrial natriuretic hormone (proANP) with the presence of subclinical atherosclerosis. METHODS: In 1272 subjects participating in the KORA F4 study, we determined plasma levels of mid-regional proANP (MR-proANP) and the intima-media thickness (IMT) of the carotid artery. We used logistic regression models to investigate the relation of MR-proANP with components of MetS and IMT. RESULTS: In multiple adjusted regression models, MR-proANP levels were inversely associated with MetS (OR = 0.66, 95% CI 0.47-0.93), central obesity (OR = 0.67, 95% CI 0.46-0.96), raised triglyceride levels (OR = 0.53, 95% CI 0.37-0.77), prediabetes (OR = 0.62, 95%, CI 0.44-0.87) and type 2 diabetes (OR = 0.55, 95% CI 0.35-0.88) when comparing the top quartile vs. the lower three quartiles. Furthermore, there was an inverse relationship between MR-proANP and IMT. After adjustment for traditional cardiovascular risk markers, individuals with high MR-proANP plasma levels in the top quartile (Q4) had significantly lower IMT values (Q4 vs. Q1-Q3: ß -0.0178, 95% CI -0.0344; -0.0013). CONCLUSIONS: In this population-based study, high plasma concentrations of MR-proANP were significantly associated with a lower incidence of MetS components and lower measures of early atherosclerosis. The data suggest a link between MR-proANP levels and the development of vascular complications.

Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A.

BACKGROUND: From October 2009 to January 2010, approximately 470,000 children and adolescents in Norway ages 4-19 years were vaccinated with Pandemrix® against influenza A (H1N1 subtype). The vaccination coverage in this age cohort was approximately 50%. OBJECTIVES: Our study was performed to evaluate the possible association between Pandemrix® vaccination and narcolepsy in Norway. METHODS: Children and adolescents with sudden onset of excessive daytime sleepiness (EDS) and cataplexy occurring after the 2009-2010 vaccination period were registered by the National Institute of Public Health in cooperation with the Norwegian Resource Center for AD/HD, Tourette Syndrome, and Narcolepsy. RESULTS: Fifty-eight vaccinated children and adolescents (35 girls, 23 boys) ages 4-19 years (mean age, 10.5 years) were diagnosed as new cases of confirmed narcolepsy and were included in our study during 2010 and 2011. Forty-two children had onset of symptoms within 6 months after vaccination, with 12 of them having symptoms within the first 6 weeks. All had EDS, 46 had documented cataplexy, 47 had mean sleep latency less than 8 min, and 43 had two or more sleep-onset rapid eye movement sleep (SOREM) periods in multiple sleep latency tests (MSLT). Cerebrospinal fluid (CSF) hypocretin levels were measured in 41 patients, with low levels in all. Thirty seven patients that were analyzed had tissue type HLADQB1*0602. During the same period, 10 unvaccinated cases were reported (mean age, 12.5 years). CONCLUSION: The data collected during 3 years following vaccination showed a significantly increased risk for narcolepsy with cataplexy (P<.0001) and reduced CSF hypocretin levels in vaccinated children ages 4-19 years the first year after Pandemrix® vaccination, with a minimum incidence of 10 of 100,000 individuals per year. The second year after vaccination, the incidence was 1.1 of 100,000 individuals per year, which was not significantly different from the incidence of 0.5-1 of 100,000 per year in unvaccinated children during the same period.

Serum potassium is associated with prediabetes and newly diagnosed diabetes in hypertensive adults from the general population: the KORA F4-study.

AIMS/HYPOTHESIS: Evidence suggests that low serum potassium concentrations or hypokalaemia induced by the intake of diuretics are associated with incident diabetes and increased risk for diabetes in persons with hypertension. We examined a possible association between serum potassium and prediabetes (defined as isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT] or combined IFG/IGT), as well as known and newly diagnosed diabetes (NDD), in 32- to 81-year-old men and women with and without hypertension. METHODS: This cross-sectional analysis was based on 2,948 participants in the Cooperative Health Research in the Region of Augsburg (KORA) F4 study conducted in 2006-2008 in southern Germany. Serum concentrations of potassium were measured by indirect potentiometry. RESULTS: In the total sample there was no association between serum potassium concentrations and prediabetes. In hypertensive persons however serum potassium levels in the first and second quartile compared with the highest quartile were independently significantly associated with prediabetes after multivariable adjustment (OR for prediabetes, 2.02 [95% CI 1.27, 3.21] for quartile 2 and 2.00 [95% CI 1.27, 3.15] for quartile 1), while in persons without hypertension no association was found. In multinomial logistic regression analysis these findings could be confirmed. In hypertensive participants after multivariable adjustment the associations were statistically significant for i-IGT and NDD (i-IGT OR 1.23; NDD OR 1.41). However, in non-hypertensive persons, all associations between serum potassium levels and each of the categories of impaired glucose regulation were non-significant. CONCLUSIONS/INTERPRETATION: Serum potassium levels were independently associated with prediabetes and NDD in hypertensive adults from the general population.

Evaluation of the Neuropad sudomotor function test as a screening tool for polyneuropathy in the elderly population with diabetes and pre-diabetes: the KORA F4 survey.

BACKGROUND: Neuropad is a novel indicator test for sudomotor dysfunction, which has not been validated as a screening tool in a population-based study. This study aimed to evaluate the utility of Neuropad as a screening tool for distal symmetric polyneuropathy among elderly subjects with diabetes and pre-diabetes in the general population. METHODS: Eligible subjects aged 61-82 years (n = 940) from the KORA F4 survey were examined, 201 of whom had diabetes and 231 had pre-diabetes (WHO 1999 criteria). Polyneuropathy was defined by the Michigan Neuropathy Screening Instrument (MNSI) score >3. RESULTS: Polyneuropathy was diagnosed in 60 (29.9%) subjects with diabetes and in 45 (19.5%) subjects with pre-diabetes, respectively (p = 0.013). The sensitivity and negative predictive value of Neuropad (reading time: 10 min) for the diagnosis of polyneuropathy were moderately high, reaching 76.7% and 78.1% in subjects with diabetes and 57.8% and 76.5% in those with pre-diabetes, respectively. Conversely, the specificity and positive predictive value for the diagnosis of polyneuropathy were rather low: 35.5% and 33.6% in diabetic individuals and 33.3% and 17.3% in subjects with pre-diabetes, respectively. Use of the >2 cut-off and MNSI combined with monofilament examination did not improve the diagnostic performance of Neuropad. CONCLUSIONS: In the elderly general population with diabetes and pre-diabetes, Neuropad has reasonable sensitivity but rather low specificity for the diagnosis of polyneuropathy. It is a useful simple and inexpensive tool to screen for and to exclude polyneuropathy as desired, while its low specificity implies that a longer reading time merits consideration.

Geographic variations in the frequency of thyroid disorders and thyroid peroxidase antibodies in persons without former thyroid disease within Germany.

OBJECTIVE: To investigate regional variations in the frequency of undiagnosed thyroid disorders among 25- to 88-year-old men and women in two communities in the northeast and the south of Germany. In addition, autoantibodies to thyroperoxidase (TPO-Abs) and urinary iodine excretion were determined. METHODS: Two population-based surveys of men and women using a common standardized protocol, the Study of Health in Pomerania (SHIP) in the northeast of Germany (2505 participants) and the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) in the south of Germany (2316 participants), were compared with regard to the frequency of undiagnosed thyroid disorders. RESULTS: Compared with the northeast of Germany, urinary iodine excretion and serum thyroid-stimulating hormone (TSH) levels were significantly higher in the south. The median urinary iodine concentration was 110 µg/l (64; 169 µg/l) in SHIP and 151 µg/l (97; 214 µg/l) in KORA, and the median TSH value was 0.81 mIU/l (0.56; 1.15 mIU/l) in SHIP and 1.22 mIU/l (0.84; 1.80 mIU/l) in KORA. The frequency of elevated TSH (TSH ≥ 2.12 mIU/l) was 4.3% in SHIP and 14.1% in KORA (P<0.001); the corresponding values for suppressed TSH (<0.25 mIU/l) were 3.5 and 1.7% (P<0.001). The proportion of ultrasonographic findings was 55.5% in SHIP and 68.0% in KORA. The frequency of serum TPO-Abs did not differ significantly between northeast and south Germany. CONCLUSIONS: There were considerable regional disparities in the frequency of thyroid disorders within Germany. These differences can be explained not only by different regional histories of natural iodine deficiency but also by current differences in the iodine supply under an identical nationwide iodine fortification program.

Impact of weight and weight change on normalization of prediabetes and on persistence of normal glucose tolerance in an older population: the KORA S4/F4 study.

BACKGROUND AND AIMS: In a population-based cohort study with older subjects and without specific interventions, we investigated the impact of body mass index (BMI) and BMI change (as well as waist circumference and change of waist circumference) on reversion from prediabetes to normal glucose tolerance (NGT) and on long-term persistence of NGT. MATERIALS AND METHODS: Oral glucose tolerance tests were conducted at baseline and at follow-up in a cohort study in Southern Germany (KORA S4/F4; 1223 subjects without diabetes aged 55-74 years at baseline in 1999-2001; 887 subjects (73%), of whom 436 had prediabetes at baseline, participated in the follow-up 7 years later). RESULTS: BMI reduction, but not initial BMI, predicted reversion from prediabetes to NGT. The odds ratio (OR) for returning to NGT was 1.43 (95% CI: 1.18-1.73) for a BMI decrease of 1 kg m(-2), after adjustment for age, sex, baseline glucose values and lifestyle factors. Initial BMI had no effect on reversion to NGT (OR=0.98, 95% CI: 0.91-1.06, per kg m(-2)). Persistence of NGT was associated with baseline BMI (OR=0.94, 95% CI: 0.88-0.998) and BMI reduction (OR=1.16, 95% CI: 1.02-1.33, per decrease by 1 kg m(-2)). For waist circumference and change of waist circumference similar results were obtained. CONCLUSION: In older adults, weight loss strongly increased the chances of returning from prediabetes to NGT irrespective of initial BMI. Long-term persistence of NGT depended both on initial BMI and on BMI change.

Age at menarche is associated with prediabetes and diabetes in women (aged 32-81 years) from the general population: the KORA F4 Study.

AIMS/HYPOTHESIS: The aim of this study was to examine the association between age at menarche and prediabetes as well as diabetes, considering confounding factors and the possible mediating role of adult obesity. METHODS: This cross-sectional study analysed data on 1,503 women aged 32-81 years from the German population-based KORA (Cooperative Health Research in the Region of Augsburg, South Germany) F4 Study (2006-2008). Data were collected by standardised interviews, physical examinations, and whole blood and serum measurements, including administration of an OGTT in non-diabetic participants. RESULTS: Of the 1,503 women, 226 showed a prediabetic state (impaired fasting glucose and/or impaired glucose tolerance) and 140 persons had diabetes (45 participants with previously undiagnosed diabetes and 95 with known diabetes). In Poisson regression analysis, age at menarche was significantly inversely associated with prediabetes or diabetes after adjustment for year of birth (RR 0.88; 95% CI 0.82, 0.94, p < 0.0001 per additional year of menarche) and after additional adjustment for a number of confounding factors (RR 0.88; 95% CI 0.83, 0.94, p = 0.0001). Further adjustment for current BMI slightly attenuated the association with prediabetes or diabetes (RR 0.89; 95% CI 0.83, 0.95, p = 0.0009), but the association remained clearly significant. CONCLUSIONS/INTERPRETATION: Age at menarche seems to be inversely associated with prediabetes and diabetes independent of confounding factors including current BMI. Women at risk for diabetes might be identified by a history of young age at menarche.