Publications by authors named "Wolfgang Kerner"

27 Publications

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[Type 1 diabetes: an update].

Internist (Berl) 2021 Jun 7;62(6):627-637. Epub 2021 Apr 7.

Klinik für Diabetes und Stoffwechselerkrankungen, Klinikum Karlsburg, Karlsburg, Deutschland.

The incidence of type 1 diabetes (T1D) has been rising steadily over the last 30 years, especially among children and adolescents, with the result that the number of cases in this age group doubles every 20 years. The development of T1D goes through three stages, which can vary in duration from individual to individual. Late diagnosis or incorrect interpretation of the symptoms leads to the life-threatening diabetic ketoacidosis, from which every third child in Germany suffers at the manifestation of T1D. Diabetes that manifests in adulthood is regularly misclassified and treated, at least initially, as type 2 diabetes. There are no fundamental differences in the insulin therapy of T1D in children, adolescents and adults. The use of insulin pump therapy and continuous glucose monitoring is steadily increasing with the aim of reducing the number and duration of hypo- and hyperglycemic episodes, increasing the time in range between 70-180 mg/dl (3,9-10 mmol/l) and reaching the treatment goal of an HbA1c below 7% (53 mmol/mol). In addition to the prevention of diabetes-related long-term microvascular complications, the timely detection and treatment of cardiovascular risk factors is of extraordinary importance also for young people with T1D.
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http://dx.doi.org/10.1007/s00108-021-01009-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024935PMC
June 2021

Demographic characteristics and acute complications among adults with type 1 diabetes: Comparison of two multicentre databases from Germany and the United States.

J Diabetes Complications 2021 03 26;35(3):107812. Epub 2020 Nov 26.

Real World Evidence and Clinical Outcome Generation, Sanofi, Paris, France.

Background: Studies on acute complications in adult T1D were previously reported from the United States (U.S.) and from Germany. The aim was to compare demographic characteristics and patterns of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) between Germany and the U.S.

Methods: Descriptive comparison on individuals aged ≥18 years, with T1D duration ≥2 years were made between the German diabetes-patient registry (DPV) and the U.S. electronic-health-record database (T1PCO). Individuals in both databases were divided into patients with haemoglobin A1c (HbA1c) <7% and HbA1c ≥7%.

Results: 5190 (DPV) and 31,430 individuals (T1PCO) fulfilled the inclusion criteria. DPV patients were younger, more often male and had lower body-mass index. In both databases, more males than females had HbA1c <7%. Individuals had higher HbA1c in T1PCO compared to DPV. The relationship between HbA1c and DKA was similar in both databases. SH revealed a U-shaped curve in T1PCO, but no clear pattern was present in DPV. SH events increased with higher age in DPV, but not in T1PCO.

Conclusion: Patterns of SH differ between Germany and U.S. Differences in capture of SH among the databases cannot be excluded, but differences in health care including patient education and level of care by specialists are likely.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107812DOI Listing
March 2021

Effect of Cold Atmospheric Plasma Therapy vs Standard Therapy Placebo on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial.

JAMA Netw Open 2020 07 1;3(7):e2010411. Epub 2020 Jul 1.

Diabeteszentrum, Herz- und Diabeteszentrum Nordrhein Westfalen (NRW), Ruhr Universität Bochum, Bad Oeynhausen, Germany.

Importance: Diabetic foot ulcers are a common complication of diabetes and require specialized treatment. Cold atmospheric plasma (CAP) has been associated with benefits in wound infection and healing in previous smaller series of case reports. Yet the effect of CAP compared with standard care therapy in wound healing in diabetic foot ulcers remains to be studied.

Objective: To determine whether the application of CAP accelerates wound healing in diabetic foot ulcers compared with standard care therapy.

Design, Setting, And Participants: A prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted at 2 clinics with recruitment from August 17, 2016, to April 20, 2019. Patients were scheduled to remain in follow-up until April 30, 2024. Patients with diabetes and diabetic foot ulcers described using the combined Wagner-Armstrong classification of 1B or 2B (superficial or infected diabetic foot ulcers extending to tendon) were eligible. A patient could participate with 1 or more wounds in both groups in both intervention and control groups. Wounds were randomized separately, allowing a participant to be treated several times within the study following a 2 × 2 × 2 randomization strata considering sex, smoking status, and age (≤68 years and >68 years).

Interventions: Standard care treatment with 8 applications of either CAP generated from argon gas in an atmospheric pressure plasma jet or 8 applications of placebo treatment in a patient-blinded manner.

Main Outcomes And Measures: Primary end points were reduction in wound size, clinical infection, and microbial load compared with treatment start. Secondary end points were time to relevant wound reduction (>10%), reduction of infection, parameters of patient's well-being, and treatment-associated adverse events.

Results: Of 65 diabetic foot ulcer wounds from 45 patients assessed for study, 33 wounds from 29 patients were randomized to CAP and 32 wounds from 28 to placebo, with 62 wounds from 43 patients (31 wounds per group) included for final evaluation (mean [SD] age, 68.5 [9.1] years for full sample). Four patients with 5 wounds of 31 (16.1%) wounds in the CAP group and 3 patients with 4 wounds of 31 (13%) wounds in the placebo group were active smokers. CAP therapy yielded a significant increase in wound healing, both in total mean (SD) area reduction (CAP vs placebo relative units, -26.31 [11.72]; P = .03) and mean (SD) time to relevant wound area reduction (CAP vs placebo relative units, 10% from baseline, 1.60 [0.58]; P = .009). Reduction of infection and microbial load was not significantly different between CAP and placebo. No therapy-related adverse events occurred during therapy; patient's perceptions during therapy were comparable.

Conclusions And Relevance: In this randomized clinical trial, CAP therapy resulted in beneficial effects in chronic wound treatment in terms of wound surface reduction and time to wound closure independent from background infection.

Trial Registration: ClinicalTrials.gov Identifier: NCT04205942.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.10411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366186PMC
July 2020

Higher HbA1c Measurement Quality Standards are Needed for Follow-Up and Diagnosis: Experience and Analyses from Germany.

Horm Metab Res 2018 Oct 14;50(10):728-734. Epub 2018 Sep 14.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Measurement of HbA1c is an essential laboratory measure for the follow-up and therapy decision-making in patients with diabetes. HbA1c is one of the measurands in laboratory medicine that have to be successfully checked according to the criteria of the guidelines of the German Medical Association (Rili-BAEK) in external quality assurance using the reference method value concept, when applied in patient care. The allowed deviation of ±18% in external quality assessment (EQA) and ± 10% in internal quality control has been ultimately met by virtually all the different manufacturers and methods. However, such broad limits for permissible deviations are not suitable in view of medical requirements in patient care. The low-level acceptance criteria also depends on the previously used EQA materials used in Germany. In fact, HbA1c measurement results that are imprecisely measured or come from incorrectly calibrated devices are difficult to identify. With implementation of unprocessed fresh EDTA blood, the situation has changed. Until now systems with unit use reagents for point-of-care testing (POCT) of HbA1c are not mandatory to participate in EQA schemes in Germany. This paper outlines why there was a need to narrow the acceptance limits listed within the Rili-BAEK for HbA1c's internal (to ± 3%) and external (to ± 8%) quality controls in EQA schemes for Germany, which will take place after a transition period in the next years. Higher quality in HbA1c measurements will help to avoid misdiagnosis of diabetes as well as potential over- or undertreatment of patients at risk for diabetes.
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http://dx.doi.org/10.1055/a-0721-2273DOI Listing
October 2018

Definition, Classification and Diagnosis of Diabetes Mellitus.

Exp Clin Endocrinol Diabetes 2018 Jul 5;126(7):406-410. Epub 2018 Jul 5.

Kommission für Labordiagnostik der Diabetologie der Deutschen Diabetes Gesellschaft (DDG) und der Deutschen Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL) (Commission for Laboratory Diagnostics in Diabetology of the German Diabetes Association (DDG) and the German Association for Clinical Chemistry and Laboratory Medicine).

Aim of recommendations like this one issued by the German Diabetes Association is to provide the GP and diabetologist and his team with information he needs for his daily practice. These recommendations are updated annually. They are written by a group of experts, but they are not evidence based guidelines. This specific recommendation for diabetes diagnosis briefly describes the diabetes types and the different options for diagnosis. Also the caveats and the practical procedure are presented.
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http://dx.doi.org/10.1055/a-0584-6223DOI Listing
July 2018

Prevalence of elevated liver enzymes in adults with type 1 diabetes: A multicentre analysis of the German/Austrian DPV database.

Diabetes Obes Metab 2017 08 10;19(8):1171-1178. Epub 2017 Apr 10.

Institute for Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.

Aims: To assess the prevalence of elevated liver enzymes in adults with type 1 diabetes mellitus (T1DM) in routine clinical care and the association with cardiovascular risk profile in the Diabetes-Prospective-Documentation (DPV) network in Germany and Austria.

Subjects And Methods: This cross sectional observational study from the DPV registry includes data from 45 519 adults with T1DM at 478 centres up to September 2016. Liver enzyme measurements were available in 9226 (29%) patients at 270 centres and were analysed for increased alanine aminotransferase (ALT; men >50 U/L, women >35U/L) and/or aspartate aminotransferase (AST; men >50 U/L, women >35U/L) and/or gamma-glutamyltransferase (GGT; men >60U/L, women >40 U/L). A subgroup analysis in patients for whom 2 or more ALT measurements were available (n = 2335, 25%) and whose ALT was increased at least twice (men >30 U/L, women >19U/L) was performed. Associations with glycaemic control, cardiovascular risk factors and late complications were investigated with multiple regression analyses.

Results: Twenty percent (19.8%, n = 1824) had increased liver enzyme(s) on one or more occasions. Increased liver enzymes were associated with worse glycaemic control and higher BMI (both P < .0001), dyslipidemia (OR, 1.75; 95% CI, 1.54-2.0), hypertension (OR, 1.48; 95% CI: 1.31-1.68), myocardial infarction (OR, 1.49; 95% CI, 1.17-1.91) and end stage renal disease (OR, 1.59; 95% CI, 1.17-2.17). ALT was increased twice in 29% and was associated with worse glycaemic control (P < .0001), higher BMI (P < .0001), hypertension (OR, 1.58; 95% CI, 1.26-1.97) and dyslipidemia (OR, 1.89; 95% CI, 1.51-2.37).

Conclusions: In this clinical audit in adults with T1DM, elevated liver enzymes on routine assessment were associated with a less favourable cardiovascular risk profile and with poorer glycaemic control.
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http://dx.doi.org/10.1111/dom.12929DOI Listing
August 2017

Distinct cytokine and chemokine patterns in chronic diabetic ulcers and acute wounds.

Exp Dermatol 2017 02 21;26(2):145-147. Epub 2016 Dec 21.

Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK plasmatis, Greifswald, Germany.

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http://dx.doi.org/10.1111/exd.13215DOI Listing
February 2017

20 Years of Pediatric Benchmarking in Germany and Austria: Age-Dependent Analysis of Longitudinal Follow-Up in 63,967 Children and Adolescents with Type 1 Diabetes.

PLoS One 2016 17;11(8):e0160971. Epub 2016 Aug 17.

Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany.

Background: To investigate changes in diabetes treatment over the last two decades in three age-groups of children and adolescents with type 1 diabetes (T1D) from Germany and Austria.

Methods: 63,967 subjects (<18yr) with T1D documented between 1995 and 2014 from the DPV-database were included and stratified according to age (0.5-<6, 6-<12, 12-<18yr). Regression models were applied for insulin regimens (<3 and ≥4 injection time points/day, or continuous subcutaneous insulin infusion (CSII)), use of rapid- and long acting insulin analogues, NPH insulin, and frequency of self-monitoring of blood glucose (SMBG)/day. Models were adjusted for sex, diabetes duration, and migration background. P-value for trend was given.

Findings: The number of subjects with <3 injection time points/day decreased from 1995 to 2014 to <5% in all age-groups (p<0.0001). Proportion of patients with ≥4 injections/day increased until the early 2000s, and then declined until 2014. This trend was not found in 6-<12yr olds (p = 0.3403). CSII increased in all age-groups (p<0.0001) with the highest increase in children <6 years (from 0.4% to 79.2%), and the lowest increase in 12-<18 year olds (from 1.0% to 38.9%). NPH insulin decreased in all age-groups (p<0.0001). Insulin analogues, especially rapid-acting, became more frequent in all age-groups (p<0.0001), accounting for 78.4% in 2014 for all subjects. The highest use was found in the youngest children (in 2014: 85.6%), the lowest use in 6-<12 year olds (in 2014: 72.9%). The number of SMBG/day increased from 2.2 to 6.4 with a similar rise in all age-groups (p<0.0001). Frequency was highest in subjects <6yr.

Conclusions: In all age-groups, T1D treatment was intensified over the last 20 years. Age-specific differences in trends were particularly observed in the number of patients on CSII, in the number of patients with 4 or more injections/day, and in the frequency of SMBG/day.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160971PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988648PMC
July 2017

Trend of antihyperglycaemic therapy and glycaemic control in 184,864 adults with type 1 or 2 diabetes between 2002 and 2014: Analysis of real-life data from the DPV registry from Germany and Austria.

Diabetes Res Clin Pract 2016 May 12;115:31-8. Epub 2016 Mar 12.

University of Ulm, Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm, Germany; German Center for Diabetes Research (DZD) , München-Neuherberg, Germany.

Aims: To analyse time trends of antihyperglycaemic therapy and glycaemic control in adult subjects with type 1, or type 2 diabetes between 2002 and 2014 in Germany/Austria.

Methods: 184,864 adults with diabetes (35,144 type 1 diabetes (T1D), 149,720 type 2 diabetes (T2D)) from the DPV-database documented between 2002 and 2014 were included. Regression models were applied for antihyperglycaemic therapy in T2D (non-pharmacological, OADs only, insulin±OADs), insulin therapy in T1D (CT, ICT, CSII) and T2D (BOT, SIT, CT, ICT, CSII), for the use of insulin analogues, and for glycaemic control (HbA1C, severe hypoglycaemia), adjusting for confounders sex, age, and diabetes duration.

Results: In T1D, CT (2002:19.7%; 2014:16.0%) and ICT (2002:66.8%; 2014:52.4%) decreased, while CSII increased from 13.5% to 31.5%. In T2D, non-pharmacological treatment became less frequent (2002:36.0%, 2014:21.8%), the use of OADs (2002:19.3%, 2014:28.9%) and insulin±OADs (2002:44.6%, 2014:49.4%) increased. BOT increased from 7.9% to 18.9%, SIT decreased from 12.0% to 8.3%. ICT slightly increased (2002:44.0%, 2014:45.3%), CT decreased (2002:35.8%, 2014:27.2%). Insulin analogues were used more frequently in T1D (rapid-acting:2002:46.8%, 2014:84.8%; long-acting:2002:26.0%, 2014:54.8%) and in T2D (rapid-acting:2002:26.0%, 2014:43.5%; long-acting:2002:13.7%, 2014:53.6%). Until 2011, HbA1C increased in T1D and T2D, but then decreased again. High variability in the rate of hypoglycaemia was observed.

Conclusions: This observational study indicates an increased use of insulin pumps in T1D. In T2D, non-pharmacological therapy decreased, and insulin therapy, particular as BOT, rose. An increase in the use of rapid- and long-acting insulin analogues was present in both patient-groups. Time trend was less clear in glycaemic control.
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http://dx.doi.org/10.1016/j.diabres.2016.03.008DOI Listing
May 2016

Do patients with type 1 and type 2 diabetes really have an impaired endothelial function? A population-based propensity score matching analysis.

Cardiovasc Diabetol 2013 Dec 5;12:174. Epub 2013 Dec 5.

Department of Internal Medicine, Medizinische Klinik B, Universitätsmedizin, Greifswald, Sauerbruchstrasse, D-17475, Germany.

Background: Previous studies suggested an impaired endothelial function in patients with diabetes. However, the validity of this finding may be limited by the lack of adequate adjustment for further cardiovascular confounders. We assessed endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in patients with either type 1 or type 2 diabetes in comparison with non-diabetic controls.

Methods: The study population comprised 1487 subjects including 122 subjects with type 2 diabetes, aged 25 to 85, from the population-based Study of Health in Pomerania, and 65 outpatients, aged 23 to 75, with type 1 diabetes. FMD measurements were performed using standardized ultrasound techniques. Subjects with type 1 and type 2 diabetes were matched 1:4 to healthy controls using propensity score matching.

Results: Neither type 1 diabetes (β = 0.142; SE = 0.568, p = 0.803) nor type 2 diabetes (β = 0.107; SE = 0.340, p = 0.752) were significantly associated with FMD in comparison with their non-diabetic controls after adjustment for major cardiovascular confounders like age, gender, body mass index, smoking status, hypertension, antihypertensive medication, LDL and HDL cholesterol levels.

Conclusions: In this population-based study comparing adjusted FMD values of diabetic individuals with adequately matched controls, propensity score analyses revealed no association between diabetes and endothelial function. Since these findings are in discordance with the majority of previous reports, we suggest performing similar analyses using data from other population-based studies.
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http://dx.doi.org/10.1186/1475-2840-12-174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234402PMC
December 2013

The influence of type 1 and type 2 diabetes on periodontal disease progression: prospective results from the Study of Health in Pomerania (SHIP).

Diabetes Care 2012 Oct 1;35(10):2036-42. Epub 2012 Aug 1.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.

Objective: To explore associations between diabetes etiology (type 1 diabetes mellitus [T1DM] vs. T2DM) and glycemic control in the prediction of 5-year periodontal status change.

Research Design And Methods: The Study of Health in Pomerania (SHIP) is a population-based stratified sample of German men and women. Healthy participants and those determined to have T2DM arose from the SHIP cohort, and T1DM participants were recruited from diabetes clinics in the catchment area that gave rise to SHIP. Dentate participants (n = 2,626; 53% women; 20-81 years of age) were included. Diabetes was determined via physician diagnosis and/or HbA(1c) ≥6.5% (uncontrolled diabetes >7.0%). Examiners blinded to diabetes status performed random half-mouth periodontal examinations, assessing probing depth (PD) and attachment loss (AL) (four sites/tooth) at baseline and follow-up. Participants were categorized into six groups as follows: 1) diabetes free (n = 2,280), 2) incident T2DM (n = 79), 3) controlled T2DM (n = 80), 4) uncontrolled T2DM (n = 72), 5) controlled T1DM (n = 43), and 6) uncontrolled T1DM (n = 72). In multivariable regressions, mean PD change (ΔMPD), mean AL change (ΔMAL), or incident tooth-loss values were regressed across the aforementioned diabetes categories.

Results: Mean (SD) ΔMPD and ΔMAL values among all participants were -0.08 ± 0.5 mm and 0.08 ± 1.03 mm, respectively, and 34% lost one or more teeth. Relative to diabetes-free participants, those with uncontrolled T2DM experienced greater ΔMPD ± SE (P < 0.05), whereas participants with either uncontrolled T1DM or uncontrolled T2DM realized greater ΔMAL (P < 0.05). Uncontrolled T1DM and T2DM were both associated with an increased risk of future tooth loss (P < 0.05).

Conclusions: Diabetes control, but not etiology, was associated with future tooth loss and accelerated AL progression.
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http://dx.doi.org/10.2337/dc11-2453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447825PMC
October 2012

Low fecal elastase 1 levels do not indicate exocrine pancreatic insufficiency in type-1 diabetes mellitus.

Pancreas 2008 Apr;36(3):274-8

Clinic for Diabetes and Metabolic Diseases, Klinikum Karlsburg, Karlsburg, Germany.

Objectives: On the basis of very low fecal elastase 1 and very high fecal fat estimations, it has been claimed that exocrine pancreatic insufficiency is frequent in diabetic patients, and that in up to 40% of the patients, pancreatic enzyme substitution would be indicated. Because this would affect millions of diabetic patients worldwide, we evaluated this suggestion by testing exocrine pancreatic function in type-1 diabetes using the criterion standard of exocrine pancreatic function tests, the secretin-cerulein test (SCT). The results of this test were then compared with those of fecal elastase 1 and fecal fat estimations.

Methods: Thirty-three patients with type-1 diabetes mellitus underwent an SCT, a fecal fat estimation, and 2 fecal elastase 1 tests (using both monoclonal and polyclonal antibodies) to evaluate their exocrine pancreatic function.

Results: The SCT results were abnormal in 11 of the 33 patients, who showed only mild to moderate exocrine pancreatic insufficiency, and the stimulated lipase secretion was never less than 10% of the level where pancreatic steatorrhea first occurs. The correlation between fecal elastase 1 and SCT showed much lower sensitivity, specificity, and positive and negative predictive values than did the correlation between SCT and fecal fat. Nonpancreatogenic steatorrhea was present in two thirds of the patients and was probably caused by bacterial overgrowth.

Conclusions: Neither low fecal elastase 1 nor raised fecal fat levels reliably indicate exocrine pancreatic insufficiency in type-1 diabetes and therefore should not be used as an indicator for expensive pancreatic enzyme substitution.
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http://dx.doi.org/10.1097/MPA.0b013e3181656f8DOI Listing
April 2008

Inverse association between periodontitis and respiratory allergies in patients with type 1 diabetes mellitus.

J Clin Periodontol 2008 Apr 20;35(4):305-10. Epub 2008 Feb 20.

Institute for Community Medicine, Ernst Moritz Arndt University Greifswald, Germany.

Aim: In a general adult population, we have demonstrated an inverse association between periodontitis and respiratory allergies that is in line with the hygiene hypothesis suggesting a protective effect of infections against the development of allergies. The objective of the present study was to investigate the association between periodontitis and respiratory allergies in a type 1 diabetes mellitus population.

Material And Methods: The study population comprised 170 patients with type 1 diabetes mellitus aged 17-80 years. Respiratory allergies were present in 22 subjects. The attachment loss (AL) was measured. Periodontitis was defined according to the percentage of surfaces that exceeded 3 mm AL (healthy, mild, moderate, severe periodontal conditions).

Results: Our adjusted analyses revealed an inverse association between periodontitis and respiratory allergies. For increasing AL, a trend towards a decreasing risk was present for respiratory allergies (p(trend)<0.05). Compared with subjects with healthy periodontal conditions, individuals with severe periodontal conditions had the lowest risk of respiratory allergies [odds ratios (OR) 0.06 (95% confidence interval (CI) 0.01-0.39)], followed by subjects with moderate AL [OR 0.14 (95% CI 0.03-0.63)] and mild AL [OR 0.32 (95% CI 0.09-1.08)].

Conclusion: There is a strong inverse association between periodontitis and respiratory allergies in patients with type 1 diabetes mellitus. These findings further support the hygiene hypothesis.
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http://dx.doi.org/10.1111/j.1600-051X.2008.01200.xDOI Listing
April 2008

Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.

Am J Hum Genet 2007 Aug 26;81(2):338-45. Epub 2007 Jun 26.

Oy Jurilab, and Research Institute of Public Health, University of Kuopio, Kuopio, Finland, and Hope Hospital, Salford, UK.

Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.
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http://dx.doi.org/10.1086/520599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950819PMC
August 2007

Intracellular calcium and sodium-lithium countertransport in type 2 diabetic patients with and without albuminuria.

Endocr J 2006 Dec 19;53(6):773-81. Epub 2006 Sep 19.

Institute of Epidemiology and Social Medicine, Ernst Moritz Arndt University Greifswald, Germany.

Increased intracellular calcium concentrations ([Ca(2+)](i)) and enhanced sodium-lithium countertransport (Na/Li CT) activities may play a role in the development of diabetic complications such as diabetic nephropathy. The present study was designed to test the hypothesis that albuminuria in patients with type 2 diabetes is associated with increased [Ca(2+)](i) in response to stimulation with platelet-activating factor (PAF) or with enhanced Na/Li CT activities. The study population comprised 203 type 2 diabetic patients. Albuminuria was defined as an albumin excretion rate exceeding 30 mg/d (117 cases). PAF-evoked rises in [Ca(2+)](i) and Na/Li CT activities were determined in Epstein-Barr-virus-immortalized lymphoblasts. Albuminuria was related to high stimulated [Ca(2+)](i) but not to high basal [Ca(2+)](i). The association was independent of age, sex and several non-diabetes related confounders, but depended on diabetes-related factors, such as the duration of diabetes. The risk of albuminuria was highest in subjects with high [Ca(2+)](i) who reported a diabetes duration of < or =10 years. There was no association between Na/Li CT activities and albuminuria. The present results support the hypothesis that albuminuria in type 2 diabetic patients is associated with a primary defect in intracellular calcium homeostasis. The association between stimulated [Ca(2+)](i) and albuminuria is most prominent in early diabetes.
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http://dx.doi.org/10.1507/endocrj.k06-065DOI Listing
December 2006

The spectrum of thyroid disorders in adult type 1 diabetes mellitus.

Diabetes Metab Res Rev 2007 Mar;23(3):227-33

Institute of Epidemiology and Social Medicine, University of Greifswald, Greifswald, Germany.

Background: Thyroid disorders such as goiter, nodules, autoimmune thyroid disease and thyroid dysfunction have rarely been investigated in adult type 1 diabetes mellitus. Our aim was to study the spectrum of thyroid disorders in adult type 1 diabetic subjects and compare them with results obtained from a sample of the general adult population.

Methods: The study population comprised 224 type 1 diabetic and 3481 non-diabetic subjects aged 20-69 years. Thyroid function (TSH, FT3 and FT4) and serum autoantibodies to thyroperoxidase (anti-TPO-Ab) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound.

Results: Type 1 diabetic subjects had a higher risk of known thyroid disease [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.11-2.85], a lower risk of goiter (OR 0.73; 95%-CI 0.54-0.99) and nodules (OR 0.54; 95%-CI 0.35-0.85), and a higher risk of anti-TPO-Ab >200 IU/mL (OR 1.94; 95%-CI 1.28-2.95) compared to the reference population. Furthermore, diabetic subjects had lower serum FT3 levels than the non-diabetic references (adjusted mean 5.00 pmol/L; 95%-CI 4.88-5.12 pmol/L versus 5.27 pmol/L; 95%-CI 5.24-5.30 pmol/L).

Conclusions: Adult type 1 diabetes mellitus is associated with a decreased risk of goiter and nodules and an increased risk of thyroid autoimmunity. A diabetes-related low T3 syndrome may contribute to the differences in thyroid function between type 1 diabetic and non-diabetic subjects.
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http://dx.doi.org/10.1002/dmrr.676DOI Listing
March 2007

Prevalence of diabetes-associated autoantibodies in schoolchildren: the Karlsburg Type 1 Diabetes Risk Study.

Ann N Y Acad Sci 2004 Dec;1037:114-7

Institute of Pathophysiology, Ernst Moritz Arndt University of Greifswald, Greifswalder Str. 11b, D-17495 Karlsburg, Germany.

This study attempts to assess the prevalence of diabetes-associated autoantibodies in a general population in the northeastern part of Germany, with emphasis on autoantibodies against glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA-2A), and insulin (IAA) by radioassays >/= 98th percentile, and AAbs binding on pancreatic sections (ICA) by immunofluorescence >/= 10 Juvenile Diabetes Foundation units. From a total of 11,840 schoolchildren tested for all four AAbs, 821 (6.9%) children were positive for single AAbs, whereas 83 (0.7%) had multiple AAbs. If the primary screening were performed by testing GADA/IA-2A/IAA, 94% of probands with single AAbs and all with multiple AAbs would be identified. The combinations of GADA/IA-2A, GADA/IAA, and IA-2A/IAA would identify 97.6, 98.8, and 85.5% of probands with multiple AAbs, respectively. Thus, combined AAb screening in the general population identifies those probands at risk for diabetes.
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http://dx.doi.org/10.1196/annals.1337.017DOI Listing
December 2004

[The metabolic syndrome in patients with type 1 diabetes mellitus. Associations with cardiovascular risk factors and cardiovascular morbidity].

Herz 2004 Aug;29(5):463-9

Klinik für Diabetes und Stoffwechselkrankheiten, Herz-Kreislaufzentrum Mecklenburg-Vorpommern, Karlsburg.

Background And Purpose: Type 1 diabetes is known to be associated with increased cardiovascular disease in the presence of nephropathy and hypertension. It was the aim of the present study to elucidate whether or not clinical findings of metabolic syndrome (MS) are further increasing cardiovascular morbidity among type 1 diabetics.

Methods: In the present cross-sectional study, 1,241 type 1 diabetics were included. These patients attended the Diabetes Clinic Karlsburg, Germany, from February 1, 2002 to December 31, 2003. The presence of the following findings was taken into consideration as clinical features of MS in type 1 diabetes: fasting triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), daily insulin requirement/kg body weight (b.w.), increased blood pressure > 130/85 mmHg, including overt arterial hypertension. In each of the five categories the highest quintile in each sample was assessed: TG 2.9 +/- 3.6 mmol/l, HDL-C 1.48 +/- 0.46 mmol/l, BMI 29.1 +/- 4.98 kg/m(2) height, insulin requirement 0.71 +/- 0.23 IU/kg b.w., systolic blood pressure 130 +/- 12.3 mmHg. MS was defined as the presence of at least three categories. Among 1,241 type 1 diabetics (651 men, 590 women), 226 patients (129 men, 97 women) fulfilled the criteria of MS. The risk of MS was assessed by multiple regression analysis. Risk variables were: age, diabetes duration, sex, glycated hemoglobin (HbA(1c)), actual smoking, neuropathy, albumin excretion rate (AER), regular alcohol consumption, retinopathy, peripheral vascular disease (PVD), coronary heart disease (CHD), TGs, HDL-C, low-density lipoprotein cholesterol (LDL-C), cholesterol, blood pressure increase, BMI, increased insulin requirement, and foot syndrome. After adjusting for age, the variables were separately included into the mathematical model. The risk of MS was assessed after excluding the variables defining MS.

Results: Type 1 diabetics with MS were characterized by higher age (46 vs. 36 years; p < 0.01), and longer diabetes duration (19 vs. 16 years; p < 0.01). The risk of MS was independently associated (odds ratios) with higher age (40-59 years; 4.21; p < 0.01), increased HbA(1c) (1.41; p < 0.01), PVD (2.28; p < 0.01), CHD (2.19; p < 0.01), and the foot syndrome (4.17; p < 0.01). There were no significant associations of MS with type 2 diabetes heredity (first and second degree).

Conclusion: Patients with type 1 diabetes and the presence of findings of MS are suffering from increased cardiovascular morbidity. The risk of MS increases with the age and HbA(1c). Life style factors such as weight gain and muscular inactivity seem to have an influence on the pathogenesis of MS in type 1 diabetes, thereby increasing cardiovascular morbidity.
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http://dx.doi.org/10.1007/s00059-004-2606-0DOI Listing
August 2004

A homozygous HFE gene splice site mutation (IVS5+1 G/A) in a hereditary hemochromatosis patient of Vietnamese origin.

Gastroenterology 2002 Mar;122(3):789-95

Institute of Clinical Chemistry and Pathobiochemistry, University of Rostock, Rostock, Germany.

The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.
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http://dx.doi.org/10.1053/gast.2002.31884DOI Listing
March 2002
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