Age at diagnosis of Type 2 diabetes in Germany: a nationwide analysis based on claims data from 69 million people.

AIM: For many European countries, including Germany, no valid estimates are available on age at diagnosis of Type 2 diabetes. Thus, we aimed to estimate the age at diagnosis in Germany. METHODS: Age at diagnosis of Type 2 diabetes in Germany was estimated based on Type 2 diabetes prevalence and incidence and the age distribution of the German population. Age- and sex-specific incidence and prevalence in 2014/2015, based on claims data from statutory health insurance (n= 69 000 000, ~85% of the German population), and the age pyramid for Germany in 2015 were used for the calculation. Age at Type 2 diabetes diagnosis was stratified by sex. CIs were estimated using bootstrap methods. In addition, the age range in which 50% of the population received a diagnosis of Type 2 diabetes was calculated (the interquartile range). RESULTS: The mean ± sd age at Type 2 diabetes diagnosis in 2015 was 61.0 ± 13.4 years (95% CI 60.9-61.0) in men. Women were diagnosed ~2 years later than men (mean age 63.4 ± 14.9 years; 95% CI 63.4-63.5). The age range in which 50% of the population was diagnosed with diabetes was 53-72 years for men and 54-76 years for women. CONCLUSIONS: The sex differences are mainly attributable to a higher incidence of Type 2 diabetes in men than women during middle age and the higher absolute number of women in the older ages. The early age at diabetes diagnosis compared to average life expectancy means that the risk of diabetes-related complications is increased.

Distinct trajectories of HbA1c in newly diagnosed Type 2 diabetes from the DPV registry using a longitudinal group-based modelling approach.

AIM: To identify groups of heterogeneous HbA1c trajectories over time in newly diagnosed Type 2 diabetes. METHODS: The study comprised 6355 adults with newly diagnosed Type 2 diabetes (55% men, median age 62 years, baseline BMI 31 kg/m2 ) from the Diabetes Patienten Verlaufsdokumentation (DPV) prospective multicentre diabetes registry (Germany, Austria). Individuals were assessed during the first 5 years after diabetes diagnosis if they had ≥ 3 aggregated HbA1c measurements during follow-up. Latent class growth modelling was used to determine distinct subgroups that followed similar longitudinal HbA1c patterns (SAS: Proc Traj). Multinomial logistic regression models were used to investigate which variables were associated with the respective HbA1c trajectory groups. RESULTS: Four distinct longitudinal HbA1c trajectory (glycaemic control) groups were found. The largest group (56% of participants) maintained stable good glycaemic control (HbA1c 42-45 mmol/mol). Twenty-six percent maintained stable moderate glycaemic control (HbA1c 57-62 mmol/mol). A third group (12%) initially showed severe hyperglycaemia (HbA1c 97 mmol/mol) but reached good glycaemic control within 1 year. The smallest group (6%) showed stable poor glycaemic control (HbA1c 79-88 mmol/mol). Younger age at diabetes diagnosis, male sex, and higher BMI were associated with the stable moderate or poor glycaemic control groups. Insulin therapy was strongly associated with the highly improved glycaemic control group. CONCLUSIONS: Four subgroups with distinct HbA1c trajectories were determined in newly diagnosed Type 2 diabetes using a group-based modelling approach. Approximately one-third of people with newly diagnosed Type 2 diabetes need either better medication adherence or earlier intensification of glucose-lowering therapy.

Effect of Periodontal Treatment on HbA1c among Patients with Prediabetes.

Evidence is limited regarding whether periodontal treatment improves hemoglobin A1c (HbA1c) among people with prediabetes and periodontal disease, and it is unknown whether improvement of metabolic status persists >3 mo. In an exploratory post hoc analysis of the multicenter randomized controlled trial "Antibiotika und Parodontitis" (Antibiotics and Periodontitis)-a prospective, stratified, double-blind study-we assessed whether nonsurgical periodontal treatment with or without an adjunctive systemic antibiotic treatment affects HbA1c and high-sensitivity C-reactive protein (hsCRP) levels among periodontitis patients with normal HbA1c (≤5.7%, n = 218), prediabetes (5.7% < HbA1c < 6.5%, n = 101), or unknown diabetes (HbA1c ≥ 6.5%, n = 8) over a period of 27.5 mo. Nonsurgical periodontal treatment reduced mean pocket probing depth by >1 mm in both groups. In the normal HbA1c group, HbA1c values remained unchanged at 5.0% (95% CI, 4.9% to 6.1%) during the observation period. Among periodontitis patients with prediabetes, HbA1c decreased from 5.9% (95% CI, 5.9% to 6.0%) to 5.4% (95% CI, 5.3% to 5.5%) at 15.5 mo and increased to 5.6% (95% CI, 5.4% to 5.7%) after 27.5 mo. At 27.5 mo, 46% of periodontitis patients with prediabetes had normal HbA1c levels, whereas 47.9% remained unchanged and 6.3% progressed to diabetes. Median hsCRP values were reduced in the normal HbA1c and prediabetes groups from 1.2 and 1.4 mg/L to 0.7 and 0.7 mg/L, respectively. Nonsurgical periodontal treatment may improve blood glucose values among periodontitis patients with prediabetes (ClinicalTrials.gov NCT00707369).

Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study.

Aims: The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results: In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German population-based cohorts. Using log-binomial regression models, an increased risk for occurrence of arterial hypertension [relative risk (RR) 1.38, 95% confidence interval (95% CI 1.21-1.57)] and dyslipidaemia [RR 1.26 (95% CI 1.12-1.42)] was found. This indicates a premature occurrence compared to the general population of approximately 6 and 8 years, respectively [rate advancement period estimator, RAPhypertension 5.75 (95% CI 3.5-8.0) and RAPdyslipidaemia 8.16 (95% CI 4.4-11.9)]. Overall, no differences were observed for obesity and diabetes. Overt CVD was present in 4.5% (95% CI 3.0-6.6%) of CCS [RR 1.89 (95% CI 1.34-2.66), RAPCVD 7.9 (95% CI 4.1-11.7)], of which the most frequent entities were congestive heart failure and venous thromboembolism. Prevalences of CVRF and CVD increased with age without reaching a plateau over time. Conclusion: This large CCS screening examination revealed consistently in comparison to three population samples a considerably increased risk for premature CVD. The findings in these young adult CCS indicate a high burden of cardiovascular morbidity and mortality in the long term. Clinicaltrials. gov-Nr: NCT02181049.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

Abdominal fat deposits determined by magnetic resonance imaging in relation to leptin and vaspin levels as well as insulin resistance in the general adult population.

BACKGROUND: Various fat depots including visceral (VAT), subcutaneous adipose tissue (SAT) or liver fat content (LFC) were supposed to have different influences on various entities including adipokine levels as well as insulin resistance/sensitivity. Therefore, the aim of the study was to investigate the associations of SAT, VAT and LFC with the levels of leptin and vaspin as well as insulin resistance in a general non-diabetic population. METHODS: In total, 1825 participants of the Study of Health in Pomerania were characterized according to body fat compartments and LFC determined by magnetic resonance imaging. Of those subjects, insulin resistance (HOMA-IR) and insulin sensitivity ([ISI(comp)) were determined in 981 participants and adipokines were assessed in 698 using enzyme-linked immunosorbent assay. Analyses of variance and linear regression models adjusted for age, sex, smoking, height, physical inactivity and alcohol consumption were used for analysis. RESULTS: Using the residual method to assess independently the effect of the various fat depots, a strong positive association of SAT (beta per standard deviation (s.d.) increase 0.54 (95% confidence interval (CI) 0.47-0.60)) but not VAT (beta 0.01 (95% CI -0.08 to 0.09)) and LFC (beta 0.01 (95% CI -0.06 to 0.08)) with log2-leptin levels was found independent of the HOMA-IR status. Moreover, a positive association of LFC (beta 0.17 (95% CI 0.07-0.26)) with log2-vaspin levels becomes apparent, which were mostly driven by subjects with a low HOMA-IR. With respect to HOMA-IR and ISI(comp) index, pronounced positive and inverse associations to all fat markers were revealed, respectively, with the strongest relation found for SAT and LFC. CONCLUSIONS: SAT and LFC were identified as predominant sites associated with leptin and vaspin levels, respectively. Residual analysis pointed towards a general adverse effect of disproportional triglyceride storage across physiological despots, in particular in ectopic sides such as the liver, with markers of insulin resistance.

Inequalities in glycaemic control, hypoglycaemia and diabetic ketoacidosis according to socio-economic status and area-level deprivation in Type 1 diabetes mellitus: a systematic review.

AIM: The aim of this systematic review was to examine the associations of individual-level as well as area-level socio-economic status and area-level deprivation with glycaemic control, hypoglycaemia and diabetic ketoacidosis in people with Type 1 diabetes mellitus. METHODS: Ovid MEDLINE was searched to identify relevant cohort, case-control or cross-sectional studies published between January 2000 and June 2015. Search results were screened by title, abstract and keywords to identify eligible publications. Decisions on inclusion or exclusion of full texts were made independently by two reviewers. The Newcastle-Ottawa Scale was used to estimate the methodological quality of included studies. Quality assessment and extracted data of included studies were synthesized narratively and reported according to the PRISMA statement. RESULTS: Literature search in Ovid MEDLINE identified 1345 eligible studies. Twenty studies matched our inclusion and exclusion criteria. Two articles were additionally identified through hand search. According to the Newcastle-Ottawa Scale, most of the studies were of average quality. Results on associations of socio-economic status and area-level deprivation with glycaemic control and hypoglycaemia were contradictory between studies. By contrast, lower socio-economic status and higher area-level deprivation were associated with a higher risk for diabetic ketoacidosis in all except one study. CONCLUSIONS: Lower socio-economic status and higher area-level deprivation are associated with a higher risk of experiencing diabetic ketoacidosis in people with Type 1 diabetes mellitus. Access to care for socially deprived people needs to be expanded to overcome impairing effects on the course of the condition and to reduce healthcare disparities.

Utility of HbA1c and fasting plasma glucose for screening of Type 2 diabetes: a meta-analysis of full ROC curves.

AIMS: There is still debate on the optimal threshold for population-based screening of diabetes (diagnosed by the oral glucose tolerance test) using tests like HbA1c or fasting plasma glucose. Meta-analyses provide meaningful input in such situations. The aim of this article is to perform a meta-analysis that includes the complete information reported in the individual studies of two existing systematic reviews. METHODS: We screened the individual studies from two systematic reviews and reconstructed the full four-fold tables for every reported threshold. Using a recently proposed meta-analysis model for the comparison of two diagnostic tests, we compared HbA1c with fasting plasma glucose, and estimated meta-analytic receiver operating characteristic curves for both tests using the 11.1 mmol/l threshold of the 2-h post-challenge glucose level (2 h-PG) as the gold standard. RESULTS: We included nine studies from two existing systematic reviews in our analysis. Based on our data set, the optimal threshold lies between 42 and 44 mmol/mol (6.0-6.2%) for HbA1c , and 6.2-6.4 mmol/l for fasting plasma glucose choosing the Youden index as the technical criterion. In addition, we found that there is no relevant difference in the performance of HbA1c and fasting plasma glucose. CONCLUSIONS: In our meta-analysis, we found that the optimal threshold with reference to the 2 h-PG should be chosen between 42 and 44 mmol/mol (6.0-6.2%) for HbA1c , and 6.2-6.4 mmol/l for fasting plasma glucose on the basis of maximal sensitivity and specificity.

Low annual frequency of HbA1c testing in people with Type 2 diabetes in primary care practices in Germany.

AIMS: To analyse the annual frequency of HbA1c testing, as well as the factors associated with higher or lower testing frequency, in people with Type 2 diabetes mellitus in general practices and specialist diabetes practices in Germany. METHODS: A total of 43 509 people diagnosed with Type 2 diabetes between January 2016 and December 2016 in 557 medical practices (51% of all practices) were included in this study. The primary outcome was the annual recorded frequency of HbA1c testing in 2016. Multivariable logistic regression analyses were performed to identify variables associated with the odds of HbA1c concentration being tested at least twice in 2016, using predefined demographic and clinical variables. RESULTS: The mean (sd) number of reported HbA1c tests was 2.7 (1.6) in 2016. Overall, 74% of individuals had at least two annual HbA1c measurements. The likelihood of receiving ≥2 HbA1c tests was inversely associated with stroke (odds ratio 0.81, 95% CI 0.74-0.89), shorter diabetes duration (≤1 year: odds ratio 0.77, 95% CI 0.70-0.84) and higher mean HbA1c concentration (≥8.5%: odds ratio 0.85, 95% CI 0.76-0.94) and was positively associated with specialist diabetes care (odds ratio 1.24, 95% CI 1.14-1.36), hypertension (odds ratio 1.10, 95% CI 1.04-1.17), hyperlipidaemia (odds ratio 1.48, 95% CI 1.41 to 1.55), renal complications (odds ratio 1.41, 95% CI 1.32 to 1.50), neuropathy (odds ratio 1.27, CI 1.20 to 1.35) and retinopathy (odds ratio 1.38, 95% CI 1.25 to 1.52). CONCLUSIONS: Only three out of four individuals with Type 2 diabetes underwent at least two HbA1c tests in Germany in 2016, which means that 25% of individuals underwent fewer tests than required by German guidelines.

Does periodontitis affect diabetes incidence and haemoglobin A1c change? An 11-year follow-up study.

AIM: As periodontitis may contribute to the pathogenesis of diabetes, the effects of periodontitis on diabetes incidence and HbA1c change was quantified in a prospective cohort. METHODS: Data from an 11-year follow-up of the Study of Health in Pomerania were analyzed to evaluate the effects of periodontitis on incident diabetes and long-term HbA1c changes in 2047 subjects aged 20-81years. Diabetes was based on self-reported physician diagnoses, antidiabetic medication use, or HbA1c≥6.5% or non-fasting blood glucose levels ≥11.1mmol/L. To assess periodontal status, periodontal pockets were probed, and their depth and clinical attachment levels measured. For both measures, means and percentages of sites≥3mm were calculated. In addition, all probing depths≥4mm were summed (cumulative probing depth). Modified Poisson and multivariable linear models were applied, adjusted for age, gender, highest level of general education, marital status, waist circumference, physical activity, smoking status and follow-up time. RESULTS: Over a mean follow-up period of 11.1years, 207 subjects developed diabetes. Baseline mean clinical attachment levels (CAL) and probing depths (PPD) were not significantly associated with either diabetes incidence [mean CALs, fourth quartile, incidence rate ratio=0.819, 95% confidence interval (CI): 0.489-1.370; P=0.446] or long-term changes in HbA1c (mean CAL, fourth quartile, ß=-0.086, 95% CI: -0.187, -0.016; P=0.098). Sensitivity analyses using alternative exposure definitions confirmed these results. CONCLUSION: Contrary to the currently available literature, no convincing evidence was found of any potential association between periodontitis and diabetes incidence or HbA1c change.

Prediabetes is associated with lower brain gray matter volume in the general population. The Study of Health in Pomerania (SHIP).

BACKGROUND AND AIMS: We investigated the associations of fasting (FG) and 2-h postload (2HG) plasma glucose from oral glucose tolerance test (OGTT) with gray (GMV) and white (WMV) matter volume. METHODS AND RESULTS: We analyzed data from 1330 subjects without known diabetes mellitus, aged 21 to 81, from the second cohort (SHIP-Trend-0) of the population-based Study of Health in Pomerania (SHIP). Following the OGTT, individuals were classified in five groups (according to the American Diabetes Association criteria): normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) and unknown type 2 diabetes mellitus (UDM). GMV and WMV were determined by magnetic resonance imaging. FG, 2HG and OGTT groups were associated with GMV and WMV by linear regression models adjusted for confounders. FG and 2HG were inversely associated with GMV. The adjusted mean GMV, when compared with the NGT group (584 ml [95% CI: 581 to 587]), was significantly lower in the groups i-IFG (578 ml [95% CI: 573 to 582]; p = 0.035) and UDM (562 ml [95% CI: 551 to 573]; p < 0.001), but not different in the i-IGT (586 ml [95% CI: 576 to 596]; p = 0.688) and IFG + IGT (579 ml [95% CI: 571 to 586]; p = 0.209) groups. There were no associations of FG, 2HG and OGTT parameters with WMV. CONCLUSION: Our findings suggest that elevated FG levels, even within the prediabetic range, might already have some harmful effects on GMV.

Healthcare costs of Type 2 diabetes in Germany.

AIM: To describe for the first time the direct costs of Type 2 diabetes treatment by analysing nationwide routine data from statutory health insurance in Germany. METHODS: This cost-of-illness-study was based on a 6.8% random sample of all German people with statutory health insurance (4.3 out of 70 million people). The healthcare expenses show direct per capita costs from the payer perspective. Healthcare expenses for physicians, dentists, pharmacies, hospitals, sick benefits and other healthcare costs were considered. Per capita costs, cost ratios for people with Type 2 diabetes and without diabetes as well as diabetes-attributable costs were calculated. RESULTS: Per capita costs for people with Type 2 diabetes amounted to €4,957 in 2009 and €5,146 in 2010. People with Type 2 diabetes had 1.7-fold higher health expenses than people without diabetes. The largest differences in health expenses were found for prescribed medication from pharmacies (cost ratio diabetes/no diabetes: 2.2) and inpatient treatment (1.8). Ten percent of the total statutory health insurance expense, in total €16.1 billion, was attributable to the medical care of people with Type 2 diabetes. CONCLUSIONS: This nationwide study indicates that one in 10 Euros of healthcare expenses is spent on people with Type 2 diabetes in Germany. In the future, national statutory health insurance data can be used to quantify time trends of costs in the healthcare system.

Prevalence of gestational diabetes and risk of complications before and after initiation of a general systematic two-step screening strategy in Germany (2012-2014).

AIMS: Information on the prevalence of gestational diabetes mellitus is scarce on national and international level. On July 1st, 2013, a general two-step screening was implemented in Germany harmonizing gestational diabetes diagnoses. We aim to provide prevalence estimates for gestational diabetes and pregnancy-related complications for the large region of North Rhine for the 12 months before and after introduction of the general screening. METHODS: Routine care data covering all outpatient diagnoses of more than 150,000 pregnancies per 12-month period in women aged 15-55 years was used to determine cases of gestational diabetes. Gestational diabetes diagnosis and pregnancy-related complications were assessed according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Relative Risks for pregnancy-related complications were calculated in pregnancies with and without gestational diabetes. RESULTS: Before the screening, diagnosis of gestational diabetes was made in 6.02% of pregnancies and in 6.81% after this date (other types of diabetes mellitus: 1.67% and 1.76% respectively). The prevalence of GDM increased with age and was highest at age 36-40 years (8.45%). The relative increase in prevalence after introduction of the screening was highest in the age group≤25 years (24.9%). The frequency of pregnancy-related complications such as hypertension, pre-eclampsia, cesarean section was increased in pregnancies with gestational diabetes in comparison to those without independent of observation period. CONCLUSIONS: We found a high prevalence of gestational diabetes, which has relatively increased by 13.12% after the introduction of the general screening.

Change in glycated haemoglobin levels after initiating second-line therapy in type 2 diabetes: a primary care database study.

The aim of the present study was to compare the absolute reduction in glycated haemoglobin (HbA1c) levels at 6 months after initiating second-line glucose-lowering therapy in patients with type 2 diabetes treated with metformin monotherapy in general practices. A total of 7009 patients were identified (Disease Analyser Germany: January 2004 to December 2014). The patients' mean ± standard deviation (s.d.) age was 63 ± 11 years, 55.5% were male and their mean ± s.d. HbA1c level was 8.0 ± 1.6%. The initiated second-line therapies included: dipeptidyl peptidase-4 (DPP-4) inhibitors (38.7%); sulphonylureas (36.3%); insulin (13.3%); glucagon-like peptide-1 receptor agonists (GLP-1RAs; 2.5%); thiazolidinediones (5%); and other agents (glinides, aldose-reductase inhibitors; 4.1%). The mean absolute HbA1c change from baseline was -0.9% (DPP-4 inhibitors, -0.9%; sulphonylureas, -0.9%; insulin, -1.1%; GLP-1RAs, -0.7%; thiazolidinediones, -0.9%; and other, -0.7%; all p < 0.001). Overall, 58% of patients reached the HbA1c target of <7% (DPP-4 inhibitors, 61.7%; sulphonylureas, 56.7%; insulin, 45.6%; GLP-1RAs, 62.2%; thiazolidinediones, 69.7%; and other, 57.5%). Compared with sulphonlyureas, DPP-4 inhibitors, GLP-1RAs and thiazolidinediones were associated with an increased odds of reaching HbA1c <7% [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.09-1.40; OR 1.43, 95% CI 1.01-2.04; and OR 1.70, 95% CI 1.30-2.23, respectively], whereas insulin was related to a lower odds (0.66, 95% CI 0.55-0.78). In conclusion, in patients with type 2 diabetes very similar reductions in HbA1c after 6 months of second-line therapy were achieved regardless of the type of therapy.

Fracture risk in patients with type 2 diabetes under different antidiabetic treatment regimens: a retrospective database analysis in primary care.

AIM: Type 2 diabetes is associated with an increased risk of fractures. There are a few studies on the effects of diabetes treatment on fracture risk. The aim was to investigate the fracture risk related to various types of insulin therapy in primary care practices. METHODS: Data from 105,960 type 2 diabetes patients from 1,072 general and internal medicine practices in Germany were retrospectively analyzed (Disease Analyzer database; 01/2000-12/2013). Fracture risk of the following therapies was compared using multivariate logistic regression models adjusting for age, sex, diabetes care, comorbidity, and glycemic control (HbAlc): 1) incident insulin therapy versus oral antidiabetic drugs, 2) basal-supported oral therapy versus supplementary insulin therapy versus conventional insulin therapy, and 3) insulin glargine versus insulin detemir versus NPH insulin. RESULTS: There was a lower odds of having incident fractures in the oral antidiabetic drug group compared to incident insulin users, although not significant (odds ratio [OR]; 95% confidence interval: 0.87; 0.72-1.06). There were increased odds for conventional insulin therapy (OR: 1.59; 95% CI [confidence interval] 0.89-2.84) and supplementary insulin therapy (OR: 1.20; 0.63-2.27) compared to basal-supported oral therapy, which was not significant as well. Overall, there was no significant difference in fracture risk for basal insulins (glargine, detemir, NPH insulin). After a treatment duration ≥2 years, insulin glargine showed a lower odds of having ≥1 fracture compared to NPH users (OR: 0.78; 0.65-0.95) (detemir vs NPH insulin: OR: 1.03; 0.79-1.36). CONCLUSION: Long-standing therapy with insulin glargine was associated with a lower odds of having any fractures compared to NPH insulin. Further studies are required to investigate whether the lower chance is due to a reduced frequency of hypoglycemia.

HbA1c levels in non-diabetic older adults - No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confounders in a meta-analysis of individual participant data from six cohort studies.

BACKGROUND: To determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations. METHODS: The associations of HbA1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects ≥50 years from six population-based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA1c were defined as <5.0, 5.0 to <5.5, 5.5 to <6.0 and 6.0 to <6.5% (equals <31, 31 to <37, 37 to <42 and 42 to <48 mmol/mol), respectively, and low HbA1c was used as reference in Cox proportional hazards models. RESULTS: Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50% of the excess risk and attenuated hazard ratios (95 confidence interval) for increased HbA1c to 1.14 (1.03-1.27), 1.17 (1.00-1.37) and 1.19 (1.04-1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA1c levels lost statistical significance in this cohort after adjusting for these confounders. CONCLUSIONS: A linear association of HbA1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results.

Temporal changes in the prevalence of diagnosed diabetes, undiagnosed diabetes and prediabetes: findings from the German Health Interview and Examination Surveys in 1997-1999 and 2008-2011.

AIMS: Nationally representative data on temporal changes in the prevalence of diagnosed diabetes, as well as undiagnosed diabetes and prediabetes, have been lacking in Germany as in most other European countries. We aimed to fill this gap using data from nationwide examination surveys of German adults. METHODS: The study population comprised 18-79-year-old participants from the German Health Interview and Examination Surveys in 1997-1999 (GNHIES98, n = 6655) and 2008-2011 (DEGS1, n = 7017). Participants were classified as having diagnosed diabetes based on self-reported physician-diagnosed diabetes or the use of anti-diabetes agents. Among those without diagnosed diabetes, HbA1c measures were used to define undiagnosed diabetes [≥ 48 mmol/mol (≥ 6.5%)] or prediabetes [39-47 mmol/mol (5.7-6.4%)]. RESULTS: Although the age- and sex-standardized prevalence of total diabetes remained stable between 1997-1999 at 9.3% (95% CI 8.3-10.5%) and 2008-2011 at 9.2% (8.3-10.3%), the prevalence of diagnosed diabetes increased from 5.6% (4.9-6.3%) to 7.2% (6.5-8.0%), whereas the prevalence of undiagnosed diabetes decreased from 3.8% (3.1-4.6%) to 2.0% (1.5-2.7%), resulting in a decreased proportion of undiagnosed diabetes (40.9% vs. 21.7%). Over the same period, the prevalence of prediabetes decreased from 27.7% (25.6-29.8%) to 20.8% (18.2-23.7%). Observed temporal changes were not explained by changes in BMI, sport activity and educational level. CONCLUSIONS: The two nationwide surveys indicate a shift from undiagnosed to diagnosed diabetes. However, the unchanged prevalence of total diabetes and the considerably high proportion of prediabetes strongly call for a continued and concerted effort in diabetes prevention among German adults.

Predictors of early discontinuation of basal insulin therapy in type 2 diabetes in primary care.

AIMS: To identify patient-related characteristics and other impact factors predicting early discontinuation of basal insulin therapy in type 2 diabetes in primary care. METHODS: A total of 4837 patients who started basal insulin therapy (glargine: n=3175; NPH: n=1662) in 1072 general and internal medicine practices throughout Germany were retrospectively analyzed (Disease Analyser Database: 01/2008-03/2014). Early discontinuation was defined as switching back to oral antidiabetic drugs (OAD) therapy within 90 days after first basal insulin prescription (index date, ID). Patient records were assessed 365 days prior and post ID. Logistic regression models were used to adjust for age, sex, diabetes duration, diabetologist care, disease management program participation, HbA1c, and comorbidity. RESULTS: Within 3 months after ID, 202 (6.8%) of glargine patients switched back to OAD (NPH: 130 (8.5%); p<0.05). In multivariable logistic regression, predictors of early basal insulin discontinuation were ≥1 documented hypoglycemia before ID (adjusted Odds ratio; 95% CI: 2.20; 1.27-3.82), diagnosed depression (1.31; 1.01-1.70) and referrals to specialists within 90 days after ID (2.06; 1.61-2.63). Diabetologist care (0.57; 0.36-0.89) and glargine treatment (vs. NPH: 0.78; 0.61-0.98) were related to a lower odds of having early insulin discontinuation. CONCLUSIONS: Less than 10% of type 2 diabetes patients switched back to oral antidiabetic drugs within 90 days after start of basal insulin therapy. In particular, patients with baseline depression and frequent or severe hypoglycemia have a higher likelihood for early discontinuation of basal insulin, whereas use of insulin glargine and diabetologist care are related to an increased chance of continuous insulin treatment.

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.

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.