Aim: To describe the prevalence, incidence, and severity of diabetes mellitus type 2 (T2D) and antidiabetic medication in older people and to assess the prognostic value of diagnostic laboratory parameters.Methods: Baseline data of 1,671 participants of the Berlin Aging Study II (68.8 ±3.7 years) and follow-up data assessed 7.4 ±1.5 years later were analysed. T2D was diagnosed based on self-report, antidiabetic medication use, laboratory parameters. T2D severity was determined by the diabetes complications severity index (DCSI). Prognostic capacity of laboratory parameters was evaluated by Receiver Operating Characteristics (ROC) and Areas Under the Curve (AUCs).Results: The proportion of participants with T2D increased from 12.9% (37.3% women) at baseline to 17.1% (41.1% women) with 74 incident cases and 22.2% not being aware of the disease at follow-up. More than half of the 41 newly identified incident T2D cases were diagnosed solely by the 2h-plasma glucose test (OGTT) and diagnosis based on OGTT as the only criterion among incident cases was found more frequently in women (p=0.028). The OGTT assessed at baseline predicted incident T2D less accurate in men (AUC: 0.671, 95% CI 0.570-0.771) when compared to women (AUC: 0.7893, 95% CI 0.7036-0.8751). No sex differences were detected with respect to antidiabetic medication used and T2D severity. Conclusions: A comprehensive picture of T2D with respect to prevalence, incidence, and severity in older people is provided. Clinically relevant sex differences in the capacity of the commonly used T2D diagnostic laboratory parameters to predict incident T2D on average 7.4 years later were detected.

Background Patients with Type 2 diabetes mellitus (T2D) are at risk for micro- and macrovascular complications. Implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The epigenetic clock estimates an individual’s biological age using DNA methylation profiles. Methods In this study, we examined older adults of the Berlin Aging Study II that were reexamined on average 7.4 years after baseline assessment as part of the GendAge study. DNA methylation age (DNAmA) and its deviation from chronological age DNAmA acceleration (DNAmAA) were calculated with the 7-CpG clock (available at both timepoints, n = 1,071), Horvath’s clock, Hannum’s clock, PhenoAge and GrimAge (available at follow-up only, n = 1,067). T2D associated complications were assessed with the Diabetes Complications Severity Index (DCSI). Results We report on a statistically significant association between oral glucose tolerance test results and Hannum and PhenoAge DNAmAA. PhenoAge was also associated with fasting glucose. In contrast, we found no cross-sectional association after covariate adjustment between DNAmAA and a diagnosis of T2D. However, longitudinal analyses showed that every additional year of 7-CpG DNAmAA at baseline increased the odds for developing one or more additional complications or worsening of an already existing complication during the follow-up period by 11% in male participants with T2D. This association persisted after covariate adjustment (OR = 1.11, p = 0.045, n = 56). Conclusion Although our results remain to be independently validated, this study shows promising evidence of utility of the 7-CpG clock in identifying patients with diabetes who are at high risk for developing complications.

Patients with diabetes mellitus are at risk for micro- and macrovascular complications that are responsible for a substantial part of the individual health burden and socio-economic costs. Therefore, implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The "epigenetic clock" estimates an individual's biological age using DNA methylation profiles and was previously shown to be associated with morbidity and mortality. In this study, we examine older adults of the BASE-II study that were reexamined on average 7.4 years after baseline assessment as part of the GendAge study. For DNA methylation age (DNAmA) estimation we used the 7-CpG clock which was available for two timepoints (n=1,071 at follow-up). In addition, we determined epigenetic age using Horvath's clock, Hannum's clock, PhenoAge and GrimAge which were available at follow-up only (n=1,067). The deviation of DNAmA from chronological age, DNA methylation age acceleration (DNAmAA), was calculated as residuals of a leukocyte cell count adjusted linear regression analysis. Diabetes associated complications were assessed with the Diabetes Complications Severity Index (DCSI). Cross-sectionally, a statistically significant association between oral glucose tolerance test results and Hannum (beta=0.8, SE=0.3, p=0.02, n=762) and PhenoAge DNAmAA (beta=0.8, SE=0.3, p=0.003, n=762) was found. PhenoAge was also associated with fasting glucose (beta=0.3, SE=0.1, p=0.013, n=966). In contrast, we observed no cross-sectional association after covariate adjustment between DNAmAA and a diagnosis of diabetes mellitus with any of the five clocks employed. This was true for longitudinal analyses with the 7-CpG clock as well. However, longitudinal analyses showed that every year in the 7-CpG-based DNAmAA estimate at baseline increased the risk for developing of one or more additional complications or worsening of an already existing complication during the follow-up period by 11% in male participants with diabetes mellitus type 2. This association persisted after adjustment for DCSI at baseline, chronological age, smoking, alcohol, diabetes medication, and BMI (OR =1.11, p=0.045, n=56). No statistically significant association was found in the subgroup of women or when the whole dataset was analyzed (p>0.05). Although our findings still need to be independently validated, the 7-CpG clock appears to be a promising biomarker which is informative about the individual risk for diabetic complications independent of age, sex, lifestyle factors, or complications at baseline.