Clinical impact of an integrated e-health system for diabetes self-management support and shared decision making (POWER2DM): a randomised controlled trial.

AIMS/HYPOTHESIS: There is a lack of e-health systems that integrate the complex variety of aspects relevant for diabetes self-management. We developed and field-tested an e-health system (POWER2DM) that integrates medical, psychological and behavioural aspects and connected wearables to support patients and healthcare professionals in shared decision making and diabetes self-management. METHODS: Participants with type 1 or type 2 diabetes (aged >18 years) from hospital outpatient diabetes clinics in the Netherlands and Spain were randomised using randomisation software to POWER2DM or usual care for 37 weeks. This RCT assessed the change in HbA1c between the POWER2DM and usual care groups at the end of the study (37 weeks) as a primary outcome measure. Participants and clinicians were not blinded to the intervention. Changes in quality of life (QoL) (WHO-5 Well-Being Index [WHO-5]), diabetes self-management (Diabetes Self-Management Questionnaire - Revised [DSMQ-R]), glycaemic profiles from continuous glucose monitoring devices, awareness of hypoglycaemia (Clarke hypoglycaemia unawareness instrument), incidence of hypoglycaemic episodes and technology acceptance were secondary outcome measures. Additionally, sub-analyses were performed for participants with type 1 and type 2 diabetes separately. RESULTS: A total of 226 participants participated in the trial (108 with type 1 diabetes; 118 with type 2 diabetes). In the POWER2DM group (n=111), HbA1c decreased from 60.6±14.7 mmol/mol (7.7±1.3%) to 56.7±12.1 mmol/mol (7.3±1.1%) (means ± SD, p<0.001), compared with no change in the usual care group (n=115) (baseline: 61.7±13.7 mmol/mol, 7.8±1.3%; end of study: 61.0±12.4 mmol/mol, 7.7±1.1%; p=0.19) (between-group difference 0.24%, p=0.008). In the sub-analyses in the POWER2DM group, HbA1c in participants with type 2 diabetes decreased from 62.3±17.3 mmol/mol (7.9±1.6%) to 54.3±11.1 mmol/mol (7.1±1.0%) (p<0.001) compared with no change in HbA1c in participants with type 1 diabetes (baseline: 58.8±11.2 mmol/mol [7.5±1.0%]; end of study: 59.2±12.7 mmol/mol [7.6±1.2%]; p=0.84). There was an increase in the time during which interstitial glucose levels were between 3.0 and 3.9 mmol/l in the POWER2DM group, but no increase in clinically relevant hypoglycaemia (interstitial glucose level below 3.0 mmol/l). QoL improved in participants with type 1 diabetes in the POWER2DM group compared with the usual care group (baseline: 15.7±3.8; end of study: 16.3±3.5; p=0.047 for between-group difference). Diabetes self-management improved in both participants with type 1 diabetes (from 7.3±1.2 to 7.7±1.2; p=0.002) and those with type 2 diabetes (from 6.5±1.3 to 6.7±1.3; p=0.003) within the POWER2DM group. The POWER2DM integrated e-health support was well accepted in daily life and no important adverse (or unexpected) effects or side effects were observed. CONCLUSIONS/INTERPRETATION: POWER2DM improves HbA1c levels compared with usual care in those with type 2 diabetes, improves QoL in those with type 1 diabetes, improves diabetes self-management in those with type 1 and type 2 diabetes, and is well accepted in daily life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03588104. FUNDING: This study was funded by the European Union's Horizon 2020 Research and Innovation Programme (grant agreement number 689444).

Q-Score: development of a new metric for continuous glucose monitoring that enables stratification of antihyperglycaemic therapies.

BACKGROUND: Continuous glucose monitoring (CGM) has revolutionised diabetes management. CGM enables complete visualisation of the glucose profile, and the uncovering of metabolic 'weak points'. A standardised procedure to evaluate the complex data acquired by CGM, and to create patient-tailored recommendations has not yet been developed. We aimed to develop a new patient-tailored approach for the routine clinical evaluation of CGM profiles. We developed a metric allowing screening for profiles that require therapeutic action and a method to identify the individual CGM parameters with improvement potential. METHODS: Fifteen parameters frequently used to assess CGM profiles were calculated for 1,562 historic CGM profiles from subjects with type 1 or type 2 diabetes. Factor analysis and varimax rotation was performed to identify factors that accounted for the quality of the profiles. RESULTS: We identified five primary factors that determined CGM profiles (central tendency, hyperglycaemia, hypoglycaemia, intra- and inter-daily variations). One parameter from each factor was selected for constructing the formula for the screening metric, (the 'Q-Score'). To derive Q-Score classifications, three diabetes specialists independently categorised 766 CGM profiles into groups of 'very good', 'good', 'satisfactory', 'fair', and 'poor' metabolic control. The Q-Score was then calculated for all profiles, and limits were defined based on the categorised groups (<4.0, very good; 4.0-5.9, good; 6.0-8.4, satisfactory; 8.5-11.9, fair; and ≥12.0, poor). Q-Scores increased significantly (P <0.01) with increasing antihyperglycaemic therapy complexity. Accordingly, the percentage of fair and poor profiles was higher in insulin-treated compared with diet-treated subjects (58.4% vs. 9.3%). In total, 90% of profiles categorised as fair or poor had at least three parameters that could potentially be optimised. The improvement potential of those parameters can be categorised as 'low', 'moderate' and 'high'. CONCLUSIONS: The Q-Score is a new metric suitable to screen for CGM profiles that require therapeutic action. Moreover, because single components of the Q-Score formula respond to individual weak points in glycaemic control, parameters with improvement potential can be identified and used as targets for optimising patient-tailored therapies.

Neutralization of pathogenic beta1-receptor autoantibodies by aptamers in vivo: the first successful proof of principle in spontaneously hypertensive rats.

Autoantibodies (AABs) against the second extracellular loop of the beta1-receptor (beta1(II)-AABs) are found as a pathogenic driver in patients with idiopathic dilated cardiomyopathy, Chagas cardiomyopathy, peripartum cardiomyopathy, and myocarditis, and have been increasingly seen as a treatment target. We recently identified an aptamer (single short DNA strand) that specifically binds and neutralizes beta1(II)-AABs. Via application of this aptamer, a new treatment strategy for diseases associated with the cardio-pathogenic beta1(II)-AABs could be developed. Spontaneously hypertensive rats (SHR) positive for beta1(II)-AABs were treated five times at weekly intervals (bolus application of 2 mg/kg body weight followed by an infusion of the same amount over 20 min). SHR responded to aptamer treatment with a strong reduction in the cardio-pathogenic beta1(II)-AABs. The AABs did not substantially return within the study period. No signs for aptamer toxicity were observed by visual examination of the heart, liver, and kidney, or by measurement of plasma CK, ALT, and creatinine. The aptamer's potential for beta1(II)-AAB neutralization and consequently for cardiomyopathy treatment has been shown for the first time in vivo.

Q-Score Complements the Time in Range in the Evaluation of Short-Term Glycemic Control.

BACKGROUND AND AIMS: The Q-Score is a single-number composite metric that is constructed based on the following components: central glycemic tendency, hyperglycemia, hypoglycemia, and intra- and interday variability. Herein, we refined the Q-Score for the screening and analysis of short-term glycemic control using continuous glucose monitoring (CGM) profiles. METHODS: Continuous glucose monitoring profiles were obtained from noninterventional, retrospective cross-sectional studies. The upper limit of the Q-Score component hyperglycemia' that is, the time above target range (TAR), was adjusted from 8.9 to 10 mmol/L (n = 1562 three-day-sensor profiles). A total of 302 people with diabetes mellitus treated with intermittent CGM for ≥14 days were enrolled. The time to stability was determined via correlation-based analysis. RESULTS: There was a strong correlation between the Q-Scores of the two TARs, that is, 8.9 and 10 mmol/L (Q-ScoreTAR10 = -0.03 + 1.00 Q-ScoreTAR8.9, r = .997, p < .001). The times to stability of the Q-Score and TIR were 10 and 12 days, respectively. The Q-Score was correlated with fructosamine concentrations, the glucose management indicator (GMI), the time in range (TIR), and the glycemic risk index (GRI) (r = .698, .887, -.874, and .941), respectively. The number of Q-Score components above the target increased as the TIR decreased, from two (1.7 ± 0.9) in CGM profiles with a TIR between 70% and 80% to four (3.9 ± 0.5) in the majority of the CGM profiles with a TIR below 50%. A conversion matrix between the Q-Score and glycemic indices was developed. CONCLUSIONS: The Q-Score is a tool for assessing short-term glycemic control. The Q-Score can be translated into clinician opinion using the GRI.

The first aptamer-apheresis column specifically for clearing blood of ß1-receptor autoantibodies.

BACKGROUND: Application of immunoapheresis to eliminate pathogenic autoantibodies targeting the second extracellular loop of the ß1-receptor (ß1-AABs) is currently investigated in patients with cardiomyopathy. Aptamers (single short DNA or RNA strands) are a new class of molecules that bind to a specific target molecule. This property qualifies aptamers for potential use in the apheresis technique. We recently identified an aptamer that specifically binds to ß1-AABs, so in the present study we tested whether this aptamer could be used as a binder to prepare an apheresis column suitable for clearing ß1-AABs from rat's blood. METHODS AND RESULTS: An apheresis column was designed containing the ß1-AAB-targeting-aptamer coupled to sepharose. As tested in vitro, this column (1) binds ß1-AABs highly specifically without marked interference with common IgGs, (2) has a capacity for clearing of approximately 1L of ß1-AAB-positive serum and (3) can be completely regenerated for subsequent use. Using the column for extracorporeal apheresis of spontaneously hypertensive rats (SHR) positive for both ß1-AABs and muscarinic 2-receptor autoantibodies (M2-AABs), only ß1-AABs were removed. In a follow-up of 9 weeks, recurrence of ß1-AABs in the blood of SHR could not be detected. CONCLUSIONS: For the first time, a newly designed apheresis column with a ß1-AAB specific aptamer as a binder was successfully used to eliminate ß1-AABs from SHR blood.

Patient-Tailored Decision Support System Improves Short- and Long-Term Glycemic Control in Type 2 Diabetes.

BACKGROUND: The increasing prevalence of type 2 diabetes mellitus (T2D) and specialist shortage has caused a healthcare gap that can be bridged by a decision support system (DSS). We investigated whether a diabetes DSS can improve long- and/or short-term glycemic control. METHODS: This is a retrospective observational cohort study of the Diabetiva program, which offered a patient-tailored DSS using Karlsburger Diabetes-Management System (KADIS) once a year. Glycemic control was analyzed at baseline and after 12 months in 452 individuals with T2D. Time in range (TIR; glucose 3.9-10 mmol/L) and Q-Score, a composite metric developed for analysis of continuous glucose profiles, were short-term and HbA1c long-term measures of glycemic control. Glucose variability (GV) was also measured. RESULTS: At baseline, one-third of patients had good short- and long-term glycemic control. Q-Score identified insufficient short-term glycemic control in 17.9% of patients with HbA1c <6.5%, mainly due to hypoglycemia. GV and hyperglycemia were responsible in patients with HbA1c >7.5% and >8%, respectively. Application of DSS at baseline improved short- and long-term glycemic control, as shown by the reduced Q-Score, GV, and HbA1c after 12 months. Multiple regression demonstrated that the total effect on GV resulted from the single effects of all influential parameters. CONCLUSIONS: DSS can improve short- and long-term glycemic control in individuals with T2D without increasing hypoglycemia. The Q-Score allows identification of individuals with insufficient glycemic control. An effective strategy for therapy optimization could be the selection of individuals with T2D most at need using the Q-Score, followed by offering patient-tailored DSS.

DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats.

GIP metabolite [GIP (3-42)] and GLP-1 metabolite [GLP-1 (9-36) amide] have been reported to differ with regard to biological actions. Systemic DPP-4 inhibition can therefore reveal different actions of GIP and GLP-1. In catheter wearing Wistar rats, insulinotropic effects of equipotent doses of GIP (2.0 nmol/kg) and GLP-1 (7-36) amide (4.0 nmol/kg) and vehicle were tested in the absence/presence of DPP-4 inhibition. Blood glucose and insulin were frequently sampled. DPP-4 inhibitor was given at -20 min, the incretin at -5 min and the intravenous glucose tolerance test (0.4 g glucose/kg) commenced at 0 min. G-AUC and I-AUC, insulinogenic index and glucose efflux, were calculated from glucose and insulin curves. Systemic DPP-4 inhibition potentiated the acute GIP incretin effects: I-AUC (115±34 vs. 153±39 ng·min/ml), increased the insulinogenic index (0.74±0.24 vs. 0.99±0.26 ng/mmol), and improved glucose efflux (19.8±3.1 vs. 20.5±5.0 min⁻¹). The GLP-1 incretin effects were diminished: I-AUC (124±18 vs. 106±38 ng·min/ml), the insulinogenic index was decreased (0.70±0.18 vs. 0.50±0.19 ng/mmol), and glucose efflux declined (14.9±3.1 vs. 11.1±3.7 min⁻¹). GLP-1 and GIP differ remarkably in their glucoregulatory actions in healthy rats when DPP-4 is inhibited. These previously unrecognized actions of DPP-4 inhibitors could have implications for future use in humans.

A Predictive Model-Based Decision Support System for Diabetes Patient Empowerment.

The main objective of POWER2DM is to develop and validate a personalized self-management support system (SMSS) for T1 and T2 diabetes patients that combines and integrates i) a decision support system (DSS) based on leading European predictive personalized models for diabetes interlinked with predictive computer models, ii) automated e-coaching functionalities based on Behavioral Change Theories, and iii) real-time Personal Data processing and interpretation. The SMSS offers a guided workflow based on treatment goals and activities where a periodic review evaluates the patients progress and provides detailed feedback on how to improve towards a healthier, diabetes appropriate lifestyle.

Model-Based Tool for Personalized Adjustment of Basal Insulin Supply in Patients With Intensified Conventional Insulin Therapy.

BACKGROUND: The decisive factor in successful intensive insulin therapy is the ability to deliver need-based-adjusted nutrition-independent insulin dosages at the closest possible approximation to the physiological insulin level. Because this basal insulin requirement is strongly influenced by the patient's lifestyle, its subtlety is of great importance. This challenge is very different between patients with type 1 diabetes and those with insulin-dependent type 2 diabetes. Furthermore, it is more difficult to finetune a basal insulin dosage with intensified conventional insulin therapy (ICT), due to delayed insulin delivery, compared to insulin pump therapy, which provides continuous delivery of small doses of exclusively short-acting insulin. In all cases, the goal is to achieve an optimal basal delivery rate. METHOD: We hypothesized that this goal could be achieved with a modeling tool that determined the optimal basal insulin supply based on the patient's anamnestic data and monitored glucose values. This type of modeling tool has been used in health insurance programs in Germany to improve insulin control in patients that receive ICT. RESULTS: Our retrospective data analysis showed that this modeling tool provided a significant improvement in metabolic control, significant reductions in HbA1c and Q scores, and improved time-in-range values, with reduced daily insulin levels. CONCLUSION: The model-based basal rate test could provide additional data of the actual effect of the basal insulin adjustment in intensified insulin treated diabetes to the physician or treatment team.

Dominance of cytokine- over FasL-induced impairment of the mitochondrial transmembrane potential (Deltapsim) in the pancreatic beta-cell line NIT-1.

Mitochondria of pancreatic beta-cells are potential targets of intrinsic and extrinsic apoptotic pathways in the autoimmune pathogenesis of type 1 diabetes. We aimed to investigate whether cytokine- and FasLigand (FasL)-induced apoptosis is associated with impaired mitochondrial transmembrane potential (Deltapsim) in the pancreatic beta-cell line NIT-1. NIT-1 cells were exposed to the interleukin-1beta/interferon-gamma (IL-1beta/IFN-gamma) cytokine combination to induce apoptosis in vitro. Low concentrations of cytokines resulted in Deltapsim impairment, and increasing concentrations had only a minor additional effect. Treatment with the inducible nitric oxide synthase (iNOS) inhibitor Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME) prevented cytokine-mediated Deltapsim impairment, implying that cytokines affect Deltapsim via nitric oxide. The broad-spectrum caspase inhibitor Z-VAD(Ome)-FMK (ZVAD) revealed dichotomic actions. In the presence of ZVAD, cytokine-induced nitrite generation was increased but cell death and Deltapsim impairment were reduced. Deltapsim impairment was also reduced by inhibitors of caspases 1, 6 and 8. Induction of Fas by IL-1beta/IFN-gamma coupled with activation by Super-FasL augmented cytokine-induced cell death. We observed a clear dominance of cytokine- over FasL-induced effects on Deltapsim. Our findings show that IL-1beta/IFN-gamma cytokines have a strong effect to impair Deltaym and prime beta-cells for apoptosis via the intrinsic pathway mediated by iNOS and caspases. Furthermore, at least in NIT-1 cells, the extrinsic FasL/Fas pathway has only a minor additive effect on cytokine-induced Deltapsim impairment.

Applications of Variability Analysis Techniques for Continuous Glucose Monitoring Derived Time Series in Diabetic Patients.

Methods from non-linear dynamics have enhanced understanding of functional dysregulation in various diseases but received less attention in diabetes. This retrospective cross-sectional study evaluates and compares relationships between indices of non-linear dynamics and traditional glycemic variability, and their potential application in diabetes control. Continuous glucose monitoring provided data for 177 subjects with type 1 (n = 22), type 2 diabetes (n = 143), and 12 non-diabetic subjects. Each time series comprised 576 glucose values. We calculated Poincaré plot measures (SD1, SD2), shape (SFE) and area of the fitting ellipse (AFE), multiscale entropy (MSE) index, and detrended fluctuation exponents (α1, α2). The glycemic variability metrics were the coefficient of variation (%CV) and standard deviation. Time of glucose readings in the target range (TIR) defined the quality of glycemic control. The Poincaré plot indices and α exponents were higher (p < 0.05) in type 1 than in the type 2 diabetes; SD1 (mmol/l): 1.64 ± 0.39 vs. 0.94 ± 0.35, SD2 (mmol/l): 4.06 ± 0.99 vs. 2.12 ± 1.04, AFE (mmol2/l2): 21.71 ± 9.82 vs. 7.25 ± 5.92, and α1: 1.94 ± 0.12 vs. 1.75 ± 0.12, α2: 1.38 ± 0.11 vs. 1.30 ± 0.15. The MSE index decreased consistently from the non-diabetic to the type 1 diabetic group (5.31 ± 1.10 vs. 3.29 ± 0.83, p < 0.001); higher indices correlated with lower %CV values (r = -0.313, p < 0.001). In a subgroup of type 1 diabetes patients, insulin pump therapy significantly decreased SD1 (-0.85 mmol/l), SD2 (-1.90 mmol/l), and AFE (-16.59 mmol2/l2), concomitantly with %CV (-15.60). The MSE index declined from 3.09 ± 0.94 to 1.93 ± 0.40 (p = 0.001), whereas the exponents α1 and α2 did not. On multivariate regression analyses, SD1, SD2, SFE, and AFE emerged as dominant predictors of TIR (ß = -0.78, -1.00, -0.29, and -0.58) but %CV as a minor one, though α1 and MSE failed. In the regression models, including SFE, AFE, and α2 (ß = -0.32), %CV was not a significant predictor. Poincaré plot descriptors provide additional information to conventional variability metrics and may complement assessment of glycemia, but complexity measures produce mixed results.

Chronic hyperglycemia but not glucose variability determines HbA1c levels in well-controlled patients with type 2 diabetes.

To determine the relationships between HbA1c, characteristics of hyperglycemia and glycemic variability in well-controlled type 2 diabetes (HbA1c<7.0%), we studied 63 primary-care patients (36 men and 27 women), aged 34-75 years, with type 2 diabetes for 2-32 years using a continuous glucose monitoring system (CGMS) and standardized meal test (MMT). Duration of hyperglycemia (>8.0 mmol/l), standard deviation score (S.D.-score) and mean amplitude of glycemic excursions (MAGE) were analyzed from CGMS data and postprandial glucose during MMT (PPG(MMT)). Patients were hyperglycemic for 5.7h/day (median), experienced 4.1 hyperglycemic episodes/day, and 78% exceeded PPG levels of 8.0 mmol/l. HbA1c, though associated with the extent of hyperglycemia (r=0.40, p<0.001), failed to correlate with S.D.-score and MAGE. Multiple regression analysis demonstrated that HbA1c was predicted only by fasting glucose (R(2)=0.24, p<0.001) but neither by PPG(MMT), duration of hyperglycemia, S.D.-score nor MAGE. CGMS and meal test provide the tools for complete characterization of glycemia in type 2 diabetes. In well-controlled type 2 diabetes, HbA1c correlates with chronic hyperglycemia but not with glucose variability. Our data suggest that chronic sustained hyperglycemia and glucose fluctuations are two independent components of dysglycemia in diabetes.

Accuracy Evaluation of a CE-Marked Glucometer System for Self-Monitoring of Blood Glucose With Three Reagent Lots Following ISO 15197:2013.

Continuous standardized verification of the accuracy of blood glucose meter systems for self-monitoring after their introduction into the market is an important clinically tool to assure reliable performance of subsequently released lots of strips. Moreover, such published verification studies permit comparison of different blood glucose monitoring systems and, thus, are increasingly involved in the process of evidence-based purchase decision making.

Incidence trends of type 1 diabetes before and after the reunification in children up to 14 years of age in Saxony, Eastern Germany.

AIMS: The aim of this study was to analyze the incidence rates of type 1 diabetes in Saxony before and after the German reunification. METHODS: The study examined two registries: one until 1990 and one since 1999. Only patients under 15 years of age with type 1 diabetes and living in Saxony were included in the study. Standardized incidence rates were described based on direct age standardization procedures using the Standard European Population for each calendar year between the observation periods 1982-1989 and 1999-2014. Age was grouped into three classes: 0-4, 5-9 and 10-14 years of age. Incidence data were presented as age-standardized incidence rates per 100,000 person-years (PY) with 95% confidence intervals [CI]. Joinpoint regression was used for trend analyses and Poisson regression was used to adjust for the effects of age and sex on the incidence. RESULTS: A total number of 2,092 incident cases of type 1 diabetes (1,109 males; 983 females) were included. The age-standardized incidence rates of type 1 diabetes per 100,000 PY was 7.9 [95%CI 6.8; 8.9] in the period from 1982-1989 and 20.1 [95%CI 14.0; 26.1] in the period from 1999-2014. The yearly increase in incidence over the entire time period (1982-2014) was 4.3% according to the average annual percent change (AAPC) method, and estimated to be 4.4% [95% CI 4.0; 4.8%] using a Poisson regression model adjusting for sex and age group. CONCLUSION: In this study, a significantly increasing incidence of type 1 diabetes was observed after reunification. In future studies it would be interesting to follow up on the question of which environmental and lifestyle factors could be causing the increasing type 1 diabetes incidence.

Aptamer BC007 for neutralization of pathogenic autoantibodies directed against G-protein coupled receptors: A vision of future treatment of patients with cardiomyopathies and positivity for those autoantibodies.

Cardiomyopathies such as idiopathic dilated cardiomyopathy (DCM), Chagas' cardiomyopathy and Peripartum cardiomyopathy present with autoantibodies against G-protein coupled receptors (GPCR-AABs) that agonistically activate their receptors. For the treatment of "agonistic autoantibody diseases" and in particular DCM, the removal of the GPCR-AABs by immunoadsorption (IA) has been studied with convincing patient benefit. To overcome cost and logistics problems of IA, the application of the aptamer BC007 for in vivo neutralization of GPCR-AABs could help. We demonstrate here, that the aptamer neutralized, in vitro, the presently known cardiovascular-pathogenic GPCR-AABs. In spontaneously hypertensive rats, the aptamer demonstrated its GPCR-AAB neutralizing potency in vivo. In the serum of DCM patients, the same GPCR-AAB reduction was achieved when patients were either immunoadsorbed or patient's serum was ex vivo treated with the aptamer. In our view, aptamer BC007 treatment in GPCR-AAB-positive patients would have a comparable benefit as that seen after IA. Not knowing all that interfering with our idea of aptamer-dependent neutralization of GPCR-AABs, the first preliminary steps have been taken for bringing the idea closer to patients.

Utility of different glycemic control metrics for optimizing management of diabetes.

The benchmark for assessing quality of long-term glycemic control and adjustment of therapy is currently glycated hemoglobin (HbA1c). Despite its importance as an indicator for the development of diabetic complications, recent studies have revealed that this metric has some limitations; it conveys a rather complex message, which has to be taken into consideration for diabetes screening and treatment. On the basis of recent clinical trials, the relationship between HbA1c and cardiovascular outcomes in long-standing diabetes has been called into question. It becomes obvious that other surrogate and biomarkers are needed to better predict cardiovascular diabetes complications and assess efficiency of therapy. Glycated albumin, fructosamin, and 1,5-anhydroglucitol have received growing interest as alternative markers of glycemic control. In addition to measures of hyperglycemia, advanced glucose monitoring methods became available. An indispensible adjunct to HbA1c in routine diabetes care is self-monitoring of blood glucose. This monitoring method is now widely used, as it provides immediate feedback to patients on short-term changes, involving fasting, preprandial, and postprandial glucose levels. Beyond the traditional metrics, glycemic variability has been identified as a predictor of hypoglycemia, and it might also be implicated in the pathogenesis of vascular diabetes complications. Assessment of glycemic variability is thus important, but exact quantification requires frequently sampled glucose measurements. In order to optimize diabetes treatment, there is a need for both key metrics of glycemic control on a day-to-day basis and for more advanced, user-friendly monitoring methods. In addition to traditional discontinuous glucose testing, continuous glucose sensing has become a useful tool to reveal insufficient glycemic management. This new technology is particularly effective in patients with complicated diabetes and provides the opportunity to characterize glucose dynamics. Several continuous glucose monitoring (CGM) systems, which have shown usefulness in clinical practice, are presently on the market. They can broadly be divided into systems providing retrospective or real-time information on glucose patterns. The widespread clinical application of CGM is still hampered by the lack of generally accepted measures for assessment of glucose profiles and standardized reporting of glucose data. In this article, we will discuss advantages and limitations of various metrics for glycemic control as well as possibilities for evaluation of glucose data with the special focus on glycemic variability and application of CGM to improve individual diabetes management.