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Diabetic neuropathy (DN) is a common complication of diabetes and can be either painful or non‐painful. It is challenging to diagnose this complication, as no biomarker or clear consensus on the clinical definition of either painful or non‐painful DN exists. Hence, a hierarchical classification has been developed categorizing the probability of the diagnosis into: possible, probable or definite, based on the clinical presentation of symptoms and signs. Pain is a warning signal of tissue damage, and non‐painful DN therefore represents a clinical and diagnostic challenge because it often goes unnoticed until irreversible nerve damage has occurred. Simple clinical tests seem to be the best for evaluation of DN in the general care for diabetes. Screening programs at regular intervals might be the most optimal strategy for early detection and interventions to possibly prevent further neuronal damage and to lower the economic burden of this complication. The present review addresses the clinical characteristics of painful and non‐painful diabetic polyneuropathy and the possibilities for diagnosing these conditions. As the majority of patients with type 2 diabetes are treated in general practice, we focused on proposals for simple assessments of diabetic polyneuropathy outside specialized hospital clinics.

Conventional clinical markers guide cardiovascular risk stratification; however, continuous glucose monitoring (CGM) data remain absent from prediction models. A synthesis of the current literature is needed to clarify the prognostic relevance of CGM data for cardiovascular outcomes in people with diabetes. This scoping review aimed to identify published studies examining (1) the associations between glycemic control and cardiovascular outcomes and (2) the predictive value of CGM-derived metrics in cardiovascular risk assessment. MEDLINE and Embase were searched from inception to March 11, 2025, for peer-reviewed, original research that included CGM-derived metrics and cardiovascular disease (CVD) outcomes. Two reviewers screened the records independently. A total of 53 studies were identified. These studies focused on type 1 diabetes, type 2 diabetes, both diabetes types, or prediabetes. Clinical outcomes were examined in 16 studies, while subclinical outcomes were assessed in 40 studies. Of the 53 studies, 47 were cross-sectional studies and 6 were longitudinal studies. All studies were association studies, and 3 included secondary analyses of predictive performance. However, none applied machine learning-based methods. A wide range of CGM-derived metrics and CVD outcomes, both clinical and subclinical, were studied in the literature. Overall, the findings were inconsistent across studies, and this was likely due to methodological weaknesses such as underpowered analyses. Time-in-range was both the most studied metric and associated with cardiovascular risk in the largest single study. Only the mean amplitude of glycemic excursions was consistently associated with CVD in most studies investigating this metric, when using statistical significance as a pragmatic indicator of consistency across heterogeneous studies. The prognostic value of CGM-derived metrics for CVD outcomes is currently underexplored. Longitudinal prediction studies on clinical CVD outcomes, leveraging the potential of routinely collected CGM data, are needed.

ObjectiveTo ascertain the cross-sectional association between cardiovascular autonomic dysfunction and arterial stiffness across glucose metabolism status.Research design and methodsWe performed a cross-sectional analysis of participants of the Maastricht study. Cardiovascular autonomic function was based on heart rate variability (HRV) indices from 24-hour ECG recordings and summarized in z-scores for time and frequency domains. Aortic and carotid stiffness were assessed by carotid-femoral pulse wave velocity (PWV) and carotid artery distensibility (CD), respectively. We used multiple linear regression to study the associations and adjusted for demographic and lifestyle factors and a range of cardiovascular risk factors. We tested for effect modification of the associations by glucose metabolism status.ResultsPWV and CD measures were available in 3673 and 1802 participants, respectively (median (25th; 75th percentile) age: 60 years (53; 66), 51% women, 20% type 2 diabetes by design. Participants with lower HRV had higher aortic stiffness. Per SD lower time-domain and frequency-domain HRV z-scores were associated with 2.8% (95% CI 2.1% to 3.4%) and 2.8% (95% CI 2.1% to 3.5%) higher PWV, respectively. Similar trends were observed for carotid stiffness, with 3.2% (95% CI 1.4% to 5.0%) and 3.1% (95% CI 1.2% to 5.0%) lower CD per SD lower time-domain and frequency-domain HRV, respectively. The magnitude of these associations was higher in groups with prediabetes and type 2 diabetes compared with those with normal glucose metabolism, with evidence of effect modification by glucose metabolism status (p value for interaction: <0.01 for prediabetes and <0.05 to <0.10 for type 2 diabetes, both compared with normal glucose metabolism).ConclusionCardiovascular autonomic dysfunction is associated with higher aortic and carotid stiffness, especially in people with dysglycemia.

Background Peripheral and central hemodynamic indices are modifiable by lifestyle and medical intervention. We aimed to determine the long-term effect of intensive multifactorial treatment on peripheral and central hemodynamic indices among people with screen-detected diabetes. Methods Between 2001 and 2006, people with screen-detected type 2 diabetes were included in the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION) trial (NCT00237549, ClinicalTrials.gov). In the Danish arm, participants were invited to a clinical examination in 2015–2016, 13 years after inclusion and 8 years after trial-end. Out of 586 eligible participants who attended the clinical examination, 411 had a valid examination of central and peripheral hemodynamic indices (242 received intensive treatment and 169 received routine care). Carotid-femoral pulse wave velocity (cfPWV), central blood pressure and augmentation index were assessed by applanation tonometry. We used mixed-effect models to examine the intervention effect adjusting for cluster randomization and heart rate. Results Randomization to intensive treatment during the trial-period was associated with a 0.58 m/s lower cfPWV (95% CI − 1.09 to − 0.06) at follow-up. Adjustment for blood pressure attenuated the association. Differences between intervention groups for central augmentation index were − 1.25% (95% CI: − 3.28 to 0.78), central pulse pressure − 1.74 mmHg (95% CI − 4.79 to 1.31), central systolic blood pressure − 3.06 mmHg (− 7.08 to 0.96), and central diastolic blood pressure − 1.70 mmHg (− 3.74 to 0.34). Conclusions Intensive multifactorial treatment of screen-detected type 2 diabetes has a sustained positive effect on aortic stiffness measured by cfPWV. Although all estimates pointed in favor of intensive treatment, we observed no clear beneficial effect on other hemodynamic indices.