Index of Plantar Pressure Alters with Prolonged Diabetes Duration Abstract Introduction Diabetic foot ulcers develop with deviations in the distribution of plantar pressure. It is difficult to interpret any alteration in plantar pressure under different conditions of type 2 diabetes mellitus (T2DM). The aim of this study was to gain a better insight into the variations in plantar pressure with increased duration of diabetes. Methods Plantar pressure was examined in 1196 participants with or without T2DM. Subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) were assigned to control groups, and those with T2DM were divided into five groups according to diabetes duration (< 2 years, 2–5 years, 5–10 years, 10–15 years, and > 15 years). The clinical characteristics, plantar peak pressure, and pressure–time integral (PTI) were compared among the seven study groups, and factors associated with peak pressure and the PTI were analyzed. Results At the hallux, peak pressure exhibited an upward trend in patients with T2DM within 5 years of diabetes duration, followed by a distinct downward slope with further progression of the disease (trend analysis, p  < 0.05). An uneven distribution of peak pressure was found at other locations, but this unevenness was ultimately lower than that in the two control groups (p  < 0.05). No obvious trend was noted for PTI among patients with different diabetes duration; however, those with diabetes for > 10 years manifested a significantly sharper increase in the PTI at the metatarsus (11.63 Ns/cm2, p  < 0.05) and heel (14.12 Ns/cm2, p  < 0.05) than at the hallux (8.76 Ns/cm2). A fluctuation in the PTI was also detected at the hallux and midfoot of diabetes patients, which was broadly flat when compared with that of the two control groups. The stepwise multiple regression analysis revealed that the variation in plantar pressure was independently associated with age, body mass index, and vibration perception threshold (VPT) (p  < 0.05). Conclusions There would appear to be an association between longer diabetes duration and decreased peak pressure for the hallux, suggesting that individuals with diabetes for > 10 years will have an increased PTI for the metatarsus and heel. The reduced pressure on the hallux is believed to be transferred to the metatarsus. Age, BMI, and VPT are distinct risk factors of abnormal plantar pressure.

Correction to: Cardiac Autonomic Neuropathy in Obesity, Metabolic Syndrome and Prediabetes: A Narrative Review The authors of the article would like to amend the article title to ‘Cardiac Autonomic Neuropathy in Obesity, Metabolic Syndrome and Prediabetes: A Narrative Review’.

Prevalence of Established Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus in the UK Abstract Introduction The results of recently completed cardiovascular outcomes trials in patients with type 2 diabetes mellitus (T2DM) suggest that sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide (GLP) 1 receptor agonists have enhanced cardioprotective properties in patients with established cardiovascular disease (eCVD), but to a lesser degree in those without eCVD. SGLT2 inhibitors appear to be particularly beneficial in patients with heart failure. As recent data for the UK are lacking, we undertook to identify the percentage of T2DM patients with eCVD and heart failure in the UK. Methods This was a retrospective cohort study that utilized the Clinical Practice Research Datalink (CPRD) database in the UK. We included de-identified adult patients with T2DM with at least one encounter in the CPRD database between 1 January 2018 and 31 December 2018 in the analysis and extracted the full health records of these patients. eCVD was defined as myocardial infarction, stroke, unstable angina pectoris, coronary artery disease and peripheral artery disease. We further assessed the number of patients with heart failure. Results From the total of 148,803 patients with T2DM analyzed (53% were male; mean age was 65 years), 52,601 (35.4%) suffered from eCVD and 8650 (5.8%) suffered from heart failure (73.7% of patients with heart failure overlap with those with atherothrombotic eCVD). Glycated hemoglobin levels of < 7% were attained by 49.5% of patients (with eCVD, 49.7%; without eCVD, 49.3%) (p < 0.001). Conclusion Approximately one-third of patients with T2DM in the UK have concomitant CVD. Funding Merck Sharp & Dohme Corp., a subsidiary Merck & Co., Inc., Kenilworth, NJ, USA.

Thyroid Dysfunction and Type 2 Diabetes Mellitus: Screening Strategies and Implications for Management Abstract Diabetes mellitus (DM) and thyroid dysfunction (TD) often tend to coexist in patients. Both hypothyroidism and hyperthyroidism are more common in type 2 diabetes mellitus (T2DM) patients than in their nondiabetic counterparts. Current guidelines are neither clear nor specific about the frequency of thyroid function monitoring in T2DM patients. Circulating thyroid hormones affect several different organs and cells, have a major impact on glucose, lipid, and protein metabolism, and can worsen glycaemic control in T2DM. Hyperthyroidism and thyrotoxicosis can worsen subclinical DM and cause hyperglycaemia in T2DM patients, increasing the risk of diabetic complications. T2DM reduces thyroid-stimulating hormone levels and impairs the conversion of thyroxine (T4) to triiodothyronine (T3) in the peripheral tissues. Poorly managed T2DM can lead to insulin resistance and hyperinsulinaemia, which causes thyroid tissue proliferation and increases nodule formation and goitre size. In addition, while metformin can be beneficial in both T2DM and TD patients, other antidiabetics such as sulfonylureas, pioglitazone, and thiazolidinediones can negatively impact TD. Antithyroid drugs such as methimazole can impair glycaemic control in T2DM patients. Thyrovigilance in T2DM patients and diabetovigilance in TD patients may therefore be necessary to facilitate individualized care and management. Funding: Abbott India Ltd.

Correction to: A Practical Guide to Delivering Nutritional Advice to People with Diabetes In the original publication, part of acknowledgement text was missing and it should read

Correction to: SGLT2 Inhibitors: Cardiovascular Benefits Beyond HbA1c—Translating Evidence into Practice In the original publication, Table 2 note was incorrectly published as “SGLT2i therapies may be initiated in people with eGFR 60 mL/min/1.73 m2. Individuals already treated with canagliflozin or empagliflozin who demonstrate renal decline may continue treatment until eGFR reaches < 45 mL/min/1.73 m2”.

Fast-Acting Insulin Aspart: The Rationale for a New Mealtime Insulin Abstract Attenuating postprandial hyperglycaemia is a critical factor in the achievement of optimal glucose control. Prandial insulin analogues have been developed to replicate the physiology of normal endogenous insulin secretion and action, with the aim of limiting postprandial glucose excursions. There is still, however, a significant unmet need, with many people failing to achieve desired glycaemic control targets despite the current armamentarium of prandial insulin analogues. Such insulins have a delayed onset and a longer duration of action than endogenous insulin production. There has been considerable focus on attempts to accelerate the time–action profile of prandial exogenous insulin in order to produce a more physiological profile. One such approach is to modify the insulin formulation. Fast-acting insulin aspart is a modified formulation of insulin aspart containing niacinamide and l-arginine. It has an earlier onset of action than aspart. In an extensive trial programme, this faster aspart demonstrated similar HbA1c reductions to those achieved with aspart but superior postprandial glucose reductions, with no increase in hypoglycaemia. Furthermore, administration of faster aspart up to 20 min after the start of a meal permitted similar glucose control to aspart given preprandially. These data, taken in totality, illustrate the potential role of faster insulin aspart in clinical practice.

Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitors in East Asians with Type 2 Diabetes: A Systematic Review and Meta-Analysis Abstract Introduction The aim of this study was to assess the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in East Asians with type 2 diabetes mellitus (T2DM). Methods A literature search that focused primarily on the PubMed, Embase, and Cochrane library databases was performed. All randomized controlled trials (RCTs) which satisfied the inclusion and exculsion criteria were eligible to be included in the meta-analysis. Risk ratios (RRs) and weighted mean differences (WMDs) were used as statistical indicators for the analysis of dichotomous data and continuous outcomes, respectively. Pooled estimates were obtained using random-effects models in RevMan version 5.3.5. Results Thirty-three RCTs (8496 randomized patients) fulfilled the eligibility criteria for inclusion in the meta-analysis. The meta-analysis showed that, compared with the control group, the use of SGLT2 inhibitors improved both glycated hemoglobin (HbA1c) in patients (WMD − 0.73%; 95% confidence interval [CI] − 0.84, − 0.61) and the percentage of patients with HbA1c  < 7% (RR 2.33; 95% CI 1.74, 3.12); lowered both fasting plasma glucose (WMD − 28.47 mg/dl; 95% CI − 32.86, − 24.08) and postprandial glucose (WMD − 52.32 mg/dl; 95% CI − 67.67, − 39.96); reduced body weight (WMD − 1.73 kg; 95% CI − 2.28, − 1.17); and did not increase the risk of hypoglycemia (RR 1.27; 95% CI 0.89, 1.82) and urinary tract infections (RR 0.93; 95% CI 0.68, 1.27). However, SGLT2 inhibitors did increase the risk of genital tract infections (GTIs) (RR 1.73; 95% CI 1.02, 2.96). The stratified analysis showed that patients with higher HbA1c levels at baseline may achieve a greater improvement in HbA1c after taking SGLT2 inhibitors, while those with higher body weight or a longer history of diabetes may have an increased risk of developing GTIs. Conclusion Current research suggests that SGLT2 inhibitors have favorable efficacy and safety in East Asian patients with T2DM.

An Evaluation System of Fundus Photograph-Based Intelligent Diagnostic Technology for Diabetic Retinopathy and Applicability for Research Abstract Introduction In April 2018, the US Food and Drug Administration (FDA) approved the world’s first artificial intelligence (AI) medical device for detecting diabetic retinopathy (DR), the IDx-DR. However, there is a lack of evaluation systems for DR intelligent diagnostic technology. Methods Five hundred color fundus photographs of diabetic patients were selected. DR severity varied from grade 0 to 4, with 100 photographs for each grade. Following that, these were diagnosed by both ophthalmologists and the intelligent technology, the results of which were compared by applying the evaluation system. The system includes primary, intermediate, and advanced evaluations, of which the intermediate evaluation incorporated two methods. Main evaluation indicators were sensitivity, specificity, and kappa value. Results The AI technology diagnosed 93 photographs with no DR, 107 with mild non-proliferative DR (NPDR), 107 with moderate NPDR, 108 with severe NPDR, and 85 with proliferative DR (PDR). The sensitivity, specificity, and kappa value of the AI diagnoses in the primary evaluation were 98.8%, 88.0%, and 0.89, respectively. According to method 1 of the intermediate evaluation, the sensitivity of AI diagnosis was 98.0%, specificity 97.0%, and the kappa value 0.95. In method 2 of the intermediate evaluation, the sensitivity of AI diagnosis was 95.5%, the specificity 99.3%, and kappa value 0.95. In the advanced evaluation, the kappa value of the intelligent diagnosis was 0.86. Conclusions This article proposes an evaluation system for color fundus photograph-based intelligent diagnostic technology of DR and demonstrates an application of this system in a clinical setting. The results from this evaluation system serve as the basis for the selection of scenarios in which DR intelligent diagnostic technology can be applied.

What Next After Metformin? Thinking Beyond Glycaemia: Are SGLT2 Inhibitors the Answer? Abstract The prevalence of type 2 diabetes continues to increase, along with a proliferation of glucose-lowering treatment options. There is universal agreement in the clinical community for the use of metformin as the first-line glucose-lowering therapy for the majority of patients. However, controversy exists regarding the choice of second-line therapy once metformin is no longer effective. The most recent treatment consensus focuses on the presence of cardiovascular disease, heart failure or kidney disease as a determinant of therapy choice. The majority of patients in routine practice, however, do not fall into such categories. Heart failure and kidney disease represent significant clinical and cost considerations in patients with type 2 diabetes and have a close pathophysiological association. Recent data has illustrated that sodium-glucose transporter 2 (SGLT2) inhibitor therapy can reduce the burden of heart failure and the progression of renal disease across a wide range of patients including those with and without established disease, supported by an increased understanding of the mechanistic effects of these agents. Furthermore, there is growing evidence to illustrate the overall safety profile of this class of agents and support the benefit–risk profile of SGLT2 inhibitors as a preferred option following metformin monotherapy failure, with respect to both kidney disease progression and heart failure outcomes.