The Fast-Glycator Phenotype, Skin Advanced Glycation End Products, and Complication Burden Among People With Type 1 Diabetes.

OBJECTIVE: Existence of a fast-glycator phenotype among people with type 1 diabetes (T1D) is debated. Routine use of glucose sensors allows the comparison of long-term average glucose levels with laboratory HbA1c values. We herein evaluated whether participants with T1D and HbA1c values higher than their glucose management indicator (GMI) had greater accumulation of advanced glycation end products (AGEs) and chronic complications. RESEARCH DESIGN AND METHODS: We included participants with T1D using the intermittently scanned continuous glucose monitoring system consecutively for at least 90 days and having a laboratory-determined HbA1c at the end of observation. Skin AGEs were estimated using the skin autofluorescence (SAF) method. The complication burden was assessed by a standardized screening. The fast-glycator phenotype was defined as having a GMI to HbA1c ratio <0.9. RESULTS: We included 135 individuals with T1D (58% men; mean age, 44.4 years) with a mean diabetes duration of 21 years and a mean HbA1c value of 7.7%. Thirty (22.2%) were defined as having the fast-glycator phenotype. As expected, fast glycators had higher HbA1c (8.6% vs. 7.5%; P < 0.001) with similar 90-day mean glucose level (172 vs. 168 mg/dL; P = 0.52). Fast glycators had higher SAF than did other participants (2.5 vs. 2.1 arbitrary units; P = 0.005) and had a significantly higher prevalence of dyslipidemia (73% vs. 44%; P = 0.005), macroangiopathy (38% vs. 9%; P = 0.001), albuminuria (25% vs. 7%; P = 0.038), and retinopathy (61% vs. 38%; P = 0.022). After adjusting for age and dyslipidemia, the fast-glycator phenotype remained significantly associated with macroangiopathy (odds ratio 3.72; 95% CI 1.22-11.4). CONCLUSIONS: In T1D, a fast-glycator phenotype defined by the GMI to HbA1c ratio is characterized by elevated skin AGEs and is associated with the complication burden.

Hyperglycemia, Reduced Hematopoietic Stem Cells, and Outcome of COVID-19.

Admission hyperglycemia has emerged worldwide as a predictor of poor coronavirus disease 2019 (COVID-19) outcome. Hyperglycemia leads to a defect in circulating hematopoietic stem/progenitor cells (HSPCs), which, in turn, predicts diabetic complications. Here, we explored whether reduced HSPCs mediated at least part of the prognostic effect of hyperglycemia on COVID-19 outcome. We found that patients with COVID-19 (n = 100) hospitalized in a nonintensive setting displayed dramatically (50-60%) reduced levels of HSPCs measured by flow cytometry as CD34+, CD34+CD45dim, or CD34+CD133+ cells, compared with control subjects (n = 595). This finding was highly significant (all P < 10-10) after multivariable adjustment, or manual 1:1 patient match, or propensity score matching. Admission hyperglycemia (≥7.0 mmol/L) was present in 45% of patients, was associated with a significant further ∼30% HSPCs reduction, and predicted a 2.6-fold increased risk of the primary outcome of adverse COVID-19 course (admittance to the intensive care unit or death). Low HSPCs were also associated with advanced age, higher peak C-reactive protein, and neutrophil-to-lymphocyte ratio. Independently from confounders, 1 SD lower CD34+ HSPCs was associated with a more than threefold higher risk of adverse outcome. Upon formal analysis, reduction of HSPCs was a significant mediator of the admission hyperglycemia on COVID-19 outcome, being responsible for 28% of its prognostic effect.

Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration.

AIMS: We investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with COVID-19 severity independently from confounders. METHODS: We retrospectively analyzed data on patients with COVID-19 hospitalized between February and April 2020 in an outbreak hospital in North-East Italy. Pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. Newly-diagnosed diabetes was defined by HbA1c and fasting glucose. The primary outcome was a composite of ICU admission or death. RESULTS: 413 subjects were included, 107 of whom (25.6%) had diabetes, including 21 newly-diagnosed. Patients with diabetes were older and had greater comorbidity burden. The primary outcome occurred in 37.4% of patients with diabetes compared to 20.3% in those without (RR 1.85; 95%C.I. 1.33-2.57; p < 0.001). The association was stronger for newly-diagnosed compared to pre-existing diabetes (RR 3.06 vs 1.55; p = 0.004). Higher glucose level at admission was associated with COVID-19 severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p < 0.001). Admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function. CONCLUSION: Newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of COVID-19 severity due to rapid respiratory deterioration.

Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study.

Because other coronaviruses enter the cells by binding to dipeptidyl-peptidase-4 (DPP-4), it has been speculated that DPP-4 inhibitors (DPP-4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP-4is among patients with type 2 diabetes (T2D) hospitalized for COVID-19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP-4is among matched patients with T2D in the same region. Of 403 hospitalized COVID-19 patients, 85 had T2D. The rate of exposure to DPP-4is was similar between T2D patients with COVID-19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID-19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID-19 who were on DPP-4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP-4is might affect hospitalization for COVID-19.