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People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes., (© 2020 by the American Diabetes Association.)

Objective: To evaluate the compliance with self-monitoring of blood glucose (SMBG) and the reliability of diabetes logbooks in women with gestational diabetes mellitus (GDM), as well as the associated determinants and outcomes., Research Design and Methods: We prospectively selected French-speaking women with newly diagnosed GDM who had been referred to our diabetes management program and understood SMBG principles. At the next follow-up visit, we collected SMBG results from glucose meters and logbooks. We analyzed pregnancy outcomes., Results: Data were analyzed over 13 ± 3 days in 91 women. Only 61.5% had performed ≥80% of the required tests. Poor compliance was associated with a family history of diabetes, social deprivation, and non-European origin. The average time between pre- and postprandial tests was 141 ± 20 min, with 46.5% of women performing ≥80% of postprandial measurements 100-140 min after meals. Inadequate timing was associated with ethnicity and higher HbA 1c at baseline. A total of 23.1% of women had <90% matched values in diary and meter memory, and a poor concordance was associated with a family history of diabetes. Poor adherence was associated with more preeclampsia (12.2 vs. 1.9%, P = 0.049), and inadequate postprandial test timing with a higher HbA 1c at delivery (5.3 ± 0.4 vs. 5.0 ± 0.3% [34 ± 2 vs. 31 ± 2 mmol/mol], P < 0.01), despite more frequent insulin therapy., Conclusions: Although women with GDM are considered to be highly motivated, SMBG adherence and reliability are of concern and may be associated with poor gestational prognosis, suggesting that caregivers should systematically check the glucose meter memory to improve GDM management., (© 2017 by the American Diabetes Association.)

Objective: We investigated whether glycation gap (G-Gap), an index of intracellular glycation of proteins, was associated with diabetes complications., Research Design and Methods: We measured concomitantly HbA1c and fructosamine in 925 patients with type 2 diabetes to calculate the G-Gap, defined as the difference between measured HbA1c, and fructosamine-based predicted HbA1c. Patients were explored for retinopathy, nephropathy, peripheral neuropathy, cardiac autonomic neuropathy (n = 512), and silent myocardial ischemia (n = 506)., Results: Macroproteinuria was the only complication that was associated with G-Gap (prevalence in the first, second, and third tertile of G-Gap: 2.9, 6.2, and 11.0%, respectively; P < 0.001). The G-Gap was higher in patients with macroproteinuria than in those without (1.06 ± 1.62 vs. 0.03 ± 1.30%; P < 0.0001). Because HbA1c was associated with both G-Gap (HbA1c 7.0 ± 1.4, 7.9 ± 1.4, and 10.1 ± 1.8% in the first, second, and third G-Gap tertile, respectively; P < 0.0001) and macroproteinuria (HbA1c 8.8 ± 2.2% if macroproteinuria, 8.3 ± 2.0% if none; P < 0.05), and because it could have been a confounder, we matched 54 patients with macroproteinuria and 200 patients without for HbA1c. Because macroproteinuria was associated with lower serum albumin and fructosamine levels, which might account for higher G-Gap, we calculated in this subpopulation albumin-indexed fructosamine and G-Gap; macroproteinuria was independently associated with male sex (odds ratio [OR] 3.2 [95% CI 1.5-6.7]; P < 0.01), hypertension (2.9 [1.1-7.5]; P < 0.05), and the third tertile of albumin-indexed G-Gap (2.3 [1.1-4.4]; P < 0.05) in multivariate analysis., Conclusions: In type 2 diabetic patients, G-Gap was associated with macroproteinuria, independently of HbA1c, albumin levels, and confounding factors, suggesting a specific role of intracellular glycation susceptibility on kidney glomerular changes.

Objective: We aimed to evaluate a selective screening strategy for gestational diabetes mellitus (GDM) based on the presence of risk factors: BMI ≥25 kg/m(2), age ≥35 years, family history of diabetes, personal history of GDM, or birth of a child with macrosomia., Research Design and Methods: Of 20,630 deliveries between 2002 and 2010, we selected 18,775 deliveries in women with no known diabetes and for whom all risk factors were known. GDM was universally screened and defined as fasting plasma glucose level ≥5.3 mmol/L and/or 2-h postload (75 g) glucose level ≥7.8 mmol/L., Results: The prevalence of at least one risk factor has increased since 2002 (P < 0.001) from 51.7 to 61.5%, with no change in the GDM prevalence (mean 14.4%, intention to screen). At least one risk factor was present in 58.5% of women who represented 65.3% of all those with GDM. The presence of risk factors was significantly associated with GDM (odds ratio 1.4 [95% CI 1.3-1.5], P < 0.001) and with GDM-related events (preeclampsia/large for gestational age/dystocia) (P < 0.001) with the following incidences: no GDM/no risk factor 8.8%, no GDM/risk factor 11.1%, GDM/no risk factor 16.7%, and GDM/risk factor 18.2%., Conclusions: The presence of risk factors increased during the last decade. This condition is predictive of GDM and GDM-related events. However, a selective screening would lead to missing one-third of the women with GDM who, even without risk factors, had more events than women without GDM. Therefore, these data stand against the present selective screening currently proposed in the French guidelines.

Objective: To evaluate if silent myocardial ischemia (SMI) and silent coronary artery disease (CAD) provide significant additional value to routine cardiovascular risk assessment in type 2 diabetic patients., Research Design and Methods: We followed up to a first cardiovascular event 688 subjects (322 men, aged 59 ± 8 years) out of 731 consecutive asymptomatic type 2 diabetic patients with ≥1 additional risk factor who had been prospectively screened between 1992 and 2006 for SMI by stress myocardial scintigraphy and for silent CAD by coronary angiography., Results: SMI was found in 207 (30.1%) patients and CAD in 76 of those with SMI. Of the patients, 98 had a first cardiovascular event during a 5.4 ± 3.5 (range: 0.1-19.2) year follow-up period. Cox regression analysis considering parameters predicting events but not SMI and CAD ("routine assessment") showed in univariate analyses that macroproteinuria (hazard ratio [HR] 3.33 [95% CI 1.74-6.35]; P < 0.001), current multifactorial care (0.27 [0.15-0.47]; P < 0.001), and peripheral/carotid occlusive arterial disease (PCOAD; 4.33 [2.15-8.71]; P < 0.001) independently predicted cardiovascular events. When added into the model, SMI (HR 1.76 [1.00-3.12]; P = 0.05) and CAD (2.28 [1.24-4.57]; P < 0.01) were also independently associated with events. SMI added to the prediction of an event in the following 5 years above and beyond routine assessment risk prediction (c statistic with or without SMI 0.788 [0.720-0.855] and 0.705 [0.616-0.794], respectively)., Conclusions: Although screening for SMI and silent CAD should not be systematic, these complications are predictive of cardiovascular events in type 2 diabetic patients in addition to routine risk predictors, especially represented by PCOAD, macroproteinuria, and nonintensive management.

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.

Objective: Microalbuminuria and impaired endothelium-dependent vasodilation are both predictors for cardiac events in patients with type 2 diabetes. The aim of the study was to evaluate whether microalbuminuria correlated with coronary endothelium-dependent vasodilation., Research Design and Methods: We evaluated 84 patients (47 men, mean age 50.5 +/- 5.9 years) with type 2 diabetes for 9.4 +/- 3.4 years, without angiographic coronary stenosis and without major cardiovascular risk factors or other confounding factors, for endothelium investigation. Quantitative coronary angiography was used to assess coronary artery response to cold pressor testing, used to assess endothelium-dependent vasodilation, and to isosorbide dinitrate (endothelium-independent vasodilation)., Results: Endothelium-dependent vasodilation differed in the patients with and without microalbuminuria (changes in coronary artery diameter during cold pressor testing: -15.0 +/- 1.9% vs. -10.2 +/- 1.3%, respectively, P < 0.05) and correlated with urinary albumin excretion rate (r = -0.39, P = 0.003), diastolic blood pressure (r = 0.29, P < 0.01), and left ventricular mass index (r = -0.24, P < 0.05). Independent predictors for endothelium-dependent vasodilation were urinary albumin excretion rate (beta -0.04 [95% CI -0.07 to -0.01], P < 0.005) and left ventricular mass index (-0.26 [-0.49 to -0.05], P < 0.05). Endothelium-independent vasodilation was similar in both groups., Conclusions: Type 2 diabetic patients with microalbuminuria have a more severely impaired coronary endothelium-dependent vasodilation than those with normoalbuminuria. These data suggest a common pathophysiological process for both coronary vasomotor abnormalities and microalbuminuria.

Objective: Silent myocardial ischemia (SMI) in asymptomatic subjects with no history of myocardial infarction or angina is a frequent condition in diabetic patients. The aim of the study was to examine the predictive value of SMI for cardiac events in a multicenter cohort and to determine whether this value is higher in patients with a particular clinical profile., Research Design and Methods: A total of 370 asymptomatic diabetic patients with at least two additional cardiovascular risk factors was recruited in four departments of diabetology. SMI was assessed by either exercise or dipyridamole single-photon emission-computed tomography myocardial perfusion imaging with thallium-201. If dipyridamole stress was used, an electrocardiogram stress test was performed separately on another day. Follow-up duration was 3-89 months (38 +/- 23 months)., Results: There was evidence of SMI in 131 patients (35.4%) on at least one positive noninvasive test. The patients with SMI were significantly older and had significantly higher serum triglycerides and lower HDL cholesterol levels. Cardiac events occurred in 53 patients (14.3%). Major cardiac events (death or myocardial infarction) occurred in 38 patients (10%) and other events (unstable angina, heart failure, or coronary revascularization) occurred in 15 patients. The patients who had cardiac events were older and had higher serum triglyceride levels at baseline. There was a significant association between SMI and cardiac events (hazard ratio 2.79 [95% CI 1.54-5.04]) and in particular major cardiac events (3 [1.53-5.87]). In the patients >60 years of age, the prevalence of SMI was higher (43.4 vs. 30.2% in those <60 years). SMI was associated with a significant risk of cardiac events (2.89 [1.31-6.39]) and in particular major cardiac events (3.66 [1.36-9.87]) for the patients >60 years old but not for those <60 years old., Conclusions: In asymptomatic diabetic patients with additional cardiovascular risk factors, SMI is a potent predictor of cardiac events and should be assessed preferably in the patients >60 years of age.

Objective: Endothelium-dependent coronary dilation is impaired in diabetic patients and has been found to independently predict cardiovascular events (CVEs) in patients with multiple coronary risk factors. The aim of this study was to evaluate the outcome of type 2 diabetic patients on the basis of epicardial coronary dysfunction., Research Design and Methods: We examined 56 control subjects (aged 51.7 +/- 6.4 years) using coronary artery response to the cold pressor test (quantitative coronary angiography) and compared them with 72 type 2 diabetic patients (aged 50.3 +/- 8.5 years) without other major coronary risk factors., Results: Average diameter change was 17.2 +/- 10.4% in the control subjects, dilation occurred in 91.1% of subjects, no change occurred in 8.9%, and there was no constriction. Average diameter change was -14.4 +/- 12.1% in diabetic patients (P < 0.001 vs. control subjects), constriction occurred in 73.6%, no change occurred in 26.4%, and there was no dilation. CVEs were recorded with a mean follow-up of 45 +/- 19 months. There was 1 CVE in the control group and 26 CVEs in 18 of 72 diabetic patients (P < 0.001 vs. control subjects), with 23 events in 16 of 53 diabetic patients with coronary artery constriction (P < 0.001 vs. control subjects), and 3 events in 2 of 19 diabetic patients with no diameter change (NS vs. control subjects)., Conclusions: In type 2 diabetic patients without other major coronary risk factors, constriction of angiographically normal coronary arteries to the cold pressor test is predictive of long-term CVEs.

Objective: To investigate, by thallium-201 scanning, circulation in the muscles of the lower limb (LL) in diabetic patients without clinical peripheral vascular disease but with a high cardiovascular risk profile., Research Design and Methods: A total of 80 diabetic patients (76 patients with type 2 diabetes, mean age 57.3 years, duration of diabetes 13.0 +/- 7.5 years) with more than one additional cardiovascular risk factor but no claudication were investigated. After stress testing, 1.5 MBq/kg thallium-201 was administered to perform myocardial single-photon emission computed tomography followed by LL scanning. Muscle blood flow was considered abnormal if the asymmetry in thallium-201 uptake between the two buttocks and/or thighs and/or calves was > 10%., Results: Muscle perfusion defects were found in 42% of the patients, mainly in the calves. These defects correlated with retinopathy (P = 0.042) and the HbA1c level (P = 0.044). In patients with defects in the buttock and/or thigh, the prevalence of nephropathy and retinopathy was higher than in those with isolated defects in the calf (P = 0.032 and 0.023, respectively)., Conclusions: This study suggests that LL scanning coupled with myocardial scintigraphy is a convenient method of investigating peripheral muscle circulation. Proximal perfusion defects in patients without clinical arterial disease are associated with increased prevalence of retinopathy and nephropathy and, therefore, may be due to microvascular disease of LL muscle. Distal defects may indicate silent macrovascular disease of the LL.

Objective: The aim of this study was to determine the predictive value of silent myocardial ischemia (SMI) and cardiac autonomic neuropathy (CAN) in asymptomatic diabetic patients., Research Design and Methods: We recruited 120 diabetic patients with no history of myocardial infarction or angina, a normal 12-lead electrocardiogram (ECG), and two or more additional risk factors. SMI assessment was carried out by means of an ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole, and 48-h ECG monitoring. CAN was searched for by standardized tests evaluating heart rate variations. Accurate follow-up information for 3-7 years (mean 4.5) was obtained in 107 patients., Results: There was evidence of SMI in 33 patients (30.7%). CAN was detected in 33 of the 75 patients (38.9%) who were tested, and a major cardiac event occurred in 11 of them. Among these 75 patients, the proportion of major cardiac events in the SMI+ patients was not significantly higher than that in the SMI- patients (6 of 25 vs. 5 of 50 patients), whereas it was significantly higher in the CAN+ patients than in the CAN- patients (8 of 33 vs. 3 of 42 patients; P = 0.04), with a relative risk of 4.16 (95% CI 1.01-17.19) and was the highest in the patients with both SMI and CAN (5 of 10 patients). After adjusting for SMI, there was a significant association between CAN and major cardiac events (P = 0.04)., Conclusions: In asymptomatic diabetic patients, CAN appears to be a better predictor of major cardiac events than SMI. The risk linked to CAN appears to be independent of SMI and is the highest when CAN is associated with SMI.

Objective: To investigate whether the fall in soluble L-selectin (sL-selectin) level constitutes a marker for myocardial ischemia., Research Design and Methods: The levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), P-selectin (sP-selectin), and L-selectin (sL-selectin), were compared in type 2 diabetic patients without inflammatory syndrome but with symptomatic coronary artery disease (CAD) (group 1, n = 11), with silent ischemic disorders and proven coronary stenoses (group 2, n = 11), with silent myocardial ischemia (SMI) and normal coronary angiography (group 3, n = 10), and without proven SMI (group 4, n = 13). These levels were compared with those of 22 control subjects., Results: The sL-selectin level was significantly lower in groups 1, 2, or 3 with symptomatic CAD or with SMI as compared with the control group (P = 0.0004). Group 4 without myocardial ischemia did not significantly differ from the control subjects (P = 0.6). In type 2 diabetic patients, after controlling for HbA1c, a partial correlation between sL-selectin and the CAD status was significant (P = 0.001). sICAM-1 and sP- or sE-selectin did not differ significantly between type 2 diabetic patients and control subjects or among the different groups of patients. The sVCAM-1 level in type 2 diabetic patients was significantly higher than in the control subjects (P = 0.001), but there were no significant intergroup differences (P = 0.4)., Conclusions: In type 2 diabetic patients, sVCAM-1 is increased with regard to glycemic control, whatever the CAD status. In type 2 diabetic patients with symptomatic CAD or SMI associated with coronary stenoses, sL-selectin is significantly decreased. A marked fall in sL-selectin might constitute a marker for silent CAD in type 2 diabetic patients.