Laure Alexandre

Comment on Andersen et al. Risk-Factor Trajectories Preceding Diabetic Polyneuropathy: ADDITION-Denmark. Diabetes Care 2018;41:1955–1962

We were interested in the article by Andersen et al. (1), who showed that diabetic polyneuropathy (DPN) was related to baseline HbA1c and its increase in 452 participants with type 2 diabetes in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) (1). If HbA1c trajectories influence DPN, it could be improved by treatment. In the Kumamoto trial, the vibration perception thresholds (VPT) stabilized in patients on intensive glucose control, whereas they increased from 22 to 37 V in those on conventional treatment (2).nnAndersen et al. (1) cautiously mentioned that their results may not apply to people with type 2 diabetes clinically diagnosed later in the disease course, with higher HbA1c that changed …

Comment on Gordin et al. Differential Association of Microvascular Attributions With Cardiovascular Disease in Patients With Long Duration of Type 1 Diabetes. Diabetes Care 2018;41:815–822

We were interested by the recent article from Gordin et al. (1), who showed that proliferative diabetic retinopathy (DR) was related to cardiovascular disease (CVD) in type 1 diabetes (T1D), even in patients without diabetic kidney disease (DKD) (1). DKD is an important marker of cardiovascular risk in T1D (2), but a residual risk persists for patients without kidney damage, and its association with DR seems important information.nnIn Bordeaux we followed a cohort of patients with T1D since 2009, and we have recently shown that DR could predict their later fast renal decline (3). The article from Gordin et al. prompted us to test whether their initial …

Normoalbuminuric chronic kidney disease in type 1 diabetes: is it real and is it serious?

To the Editor: We were interested by the recent article by Penno et al, who reported that the majority (17/29) of their participants with stage ≥3 chronic kidney disease (CKD) and type 1 diabetes had the non-albuminuric phenotype (Alb; albuminuria <3.4 mg/mmol) [1]; this is an unexpectedly high proportion. As reported by the authors, these participants had higher Modification of Diet in Renal Disease (MDRD) Study equation-estimated GFR (eGFR) (52 ± 7 ml min [1.73 m]) vs those with the albuminuric phenotype (Alb; albuminuria ≥3.4 mg/mmol), who had an eGFR of 45 ± 11 ml min [1.73 m] (p < 0.05); this was not commented on to a great extent in the article. Two hypotheses may explain this less advanced renal failure in the Alb group. First, participants with Alb phenotype may not really have CKD. Although it works better than the old Cockcroft and Gault formula [2], the MDRD equation was built by multiple regression analysis from a population with renal insufficiency, and it is well-known to underestimate normal and high GFR: according to the analysis from Froissard et al, 20.5% of MDRD equation-estimated stage 3 CKD was, in fact, stage 2 CKD based on Cr-EDTA analysis [3]. Penno et al recognised that estimation by the MDRD equation was a limitation of their study [1]. To investigate whether the higher MDRD equationdeduced eGFR in the Alb group might have resulted from such underestimated eGFR, we compared the MDRD equation-eGFR to isotopically measured GFR (mGFR), analysed using Cr-EDTA, in 40 individuals with type 1 diabetes and MDRD equation-eGFR below 60 ml min [1.73 m]. Participants included 21 men (52.5%) aged 57 ± 13 years old, with a median albumin excretion rate (AER) of 189 mg/24 h (range 5–2500). Only three individuals had the Alb phenotype. In our participants, the MDRD equation-eGFR was 41.7 ± 12.4 ml min [1.73 m], which was similar to the mGFR (42.0 ± 21.9 ml min [1.73 m]). Regarding eGFR, individuals with stage 3a CKD in our study (n = 22) were similar to the individuals with stage 3 CKD in the study by Penno et al [1], and their MDRD equation-eGFR did not differ from mGFR (MDRD equation-eGFR: 51.1 ± 3.7 ml min [1.73 m]; mGFR: 50.7 ± 15.1 ml min [1.73 m]) (unpublished results, V. Rigalleau). As demonstrated using data from the DCCT, in the 60–80 ml min [1.73 m] MDRD equation-eGFR range, ~80% of eGFR values may be underestimated by more than 20 ml min [1.73 m] as compared with the iothalamate clearance method [4]. This may explain the large number of individuals with MDRD equation-eGFR 60–74 ml min [1.73 m] in Penno et al’s study who were categorised as Alb (n = 63) vs Alb (n = 8). However, this does not seem to explain the high number of individuals with the Alb phenotype with stage 3 CKD, who were probably highly renal insufficient. * Vincent Rigalleau vincent.rigalleau@chu-bordeaux.fr

Sudomotor function in diabetic peripheral artery disease: a role for diabetic neuropathy?

Dear Sir, We were interested in the recent article from Chahal et al. [1] who found low electrochemical skin conductance (ESC) in patients with type 2 diabetes and peripheral artery disease (PAD). This original finding seems relevant because ESC is usually considered as a marker of diabetic peripheral neuropathy (DPN) [2] related to the loss of small fibers in the skin and sweat glands [3]. The neurological evaluation of patients studied by Chahal et al. was not reported in the paper [1], and we wonder whether an abnormal Semmes-Weinstein monofilament (10 g) test could be related to an altered ESC in patients with diabetes. In 36 patients with diabetes (50% type 1, 50% type 2) free of PAD (no history of foot ulcer, distal pulses present), we measured the ESC (Sudoscan, Impeto Medical) and we performed neurological tests: 10 g monofilament test, vibration perception threshold (VPT; Neurothesiometer, Horwell) instead of a tuning fork, and sural nerve conduction velocity and amplitude potential (SNCV and SNAP; DPN-Check, Neurometrix). The comparison between the patients who did not perceive the monofilament and the patients who perceived it was performed by ANOVA and Chi-2 as appropriate and is summarized in Table 1. As expected, the patients who did not perceive the monofilament were more men, older, with a longer duration of diabetes, and their VPT and nerve conduction tests were altered. The ESC was reduced in our patients who did not perceive the monofilament (47 ± 8 μS), very near of the values reported by Chahal et al. (48 ± 8 μS). The difference between ESC in patients perceiving vs not perceiving the monofilament was still significant after adjusting for age, gender, and diabetes duration by multivariate regression analysis. In patients with diabetes, PAD and DPN usually coexist [4] and vascular risk factors have also been related to the polyneuropathy even in non-diabetic population [5]. A reduced ankle/brachial index as used by Chahal et al. has been related to a twice higher risk of diabetic neuropathy in the Verona study [6]. We therefore wonder whether neuropathy may contribute to the low ESC in patients with PAD, and we suggest that their conclusions would get stronger if the authors could adjust the relation between the ankle/brachial index and ESC to the presence of DPN. The most accurate approach for the evaluation of DPN would be the objective measurement of SNCV and SNAP or the quantified and more sensitive measurement of the VPT, which we performed. But our result shows that a simple, recommended, monofilament test may be used for this adjustment. It should, however, be noticed that SNCV, SNAP, and VPT only test for large nerve fibers. This is a limitation, considering that often the autonomic and small fiber impairment is unrelated to the presence of large nerve fiber neuropathy. The ESC, as A comment on: Chahal S, Vohra K, Syngle A. Association of sudomotor function with peripheral artery disease in type 2 diabetes. Neurol Sci (2017) 38:151–6

Longitudinal trends in HbA1c in diabetes: Stable means can hide meaningful long-term changes

We were interested by the recent article from Miyang Luo et al, who reviewed longitudinal studies of subjects with both types of diabetes and described long‐term trends in HbA1c. For type 1 diabetes, they identified stable, low to moderate (7.1% to 9% HbA1c) as the main pattern, whereas extremely low or high but stable, deteriorating or improving HbA1c were possible for a minority of subjects: 2% to 45% among the 11 reviewed studies. In Bordeaux university hospital, we follow a cohort of subjects with type 1 diabetes since 2009. One hundred and eighty‐five participants had HbA1c measurements both at inclusion and 7 years later (from 2009 to 2016). They were mainly men (N = 105, 56%), 51 ± 14 years old, with 22 ± 13 years of diabetes duration. HbA1c was 7.5 ± 0.9% at baseline, which did not differ from the values 6 months before (7.6 ± 0.8%) and 12 months before (7.6 ± 0.8%). Seven years later, the mean HbA1c remained at 7.5 ± 0.9% and related with baseline value (ß = +0.523, P < 0.001). We registered HbA1c at a limited number of time points, which is less accurate than clustering from serial HbA1c measurements, but on the mean our participants seemed to track in the main “stable, low to moderate” HbA1c pattern identified by Luo, at first view. However, these findings contrast with our daily practice, as we often see subjects with important HbA1c excursions, a common cause for seeking specialized diabetology care. We investigated these subjects, by categorizing our participants according to the changes of HbA1c from 2009 to 2016: HbA1c declinors were defined as < −0.7% decline, and HbA1c progressors as > +0.7% HbA1c progression. We chose a ±0.7% HbA1c change because this was the maximal amplitude of initial long‐term changes in the recent report from Nirantharakumar K et al on HbA1c tracking in type 1 diabetes. As

Comment on Jaiswal et al. Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study. Diabetes Care 2017;40:1226–1232

We were interested by the recent article by Jaiswal et al. (1), who reported a high prevalence (22%) of diabetic peripheral neuropathy (DPN) in young subjects with type 2 diabetes in the SEARCH for Diabetes in Youth (SEARCH) study. Although significance was not reached for all the analyses in the type 2 diabetes group, long-term poor glycemic control, dyslipidemia, and smoking emerged as modifiable risk factors, and the authors suggested that their management may help to prevent or delay irreversible nerve damage. This optimistic view is, however, challenged by the results of multifactorial interventions: no improvement of vibration perception thresholds (VPT) in the Steno-2 study (2) and only a small initial improvement with later seemingly inexorable progression …

Comment on Kelly et al. Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care 2018;41:120–127

We were interested by the article from Kelly et al. (1), who reported that markers of subclinical renal damage predicted later preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM). Although the best predictor was neutrophil gelatinase-associated lipocalin, our interest focused on the higher estimated glomerular filtration rates (determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) before preeclampsia. Hyperfiltration is considered an important early step of diabetic nephropathy, but it should be noted that glomerular filtration rates are not properly predicted in pregnancy, by any formula, including the CKD-EPI (2).nnMuch more common than T1DM, gestational diabetes mellitus (GDM) also …

Lower extremity arterial disease in patients with diabetes: a contemporary narrative review

Lower-extremity arterial disease (LEAD) is a major endemic disease with an alarming increased prevalence worldwide. It is a common and severe condition with excess risk of major cardiovascular events and death. It also leads to a high rate of lower-limb adverse events and non-traumatic amputation. The American Diabetes Association recommends a widespread medical history and clinical examination to screen for LEAD. The ankle brachial index (ABI) is the first non-invasive tool recommended to diagnose LEAD although its variable performance in patients with diabetes. The performance of ABI is particularly affected by the presence of peripheral neuropathy, medial arterial calcification, and incompressible arteries. There is no strong evidence today to support an alternative test for LEAD diagnosis in these conditions. The management of LEAD requires a strict control of cardiovascular risk factors including diabetes, hypertension, and dyslipidaemia. The benefit of intensive versus standard glucose control on the risk of LEAD has not been clearly established. Antihypertensive, lipid-lowering, and antiplatelet agents are obviously worthfull to reduce major cardiovascular adverse events, but few randomised controlled trials (RCTs) have evaluated the benefits of these treatments in terms of LEAD and its related adverse events. Smoking cessation, physical activity, supervised walking rehabilitation and healthy diet are also crucial in LEAD management. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in LEAD management. The revascularization strategy should take into account several factors including anatomical localizations of lesions, medical history of each patients and operator experience. Further studies, especially RCTs, are needed to evaluate the interest of different therapeutic strategies on the occurrence and progression of LEAD and its related adverse events in patients with diabetes.

Skin autofluorescence predicts major adverse cardiovascular events in patients with type 1 diabetes: a 7-year follow-up study

BackgroundAdvanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7xa0year follow-up.MethodsDuring year 2009, 232 subjects with T1D were included. SAF measurement, clinical [age, sex, body mass index (BMI), comorbidities] and biological data (HbA1C, blood lipids, renal parameters) were recorded. MACE (myocardial infarction, stroke, lower extremity amputation or a revascularization procedure) were registered at visits in the center or by phone call to general practitioners until 2016.ResultsThe participants were mainly men (59.5%), 51.5u2009±u200916.7xa0years old, with BMI 25.0u2009±u20094.1xa0kg/m2, diabetes duration 21.5u2009±u200913.6xa0years, HbA1C 7.6u2009±u20091.1%. LDL cholesterol was 1.04u2009±u20090.29xa0g/L, estimated Glomerular Filtration Rates (CKD-EPI): 86.3u2009±u200926.6xa0ml/min/1.73xa0m2. Among these subjects, 25.1% were smokers, 45.3% had arterial hypertension, 15.9% had elevated AER (≥u200930xa0mg/24xa0h), and 9.9% subjects had a history of previous MACE. From 2009 to 2016, 22 patients had at least one new MACE: 6 myocardial infarctions, 1 lower limb amputation, 15 revascularization procedures. Their SAF was 2.63u2009±u20090.73 arbitrary units (AU) vs 2.08u2009±u20090.54 for other patients (pu2009=u20090.002). Using Cox-model, after adjustment for age (as the scale time), sex, diabetes duration, BMI, hypertension, smoking status, albumin excretion rates, statin treatment and a previous history of MACE, higher baseline levels of SAF were significantly associated with an increased risk of MACE during follow-up (HRu2009=u20094.13 [1.30–13.07]; pu2009=u20090.02 for 1 AU of SAF) and Kaplan–Meier curve follow-up showed significantly more frequent MACE in group with SAF upper the median (pu2009=u20090.001).ConclusionA high SAF predicts MACE in patients with T1D.