Corneal nerve fibre damage precedes diabetic retinopathy in patients with Type 2 diabetes mellitus

Bitirgen, Gülfidan; Özkağnıcı, Ahmet; Malik, Rayaz A.; Kerimoğlu, Hürkan

doi:10.1111/dme.12324

Cited by 85 publications

(98 citation statements)

References 27 publications

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“…Clearly, only a longitudinal follow-up study will be able to identify which of these parameters-particularly corneal nerve fiber density or IENFD-best predict development and progression of diabetic neuropathy. Furthermore, the prevalence of microalbuminuria (15.1%) and background retinopathy (2.3%) were lower than the prevalence of neuropathy, an observation that is consistent with another recent study showing corneal nerve loss even in patients with type 2 diabetes who do not have diabetic retinopathy (20). These findings challenge the dogma that the earliest microvascular complications of diabetes are retinopathy and microalbuminuria.…”

supporting

confidence: 87%

Which Test for Diagnosing Early Human Diabetic Neuropathy?

Malik

2014

Diabetes

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Epidemiological studies show that diabetic neuropathy can affect 50-90% of patients with diabetes. Diabetes increases the risk of foot ulceration and amputation more than 23-fold (1), and neuropathy is the major contributory factor to this increased risk. Neuropathy presents as painful neuropathy in ;20% of patients (2), and it independently predicts all-cause and diabetes-related mortality (3).Several longitudinal studies have shown that glycemic control and vascular risk factors are important in the development of diabetic neuropathy in patients with both type 1 (4) and type 2 (5) diabetes. However, the time of onset and exact deficits associated with early diabetic neuropathy have not been established using a comprehensive neuropathy assessment. In an early study of 132 newly diagnosed patients with type 2 diabetes, symptoms and clinical signs of neuropathy had a low prevalence (1.5 and 2.3%, respectively), while polyneuropathy assessed by electrophysiology was identified in 15.2% of patients and autonomic neuropathy based on an abnormal expirationto-inspiration ratio was increased threefold compared with healthy control subjects (6). In a 5-year follow-up of this cohort, there was only a minimal deterioration in electrophysiology (7).The latest recommendations continue to advocate a multimodal approach to assessing diabetic neuropathy. This should include symptoms and signs, quantitative sensory testing, and electrophysiology (8). There is no doubt that symptoms and neurological deficits matter most to patients. However, the excessive variability and poor reproducibility (9) of these measures limit their utility in observational studies as well as in clinical trials. Although neurophysiology has been considered to be the most objective measure of diabetic neuropathy, it assesses only large myelinated fibers, which constitute about 10% of peripheral nerves. Further, the reproducibility of this approach has been questioned (10).Small fibers constitute the majority of peripheral nerve fibers, are the earliest to be damaged, and have direct pathophysiological relevance to generation of nociceptive signals, leading to both neuropathic pain (11) and impaired pressure-induced vasodilation (12) predisposing to foot ulceration. Despite these factors, small nerve fibers receive considerably less attention than large ones. Perhaps not surprisingly, a reduction in intraepidermal nerve fiber density (IENFD) has been demonstrated in subjects with impaired glucose tolerance, which improved after lifestyle intervention (13). In contrast, Dyck et al. (14) found no evidence of neuropathy in subjects with impaired glycemia. However, their diagnosis of neuropathy was based on composite abnormality in nerve conduction. Although small fibers can be assessed objectively by quantifying IENFD in skin biopsies, this is an invasive procedure requiring expert laboratory assessment (15).We have pioneered corneal confocal microscopy (CCM), a rapid and noninvasive ophthalmic technique. The technique has been shown to be reproducible and h...

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supporting

confidence: 87%

Which Test for Diagnosing Early Human Diabetic Neuropathy?

Malik

2014

Diabetes

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“…A study has shown progressive deterioration of corneal nerve fiber pathology with increasing severity of retinopathy [149]. Another group has shown progression of corneal nerve fiber pathology in parallel with diabetic retinopathy and DSPN [150].…”

Section: Retinopathymentioning

confidence: 99%

“…Similarly to nephropathy, retinopathy may also be regarded as a comorbidity of DSPN [146,148,149]. A study has shown progressive deterioration of corneal nerve fiber pathology with increasing severity of retinopathy [149].…”

Section: Retinopathymentioning

confidence: 99%

Risk Factors and Comorbidities in Diabetic Neuropathy: An Update 2015

2015

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■ AbstractDistal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes. Antilipidemic treatment, especially with fenofibrate, and multi-factorial intervention have produced encouraging results, but more experience is necessary. The major comorbidities of DSPN are depression, autonomic neuropathy, peripheral artery disease, cardiovascular disease, nephropathy, retinopathy, and medial arterial calcification. Knowledge of risk factors and comorbidities has the potential to enrich the therapeutic strategy in clinical practice as part of the overall medical care for patients with neuropathy. This article provides an updated overview of DSPN risk factors and comorbidities.

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“…8 Bu yönüyle korneal konfokal mikroskopi periferik sinir hastalık-larının ve özellikle diyabetik nöropatinin teşhis ve takibinde giderek artan sıklıkta kullanım alanı bulmaktadır. 5,[27][28][29] Bir çalışmada ise, diyabet hastalarındaki periferik sinir hasarının cilt biyopsilerinin patolojik inceleme sonuçlarına kıyasla konfokal mikroskopi ile daha erken evrede tespit edilebildiği gösterilmiştir. 30 Kornea duyarlılığının yaş ile birlikte azaldığı bilinmektedir.…”

Section: Discussionunclassified