Remission of corneal and peripheral neuropathy after bariatric surgery in people with diabetes.

PURPOSE: Diabetic peripheral neuropathy can be detected using non-invasive in vivo confocal microscopy of the cornea (IVCM) and such abnormalities may precede the development of clinical neuropathy. The current study aimed to assess any progression or remission of corneal and peripheral neuropathy in patients with type 2 diabetes undergoing bariatric surgery. METHODS: People with known type 2 diabetes for at least five years and listed for bariatric surgery were recruited. Participants were assessed before, and 12, 26, and 52 weeks following bariatric surgery. IVCM and corneal sensitivity measurements were performed. A modified total neuropathy score (mTNS) was obtained from neuropathy questionnaire, clinical assessment and biothesiometry. RESULTS: Twenty-nine participants (M:F, 11:18) with mean BMI of 44.7 ± 6.4 kg/m2, and 11 ± 7.6 years duration of diabetes, were assessed. Corneal sub-basal nerve fibre length (CNFL), displayed an increase from a baseline mean of 12.20 ± 1.00 to 17.48 ± 0.92 mm/mm2 at 52 weeks (p < 0.0001). Corneal sensitivity threshold displayed a decrease over time, thus corneal sensitivity improved, falling from a mean of 1.11 ±0 .15 to 0.62 ± 0.11 (mBAR) (p < 0.0001). Clinical neuropathy scores demonstrated significant improvements from baseline, displaying a decrease in average mTNS score from 3.29 ± 0.68 to 0.76 ± 0.30 (p < 0.0001). A significant inverse relationship was shown between CNFL and sensitivity (ß coefficient = -0.047, p < 0.001), and CNFL and mTNS (ß coefficient = -0.178, p < 0.001). CONCLUSION: Bariatric surgery led to an improvement in metabolic control of diabetes and weight loss, along with improvement in corneal nerve microstructure, corneal sensitivity, and neuropathic symptoms, suggesting a reversal of both small and large fibre neuropathy.

Corneal Nerve Changes Observed by In Vivo Confocal Microscopy in Patients Receiving Oxaliplatin for Colorectal Cancer: The COCO Study.

An objective method of early identification of people at risk of chemotherapy-induced peripheral neuropathy is needed to minimize long-term toxicity and maximize dose intensity. The aims of the study were to observe corneal nerve microstructure and corneal sensitivity changes and peripheral neuropathy in patients receiving oxaliplatin, and to determine its association with corneal parameters at different stages of treatment and assess utility as non-invasive markers to detect and monitor peripheral neuropathy. Twenty-three patients scheduled to receive oxaliplatin chemotherapy with intravenous 5-FU for gastro-intestinal cancer were recruited and followed up with for 12 months. Ocular examinations including corneal and retinal evaluations, alongside peripheral neuropathy assessment, were performed. The corneal nerve density did not show significant change after chemotherapy when measured with a widely used semi-automated program or an automated analysis technique. Macula and optic nerve function did not change during or after oxaliplatin chemotherapy. However, the corneal nerve density modestly correlated with clinical peripheral neuropathy after 20 weeks of chemotherapy (r = 0.61, p = 0.01) when peripheral neuropathy is typical most profound, and corneal nerve sensitivity correlated with neuropathy at 12 (r = 0.55, p = 0.01) and 20 weeks (r = 0.64, p = 0.006). In conclusion, corneal changes detected on confocal microscopy show moderate association with peripheral neuropathy, indicating their potential to identify the development of oxaliplatin-induced peripheral neuropathy. However, further studies are required to confirm these findings.

Corneal Confocal Microscopy in Type 1 Diabetes Mellitus: A Six-Year Longitudinal Study.

Purpose: The current study describes corneal nerve morphology using in vivo confocal microscopy (IVCM) in patients with type 1 diabetes (T1D) who were followed up for 6 years, and it examines the relationship between corneal parameters and metabolic control of glucose and peripheral neuropathy. Methods: Sixty-two participants (37 with T1D and 25 control participants) were assessed in 2011 and 2017. Participants with bilateral cataract surgery or controls who developed diabetes were excluded. All underwent HbA1c, IVCM, and central corneal sensitivity measurements at both time points in the eye previously examined. A modified total neuropathy score was obtained. Results: Participants were age and sex matched. The mean duration of diabetes was 32.1 ± 12.0 years at the follow-up visit. The sub-basal nerve density in participants with T1D was lower than that of the controls and did not change (mean ± SD, 11.07 ± 4.0 to 11.41 ± 4.1 mm/mm2; P = 0.71), but it showed a marginal change in controls (19.5 ± 3.7 to 21.63 ± 4.03 mm/mm2; P = 0.06). The corneal sensitivity in T1D did not change (1.3 ± 1.5 to 1.4 ± 1.0 mbar; P = 0.8), and it declined in the controls (0.2 ± 0.3 to 0.6 ± 0.3 mbar; P < 0.001). There were no significant changes in HbA1c (60.5 ± 12.5 to 61.6 ± 13.7 mmol/mol) or in modified total neuropathy scores (2.4 ± 3.2 to 3.4 ± 3.8; P = 0.2). Conclusions: The corneal nerve damage and poorer corneal sensitivity reported in the patients with T1D did not change and displayed improvement with good glycemic control. Translational Relevance: The corneal nerve changes may be of more value in those with a shorter duration of diabetes for the timely prediction of at-risk individuals likely to develop peripheral neuropathy, particularly in type 1 diabetes.

Impact of diabetes mellitus on the ocular surface: a review.

Although diabetes mellitus is reaching epidemic proportions worldwide, ocular surface complications are still largely believed to be uncommon. Although these complications are not often sight threatening, the general well-being of patients and the cost of their health care can be respectively compromised and added by them. Over the last decade, an association of ocular surface complications (in particular reduced corneal sub-basal nerve density and corneal sensitivity) with peripheral neuropathy has emerged, which could help recognize the development of peripheral complications at an earlier stage and also provide research opportunities for examining new treatment modalities of diabetic neuropathies. The ocular surface complications of diabetes mellitus and their association with peripheral neuropathy are reviewed by this report.

In Vivo Confocal Microscopy of Corneal Nerves: An Ocular Biomarker for Peripheral and Cardiac Autonomic Neuropathy in Type 1 Diabetes Mellitus.

PURPOSE: We investigated the relationship between corneal subbasal nerve (SBN) plexus density, corneal sensitivity, and peripheral and cardiac autonomic neuropathy in patients with type 1 diabetes mellitus. METHODS: We recruited 53 patients with type 1 diabetes mellitus and 40 normal control participants. Corneal in vivo confocal microscopy (IVCM) and sensitivity testing were performed on one eye of each subject. Autonomic function testing was done and an overall neuropathy score obtained from a combination of a symptomatic neuropathy score, clinical assessment, biothesiometry, and nerve conduction tests. RESULTS: The corneal SBN density (P < 0.001) and corneal sensitivity (P < 0.001) were significantly lower in subjects with diabetes compared to controls. A modest negative correlation between total neuropathy score and SBN density was observed (r = -0.33, P = 0.01). A negative correlation between corneal sensitivity and expiration/inspiration component of the autonomic nerve analysis (ANS-EI) also was noted (r = -0.36, P = 0.008). Corneal SBN density was abnormal in 50% of diabetic subjects classified as "Normal" by the clinical and electrophysiological based tests of total neuropathy score. CONCLUSIONS: The correlation of corneal SBN density with total neuropathy score suggests that reduced corneal nerve density reflects peripheral neuropathy in diabetes. Corneal SBN changes precede other clinical and electrophysiology tests of neuropathy supporting a possible role for corneal IVCM and corneal sensitivity testing as surrogate markers in the assessment of diabetic peripheral and cardiac autonomic neuropathy.

Peripheral neuropathy and tear film dysfunction in type 1 diabetes mellitus.

PURPOSE: To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. METHODS: Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. RESULTS: Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P = 0.12 and P = 0.33, resp.). Tear lipid thickness (P = 0.02), stability (P < 0.0001), and quantity (P = 0.01) were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P < 0.001) and tear film stability was inversely associated with total neuropathy score (r = -0.29, P = 0.03). CONCLUSION: The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.

The clinical course of patients with type 2 diabetes presenting to the hospital with sulfonylurea-induced hypoglycemia.

BACKGROUND: This study describes the clinical course of adult patients with type 2 diabetes taking a sulfonylurea and presenting to the hospital with severe hypoglycemia. SUBJECTS AND METHODS: This was a retrospective chart review of all patients >15 years of age with type 2 diabetes and taking a sulfonylurea who presented to the emergency services of Auckland City Hospital over a 6-year period with severe hypoglycemia. RESULTS: One hundred eighty-five patients met the inclusion criteria. Their mean ± SD age was 71 ± 11 years, and known duration of diabetes was 14.7 ± 10 years. Of the patients, 167 had micro- and/or macrovascular complications of diabetes, and one-third had had a previous admission with hypoglycemia. Only 61 patients (33%) had a glomerular filtration rate of >60 mL/min. The length of stay was not correlated with admission creatinine level (highest tertile of creatinine, 71 ± 93 h; lowest tertile, 51 ± 79 h). Recurrent in-hospital hypoglycemia occurred in over one-third of patients, and 28 (15%) were re-admitted to the hospital within 28 days of discharge for various reasons, including further hypoglycemia in 13 patients. Two patients died during their admission. CONCLUSIONS: Patients with type 2 diabetes presenting to the hospital with sulfonylurea-associated hypoglycemia have a high burden of comorbidity, require a long hospital stay, and are at risk of subsequent re-admission to hospital. Careful evaluation of their best future treatment strategies must be undertaken taking account of their comorbidities, including their renal function.

Glucagon is absorbed from the rectum but does not hasten recovery from hypoglycaemia in patients with type 1 diabetes.

AIMS: A failure to secrete glucagon during hypoglycaemia is near universal in patients with type 1 diabetes 5 years after disease onset and may contribute to delayed counter-regulation during hypoglycaemia. Rectal glucagon delivery may assist glucose recovery following insulin-induced hypoglycaemia in such patients and has not been previously studied. METHODS: Six male patients (age 21-38 years) with type 1 diabetes (median duration 10 years) without microvascular complications, were studied supine after an overnight fast on two separate occasions at least 14 days apart. After omission of their usual morning insulin and 45 min rest, hypoglycaemia was induced by an intravenous insulin infusion which was terminated when capillary glucose concentration reached 2.5 mmol l(-1). Subjects were randomized to insert a rectal suppository containing 100 mg indomethacin alone (placebo) or 100 mg indomethacin plus 1 mg glucagon at the hypoglycaemic reaction. Serial measurements were made for 120 min. RESULTS: In the two groups, mean (SD) plasma glucose concentrations fell to a similar nadir of 1.8 (0.7) mmol l(-1) (placebo) and 2.1 (1.2) mmol l(-1) (glucagon). Peak plasma glucagon following hypoglycaemia was higher in the glucagon group; 176 (32) ng l(-1)vs. 99 (22) ng l(-1) after placebo (P = 0.006). However, the glucose recovery rate over 120 min after hypoglycaemia did not differ significantly. CONCLUSIONS: Our results provide evidence for the absorption of glucagon from the rectum. They also indicate that 1 mg does not constitute a useful mode of therapy to hasten recovery from hypoglycaemia in patients with type 1 diabetes.

Current and former smoking increases mortality in patients on peritoneal dialysis.

AIMS: There is limited information on the effects of smoking behaviour on mortality in patients with end-stage renal failure (ESRF). This study aimed to assess the interaction of smoking on death rate in patients with renal failure on dialysis. METHODS: All patients (n=1293) commencing peritoneal dialysis between 1985 and 1995 for renal failure in New Zealand were prospectively followed 6 monthly until 1997 and data entered on the National database. Mortality rates were calculated from the national database and rates in patients with diabetes compared with those without diabetes and in those who did or did not smoke. RESULTS: Follow-up data was available on all patients for a range of 20-40 months. 35% of the patients were clinically classified as having diabetic nephropathy as the cause of renal failure (11% type 1, 24% type 2). Seventeen percent of the total cohort were current smokers, 45% former smokers and 38% lifetime non smokers at dialysis commencement. These rates were similar between patients with diabetes (18% current, 51% former, 32% non-smoker) and those without diabetes (17% current, 42% former, 41% non-smoker). At survey end in 1997, 43% of the patients without diabetes had died compared with 59% of patients with type 1 diabetes (p<0.05) and 62% of patients with type 2 diabetes (p<0.05). The age-adjusted mortality of patients with a history of current or former smoking was higher than non-smokers. Those patients with diabetes and a history of smoking had even higher mortality. CONCLUSIONS: Patients with a current or former history of smoking on peritoneal dialysis are at greatly increased risk of death. A strategy of aggressive smoking cessation efforts should be adopted for these patients at the earliest opportunity.