Aims/Introduction: Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years. Materials and Methods: Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow-up. Results: Participants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P < 0.05-0.0001), whilst there was no change in CNFD (P = 0.07) or CNFL (P = 0.85) in physically active subjects. Furthermore, there was no change in CNFD (P = 0.82), CNBD (P = 0.08), or CNFL (P = 0.66) in patients treated with glucose lowering medication associated with weight loss, whilst CNBD (P = 0.001) decreased in patients on glucose lowering medication associated with weight gain. Conclusions: In participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss.

Objective: Continuous glucose monitoring has revealed that glycemic variability and low time in range are associated with albuminuria and retinopathy. We have investigated the relationship between glucose metrics derived from continuous glucose monitoring and a highly sensitive measure of neuropathy using corneal confocal microscopy in participants with type 1 and type 2 diabetes. Methods: A total of 40 participants with diabetes and 28 healthy controls underwent quantification of corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length and inferior whorl length and those with diabetes underwent continuous glucose monitoring for 4 consecutive days. Results: Corneal nerve branch density was significantly lower in patients with high glucose variability compared to low glucose variability (median (range) (25.0(19.0-37.5) vs. 38.6(29.2-46.9); P=0.007); in patients who spent >4% compared to <4% time in level 1 hypoglycemia (54-69 mg/dl) (25.0(22.9-37.5) vs. 37.5(29.2-46.9); P=0.045) and in patients who spent >1% compared to <1% time in level 2 hypoglycemia (<54 mg/dl) (25.0 (19.8-41.7) vs. 35.4 (28.1-44.8); P=0.04). Duration in level 1 hypoglycemia correlated with corneal nerve branch density (r=-0.342, P=0.031). Duration in level 1 (181-250 mg/dl) and level 2 (>250mg/dl) hyperglycemia did not correlate with corneal nerve fiber density (P>0.05), corneal nerve branch density (P>0.05), corneal nerve fiber length (P>0.05) or inferior whorl length (P>0.05). Conclusions: Greater glucose variability and duration in hypoglycemia, rather than hyperglycemia are associated with nerve fiber loss in diabetes.

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IntroductionComplement factors mediate the recruitment and activation of immune cells and are associated with metabolic changes during pregnancy. The aim of this study was to determine whether complement factors in the maternal serum and follicular fluid (FF) are associated with in vitro fertilization (IVF) outcomes in overweight/obese women.MethodsForty overweight/obese (BMI = 30.8 ± 5.2 kg/m2) female patients, 33.6 ± 6.3 years old, undergoing IVF treatment for unexplained infertility were recruited. Baseline demographic information, including biochemical hormonal, metabolic, and inflammatory markers, and pregnancy outcome, was collected. Levels of 14 complement markers (C2, C4b, C5, C5a, C9, adipsin, mannose-binding lectin, C1q, C3, C3b/iC3b, C4, factor B, factor H, and properdin) were assessed in the serum and FF and compared to IVF outcome, inflammatory, and metabolic markers using multivariate and univariate models.ResultsOut of 40 IVF cycles, 14 (35%) resulted in pregnancy. Compared to women with failed pregnancies, women with successful pregnancies had higher levels of adipsin in the serum and FF (p = 0.01) but lower C5a levels (p = 0.05). Serum adipsin levels were positively correlated with circulating levels of vitamin D (R = 0.5, p = 0.02), glucagon (R = 0.4, p = 0.03), leptin (R = 0.4, p = 0.01), resistin (R = 0.4, p = 0.02), and visfatin (R = 0.4, p = 0.02), but negatively correlated with total protein (R = −0.5, p = 0.03). Higher numbers of top-quality embryos were associated with increased levels of C3, properdin, C1q, factors H and B, C4, and adipsin, but with reduced C2 and C5a levels (p ≤ 0.01).ConclusionsHigher adipsin and lower C5a levels in the maternal serum during implantation are potential markers of successful outcome in obese women undergoing IVF-assisted pregnancies.

Glucose monitoring is key to the management of diabetes mellitus to maintain optimal glucose control whilst avoiding hypoglycemia. Non-invasive continuous glucose monitoring techniques have evolved considerably to replace finger prick testing, but still require sensor insertion. Physiological variables, such as heart rate and pulse pressure, change with blood glucose, especially during hypoglycemia, and could be used to predict hypoglycemia. To validate this approach, clinical studies that contemporaneously acquire physiological and continuous glucose variables are required. In this work, we provide insights from a clinical study undertaken to study the relationship between physiological variables obtained from a number of wearables and glucose levels. The clinical study included three screening tests to assess neuropathy and acquired data using wearable devices from 60 participants for four days. We highlight the challenges and provide recommendations to mitigate issues that may impact the validity of data capture to enable a valid interpretation of the outcomes.