Improvements in Diabetic Neuropathy and Nephropathy After Bariatric Surgery: a Prospective Cohort Study

Abstract

Purpose There are limited data on the impact of bariatric surgery on microvascular complications of type 2 diabetes (T2D), particularly diabetic neuropathy. We assessed microvascular complications (especially neuropathy) in obese patients with T2D before and 12 months after bariatric surgery. Materials and Methods This was a prospective observational cohort study. Measurements of neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration (VPT), cold (CPT) and warm (WPT) perception thresholds, nerve conduction studies (NCS) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL); urinary albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFRcyst-creat) and retinal grading were taken. Results Twenty-six (62% female; median age 52 years) obese patients with T2D were recruited. Body mass index (BMI) (47.2 to 34.5 kg/m2; p < 0.001) decreased post-operatively. There were improvements in CNFD (27.1 to 29.2/mm2; p = 0.005), CNBD (63.4 to 77.8/mm2; p = 0.008), CNFL (20.0 to 20.2/mm2; p = 0.001), NSP (3 to 0/38; p < 0.001) and eGFRcyst-creat (128 to 120 ml/min; p = 0.015) post-bariatric surgery. Changes in (Δ) triglycerides were independently associated with ΔCNFL (β = − 0.53; p = 0.024) and Δsystolic blood pressure (β = 0.62;p = 0.017), and %excess BMI loss (β = − 0.004; p = 0.018) were associated with ΔeGFRcyst-creat. There was no significant change in NDS, VPT, CPT, WPT, NCS, uACR or retinopathy status. Glomerular hyperfiltration resolved in 42% of the 12 patients with this condition pre-operatively. Conclusion Bariatric surgery results in improvements in small nerve fibres and glomerular hyperfiltration in obese people with T2D, which were associated with weight loss, triglycerides and systolic blood pressure, but with no change in retinopathy or uACR at 12 months.

Distal Corneal Small Nerve Fibre Damage in Subjects With Obesity

“…The underlying pathophysiology of obesity-related peripheral neuropathy is poorly understood [12]. This study shows a signi cant reduction in central corneal nerve bre parameters in obese subjects with and without diabetes, in agreement with our previously published studies in subjects with obesity [13,23] and diabetes [5,24]. We now further report greater corneal nerve damage in the more distal inferior whorl compared to the central region providing support for a dying-back neuropathy, consistent with studies in adults [25,26] and children [27] with diabetes.…”

“…Despite a mild neuropathy, there was signi cant distal and proximal corneal nerve loss in subjects with and without diabetes. There was also evidence of cardiac autonomic neuropathy only in obese subjects with diabetes, consistent with previous studies [23]. CCM has been used to show both progression of neuropathy in patients with type 2 diabetes over 6.5 year [5] and nerve regeneration in patients with type 1 diabetes after simultaneous pancreas-kidney transplantation [30] and in subjects with obesity with [23] and without diabetes [31] after bariatric surgery.…”

“…Small bre damage is known to precede large bre damage in diabetes [28], although the diagnosis of small bre neuropathy (SFN) is not made easily given that the current diagnostic gold standard -skin biopsy -is not widely available in routine clinical practice [29]. Our cohort of patients had mild clinical neuropathy based on the NSP and ND and the thermal thresholds were normal, which contrasts with our previous study in patients with obesity with more severe neuropathy [13,23]. Despite a mild neuropathy, there was signi cant distal and proximal corneal nerve loss in subjects with and without diabetes.…”

The role of abnormalities of lipoproteins and HDL functionality in small fibre dysfunction in people with severe obesity

“…We and others have previously demonstrated significant small fibre damage in people with metabolic syndrome and IGT 3 , 5 , 12 . A study has shown that 11% of women with severe obesity have peripheral neuropathy 32 and we have recently reported small nerve fibre regeneration after bariatric surgery 33 .…”

“… Parameters Obese (−ve) (n = 23) Obese (+ ve) (n = 24) P Demographics Age (years) 47.4 ± 9.6 45.9 ± 9 0.9 Sex(Female/Male) 14/7 16/8 0.7 Ethnicity (Caucasian/Asian) 21/2 22/2 0.1 Smoking (no. per day) 0 2.15 ± 5.8 0.5 Alcohol (units per week) 2.3 ± 4.6 0.5 ± 1.1 0.7 Systolic BP (mmHg) 133.6 ± 22.1 126.7 ± 17.5 0.7 Diastolic BP (mmHg) 73.5 ± 11.0 71.9 ± 10.3 0.6 BMI (kg/m 2 ) 50.6 ± 8.7 48.2 ± 8.2 0.1 Number on statin therapy (%) 3 13 8 33 0.1 Number (%) metabolic syndrome 5 23 14 58 0.02 HbA1c (mmol/mol) 38.5 ± 5.9 38.0 ± 4.6 0.9 Serum triglycerides (mmol/l) 1.4 ± 0.7 1.9 ± 1.3 0.02 LDL-C (mmol/l) 2.9 ± 0.8 2.8...…”