Bariatric Surgery Leads to a Reduction in Antibodies to Apolipoprotein A-1: a Prospective Cohort Study.

PURPOSE: Autoantibodies against apolipoprotein A-1 have been associated with cardiovascular disease, poorer CV outcomes and all-cause mortality in obese individuals. The impact of bariatric surgery (BS) on the presence of circulating anti-apoA-1 IgG antibodies is unknown. This study aimed to determine the effect of bariatric surgery on auto-antibodies titres against Apolipoprotein A-1 (anti-apoA-1 IgG), looking for changes associated with lipid parameters, insulin resistance, inflammatory profile and percentage of excess body mass index loss (%EBMIL). MATERIALS AND METHODS: We assessed 55 patients (40 women) before, 6 and 12 months post-operatively. Baseline and post-operative clinical history and measurements of body mass index (BMI), serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), apoA-1, highly sensitive C-reactive protein (hsCRP), fasting glucose (FG), glycated haemoglobin (HbA1c) and HOMA-IR were taken at each point. Human anti-apoA-1 IgG were measured by ELISA. RESULTS: The mean age of participants was 50 years. BS significantly improved BMI, %EBMIL triglycerides, HDL-C, apoA-1, hsCRP, HBA1c, FG and HOMA-IR. Baseline anti-apoA-1 IgG seropositivity was 25% and was associated with lower apoA-1 and higher hsCRP levels. One year after BS, anti-apoA-1 IgG seropositivity decreased to 15% (p = 0.007) and median anti-apoA-1 IgG values decreased from 0.70 (0.56-0.84) to 0.47 (0.37-0.61) AU (p < 0.001). Post-operative anti-apoA-1 IgG levels were significantly associated with a decreased post-surgical %EBMIL at 1 year. CONCLUSION: Bariatric surgery results in significant reduction in anti-apoA-1 IgG levels, which may adversely influence weight loss. The exact mechanisms underpinning these results are elusive and require further study before defining any clinical recommendations.

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

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 (ß = - 0.53; p = 0.024) and Δsystolic blood pressure (ß = 0.62;p = 0.017), and %excess BMI loss (ß = - 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.

Male sexual dysfunction in obesity: The role of sex hormones and small fibre neuropathy.

CONTEXT: Multiple factors contribute to sexual dysfunction in men with obesity. Sex hormone levels are commonly abnormal in men with obesity and this abnormality is often the focus of management in clinical practice. The role of small fibre neuropathy in obesity-related sexual dysfunction is not well established. OBJECTIVE: We aimed to investigate the relationship between sexual function, sex hormone levels and small nerve fibre morphology in men with severe obesity. MATERIALS AND METHODS: A prospective study of 29 men with severe obesity was undertaken. Sexual function was assessed using the European Male Ageing Study Sexual Function Questionnaire. Small nerve fibre morphology was quantified using corneal confocal microscopy. Sex hormone levels were measured by mass spectrophotometry. RESULTS: Erectile dysfunction was present in 72% of the cohort with a higher prevalence of diabetes among the symptomatic group (88% vs 38%, p = 0.006). Corneal nerve fibre length (CNFL) and corneal nerve fibre density (CNFD) were both significantly lower in participants with erectile dysfunction compared to those without (p = 0.039 and p = 0.048 respectively). The erectile function score correlated with CNFL (r = -0.418, p = 0.034) and CNFD (r = -0.411, p = 0.037). Total testosterone and calculated free testosterone levels did not differ significantly between men with or without erectile dysfunction (median 8.8 nmol/L vs 9.0 nmol/L, p = 0.914; and median 176 pmol/L vs 179 pmol/L, p = 0.351 respectively), infrequent sexual thoughts (median 8.1 nmol/L vs 9.2 nmol/L, p = 0.650; and median 184 pmol/L, vs 176 pmol/L, p = 0.619 respectively) and decreased morning erections (median 9.0 nmol/L vs 8.8 nmol/L, p = 0.655; and median 170 pmol/L vs 193 pmol/L, p = 0.278 respectively). CONCLUSION: Sexual dysfunction is highly prevalent in men with severe obesity. We found an association between small fibre neuropathy with erectile dysfunction with presence of diabetes a likely a significant contributing factor. We found no associations between testosterone levels with sexual symptoms (including frequency of sexual thoughts). The influence of small nerve fibre neuropathy on response to therapeutic interventions and whether interventions that improve small fibre neuropathy can improve erectile function in this population merits further study.

Bariatric surgery as a model to explore the basis and consequences of the Reaven hypothesis: Small, dense low-density lipoprotein and interleukin-6.

BACKGROUND: Reaven originally described the clustering of insulin resistance/hyperinsulinaemia, obesity (particularly visceral), altered cytokine levels, glucose intolerance, hypertriglyceridaemia and low high-density lipoprotein cholesterol. Subsequently, a potentially highly atherogenic small, dense low-density lipoprotein was also reported. We have studied the effect of bariatric surgery on this and other risk factors for atherosclerosis. METHODS: Forty patients (20 with type 2 diabetes mellitus) undergoing bariatric surgery were studied before and 1 year after bariatric surgery. RESULTS: Twelve months after bariatric surgery, median body mass index had decreased from 49.5 to 36.5 kg/m2, fasting insulin from 21.3 to 7.8 mU/L and insulin resistance (homeostatic model assessment of insulin resistance) from 5.9 to 1.8 (all p < 0.001). Thirteen out of 20 patients had remission from type 2 diabetes mellitus. Highly sensitive C-reactive protein, interleukin-6, fasting triglycerides ( p < 0.001) and small, dense low-density lipoprotein ( p < 0.001) decreased, while high-density lipoprotein cholesterol increased ( p < 0.001) significantly, irrespective of having type 2 diabetes mellitus and/or being treated with statin therapy before surgery. CONCLUSION: The association between marked weight loss and change in insulin resistance and hyperinsulinaemia with the change in small, dense low-density lipoprotein and interleukin-6 warrants further investigation. Bariatric surgery provides a model for investigating the mechanisms linking insulin resistance/hyperinsulinaemia to atherosclerosis.

Hypercholesterolaemia - practical information for non-specialists.

Hypercholesterolaemia is amongst the most common conditions encountered in the medical profession. It remains one of the key modifiable cardiovascular risk factors and there have been recent advances in the risk stratification methods and treatment options available. In this review, we provide a background into hypercholesterolaemia for non-specialists and consider the merits of the different risk assessment tools available. We also provide detailed considerations as to: i) when to start treatment, ii) what targets to aim for and iii) the role of low density lipoprotein cholesterol.