Effects of exercise training on metabolic syndrome risk factors in post-menopausal women - A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND & AIMS: Alterations in the hormonal profiles as women transition to the menopause predisposes individuals to the metabolic syndrome (MetS). In post-menopausal women, this can be exacerbated by sedentary behaviour and physical inactivity. Physical activity can convey many health benefits including improvement in MetS risk factors. However, it remains to be elucidated how differing exercise intensities and its mode of delivery can ameliorate MetS risk factors and resultant progression amongst post-menopausal women. The purpose of this systematic review and meta-analysis was to investigate the effects and efficacy of exercise training on MetS risk factors in post-menopausal women. METHODS: Database searches using PubMed, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were conducted from inception to December 2021 for randomised controlled studies (RCTs) investigating exercise training (>8 weeks) in at least one of the MetS risk factors in post-menopausal women. Utilising the random-effects model, appropriate standardised mean differences (SMD) or mean differences (MD) with 95% confidence interval (CI) for each MetS risk factor were used to calculate the overall effect size between the exercise and control groups. Sub-group analyses were performed for exercise intensity, modality, and duration for each risk factor. Meta-regression was performed for categorical (health status) and continuous (body mass index) covariates. RESULTS: 39 RCTs (40 studies) involving 2132 participants were identified as eligible. Overall, the meta-analysis shows that exercise training significantly improved all MetS risk factors: waist circumference (WC) [MD: -2.61 cm; 95% CI: -3.39 to -1.86 cm; p < 0.001; 21 studies]; triglycerides (TG) [SMD: -0.40 mmol/L; 95% CI: -0.71 to -0.09 mmol/L; p = 0.01; 25 studies]; high-density lipoprotein (HDL) [SMD: 0.84 mmol/L (95% CI: 0.41-1.27 mmol/L; p < 0.001; 26 studies]; fasting glucose (BG) [SMD: -0.38 mmol/L (95% CI: -0.60 to -0.16 mmol/L; p < 0.001; 20 studies]; systolic blood pressure (SBP) [MD: -5.95 mmHg (95% CI: -7.98 to -3.92 mmHg; p < 0.001; 23 studies]; and diastolic blood pressure (DBP) [MD: -4.14 mmHg (95% CI: -6.19 to -2.08 mmHg; p < 0.001; 23 studies]. Furthermore, sub-group analyses identified that moderate intensity and combined exercise training significantly improved MetS risk factors (p < 0.05) except for HDL, with combined exercise being the most effective. Long duration (≥12 weeks) training also significantly improved MetS risk factors except for TG. Meta-regression revealed no moderating effects on any MetS risk variables. CONCLUSION: This study reinforces the importance of regular physical activity as a non-pharmacological tool in the reduction of MetS risk in post-menopausal women, with significant metabolic improvements seen in interventions spanning 8-10 weeks. Moderate intensity and combined training significantly benefitted abdominal obesity, dyslipidaemia, dysglycaemia and hypertension in post-menopausal women. Improvements in at least one MetS risk were also seen with other exercise modalities and intensities.

The polyphenol epigallocatechin gallate lowers circulating catecholamine concentrations and alters lipid metabolism during graded exercise in man: a randomized cross-over study.

PURPOSE: Physical exercise is shown to mitigate catecholamine metabolites; however, it is unknown if exercise-induced increases in sympatho-adrenal activity or catecholamine metabolites are influenced by ingestion of specific catechins found within green tea. This study explored the impact of epigallocatechin gallate (EGCG) ingestion on catecholamine metabolism during graded cycle exercise in humans. METHODS: Eight males (22.4 ± 3.3 years, BMI:25.7 ± 2.4 kg.m2) performed a randomised, placebo-controlled, single-blind, cross-over trial after consumption (1450 mg) of either EGCG or placebo (PLAC) and performed graded cycling to volitional exhaustion. Venous bloods were taken at rest, 2 h post-ingestion and after every 3-min stage. Blood variables were analysed for catecholamines, catecholamine metanephrines and metabolic variables at rest, 2 h post-ingestion (POST-ING), peak rate of lipid oxidation (FATpeak), lactate threshold (LT) and peak rate of oxygen consumption (VO2peak). Data were analysed using SPSS (Version 26). RESULTS: Resting catecholamine and metanephrines were similar between trials. Plasma adrenaline (AD) was lower in ECGC treatment group between trials at FATpeak (P < 0.05), LT (P < 0.001) and VO2peak (P < 0.01). Noradrenaline (NA) was lower under EGCG at POST (P < 0.05), FATpeak (P < 0.05), LT (P < 0.01) and VO2peak (P < 0.05) compared to PLAC. Metanephrines, glucose and lactate increased similarly with exercise intensity in both trials. Lipid oxidation rate was 32% lower in EGCG at FATpeak (EGCG 0.33 ± 0.14 vs. PLAC 0.49 ± 0.11 g.min-1, P < 0.05). Cycle time to exhaustion was similar (NS). CONCLUSION: Acute EGCG supplementation reduced circulating catecholamines but not; metanephrine, glucose or lactates, response to graded exercise. Lower circulating catecholamines may explain a lower lipid oxidation rate.

Temporal Effects of Bariatric Surgery on Adipokines, Inflammation and Oxidative Stress in Subjects with Impaired Glucose Homeostasis at 4 Years of Follow-up.

BACKGROUND: Previous studies have examined changes in plasma markers of inflammation and oxidative stress up to 24 months following bariatric surgery, but there is limited evidence on the long-term effects of bariatric surgery. OBJECTIVES: To examine the effects of bariatric surgery on adipokines (adiponectin, leptin), inflammatory cytokines [C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10(IL-10)] and global plasma measures of oxidative stress [thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAOS) 1 and 6 months, and 4 years post-surgery in subjects with obesity and impaired glucose regulation. METHODS: A prospective study comprising of 19 participants (13 females, mean age 50.4 ± 6.2 years, mean body mass index (BMI) 54 ± 14 kg/m2, 17 type 2 diabetes) undergoing bariatric surgery (10 sleeve gastrectomy, 6 biliopancreatic diversion, 2 Roux-en-Y gastric bypass and 1 laparoscopic adjustable gastric banding). Serial measurements of the above markers were made pre-operatively, 1 and 6 months and 4 years post-operatively. RESULTS: Compared to pre-operative levels, significant decreases were seen 4 years post-operatively in CRP (11.4 vs 2.8 ng/mL, p < 0.001), IL-6 (8.0 vs 2.1 pg/mL, p < 0.001) and leptin (60.7 vs 32.1 pg/mL, p = 0.001). At 4 years, both fasting and 120 min TAOS significantly increased by 35% and 19% respectively. However, fasting and 120 min TBARS did not show any significant changes. CONCLUSION: To our knowledge, no other studies have described changes in inflammation and oxidative stress at 4 years following bariatric surgery. This study contributes to the current literature supporting the longer-term beneficial effect of bariatric surgery on chronic inflammation and oxidative stress.

Effect of Laparoscopic Sleeve Gastrectomy on Static and Dynamic Measures of Glucose Homeostasis and Incretin Hormone Response 4-Years Post-Operatively.

INTRODUCTION: There is limited literature available on the long-term effect of bariatric surgery especially laparoscopic sleeve gastrectomy (LSG) on the incretin hormone response. AIM: Our primary aim was to investigate changes in glucose metabolism and incretin hormone responses in participants with impaired glucose regulation approximately 4 years after LSG. The secondary aim was to examine the long-term incretin hormone changes of biliopancreatic diversion (BPD). METHOD: A non-randomised prospective study comprising of 10 participants undergoing LSG and 6 participants undergoing BPD. Serial measurements of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were performed during an oral glucose tolerance test pre-operatively and 1 month, 6 months and at approximately 4-7 years post-operatively. Area under the curve (AUC) was examined at 60 and 120 min. RESULTS: In the LSG group, a significant reduction in 2-h plasma glucose (2 h PG), HbA1c and HOMA-IR was observed at 4 years. Compared with pre-operative levels, significant increases in post-glucose GLP-1 secretion were observed at 1 and 6 months, but not maintained at 4 years. A linear increase was seen in post-glucose GIP response at 1 month and 6 months and 4 years. Within the BPD group, a reduction in HbA1c along with an increase GLP-1 response was observed at 7 years. CONCLUSION: An increase in GLP-1 response was not preserved at 4 years, but a significant increase in GIP response was observed along with improved glycaemic control following LSG.

Temporal effects of laparoscopic sleeve gastrectomy on adipokines, inflammation, and oxidative stress in patients with impaired glucose homeostasis.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity and metabolic dysfunction. OBJECTIVES: The aim of this work was to examine the early temporal effects of laparoscopic sleeve gastrectomy (LSG) on adipokines (adiponectin, leptin), inflammatory cytokines (interleukin-6, C-reactive protein, interleukin-10), and global plasma measures of oxidative stress (thiobarbituric acid reactive substances and total antioxidant status) in a sample of 55 participants preoperatively, and 1 and 6 months postoperatively. The focus was on a sample of patients with impaired glucose tolerance and type 2 diabetes, which is associated with increased low-grade systemic inflammation and oxidative stress. SETTING: University hospital, United Kingdom. METHODS: This was a prospective study comprising 55 participants with impaired glucose homeostasis and type 2 diabetes undergoing LSG (mean body mass index 50.4 kg/m2, mean glycated hemoglobin 7.4%). Serial measurements of the above markers were made preoperatively, 1 and 6 months postoperatively (43 had measurable cytokines and oxidative stress at 1- and 6-mo follow-up). RESULTS: We observed a significant reduction in interleukin-6, C-reactive protein, leptin, and thiobarbituric acid reactive substances, along with an increase in adiponectin 6 months postoperatively. CONCLUSIONS: To our knowledge the effects of LSG on inflammatory cytokines and plasma markers of oxidative stress have not been examined temporally in a sizeable sample of participants who have undergone LSG. This present study supports the role of LSG for the treatment of the proinflammatory and pro-oxidant status associated with obesity-related glucose dysregulation.

Development and characterization of an in vitro system of the human retina using cultured cell lines.

BACKGROUND: Previously developed in vitro cultures of the human retina have been solo or dual cell cultures. We developed a triple-cell culture in vitro model utilizing a membrane system to produce a better representation of a functional and morphological human retina. METHODS: Retinal microvascular endothelial cells (HRMVEC/ACBRI181, cell systems), retinal pigment epithelium cells (RPE/ARPE-19, ATCC) and Müller glial cells (Moorfield Institute of Ophthalmology-Müller 1, UCL) were grown in a triple culture. Our optimized triple-culture media contained a mix of specific endothelial medium and high glucose Dulbecco's Modified Eagle's medium, where all three layers were viable for up to 5 days. Co-culture effect on morphological changes (cell staining) and gene expression of functional genes (pigment epithelium derived factor [PEDF] and vascular endothelial growth factor [VEGF]) were measured from RNA via real-time polymerase chain reaction. Expression of tight junction protein 1 (TJP1) was measured in RNA isolated from ARPE-19s, to assess barrier stability. RESULTS: The triple-culture promotes certain cell functionality through up-regulation of TJP1, increasing PEDF and decreasing VEGF expression highlighting its importance for the assessment of disease mechanisms distinct from a solo culture which would not allow the true effect of the native microenvironment to be elucidated. CONCLUSIONS: This model's novelty and reliability allows for the assessment of singular cellular function within the retinal microenvironment and overall assessment of retinal health, while eliminating the requirement of animal-based models.

Bariatric Surgery Is Accompanied by Changes in Extracellular Vesicle-Associated and Plasma Fatty Acid Binding Protein 4.

BACKGROUND: Bariatric surgery markedly reduces fat mass with beneficial effects on cardiometabolic health but the mechanisms involved are not fully understood. Extracellular vesicles (EVs) are secreted by a variety of cells, including adipocytes, and may mediate some of these benefits. However, the effects of bariatric surgery on circulating EVs are unclear. METHODS: Concentration of plasma EVs isolated by ultracentrifugation at baseline, 1 and 6 months post-bariatric surgery (n = 20) was established using Nanoparticle Tracking Analysis. EV origin (CD9: exosome; CD41: platelet; CD235a: erythrocyte; CD11b: leukocyte; CD144: endothelial), cytokine (interferon γ, interleukin-6, TNF-α) and adipocyte marker (adiponectin, FABP4, PPARγ) expression was measured by time-resolved fluorescence immunoassay. RESULTS: EV concentration and cell-of-origin markers (CD41, CD235a, CD11b, CD144) did not alter in response to surgery, neither did EV-expressed interferon γ, IL-6, TNF-α, adiponectin, PPARγ or CD9. EV-derived fatty acid binding protein 4 (FABP4) increased at 1 month (+ 49%) before returning to baseline by 6 months (- 51%, p < 0.05), corresponding to similar changes in circulating plasma FABP4 (+ 22 and - 24% at 1 and 6 months, respectively; p < 0.001). Patients who underwent biliopancreatic diversion had lower FABP4-expressing EVs at 6 months compared to those who underwent sleeve gastrectomy/gastric banding (p < 0.05), despite similar percentage weight reduction (- 19 vs - 20%, respectively). CD9 expression correlated with EV-expressed FABP4, adiponectin, TNF-α and interferon γ (r = 0.5, r = 0.59, r = 0.53, r = 0.41, respectively, p < 0.005), suggesting transport by an EV population of exosomal rather than microvesicular origin. CONCLUSIONS: Bariatric surgery leads to a transient change in circulating EV- and plasma-derived FABP4, reflecting alterations in adipose tissue homeostasis.

Temporal changes in plasma markers of oxidative stress following laparoscopic sleeve gastrectomy in subjects with impaired glucose regulation.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity and associated metabolic complications. Obesity and type 2 diabetes are associated with increased oxidative stress. Previous studies have examined changes in plasma oxidative stress after laparoscopic Roux-en-Y gastric bypass, but there is limited evidence of the effects of LSG. OBJECTIVES: To examine the effects of LSG on plasma thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAOS) at 1 and 6 months after LSG in patients with obesity and impaired glucose regulation. SETTING: University hospital, United Kingdom. METHODS: Twenty-two participants with impaired glucose homeostasis undergoing LSG (body mass index 50.1 kg/m2, glycated hemoglobin 53 mmol/mol) were studied. Measurements of fasting and 120-minute TBARS and TAOS were performed during an oral glucose tolerance test preoperatively and postoperatively. RESULTS: Compared with preoperative levels, significant decreases were seen 6 months postoperatively in fasting TBARS (61.0±17.9 versus 39.4±13.8 ng/mL, P = .04) and 120-minute TBARS (76.0±29.5 versus 46.5±16.3 ng/mL, P = .02). No significant changes were observed in plasma TAOS. No significant association was observed between changes in TBARS and other clinical or biochemical measures. CONCLUSION: We observed a significant reduction in TBARS, a global measure of lipid peroxidation 6 months after LSG in participants with obesity and impaired glucose regulation.

Temporal Effect of Bariatric Surgery on Predicted 10-Year and Lifetime Cardiovascular Risk at 1 Month, 6 Months, and 5 Years Following Surgery: A Pilot Study.

BACKGROUND AND AIMS: Cardiovascular (CV) risk equations are routinely used to predict risk in nonbariatric populations, but have not been studied in depth in patients undergoing bariatric surgery and specifically those with impaired glucose regulation. The aim of this pilot study was to investigate changes in the 10-year and lifetime predicted CV risk in subjects with impaired glucose regulation before, 1 month, 6 months, and 5 years after bariatric surgery. METHOD AND RESULTS: A nonrandomized prospective study was conducted of 45 participants with impaired glucose regulation undergoing temporal assessments during follow-up. Body weight, body mass index (BMI), blood pressure, lipid profile, and HbA1c were recorded preoperatively, 1 month, 6 months, and 5 years postoperatively. Preoperative and postoperative predicted CV risk was calculated using the QRISK2, QRISK lifetime, and JBS3 calculators. Follow-up rates were 93%, 91%, and 71% at 1 month, 6 months, and 5 years, respectively. The sample had a mean age of 48.8 ± 7.0 years, a mean BMI of 53.9 ± 11.1 kg/m2, and a mean HbA1c of 7.5% ± 1.7%. The predicted 10-year QRISK2 score decreased by 35%, 54%, and 24% at 1 month, 6 months, and 5 years, respectively (P < 0.001). The predicted lifetime risk also decreased with the greatest reduction (24.5% with QRISK lifetime and 26.7% with JBS3 lifetime score) observed at 5 years even though the subjects were 5 years older. CONCLUSION: Bariatric surgery in patients with impaired glucose regulation is associated with a significant reduction in predicted 10-year and lifetime CV risk in a population that was 5 years older compared to baseline.

Association between the preoperative fasting and postprandial C-peptide AUC with resolution of type 2 diabetes 6 months following bariatric surgery.

BACKGROUND AND AIMS: Bariatric surgery results in the remission of type 2 diabetes mellitus (T2DM) in morbidly obese subjects. The aim of the study was to investigate the predictive value of both static and dynamic measures of C-peptide in relation to T2DM resolution 6 months after bariatric surgery regardless of the operation type. METHODS AND RESULTS: A non-randomized prospective study of 24 participants with T2DM undergoing bariatric surgery. Measurements of fasting and 2-hour plasma glucose, insulin, C-peptide and measures of insulin sensitivity were recorded temporally during an oral glucose tolerance test pre-operatively and 6 months post-operatively. A responder was defined with a fasting glucose <5.6 mmol/L and HbA1c <6.0% postoperatively. Within the sample there were 11 responders and 13 non-responders at 6 months. There was a significant difference in the duration of diabetes between the groups. Fasting C-peptide (P≤0.05) and 2-hour C-peptide (P≤0.05) were higher in responders compared to non-responders. Significantly higher C-peptide levels were observed preoperatively at all time points for responders, with significantly higher area under the curve (AUC0-60 and AUC0-120). Using the lower quartiles for C-peptide levels, both fasting C-peptide (>2.5 ng/mL [0.83 nmol/L]) and 2-hour C-peptide (>5.2 ng/mL [1.73 nmol/L]) had a sensitivity and negative predictive value of 100% to predict T2DM remission. Logistic regression showed that C-peptide, duration of diabetes and BMI were associated with response. The area under the ROC curve was 0.94 and a regression model predicted diabetes remission with a sensitivity of 85.7% and a specificity of 88.9%. CONCLUSIONS: This study demonstrated that static (fasting) and dynamic (AUC, 2-hour) C-peptide measurements predict T2DM resolution 6 months following bariatric surgery. This work provides insight into C-peptide dynamics as a predictor of response to bariatric surgery.

Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis.

AIM: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. METHODS: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). RESULTS: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). CONCLUSION: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.

Changes in inflammatory markers after sleeve gastrectomy in patients with impaired glucose homeostasis and type 2 diabetes.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. Obesity and type 2 diabetes are associated with chronic inflammation. There is lack of data examining the effects of sleeve gastrectomy (SG) on inflammatory biomarkers. Our aim was to study the effects of SG on specific cytokines associated with obesity including interleukin-6 (IL-6), interleukin-10 (IL-10), leptin, adiponectin, and C-reactive protein (CRP) preoperatively, 1 and 6 months after surgery. METHODS: A nonrandomized prospective study comprising of 22 participants with impaired glucose homeostasis and type 2 diabetes undergoing SG (body mass index 50.1 kg/m(2), glycated hemoglobin [HbA1c] 53 mmol/mol). Serial measurements of IL-6, IL-10, leptin, adiponectin, and CRP were performed during oral glucose tolerance testing preoperatively, 1 and 6 months postoperatively. RESULTS: We observed significant improvements at 1 and 6 months in leptin (P≤.001) and CRP (P = .003) after SG. We also observed a significant reduction in IL-6 at 6 months (P = .001). No statistically significant differences were observed for adiponectin and IL-10. CONCLUSION: This study is the first to examine the detailed changes in the inflammatory cytokines after SG. Our study shows significant improvements in the inflammatory biomarkers after SG in patients with impaired glucose homeostasis and type 2 diabetes.

Temporal changes in glucose homeostasis and incretin hormone response at 1 and 6 months after laparoscopic sleeve gastrectomy.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. Current literature reports significant improvements in glucose homeostasis after malabsorptive surgery. There is limited evidence on the effects of laparoscopic sleeve gastrectomy (SG) on glucose-insulin homeostasis and postoperative incretin hormone response. The objective of this study was to examine the metabolic effects of SG on temporal changes in insulin and glucose homeostasis, incretin hormones and hepatic insulin clearance in patients with impaired glucose tolerance (IGT) and type 2 diabetes (T2 DM). METHODS: A nonrandomized prospective study comprising 22 participants undergoing SG (body mass index [BMI] 50.1 kg/m(2), glycated hemoglobin [HbA1c] 53 mmol/mol) and 15 participants undergoing biliopancreatic diversion (BPD) (BMI 62.1 kg/m(2), HbA1c 58 mmol/mol). Serial measurements of glucose, insulin, C-peptide, glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic hormone (GIP) were performed during oral glucose tolerance testing preoperatively and 1 and 6 months postoperatively. Areas under the curve (AUC) were examined at 30, 60, and 120 minutes. RESULTS: Within the SG group, significant improvements were observed respectively at 1 and 6 months in glucose control (HbA1c: -0.9%, -1.3%), measures of insulin sensitivity (fasting insulin: -4.8 mU/L, -8.5 mU/L; fasting C-peptide: -0.6 pmol/L, -1.1 pmol/L; Homeostasis Model Assessment [HOMA-IR]: -0.144, -0.174; HOMA %S:+29.6,+92.4), hepatic insulin clearance (+0.07,+0.13) and postprandial GLP-1 response (AUC0-30 pmol h L(-1):+300,+331, AUC0-60:+300,+294, AUC0-120:+316,+295). These results were comparable to the BPD group. CONCLUSIONS: SG is associated with significant early improvements in insulin sensitivity and incretin hormone response and results in significant improvements in IGT/T2 DM.

Does bariatric surgery adversely impact on diabetic retinopathy in persons with morbid obesity and type 2 diabetes? A pilot study.

AIMS: To assess the incidence and progression of diabetic retinopathy (DR) 12 months post bariatric surgery in persons with morbid obesity and type 2 diabetes. METHODS: A retrospective pilot analysis of electronic hospital records between 1998 and 2012. RESULTS: 40 of 148 subjects had pre- and post-surgery DR screening. Of those without DR pre-surgery 1.5% (n = 26) progressed to minimum background DR (BDR) post surgery. Those with minimum BDR (n = 9) pre-surgery revealed no progression, with 55.6% (n = 5) showing evidence of regression. One person with moderately severe BDR and two with pre-proliferative DR (PPDR) prior to surgery experienced progression. Two persons with PPDR prior to surgery remained under the hospital eye services and were therefore not eligible to be re-assessed by the screening service. CONCLUSIONS: There was a low incidence of new DR and progression of DR in those either without evidence of retinopathy or with minimal BDR prior to surgery with some subjects showing evidence of regression. There was however a risk of progression of DR in those with moderate BDR or worse, and should therefore be monitored closely post-surgery.

Association of the PGC-1α rs8192678 variant with microalbuminuria in subjects with type 2 diabetes mellitus.

PPAR-γ co-activator-1α (PGC-1α) is a tissue-specific transcriptional co-activator involved in the regulation of antioxidant enzymes. The A-allele of the rs8192678 PGC-1 α} (G>A) gene variant has previously been associated with nephropathy in Korean and Indian-Asian type 2 diabetes mellitus (T2DM) samples. Our aim was to examine the association between this variant and urine albumin exccretion in European subjects with T2DM. Genotyping was performed on 583 European subjects with T2DM and examined in relation to urinary albumin, plasma oxidized-LDL and small dense-LDL percentage. We observed a significant association between genotype (GG/GA/AA) and urinary albumin (normoalbuminuria v micro/macroalbuminuria: 48.6/39.7/11.7% v 38.2/51.2/10.5%, p=0.02; for GG v GA/AA, p=0.01). The odds ratio for micro/macroalbuminuria in GA and AA subjects relative to GG were 1.70 [1.15-2.50], p=0.008 and 1.20 [0.66-2.16], p=0.56 respectively (for GA/AA v GG: 1.58 [95% CI: 1.09-2.27], p=0.02). There was a significant association between the A allele and a higher percentage of small dense-LDL particles (GG v GA v AA: 70.8 [58.01-81.06] % v 72.8 [56.18-81.19] % v 78.9 [67.16-85.33] %, p=0.03). In European subjects with T2DM the GA relative to the GG genotype is associated with a 70% increase in the risk of micro/microalbuminuria. Furthermore, homozygosity for the A-allele is also associated with a preponderance of small dense-LDL particles.

Association of the adiponectin rs266729 C>G variant and coronary heart disease in the low risk 'Golden Years' type 1 diabetes cohort.

The C-allele of rs266729 is associated with CHD, while the G-allele of rs17300539 is associated with metabolic traits. We examined these in type 1 diabetes. For rs266729, the C-allele was associated with 8-fold increase in CHD. For rs17300539, the G-allele was associated with increases in triglycerides and waist circumference.

Adiponectin levels in people with Latent Autoimmune Diabetes-a case control study.

BACKGROUND: To examine adiponectin levels in people with Latent Autoimmune Diabetes in Adults using a matched pair case control study. FINDINGS: Patients with LADA (n = 64), were matched for sex with type 2 diabetic and non-diabetic controls. A matched paired T-test was used to examine average adiponectin levels in the LADA patients' versus controls. The average adiponectin level for the LADA patients was 9.96 µg/ml compared to 6.4 µg/ml for Type 2 matched controls and 9.6 µg/ml for non-diabetic controls. Mean difference for the LADA-type 2 comparison was calculated after data was log transformed and showed a difference of 1.58 µg/ml (95%CI: 1.28-1.95, p = 0.0001). There was no significant difference between LADA and non-diabetic controls (p = 0.54). CONCLUSIONS: Adiponectin levels are higher among people with LADA compared to those with type 2 diabetes and are equivalent to levels seen in non-diabetic controls. This suggests that risk of complications in LADA, as with type 1 diabetes may be related more to glycaemic control rather than to factors of the metabolic syndrome.

Association between the adiponectin promoter rs266729 gene variant and oxidative stress in patients with diabetes mellitus.

AIMS: Low levels of adiponectin are associated with type 2 diabetes and coronary heart disease (CHD). Recent evidence also suggests that low levels of adiponectin are associated with increased oxidative stress. Our aim was to examine the association between the rs266729 promoter gene variant (-11377C > G) and plasma markers of oxidative stress in diabetes subjects. METHODS AND RESULTS: Seven hundred and sixty-seven Caucasian subjects with diabetes were successfully genotyped (CC/CG/GG). Genotype data were analysed in relation to plasma total antioxidant status (TAOS) and Oxidized-LDL (Ox-LDL). Plasma adiponectin measurements were available in 206 samples. There was a significant association between genotype and plasma TAOS (CC: 42.1 +/- 13.4% vs. CG: 42.0 +/- 12.0% vs. GG: 47.9 +/- 12.0%, P = 0.02; for CC/CG vs. GG, P = 0.006). With respect to Ox-LDL, CC subjects had 8% higher plasma Ox-LDL compared with CG/GG [CC vs. CG vs. GG: 48.5 (36.3-60.2) U/L vs. 44.8 (35.6-54.1) U/L vs. 44.9 (41.2-49.1) U/L, for CC vs. CG/GG P = 0.03]. For plasma adiponectin, GG subjects had the highest levels [CC vs. CG vs. GG: 8.18 (5.69-15.38) microg/mL vs. 7.12 (5.34-12.97) microg/mL vs. 11.84 (6.98-25.25) microg/mL, P = 0.09; for CC/CG vs. GG, P = 0.05]. CONCLUSION: This study shows an association between a promoter variant in the adiponectin gene and plasma markers of oxidative stress. In line with previous studies, this work supports an antioxidant role for adiponectin which may explain its cardioprotective effect. Further prospective study is necessary to explore the effect of this gene variant in diabetes in relation to CHD risk and oxidative stress.