Blood glucose control and metabolic dysfunction-associated steatotic liver disease in people with type 1 diabetes.

PURPOSE: Metabolic dysfunction-associated steatotic liver disease (MASLD) may have distinctive pathophysiological features in type 1 diabetes (T1D). We evaluated the independent role of blood glucose control on MASLD in T1D. METHODS: In a cross-sectional study on 659 T1D adult patients, MASLD was assessed by the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI). Anthropometric, biochemical, and clinical parameters were retrieved from electronic records. Blood glucose control status was evaluated by dividing participants into subgroups according to the median value of HbA1c [7.6% (60 mmol/mol)], and this analysis was repeated excluding overweight/obese patients. RESULTS: Patients with HbA1c above 7.6% (60 mmol/mol) showed significantly higher MASLD indices (HSI 38 ± 6 vs. 36 ± 5, p < 0.001; FLI 26 ± 26 vs.19 ± 19, p < 0.001), and higher proportions of MASLD identified by HSI (57 vs. 44%, p < 0.001) and FLI (14 vs. 7%, p < 0.001) than patients with HbA1c below 7.6% (60 mmol/mol). Similar results were obtained for HSI after the exclusion of overweight/obese patients. Stepwise linear regression analysis confirmed that HbA1c was independently associated with HSI (r = 0.496, p = 0.009) and FLI (r = 0.722, p = 0.007); waist circumference with HSI (r = 0.492, p < 0.001); and waist circumference (r = 0.700, p < 0.001), HDL cholesterol (r = 0.719, p < 0.001), and LDL cholesterol (r = 0.712, p < 0.001) with FLI. CONCLUSIONS: Blood glucose control is a main factor associated with MASLD in adults with T1D, also independently of overweight and obesity. Appropriate therapeutic strategies focused on tight blood glucose control may also be needed for the prevention and treatment of MASLD in T1D.

Diabetes remission after bariatric surgery is characterized by high glycemic variability and high oxidative stress.

BACKGROUND AND AIM: To evaluate glycemic variability (GV) and oxidative stress in patients who achieved type 2 diabetes (T2DM) remission after bariatric surgery (BS). METHODS AND RESULTS: Twenty-two patients (M/F10/12, age 50 ± 9 years, BMI 31 ± 6 kg/m2) who were in remission of T2DM (T2DM remitters) after BS since at least 1 year and 22 age-, sex- and BMI-matched control subjects were studied. Of the BS group, eleven subjects had undergone Roux-en-Y gastric bypass (RYGB) and eleven subjects sleeve gastrectomy (SG). Oral glucose tolerance test (OGTT), 7 days-continuous glucose monitoring, 24-h urinary excretion of 8-isoprostaglandin F2α (8-isoPGF2α) and dietary intake evaluation were performed. According to general linear model for repeated measures, glucose and insulin response during OGTT were significantly different in T2DM remitter than in control subjects (p < 0.001, for both). All measures of GV (standard deviation, coefficient of variation and mean amplitude of glucose excursions) were significantly higher in T2DM remitters than in controls, (p < 0.001 for all). These indexes were higher among RYGB than SG patients (p < 0.05). The time spent out of the 60-160 mg/dl range was significantly longer in T2DM remitters undergoing RYGB than in controls (p < 0.02). Mean 24-h urinary 8-isoPGF2α excretion was significantly higher in T2DM remitters than that of control subjects (p = 0.04). All GV indexes were directly correlated with blood glucose levels at 30 and 60 min during OGTT (p < 0.05-0.001). CONCLUSION: Remission of T2DM after BS is characterized by high GV and high oxidative stress in the face of fasting blood glucose and HbA1c within the normal range.

Comparative Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Glucose Homeostasis and Incretin Hormones in Obese Type 2 Diabetic Patients: A One-Year Prospective Study.

The aim of the work was to compare the hormonal and the metabolic mechanisms involved in weight loss and remission of T2DM one year after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in morbidly obese type 2 diabetic (T2DM) patients. Insulin sensitivity, insulin secretion, and the gastrointestinal (GI) hormone response to a mixed meal test (MMT) were evaluated before and one year after BS (14 RYGB and 19 VSG). RYGB and VSG groups had similar characteristics at baseline. Weight loss at one year was similar in the 2 groups (ΔBMI%: - 32±10 and - 30±7%, p=0.546). Insulin sensitivity and insulin secretion improved similarly after either procedures with a similar rate in T2DM remission (86% in RYGB and 76% in VSG). Meal-stimulated GLP-1 levels increased after both procedures reaching significantly higher levels after RYGB (p=0.0001). GIP response to MMT decreased to a similar extent after the 2 interventions (p=0.977). Both fasting and post-meal ghrelin concentrations were markedly suppressed after VSG and significantly lower than RYGB (p=0.013 to p=0.035). The improvement of insulin sensitivity and beta-cell function was significantly associated with weight loss (p=0.014 to p=0.035), while no relation was found with the changes in GI hormones. In conclusion, in morbidly obese T2DM patients, RYGB and VSG result in similar improvements of the glucose status in the face of different GI hormonal pattern. Weight loss is the key determinant of diabetes remission one year after surgery.

Effects of bariatric surgery on markers of subclinical atherosclerosis and endothelial function: a meta-analysis of literature studies.

BACKGROUND/OBJECTIVES: Several studies confirmed a significantly increased carotid intima-media thickness (IMT) and impaired flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) in obese subjects, but few data are available on the effects of bariatric surgery on these markers of cardiovascular (CV) risk. We performed a meta-analysis of studies evaluating changes in IMT, FMD and NMD in obese patients after bariatric surgery. METHODS: A systematic search was performed in the PubMed, Web of Science, Scopus and EMBASE databases without any language or publication year restriction. The last search was performed in January 2015. In addition, the reference lists of all retrieved articles were manually reviewed. Prospective studies evaluating the impact of bariatric surgery on the markers of CV risk were included. Changes in IMT, FMD and NMD after bariatric surgery were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CIs). IMT has been expressed in millimeters (mm); FMD and NMD as percentage (%). Impact of clinical and demographic features on effect size was assessed by meta-regression. RESULTS: Ten articles (314 obese patients) were included in the analysis. Six studies contained data on IMT (7 data sets; 206 patients), 8 studies on FMD (9 data sets; 269 patients) and 4 on NMD (4 data sets; 149 patients). After bariatric surgery, there was a significant reduction of IMT (MD: -0.17 mm; 95% CI: -0.290, -0.049; P=0.006) and a significant improvement in FMD (MD: 5.65%; 95% CI: 2.87, 8.03; P<0.001), whereas NMD did not change (MD: 2.173%; 95% CI: -0.796, 5.142; P=0.151). Interestingly, percentage of changes in the body mass index were associated with changes in IMT (Z=11.52, P<0.001), FMD (Z=-4.26, P<0.001) and NMD (Z=-3.81, P<0.001). CONCLUSIONS: Despite heterogeneity among studies, bariatric surgery is associated with improvement of subclinical atherosclerosis and endothelial function. These effects may significantly contribute to the reduction of the CV risk after bariatric surgery.

Clinical efficacy of bariatric surgery versus liraglutide in patients with type 2 diabetes and severe obesity: a 12-month retrospective evaluation.

AIMS: To evaluate the clinical efficacy of bariatric surgery vs medical therapy with liraglutide on weight loss, glycemic control and cardiovascular risk profile in patients with type 2 diabetes and severe obesity. METHODS: A retrospective evaluation was conducted in 31 patients with type 2 diabetes and severe obesity who had undergone bariatric surgery and in 31 patients with type 2 diabetes and comparable body weight who had added liraglutide to their background medical treatment in the period 2009-2013. Anthropometric parameters, glycemic control, treatment of diabetes and other comorbidities, safety and side effects before and 12 months after treatment were assessed. RESULTS: Age was 47 ± 8 years (mean ± SD) in bariatric surgery and 56 ± 9 years in medical treatment group (p < 0.001); body mass index before treatment was 44 ± 7 and 40 ± 4 kg/m(2) in bariatric surgery and medical treatment, respectively (p = 0.03). Twelve months after treatment, average weight loss was 38 ± 15 kg among bariatric surgery patients, and 5 ± 8 kg in medical treatment group (p < 0.001). Glycemic control improved in both groups with greater improvement in bariatric surgery patients. The UKPDS risk score decreased in both groups, although it remained higher in medical treatment than in bariatric surgery patients (p < 0.001). Of note, almost 60 % of patients on liraglutide met the target of glycated hemoglobin <7 % (53 mmol/mol) and lost ≥5 % of body weight. CONCLUSIONS: In severely obese type 2 diabetic patients, bariatric surgery reduced body weight and improved overall metabolic control to a greater extent than medical treatment. Randomized clinical studies are necessary.

Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study.

Bleeding is a common and feared complication of oral anticoagulant therapy. Several prediction models have been recently developed, but there is a lack of evidence in patients with venous thromboembolism (VTE). The aim of this study was to validate currently available bleeding risk scores during long-term oral anticoagulation for VTE. We retrospectively included adult patients on vitamin K antagonists for VTE secondary prevention, followed by five Italian Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between January 2010 and August 2012. All bleeding events were classified as major bleeding (MB) or clinically-relevant-non-major-bleeding (CRNMB). A total of 681 patients were included (median age 63 years; 52.0% female). During a mean follow-up of 8.82 (± 3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB), for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding was higher in the first three months of treatment (15.86/100 patient-years) than afterwards (7.13/100 patient-years). The HAS-BLED showed the best predictive value for bleeding complications during the first three months of treatment (area under the curve [AUC] 0.68, 95% confidence interval [CI] 0.59-0.78), while only the ACCP score showed a modest predictive value after the initial three months (AUC 0.61, 95%CI 0.51-0.72). These two scores had also the highest sensitivity and the highest negative predictive value. None of the scores predicted MB better than chance. Currently available bleeding risk scores had only a modest predictive value for patients with VTE. Future studies should aim at the creation of a new prediction rule, in order to better define the risk of bleeding of VTE patients.

Early improvement of postprandial lipemia after bariatric surgery in obese type 2 diabetic patients.

BACKGROUND: Bariatric surgery (BS) is able to positively influence fasting lipid profile in obese type 2 diabetic patients (T2DM), but no data is available on the impact of BS on postprandial lipid metabolism neither on its relation with incretin hormones. We evaluated the short-term (2 weeks) effects of BS on fasting and postprandial lipid metabolism in obese T2DM patients and the contribution of changes in active GLP-1. METHODS: We studied 25 obese T2DM patients (age = 46 ± 8 years, BMI = 44 ± 7 kg/m2), of which 15 underwent sleeve gastrectomy and 10 underwent gastric bypass. Lipid and incretin hormone concentrations were evaluated for 3 h after ingestion of a liquid meal before and 2 weeks after BS. RESULTS: After BS, there was a significant reduction in body weight (p < 0.001), fasting plasma glucose (p < 0.001), fasting plasma insulin (p < 0.05), HOMA-IR (p < 0.001), and fasting plasma lipids (p < 0.05). The meal response of plasma triglycerides, total cholesterol, and HDL cholesterol was significantly lower compared to pre-intervention (p < 0.05, p < 0.001). In particular, the incremental area under the curve (IAUC) of plasma triglycerides decreased by 60% (p < 0.005). The meal-stimulated response of active GLP-1 increased, reaching a statistical significance (p < 0.001). CONCLUSIONS: BS leads to an early improvement of fasting and postprandial lipemia. The fall in fasting triglycerides is associated with an improvement of insulin resistance, while the reduction of postprandial lipemia is likely related to reduced intestinal lipid absorption consequent to bariatric surgery.

Ropivacaine infusion in diabetics subject with peripheral arterial disease. A prospective study.

BACKGROUND: Peripheral arterial disease (PAD) predicts cardiovascular and cerebrovascular ischemic events. PAD treatment is aimed at reducing clinical symptoms, local tissue loss and at preventing complications. AIMS: To evaluated the effect of peridural analgesia on peripheral perfusion and pain control. METHODS: In 280 diabetic subjects with severe limb ischemia (65.7% males and 34.3% females, mean age 59.3±14.4 years) with a failure of medical treatment and contraindications to endovascular and/or surgical reperfusion, we performed a 30-day long peridural ropivacaine infusion, monitoring blood pressure, VAS and ABI periodically. RESULTS: During ropivacaine infusion VAS significantly decreased (from 4.06±0.343 to 1.96±0.413, p<0.001). Furthermore, in the 261 (93.2%) subjects achieving a VAS value ≤2 during infusion, the effect was maintained after infusion withdrawing. ABI significantly improved both during infusion (from 0.30±0.04 at baseline to 0.65±0.05 at T30, p<0.001) and after infusion withdrawing as compared with baseline values. CONCLUSIONS: 30-day peridural analgesia with ropivacaine is a valuable therapeutic option in severe peripheral limb ischemia subjects with contraindication to surgery and with pharmacological therapy failure.

Late micronutrient deficiency and neurological dysfunction after laparoscopic sleeve gastrectomy: a case report.

Although the micronutrient deficiencies and the related neurological manifestations are widely reported after malabsorbitive weight loss surgery, little is known about cerebral dysfunction secondary to micronutrient impairment in subjects undergoing restrictive interventions (that is, sleeve gastrectomy). We describe a case of a 27-year-old woman with a late development of a Wernicke's encephalopathy (WE) and of severe polyneuropathy following a sleeve gastrectomy without any sleeve stenosis. The impact of WE after bariatric surgery is significantly underestimated. Such a risk should be taken into consideration also after restrictive weight loss surgery. Thus, surgeon/clinicians involved in bariatric patients management must be aware of neurological sequelae related to this intervention.

Impact of sleeve gastrectomy on weight loss, glucose homeostasis, and comorbidities in severely obese type 2 diabetic subjects.

This study was undertaken to assess medium-term effects of laparoscopic sleeve gastrectomy (LSG) on body weight and glucose homeostasis in severely obese type 2 diabetic (T2DM) subjects. Twenty-five obese T2DM subjects (10 M/15 F, age 45 ± 9 years, BMI 48 ± 8 kg/m(2), M ± SD) underwent evaluation of anthropometric/clinical parameters and glucose homeostasis before, 3 and 9-15 months after LSG. Mean BMI decreased from 48 ± 8 kg/m(2) to 40 ± 9 kg/m(2) (P < .001) at 3 months and 34 ± 6 kg/m(2) (P < .001) at 9-15 months after surgery. Remission of T2DM (fasting plasma glucose < 126 mg/dL and HbA1c < 6.5% in the absence of hypoglycemic treatment) occurred in all patients but one. There was a remarkable reduction in the percentage of patients requiring antihypertensive and hypolipidemic drugs. Our study shows that LSG is effective in producing a significant and sustained weight loss and improving glucose homeostasis in severely obese T2DM patients.