1,721,106 research outputs found
High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).
Full text linkThe aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up.
This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression.
RESULTS:
During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ???25???kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95).
CONCLUSIONS:
High GADA titer, BMI ??? 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients
Preoperative weight loss by noninvasive approach in patients with obesity scheduled for bariatric and metabolic surgery: an update narrative review of indications and results available until 2024
No full textMetabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity and its metabolic complications. Currently, most MBSs are performed laparoscopically. However, high weight associated with an enlarged liver (especially the left lobe liver section, LLLS) may complicate the technical aspects of this surgery. Therefore, before MBS, moderate preoperative weight loss (PreopWL), and reduction in LLLS are desirable. Moreover, studies are inconclusive regarding which is the best approach to apply. This narrative review aimed to describe the current scientific evidence on the effect of a noninvasive approach, such as dietary or pharmacotherapy or space-occupying devices on PreopWL, peri-operative complications, hospital length of stay, and post-operative complications in patients with obesity scheduled for MBS. We conducted a literature search and screening for relevant publications from January 2010 to June 2024. We found that PreopWL before MBS is helpful for both patients and surgeons, as it leads to various benefits, such as a decrease in body weight and LLLS size, a lower risk of intra- and post-operative complications, shorter surgery times, and reduced hospital stays. In this context, concerning dietary approaches, several dietary protocols have been introduced over time, among which very low-calorie diets and very low energy ketogenic therapy are widely prescribed; however, larger randomized-controlled trials (RCTs) with well-defined dietary protocols are necessary to make definitive conclusions. Obesity management medications, such as the lipase inhibitor orlistat, phentermine/topiramate, naltrexone/bupropion, the glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide, and the novel dual glucose dependent insulinotropic peptide (GIP)/GLP-1 receptor agonist tirzepatide, has shown to be effective in promoting PreopWL before MBS; however, larger, well-designed RCTs are needed to establish optimal treatment protocols and assess their true benefits in patients scheduled for MBS. Space-occupying devices such as the swallowable intragastric balloon and hydrogel capsules, represent a promising tools but further research is essential to confirm their role
High glucose and homocysteine synergistically affect the metalloproteinases-tissue inhibitors of metalloproteinases pattern, but not TGFbeta expression, in human fibroblasts
No full textAIMS/HYPOTHESIS:
Atherosclerosis is particularly aggressive in patients with diabetes. Hyperhomocysteinaemia causes oxidative stress and cytokine secretion: its atherogenic effect is mediated by an enhanced inflammatory response. Matrix metalloproteinases (MMPs) regulate extracellular matrix degradation and remodelling, and contribute to the vulnerability of the atherosclerotic lesion. Fibroblasts contribute to collagen biosynthesis and participate in plaque remodelling via expression and release of MMP2 and MMP9. To explore the role of hyperhomocysteinaemia in cellular pathways involved in plaque growth and stability in diabetic patients, we studied the effect of hyperhomocysteinaemia in human fibroblasts grown in the presence of normal or high glucose concentrations.
MATERIALS AND METHODS:
In fibroblasts of five normal subjects, grown at 5.5 or 22 mmol/l glucose and treated with homocysteine, we determined: (1) MMP2, MMP9 and tissue inhibitor of metalloproteinases (TIMP)-1 (an MMP inhibitor) production by western blot analysis; (2) their activity by zymography; (3) TGFB1 expression by real-time PCR; and (4) TGFB, fibronectin and IL6 release by ELISA.
RESULTS:
Hyperhomocysteinaemia increased the production and enzymatic activity of MMP2 and MMP9, the effect being more pronounced in high glucose. Conversely, TIMP1 production was reduced by hyperhomocysteinaemia in both conditions, especially in high glucose. Hyperhomocysteinaemia also stimulated IL6 release, at least in part through nuclear factor-kappaB activation. TGFB1 expression was not affected by hyperhomocysteinaemia either in normal or in high glucose.
CONCLUSIONS/INTERPRETATION:
Homocysteine upregulates the MMP-TIMP pathway and IL6 release, the effect being stronger in the presence of high glucose. These actions of homocysteine may contribute to the increased atherogenesis observed in diabetic patients with poor metabolic control
Reply to Landry et al. Findings from Diet Comparison Difficult to Interpret in the Absence of Adherence Assessment. Comment on “Tricò et al. Effects of Low-Carbohydrate versus Mediterranean Diets on Weight Loss, Glucose Metabolism, Insulin Kinetics and β-Cell Function in Morbidly Obese Individuals. Nutrients 2021, 13, 1345”
No full textWe thank Dr. Landry and colleagues [...
Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis
Full text linkWhile hyperthyroidism and hypothyroidism cause dysglycemia, the relationship between thyroid hormone levels within the normal range and insulin resistance (IR) is unclear. In 940 participants with strictly normal serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) followed up for 3 yr, we measured insulin sensitivity (by the insulin clamp technique) and 35 circulating metabolites. At baseline, across quartiles of increasing fT3 levels (or fT3/fT4 ratio) most features of IR emerged [i.e., male sex, greater body mass index (BMI), waist circumference, heart rate, blood pressure, fatty liver index, free fatty acids, and triglycerides; reduced insulin-mediated glucose disposal; and β-cell glucose sensitivity). In multiadjusted analyses, fT3 was reciprocally related to insulin sensitivity and, in a subset of 303 subjects, directly related to endogenous glucose production. In multiple regression models adjusting for sex, age, BMI, and baseline value of insulin sensitivity, higher baseline fT3 levels were significant predictors of decreases in insulin sensitivity. Moreover, baseline fT3 predicted follow-up increases in glycemia independently of sex, age, BMI, insulin sensitivity, β-cell glucose sensitivity, and baseline glycemia. Serum tyrosine levels were higher with IR and were directly associated with fT3; higher α-hydroxybutyrate levels signaled enhanced oxidative stress, thereby impairing tyrosine degradation. In 25 patients with morbid obesity, surgery-induced weight loss improved IR and consensually lowered fT3 levels. High-normal fT3 levels are associated with IR both cross-sectionally and longitudinally, and predict deterioration of glucose tolerance. This association is supported by a metabolite pattern that points at increased oxidative stress as part of the IR syndrome
Skin Vasodilator Function and Vasomotion in Patients with Morbid Obesity: Effects of Gastric Bypass Surgery
No full textObesity-associated microvascular dysfunction (MVD) involves different body tissues, including skin, and concurs to increased cardiovascular risk in obese patients (Ob-P). Generalized improvement of MVD is an important goal in obesity treatment. Since skin MVD mirrors generalized systemic MVD, skin microvascular investigation in prospective studies in Ob-P may surrogate microvascular investigation in organs more important for cardiovascular risk of the studied patients. In this prospective study, we measured forearm skin post-occlusive reactive hyperaemia (PORH), as percentage flow increase from baseline, and skin vasomotion in 37 Ob-P before Roux-en-Y gastric bypass (RYGB), and in 24 of them about 1 year after RYGB, using laser Doppler flowmetry (LDF). The spectral contribution of skin LDF signal oscillations in the frequency intervals of 0.01-0.02 Hz, 0.02-0.06 Hz, and 0.06-0.2 Hz--corresponding to endothelial-, sympathetic-, and myogenic-dependent vasomotion, respectively, was measured by means of spectral Fourier analysis. The same measurements were also performed in 28 healthy, lean subjects (HLS). Before RYGB, Ob-P had a significant reduction in PORH and in the all vasomotion parameters investigated, compared with HLS. After RYGB, Ob-P who completed the follow-up, had a significant weight loss (∼40 kg on average), together with a full normalisation in PORH and in vasomotion parameters, regardless of diabetes status. Surgically induced sustained weight loss resulted in full normalisation of skin microvascolar function in Ob-P about 1 year after RYGB. This result suggests a beneficial effect of sustained weight loss on generalized MVD of the studied Ob-P
The Beneficial Effects of Bariatric-Surgery-Induced Weight Loss on Renal Function.
No full textObesity represents an independent risk factor for the development of chronic kidney disease (CKD), leading to specific histopathological alterations, known as obesity-related glomerulopathy. Bariatric surgery is the most effective means of inducing and maintaining sustained weight loss. Furthermore, in the context of bariatric-surgery-induced weight loss, a reduction in the proinflammatory state and an improvement in the adipokine profile occur, which may also contribute to the improvement of renal function following bariatric surgery. However, the assessment of renal function in the context of obesity and following marked weight loss is difficult, since the formulas adopted to estimate glomerular function use biomarkers whose production is dependent on muscle mass (creatinine) or adipose tissue mass and inflammation (cystatin-c). Thus, following bariatric surgery, the extent to which reductions in plasma concentrations reflect the actual improvement in renal function is not clear. Despite this limitation, the available literature suggests that in patients with hyperfiltration at baseline, GFR is reduced following bariatric surgery, whereas GFR is increased in patients with decreased GFR at baseline. These findings are also confirmed in the few studies that have used measured rather than estimated GFR. Albuminuria is also decreased following bariatric surgery. Moreover, bariatric surgery seems superior in achieving the remission of albuminuria and early CKD than the best medical treatment. In this article, we discuss the pathophysiology of renal complications in obesity, review the mechanisms through which weight loss induces improvements in renal function, and provide an overview of the renal outcomes following bariatric surgery
Efficacy of Lisosan G (fermented wheat) on reactive hypoglycemia after bariatric surgery
No full textIntroduction: post-bariatric hypoglycemia (PBH) is considered a chronic complication after gastric bypass (RYGB) impacting roughly 30 % of patients. Current treatments often focus on nutritional interventions to reduce the frequency of episodes. This prospective study evaluated the effectiveness of Lisosan G (LG), a fermented wheat-based supplement added to the diet, in mitigating PBH episodes and elucidating its mechanism of action on the gut-pancreas axis. Methods: twenty subjects with PBH, who had undergone RYGB between 2015 and 2018, were enrolled. Subjects underwent clinical examination, blood test, and a 3-hour oral glucose load test (OGTT). Then, they were monitored for 2-weeks on a free diet with continuous glucose monitoring (CGM), which was extended for another 2-weeks after introduction of LG supplementation (5 g, twice daily) on the same diet. Finally, subjects repeated OGTT and blood test. PBH was defined as interstitial glucose ≤ 54 mg/dl. Results: after treatment, a marked reduction in PBH time was observed (75[23–113] vs 16 [0–33], minutes, p < 0.001). During OGTT, there was an increase in glucose nadir (44 ± 11 vs 56 ± 10, mg/dl, p = 0.038), and a significantly decrease in total GLP-1 AUC (7.6 ± 4.1 vs 6.5 ± 3.8, nmol/L*min, p = 0.043), in potentiation factor ratio (p = 0.037) and in total insulin AUC (57 ± 12 vs 49 ± 9, nmol/L*min, p = 0.043). Conclusion: LG effectively reduces PBH frequency and duration, probably by attenuating GLP-1 concentrations and leading to a decrease in the second phase of insulin secretion in response to glucose. These findings underscore the promise of LG as a novel adjunct therapy for PBH, particularly when added to the diet, and emphasize the need for further exploration into its microbiota-modulating and anti-inflammatory effects
Effects of hemodialysis and vitamin E supplementation on low-density lipoprotein oxidizability in end-stage renal failure.
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