Fasting plasma triglycerides predict the glycaemic response to treatment of Type 2 diabetes by gastric electrical stimulation. A novel lipotoxicity paradigm

Abstract

BackgroundNon-stimulatory, meal-mediated electrical stimulation of the stomach (TANTALUS-DIAMOND) improves glycaemic control and causes modest weight loss in patients with Type 2 diabetes who are inadequately controlled on oral anti-diabetic medications. The magnitude of the glycaemic response in clinical studies has been variable. A preliminary analysis of data from patients who had completed 6 months of treatment indicated that the glycaemic response to the electrical stimulation was inversely related to the baseline fasting plasma triglyceride level.MethodAn analysis of 40 patients who had had detailed longitudinal studies for 12 months.ResultsTwenty-two patients with fasting plasma triglycerides ≤ 1.7 mmol/l had mean decreases in HbA1c after 3, 6 and 12 months of gastric contraction modulation treatment of −15 ± 2.1 mmol/mol (−1.39 ± 0.20%), −16 ± 2.2 mmol/mol (−1.48 ± 0.20%) and −14 ± 3.0 mmol/mol (−1.31 ± 0.26%), respectively. In contrast, 18 patients with fasting plasma triglyceride > 1.7 mmol/l had mean decreases in HbA1c of −7 ± 1.7 mmol/mol (−0.66 ± 0.16%), −5 ± 1.6 mmol/mol (−0.44 ± 0.18%) and −5 ± 1.7 mmol/mol (−0.42 ± 0.16%), respectively. Pearson's correlation coefficient between fasting plasma triglyceride and decreases in HbA1c at 12 months of treatment was 0.34 (P < 0.05). Homeostasis model assessment of insulin resistance was unchanged during 12 months of treatment in patients with high baseline fasting triglycerides, while it progressively improved in patients with low fasting plasma triglycerides. Patients with low fasting plasma triglycerides had a tendency to lose more weight than those with high fasting plasma triglycerides, but this did not achieve statistical significance.ConclusionsThe data presented suggest the existance of a triglyceride lipotoxic mechanism that interferes with gastric/neural mediated pathways that can regulate glycaemic control in patients with type 2 diabetes. The data suggest the existence of a triglyceride lipotoxic pathway that interferes with gastric/neural mediated pathways that can regulate glycaemic control.

A Pilot Study to Compare Meal-Triggered Gastric Electrical Stimulation and Insulin Treatment in Chinese Obese Type 2 Diabetes

“…However, none of them reported clinical evidence of neuropathy during preoperative screening tests. On the other hand, Lebovitz et al 26 recently reported increased HbA1c responses to GCM therapy in patients with low TG and proposed that TG-associated lipotoxicity might interfere with gastric/neural-mediated pathways in the regulation of glycemic control in T2D. In support of these findings, we also found that patients with GCM implantation and a low TG level had a greater and more sustained reduction in body weight and HbA1c than those with high TG levels.…”

Modulacja kurczliwości żołądka — nowa metoda leczenia cukrzycy typu 2 u osób z otyłością

“…In a discussion of this finding a direct or indirect impact of elevated serum levels of triglycerides (i.e. above 150 ng/mL) on inhibiting the glycaemic effect of gastric stimulation was considered [30]. In animal studies an intestine-brain-liver axis was found, by which the lipids in the upper intestine with the specific mechanisms underlying this effect stimulate neural transmission to the hindbrain; therefore, after transformation, signals are efferently conducted through vagus nerve branches and suppress hepatic glucose production [31,32].…”

“…W dyskusji nad tym zjawiskiem autorzy podnoszą możliwość bezpośredniego lub pośredniego hamujące-go wpływu hipertriglicerydemii (powyżej 150 ng/ml) Tabela I. cd. Wyniki badań klinicznych z zastosowaniem modulacji kurczliwości żołądka u ludzi PRACE POGLĄDOWE na efekt glikemiczny stymulacji żołądka [30]. Wyniki wcześniej opublikowanych badań na zwierzętach ujawniły istnienie osi jelitowo-mózgowo-wątrobowej, poprzez którą lipidy obecne w górnym odcinku przewodu pokarmowego w następstwie uruchomienia specyficznych mechanizmów pobudzają przewodzenie impulsów drogą neuralną do tyłomózgowia, skąd po transformacji sygnały przesyłane są za pośrednictwem eferentnych włókien nerwu błędnego do wątroby, gdzie hamują procesy glukonegonezy [31,32].…”

Updates on gastric electrical stimulation to treat obesity: Systematic review and future perspectives

“…Five Transcend ® studies [20,21,30,35,36] had large participant numbers, but most of them had a drop-out rate of more than 50% by the end of their trials. The studies with low drop-out numbers were the SHAPE trial by Shikora et al [21] , 2009 (10 drop-outs), and the two TANTALUS ® trials [37,38] (0 drop-out in both trials). The EMPOWER study by Sarr et al [34] in 2012 had 41 drop-outs but had a large population group of 294 at the beginning of the study, Duplicate articles (i.e., these articles are already included in the results of the Pubmed literature search).…”

“…Lebovitz et al [38] , [43] , 2007 12/11 39.1 ± 8.9 NR/41.6 ± 3.4 1.5 N/NR T2DM Bohdjalian et al [72] , 2006 12 [20] , Favretti et al [74] , All trials were non-randomized; no follow-up length and lifestyle change advice reported.…”