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

Abstract

Background: Non-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.

Method: An analysis of 40 patients who had had detailed longitudinal studies for 12 months.

Results: Twenty-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.

Conclusions: The data presented suggest the existence 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.

FIGURE 1

The TANTALUS-DIAMOND device. Three pairs of Tizer electrodes are implanted in the stomach by laparoscopic surgery. The electrodes are externalized and attached to a pulse generator that is placed in a pocket created in the abdominal subcutaneous fat. The fundal electrodes detect nutrient ingestion. They send the signal to the pulse generator, which activates the anterior and posterior antral electrodes. The non-stimulatory impulse increases the force of antral contractions and not the rate. The pulse generator is recharged once a week through the rechargeable port.

FIGURE 2

The relationship between the fasting plasma triglyceride (mean baseline and 6 months) and the decrease in HbA_1c in patients with Type 2 diabetes inadequately controlled on oral agents. Patients with low triglycerides (black bars, n = 22) had fasting plasma triglycerides ≤ 1.7 mmol/l. Patients with high triglycerides (grey bars, n = 18) had fasting plasma triglycerides > 1.7 mmol/l. The decreases in HbA_1c from baseline in the patients with low triglycerides at 3, 6 and 12 months, respectively, were −15 ± 2.1, −16 ± 2.2 and −14 ± 3.0 mmol/mol (−1.4 ± 0.20,– −1.5 ± 0.20 and −1.3 ± 0.26%) and in the patients with high triglycerides −7 ± 1.7, −5 ± 1.6 and −5 ± 1.7 mmol/mol (−0.7 ± 0.16, −0.4 ± 0.18 and −0.4 ± 0.16%). P-values between the groups with low and high triglycerides at 3 and 12 months were 0.008 and at 6 months < 0.0001.

FIGURE 3

Pearson correlation between fasting plasma triglyceride level and the decrease in HbA_1c at 1 year of electrical stimulation treatment in all 40 patients.