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Hypoglycaemia

IGF-1 testing could prevent hypoglycaemia

Post-load hypoglycaemia detected in half of all patients, mainly those who underwent RYGB

Testing for insulin-like growth factor 1 (IGF-1) could help to prevent postprandial hypoglycaemia following bariatric surgery, according to paper published by researchers from the Medical University Vienna, Vienna, Austria. The study was published online in the journal PlosOne.

“Post- and particularly pre-operative IGF-1 serum concentrations help in identifying patients at risk for developing post-load hypoglycaemia,” the authors write. “Identification of patients at hypoglycaemia risk based on IGF-1 may improve patient selection for gastric bypass surgery, help to tailor dietary recommendations, promote awareness of patients and health-care professionals for this complication, and may hence further improve the prognosis of these patients.”

A major cause of hypoglycaemia postsurgery is hyperinsulinemic nesidioblastosis. As it is known that pancreatic islets in nesidioblastosis overexpress insulin-like growth factor 1 (IGF-1) receptor α and administration of recombinant IGF-1 provokes hypoglycaemia, the investigators assessed the occurrence of post-load hypoglycaemia one year after bariatric surgery and its relation to pre- and post-operative IGF-1 serum concentrations.

For the study, they performed longitudinal measurements of metabolic and routine parameters in 36 non-diabetic patient s (29 f/7 m; aged 41.3±2.0 y with a median (IQR) BMI of 30.9 kg/m2 (27.5–34.3)), shortly before and approximately one year after the patients underwent elective bariatric surgery (mean follow up time 14±1.9 months).

Thirty patients underwent RYGB, threepatients underwent gastric banding and three patients underwent sleeve gastrectomy. None of the subjects were on oral antidiabetics of any kind, insulin, or corticosteroids.

Outcomes

The researcher report that on average patients lost 15.1±0.8 BMI units, corresponding to a mean weight loss of 43.2±2.5. In addition to the weight loss, they noted a significant reduction in the number of patients with metabolic syndrome, from 19 before surgery to two one year after (p<0.0001). They also recorded a significant improvement in patients' lipid profiles (triglycerides, total, LDL- and HDL-cholesterol, all p<0.01). Circulating concentration of liver enzymes ALT and GGT was also reduced, as was the fatty liver index (FLI) (all p<0.01), indicating a reduction of obesity-associated fatty liver disease.

Plasma HbA1c concentration after surgery was lower than before surgery and in the normal range at both time-points. Fasting plasma glucose and fasting serum insulin concentrations were significantly reduced after the surgery, as was HOMA-IR (all p<0.0001). Glucose concentration during the course of the 2 h-OGTT was drastically changed in the postoperative setting, with significantly lower concentrations after the first hour (Figure 1A).

Moreover, post-load hypoglycaemia (defined as blood plasma glucose concentration <60 mg/dl at 2 h of the OGTT) was detected in half of all patients (n=18, Figure 1B). These were mainly patients who underwent RYGB (n=16).

First phase insulin response to glucose load (calculated as the insulinogenic index) remained similar to the response observed before surgery, but insulin levels were significantly reduced during the second hour of the OGTT (Figure 1C). The post-operative AUC for insulin concentration was significantly lower than before surgery (p=0.019;). Interestingly, the C-peptide concentration at 30 minutes of the test was higher after compared to before the operation (Figure 1D; p = 0.001), but the AUC for C-peptide concentration was not significantly different. Serum IGF-1 concentration increased after surgery by a mean of 20.5±10.2 ng/dl and the increase was significant in trend (p=0.053).

Figure 1: Glucose, insulin and C-peptide concentration during pre-operative and post-operative OGTT - (A) Glucose concentrations during the course of the pre-operative 2 h OGTT (n=35, full lines) compared to the post-operative OGTT (n=35, dashed lines). (B) Histogram of post-operative 2 h glucose concentrations during the OGTT (n=35). Post-load hypoglycemia was defined by a 2 h glucose concentration<60 mg/dl. (C) Insulin and (D) C-peptide concentrations during the course of the pre-operative 2 h OGTT (n=35, full lines) compared to the post-operative OGTT (n=35, dashed lines).

The patients were split into two groups according to their glycaemic condition at 2h during the post-operative OGTT and compared the changes in glucose, insulin and C-peptide concentrations and respective AUC. The researchers noted significant differences in glucose concentration at time point 0′, 90′ and 120′ during the OGTT (p=0.020, p=0.003 and p<0.0001 respectively), but insulin or C-peptide concentrations during the course of the OGTT were not altered except for a slight elevation of C-peptide concentration at 30 minutes (p = 0.06).

“The main finding of our study was that post-load hypoglycaemia approximately one year after bariatric surgery was closely associated with increased circulating IGF-1 concentrations before and after surgery,” they write. “This could indicate that IGF-1 plays an important role in glucose homeostasis following RYBG.”

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