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T2DM

ß-cell incompetence linked to metabolic outcome of BPD

Resaerchers note a weight-independent effect of the operation

Biliopancreatic diversion can improve metabolic control in non-obese patients with type 2 diabetes but induces remission in only 40% of patients with the initial extent of ß-cell incompetence reported as the main predictor of the metabolic outcome, according to a paper published in the Journal of Clinical Endocrinology and Metabolism.

The investigation also notes that peripheral insulin sensitivity was restored early after surgery and also in remitters and non-remitters, “indicating a weight-independent effect of the operation”, write the study researchers from the University of Pisa School of Medicine, Consiglio Nazionale delle Ricerche, Institute of Clinical Physiology, Pisa, Italy.

Although the resolution of type 2 diabetes is commonly associated after biliopancreatic diversion in morbidly obese patients, there is little data on the effect of the procedure on nonobese type 2 diabetic patients.

Therefore, the researchers wanted to record the rate of resolution and examine the role of investigate insulin sensitivity and ß-cell function after the procedure in this group of patients.

Fifteen patients (nine women) with type 2 diabetes were recruited to the study with a mean aged of 55, BM 28.3. The mean duration of type 2 diabetes was 16.2 years.

Each patient was studied at baseline, two months after surgery and one year after surgery. Resolution was defined as an HbA1c <6.5% (<44mmol/mol), a fasting plasma glucose <7.0 mmol/L, and a 2-h plasma glucose <11.1 mmol/L two hours into the oral gloucose tolerance test.

Fifteen non-diabetic volunteers were matched to the patient group by gender, age and BMI, as a comparative weight-matched control group.

Outcomes

The outcomes showed that biliopancreatic diversion resulted in weight loss on average of 12kg at two months and 14kg after one year, while HbA1c reduced from 8.6% to 6.7%, to 6.0% (p<0.0001), during the same time periods.

A total of four patients’ diabetes was resolved at two and six at one year. In addition, LDL-cholesterol concentrations were markedly reduced to levels significantly lower than in controls, although plasma triglycerides did not show significant changes and HDL-cholesterol concentrations were marginally reduced.

The researchers also noted that both insulin resistance and ß-cell dysfunction abated to a substantial and statistically significant extent (Figure 1)

Figure 1. Insulin sensitivity (M value from the euglycemic clamp) in nondiabetic control subjects and diabetic patients before, two months and 12 months after biliopancreatic diversion.

“ß-cell glucose sensitivity increased in the face of a reduction in insulin output, thereby relieving the secretory burden on the ß-cell,” the researchers write.

However, at one post-surgery ß-cell function was on average 30% of that of nondiabetic controls, which the authors claim indicates that a substantial fraction of the ß-cell dysfunction in long-standing diabetes cannot be reversed by biliopancreatic diversion. ß-cell glucose sensitivity at one year was 50% of normal and rate sensitivity was 30% reduced.

“Therefore, the effect of biliopancreatic diversion on peripheral insulin sensitivity is very likely to be, at least in part, independent of weight loss.,” the surmise. “Moreover, in the face of biliopancreatic diversion-induced resolution of insulin resistance, the worse outcome of glycaemic control of the nonobese type 2 diabetic patient presumably is the consequence of poorer initial degree and stunted postoperative recovery of ß-cell function.”

Conclusion

The authors state that in nonobese patients with long-standing type 2 diabetes, biliopancreatic diversion improved metabolic control in all, but induced remission in only one third of them.

“Increases in both insulin sensitivity and ß-cell function were primarily responsible for bringing down glucose and HbA1c levels…peripheral insulin sensitivity was restored to control levels already two months after surgery, and similarly in remitters and nonremitters, implying a weight-independent effect of the operation. Thus, the initial extent of ß-cell incompetence emerges an important predictor of the metabolic outcome of biliopancreatic diversion.”

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