Mitigation of Type 2 Diabetes by Partial Ileal Bypass
Mitigation of Type 2 Diabetes by Partial Ileal Bypass
This is a study of people with type 2 diabetes and high cholesterol between age 18 and 65.
 This study is trying to figure out if a partial bypass of the small intestine can reverse
 type 2 diabetes for people who require cholesterol lowering and who cannot tolerate the
 statin drugs.
The partial ileal bypass (PIB) operation is a standard procedure used in the management of
 hyperlipidmia since 1963. POSCH was the intervention modality in the National Institutes of
 Health, National Heart Lung and Blood Institute-funded Program on the Surgical Control of the
 Hyperlipidemias (POSCH) trial. The POSCH study was a secondary trial in patients with a
 documented prior myocardial infarction. The trial compared the post-dietary lipid therapy
 changes in 421 PIB-intervention patients to 417 controls, with a lowering of total plasma
 cholesterol of 24% (P<0.0001), a lowering of low density lipoprotein (LDL)-cholesterol of 38%
 (P<0.0001), and an elevation of high density lipoprotein (HDL)-cholesterol of 4% (P=0.02).
 These lipid changes were associated with a 35% (P<0.001) reduction in the intervention group
 of death due to coronary heart disease and confirmed recurrent myocardial infarction, as well
 as a 27% (P<0.038) reduction in peripheral vascular disease, and a 54% (P<0.005) diminution
 in the occurrence of coronary artery surgery or angioplasty. Concurrently with the clinical
 study, POSCH assessed sequential coronary arteriograms at 0, 3, 5, 7, and 10 years, which
 showed less disease progression in the surgery group, and even statistically significant
 plaque regression in the PIB cohort. POSCH PIB patients exhibited a statistically significant
 increase in life expectancy; this finding persisted at a 25-year follow-up assessment.

 In the field of metabolic/bariatric surgery, resolution of type 2 diabetes by
 gastrointestinal tract manipulations was clearly demonstrated by 1998. In three
 meta-analyses, the procedures that involved shortening of the ileum (biliopancreatic
 diversion and duodenal switch) were responsible for the highest percentage of type 2 diabetes
 resolution. Recently under evaluation are standard metabolic/bariatric and experimental
 metabolic operations that will engender type 2 diabetes resolution with minimal or no weight
 loss in non-obese diabetic patients.

 The gut-diabetes relationship has often been attributed to an increased elaboration of the
 hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), both secreted by the L-cells
 of the intestinal mucosa. These hormones seem to work in concert, either eliciting the same
 metabolic response or augmenting the actions of the other. With respect to pancreatic
 endocrine function, GLP-1 and PYY contribute to the incretin effect, counteract the insulin
 depression action of gastrin stimulating peptide and gastrin-releasing peptide, and stimulate
 glucose-dependent insulin secretion, preinsulin gene expression, beta-cell proliferation, and
 antiapoptopic pathways. It has been shown that GLP-1 secretion is reduced in patients with
 type 2 diabetes. In a recent study of the effects of direct human terminal ileum and cecal
 contact with a food hydrolysate, significant plasma GLP-1 and PYY elevations were
 demonstrated, confirming the ability of the cecum, as well as the ileum, to secrete GLP-1 and
 PYY on stimulation. In the Goto-Kakizaki rat with naturally occurring type 2 diabetes, ileal
 bypass or excision did not lower GLP-1 production, but interestingly increased it five- to
 six-fold.

 These complementary studies gave rise to the hypothesis that: the PIB operation, in addition
 to its action on cholesterol metabolism, may aslo prevent and resolve type 2 diabetes.

 In our laboratory at the University of Minnesota, the investigators have clearly established
 the mechanism for the reduction of total cholesterol and LDL-cholesterol by PIB: interference
 with the cholesterol and bile acid enterohepatic cycles, markedly decreased absorption and
 reabsorption of cholesterol and bile acids, increased excretion of cholesterol and bile
 acids, increased turnover of cholesterol to generate bile acids and replenish the cholesterol
 pool, and the insufficient ability of the body (even in familial hypercholesterolemics) to
 maintain the miscible (plasma and liver) and less-freely miscible (tissues, including the
 arteries) body pools, and, thereby, a depletion of the cholesterol content of atherosclerotic
 plaques. the investigators have now (see above) added to that knowledge that the elimination
 of the terminal ileum from the intestinal pathway will increase circulating GLP-1 levels,
 with this incretin probably emanating from the cecum.

 The investigators have now completed and submitted for publication our study on the incidence
 of type 2 diabetes in the POSCH program 25 plus years after formal trial closure (IRB Code
 Number: 1408M53283). The title of our paper is "Partial Ileal Bypass Affords Protection from
 Onset of Type 2 Diabetes". Of the 66 control patient responders in POSCH, 17 contracted type
 2 diabetes (25.8%); of 80 PIB responders, 8 contracted type 2 diabetes (10%). The difference
 between groups was significant (P=0.015 by Fisher Exact Test) with an odds ratio of 0.320 for
 the PIB group and an over two-fold (2.6) increase in the incidence of type 2 diabetes in the
 controls. Including borderline type 2 diabetes (prediabetic) patients, these values were 22
 of 66 controls (33.3%) and 10 of 80 PIB patients (12.5%), with an odds ratio of 0.286 and a
 P<0.004, and again an over two-fold (2.7) increase in the incidence of type 2 diabetes in the
 control patients. Therefore, PIB appeared to afford protection from the onset of type 2
 diabetes for over 30 years.
Inclusion Criteria:

 -  Hyperlipidemia patients referred for partial ileal bypass, who also have type 2
 diabetes.

 Exclusion Criteria:

 -  Preoperative C-peptide indicative of non-functioning islet cells.