Clinical trial NCT02532829: Human Intestinal Peptides Evaluation and Research
Official title: Effects of Different Metabolic States and Surgical Models on Glucose Metabolism and Secretion of Ileal L-cell Peptides
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Obesity
Diabetes Mellitus, Type 2
Lead sponsor: Turkish Metabolic Surgery Foundation
Sponsor class: OTHER
First posted: 2015-08-26
Enrollment: 240
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. GROUP NS-A: Healthy participants, no known disease, no previous surgery, HbA1c\<5.7%, BMI\<25 kg/m2.
2. GROUP NS-B: Obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI\>30 kg/m2.
3. GROUP NS-C: Non-obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI\<30 kg/m2.
4. GROUP NS-D: Obese non-diabetics, HbA1c\<5.7%, No signs and history of T2D, and BMI\>30 kg/m2.
5. Group SG: Participants who underwent sleeve gastrectomy
6. Group MGB: Participants who underwent mini-gastric bypass
7. Group IT: Participants who underwent sleeve gastrectomy with ileal transposition
8. Group TB: Participants who underwent sleeve gastrectomy with transit bipartition

Brief summary: The HIPER-1 study is a single centre cross sectional study in which a total of 240 participants (in different metabolic states and surgical models) will receive an Oral Mixed Meal Tolerance Test (OMTT). At baseline and after 30, 60 and 120 minutes the PYY levels, GLP-1 levels, glucose and insulin sensitivity will be measured. The primary endpoint of the study will be the area under the GLP-1 and Peptide - YY curves and insulin sensitivity following the OMTT.

Detailed description: Obesity and type 2 diabetes mellitus (T2DM) are increasing worldwide, thus reaching pandemic proportions. Diet, exercise and medication remain the cornerstones of type 2 diabetes mellitus treatment. But, apart from studies demonstrating promising results in some of the developed countries; the long-term success rates of lifestyle and drug modifications are disappointing. In cases where classic strategies proved to be inadequate, broad type of gastrointestinal (GI) surgery methods offer new alternatives to treat obesity and T2DM. The variable levels of incretin stimulation (especially GLP-1) and improved glycaemic control in those with diabetes have been shown following various bariatric techniques.

Therefore, investigators aimed to analyze the levels of GLP-1 and Peptide YY hormones together with indices of insulin sensitivity in participants with various health conditions and in participants who underwent different surgical options including sleeve gastrectomy, minigastric bypass, sleeve gastrectomy with ileal transposition and sleeve gastrectomy with transit bipartition.

Eligibility criteria: For NON-SURGERY GROUPS

Inclusion Criteria:

1. GROUP NS-A: Healthy participants, no known disease, no previous surgery, HbA1c\<5.7%, BMI\<25 kg/m2 (n=30).

   GROUP NS-B: Obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI\>30 kg/m2 (n=30).

   GROUP NS-C: Non-obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI\<30 kg/m2 (n=30).

   GROUP NS-D: Obese non-diabetics, HbA1c\<5.7%, No signs and history of T2D, and BMI\>30 kg/m2 (n=30).
2. Preferably not on any kind of anti-diabetic drugs or will accept cessation of all anti-diabetic drugs 2 days prior to evaluation.
3. Absence of co-morbidities (dyslipidemia, hypertension, neuropathy, retinopathy, cardiovascular disease, stroke events or lower extremity amputation).
4. Possibility to participate to the quadruplicate measurement protocol.

Exclusion Criteria:

1. Anti insulin / islet antibody and glutamic acid decarboxylase antibody (antiGAD) positivity, plasma fasting C-peptide lesser than 1 ng/ml.
2. Liver cirrhosis, severe renal failure, collagen diseases, severe endocrinopathies, blindness.
3. Heart failure, acute myocardial infarction, stroke or transient ischemic attack, unstable angina pectoris.
4. History of malignancy or malignant neoplasm in place, severe inflammatory complications, neurological or cardiovascular in act.
5. Pregnancy
6. Any conditions that at the discretion of the head of the study can represent risk to the participant or could affect the protocol results.

For SURGERY GROUPS

Inclusion Criteria:

1. Type 2 Diabetic participants who underwent a sleeve gastrectomy, a mini-gastric bypass, a sleeve gastrectomy with ileal transposition or a sleeve gastrectomy with transit bipartition performed more than 6 months ago, but within the last 2 years, with steady weight profile.
2. Preferably not on any kind of anti-diabetic drugs or will accept cessation of all anti-diabetic drugs 2 days prior to evaluation.
3. Absence of or resolved co-morbidities (dyslipidemia, hypertension, neuropathy, retinopathy, cardiovascular disease, stroke events or lower extremity amputation).
4. Possibility to participate to the quadruplicate measurement protocol.

Exclusion Criteria:

1. Liver cirrhosis, severe renal failure, collagen diseases, severe endocrinopathies, blindness.
2. Heart failure, acute myocardial infarction, stroke or transient ischemic attack, unstable angina pectoris.
3. History of malignancy or malignant neoplasm in place, severe inflammatory complications, neurological or cardiovascular in act.
4. Pregnancy
5. Any conditions that at the discretion of the head of the study can represent risk to the participant or could affect the protocol results.

Primary outcomes:
measure: Plasma GLP-1 and P-YY measurements by ELISA in participants with various health conditions.
timeFrame: Up to 6 months.
measure: Plasma GLP-1 and P-YY measurements by ELISA in participants treated by different bariatric and metabolic surgical techniques.
timeFrame: Up to 6 months.
Secondary outcomes:
measure: Body Mass Index (BMI) in participants with various health conditions.
timeFrame: Up to 6 months.
measure: Body Mass Index (BMI) in participants treated by different bariatric and metabolic surgical techniques.
timeFrame: Up to 6 months.
measure: Waist and hip circumference in participants with various health conditions.
timeFrame: Up to 6 months.
measure: Waist and hip circumference in participants treated by different bariatric and metabolic surgical techniques.
timeFrame: Up to 6 months.
measure: Plasma glucose levels in participants with various health conditions.
timeFrame: Up to 6 months.
measure: Plasma glucose levels in participants treated by different bariatric and metabolic surgical techniques.
timeFrame: Up to 6 months.
measure: Plasma insulin levels in participants with various health conditions.
timeFrame: Up to 6 months.
measure: Plasma insulin levels in participants treated by different bariatric and metabolic surgical techniques.
timeFrame: Up to 6 months.
Other outcomes:
measure: Plasma HbA1c levels in participants with various health conditions.
timeFrame: Up to 6 months.
measure: Plasma HbA1c levels in participants treated by different bariatric and metabolic surgical techniques.
timeFrame: Up to 6 months.
measure: Plasma Liver Function Tests (SGOT, SGPT and GGT levels) in participants with various health conditions.
timeFrame: Up to 6 months.
measure: Plasma Liver Function Tests (SGOT, SGPT and GGT levels) in participants treated by different bariatric and metabolic surgical techniques.
timeFrame: Up to 6 months.
Locations:
Study officials:
affiliation: Turkish Metabolic Surgery Foundation
name: Alper Celik, MD
role: STUDY_DIRECTOR
References:
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citation: Essah PA, Levy JR, Sistrun SN, Kelly SM, Nestler JE. Effect of weight loss by a low-fat diet and a low-carbohydrate diet on peptide YY levels. Int J Obes (Lond). 2010 Aug;34(8):1239-42. doi: 10.1038/ijo.2010.48. Epub 2010 Mar 30.
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citation: Santoro S. From Bariatric to Pure Metabolic Surgery: New Concepts on the Rise. Ann Surg. 2015 Aug;262(2):e79-80. doi: 10.1097/SLA.0000000000000590. No abstract available.
citation: Celik A, Ugale S. Functional restriction and a new balance between proximal and distal gut: the tools of the real metabolic surgery. Obes Surg. 2014 Oct;24(10):1742-3. doi: 10.1007/s11695-014-1368-x. No abstract available.
citation: Cagiltay E, Celik A, Dixon JB, Pouwels S, Santoro S, Gupta A, Ugale S, Abdul-Ghani M. Effects of different metabolic states and surgical models on glucose metabolism and secretion of ileal L-cell peptides: results from the HIPER-1 study. Diabet Med. 2020 Apr;37(4):697-704. doi: 10.1111/dme.14191. Epub 2019 Dec 15.
citation: Celik A, Dixon JB, Pouwels S, Celik BO, Karaca FC, Gupta A, Santoro S, Ugale S. Effects of different metabolic states and surgical models on glucose metabolism and secretion of ileal L-cell peptides: protocol for a cross-sectional study. BMJ Open. 2016 Mar 14;6(3):e010245. doi: 10.1136/bmjopen-2015-010245.