Investigation of the anatomical distribution of enteroendocrine cells by a systematic approach along the entire human intestinal tract in healthy individuals and patients with type 2 diabetes.

Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis, but knowledge of their distribution in man is sparse and it is unknown whether alterations occur in type 2 diabetes. Twelve patients with type 2 diabetes and 12 age and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from every ~30 cm of the small intestine and specific locations in the large intestine. The investigators evaluated the distribution of enteroendocrine cells (using IHC staining for their specific hormonal products) and evaluated mRNA expression of the corresponding genes along the entire intestinal tract in patients with type 2 diabetes and in healthy individuals.

Inclusion criteria:

Type 2 diabetes patients

• Diagnosis of type 2 diabetes (at least 3 months prior to study inclusion)
• Treatment with diet counseling alone or combined with an glucose-lowering drugs: metformin or sulphonylurea
• Caucasian ethnicity
• Age >25 and <70 years
• Normal hemoglobin
• Negative for autoantibodies to glutamic acid decarboxylase (GAD-65) and islet cell autoantibodies (ICA).

Healthy individuals

• Fasting plasma glucose <6.0 mM
• Plasma glucose 2 hours after a 75 g-oral glucose tolerance test <7.8 mM
• Negative for GAD-65 antibodies and ICA
• Caucasian ethnicity
• Age >25 and <70 years
• Normal hemoglobin

Exclusion criteria:

Type 2 diabetes patients

• Liver disease (evaluated by alanine aminotransferase and/or aspartate aminotransferase >2 times normal value)
• Treatment with dipeptidyl peptidase 4 inhibitors or medicine that could not be paused for 12 hours
• Previous hysterectomy, appendectomy, cholecystectomy or caesarean
• Sleep apnea
• American Society of Anesthesiologists class >3
• Allergy to soy protein or eggs
• BMI >35 kg/m2 or any other condition that would contraindicate propofol sedation or enteroscopy.

Healthy individuals

• Liver disease (evaluated by alanine aminotransferase and/or aspartate aminotransferase >2 times normal value)
• Liver disease (evaluated by alanine aminotransferase and/or aspartate aminotransferase >2 times normal value)
• Treatment with dipeptidyl peptidase 4 inhibitors or medicine that could not be paused for 12 hours
• Previous hysterectomy, appendectomy, cholecystectomy or caesarean
• Sleep apnea
• American Society of Anesthesiologists class >3
• Allergy to soy protein or eggs
• BMI >35 kg/m2 or any other condition that would contraindicate propofol sedation or enteroscopy
• First-degree relative(s) with type 1 or type 2 diabetes.