Clinical trial NCT00776243: Short-term Effect of Intensive Insulin Therapy on Incretin Secretion
Official title: Short-term Effect of Intensive Insulin Therapy on Incretin Secretion
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes
Keywords: incretin
GLP-1
GIP
intensive insulin therapy
Lead sponsor: The Catholic University of Korea
Sponsor class: OTHER
First posted: 2008-10-21
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Subjects with normal glucose tolerance
2. Early diabetic patients with disease duration of less than 5years
3. Uncontrolled diabetic patients

Brief summary: In type 2 diabetic patients, abnormality in secretion or action of incretin(GLP-1, GIP) is observed. Although controversy still exists, the secretion of GLP-1 is thought to be reduced by 20-30% while GIP secretion is normal or slightly elevated, in type 2 diabetic patients. Various parameters such as the duration of diabetes, the amount of meal and their constitution, gastric bypass surgery, and some antidiabetic drugs affect the secretion of incretin. However, the secretion of GLP-1 and GIP in glucotoxic condition and whether they recover after improvement of glycemic status is not known. The investigators aim to study the effect of intensive insulin treatment in uncontrolled diabetic patients.


Eligibility criteria: Inclusion Criteria:

* type 2 diabetic patients with disease duration of less than 15years
* age of 20-70 years
* BMI 22-27
* HbA1c 9-13%
* patients willing to receive intensive glucose control
* patients who are able to monitor their glucose level at home

  * for normal glucose tolerance group : NGT subjects with same range of age and BMI
  * for early diabetes group : patients with diabetic duration of less than 5 years and HbA1c level less than 7.5% for at least last 6 months

Exclusion Criteria:

* previous history of insulin treatment
* patients taking alpha-glucosidase inhibitor or thiazolidinedione
* serum creatinine \>= 1.5 mg/dL
* hemoglobin \< 10 g/dL
* AST/ALT greater than 3 times normal range
* ischemic heart disease, congestive heart failure (NYHA grade \>=2)
* chronic renal failure, proliferative diabetic retinopathy, CVA
* patients with gastroparesis or taking medications altering gastric motility
* usage of steroid or other agents affecting glucose metabolism
* pregnant or breast-feeding women

Primary outcomes:
measure: Difference of incretin secretion before and after intensive insulin therapy
timeFrame: 2 months
Secondary outcomes:
measure: Difference in incretin secretion according to the duration of diabetes
timeFrame: basal
measure: Factors affecting incretin secretion
timeFrame: basal
Other outcomes:
Locations:
city: Suwon
country: Korea, Republic of
facility: Division of Endocrinology and Metabolism, St.Vincent's Hospital
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Division of Endocrinology and Metabolism, Kangnam St.Mary's Hospital
Study officials:
affiliation: The Catholic University of Korea
name: Kun-Ho Yoon, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meier JJ, Nauck MA. Is secretion of glucagon-like peptide-1 reduced in type 2 diabetes mellitus? Nat Clin Pract Endocrinol Metab. 2008 Nov;4(11):606-7. doi: 10.1038/ncpendmet0946. Epub 2008 Aug 26. No abstract available.
citation: Vollmer K, Holst JJ, Baller B, Ellrichmann M, Nauck MA, Schmidt WE, Meier JJ. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes. 2008 Mar;57(3):678-87. doi: 10.2337/db07-1124. Epub 2007 Dec 5.
citation: Nauck MA, Baller B, Meier JJ. Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes. Diabetes. 2004 Dec;53 Suppl 3:S190-6. doi: 10.2337/diabetes.53.suppl_3.s190.
citation: Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, Holst JJ. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab. 2001 Aug;86(8):3717-23. doi: 10.1210/jcem.86.8.7750.