Effect of DPP-IV Inhibitor on Glycemic Control and Autonomic Neuropathy in Adult Patients With Diabetes Mellitus

Rocca et al. reported first that the secretion of incretins, particular GLP-1 in rat is regulated by the enteric nervous system, the afferent and efferent vagus nerves [1]. Further, Kazakos et al. [2] reported that autonomic nerve disturbance (AND) in patients with T2DM impaired the incretin effect owing to decreased GLP-1 secretion. However, Toft-Nielsen et al. [3] reported that the decreased GLP-1 responses in the patients with type 2 diabetes mellitus (T2DM) are unlikely to be related to the AND and, thus, did not support the results of Rocca et al. and Kazakos et al. Recently, Yabe at al. [4] also observed the same observations in Japanese patients with T2DM. Meanwhile, Jin et al. reported that administration of DPP-IV inhibitor recovered the disturbance of diabetic nerve dysfunction in rat [5]. However, it is unknown whether the administration of DPP-IV inhibitor effects on the AND in human, although many studies are performed to investigate the effect of the DPP-IV inhibitors on glycemic control.

Accordingly, it is significant to reinvestigate an effect of DPP-IV inhibitor on glycemic control and autonomic neuropathy in diabetic patients.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sitagliptin, 50 mg once per day per os

Detailed Description

Autonomic nerve disturbance (AND) is estimated to use coefficient of variance of electrocardiographic beat-to-beat intervals (C.V. R-R). Maximal change of the C,V. R-R with from usual breathing to deep breathing at the resting was used for the evaluation of AND. Less than 2.0 % of the maximal value is estimated to have a positive to AND.

Glycemic control is estimated to measure change of HbA1c value once three months per year.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Kyuzi Kamoi, MD; Phone Number: -81-0258-28-3600; Email: kkam-int@echigo.ne.jp

Study Locations

• Japan
  • Niigata
    • Nagaoka, Niigata, Japan, 940-2085
      • Recruiting
      • Nagaoka Red Cross Hospital
      • Contact: Kyuzi Kamoi, MD; Phone Number: +81-0258-28-3600; Email: kkam-int@echigo.ne.jp
      • Principal Investigator: Kyuzi Kamoi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Type 1 and 2 diabetic patients who have AND determined by C.V. R-R, outpatients regularly visiting hospital and more than 20 years old (gender is disregarded). Type 1 diabetic patients are treated with Epalrestat 50 mg. 150 mg t.i.d., while type 2 diabetic patients are treated with DPP-IV inhibitors.

Description

Inclusion Criteria:

type 1 and 2 diabetes mellitus patients

• Patients who have AND determined by C.V. R-R.
• Outpatients regularly visiting hospital
• Patients 20 years old (gender is disregarded)

Exclusion Criteria:

Patients with a serious complication in the heart, liver or kidney

• Pregnant or possibly pregnant patients, or lactating patients
• Patients complicated with a malignant tumor at present.
• Patients participating in other clinical study.
• Other than the above, patients judged inappropriate as the subjects of this study by the investigator

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DPP-IV inhibitor	Drug: Sitagliptin, 50 mg once per day per os; Before and one year after treatment with DPP-IV inhibitor in diabetic patients with AND.; Other Names: Nothing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic control	As marker of HbA1c	For one year after treatment wih DPP-IV inhibitor

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
autonomic nerve disturbance	Before and after measurment with R-R CV in ECG at rest and respiratory deeping	Before and one year after treatment with DPP-IV inhibitor

Collaborators and Investigators

• Sponsor: Nagaoka Red Cross Hospital
• Investigators: Principal Investigator: Kyuzi Kamoi, MD, Nagaoka Red Cross Hospital

Publications and helpful links

General Publications

• 1. Rocca AS, Brubaker PL. Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 1999;140:1687-1694. 2. Kazakos KA, Sarafidis PA, Yovos JG. The impact of diabetic autonomic neuropathy on the incretin effect. Med Sci Monit 2008; 14:CR213-220. 3. 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;86:3717-3723. 4. Yabe D, Watanabe K, Sugawara K, Kuwata H, Kitamoto Y, Sugizaki K, Fujiwara S, Hishizawa M, Hyo T, Kuwabara K, Yokota K, Iwasaki M, Kitatani N, Kurose T, Inagaki N, Seino Y (2011) Comparison of incretin immunoassays with or without plasma extraction: incretin secretion in Japanese patients with type 2 diabetes. J Diabetes Invest 2011;2:DOI. 5. Jin HY, Liu WJ, Park JH, Baek HS, Park TS. Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor (Vildagliptin) on peripheral nerves in streptozotocin-induced diabetic rats. Arch Med Res 2009;40:536-544.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): January 1, 2013

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: February 29, 2012
• First Posted (Estimate): March 6, 2012

Study Record Updates

• Last Update Posted (Estimate): March 14, 2012
• Last Update Submitted That Met QC Criteria: March 13, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 4-Kamoi