Relationships Between Mean Plasma Glucose and HbA1c in Cirrhotic Patients With Hepatogenous Diabetes

Diabetes Mellitus Clinical Trial

Official title:

Relationships Between Mean Plasma Glucose and HbA1c in Compensated and Decompensated Cirrhotic Patients With Hepatogenous Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02325622
• Other study ID #: A1C-2014
• Status: Recruiting
• Phase: N/A
• First received: December 16, 2014
• Last updated: December 24, 2014
• Start date: December 2013
• Est. completion date: February 2017

Study information

• Verified date: December 2014
• Source: Yonsei University
• Contact: Moon Young Kim, MD. PhD
• Phone: +82-33-7411229
• Email: drkimmy[@]yonsei.ac.kr
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The liver plays a crucial role in physiological glycemic control through its involvement in several glucose metabolism processes, including glycogenogenesis and glycogenolysis. Liver diseases result in impaired glucose metabolism due to hepatocyte dysfunction, termed as "hepatogenous diabetes". Abnormal glucose metabolism is found in over 90% of patients with liver cirrhosis. and clinically significant diabetes is known to occur in 30% to 70% of the patients.

A cohort study of cirrhotic patients with hepatogenous diabetes reported a relatively low diabetic complication rate, and the majority of mortality causes were complications related to liver cirrhosis; furthermore, mortality rate due to diabetic complications were reported to be low. Nonetheless, the average survival rate following the diagnosis of liver cirrhosis is rising due to increasing early detection rate and improvements in treatment modalities, and such rise in survival is expected to result in increased prevalence of hepatogenous diabetes and its complications. Therefore, it is necessary to formulate an accurate diagnosis of hepatogenous and to provide appropriate treatment.

Analyses of the Diabetes Control and Complications Trial (DCCT) demonstrated an association between glycated hemoglobin (HbA1c) and mean plasma glucose concentration in diabetic patients, and currently, HbA1c is being employed as an appropriate marker in diagnosing diabetes mellitus and in monitoring the control of mean blood glucose.

The association between mean plasma glucose concentration and HbA1c in cirrhotic patients has not been clearly established as of yet; however, HbA1c in cirrhotic patients is expected to be influenced by various factors resulted by liver cirrhosis and splenomegaly, including rapid erythrocyte turnover rate and other glycation processes.

Therefore, HbA1c may not be an appropriate indicator in the diagnosis of hepatogenous diabetes or the monitoring of glycemic control; however, no systemic study on this issue has been performed so far. Therefore, the investigators are aiming to investigate the association between mean plasma glucose concentration and HbA1c in patients with compensated or decompensated liver cirrhosis who also have hepatogenous diabetes.

Description:

1. Primary end outcome Association between mean plasma glucose concentration and glycated hemoglobin in patients with compensated or decompensated liver cirrhosis who also have hepatogenous diabetes

2. Secondary end outcome

1. HbA1c distribution in patients diagnosed with hepatogenous diabetes confirmed by 75-gram oral glucose tolerance test (OGTT)

2. Association between mean preprandial blood glucose concentration and glycated hemoglobin in patients with compensated or decompensated liver cirrhosis who also have hepatogenous diabetes

3. Association between mean postprandial blood glucose concentration and glycated hemoglobin in patients with compensated or decompensated liver cirrhosis who also have hepatogenous diabetes

4. Association between mean plasma glucose concentration and glycated hemoglobin according to Child-pugh's classification and liver stiffness severity

5. Factors contributing to discrepancy between mean plasma glucose concentration and HbA1c in patients with compensated or decompensated liver cirrhosis who also have hepatogenous diabetes

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Inclusion Criteria:

• Liver cirrhosis

• Age greater than 20 years and less than 70 years

• Diabetes mellitus that occurred after the diagnosis of liver cirrhosis

• Diagnostic criteria for diabetes mellitus

• Fasting plasma glucose = 126 mg/dL

• 2-hour plasma glucose = 200 mg/dL after 75-g OGTT

• Able to consent to study participation (either by the patient him/herself or by legal guardian)

Exclusion Criteria:

• Patients in shock requiring vasopressors

• Patients with heart or respiratory failure

• Patients with uncontrolled infection (such as spontaneous bacterial peritonitis)

• Patients with acute renal failure due to medication or renal causes

• Hemoglobin = 10mg/dl

• Patients using insulin, steroid, or beta-blockers

• History of hepatocellular carcinoma or other malignancies, or history of diagnosed malignancy that has not been completely remitted

• Patients with medical or psychiatric problems that disables them from performing clinical trial

• Pregnant or lactating women

• Patients unable to comply to trial plan or follow-up monitoring

• Patients deemed by the investigator(s) to be inappropriate for study participation

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Diabetes Mellitus
• Liver Cirrhosis

Locations

Country	Name	City	State
Korea, Republic of	Yonsei University Wonju Severance Cristian Hospital	Wonju	Kangwon-do

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (5)

Bando Y, Kanehara H, Toya D, Tanaka N, Kasayama S, Koga M. Association of serum glycated albumin to haemoglobin A1C ratio with hepatic function tests in patients with chronic liver disease. Ann Clin Biochem. 2009 Sep;46(Pt 5):368-72. doi: 10.1258/acb.2009.008231. Epub 2009 Aug 12. — View Citation

Kilpatrick ES, Rigby AS, Atkin SL. Variability in the relationship between mean plasma glucose and HbA1c: implications for the assessment of glycemic control. Clin Chem. 2007 May;53(5):897-901. Epub 2007 Mar 23. — View Citation

Koga M, Kasayama S, Kanehara H, Bando Y. CLD (chronic liver diseases)-HbA1C as a suitable indicator for estimation of mean plasma glucose in patients with chronic liver diseases. Diabetes Res Clin Pract. 2008 Aug;81(2):258-62. doi: 10.1016/j.diabres.2008.04.012. Epub 2008 Jun 2. — View Citation

Lahousen T, Hegenbarth K, Ille R, Lipp RW, Krause R, Little RR, Schnedl WJ. Determination of glycated hemoglobin in patients with advanced liver disease. World J Gastroenterol. 2004 Aug 1;10(15):2284-6. — View Citation

Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE. Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial. Diabetes Care. 2002 Feb;25(2):275-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association between mean plasma glucose concentration and glycated hemoglobin in cirrhosis	The patient choose 3 days within each month, during which they shall check blood glucose level 7 times daily (fasting and 2-hour postprandial glucose for each meal plus bedtime glucose). This shall be done for 3 months.; The study shall be concluded after laboratory studies, including glycated hemoglobin, after 3 months.; Safety assessment : The subjects shall be educated on hypoglycemic symptoms, checking blood glucose upon onset of hypoglycemia, and immediate food intake. They shall also be instructed to report such events immediately by phone. The cause of hypoglycemia shall be evaluated, and the medications shall be adjusted.; Efficacy assessment : To assess the primary outcome, the mean plasma glucose shall be calculated by first obtaining the mean of self-monitored blood glucose across 3 days every month and then by adding 11% of the value to the mean- this shall be compared with glycated hemoglobin level measured at 3 months after baseline to check for association.	3 months	Yes