Clinical trial NCT02325622: Relationships Between Mean Plasma Glucose and HbA1c in Cirrhotic Patients With Hepatogenous Diabetes
Official title: Relationships Between Mean Plasma Glucose and HbA1c in Compensated and Decompensated Cirrhotic Patients With Hepatogenous Diabetes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Cirrhosis
Diabetes Mellitus
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2014-12-25
Enrollment: 48
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: liver cirrhosis diagnosed after combining clinical symptoms (thrombocytopenia, gastric/esophageal varices, ascites), histologic studies, and imaging studies (ultrasound, Fibroscan)

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Association between mean plasma glucose concentration and glycated hemoglobin in cirrhosis
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Wonju
country: Korea, Republic of
facility: Yonsei University Wonju Severance Cristian Hospital
state: Kangwon-do
Study officials:
affiliation: Department of Internal Medicine, Wonju Severance Christian Hospital
name: Moon Young Kim, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.2337/diacare.25.2.275.
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. doi: 10.1373/clinchem.2006.079756. Epub 2007 Mar 23.
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.
citation: 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.
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. doi: 10.3748/wjg.v10.i15.2284.