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Li BY, Tan W, Zou JL, He Y, Yoshida S, Jiang B, Zhou YD. Role of interferons in diabetic retinopathy. World J Diabetes 2021; 12:939-953. [PMID: 34326947 PMCID: PMC8311473 DOI: 10.4239/wjd.v12.i7.939] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 04/15/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic retinopathy (DR) is one of the major causes of visual impairment and irreversible blindness in developed regions. Aside from abnormal angiogenesis, inflammation is the most specific and might be the initiating factor of DR. As a key participant in inflammation, interferon-gamma (IFN-γ) can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines, which accelerate neovascularization and neuroglial degeneration. In addition, IFN-γ is involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases, such as diabetic nephropathy, cerebral microbleeds, and age-related macular degeneration. Traditional treatments, such as anti-vascular endothelial growth factor agents, vitrectomy, and laser photocoagulation therapy, are more effective for angiogenesis and not tolerable for every patient. Many ongoing clinical trials are exploring effective drugs that target inflammation. For instance, IFN-α acts against viruses and angiogenesis and is commonly used to treat malignant tumors. Moreover, IFN-α has been shown to contribute to alleviating the progression of DR and other ocular diseases. In this review, we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR, such as diagnosis, prognosis, and therapeutic treatment.
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Affiliation(s)
- Bing-Yan Li
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Wei Tan
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Jing-Ling Zou
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Yan He
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Shigeo Yoshida
- Department of Ophthalmology, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan
| | - Bing Jiang
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Ye-Di Zhou
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
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Cha BS, Moon JH. Management of Posttransplantation Diabetes Mellitus (PTDM). KOREAN JOURNAL OF TRANSPLANTATION 2011. [DOI: 10.4285/jkstn.2011.25.1.8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Bong Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hoon Moon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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3
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Abstract
New-onset diabetes mellitus is a common complication of solid organ transplantation and is likely to become even more common with the current epidemic of obesity in some countries. It has become clear that both new-onset diabetes and prediabetic states (impaired fasting glucose and impaired glucose tolerance) negatively influence graft and patient survival after transplantation. This observation forms the basis for recommending meticulous screening for glucose intolerance before and after transplantation. Although a number of clinical factors including age, weight, ethnicity, family history, and infection with hepatitis C are closely associated with the new-onset diabetes mellitus, immunosuppression with corticosteroids, calcineurin inhibitors and possibly sirolimus plays a dominant role in its pathogenesis. Management of new-onset diabetes after transplantation generally conforms to the guidelines for treatment of type 2 diabetes mellitus in the general population. However, further studies are needed to determine the optimal immunosuppressive regimens for patients with this disorder.
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Affiliation(s)
- Kenneth A Bodziak
- Department of Medicine, Division of Nephrology and Hypertension, Case Western Reserve University and the Transplantation Service, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
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4
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Lv YY, Shi BY, Guo H. Abrupt onset of type 1 diabetes mellitus during recombinant interferon-alpha 2b therapy in a patient with chronic hepatitis B. World J Gastroenterol 2008; 14:4713-5. [PMID: 18698691 PMCID: PMC2738801 DOI: 10.3748/wjg.14.4713] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hyperglycemia, diabetic ketoacidosis, combined with C-peptide secretion deficiency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and instead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.
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5
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Itou M, Kawaguchi T, Taniguchi E, Sumie S, Oriishi T, Mitsuyama K, Tsuruta O, Ueno T, Sata M. Altered expression of glucagon-like peptide-1 and dipeptidyl peptidase IV in patients with HCV-related glucose intolerance. J Gastroenterol Hepatol 2008; 23:244-51. [PMID: 17944883 DOI: 10.1111/j.1440-1746.2007.05183.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM The pathogenesis of hepatitis C virus (HCV)-associated glucose intolerance remains unclear. Glucagon-like peptide-1 (GLP-1), a gut hormone, synthesizes hepatic glycogen and is inactivated by dipeptidyl peptidase IV (DPPIV). The aims of this study were to investigate the alterations in the expression of GLP-1 and DPPIV in HCV-associated glucose intolerance. METHODS We enrolled patients with HCV- or hepatitis B virus (HBV)-related liver disease (n = 94 and 37, respectively), patients with inflammatory bowel disease (IBD; n = 14) as disease controls, and healthy controls (n = 48). The serum or tissue GLP-1 and DPPIV expression levels were determined by enzyme immunoassay, immunoblotting, or immunostaining. The hepatic glycogen content was assayed by periodic acid-Schiff staining. RESULTS The serum GLP-1 levels were significantly decreased in the HCV group (4.9 +/- 0.3 ng/mL) than those in the controls (7.5 +/- 0.6 ng/mL), the HBV group (7.0 +/- 0.5 ng/mL), or the IBD group (10.8 +/- 1.0 ng/mL, P < 0.01). Although the ileum GLP-1 expression was not significantly different between the controls and the HCV group, the DPPIV expression was significantly increased in the ileum, liver, and serum in the HCV group. Hepatic glycogen content was decreased to a greater extent in the HCV group than that in the HBV group (127.5 +/- 5.3 vs 187.7 +/- 6.6 arbitrary units; n = 19, P < 0.01). CONCLUSION We demonstrated the altered expressions of GLP-1 and DPPIV in patients with HCV-associated glucose intolerance. Since hepatic glycogen synthesis, a GLP-1 action, was impaired, the altered expressions of GLP-1 and DPPIV may be involved in the development of HCV-associated glucose intolerance.
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Affiliation(s)
- Minoru Itou
- Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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6
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Greenberg PD, Rosman AS, Eldeiry LS, Naqvi Z, Bräu N. Decline in haemoglobin A1c values in diabetic patients receiving interferon-alpha and ribavirin for chronic hepatitis C. J Viral Hepat 2006; 13:613-7. [PMID: 16907848 DOI: 10.1111/j.1365-2893.2006.00729.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Haemoglobin A1c (A1c) levels are lower during haemolysis because of the shorter exposure of haemoglobin (Hb) to plasma glucose. Ribavirin (RBV) used in combination with interferon-alpha (IFN) for chronic hepatitis C causes reversible haemolytic anaemia. This study examined the extent to which RBV treatment influences A1c levels in diabetic patients. A retrospective analysis identified 32 diabetic patients who underwent hepatitis C treatment with IFN and RBV. Each subject had at least three measures of A1c, Hb and glucose: before, during and after therapy. A1c values decreased from a mean pretreatment level of 7.2% to an on-treatment A1c level of 5.2% [mean paired difference -2.01%; 95% confidence interval (CI) -1.59% to -2.43%; P < 0.001]. During therapy, mean Hb levels decreased from 15.1 g/dL at baseline to a nadir of 11.7 g/dL (P < 0.001) with a rise in lactose dehydrogenase levels and reticulocyte counts, and unchanged mean corpuscular volume values confirming haemolysis. At the same time, glucose levels declined by a mean of 38.4 mg/dL (95% CI 13.4-63.5 mg/dL; P = 0.002) as did body weights by a mean of 3.15 kg (P < 0.001). According to published glucose-A1c correlation tables, this decline of glucose concentration by 38.4 mg/dL correlates to a decline in A1c level of 1.08%. In conclusion, reductions of A1c levels by a mean of 2.01% during hepatitis C therapy with IFN + RBV are due to a combination of decreased glucose levels (1.08%) and RBV-induced haemolysis (0.93%). A1c levels should not be measured during hepatitis C treatment with IFN + RBV because they do not adequately reflect glycaemic control.
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Affiliation(s)
- P D Greenberg
- Bronx Veterans Affairs Medical Center, New York, USA
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7
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Abstract
Hepatitis C affects approximately 170 million people worldwide. Extrahepatic manifestations of chronic hepatitis C infection are clinically evident in nearly 40% of patients. Much research has been done over the last decade to better understand their incidence, clinical presentation, mechanism of disease, and the role of antiviral therapy in their treatment. Of the commonly reported manifestations, cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda remain the best understood manifestations. More recently, the association of insulin resistance and diabetes mellitus with chronic hepatitis C has been demonstrated. This paper serves to review the growing body of literature detailing the extrahepatic manifestations of chronic hepatitis C.
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Affiliation(s)
- Nicole A Palekar
- Department of Medicine, Gastroenterology and Hepatology Service, Brooke Army Medical Center, Fort Sam Houston, TX, USA.
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8
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Lu JY, Chuang LM, Yang WS, Tai TY, Lai MY, Chen PJ, Kao JH, Lee CZ, Lee HS. Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN-alpha therapy. Liver Int 2005; 25:752-9. [PMID: 15998426 DOI: 10.1111/j.1478-3231.2005.1007.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
AIMS The study was designed to survey the change of adiponectin levels before and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis B and C infections. METHODS Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin suppression test was conducted before and within 1 week after IFN-alpha therapy. RESULTS The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (-4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-alpha (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1 vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1-11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. CONCLUSIONS IFN-alpha resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-alpha treatment, contributes to the lowering of adiponectin levels needs to be further investigated.
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Affiliation(s)
- Jin-Ying Lu
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
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9
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Abstract
New-onset diabetes mellitus (NODM) develops in approximately 15% of liver transplant recipients, and a similar proportion of patients have diabetes prior to transplantation. Preexisting diabetes and probably NODM are associated with increased mortality and risk of infection. NODM occurs more frequently among patients with hepatitis C infection; additional risk factors include family history, male gender, increasing weight, and alcoholic cirrhosis. Corticosteroid therapy, particularly bolus injections, increases likelihood of NODM, and randomized clinical trials and retrospective studies have shown NODM to occur more frequently with tacrolimus compared with cyclosporine. Patients undergoing liver transplantation should be screened for diabetes risk factors, and fasting plasma glucose should be monitored regularly in all transplant recipients. Management of NODM is essentially similar to that of diabetes in the nontransplant population, and includes dietary and lifestyle modifications. In choosing oral agents and/or insulin, the individual medical profile of the patient must be considered carefully. Corticosteroid exposure should be limited as much as possible, and reduction of calcineurin inhibitor dose is prudent. Switching from tacrolimus to cyclosporine may be required in some cases to achieve improvement or resolution. In conclusion, prospective trials are necessary to properly define antidiabetic therapy and immunosuppressive strategies in this population.
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Affiliation(s)
- Piero Marchetti
- Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa, Italy.
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10
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Balasubramanian S, Kowdley KV. Effect of alcohol on viral hepatitis and other forms of liver dysfunction. Clin Liver Dis 2005; 9:83-101. [PMID: 15763231 DOI: 10.1016/j.cld.2004.10.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Alcohol is a known hepatotoxic agent, which may exacerbate liver injury caused by other agents. The wide prevalence of alcohol use and abuse in society makes it an important cofactor in many other liver diseases. Examples of liver diseases that are significantly influenced by ingestion of alcohol include chronic viral hepatitis, disorders of iron overload, and obesity-related liver disease.
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MESH Headings
- Comorbidity
- Disease Progression
- Female
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/epidemiology
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/epidemiology
- Hepatitis, Alcoholic/diagnosis
- Hepatitis, Alcoholic/epidemiology
- Hepatitis, Viral, Human/diagnosis
- Hepatitis, Viral, Human/epidemiology
- Humans
- Incidence
- Liver Cirrhosis, Alcoholic/diagnosis
- Liver Cirrhosis, Alcoholic/epidemiology
- Liver Function Tests
- Male
- Risk Assessment
- Severity of Illness Index
- United States/epidemiology
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Affiliation(s)
- Sripriya Balasubramanian
- Division of Gastroenterology and Hepatology, University of California at Davis, 4150 V Street #3500, Sacramento, California 95817, USA
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Gourishankar S, Jhangri GS, Tonelli M, Wales LH, Cockfield SM. Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant 2004; 4:1876-82. [PMID: 15476489 DOI: 10.1111/j.1600-6143.2004.00591.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The onset of diabetes mellitus following kidney transplantation or post-transplant diabetes mellitus (PTDM) is now recognized as being an increasingly common complication that is associated with poor graft and patient survival. The incidence and clinical correlates of PTDM in a Canadian kidney transplant population has not been examined and may vary based on differences in demographics (i.e. race). Furthermore, little information exists on the association of variables such as cumulative dose of corticosteroids and trough calcineurin inhibitor levels and PTDM. We examined all recipients of a kidney transplant in our center between 1995 and 2001 and found an overall PTDM rate of 9.8%. Five clinical factors were independently associated with PTDM: older recipient age, deceased donor, hepatitis C antibody status, rejection episode and use of tacrolimus (vs. cyclosporine). Furthermore, cumulative corticosteroid dose and calcineurin inhibitor trough level were not associated with PTDM. This study demonstrates that in a Canadian kidney transplant population that there is a significant risk of PTDM following kidney transplantation, and it is therefore advisable to minimize this risk.
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Affiliation(s)
- Sita Gourishankar
- Division of Nephrology and Transplantation Immunology, 11-108E Clinical Sciences Building, University of Alberta, Edmonton, Alberta, Canada.
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Kim JD, Sherker AH. Antiviral therapy: role in the management of extrahepatic diseases. Gastroenterol Clin North Am 2004; 33:693-708, xi. [PMID: 15324951 DOI: 10.1016/j.gtc.2004.04.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
This article considers the extrahepatic manifestations associated with HBV and HCV infection, the strength of the evidence for the association, potential pathological mechanisms, and evidence based therapeutic recommendations. As many of these extra hepatic conditions are uncommon, published reports have been largely uncontrolled or anecdotal.
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Affiliation(s)
- Jae D Kim
- Section of Gastroenterology and Hepatology, Washington Hospital Center, 110 Irving Street Northwest, Washington, DC 20010, USA
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Chen LK, Hwang SJ, Tsai ST, Luo JC, Lee SD, Chang FY. Glucose intolerance in Chinese patients with chronic hepatitis C. World J Gastroenterol 2003; 9:505-8. [PMID: 12632506 PMCID: PMC4621570 DOI: 10.3748/wjg.v9.i3.505] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence and the risk factors of glucose intolerance in Chinese patients with chronic hepatitis C and to evaluate the relationship between interferon (IFN) treatment and glucose intolerance in these patients.
METHODS: Prospective cross-sectional study was done to evaluate the prevalence of glucose intolerance in Chinese patients with chronic hepatitis C virus (HCV) infection from the outpatient clinic of Department of Family Medicine, Taipei Veterans General Hospital. Chronic hepatitis C was defined as persistent presence of anti-HCV and persistent elevation of liver transaminase for at least 1.5 folds for at least 6 months. Moreover, patients were further categorized into normal fasting glucose and glucose intolerance (diabetes mellitus (DM) and impaired fasting glucose) according to the diagnostic criteria of American Diabetic Association.
RESULTS: Totally, 359 Chinese patients with chronic hepatitis C were enrolled (212 males and 147 females, mean age = 58.1 ± 13.0 years). One hundred and twenty-three patients (34.3%) had received various forms of IFN treatment. One hundred and twenty-five patients (34.6%) had glucose intolerance, including 99 patients (27.6%) with DM and 26 patients (7.0%) with impaired fasting glucose. In comparison with those with normal fasting glucose levels, patients with chronic hepatitis C with glucose intolerance were significantly older, had a significantly higher body mass index, and they were more likely to suffer from obesity, to have family history of diabetes and to have had previous IFN treatment. Stepwise multivariate logistic regression revealed significantly that age 57 years, obesity, previous history of IFN treatment and the presence of family history of diabetes were independent risk factors associated with the presence of glucose intolerance in chronic hepatitis C patients.
CONCLUSION: In conclusion, 34.6% of Chinese patients with chronic hepatitis C had glucose intolerance. Chronic hepatitis C patients who were older in age, obese, had previous IFN treatment history and had family history of diabetes were prone to develop glucose intolerance. To our knowledge, this is the first population-based report to confirm that interferon treatment to be an independent risk factor to develop glucose intolerance.
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Affiliation(s)
- Liang-Kung Chen
- Department of Family Medicine, Taipei Veterans General Hospital, No. 201, Shih-Pai Road Sec 2, Taipei, 11217, Taiwan, China.
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Baid S, Cosimi AB, Farrell ML, Schoenfeld DA, Feng S, Chung RT, Tolkoff-Rubin N, Pascual M. Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal relationship with hepatitis C virus allograft hepatitis, and impact on mortality. Transplantation 2001; 72:1066-72. [PMID: 11579302 DOI: 10.1097/00007890-200109270-00015] [Citation(s) in RCA: 215] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Recent studies suggest an association between diabetes mellitus and hepatitis C virus (HCV) infection. Our aim was to determine (1) the prevalence and determinants of new onset posttransplant diabetes mellitus (PTDM) in HCV (+) liver transplant (OLT) recipients, (2) the temporal relationship between recurrent allograft hepatitis and the onset of PTDM, and (3) the effects of antiviral therapy on glycemic control. METHODS Between January of 1991 and December of 1998, of 185 OLTs performed in 176 adult patients, 47 HCV (+) cases and 111 HCV (-) controls were analyzed. We reviewed and analyzed the demographics, etiology of liver failure, pretransplant alcohol abuse, prevalence of diabetes mellitus, and clinical characteristics of both groups. In HCV (+) patients, the development of recurrent allograft hepatitis and its therapy were also studied in detail. RESULTS The prevalence of pretransplant diabetes was similar in the two groups, whereas the prevalence of PTDM was significantly higher in HCV (+) than in HCV (-) patients (64% vs. 28%, P=0.0001). By multivariate analysis, HCV infection (hazard ratio 2.5, P=0.001) and methylprednisolone boluses (hazard ratio 1.09 per bolus, P=0.02) were found to be independent risk factors for the development of PTDM. Development of PTDM was found to be an independent risk factor for mortality (hazard ratio 3.67, P<0.0001). The cumulative mortality in HCV (+) PTDM (+) versus HCV (+) PTDM (-) patients was 56% vs. 14% (P=0.001). In HCV (+) patients with PTDM, we could identify two groups based on the temporal relationship between the allograft hepatitis and the onset of PTDM: 13 patients developed PTDM either before or in the absence of hepatitis (group A), and 12 concurrently with the diagnosis of hepatitis (group B). In gr. B, 11 of 12 patients received antiviral therapy. Normalization of liver function tests with improvement in viremia was achieved in 4 of 11 patients, who also demonstrated a marked improvement in their glycemic control. CONCLUSION We found a high prevalence of PTDM in HCV (+) recipients. PTDM after OLT was associated with significantly increased mortality. HCV infection and methylprednisolone boluses were found to be independent risk factors for the development of PTDM. In approximately half of the HCV (+) patients with PTDM, the onset of PTDM was related to the recurrence of allograft hepatitis. Improvement in glycemic control was achieved in the patients who responded to antiviral therapy.
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Affiliation(s)
- S Baid
- Department of Medicine, Massachusetts General Hospital, Harvard Medical Schoool, Boston, MA 02114, USA
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Recasens M, Aguilera E, Ampurdanés S, Sánchez Tapias JM, Simó O, Casamitjana R, Conget I. Abrupt onset of diabetes during interferon-alpha therapy in patients with chronic hepatitis C. Diabet Med 2001; 18:764-7. [PMID: 11606177 DOI: 10.1046/j.1464-5491.2001.00562.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
INTRODUCTION Interferon-alpha (IFN-alpha) is now widely used in the treatment of chronic hepatitis C. Few patients have been reported as developing impaired glucose tolerance or diabetes mellitus (DM) using this therapy. The explanation for the development of DM in chronic hepatitis C treated with IFN-alpha is unclear. We report two patients who developed an abrupt onset of diabetes during IFN-alpha for chronic hepatitis C. CASE REPORTS Two male middle-aged patients were admitted to our hospital for an abrupt onset of diabetes, in diabetic ketoacidosis, with a very short duration of hyperglycaemic symptoms. Their clinical course was similar. Case 1 never demonstrated any markers of pancreatic immunogenicity. Case 2 had high levels of decarboxylase glutamic acid autoantibodies (GADAb), before the IFN-alpha treatment that persisted. We compared initial beta-cell function and metabolic control with a group of middle-aged patients from our hospital who had recently been diagnosed with Type 1 diabetes mellitus (DM1). In contrast to these, the onset of the disease was particularly severe with beta-cell function substantially impaired and displaying unstable short-term metabolic control. CONCLUSIONS Type 1 diabetes should be considered as a potential complication if IFN is administered to patients with chronic hepatitis C. Its onset may be severe and result in short-term difficulties in metabolic control.
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Affiliation(s)
- M Recasens
- Endocrinology and Diabetes Unit, IDIBAPS, Hospital Clínic i Universitari, Barcelona, Spain
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17
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Shetty A, Wilson S, Kuo P, Laurin JL, Howell CD, Johnson L, Allen EM. Liver transplantation improves cirrhosis-associated impaired oral glucose tolerance. Transplantation 2000; 69:2451-4. [PMID: 10868659 DOI: 10.1097/00007890-200006150-00043] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Thirty-five percent to 80% of cirrhotic patients have impaired glucose tolerance (IGT) or diabetes mellitus (DM). Diabetic cirrhotics have higher morbidity and mortality than nondiabetics. Therefore, it would be worthwhile to determine whether liver transplantation improves glucose homeostasis in these patients. METHOD A total of 26 patients awaiting liver transplantation were evaluated for impaired glucose homeostasis by fasting blood glucose and/or oral glucose tolerance tests (OGTT). Five patients underwent transplant surgery within 1 year of OGTT and had a repeat OGTT 3-6 months after transplantation. RESULTS Sixty-five percent (17/26) of the patients had abnormal glucose homeostasis. Twenty-three percent (6/26) met American Diabetes Association criteria for DM, and another 42.3% (11/26) had IGT. All patients had normal HbA1C levels. After transplantation, the 2-hr blood glucose improved in four patients and the mean 2-hr glucose level was reduced (204 +/- 94 vs. 132 +/- 53 mg/dl [mean +/- SD, P=0.051]). CONCLUSION Liver transplantation can reverse cirrhosis-associated impaired glucose tolerance.
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Affiliation(s)
- A Shetty
- Department of Medicine, University of Maryland Medical System, Baltimore, USA
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