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Query: UMLS:C0011860 (type 2 diabetes)
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Tacrolimus (FK-506) is a calcium-calcineurin inhibitor, successfully used in transplant recipients. We report the successful use of tacrolimus as a single immunosuppressant in a patient who had developed myasthenia gravis (MG) during interferon alpha treatment. In this case, the coexistence of hepatitis C and type 2 diabetes mellitus contraindicated the use of both steroids and azathioprine, and cyclosporine A, although effective, had induced renal failure. Tacrolimus proved to be effective in the treatment of MG, was not significantly hepatotoxic, and was less nephrotoxic than cyclosporine.
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PMID:Successful treatment of myasthenia gravis with tacrolimus. 1175 94

Type 2 diabetes mellitus, which affects approximately 7% of the population, is a disease of relative insulin insufficiency manifested by insulin resistance in skeletal muscle, liver and adipose tissue. This results in increased hepatic glucose production with compensatory hyperinsulinaemia. The secondary hyperinsulinaemia is associated with an increased incidence of hepatocellular carcinoma and non-alcoholic steatohepatitis (NASH). It is estimated that insulin resistance is present in 50-70% of patients with NASH and that the incidence of NASH in type 2 diabetes is 60-80%. The prevalence of cirrhosis in established type 2 diabetes is as high as 10% and the prevalence of hepatitis C is 3-11%. It was in this setting that the insulin sensitisers were developed. The thiazolidinediones represent a significant and unique pharmacological breakthrough for the management of type 2 diabetes mellitus. The first of the drugs, troglitazone, proved to be hepatotoxic and has been withdrawn from the market. Two cases of hepatotoxicity of rosiglitazone have been reported. It remains unclear whether or not hepatotoxicity is a class effect or is related to the unique tocopherol side chain of troglitazone. However, it appears that the incidence of hepatotoxicity of rosiglitazone is much lower than that of troglitazone. It is not yet known if any hepatotoxicity occurs with pioglitazone.
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PMID:Thiazolidinedione hepatotoxicity: a class effect? 1196 28

The aim of this study was to investigate the prevalence of hepatitis B and hepatitis C virus infections in type 2 diabetic patients in Gaziantep, Turkey. Six hundred and ninety-two type 2 diabetic patients and 1014 healthy blood donors were included in the study. No significant difference was found between type 2 diabetic patients and the control group for seropositivity of HBsAg (5.3% vs 5.1%, p>0.05). In contrast, anti-HCV was significantly more frequent in type 2 diabetic patients (7.5% vs 0.1%, p>0.0001). We found no significant difference for HBsAg seropositivity between type 2 diabetic patients with a disease duration of 12 months or less, but anti-HCV seropositivity was significantly more frequent in diabetic patients with a longer disease duration (p<0.05). We suggest that HCV infection is not a trigger factor for type 2 diabetes mellitus but is frequently associated with it.
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PMID:Increased frequency of HCV but not HBV infection in type 2 diabetic patients in Turkey. 1201 20

Steatosis has emerged as a histologic finding of importance to the progression of hepatitis C virus (HCV)-associated liver disease. However, most studies of HCV-associated steatosis have excluded alcohol drinkers and individuals with diabetes and thus have not addressed the relative contribution of known causes of steatosis to liver injury in HCV-associated disease. To address this issue, we studied 297 consecutive patients with HCV who met inclusion criteria. Alcohol consumption, demographics, and serologic tests were correlated with degrees of steatosis and fibrosis on liver biopsy. Liver biopsy specimens were also examined for evidence of significant alcohol or nonalcoholic steatohepatitis (NASH) injury. In univariate analysis, steatosis correlated with type 2 diabetes mellitus (P =.005) and body mass index (BMI) (P =.0001) but not with the intensity of alcohol intake (in grams per day). In multivariate analysis, BMI (P =.0002) and genotype 3a infection (P =.02) were independent predictors of steatosis. When patients with risk factors for NASH were excluded, genotype 3a infection was the only independent predictor of steatosis. Steatosis (P =.04) and inflammation (P <.0001) scores on liver biopsy were the only independent predictors of fibrosis. Significant alcohol or NASH injury was found in only 6% of biopsy specimens. In conclusion, steatosis in HCV infection is associated with risk factors for NASH, particularly obesity, rather than alcohol consumption.
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PMID:Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. 1219 67

OBJECTIVE To evaluate the strategies instituted by the authors' center to decrease the time to transplantation and increase the rate of transplantation for African-Americans, consisting of a formal education program concerning the benefits of living organ donation that is oriented to minorities; a laparoscopic living donation program; use of hepatitis C-positive donors in documented positive recipients; and encouraging vaccination for hepatitis B, allowing the use of hepatitis B core Ab-positive donors. SUMMARY BACKGROUND DATA The national shortage of suitable kidney donor organs has disproportional and adverse effects on African-Americans for several reasons. Type II diabetes mellitus and hypertension, major etiologic factors for end-stage renal disease, are more prevalent in African-Americans than in the general population. Once kidney failure has developed, African-Americans are disadvantaged for the following reasons: this patient cohort has longer median waiting times on the renal transplant list; African-Americans have higher rates of acute rejection, which affects long-term allograft survival; and once they are transplanted, the long-term graft survival rates are lower in this population than in other groups. METHODS From March 1990 to November 2001 the authors' center performed 2,167 renal transplants; 944 were in African-Americans (663 primary cadaver renal transplants and 253 primary Living donor renal transplants). The retransplants consisted of 83 cadaver transplants and 17 living donor transplants. Outcome measures of this retrospective analysis included median waiting time, graft and patient survival rates, and the rate of living donation in African-Americans and comparable non-African-Americans. Where applicable, data are compared to United Network for Organ Sharing national statistics. Statistical analysis employed appropriate SPSS applications. RESULTS One- and 5-year patient survival rates for living donor kidneys were 97.1% and 91.3% for non-African-Americans and 96.8% and 90.4% for African-Americans. One- and 5-year graft survival rates were 95.1% and 89.1% for non-African-Americans and 93.1% and 82.9% for African-Americans. One- and 4-year patient survival rates for cadaver donor kidneys were 91.4% and 78.7% for non-African-Americans and 92.4% and 80.2% for African-Americans. One- and 5-year graft survival rates for cadaver kidneys were 84.6% and 73.7% for non-African-Americans and 84.6% and 68.9% for African-Americans. One- and 5-year graft and patient survival rates were identical for recipients of hepatitis C virus-positive and anti-HBc positive donors, with the exception of a trend to late graft loss in the African-American hepatitis C virus group due to higher rates of noncompliance, an effect that disappears with censoring of graft loss from that cause. The cadaveric renal transplant median waiting time for non-African-Americans was 391 days compared to 734 days nationally; the waiting time for African-Americans was 647 days compared to 1,335 days nationally. When looking at all patients, living and cadaver donor, the median waiting times are 220 days for non-African-Americans and 462 days for African-Americans. CONCLUSIONS Programs specifically oriented to improve volunteerism in African-Americans have led to a marked improvement in overall waiting time and in rates of living donation in this patient group. The median waiting times to cadaveric renal transplantation were also significantly shorter in the authors' center, especially for African-American patients, by taking advantage of the higher rates of hepatitis C infection and encouraging hepatitis B vaccination. These policies can markedly improve end-stage renal disease care for African-Americans by halving the overall waiting time while still achieving comparable graft and patient survival rates.
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PMID:A decade of experience with renal transplantation in African-Americans. 1245 18

Non-alcoholic steatohepatitis (NASH), is a critical link in the chain of metabolic fatty liver disorders that spans steatosis to cryptogenic cirrhosis. It is the hepatic manifestation of the insulin resistance (or metabolic) syndrome, and provides a clue to understanding fibrotic progression of other chronic liver diseases, particularly hepatitis C. Non-alcoholic steatohepatitis is often the first clinical indication of insulin resistance, with its complications of high blood pressure, coronary heart disease and type 2 diabetes. Among those with risk factors, NASH is common: present in at least 20% of obese adults or children with or without type 2 diabetes, and at least 5% of those overweight. With emerging urbanization, increasing affluence and behavioral changes of physical inactivity and high fat/energy-excessive diet, type 2 diabetes has become common in Asia and the western Pacific rim. The rates range from 7-40%, which in countries like Japan represents a 3-20-fold increase (depending on age) over the last 20 years. The increase is associated with central adiposity, insulin resistance, hepatic steatosis and NASH. After cancer, cirrhosis from NASH is now the second most common age-related cause of death in type 2 diabetes. Reversing these trends must become a public health priority; the first awakenings were evident in Taiwan at the time of this meeting. In order to stimulate clinicians to think more about the importance of metabolic liver disease for development of cirrhosis, this review will cover clinical and laboratory features, natural history and an approach to diagnosis and management of NASH. Some emerging concepts on pathogenesis will be mentioned briefly, but the emphasis will be on the potency of lifestyle adjustments (physical activity and diet) to prevent or reverse fatty liver disorders.
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PMID:Non-alcoholic steatohepatitis: what is it, and why is it important in the Asia-Pacific region? 1254 95

The aim of this study was to investigate whether or not the diabetes mellitus may be considered a risk factor for the HCV infection. The HCV seroprevalence was evaluated in 254 diabetic subjects, whose anamnestic data and risk factors are known, in comparison to 223 first-time blood donors, carefully age- and gender-matched. The statistical analysis showed that the studied groups belonged to the same population (Mann-Whitney U test) and that there were no significant differences between cases and controls as regards HCV prevalence (Yates corrected chi 2 test). The obtained data underline the importance of the control group selection, especially in the studies considering age-related pathologies. The authors disprove type 2 diabetes as a risk factor for the HCV infection and consider that this is a valid hypothesis only when the hepatitis C was unknown and not adequate prevention was used.
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PMID:Is diabetes mellitus a risk factor for HCV infection? 1263 50

A high prevalence of type 2 diabetes mellitus in patients with hepatitis C virus (HCV)-related chronic liver diseases has been reported in numerous studies. Other studies failed to confirm this observation. We have studied the relative prevalence of type 2 diabetes mellitus in two groups of patients respectively presenting with HCV-related chronic liver disease (224 patients) and chronic liver diseases of other etiologies (30 hepatitis B virus-HBV-related chronic liver disease, 22 alcoholic liver cirrhosis), in order to confront them. Our study revealed a higher prevalence of diabetes mellitus in the group of patients with HCV-related chronic liver disease in comparison with the group of patients with chronic liver disease of other etiologies (32.5 vs 15.3%; p = 0.03). Patients with HBV-related liver disease had diabetes in 6.6% of cases, and the difference with patients with HCV-related disease was significant (p = 0.007). Our study confirms a higher prevalence of type 2 diabetes mellitus in patients with HCV-related chronic liver disease. It could be suggested that type 2 diabetes mellitus in patients with HCV-related chronic liver disease could be facilitated by hepatic iron overload and mitochondrial damage.
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PMID:[Prevalence and significance of type-2 diabetes mellitus in chronic liver disease, correlated with hepatitis C virus]. 1273 22

Although hepatitis C virus (HCV) infection is more common among adults with type 2 diabetes, it is uncertain whether HCV precedes the development of diabetes. Thus, we performed a prospective (case-cohort) analysis to examine if persons who acquired type 2 diabetes were more likely to have had antecedent HCV infection when enrolled in a community-based cohort of men and women between the ages of 44 and 65 in the United States (Atherosclerosis Risk in Communities Study [ARIC]). Among 1,084 adults free of diabetes at baseline, 548 developed diabetes over 9 years of follow-up evaluation. Incident cases of diabetes were identified by using fasting glucose and medical history and HCV antibodies were assessed at baseline. A priori, persons were categorized as low-risk or high-risk for diabetes based on their age and body mass index, factors that appeared to modify the type 2 diabetes-HCV infection incidence estimates. The overall prevalence of HCV in this population was 0.8%. Among those at high risk for diabetes, persons with HCV infection were more than 11 times as likely as those without HCV infection to develop diabetes (relative hazard, 11.58; 95% confidence interval, 1.39-96.6). Among those at low risk, no increased incidence of diabetes was detected among HCV-infected persons (relative hazard, 0.48; 95% confidence interval, 0.05-4.40). In conclusion, pre-existing HCV infection may increase the risk for type 2 diabetes in persons with recognized diabetes risk factors. Additional larger prospective evaluations are needed to confirm these preliminary findings.
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PMID:Hepatitis C virus infection and incident type 2 diabetes. 1282 86

Type 1 diabetes mellitus is the result of an autoimmune process characterized by pancreatic beta cell destruction. It has been reported that chronic hepatitis C infection is associated with type 2 diabetes mellitus, but not with type 1. Although the prevalence of markers of pancreatic autoimmunity in hepatitis C virus-positive patients is not significantly different to that reported in the general population, it increases during alpha-interferon therapy from 3 to 7%, probably due to the immunostimulatory effects of this cytokine. To date, 31 case reports of type 1 diabetes mellitus related to interferon treatment have been published. Type 1 diabetes mellitus occurs more frequently in patients treated for chronic hepatitis C than for other conditions and is irreversible in most cases. In 50% of these patients, markers of pancreatic autoimmunity predated treatment, the majority of cases having a genetic predisposition. Thus, in predisposed individuals, alpha-interferon can either induce or accelerate a diabetogenic process already underway. We suggest that islet cell autoantibodies and glutamic acid decarboxylase autoantibodies should be investigated before and during interferon treatment in order to identify subjects at high risk of developing type 1 diabetes mellitus.
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PMID:Type 1 diabetes mellitus in patients with chronic hepatitis C before and after interferon therapy. 1296 81


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