Dr. Ron’s Research Review – September 8, 2010

This week’s research review begins with a recent NEJM article showing that vitamin E is better than Pioglitazone for nonalcoholic steatohepatitis; Folate improves lipoprotein; Autoimmune gastritis in type 1 diabetes; and Subclinical hypothyroidism.

Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis

(Sanyal, Chalasani et al. 2010)

Vitamin E (800 IU daily for 96 weeks) reduced serum alanine and aspartate aminotransferase levels; reduced hepatic steatosis and lobular inflammation; and improved in fibrosis scores in adults with nonalcoholic steatohepatitis without diabetes.

Plasma folate levels are associated with the lipoprotein profile

(Semmler, Moskau et al. 2010)

Higher serum folate levels were associated with lower LDL, higher HDL and improved LDL/HDL ratio.

Autoimmune gastritis in type 1 diabetes: a clinically oriented review

(De Block, De Leeuw et al. 2008)

Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3- to 5-fold increased.

Subclinical hypothyroidism: an update for primary care physicians

(Fatourechi 2009)

Subclinical hypothyroidism (SCH), also called mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. This condition occurs in 3% to 8% of the general population. It is more common in women than men, and its prevalence increases with age. Of patients with SCH, 80% have a serum TSH of less than 10 mIU/L. The most important implication of SCH is high likelihood of progression to clinical hypothyroidism.

Dr. Ron


Articles

Plasma folate levels are associated with the lipoprotein profile

            (Semmler, Moskau et al. 2010) Download

ABSTRACT: BACKGROUND: Several studies demonstrated an association of homocysteine plasma levels and the plasma lipoprotein profile. This cross-sectional pilot study aimed at analyzing whether blood levels of the two important cofactors of homocysteine metabolism, folate and vitamin B12, coincide with the lipoprotein profile. METHODS: In a retrospective single center approach, we analyzed the laboratory database (2003-2006) of the University Hospital Bonn, Germany, including 1743 individuals, in whom vitamin B12, folate and at least one lipoprotein parameter had been determined by linear multilogistic regression. RESULTS: Higher folate serum levels were associated with lower serum levels of low density lipoprotein cholesterol (LDL-C; Beta=-0.164; p<0.001), higher levels of high density lipoprotein cholesterol (HDL-C; Beta=0.094; p=0.021) for trend and a lower LDL-C-C/HDL-C-ratio (Beta=-0.210; p<0.001). Using ANOVA, we additionally compared the individuals of the highest with those of the lowest quartile of folate. Individuals of the highest folate quartile had higher levels of HDL-C (1.42+/-0.44 mmol/l vs 1.26+/-0.47 mmol/l; p=0.005), lower levels of LDL-C (3.21+/-1.04 mmol/l vs 3.67+/-1.10 mmol/l; p=0.001) and a lower LDL-C/HDL-C- ratio (2.47+/-1.18 vs 3.77+/-5.29; p=0.002). Vitamin B12 was not associated with the lipoprotein profile. CONCLUSION: In our study sample, high folate levels were associated with a favorable lipoprotein profile. A reconfirmation of these results in a different study population with a well defined status of health, diet and medication is warranted.

Autoimmune gastritis in type 1 diabetes: a clinically oriented review

            (De Block, De Leeuw et al. 2008) Download

CONTEXT: Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3- to 5-fold increased. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of autoimmune gastritis in type 1 diabetic patients. SYNTHESIS: Autoimmune gastritis is characterized by: 1) atrophy of the corpus and fundus; 2) autoantibodies to the parietal cell and to intrinsic factor; 3) achlorhydria; 4) iron deficiency anemia; 5) hypergastrinemia; 6) pernicious anemia may result from vitamin B12 deficiency; and 7) in up to 10% of patients, autoimmune gastritis may predispose to gastric carcinoid tumors or adenocarcinomas. This provides a strong rationale for screening, early diagnosis, and treatment. The management of patients with autoimmune gastritis implies yearly determination of gastrin, iron, vitamin B12 levels, and a complete blood count. Iron or vitamin B12 should be supplemented in patients with iron deficiency or pernicious anemia. Whether regular gastroscopic surveillance, including biopsies, is needed in patients with autoimmune gastritis/pernicious anemia is controversial. The gastric carcinoids that occur in these patients generally do not pose a great threat to life, whereas the danger of developing carcinoma is controversial. Nevertheless, awaiting a consensus statement, we suggest performing gastroscopy and biopsy at least once in patients with autoantibodies to the parietal cell, iron-, or vitamin B12-deficiency anemia, or high gastrin levels. CONCLUSION: The high prevalence of autoimmune gastritis in type 1 diabetic patients and its possible adverse impact on the health of the patient provide a strong rationale for screening, early diagnosis, periodic surveillance by gastroscopy, and treatment.

Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis

(Sanyal, Chalasani et al. 2010) Download

BACKGROUND: Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. METHODS: We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indicate statistical significance. RESULTS: Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P=0.001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P=0.04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pioglitazone, as compared with placebo (P<0.001 for both comparisons), and both agents were associated with reductions in hepatic steatosis (P=0.005 for vitamin E and P<0.001 for pioglitazone) and lobular inflammation (P=0.02 for vitamin E and P=0.004 for pioglitazone) but not with improvement in fibrosis scores (P=0.24 for vitamin E and P=0.12 for pioglitazone). Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo; the rates of other side effects were similar among the three groups. CONCLUSIONS: Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes. (ClinicalTrials.gov number, NCT00063622.)

Subclinical hypothyroidism: an update for primary care physicians

         (Fatourechi 2009) Download

Subclinical hypothyroidism (SCH), also called mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. This condition occurs in 3% to 8% of the general population. It is more common in women than men, and its prevalence increases with age. Of patients with SCH, 80% have a serum TSH of less than 10 mIU/L. The most important implication of SCH is high likelihood of progression to clinical hypothyroidism. The possibility that it is a cardiovascular risk factor has been a subject of debate. Large-scale randomized studies are needed for evidence-based recommendations regarding screening for mild thyroid failure and levothyroxine therapy for this condition. Currently, the practical approach is routine levothyroxine therapy for persons with a persistent serum TSH of more than 10.0 mIU/L and individualized therapy for those with a TSH of less than 10.0 mIU/L.


References

De Block, C. E., I. H. De Leeuw, et al. (2008). "Autoimmune gastritis in type 1 diabetes: a clinically oriented review." J Clin Endocrinol Metab 93(2): 363-71.

Fatourechi, V. (2009). "Subclinical hypothyroidism: an update for primary care physicians." Mayo Clin Proc 84(1): 65-71.

Sanyal, A. J., N. Chalasani, et al. (2010). "Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis." N Engl J Med 362(18): 1675-85.

Semmler, A., S. Moskau, et al. (2010). "Plasma folate levels are associated with the lipoprotein profile: a retrospective database analysis." Nutr J 9(1): 31.