Subject(s)
Diabetes Complications/diagnosis , Diabetes Complications/therapy , Emergencies , Diabetes Complications/etiology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/therapy , Diabetic Foot/diagnosis , Diabetic Foot/etiology , Diabetic Foot/therapy , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/etiology , Diabetic Ketoacidosis/therapy , Germany , Humans , Hyperglycemic Hyperosmolar Nonketotic Coma/diagnosis , Hyperglycemic Hyperosmolar Nonketotic Coma/etiology , Hyperglycemic Hyperosmolar Nonketotic Coma/therapy , Hypoglycemia/diagnosis , Hypoglycemia/etiology , Hypoglycemia/therapy , Patient Admission , Recurrence , Risk FactorsABSTRACT
BACKGROUND: Genetic hemochromatosis leads to iron overload in many tissues and may lead to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and therapy are crucial. Since 80-100% of hemochromatosis patients of European origin are homozygous for a cysteine to tyrosine exchange in the HFE gene at codon 282, genetic screening might be useful. Representative population studies are needed to evaluate the phenotype of people heterozygous and homozygous for the C282Y mutation. OBJECTIVE: To determine the correlation between parameters of iron metabolism and the hemochromatosis genotype in a large population-based study. METHODS: A representative population-based survey, the Diabetomobil study, analyzed 5,083 German probands. Serum transferrin saturation and ferritin levels were determined, and the C282Y mutation of the HFE gene was analyzed by restriction fragment length polymorphism-polymerase chain reaction analysis. RESULTS: Nine of 373 probands with a transferrin saturation > 55% (2.4%) and none of 264 randomly selected probands with a transferrin saturation < or = 55% (0%) were homozygous for the C282Y mutation. Three of the nine homozygous probands had ferritin values less than 250 micrograms/L. The frequency of the heterozygous genotype was 8.8%, and the percentage of heterozygous probands increased with increasing levels of transferrin saturation. CONCLUSION: We propose a population screening strategy with an initial transferrin saturation test, followed by genotyping for the C282Y mutation if the transferrin saturation is above 55%, regardless of the ferritin level. Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.
Subject(s)
Hemochromatosis/genetics , Hemochromatosis/metabolism , Histocompatibility Antigens Class I/genetics , Iron/metabolism , Membrane Proteins/genetics , Mutation/genetics , Adult , Aged , Female , Ferritins/blood , Gene Frequency , Genetic Testing , Genotype , Germany/epidemiology , Hemochromatosis/complications , Hemochromatosis/epidemiology , Hemochromatosis Protein , Heterozygote , Homozygote , Humans , Iron Overload/genetics , Iron Overload/metabolism , Male , Middle Aged , Penetrance , Phenotype , Polymorphism, Restriction Fragment Length , Population Surveillance , Prevalence , Transferrin/metabolismABSTRACT
Glitazones are known to modulate fatty acid-induced effects on insulin secretion in the pancreatic beta-cell. The present study focused on combined effects of troglitazone and oleate on preproinsulin (PPI) biosynthesis. Insulin-producing INS-1 cells were incubated for 4 hr at 11.2mM glucose in the presence (O(+)) or absence (O(-)) of 200 microM oleate with (T(+)) or without (T(-)) 10 microM troglitazone. After cell lysis, cytoplasmic RNA was extracted and employed for Northern blotting and corresponding in vitro translation. Compared with untreated controls (CTRL=O(-)/T(-)), the cellular content of PPI-mRNA from cells which had been simultaneously treated by troglitazone and oleate (O(+)/T(+)) was significantly diminished (O(+)/T(+)=75+/-10% x CTRL; P=0.015). The PPI-mRNA content from those cells which had been exclusively exposed either to oleate (O(+)/T(-)) or troglitazone (O(-)/T(+)) did not significantly differ from that of the untreated controls. In spite of that decreased PPI-mRNA content, in vitro translation revealed the highest yield of newly synthesized PPI in RNA samples from those cells which had been simultaneously exposed to oleate and troglitazone before (O(+)/T(+)=1.6+/-0.3 x CTRL; P=0.01). It is concluded that troglitazone and oleate synergistically affect the translational rate at the level of the PPI-mRNA molecule.
