Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide 1/analogs & derivatives , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Insulin Antibodies/drug effects , Sulfonylurea Compounds/therapeutic use , Aged , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/immunology , Drug Therapy, Combination , Glucagon-Like Peptide 1/administration & dosage , Glucagon-Like Peptide 1/therapeutic use , Humans , Hypoglycemic Agents/administration & dosage , Liraglutide , Male , Sulfonylurea Compounds/administration & dosage , Treatment OutcomeABSTRACT
A 47-year-old woman presented with hypokalemia (2.4 mmol/L). She also had hypomagnesemia, hypocalciuria, and hyperreninemic hyperaldosteronism. Sequence analysis revealed a compound heterozygous mutation, R655C and R955Q, in the SLC12A3 gene. These findings were compatible with Gitelman's syndrome (GS). Eplerenone, a selective aldosterone blocker, in combination with oral potassium chloride improved serum potassium level (3.6 mmol/L) with no apparent adverse effect. Although eplerenone has an advantage over spironolactone for its selective affinity for the aldosterone receptor, the efficacy and safety of eplerenone for GS is little understood. Our observation suggests that eplerenone is a useful treatment option for GS.
Subject(s)
Gitelman Syndrome/complications , Gitelman Syndrome/drug therapy , Hypokalemia/drug therapy , Hypokalemia/etiology , Mineralocorticoid Receptor Antagonists/therapeutic use , Spironolactone/analogs & derivatives , Base Sequence , DNA Mutational Analysis , Eplerenone , Female , Gitelman Syndrome/genetics , Humans , Hypokalemia/blood , Hypokalemia/genetics , Middle Aged , Mutation, Missense , Potassium/blood , Receptors, Drug/genetics , Solute Carrier Family 12, Member 3 , Spironolactone/therapeutic use , Symporters/genetics , Treatment OutcomeSubject(s)
Adrenal Glands/pathology , Adrenocorticotropic Hormone/physiology , Cushing Syndrome/drug therapy , Metyrapone/adverse effects , Metyrapone/therapeutic use , Adrenal Glands/physiopathology , Aged , Cushing Syndrome/physiopathology , Dose-Response Relationship, Drug , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/therapeutic use , Female , Humans , Hyperplasia , Steroid 11-beta-Hydroxylase/antagonists & inhibitors , Treatment OutcomeABSTRACT
The aim of this study is to determine the contribution of human leukocyte antigen (HLA) class II genes to insulin deficiency in slow-onset type 1 diabetes (T1D). Our results suggest that the susceptibility conferred by HLA subtypes to slow-onset T1D differs between insulin-deficient patients and non-insulin-deficient patients.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/metabolism , Histocompatibility Antigens Class II/genetics , Insulin/deficiency , Adolescent , Adult , Age of Onset , Aged , Asian People , Female , Genetic Predisposition to Disease/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Haplotypes , Humans , Male , Middle Aged , Young AdultABSTRACT
The contribution of the human leukocyte antigen (HLA) subtype to slow-onset type 1 diabetes (T1D), which includes latent autoimmune diabetes in adults (LADA), remains unclear in the Japanese population. We compared the frequencies of HLA DR-DQ haplotypes and genotypes of 72 acute-onset T1D patients, 100 slow-onset T1D patients, and 292 control subjects. The frequencies of DRB1*0405-DQB1*0401 (DR4) and DRB1*1302-DQB1*0604 (DR13) haplotypes were significantly higher in acute-onset patients, whereas that of the DRB1*1502-DQB1*0601 haplotype was significantly lower than those in slow-onset diabetes patients and controls. In contrast, DRB1*0802-DQB1*0302 (DR8) and DRB1*0901-DQB1*0303 (DR9) haplotypes were significantly more frequent, and the DRB1*1501-DQB1*0602 haplotype was extremely rare, in acute-onset patients and slow-onset diabetes patients. Genotype analysis revealed that DR4/9, DR4/13, and DR9/13 in acute-onset patients indicated high odds ratios (6.81, 12.0, and 15.6, respectively), whereas DR4/8 was significantly more frequent in slow-onset diabetes patients, but not in acute-onset patients. Our study demonstrated for the first time that the DR8 haplotype confers susceptibility to slow-onset T1D in the Japanese population. Moreover, there potentially are hierarchies for predisposing haplotypes, namely, DR13 > DR4 > DR9 > DR8 and for protective haplotypes, namely, DRB1*1501-DQB1*0602 > DRB1*1502-DQB1*0601.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Haplotypes , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Asian People/genetics , Child , Child, Preschool , Diabetes Mellitus, Type 1/ethnology , Gene Frequency , Genotype , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Japan , Linkage Disequilibrium , Middle Aged , Sequence Analysis, DNA , Young AdultABSTRACT
AIM: Type 1 diabetes (T1D) is associated with autoimmune thyroid disease (AITD). The human leukocyte antigen (HLA) has been extensively studied in these diseases. We aimed to clarify the contribution of AITD on the susceptibility and resistance of the HLA subtype to autoimmune T1D in the Japanese population. METHODS: The frequency of the HLA DR-DQ haplotype was compared between 56 autoimmune T1D patients with AITD and 71 autoimmune T1D patients without AITD, and control subjects. RESULTS: The frequencies of DRB1 0405-DQB1 0401, DRB1 0802-DQB1 0302, and DRB1 0901-DQB1 0303 haplotypes were significantly higher in T1D patients with AITD than in control subjects. The frequencies of DRB1 0101-DQB1 0501, DRB1 0901-DQB1 0303, and DRB1 1302-DQB1 0604 haplotypes were significantly higher in T1D patients without AITD than in control subjects. The frequencies of DRB1 1101-DQB1 0301 and DRB1 1501-DQB1 0602 haplotypes were significantly lower in T1D patients with or without AITD than in control subjects. CONCLUSIONS: Our results suggest that the susceptibility of the HLA subtype to autoimmune T1D differs between T1D with AITD and T1D without AITD, whereas there is no difference between the two groups with regard to HLA subtypes that confer protection against autoimmune T1D.
