The benefit observed with this medication is possibly associated with its immunological effects. T1DM patients from those with atypical or ketosis-prone diabetes. Background Type 1 diabetes mellitus (T1DM) is usually a chronic disease characterized by the autoimmune destruction of pancreatic -cells in genetically susceptible subjects, IKK epsilon-IN-1 which results in absolute insulin deficiency. This pathology is usually diagnosed between the age of 6 months and adulthood, and is clinically manifested through polyuria, polydipsia, and weight loss associated with glycosuria and ketonuria (1). Several agents used to reestablish immunological tolerance over the past few years have successfully prevented and even reverted T1DM in nonobese diabetic mice; however, these outcomes have not been achieved in humans (1). This paper describes the case of a male patient aged 19 who presented with T1DM and whose condition has been remitted for a year, being currently treated only with sitagliptin. Case presentation The case is usually a 19-year-old male patient from Ciudad Bolvar, Venezuela, without any familial history of diabetes, IKK epsilon-IN-1 presented with polyuria, polydipsia, and weight loss (16?kg) with 3 months of evolution. The physical examination showed a weight of 61?kg; a height of 1 1.71?m; BMI of 20.8?kg/m2; a waist circumference of 76?cm; blood pressure at 100/60?mmHg. Investigation The blood assessments showed: fasting blood glucose: 432?mg/dl; HbA1c: 12.3%, basal insulin: 3.2?mUI/ml, C-peptide: 1.2?ng/ml, venous pH: 7.2, bicarbonate: 13?mEq/l, total cholesterol: 178?mg/dl, triglycerides: 196?mg/dl, HDL cholesterol: 41?mg/dl, and LDL cholesterol: 97?mg/dl. Urinalysis revealed glycosuria and ketonuria. Glutamic acid IKK epsilon-IN-1 decarboxylase (GAD) antibody resulted positive (46?U/ml, reference range 1C5), but islet cell antibody and anti-insulin assessments were negative. Human leukocyte antigen (HLA) genotyping for DR and DQ-encoding loci was carried out by next generation sequencing around the Roche 454 GS Junior platform as previously described (2) and resulted in the following genotypes: DQA1*01:01:01, DQA1*05:01:01; DQB1*02:01:01, DQB1*05:01:01; DRB1*03:01:01, DRB1*10:01:01; and DRB3*02:02:01. Based on established patterns of linkage disequilibrium for these loci, the genotypes can be assigned to the following haplotypes: DRB1*03:01:01-DRB3*02:02:01-DQA1*05:01:01-DQB1*02:01:01 (DR3) and DRB1*10:01:01-DQA1*01:01:01-DQB1*05:01:01 (DR10). Treatment An intensive s.c. regimen of both insulin glargine and insulin glulisine was prescribed at a dose of 0.5?models/kg per 24?h, reaching an adequate metabolic control in 72?h, after which sitagliptin at a dose of 100?mg was initiated with a frequency of once a day. Outcome and follow-up Upon completion of the first month of treatment, the patient started to show a significant reduction in daily insulin requirement, until its complete discontinuance eight weeks after diagnosis, when the patient joined remission and continued on sitagliptin alone, reaching fasting plasma glucose concentrations between 70 and 130?mg/dl and an HbA1c of 7.8%. The insulin-dose-adjusted HbA1c, defined as actual HbA1c (%)+(4insulin dose (models/kg per 24?h)) (3), was 7.8 (value defining partial remission 9). By this time, the patient had gained 7?kg of weight. The GAD antibody levels were significantly decreased (8?U/ml). The levels of C-peptide plasma concentration remained the same. After one year of treatment with only 100?mg of sitagliptin, the blood test report of the patient shows the following values: HbA1c, 5.8%; fasting plasma glucose, 108?mg/dl; basal insulin, 2.6?mIU/ml; fasting C-peptide, 1.0?ng/ml; 2?h, 75?g postprandial glucose, 152?mg/dl, and an insulin value of 25.7?mIU/ml with a C-peptide of 4.3?ng/ml. Currently, after 15 months on sitagliptin treatment, the patient’s last assessment showed the following report: HbA1c, 6.3%; fasting plasma glucose, 122?mg/dl; basal insulin, 2.4?mIU/ml; fasting C-peptide, 0.9?ng/ml; 2?h, 75?g postprandial glucose 164?mg/dl, and an insulin value of 18.3?mIU/ml with a C-peptide of 3.9?ng/ml. The GAD-antibodies remain positive (6?U/ml). Discussion The pathogenesis of T1DM is usually predicated on both genetic predisposition factors (predominantly HLA alleles) and the presence of autoantibodies in the serum against islet cells, insulin, tyrosine phosphatase (IA-2), and Rabbit Polyclonal to RRM2B GAD (1). The subject was diagnosed with T1DM based on HLA alleles, the HbA1c test, and the presence of positive antiGAD. The haplotypes DRB1*03:01-DQA1*05:01 and DQB1*02:01 (DR3) are well established to be predisposing for T1DM, with odds ratios in the range of 3C5, depending on the populace (4). A recent report has shown that DR3 haplotypes carrying the allele DRB3*02:02 are more predisposing than those carrying the allele DRB3*01:01 (2). Thus, the DR3 haplotype in the patient is consistent with T1DM autoimmunity and the presence of anti-GAD antibodies. At.
The benefit observed with this medication is possibly associated with its immunological effects