Association of HLA-DR-DQ polymorphisms with diabetes in Tunisian patients.

OBJECTIVE: Type 1 diabetes (T1D) is a polygenic disease whose principal locus is the human leukocytes antigen (HLA) region. The aim of this study was to evaluate HLA DR-DQ alleles and to asses them as risk factors for type 1 diabetes in the Tunisian population. MATERIALS AND METHODS: A total of 119 subjects with diabetes were tested for HLA class II alleles and compared with 292 healthy controls. HLA DRB1 and DQB1 alleles were genotyped using polymerase chain reaction sequence-specific primers (PCR-SSPs). RESULTS: The results revealed that the most susceptible haplotypes are the DRB1(*)03-DQB1(*)02 (pc<10(-3)) and DRB1(*)0401-DQB1(*)0302 (pc=0.001). (pc denotes Bonferroni corrected probability values.) The most protective haplotypes are DRB1(*)11-DQB1(*)03, DRB1(*)07-DQB1(*)02, and DRB1(*)13-DQB1(*)06 (pc=0.0026, pc=0.0065, and pc=0.02 respectively). Our results showed some particularities unique to Tunisians, there was a lack of a significant protective effect of the DRB1(*)15-DQB1(*)06 haplotype that usually is the dominant combination associated with protection in most other populations. CONCLUSION: Tunisian diabetic patients share the most susceptible and protective HLA haplotypes with Caucasians and those in neighbor Mediterranean countries. This is most likely explained by the history and admixture events of Tunisia and North Africa.

Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the single greatest cause of end-stage renal disease (ESRD). Without specific interventions, microalbuminuria (incipient nephropathy) gradually progresses to macroalbuminuria (overt nephropathy) within 10-15 years in about 80% of type 1 and 30% of type 2 diabetic patients, and to ESRD within further 20 years in about 75% and 20%, respectively. A primary alteration in DN consists of decreased concentration of glycosaminoglycans (GAGs) in the glomerular extracellular matrix. This evidence has prompted interest in using exogenous GAGs and specifically sulodexide in DN treatment. PATIENTS AND METHODS: In this uncontrolled multicenter study, diabetic patients with albumin excretion rate (AER) >or=30 mg/24 hours were treated with oral sulodexide 50 mg/day for 6 months, while receiving concomitant medication as required. Two hundred thirty-seven patients (54% males and 46% females, mean age 55 years, mean diabetes duration 11 years) were evaluated; 89% had type 2 and 11% type 1 diabetes mellitus, 67% microalbuminuria and 33% macroalbuminuria. RESULTS: AER was significantly and progressively reduced during sulodexide treatment (p<0.0001): geometric mean after 3 and 6 months was 63.7% (95% confidence interval [95% CI], 59.3%-68.4%) and 42.7% (95% CI, 37.8%-48.2%) of baseline, respectively. The reduction was similar in type 1 and type 2 diabetes and was slightly greater in macroalbuminuric than in microalbuminuric patients. Blood pressure was slightly lowered, while fasting glucose and glycosylated hemoglobin were moderately reduced. Adverse effects were observed in 5.5% of patients, including gastrointestinal in 3.8%. CONCLUSIONS: Sulodexide therapy was shown to reduce AER in patients with DN.

Methylenetetrahydrofolate Reductase (MTHFR) (C677T and A1298C) Polymorphisms and Vascular Complications in Patients with Type 2 Diabetes.

OBJECTIVES: To assess whether 2 polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, are risk factors for vascular complications in Tunisian patients with type 2 diabetes mellitus. METHODS: The MTHFR polymorphisms were genotyped, and plasma homocysteine levels were evaluated in 160 Tunisian patients with type 2 diabetes mellitus. RESULTS: Prevalence of the 2 heterozygous polymorphisms of the thermolabile MTHFR gene (CT and AC) was encountered more commonly in patients with diabetes mellitus than in the healthy controls (p<10-3). Subjects with diabetes had significantly higher homocysteine (Hcy) levels than the control subjects; however, there was no statistical difference in plasma Hcy values between carriers of mutant genotypes (CT/TT for C677T and AC/CC for A1298C) and wild types (CC and AA) in patients with diabetes. Retinopathy was found to be a vascular complication in patients with either the 677CT or the 1298(AC+CC) genotype more commonly than in those with the wild-type genotypes (p=0.003; OR=3.2, 95% CI, 1.4 to 7.4; p<10-3; OR=5.9, 95% CI, 2.7 to 13). Only patients who carry the A1298C mutation (AC+CC) are at risk for at least 1 complication (p=0.002). Double heterozygous mutants were at the greatest risk for retinopathy and for suffering at least 1 complication (p<10-3). CONCLUSIONS: Studies involving a larger study population and various ethnic groups are required before ruling out the role of MTHFR gene in type 2 diabetes mellitus and in vascular complications.

[Hypothalamic-pituitary Langerhans cell histiocytosis in adults]. / Atteinte hypothalamo-hypophysaire dans l'histiocytose de l'adulte.

INTRODUCTION: Langerhans cell histiocytosis is a rare entity. Involvement of the pituitary region is frequently delayed and rarely studied. CASES: We report some clinical and paraclinical particularities of the disease in four women. Diabetes insipidus was the initial symptom in all cases, accompanied by panhypopituitarism at initial presentation in one woman. Hypopituitarism was diagnosed from 6 months to 4 years after the diabetes insipidus in the other cases, and systemic lesions appeared 3 to 6 years thereafter. Magnetic resonance imaging of the hypothalamic-pituitary axis found tumors in two patients and infundibular thickening in the other two. One patient also had a partially empty sella. DISCUSSION: In adults, pituitary involvement seems to occur predominantly in women, and panhypopituitarism is possible at initial presentation. The clinical polymorphism of Langerhans cell histiocytosis makes this disease difficult and often slow to diagnose.

[Factors influencing homocysteineamia in type 2 diabetic patients]. / Facteurs modifiant l'homocysteinemie chez un groupe de diabetiques de type 2.

Previous studies have suggested that hyperhomocysteinaemia (Hcy) could be a strong and independent cardiovascular risk factor. Many factors could influence the serum concentration of Hcy such as vitamin B 12, folic acid, renal failure, hypothyroid status, ovarian failure and cancers. So the aim of our study was to evaluate the prevalence of hyperhomocysteinaemia among 54 type 2 diabetic patients and to study, its relationship with vitamin B12, folic acid and Metformin. Were excluded all patients with an evident cause of hyperhomocysteinaemia. Mean age of patients was 52.8 years. Mean Hcy was 11.7 + 6.9 micromol/l. The prevalence of hyperhomocysteinaemia was 27.8% in our group. There were eight (14%) patients with vitamin B12 deficiency and three among them had hyperhomocysteinaemia. There was no folic acid deficiency and no relationship with Metformin treatment. We suggest a wide screening of hyperhomocysteinaemia in type 2 diabetic patients and folic acid or vitamin B12 supplements if necessary.

[HbA1c in the monitoring of type 1 diabetic patients]. / Hemoglobine A1C (HbA1c): interet dans le suivi du diabete type 1.

We conducted this study to determine quality of glycemic control in patients with type 1 diabetes, based on evaluation of mean HbA1c. We enrolled 125 patients with type 1 diabetes who were hospitalized during the period from December 1998 to December 2001. Glycemic control was evaluated on mean of HbA1c in 82 patients and on mean of fasting glycemia values in 43 patients. Mean HbA1c was 9.9%. Mean of plasma fasting glycemia was 11 mmol/l. 22% of patients were perfectly or good controlled (HbA1c < or = 7% or HbA1c 7-7.5%). 12% had a moderate control (HbA1c 7.5 et 9%) and finally 66% of patients had a worse control (HbA1c > 9%). There was an excellent correlation between HbA1c and mean fasting glycemic values (p = 0.00028). Most of patients had unsatifactory control. We stressed on the absolute necessity of intensified insulin therapy and self-monitoring blood glucose.

[Primary hyperaldosteronism. A study of 18 cases]. / Les hyperaldostéronismes primaires. Etude de 18 cas.

Primary aldosteronism (PA) is defined as an autonomous over-production of aldosterone by the zona glomerulosa of the adrenal glands. It is classically considered as a rare cause of hypertension. Aldosterone producing adenoma (APA) and idiopatic hyperoldosteronism (IHA) represent the most frequent subtypes of PA. The authors report 18 cases of PA (14 women an 4 men) with a mean age of 42 +/- 13.5 years. All patients have hypertension and hypokaliemia (K < 3.5 mmol/l). Eleven patients have an APA, one patient has an adrenal carcinoma and three patients have IHA. The subtype of PA has not been established in three patients. We discuss in this article the clinical, biological, radiological and evolutif characteristics of our cases, and we insist on the necessity of making a precise etiologic diagnosis to propose the most adequate treatment.