Efficacy and safety of insulin glargine and glimepiride in subjects with Type 2 diabetes before, during and after the period of fasting in Ramadan.

AIMS: To determine the safety and efficacy of insulin glargine and glimepiride in patients with Type 2 diabetes before and after Ramadan and during fasting for Ramadan. METHODS: In this open, descriptive, multi-centre, prospective study, insulin-naïve (n = 100) or previously insulin-treated (n = 249) patients with Type 2 diabetes received insulin glargine [titrated from 10 U daily according to fasting blood glucose (FBG)] and glimepiride (4 mg daily). The number and type of hypoglycaemic episodes and glycaemic control were assessed before, during and after Ramadan. Bivariate logistic regression analyses were used to identify factors which predicted hypoglycaemia during Ramadan. RESULTS: Only one episode of severe hypoglycaemia occurred in each time period before, during and after Ramadan. Mild hypoglycaemic episodes increased from 156 pre-Ramadan to 346 during Ramadan (P < 0.001) and decreased to 153 post-Ramadan (P = 0.0002).The increase during Ramadan was mainly attributed to increased symptomatic hypoglycaemic episodes. FBG and glycated haemoglobin improved during the titration period and did not change during the rest of the study. Risk of hypoglycaemic events during Ramadan was higher in countries where fasting is strict [odds ratio (OR) 3.69 (2.06-6.63), P < 0.0001]. Lower weight [< 70.0 kg; OR 2.56 (1.46-4.48), P = 0.001] and waist circumference [< 90 cm; OR 3.06 (1.62-5.78), P = 0.001] increased the risk of hypoglycaemia during Ramadan whilst FBG > 6.7 mmol/l [OR 0.3 (0.17-0.54), P < 0.0001] had a protective effect. CONCLUSIONS: Combination of insulin glargine and glimepiride may be used during Ramadan in patients with Type 2 diabetes who wish to fast, provided glimepiride is given at the time of breaking the fast and insulin glargine titrated to provide FBG > 6.7 mmol/l.

Enhancing nonmydriatic color photographs of the retina with monochromatic views and a stereo pair to detect diabetic retinopathy.

BACKGROUND AND OBJECTIVE: Nonmydriatic digital color imaging is rapidly gaining an important role in screening for diabetic retinopathy. However, it has yet to equal a dilated fundus examination or seven Early Treatment Diabetic Retinopathy Study field 35-mm photography. The authors therefore attempted to enhance efficacy and validity by adding two low-cost steps to the nonmydriatic digital image evaluation. PATIENTS AND METHODS: The fundi of 145 consecutive patients with diabetes mellitus were evaluated for diabetic retinopathy using two different nonmydriatic reading techniques: creating a red-free view (using digital filters) and looking at a stereo pair of each field taken. These methods were each compared to a mydriatic fundus examination. RESULTS: Although the first technique yielded views with sensitivities and specificities similar to what exists in the literature using this same technique, enhancing these photographs (second technique) yielded a statistically significant increase in sensitivity and specificity (P < .005). CONCLUSION: The authors recommend using both low-cost steps when screening for diabetic retinopathy through nonmydriatic digital color imaging.

Endocrinologic manifestations of the antiphospholipid syndrome.

Our objective was to study the endocrinologic manifestations of the antiphospholipid syndrome (APS). We reviewed the medical literature from 1968 until 2005 using MEDLINE and the key words: APS, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid antibodies, adrenal, thyroid, parathyroid, pituitary, diabetes, ovaries and testes. Adrenal insufficiency is the most common endocrinologic manifestation and can be the presenting symptom of APS. In patients with autoimmune thyroid disease circulating aPL have been detected. However, no clinical manifestations of APS have been described. A few cases of hypopituitarism have been reported, including a case of Sheehan's syndrome. aPL has been detected in the sera of diabetic patients, probably associated with some macroangiopathic complications. Finally only very few cases of ovarian and testicular involvement have been reported. The adrenals are the most commonly involved glands in the APS. Clinicians should keep a high index of suspicion for adrenal insufficiency in patients with APS.

Virus-induced chalazion.

PURPOSE: To investigate a viral etiology in certain chalazia. METHODS: A prospective study over 7.5 years of all newly presenting chalazia associated with diffuse follicular conjunctivitis but without any other aetiological factors. Patients were investigated for ocular or systemic infections by history, physical exam, slit-lamp exam, and/or histology of conjunctival biopsy (including transmission electron microscopy). RESULTS: A total of 27 patients developed follicular conjunctivitis without meibomian gland dysfunction, blepharitis, or sexually transmitted diseases. Evidence for a viral aetiology included: recent systemic viral illness (15/27), recent contact with subjects with chalazia or follicular conjunctivitis (5/27), preauricular lymphadenopathy (4/27), viral corneal disease (4/27), or viral particles by ultrastructure (4/4). CONCLUSIONS: Chalazia may be associated with viral conjunctivitis. Intralesional corticosteroids should be considered with great caution for viral-induced chalazia.

Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome.

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumours, which are frequently carcinomas, and ossifying jaw fibromas. In addition, some patients may develop renal tumours and cysts. The gene causing HPT-JT, which is referred to as HRPT2 and is located on chromosome 1q31.2, encodes a 531 amino acid protein called PARAFIBROMIN. To date 42 mutations, of which 22 are germline, have been reported and 97% of these are inactivating and consistent with a tumour suppressor role for HRPT2. We have investigated another four HPT-JT families for germline mutations, searched for additional clinical phenotypes, and examined for a genotype-phenotype correlation. Mutations were found in two families. One family had a novel deletional-insertion at codon 669, and the other had a 2 bp insertion at codon 679, which has been reported in four other unrelated patients. These five unrelated patients and their families with the same mutation were not found to develop the same tumours, thereby indicating an absence of a genotype-phenotype correlation. An analysis of 33 HPT-JT kindreds revealed that affected women in 13 HPT-JT families suffered from menorrhagia in their second to fourth decades. This often required hysterectomy, which revealed the presence of uterine tumours. This resulted in a significantly reduced maternal transmission of the disease. Thus, the results of our analysis expand the spectrum of HPT-JT-associated tumours to include uterine tumours, and these may account for the decreased reproductive fitness in females from HPT-JT families.

Ring chromosome 18q and jumping translocation 18p in an adult male with hypergonadotrophic hypogonadism.

Constitutional jumping translocations (JT) are rare, especially in phenotypically normal individuals. We report on an adult male with partial hypogonadism as the sole phenotypic abnormality with an unusual chromosome abnormality. In this patient, centric fission of chromosome 18 lead to formation of a ring 18q chromosome, while 18p formed a JT through centromere-telomere fusion with chromosome 8q (66%) or 20q (13%). In 21% of cells, the 18p fragment was missing. Fluorescent in situ hybridization revealed the presence of interstitial telomeres at the junction site of the fusion and unequal distribution of the alphoid sequences through the centric fission, leaving a small, yet functional centromere within the ring. We discuss the phenotype of the patient in light of this unusual karyotype.

CTLA-4 gene polymorphism and its association with Graves' disease in the Lebanese population.

Graves' disease is an organ-specific autoimmune disease that has a female predominance. It is probably the result of a complex interaction of genetic and environmental factors. This disease is characterized by immune system activation, evidenced by elevated serum thyroid-specific autoantibodies and lymphocytic infiltration of the target organ (the thyroid gland), associated with raised levels of circulating activated T lymphocytes. Several reports have demonstrated genetic linkage and association between the genetic markers of the CTLA-4 gene on chromosome 2q33 and Graves' disease. In order to confirm this association in the Lebanese population, a bi-allelic A/G polymorphism at position 49 of CTLA-4 exon 1 was studied in 34 patients with Graves' disease, and in 38 healthy individuals, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results showed a significant increase in allele and genotype frequencies in patients with Graves' disease compared to controls. This suggests that the CTLA-4 gene might play a role in the development of Graves' disease in the Lebanese population.

Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population.

Wolfram syndrome (WFS) is a rare hereditary neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). WFS seems to be a heterogeneous disease that has not yet been fully characterized in terms of clinical features and pathophysiological mechanisms because the number of patients in most series was small. In this study we describe 31 Lebanese WFS patients belonging to 17 families; this, to our knowledge, is the largest number of patients reported in one series so far. Criteria for diagnosis of WFS were the presence of insulin-dependent diabetes mellitus and optic atrophy unexplained by any other disease. Central diabetes insipidus was found in 87% of the patients, and sensorineural deafness confirmed by audiograms was present in 64.5%. Other less frequent features included neurological and psychiatric abnormalities, urodynamic abnormalities, limited joint motility, cardiovascular and gastrointestinal autonomic neuropathy, hypergonadotropic hypogonadism in males, and diabetic microvascular disease. New features, not reported in previous descriptions, such as heart malformations and anterior pituitary dysfunction, were recognized in some of the patients and participated in the morbidity and mortality of the disease. Genetic analysis revealed WFS1 gene mutations in three families (23.5%), whereas no abnormalities were detected in mitochondrial DNA. In conclusion, WFS is a devastating disease for the patients and their families. More information about WFS will lead to a better understanding of this disease and hopefully to improvement in means of its prevention and treatment.

Leptin levels in patients with type 1 diabetes receiving intensive insulin therapy compared with those in patients receiving conventional insulin therapy.

Several reports suggest that insulin may have a role in the regulation of serum leptin levels, and this is related to the fact that serum leptin levels generally indicate the amount of body fat. Studies show that leptin levels are low in newly diagnosed patients with Type-1 diabetes (T1 DM) and increase after institution of insulin therapy. This study was designed to test whether serum leptin levels are higher in patients receiving intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT). Young patients with T1 DM were studied, 23 on IIT and 23 on CIT. The patients were matched for age (19+/-3 and 20+/-5 yr, respectively), duration of diabetes (8+/-5 and 10+/-6 yr, respectively) and BMI (24+/-4 and 23+/-3 kg/m2, respectively). Leptin levels were higher in IIT compared to CIT (13+/-12 vs 7+/-7 ng/ml, respectively, p<0.05). The results of this study demonstrate that patients on IIT have higher leptin levels than patients on CIT. This increase in leptin level in IIT patients is independent of changes in bw and is probably due to the stimulatory effect of insulin on leptin production.

Transient renal tubular acidosis in pregnancy.

Renal tubular acidosis in pregnancy is a very rare disorder. Most cases are either inherited or secondary to maternal disease or ingestion of toxic chemicals. We report a 22-year-old woman, previously healthy, who presented at 27 weeks of gestation with preterm labor. Investigation revealed renal tubular acidosis with no obvious etiology. Labor was stopped with various tocolytic drugs and her electrolyte imbalance was corrected. She was delivered at 36 weeks, by cesarean for a nonreassuring fetal heart tracing, of an appropriate-for-gestational-age infant weighing 2905 g. Evaluation 3 and 6 months postpartum revealed gradual, but complete resolution of the acidosis and electrolyte abnormality. The infant is now 7 months old, is growing normally with normal electrolytes, and with no evidence of acidosis.

Alterations in plasma transforming growth factor beta in normoalbuminuric type 1 and type 2 diabetic patients.

Transforming growth factor ss (TGF-ss) is an immunosuppressor. It plays a role in regulating cell proliferation, and deletion of its gene in transgenic mice leads to an autoimmune-like disorder. A role of this cytokine has been proposed in the pathogenesis of type 1 diabetes and probably type 2 diabetes. Previous studies had shown an elevated serum level in type 2 diabetes and a reduced serum level in type 1 diabetes; however, these studies did not address the onset of the alterations of TGF-ss with regard to the duration of diabetes. In this study, we compared the levels of TGF-ss in the serum of groups of patients with type 1 and type 2 diabetes mellitus divided according to the duration of their disease. Twenty-six normoalbuminuric patients with type 1 diabetes and 25 normoalbuminuric patients with type 2 diabetes were divided into three groups according to the onset of their diabetes and were compared with 27 and 15 age-matched normal subjects, respectively. We conclude that in normoalbuminuric patients serum TGF-ss levels increased at the onset of type 2 diabetes and remained elevated throughout the disease; they did not change at the onset of type1 diabetes, however, they started to decrease around 2 yr after the onset of the disease.

Successful treatment of parathyroid cyst using ethanol sclerotherapy.

Simple parathyroid cysts are rare; only about 200 cases have been reported in the literature. The diagnosis was facilitated recently by parathyroid hormone assay of the cyst fluid. Standard treatment consists of percutaneous aspiration of the cyst and surgical excision for recurrent lesions. Sclerotherapy of recurrent lesions was described in two cases and results were promising. The authors report a new case of recurrent nonfunctioning parathyroid cyst in a 34-year-old female, with complete resolution after ethanol sclerosis and no recurrence for 15 months of follow-up. Ethanol sclerotherapy is recommended as a simple and safe treatment for recurrent parathyroid cysts.

Managing diabetes mellitus in a Lebanese primary care centre. Working towards change.

OBJECTIVES: Demand for medical care in Lebanon is dominated by diseases, such as diabetes. Quality of documentation of care given to these patients in a primary care centre, prior to and after introducing a diabetes initiative (DI) is reported. METHODS: Chart audit of diabetic patients attending an inner city health centre in Beirut, during 1/6/94-30/8/96 was conducted. DI was introduced in 1/1/97, and audit repeated six months later. RESULTS: First and second audits identified 213 and 162 patients respectively. Audit I showed poor recording for almost all parameters; example: family history (3%), smoking status (11%), hypertension (9%), dyslipidaemia (4%), BMI (nil), blood pressure (46%), foot exam (16%), HbA1c (nil), serum cholesterol and triglyceride (27%) and urine analysis (12%). Audit II revealed an improvement in the recording of most parameters, risk factors such as: smoking status, hypertension, hyperlipidaemia (98-99%), physical examination: BMI (39%), foot and peripheral circulation (91-92%), blood pressure (87%). Over half the patients had undergone a complete metabolic workup. CONCLUSION: Over the short period of time, there appears to have been an important improvement in the documentation of medical care for these diabetic patients. Effects of this change in terms of clinical outcomes is currently being assessed.

Continuing medical education.

While continuing medical education (CME) is receiving increasing attention from medical educators and health administrators worldwide, many efforts need to be made to improve its performance and overall effectiveness. Traditionally, CME has depended primarily on periodic courses and conferences. These remain of unproven cost-effectiveness and often the choice of their content is not tailored to meet best the needs of the learners. It is proposed that CME activities be reshaped to depend more on supervised small-group tutorials in which the learner is an active participant in preparation and presentation. Moreover, instead of having CME activities take place once or twice a year in a distant location, a more practical format would be to plan additional activities more frequently, but less condensed, on an ongoing basis and preferably at the place of work all year round. Factors that may increase learner motivation would be to depend not only on attendance at CME activities but also on the introduction of assessment mechanisms that will measure objectively the actual desired advancement of the learners. Incentives for good learners and teachers need to be introduced. The cost of CME is heavy and can be a burden on health authorities and medical institutions. Contributions from the medical/pharmaceutical industry are acceptable provided quality control is assured and conflict of interest is avoided. Increasing use of computer-assisted teaching and modern telecommunication should, in the near future, help to reduce costs and improve effectiveness of most CME programmes.

A case of granulomatous hypophysitis with hypopituitarism and minimal pituitary enlargement.

A case of hypopituitarism and minimal sellar enlargement was found at hypophysectomy to have a giant cell granuloma of the pituitary. The clinical and histopathological features of this rare entity are reviewed. It is proposed that hypopituitarism which is out of proportion to minimal sellar enlargement may be a suggestive clue to the preoperative diagnosis of giant cell granulous which normally simulates a pituitary tumour.

Hypophyseal-gonadal dysfunction in men with non-alcoholic liver cirrhosis.

Seven males with liver cirrhosis associated with hepatitis and one with schistosomal liver fibrosis were studied for hypophyseal gonadal dysfunction and compared to six age matched controls. Cirrhotics as a group had higher serum 17 beta estradiol levels (22.1 +/- 6.3 vs 7.8 +/- 0.8 pg/ml, p less than 0.05) which did not rise after four days of human chorionic gonadotropin (hCG) stimulation. Conversely, there was an adequate rise in serum testosterone level after hCG stimulation (332.8 +/- 99.7 ng/dl baseline to 887.6 +/- 67.1 ng/dl, p less than 0.01). Compared to the controls, cirrhotics had lower baseline serum follicle stimulating hormone (FSH) (3.6 +/- 1.7 vs. 10.2 +/- 1.5 mIu/ml, p less than 0.02) and higher serum prolactin (13.5 +/- 2.5 vs. 6.8 +/- 1.0 ng/ml, p less than 0.05). Pituitary dynamic function testing in cirrhotics revealed blunted response of luteinizing hormone (LH) and FSH, to luteinizing hormone releasing hormone (LHRH) in four out of eight subjects tested. We conclude that the mechanism of hypogonadism in non-alcoholic cirrhosis is mostly hypogonadotropic in origin rather than primary gonadal injury which is common in alcoholic cirrhosis.

Anaplastic transformation of thyroid cancer: report of two cases and review of the literature.

Transformation of well-differentiated thyroid adenocarcinoma to anaplastic cancer has been occasionally reported. Two new cases of such transformation are now described. The time interval from diagnosis to the development of anaplastic cancer was 15 years in the first patient and 10 years in the second. Both patients ultimately developed extensive bilateral pulmonary metastases and died within 6 months from the diagnosis of the transformation. Hypotheses concerning the pathogenesis of the transformation and the literature were reviewed. We believe that histopathological confirmation of recurrent and rapidly progressive thyroid tumors is necessary prior to initiation of therapy.