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Khaled El Baba, Mira S Zantout, Randa Akel, Sami T AzarDepartment of Internal Medicine, Division of Endocrinology and Metabolism, American University of Beirut Medical Center, Beirut, LebanonIntroduction: The discovery that many tissues express the vitamin D receptor and are able to transform the 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D (active metabolite) has led to the hypothesis that vitamin D could have a role in the pathogenesis and prevention of diabetes mellitus. Accumulating evidence has linked vitamin D deficiency with immunological disturbance in type 1 diabetes mellitus. Several epidemiological studies have shown lower serum 25-hydroxyvitamin D concentrations in diabetic individuals compared to nondiabetic individuals.Patients and methods: A total of 105 Lebanese patients with type 1 diabetes mellitus were recruited. Levels of HbA1c and vitamin D were recorded during two phases with phase 1 being the period from June–September 2009 and phase 2 from January–April 2009.Results: Vitamin D levels at the end of sunny season (phase 2), reflecting the previous sunny months, were found to be higher than in the early summer season (phase 1) reflecting the previous cloudy months season, with a mean change of 0.70 ± 6.87 ng/mL (P = 0.029). HbA1c levels were higher in phase 2 than in phase 1 with an increase of 0.175% ± 1.46% (P = 0.113).Conclusion: Vitamin D levels were higher at the end of the sunny season than at the end of cloudy season. HbA1c was also lower (but not significantly so) in the early summer season (cloudy months). There was a weak correlation between seasonal changes of vitamin D levels and the control of blood glucose as monitored by HbA1c in a cohort of Lebanese patients with type 1 diabetes mellitus.Keywords: type 1 diabetes, vitamin D, HbA1c, seasonal variation

Gestational diabetes mellitus (GDM) is a complication of pregnancy that is characterized by impaired glucose tolerance with onset or first recognition during pregnancy. The reported prevalence of GDM varies between 0.6% and 20% of pregnancies depending on screening method, gestational age and the population studied. GDM is characterized by pancreatic β-cell function that is insufficient to meet the body's insulin needs. Available evidence suggests that β-cell defects in GDM result from the same spectrum of causes that underline hyperglycemia in general, including autoimmune disease, monogenic causes and insulin resistance. Adipokines are proteins secreted from the adipocytes and are believed to have a metabolic influence. Our review suggests that, in GDM, various adipokines, mainly leptin and adiponectin, are dysregulated. These two adipokines might have both prognostic and pathophysiological significance in this disease., Competing Interests: The authors declare no conflict of interest in preparing this article.

The objective of this paper is to review the evidence testing the possible benefit of vitamin D replacement on diabetes control and complications. Type 2 diabetes mellitus (DM 2) has become a significant global health care problem and its reported incidence is increasing at an alarming rate. Despite the improvement in therapy and development of new drugs, treatment is still not optimal especially with the associated adverse effects of most of the available drugs. New efforts are shifted toward disease prevention and a search for safer drugs. New mounting evidence is associating low vitamin D to diabetes mellitus and as such many studies were conducted to test the effect of vitamin D replacement on incidence of diabetes, diabetes control as well as diabetes complications. Although these studies present several limitations, vitamin D replacement seems to have beneficial effect on all aspects of diabetes: incidence, control and complications. Further longer term and more powered controlled trials are necessary to draw firmer conclusions on this beneficial role of vitamin D treatment on DM.

Objective: To study the incidence of hypoglycemia, glycemic control and body weight changes in patients with type 2 diabetes treated with vildagliptin and metformin versus another group treated with sulphonylureas and metformin during and after the period of fasting in Ramadan., Patients and Methods: This is a randomized open-label clinical trial that recruited 69 patients previously treated with a combination therapy of metformin and sulphonylurea. Patients in the control group were maintained on their usual metformin and sulphonylurea regimen with dose adjustment for the fasting period. Patients in the study group were given vildagliptin 50 mg twice daily (at Suhur and at Iftar). One group remained on the previous background therapy unchanged and the other group was switched from sulphonylurea to vildagliptin in combination with metformin. Four visits were scheduled, one before the beginning of Ramadan (baseline), a second visit at mid Ramadan, a third at the end of Ramadan and a final visit 1 month after the end of Ramadan. At every visit, patients were assessed for hypoglycemic events and patient education was given on lifestyle needs and hypoglycemia monitoring and management., Results: The calculated change in hemoglobin A1c from baseline to last visit was similar for both groups. The incidence of hypoglycemia during Ramadan was higher in the control group (26 episodes versus 19 episodes in the study group); this result was not statistically significant (p = 0.334). However, the number of patients who dropped out from the study because of discomfort due to treatment and fear of hypoglycemia was higher in the control group., Conclusion: For patients who insist on observing the fast, physicians can allow it only with close follow up and monitoring for hypoglycemic events, and vildagliptin may be a better agent than sulphonylurea.

Background: The IDMPS is a study to identify changes in diabetes treatment practice in several developing countries. This paper focuses on diabetes management and compliance with guidelines in a Middle Eastern country like Lebanon., Methods: The cross-sectional data from the 2006 wave of two weeks duration on the Lebanese population along with the longitudinal data of a 9-month follow-up study were collected., Results: A large proportion of Lebanese patients were not adequately controlled or followed up. A slight proportion was managed by diet and exercise alone while most patients were on two or more oral anti-hyperglycemics. Metformin was the most common monotherapy followed by sulfonylureas. 22.6% of Lebanese patients were on insulin, most commonly basal insulin alone followed by premix insulin alone. Blood glucose self-monitoring was more frequently done by insulinized patients and was associated with better glycemic control. Glycemic control was reached in 29.6% of type 2 patients (HbA1c < 7%) with poorest outcome for patients on insulin and was more frequently achieved in patients who had more frequent monitoring of HbA1c levels., Conclusion: For a proper assessment of diabetic control, maintaining adherence to international guidelines needs to be evaluated. Promoting patient education, improving physician knowledge with better implementation of guidelines is recommended.

Multiple myeloma is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers. It is characterized by accumulation of clonal plasma cells, predominantly in the bone marrow. The prevalence of type 2 diabetes is increasing; therefore, it is expected that there will be an increase in the diagnosis of multiple myeloma with concomitant diabetes mellitus. The treatment of multiple myeloma and diabetes mellitus is multifaceted. The coexistence of the two conditions in a patient forms a major challenge for physicians.

Osteoporosis is more common in women than in men. The prevalence in men is not defined yet; however it is becoming much more recognized as its prevalence and impact have become explicable. It is estimated that around 1% of bone mineral density is lost in men every year. Studies show that secondary osteoporosis is the major cause thus, making it important to define the disorders associated with male osteoporosis. Diabetes is a risk factor for bone fractures. In male patients with diabetes measures should be undertaken such as encouraging exercise, assuring adequate calcium and vitamin D intake, and treating diabetic complications.

Studies have found that diabetes and thyroid disorders tend to coexist in patients. Both conditions involve a dysfunction of the endocrine system. Thyroid disorders can have a major impact on glucose control, and untreated thyroid disorders affect the management of diabetes in patients. Consequently, a systematic approach to thyroid testing in patients with diabetes is recommended.

Patients with type 1 diabetes (a TH1 disease) have been reported to be at a lower risk of developing asthma (a TH2 disease). Both diseases are affected by environmental and genetic factors. Our objective is to examine this relationship in Lebanon, a Middle-Eastern country, where no previous similar studies are available. This is a cross-sectional observational study conducted at the Chronic Care Center, a referral medical center for type 1 diabetics. Patients with type 1 diabetes aged 6-39 years old, their unaffected siblings and age-matched control completed the International Primary Care Airways Group asthma screening questionnaire. The prevalence of asthma symptoms was compared among the three groups and separately within a subgroup of diabetics in relation to their carrier state of previously collected genetic data. Among 305 diabetics, 776 siblings and 187 controls, diabetics were at lower risk of having any asthma symptoms than controls; OR 0.48 (95% CI 0.32-0.72, p < 0.001) and siblings were at lower risk than diabetics and controls; OR 0.64 (95% CI 0.45-0.91, p = 0.01) and 0.28 (95% CI 0.19-0.42, p < 0.001), respectively. Among 66 diabetics, carriers of the HLA-DQB1*0201 allele were at lower risk of having any asthma symptoms than non-carriers (25.5 vs. 53.3%, p = 0.04). Only a statistically non-significant trend of higher risk was observed in carriers of HLA-DQB1*0301 and G allele at the 49 (A/G) nucleotide of CTLA-4 gene. The TH1-TH2 paradigm might partially explain these findings, since siblings were the least to report asthma symptoms. Future research is needed with diagnostic tests for asthma and extensive genetic testing.

Objective: To report a case of PHACE syndrome-Posterior fossa brain abnormalities, Hemangioma (usually facial), Arterial anomalies, Coarctation of the aorta along with cardiac defects, and Eye abnormalities-in a 16-year-old female patient with a port-wine stain of the right periorbital area present since birth in conjunction with hypoplasia of the contralateral internal carotid artery., Methods: Thyroid-stimulating hormone, free thyroxine, and growth hormone (GH) levels were measured, and insulin-induced hypoglycemia and arginine infusion tests were done. Radiologic investigations included sagittal enhanced T1-weighted magnetic resonance imaging of the brain and the pituitary gland as well as computed tomography and magnetic resonance angiography of the head and neck., Results: The patient had a normal karyotype. Her height and weight were below the 5th percentile for her chronologic age, and she had amenorrhea. Laboratory investigations revealed both thyroid and GH deficiencies and confirmed the diagnosis of hypogonadotropic hypogonadism. The imaging studies showed a right intraorbital hemangioma as well as an enhancing mass in the right internal auditory canal at the cerebellopontine angle, consistent with a posterior fossa hemangioma. Initiation of both thyroid and GH replacement therapy improved her growth rate and yielded a good clinical outcome., Conclusion: In patients with facial or neck hemangiomas, PHACE syndrome should be suspected, and brain imaging and cardiac, ophthalmologic, and endocrinologic evaluations are recommended to screen for other potential PHACE abnormalities.

Background: Ramadan, the ninth month of the Islamic lunar calendar, is the holy month of fasting for adolescent and adult Muslims. Observance of Ramadan is considered obligatory for every healthy adult Muslim. During this time, Muslims refrain from eating, drinking, smoking, and administering oral or parenteral medications from sunrise to sunset daily for 28 to 30 days., Case Summary: We evaluated the need for changes in basal insulin regimen in 5 patients (4 males and 1 female; age range, 15-19 years) with type 1 diabetes mellitus (T1DM) who fasted during Ramadan. The patients were receiving insulin pump therapy with regular human insulin and maintained weekly visits with their endocrinologist at The Chronic Care Center (Beirut, Lebanon). They were instructed to break the fast after any episode of hypoglycemia (finger stick glucose <70 mg/dL) or severe hyperglycemia (finger stick glucose ≥300 mg/dL or any hyperglycemia associated with presence of urine ketone bodies on urinary dipstick). Blood glucose concentrations did not change significantly with fasting. Finger stick blood glucose taken at 4-hour intervals decreased in the afternoon (at 4 pm) and increased in the evening and morning (10 pm and 8 am, respectively) during this month in 4 of 5 patients, while no significant change in circadian rhythm of finger stick blood glucose was observed in 1 patient. Based on the investigators' findings, the basal insulin requirement decreased by 5.5% to 25.0% (4 patients) or did not change (1 patient) during the fast. Changes in regimens, based on collaboration between the endocrinologist and diabetes educational nurse, were determined by blood glucose self-monitoring done at 4-hour intervals during the fasting period, pre-Suhur (predawn breakfast), and ≥2 hours after Iftar (evening fast-breaking meal). No cases of keto-acidosis or severe hypoglycemia were reported., Conclusion: These 5 adolescent and adult patients with T1DM who were using an insulin pump were able to fast during Ramadan without incidences of severe hypoglycemia or ketoacidosis by using close blood glucose self-monitoring and weekly follow-up with their endocrine team, which consisted of an endocrinologist, a registered nutritionist, and a diabetes educational nurse.

Studies investigating the effect of leptin on bone mass were inconsistent and some related it to the effect of insulin. We intend in this cross-sectional study to investigate the effect of leptin on bone mass in type 1 diabetic patients. We recruited 42 patients with type 1 diabetes for which we determined weight, height, HbA1c, microalbuminuria, serum leptin, bone mineral content (BMC) and density (BMD), and body composition. The patients had an average age of 20.1 +/- 0.6 years, an average body mass index (BMI) of 23.6 +/- 0.5 kg/cm(2) and an average duration of diabetes of 9.1 +/- 1.0 years. The Z-score was not correlated with HbA1c or duration of the disease, and the average Z-score was not different in patients with microalbuminuria as compared to patients with no reported microalbuminuria. On the other hand, Z-score and BMC correlated negatively with leptin (r = -0.31; p = 0.04 and -0.60, p < 0.01, respectively). These correlations persisted after adjustment for fat mass. We conclude that not metabolic control of diabetes, but serum leptin has a negative effect on bone density in young patients with type 1 diabetes. This negative effect of leptin on bone density maybe, in part, due to deficiency of endogenous insulin secretion in these patients.

Objectives: This paper reviews available information on insulin regimens that may enable patients with type 1 diabetes mellitus to fast during the month of Ramadan with minimal complications. It also provides guidance for health care professionals in managing patients who wish to observe the fast., Methods: Relevant English-language articles were identified through searches of the MEDLINE, EMBASE, and Index Medicus Eastern Mediterranean Region databases (all, 1980-2008) conducted in February 2008 using the terms Ramadan, fasting, type 1 diabetes mellitus, hypoglycemia, and hypotension. Only original research and review articles related to adult patients with type 1 diabetes were considered for review, excluding pregnant women and patients with poorly controlled disease., Results: The literature review identified 5 clinical trials relevant to type 1 diabetes and fasting. Two main meals are eaten during Ramadan, one before dawn (Suhur) and the other at sunset (Iftar). Suggested adjustments to the insulin regimen during fasting include using 70% of the pre-Ramadan dose, divided as follows: 60% as insulin glargine given in the evening and 40% as an ultra-short-acting insulin (insulin aspart or lispro) given in 2 doses, 1 at Suhur and 1 at Iftar. Alternatively, 85% of the pre-Ramadan dose may be divided as 70% Ultralente and 30% regular insulin, both given in 2 doses, 1 at Suhur and 1 at Iftar. Another option is to give 100% of the pre-Ramadan morning dose of 70/330 premixed insulin at Iftar and 50% of the usual evening dose at Suhur. Patients who observe the fast should be advised to monitor their blood glucose regularly,avoid skipping meals or overeating,and maintain contact with their physician throughout the fast. The fast should be broken immediately if blood glucose drops below 60 mg/dL (3.3 mmol/L). Breaking the fast should be considered when blood glucose drops below 80 mg/dL (4.4 mmol/L), and the fast should be interrupted if blood glucose rises above 300 mg/dL (16.7 mmol/L) to avoid diabetic ketoacidosis. Fasting is contraindicated in patients with poorly controlled type 1 diabetes,including those with a history of severe hypoglycemia and/ or diabetic ketoacidosis at least 3 months before Ramadan; those with comorbid conditions (eg, unstable angina, uncontrolled hypertension, advanced macrovascular complications, infections, renal insufficiency);; those who are noncompliant with diet and medication; those who engage in intense physical activity; pregnant women; and the elderly., Conclusion: Patients with type 1 diabetes who wish to fast during Ramadan should follow specific recommendations and be closely monitored by their physician.

Objectives: In this study we intended to find a correlation between hypertriglyceridemia and peripheral neuropathy (PN) in patients with a high triglyceride level and no neurological complaints., Methods: We recruited 24 patients (21 males and 3 females) having a triglyceride level above 300 mg/dl with no neurologic complaints and none of the other common causes of PN and they underwent an electroneurographic study. The distal motor or sensory latencies (DL), motor or sensory conduction velocities (CV), and motor or sensory amplitudes (AMP) were collected for the peroneal, posterior tibial, sural, median, and ulnar nerves and were considered abnormal if they fall above or below 2 standard deviations of reference values., Results: Our results show that 70.8% of the patients had a significant delay in the DL of the sural nerves and 66.7% had a significant delay in the DL of the median sensory fibers. 54.2% of the patients had a significant decrease in the motor CV in the posterior tibial nerves and 33.3% had a significant decrease in the sensory CV in the sural nerves. The means of the DL and CV were significantly different from reference values in most of the nerves. Amplitudes were the least if at all affected., Conclusion: The pattern of the abnormalities affecting more the DL, the sensory nerves and the longer nerves of the lower extremities is suggestive of an early axonal polyneuropathy. We conclude that hypertriglyceridemia affects conduction parameters in peripheral nerves in a trend suggestive of early peripheral neuropathy.

Patients with Type 1 diabetes (T1D) are normally exempt from the Ramadan fast; however, some patients insist on following the fast, often without the approval of their physicians. The aim of this study is to provide patients with T1D, who insist on fasting, with the most appropriate insulin regimen during the month of Ramadan. Seventeen patients with T1D who insisted on fasting were studied. Prior to Ramadan, the intermediate insulin was changed to ultralente in all patients. The total dose of insulin given to fasting patients by the end of Ramadan (45.7 +/- 14.4 U/day) was less than the total dose of insulin given before fasting (52.8 +/- 13.1 U/day) p<0.05. The ultralente and regular insulin constituted 70 and 30%, respectively, of the total insulin dose by the end of Ramadan, divided equally between Suhur (before sunrise) and Iftar (after sunset). There was no change in the glycosylated hemoglobin before and after fasting. Patients were instructed to break their fast after any episode of hypoglycemia. There were no severe daytime hypoglycemia episodes. We recommend that patients with T1D wishing to fast be switched to long acting insulin such as ultralente. The total insulin dose should consist of around 85% of their initial insulin dose and it should be composed of around 70% ultralente and 30% rapid insulin, divided equally between Suhur and Iftar.

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.

Leptin is the protein product of the obese (ob) gene, a lipostatic hormone that contributes to body weight regulation through suppressing appetite and/or stimulating energy expenditure in humans and/or rodents. In humans, serum leptin concentrations are increased in relation to increased body fat content. Studies have shown a higher leptin level in women compared with men. However, the gender influence on serum leptin concentrations has never been evaluated in patients with type 1 diabetes. In this study, serum leptin levels and percentage body fat mass were measured in men and women with type 1 diabetes. Fasting serum leptin levels were higher in women (16.7 + 11.6 ng/mL) than in men (3.0 +/- 1.5 ng/mL; P < 0.05) and were independent of exogenous insulin intake and of glucose control. Percentage body fat and fat mass were significant determinants of leptin concentration, whereas age and duration of diabetes were not related to leptin concentration. Subgroups of men (n = 12) and women (n = 11) with total body fat between 20 and 30% were compared. Leptin levels were also higher in women compared with men (13.5 +/- 8.3 ng/mL versus 3.2 +/- 1.7 ng/mL; P < 0.05, respectively). In conclusion, our findings indicate that gender is an important determinant of serum leptin concentration in type 1 diabetics, this gender difference is partly explained by body fat distribution and that type 1 diabetic women may be more resistant than type 1 diabetic men to leptin's alleged lipostatic actions.

Pseudotumor Cerebri is a disease of cerebrospinal fluid pressure regulation. This disease has also been associated with endocrine disorders like Cushing's syndrome, hypoparathyroidism, hypothyroidism, hyperthyroidism and Addison's disease. In this paper we report a 30-year-old male patient with hypoparathyroidism presenting with pseudotumor cerebri and diminished anterior pituitary function that improved after a ventricular-peritoneal (VP) shunt insertion.

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.