Optimizing Ramadan fasting: A randomised controlled trial for people with type 2 diabetes during Ramadan applying the principles of the ADA/EASD consensus.

BACKGROUND: Fasting during the holy month of Ramadan is one of the five pillars of Islam. Fasting is not meant to create excessive hardship on the Muslim individual according to religious tenets. It is important that health professionals are aware of potential risks associated with fasting during the month of Ramadan (mainly hypoglycemia and hyperglycemia). AIMS: To explore the impact of applying the principles of our 2020 recommendations for the management of type 2 diabetes (T2D) during the month of Ramadan. METHODS: A multinational randomized controlled trial (RCT) was conducted in five Muslim majority countries. Six hundred and sixty participants were deemed eligible for the study; however, 23% declined to participate later for various reasons. In total, 506 participants were enroled and were equally randomized to the intervention or the control group. At the end of the study, data from 231 participants in the intervention group and 221 participants from the control group were collected after 12.6% and 8.7% were, respectively, lost to follow-up. Participants were randomized to receive a Ramadan-focussed education with treatment for diabetes adjusted as per our 2020 recommendation update compared with the local usual care (control group). Results are presented using mean, standard deviation, odds ratio (OR), and percentages. RESULTS: At the end of the study, the number of hypoglycemic episodes in the intervention group was less than in participants who received usual care. The intervention group had significantly lower severe hypoglycemia compared to the control group with an OR of 0.2 [0.1-0.8]. Compared to baseline, both groups had a significant reduction in glycated haemoglobin (HbA1c), but the improvements were significantly greater in the intervention group. Whilst body weight reduced and high-density lipoprotein cholesterol increased with the intervention, these changes were not significantly different from usual care. CONCLUSIONS: A pre-Ramadan assessment of people with T2D coupled with pre-Ramadan education and an adjustment of glucose-lowering treatment as per our updated 2020 recommendations can prevent acute complications and allow a safer fast for people with T2D. We have shown that such an approach reduces the risk of developing severe hypoglycemia and improves the metabolic outcomes in people with T2D.

Identification of the novel SDR42E1 gene that affects steroid biosynthesis associated with the oculocutaneous genital syndrome.

Hereditary connective tissue diseases form a heterogeneous group of disorders that affect collagen and extracellular matrix components. The cornea and the skin are among the major forms of connective tissues, and syndromes affecting both organs are often due to mutations in single genes. Brittle cornea syndrome is one of the pathologies that illustrates this association well. Furthermore, sex hormones are known to play a role in the maintenance of the structure and the integrity of the connective tissue including the skin and cornea, and may be involved in pathogenesis of oculocutaneous diseases. Herein, a double consanguineous family of Moroccan origin with two affected siblings, with suspected brittle cornea syndrome, was recruited. Ophthalmic examinations and genetic testing were performed in all the nuclear family individuals. Clinical examinations showed that the two affected boys presented with thinning of the cornea, blue sclera, keratoconus, hyperelasticity of the skin, joint hypermobility, muscle weakness, hearing loss and dental abnormalities that are compatible with the diagnosis of BCS disease. They showed however additional clinical signs including micropenis, hypospadias and cryptorchidism, suggesting abnormalities in endocrine pathways. Using a duo exome sequencing analysis performed in the mother and the propositus, we identified the novel homozygous missense mutation c.461G > A (p.Arg154Gln) in the short-chain dehydrogenase/reductase family 42E member 1 (SDR42E1) gene. This novel mutation, which co-segregated with the disease in the family, was predicted to be pathogenic by bioinformatics tools. SDR42E1 stability analysis using DynaMut web-server showed that the p.Arg154Gln mutations has a destabilizing effect with a ΔΔG value of -1.039 kcal/mol. As this novel gene belongs to the large family of short-chain dehydrogenases/reductases (SDR) thought to be involved in steroid biosynthesis, endocrinological investigations subsequently revealed that the two patients also had low levels of cholesterol. Karyotyping revealed a normal 46,XY karyotype for the two boys, excluding other causes of disorders of sex development due to chromosomal rearrangements. In conclusion, our study reveals that mutation in the novel SDR42E1 gene alters the steroid hormone synthesis and associated with a new syndrome we named oculocutaneous genital syndrome. In addition, this study highlights the role of SDR42E1 in the regulation of cholesterol metabolism in the maintenance of connective tissue and sexual maturation in humans.

The glycaemic personality: A SURE framework of person-centred choice in diabetes care.

Diabetology is becoming more and more complex, and requires simple yet comprehensive models to facilitate appropriate management of the syndrome. This communication highlights the concept of glycaemic personality, defined as the sum of all attributes, both biomedical and psychosocial, which influence the glucophenotype of an individual. This concept can be explained by using the SURE model, which lists four factors that influence choice of glucose-lowering therapies and their targets. These include the Severity and Style of hyperglycaemia, Urgency and Utility of glucose control, Relative Risk of hypoglycaemia, and Expected adherence to therapy and Expectations of the person living with diabetes.

[Which place occupies the free drug sample in the prescription of the physicians in Morocco?] / Quelle place occupe l'échantillon médical gratuit dans la prescription des médecins au Maroc ?

OBJECTIVES: Do the state of affairs of the perception of free drug samples by a group of prescribers of drugs in the Morocco. METHODS: This was a cross-sectional study of 381 physicians practising in different sectors (public, private) using a self-administered anonymous questionnaire, conducted between December 2016 and March 2017. The questionnaire focused on assessing the general knowledge of prescriber on free drug sample, medical visit of medical representative of pharmaceutical laboratory, drug prescribing and free drug sample use. RESULTS: In total, 381 prescribers were interviewed. Sex M/F ratio was 0.53 with a mean age of 37.4±11.2 years exerting mainly in the public sector in urban areas. According to surveyed prescribers, the drug specialties presented as free drug sample occupied 52.1 percent of their prescription. The main interest in having the free drug sample was to help the patient at low socioeconomic level but it influences the physician's prescription. CONCLUSION: This survey puts in perspective the place of the free drug sample in the medical prescription with prescribers, in order to raise awareness about the ability of free drug sample to influence the medical prescription although it allows to help the patient low socio-economic level.

Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism.

BACKGROUND/OBJECTIVES: Congenital hypopituitarism is a rare disease which, for most patients, has no identified molecular cause. We aimed to document the molecular basis of growth retardation in a Moroccan cohort. DESIGN/PATIENTS: 80 index cases [54 with isolated growth hormone deficiency (IGHD), 26 with combined pituitary hormone deficiency (CPHD)] were screened for molecular defects in GH1 (including LCR-GH1), GHRHR, GHSR, GHRH, PROP1, POU1F1, HESX1, LHX3, LHX4 and SOX3. RESULTS: Five different deleterious mutations were identified in 14 patients from eight families. In the IGHD group, three genes were found to be involved: GH1, GHRHR and GHSR. In the CPHD group, PROP1 was the only mutated gene. In addition, two heterozygous variations whose deleterious effect remains to be demonstrated were identified (in GH1 and LHX4), and two polymorphisms (missense variations) were detected (in LHX3 and in GHSR). The prevalence of mutations in this Moroccan GHD cohort was 10% (8/80), 11·1% (6/54) in the IGHD group and 7·7% (2/26) in the CPHD group. CONCLUSION: This is the first molecular screening of congenital GHD in a Moroccan population and, like other studies, mutations were preferentially identified in familial cases (75%); mutations in genes such as POU1F1, HESX1, SOX3, LHX3 and LHX4 are extremely rare. The p.R73C PROP1 mutation was the most frequent mutation in CPHD; this should be the first one to screen in this population. Our results should contribute to a better diagnosis and management of this heterogeneous disease condition.

[A rare cause of hypercorticism: ACTH-secreting pheochromocytoma (a case report)]. / Une cause rare d'hypercorticisme: un phéochromocytome sécrétant l'ACTH (à propos d'un cas).

Ectopic ACTH-secreting pheochromocytoma is a very rare cause of Cushing´s syndrome, posing diagnostic and therapeutic challenges. We here report the case of a female patient with suspected severe Cushing´s syndrome associated with melanoderma, arterial hypertension resistant to triple therapy and unbalanced diabetes treated with insulin therapy. Biologically, urinary ethoxylated, 24-hour urinary free cortisol and ACTH were very high. Imaging showed a 3.5 cm left adrenal mass. The patient underwent left adrenalectomy after medical preparation, with good clinico-biological outcome. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. This case study highlights the importance of measuring methoxylated derivatives in any patient with ACTH-dependent Cushing´s syndrome associated with an adrenal mass. The aim is to ensure early treatment and avoid life-threatening complications.

Whole Pancreas and Islet Cells Transplantation for Patients with Type 1 Diabetes Mellitus: A Mini-Review and Middle East-North Africa Experience.

Pancreatic and islet cell transplantation are considered surgical therapeutic modalities for type 1 diabetes mellitus with or without end-stage renal disease. The pancreatic transplant can be performed alone or with the kidney transplant simultaneously or at different times. It contributed to an improved quality of life in those patients. Pancreatic transplantation and islet cell transplantation provide different degrees of insulin independence. Although the latter needs less monitoring, yet, it is more expensive and tedious. The experiences in the Middle East and North African countries for both procedures are young but mature. They need more scheduled national and/or regional programs to provide diverse options for their citizens.

Current gaps in management and timely referral of cardiorenal complications among people with type 2 diabetes mellitus in the Middle East and African countries: Expert recommendations.

The upsurge of type 2 diabetes mellitus is a major public health concern in the Middle East and North Africa (MENA) and Africa (AFR) region, with cardiorenal complications (CRCs) being the predominant cause of premature morbidity and mortality. High prevalence of cardiometabolic risk factors, lack of awareness among patients and physicians, deficient infrastructure, and economic constraints lead to a cascade of CRCs at a significantly earlier age in MENA and AFR. In this review, we present consensus recommendations by experts in MENA and AFR, highlighting region-specific challenges and potential solutions for management of CRCs. Health professionals who understand sociocultural barriers can significantly increase patient awareness and encourage health-seeking behavior through simple educational tools. Increasing physician knowledge on early identification of CRCs and personalized treatment based on risk stratification, alongside optimum glycemic control, can mitigate therapeutic inertia. Early diagnosis of high-risk people with regular and systematic monitoring of cardiorenal parameters, development of region-specific care pathways for timely referral to specialists, followed by guideline-recommended care with novel antidiabetics are imperative. Adherence to guideline-recommended care can catalyze utilization of sodium glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists with demonstrated cardiorenal benefits-thus paving the way for overcoming care gaps in a cost-effective manner. Leveraging digital technology like electronic medical records can help generate real-world data and provide insights on voids in adoption of newer antidiabetic medications. A patient-centric approach, collaborative care among physicians from different specialties, alongside involvement of policy makers are key for improving patient outcomes and quality of care in MENA and AFR.

Diabetes and Ramadan: Practical guidelines 2021.

Fasting during Ramadan is one of the five pillars of Islam and is obligatory for all healthy Muslims from the age of puberty. Though individuals with some illness and serious medical conditions, including some people with diabetes, can be exempted from fasting, many will fast anyway. It is of paramount importance that people with diabetes that fast are given the appropriate guidance and receive proper care. The International Diabetes Federation (IDF) and Diabetes and Ramadan (DaR) International Alliance have come together to provide a substantial update to the previous guidelines. This update includes key information on fasting during Ramadan with type 1 diabetes, the management of diabetes in people of elderly ages and pregnant women, the effects of Ramadan on one's mental wellbeing, changes to the risk of macrovascular and microvascular complications, and areas of future research. The IDF-DAR Diabetes and Ramadan Practical Guidelines 2021 seek to improve upon the awareness, knowledge and management of diabetes during Ramadan, and to provide real-world recommendations to health professionals and the people with diabetes who choose to fast.

Diabetes Care During Hajj.

Diabetes mellitus affects over 463 million individuals worldwide. Religious activities such as the Hajj pilgrimage have a major impact on patients with diabetes mellitus, including increasing the risk of hyperglycaemia and hypoglycaemia. This increased risk is due to dietary changes and intense physical activity during pilgrimage while being on antidiabetic medications. Approximately 20% of the pilgrims with underlying illnesses who visit Mecca are diabetic, and complications, such as diabetic ketoacidosis, nonketotic hyperosmolar state, and fatigue/unconsciousness due to hypoglycaemia, have been observed among these patients. Diabetic patients are also at a high risk for foot complications and infections. To avoid any aggravation of the diabetes, a complete biochemical evaluation of the patient must be conducted before Hajj, and the patients must be provided contextualized educational guidance to avert these potential health challenges. This counselling should include the importance of carrying with them at all time their relevant medical history, summaries of the current treatment regimen and emergency snacks. In addition, to reduce the risk of hypoglycaemia, the dosage of insulin should be reduced in selected patients by 20% and that of sulfonylurea should be reduced as needed. Basal insulin and glucagon-like peptide 1 receptor agonists are associated with fewer complications and can be preferentially prescribed. Those patients with type 1 diabetes can continue with the use of insulin pump with suitable education prior to Hajj. For the prevention of foot problems, the use of padded socks and well-fitting shoes is recommended along with an insistence on not walking barefoot. After Hajj, the patient must be followed up, and necessary investigations must be made along with readjustment of insulin dosage in those patients for whom it was reduced. Until the pandemic situation abates, all diabetic patients should avoid making the Hajj journey.

Recommendations for management of diabetes during Ramadan: update 2020, applying the principles of the ADA/EASD consensus.

Fasting the Holy month of Ramadan constitutes one of the five pillars of the Muslim faith. Although there is some evidence that intermittent fasting during Ramadan may be of benefit in losing weight and cardiometabolic risk factors, there is no strong evidence these benefits apply to people with diabetes. The American Diabetes Association/European Association for the Study of Diabetes consensus recommendations emphasize the importance of patient factors and comorbidities when choosing diabetes medications including the presence of comorbidities, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, hypoglycemia risk, weight issues and costs. Structured education and pre-Ramadan counseing are key components to successful management of patients with diabetes. These should cover important aspects like glycemic targets, self-monitoring of blood glucose, diet, physical activity including Taraweeh prayers, medication and dose adjustment, side effects and when to break the fast. The decision cycle adapted for the specific situation of Ramadan provides an aid for such an assessment. Children with type 1 diabetes should strongly be advised not to fast due to the high risk of acute complications such as hypoglycemia and probably diabetic ketoacidosis (DKA), although there is very little evidence that DKA is increased in Ramadan. Pregnant women with diabetes or gestational diabetes should be advised to avoid fasting because of possible negative maternal and fetal outcomes. Hypoglycemia is a common concern during Ramadan fasting. To prevent hypoglycemic and hyperglycemic events, we recommend the adoption of diabetes self-management education and support principles. The use of the emerging technology and continuous glucose monitoring during Ramadan could help to recognize hypoglycemic and hyperglycemic complications related to omission and/or medication adjustment during fasting; however, the cost represents a significant barrier.

Diagnostic procedure in suspected Graves' disease.

Diagnostic procedure in suspected Graves' disease has never been studied scientifically and actual practice seems quite variable, notably between countries. Recommendations are few and weak (expert opinion). This article presents the recommendations of an expert consensus meeting organized by the French Society of Endocrinology in 2016. In case of clinically suspected thyrotoxicosis, the first-line biological assessment is of thyroid-stimulating hormone (TSH). Free T4 and possibly free T3 assays assess biological severity and are necessary for treatment efficacy monitoring. Positive diagnosis of Graves' disease after biological confirmation of thyrotoxicosis does not always require complementary etiological examinations if clinical presentation is unambiguous, notably including extra-thyroid signs. Otherwise, first-line anti-TSH-receptor (TSH-R) antibody screening is recommended for its good intrinsic performance (sensitivity and specificity) and ease of access in France. Scintigraphy is reserved to rare cases of Graves' disease with negative antibody findings or when another etiology is suspected. Thyroid ultrasound scan may be contributive, but is not recommended in first line.

Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care.

Premixed insulins are an important tool for glycemic control in persons with diabetes. Equally important in diabetes care is the selection of the most appropriate insulin regimen for a particular individual at a specific time. Currently, the choice of insulin regimens for initiation or intensification of therapy is a subjective decision. In this article, we share insights, which will help in rational and objective selection of premixed formulations for initiation and intensification of insulin therapy. The glycemic status and its variations in a person help to identify the most appropriate insulin regimen and formulation for him or her. The evolution of objective glucometric indices has enabled better glycemic monitoring of individuals with diabetes. Management of diabetes has evolved from a 'glucocentric' approach to a 'patient-centered' approach; patient characteristics, needs, and preferences should be evaluated when considering premixed insulin for treatment of diabetes.Funding: Novo Nordisk, India.

[Familial hypertriglyceridemia: biochemical, clinical and molecular study in a Moroccan family]. / Hypertriglycéridémie familiale : étude biochimique, clinique et moléculaire dans une famille marocaine.

Familial hypertriglyceridemia is a rare autosomal recessive inborn error of metabolism. Mutation within the LPL gene constitutes the first cause of monogenic etiology. Lipoprotein lipase (LPL) is the key enzyme in triglyceride-rich lipoproteins catabolism. Familial LPL deficiency is expressed by eruptive xanthomatosis and acute pancreatitis. We report a Moroccan case with a monstrous hypertriglyceridemia caused by LPL gene mutation. We discuss pathophysiology aspects according to available investigations data and the relevance of familial screening. The proband is a 19-year-old woman originating from the village of Taourirt (South of Morocco). She was admitted in emergency for diabetic ketoacidosis. Clinical investigations and routine laboratory tests were performed upon admission. Then lipoprotein electrophoresis and sequencing of the LPL gene were practiced. A monstrous hypertriglyceridemia up to 199 mmol/L was found. Lipoprotein electrophoresis has objectified profound disturbances on chylomicrons, VLDL and IDL. The sequencing detected a missense mutation p.S286R at homozygous state in a consanguinity context. Discovery of this LPL gene mutation is the first indigenous and documented case, never related in any other ethnic group. It constitutes a novel proof of a founder effect in the south Moroccan population. Prevalence studies with familial screening should be done for preventative action which is the only acceptable way to limit the cardiovascular and pancreatitis risks in this population where inbreeding is a general rule.

Management of Type 2 diabetes in Ramadan: Low-ratio premix insulin working group practical advice.

The challenge of insulin use during Ramadan could be minimized, if people with diabetes are metabolically stable and are provided with structured education for at least 2-3 months pre-Ramadan. Although, American diabetes association (ADA) recommendations 2010 and South Asian Consensus Guideline 2012 deal with management of diabetes in Ramadan and changes in insulin dosage, no specific guidance on widely prescribed low-ratio premix insulin is currently available. Hence, the working group for insulin therapy in Ramadan, after collective analysis, evaluation, and opinion from clinical practice, have formulated a practical advice to empower physicians with pre-Ramadan preparation, dose adjustment, and treatment algorithm for self-titration of low-ratio premix insulin.