Intriguing association between type 1 diabetes mellitus, Gitelman syndrome and Cacci-Ricci disease: Triad of rare diseases: A case report.

We report the case of a patient who exhibits a concurrent diagnosis of type 1 diabetes mellitus, Gitelman syndrome and Cacci-Ricci disease. A 27-year-old male patient was diagnosed with Gitelman syndrome at the age of 3 years. Fourteen years later, he developed an autoantibody-negative type 1 diabetes mellitus. Cacci-Ricci's disease was revealed by terminal hematuria and considered in view of the appearance found on the computed tomography (CT) scan. The finger-prick blood glucose level was 6 g/dl with no acetonuria. Creatinine clearance was 60 ml/min. Thyroid function tests were normal. Calcium, phosphorus and parathormone (PTH) levels were normal. Discussion: Gitelman syndrome is a rare disorder. The association between Gitelman syndrome and type 1 diabetes mellitus has been reported in the literature in two patients. Authors have investigated the association between Gitelman syndrome and type 2 diabetes mellitus. Several pathophysiological explanations have been put forward. Cacci-ricci disease is a rare, benign congenital anomaly. No association between type 1 diabetes mellitus, Gitelman syndrome and Cacci-Ricci disease has been reported in the literature. To our knowledge, this is the first case described in the literature.

Unmasking the escalation: a comparative analysis of diabetic ketoacidosis severity before and during the COVID-19 pandemic in a Tunisian pioneer study.

BACKGROUND: The severity of diabetic ketoacidosis (DKA) at diagnosis increased during the global COVID-19 pandemic. This study aimed to analyze the impact of the pandemic on the clinical and biological severity of DKA in patients with new-onset diabetes mellitus (DM) in Tunisia. RESEARCH DESIGN AND METHODS: The study included patients hospitalized for new-onset DKA 2 years prior and 2 years during the COVID-19 pandemic. Data was collected retrospectively, and DKA severity was classified based on biological parameters like potential of hydrogen (pH) and HCO3-. RESULTS: The results showed that DKA was more severe during COVID-19, as evidenced by lower potential of hydrogen (pH) (p = 0.006), and serum bicarbonate (HCO3-) levels (p = 0,005). Despite the higher severity of DKA was higher during COVID-19, intensive care unit hospitalizations remained equivalent (p = 0.359). The prevalence of hyponatremia was also higher during COVID-19 (p = 0.024). CONCLUSION: The findings suggest that delayed diagnosis and COVID-19 May contribute to the increased severity of DKA and electrolyte imbalance during the pandemic. Further research is needed to better understand the underlying mechanisms and develop appropriate strategies to address this issue.

Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis.

Context: In some patients, symptoms may persist after COVID-19, defined as long COVID. Its pathogenesis is still debated and many hypotheses have been raised. Objective: Our primary objective was to evaluate the corticotroph and somatotroph functions of patients previously infected with SARS-CoV-2 and experiencing post-COVID-19 syndrome to detect any deficiencies that may explain long COVID. Methods: A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a postinfection period of 3 months or less to 15 months, divided into 2 groups. The first group (G1) comprised fully recovered patients, while the second group (G2) included patients experiencing long COVID. The primary outcome was the comparison of corticotroph and somatotroph functions. Results: A total of 64 patients were divided into 2 groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1 (P = .045): for the corticotroph axis (G1: 6.3% vs G2: 28.1%) and for the somatotroph axis (G1: 31.3% vs G2: 59.4%). Baseline cortisol level was significantly lower in G2 (G1: 13.37 µg/dL vs G2: 11.59 µg/dL) (P = .045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (P = .01). For the somatotroph axis, the insulin growth factor-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (P = .369). The peak growth hormone level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (P = .041). Conclusion: The results showed that long COVID patients in our cohort were more likely to have anterior pituitary deficiencies. The endocrine hypothesis involving anterior pituitary insufficiency can be considered to explain long COVID.

Uncovering the alarming rise of diabetic ketoacidosis during COVID-19 pandemic: a pioneer African study and review of literature.

Introduction: Reports around the world indicate that COVID-19 pandemic may be contributing to an increase in the incidence of new onset diabetic ketoacidosis (DKA). This has yet to be studied in Africa. We aimed to compare the incidence trend of new onset DKA before and during the COVID-19 pandemic, with a focus on the type of diabetes mellitus (DM).Materials and methodsThis was a cross sectional analytical study, over a 4-year period, between March 2018 until February 2022 conducted in the referral center: diabetology department of university hospital Farhat Hached Sousse, Tunisia. The study population included patients hospitalized for new onset DKA divided in two groups: G1: before COVID-19 pandemic and G2: during COVID-19 pandemic. Patients younger than 14, new onset DM not presenting with DKA, other types of diabetes (monogenic, secondary or pancreatic diabetes) were not included. A statistical analysis of the monthly incidence trend was conducted using the Jointpoint software providing the average monthly percentage of change (AMPC). Results: a total of 340 patients were included:137 registered before the pandemic and 203 during the pandemic, representing a 48.17% increase. The mean monthly incidence of new onset DKA during COVID-19 pandemic was statistically higher than that before COVID-19 pandemic (8.42 ± 4.87 vs 5.75 ± 4.29 DKA per month) (p=0.049). The temporal trend of DKA during the 4-year study showed a significant upward trend with a change in AMPC of +0.2% (p=0.037). The incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) increased by 50% and 44% respectively during COVID-19 pandemic. Anti-glutamic acid decarboxylase (anti-GAD) antibodies' titers significantly increased in G2 compared with G1 (median of 330[Q1-Q3]=[58.5-1795]vs 92.5[Q1-Q3]=[22.5-1074] respectively)(p=0.021). Discussion: The incidence trend of DKA showed an increase during the COVID-19 pandemic along with an increase of T1D and T2D implying that the pandemic may have been the underlying factor of this upward trend.

Esthesioneuroblastoma presenting as syndrome of inappropriate antidiuretic hormone secretion.

Hyponatremia is the most common fluid electrolyte disorder in hospitalized patients. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the main cause of normovolemic hyponatremia, it can be caused by diverse etiologies: malignant tumors are the most feared cause that clinician persists in finding. Exceptionally, SIADH can complicate Esthesioneuroblastoma (ENB) or olfactory neuroblastoma, a rare tumor of the nasal sinus cavities. We report the case of a 26-year-old female patient admitted for recurrent headaches and vomiting, with a profound normovolemic hyponatremia at the initial assessment. Biological explorations have concluded in a SIADH. Imaging showed a mass of the left nasal cavity with extensions to the ipsilateral paranasal sinuses. The biopsy of the lesion, under endoscopic control, was inconclusive. The anatomopathological study, after surgical removal, concluded in ENB. The postoperative evolution was marked by the normalization of the natremia.

Risk factors for impaired quality of life in diabetic patients in Tunisia.

INTRODUCTION: Quality of life preservation is crucial in the management of chronic diseases, in particular diabetes. AIM: To identify risk factors for the impaired quality of life of Tunisian diabetic patients. METHODS: A cross-sectional study that collected type 1 and type 2 diabetic patients, selected by convenience sampling was conducted. Diabetic patients received a self-administered questionnaire in Arabic containing general and clinical data and a validated Arabic version of the "Diabetes Health Profile -18". RESULTS: Three hundred and thirty-three type 1 and type 2 diabetic patients, whose age was ≥ 40 years in 78.1% of cases with a sex ratio of 0.94, were collected. The answers to the questionnaire highlighted a globally impaired quality of life for the diabetic patients with an average of 30.21 (7.06). Binary regression analysis presented globally significant models reflecting impairment risk factors for diabetic patients' quality of life. Female gender (AOR= 1.7; p= 0.036), comorbidities associated with diabetes (AOR = 1.23; p<10-3), diabetes complications (AOR= 1.45; p=0.041) and irregular medical follow-up (AOR=4.19; p<10-3) were risk factors for impaired diabetic patients' quality of life. CONCLUSION: This study underlines the major role of a holistic diabetic patient care for better identification and management of risk factors of impaired quality of life.

Arabic version of the simplified diabetes knowledge scale: psychometric and linguistic validation.

Introduction: the simplified diabetes knowledge scale is used to obtain a general assessment of diabetic´s knowledge about diabetes and its care. For clinical and methodological purposes, it was relevant and necessary to develop an Arabic version of this instrument. Thus, the aim of this study was to translate and validate the simplified diabetes knowledge scale (SDKS) into Arabic to measure the knowledge of Arabic-speaking diabetics. Methods: a methodological validation study of the simplified diabetes knowledge scale, following the guidelines of Vallerand was carried out. A convenience sample of diabetics followed in eight basic health centers in Sousse region and in Farhat Hached and Sahloul University Hospitals was recruited. An Arabic questionnaire including the demographic and clinical data of the diabetic and the final experimental version of the simplified diabetes knowledge scale was used. Results: a sample of 333 diabetics was recruited. Content validity of the final experimental version was 0.94. Reliability assessed by Cronbach´s alpha coefficient (0.812), by test-retest correlation coefficient (> 0.60) and by internal consistency after deletion of each item (from 0.788 to 0.816) were acceptable except items 19 and 20 which had to be reformulated. Construct validity analysis identified that three items among the 20 ones (12, 17 and 20) required reformulation. Inter-item correlation matrix showed that the majority of items were not correlated with each other. Validation process was ended by establishing standards table. Conclusion: this study showed the Arabic version of the simplified diabetes knowledge scale had good validity and reliability.

Clinical, immunological, and genetic investigations in a rare association of type 1 diabetes with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare genodermatosis predisposing to skin cancers. Autoimmune diseases related to XP are rarely discussed in the literature. Type 1 diabetes (T1D) has been associated with other genodermatoses like Cockayne syndrome, but it has never been described in XP. In the present study, we report the rare occurrence of T1D in XP patients. Five XP patients belonging to 4 consanguineous families originating from different regions of Tunisia were investigated. Their ages ranged between 8 and 18 years. All the patients had a severe hypovitaminosis D. All the patients had positive GAD antibody levels, and 4 of them had familial history of other autoimmune diseases. The spectrum of XP was variable in all the patients, with dermatological and neurological symptoms, and the occurrence of some cancers. Various hypotheses have been proposed to explain this association, among of which we cite the role of immunomodulation and down-regulation of ATP-dependent DNA excision repair protein genes, implying that impaired DNA repair may contribute to the development of some autoimmune diseases. Vitamin D3 deficiency secondary to sun protective measures was found in all patients and thus may play a role in increasing T1D risk in these patients.

Safety Assessment and Potential Risks of the Glucagon Stimulation Test in the Diagnosis of Secondary Adrenal Insufficiency.

BACKGROUND: Although it takes more time, the Glucagon Stimulation Test (GST) is a reliable measure for assessing growth hormone (GH) and Adrenocorticotropic Hormone (ACTH) secretion. The GST is considered to be a safe test; however, it still has mild side effects and potential risks. OBJECTIVES: The objective of this study was to analyze the side effects of the GST while testing adrenal-insufficient patients. METHODS: This was a prospective study in which GST was performed in eighty-one patients (44 men, 37 women, mean age: 35.83A9.62 years) with the pituitary disorder. The GST consisted of an intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60, 90, 120, 150, 180, and 210 min after glucagon injection for cortisol measurements. All patients were asked to report side effects associated with this test. RESULTS: The mean peak blood glucose level under GST was 9.01A.03 mmol/L, and the mean glycemic nadir was 4.34A.75 mmol/L most frequently found during the 30th minute (p <10-3). During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 A19.75 years. Frequent side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly more prevalent in patients older than 50 years (p=0.012). CONCLUSIONS: The GST is a reliable alternative to assess the hypothalamic pituitary adrenal axis but should be cautiously used especially in the elderly, despite minor side effects.

Association of an empty sella and grave´s disease in a patient with acromegaly: a case report.

Acromegaly is, in most cases, caused by growth hormone secreting pituitary adenomas. Those patients often develop different pathologies of the thyroid gland, however, the occurrence of Grave´s disease is quite a rare situation. We report a case of a 64-year-old female patient who presented with signs of hyperthyroidism and imbalance of her diabetes mellitus. On physical examination, she had facial features of acromegaly. Biochemical testing confirmed the suspicion of acromegaly and Grave´s disease, with an elevated insulin-like growth factor-1 and a suppressed thyroid stimulation hormone (TSH) with positive TSH-receptor antibodies. A pituitary Magnetic Resonance Imaging (MRI) was performed, revealing a macro-adenoma and an empty sella. The patient successfully underwent a transsphenoidal surgery and obtained a remission of her hyperthyroidism under anti-thyroid drugs.

Pituitary apoplexy of a giant prolactinoma during pregnancy.

AIMS AND METHODS: Prolactinomas are a common cause of sexual dysfunction and infertility. We aimed, through this case report, to illustrate the difficulties of management of women with giant prolactinoma, especially in cases of desire of pregnancy. RESULTS: A 30-year-old woman was referred to our department for secondary amenorrhea. Investigations showed a prolactin level of 5168 ng/mL and giant pituitary adenoma of 4 cm in diameter. Cytoreductive surgery was performed after failure to normalize prolactin levels during three years with medical treatment by cabergoline. After seven months, menstrual cycles have resumed, and after 13 months, the patient became pregnant. At 22nd week of gestation, she was admitted in our hospital for pituitary apoplexy. Medical treatment with bromocriptine was chosen. The vaginal premature delivery at 28 weeks gave birth to twins weighing 1 Kg each who died on the 7th day of life. CONCLUSION: This is a relevant clinical case that illustrates the efficacy of cytoreductive surgery in case of insufficient response to dopamine agonists to restore gonadal function. The possibility of a pregnancy should be considered in these patients since it can be associated with high maternal and fetal risks.

Translation, psychometric evaluation and validation of the "diabetes health profile-18" questionnaire in Arabic.

INTRODUCTION: measuring quality of life requires an instrument validated in the population language. The purpose of our study was to translate and analyze the psychometric properties of the literary Arabic version of the "diabetes health profile (DHP)-18". METHODS: we conducted a methodological study for psychometric evaluation and validation of the DHP-18, following the steps of the cross-cultural validation described by Vallerand. A convenience sample of people with diabetes was collected for this purpose. The developed questionnaire included participants' demographic characteristics, diabetes data and the experimental version of the DHP-18 questionnaire. Validity, reliability and questionnaire standards establishment were carried out. RESULTS: a sample of 333 diabetics was recruited. Test-retest correlation coefficient (r = 0.985; p<0.01) and Cronbach's alpha coefficient (alpha = 0.840) showed that the experimental version was accurate in terms of temporal stability and internal consistency. The content validity index was 0.84 and showed that the questionnaire statements accurately measured the concepts under study. The exploratory principal axis factoring, using the orthogonal varimax rotation, allowed the extraction of a factorial solution with four independent factors, grouping the 18 items of the questionnaire. Correlation coefficients between the three corresponding dimensions of the theoretical model of the questionnaire were low and positive, between 0.431 and 0.535, confirming that each dimension measured a unique content. CONCLUSION: the literary Arabic version of the DHP-18 has proven to be valid, reliable and ready for use in clinical practice in Tunisian people with diabetes.

Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries.

BACKGROUND: Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically. AIMS: To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries. METHODS: We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data. RESULTS: Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients. CONCLUSIONS: Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes.

[Posttraumatic type 1 diabetes in an army soldier]. / Diabète de type 1 post-traumatique chez un soldat de l'armée.

The influence of stress as a precipitating factor associated with the onset of type 1 diabetes have been widely studied in the literature. The relationship between physical and psychological traumas and diabetes has been rarely studied in the military environment. Posttraumatic diabetes is a controversial topic. We here report the case of a Tunisian soldier, with no previous medical and family history of autoimmune disease who was diagnosed with Type 1 diabetes after a physical aggression occurred during a social conflict between the forces of law and order and the citizens.

[Study of acute inaugural ketosis-prone diabetes in a Hospital in Central-Eastern Tunisian]. / Etude sur le diabète aigu cétosique inaugural dans un hôpital du Centre-Est Tunisien.

Ketosis-prone diabetes is an acute complication of diabetes resulting from ketone accumulation in the blood. Despite the high rate of ketosis-prone diabetes described, there is very little information on the epidemiology of this inaugural complication of diabetes in Tunisia. This study aims to determine the epidemiological and clinical features and the laboratory tests parameters of inaugural ketoses in a Hospital in Tunisian. We conducted a retrospective, cross-sectional exhaustive study of patients admitted with inaugural ketosis over the period January 2010 - August 2016. The study population was divided into 2 groups according to the presence or not of anti-pancreatic autoimmunity: the DAI group consisted of all patients with autoimmunity, the DNAI group consisted of all patients without autoimmunity. Our study included 391 patients, with a sex ratio of 226 men/125 women, the average age was 34 ± 14.33 years. There was a male predominance (68%) in the general population. The age of disease onset was significantly lower in the DAI group. A factor that contributed to ketosis onset was found in 77.7% of the overall study population, it was significantly more frequent in the DAI group than in the DNAI group. The most common factor was viral infections. Thyroid antibodies were significantly higher in the DAI group. Ketosis is a common factor leading to inaugural decompensation of diabetes in Tunisia. Young adult male is the most affected group of population reported in the literature, with the absence of autimmunity, and a clinical profile of type 2 diabetes.

Clustering of chronic diseases risk factors among adolescents: a quasi-experimental study in Sousse, Tunisia.

Background The objective of the study was to evaluate the effectiveness of a school-based physical activity and nutritional behavior intervention, on the reduction of clustering of chronic diseases risk factors among school children. Materials and methods A quasi-experimental school-based intervention was conducted with an intervention group and a control group in the region of Sousse in Tunisia. The intervention was implemented between 2010 and 2013, with data collected at pre and at post intervention. Studied risk factors were: smoking, sedentary behavior, low fruit and vegetable intake and obesity. Odds ratios (ORs) were used to calculate the clustering of two risk factors. We calculated ORs in each group before and after the intervention. Results In the intervention group, the prevalence of adolescents that had no risk factors has significantly increased (p = 0.004). In the control group the prevalence of adolescents carrying two or more risk factors has increased (p = 0.06). The results showed that all risk factors tended to cluster together in both groups. In the intervention group, the calculated OR for smoking and sedentary behavior decreased after assessment (OR = 5.93) as well as the OR for smoking and low fruit and vegetable intake (OR = 3.26). In the control group, all ORs increased, showing an enhancement of the association. Conclusion This study showed the effectiveness of a school-based intervention in reducing the clustering of chronic diseases risk factors.

Analysis of FMR1 gene premutation and X chromosome cytogenetic abnormalities in 100 Tunisian patients presenting premature ovarian failure.

OBJECTIVE: To evaluate the prevalence of FMR1 premutations and X chromosome cytogenetic abnormalities in a large cohort of Tunisian women with premature ovarian failure (POF). PATIENTS AND METHODS: The cohort consisted of 127 Tunisian women with POF referred by endocrinologists and gynecologists for genetic investigation in the context of idiopathic POF and altered hormonal profiles. Clinical information concerning the reproductive function in the family, previous hormonal measurements and/or possible fertility treatment were collected. Karyotype, FISH analyses, FMR1 and FMR2 testing were performed for all patients. RESULTS: Fifteen patients (11.81%) presented structural or numerical X chromosomal abnormalities. Moreover, we detected in 12 patients (10.71%) a high level of X mosaicism. Analysis of FMR1 gene in the 100 patients without X chromosomal abnormalities showed that five percent of the patients carried a FMR1 premutation allele. On the other hand, the FMR2 screening did not reveal any deletion. CONCLUSION: Our study confirms the major role of X chromosome abnormalities in POF and highlights the importance of karyotype analyses and FMR1 screening. These investigations provide valuable information for diagnosis and genetic counseling for these women who still have a 5% chance of spontaneous conception.

Frequency of HNF4A-P.I463V Variant in the Tunisian North-African Population and Its Relation with Diabetes Mellitus.

BACKGROUND: HNF4A-p.I463Vvariant, reported previously in two distinct families suspected of MODY-1, is assessed in this report to determine whether it is a mutation or a polymorphism (frequency >1%). METHODS: 200 Tunisian healthy people were screened for the presence of HNF4A-p.I463V variant, using RFLP-PCR technique and sequencing. Then, the frequency of this variant was estimated in the Tunisian population and compared to other populations registered in genetic databases. We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant. RESULTS: HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population. PolyPhen2 predicted that it is a polymorphism, whereas mutation T@sting suggested a probably affected mutant protein. CONCLUSION: HNF4A-p.I463V has a relatively high frequency (>1%) in our control cohort. It is also present in different ethnicities and in- silico analysis showed conflicting results. For these reasons, HNF4A-p.I463V should not be considered as a mutation responsible for MODY-1.