A multicenter, open-label, single-arm trial of the long-term safety of empagliflozin treatment for refractory diabetes mellitus with insulin resistance (EMPIRE-02).

AIMS/INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment-refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single-arm trial (EMPIRE-01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE-02) that followed on from EMPIRE-01. MATERIALS AND METHODS: The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE-01 trial participated in EMPIRE-02. RESULTS: Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE-02. The improvement in mean values of glycemic parameters observed in EMPIRE-01 was not sustained in EMPIRE-02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE-02 after exclusion of this subject from analysis. CONCLUSIONS: Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

The Global Prevalence of Metabolic Syndrome in Connection with Sleep Duration: A Systematic Review and Meta-Analysis.

The duration and quality of sleep are believed to significantly influence the onset of metabolic syndrome (MetS), but existing data lack consistency. The meta-analysis aims to evaluate the prevalence of the MetS in association with sleep duration. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. A comprehensive search of PubMed, Google Scholar, and Research Gate databases was performed to identify cohort and cross-sectional studies published in English between 2013 and 2023. We included studies that examined the association between sleep duration/quality and MetS, and two independent reviewers assessed study quality and bias using the Newcastle-Ottawa scale. The systematic review included 11 studies with a total of 343,669 participants, including 4 cohort studies and 7 cross-sectional studies. Sample sizes varied widely, ranging from 293 to 162,121 individuals. The studies had different follow-up periods, participant ages ranging from 10 to 80 years, and predominantly male populations. The prevalence of MetS was higher in average sleepers [52%, 95% confidence interval (CI): 40%-64%] compared with short sleepers (13%, 95% CI: 8%-18%) and long sleepers (15%, 95% CI: 9%-24%). Globally, North American countries exhibit the highest prevalence of MetS across short- (25.3%, 95% CI: 4.2%-72.4%) and long-sleeper (22.4%, 95% CI: 2.8%-74.1%) categories, whereas Asian countries experience the highest prevalence among the average sleeper category (58.7%, 95% CI: 44.1%-71.9%). Our meta-analysis indicates an elevated prevalence of MetS in average sleepers. Future research endeavors address delve into the underlying mechanisms and incorporate objective measures to understand the multifaceted connection between sleep patterns and MetS, guiding more effective preventive and management strategies.

An umbrella review and meta-analysis of meta-analyses of the impact of Ramadan fasting on the metabolic syndrome components.

CONTEXT: Ramadan is a holy month of fasting, spiritual reflection, and worship for Muslims worldwide. However, the Ramadan fast - which involves abstaining from all food and drink, sunrise to sunset for 29 days-30 days annually - may also influence physical health outcomes, especially relating to the risk of metabolic syndrome. OBJECTIVE: The literature from the top of the pyramid of evidence was gathered and synthesized for this comprehensive umbrella review and meta-analysis of meta-analyses in order to provide an overall conclusion on the impact of Ramadan fasting with regard to metabolic syndrome components. DATA EXTRACTION: Eleven systematic reviews and meta-analyses were included in the current umbrella review. Nine components, including waist circumference, body weight), high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure), and fasting blood plasma glucose were analyzed. DATA ANALYSIS: The random-effects meta-analysis results revealed standard mean differences as follows: waist circumference -0.30 (95% confidence interval [CI] -0.33 to -0.27), body weight -0.34 (95% CI -0.39 to -0.29), high-density lipoprotein 0.20 (95% CI 0.10 to 0.30), low-density lipoprotein -0.10 (95% CI -0.13 to -0.07), total cholesterol -0.15 (95% CI -0.21 to -0.09), triglycerides -0.16 (95% CI -0.24 to -0.08), systolic blood pressure -0.20 (95% CI -0.23 to -0.17), diastolic blood pressure -0.20 (95% CI -0.22 to -0.18), fasting blood plasma glucose -0.10 (95% CI -0.12 to -0.08). CONCLUSION: Ramadan fasting appears to benefit body weight, lipid profile, blood pressure, and fasting blood glucose levels. Therefore, engaging in fasting during Ramadan may contribute to weight reduction, decreased cardiovascular disease risk, improved blood pressure, and enhanced glycemic control. Nevertheless, the methodological quality of the included reviews ranged from low to critically low, necessitating cautious interpretation of conclusions drawn from these data. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework Identifier: DOI 10.17605/OSF.IO/9WVJZ.

A Multicenter, Open-Label, Single-Arm Trial of the Efficacy and Safety of Empagliflozin Treatment for Refractory Diabetes Mellitus with Insulin Resistance (EMPIRE-01).

INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are characterized by severe insulin resistance and are often refractory to treatment. Trials assessing the efficacy of antidiabetes drugs for these rare conditions have been limited, however. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which lower glycemia independently of insulin action, have shown efficacy for type 2 diabetes with insulin resistance. We here investigated the efficacy and safety of the SGLT2 inhibitor empagliflozin for treatment of insulin resistance syndrome and lipoatrophic diabetes. METHODS: The trial was conducted at five academic centers in Japan and included seven patients with insulin resistance syndrome and one patient with lipoatrophic diabetes. Participants received 10 mg of empagliflozin daily. If the hemoglobin A1c (HbA1c) level was ≥ 7.0% (52 mmol/mol) after 12 weeks, the dose was adjusted to 25 mg. The study duration was 24 weeks, and the primary outcome was the change in HbA1c level by the end of the treatment period. Safety evaluations were performed for all participants. RESULTS: By the end of the 24-week treatment period, the mean HbA1c level for all eight patients had decreased by 0.99 percentage points (10.8 mmol/mol) (95% confidence interval [CI], 0.59 to 1.38 percentage points, 6.6 to 14.9 mmol/mol) and the mean fasting plasma glucose concentration had declined by 63.9 mg/dL (3.55 mmol/L) (95% CI 25.5 to 102.3 mg/dL, 1.42 to 5.68 mmol/L). Continuous glucose monitoring revealed a reduction in mean glucose levels from 164.3 ± 76.1 to 137.6 ± 46.6 mg/dL (9.13 ± 4.23 to 7.65 ± 2.59 mmol/L) as well as an increase in the time in range (70-180 mg/dL) from 58.9 ± 36.1% to 70.8 ± 18.3%. Seventeen mild adverse events were recorded in five individuals throughout the study period. No severe events were reported. The mean body mass showed a slight decrease and the mean serum ketone body concentration showed a slight increase during treatment. CONCLUSION: Our results demonstrate that empagliflozin shows a certain level of efficacy and safety for treatment of insulin resistance syndrome and lipoatrophic diabetes. TRIAL REGISTRATION: jRCTs2051190029 and NCT04018365.

A case of systemic lupus erythematosus in a patient with Noonan syndrome with recurrent severe hypoglycaemia.

Noonan syndrome (NS) is a dominantly inherited genetic disorder with mutations in genes encoding components or regulators of the Rat sarcoma virus/mitogen-activated protein kinase pathway. Its diagnosis is based on characteristic features, including typical facial features, a short stature, congenital heart disease, mild developmental delay, and cryptorchidism. Patients with NS sometimes develop autoimmune diseases, such as Hashimoto's thyroiditis and, rarely, systemic lupus erythematosus (SLE). We herein present a 29-year-old Japanese female with NS complicated by SLE and repeated severe hypoglycaemia. The patient was diagnosed with SLE based on thrombocytopenia, nephritis, a positive antinuclear antibody titre (1:640), and a positive anti-dsDNA antibody. The patient was treated with a glucocorticoid, mycophenolate mofetil, and tacrolimus, which attenuated both SLE and hypoglycaemia. Since insulin receptor antibody levels were higher to the upper normal range and decreased after treatment, hypoglycaemia probably appeared to be attributed to type B insulin resistance syndrome. We herein present the first case of SLE in NS complicated by type B insulin resistance syndrome. Although NS is a rare disease, we need to consider the complication of autoimmune diseases, including SLE.

Clinical Utility of GnRH Analogues in Female Androgen Excess: Highlighting Diagnostic and Therapeutic Applications.

Female androgen excess typically presents with hirsutism, acne, and frontotemporal alopecia. Although the majority of cases are due to underlying polycystic ovary syndrome, non-polycystic ovary syndrome pathology can present a diagnostic and therapeutic challenge. We present 3 cases highlighting the utility of GnRH analogues in diagnosis and treatment of ovarian hyperandrogenism. In case 1, we highlight the role of GnRH analogue testing to localize severe postmenopausal androgen excess, allowing full resolution of symptoms following resection of a benign ovarian steroid-cell tumor. Our second case demonstrates the dual utility of GnRH analogues as both a diagnostic and therapeutic agent for hyperandrogenism in a premenopausal woman with severe insulin resistance. We observed suppression of serum testosterone coupled with significant improvement in hirsutism scores. The final case describes GnRH analogue suppression as a therapeutic option for a postmenopausal woman with ovarian hyperthecosis wishing to avoid surgical intervention, with successful symptom resolution. This case series delineates the applications of GnRH analogue suppression in a variety of clinical contexts, in particular their potential role in controlling symptoms in cases of refractory androgen excess and an alternative to surgery in cases of benign ovarian hyperandrogenism.

Type B Insulin Resistance Syndrome: A Rare Cause of Hypoglycemia.

We describe a case of a Black female patient with a history of type 2 diabetes mellitus and systemic lupus erythematosus, who had a subacute onset of severe hypoglycemia that persisted after cessation of insulin therapy. Biochemical testing revealed hyperinsulinemic hypoglycemia, normal serum triglycerides, and high-normal serum adiponectin levels. Abdominal imaging demonstrated an 11-mm cystic pancreatic lesion. Her clinical history and biochemical test results raised suspicion for type B insulin resistance syndrome (TBIRS), which was confirmed on anti-insulin receptor antibody testing. The patient's hypoglycemia was managed with dietary modification therapy and continuous glucose monitoring. The severity and frequency of hypoglycemic episodes decreased spontaneously. We describe TBIRS and its uncommon hypoglycemic presentation, analyze factors that put TBIRS among the differential diagnosis, and discuss the treatment of TBIRS-associated hypoglycemia.

Polycystic ovary syndrome in a patient with type B insulin resistance syndrome can improve with glucocorticoid treatment: a case report and literature review.

Polycystic ovary syndrome (PCOS) frequently exhibits hyperinsulinemia due to insulin resistance, but there are many unknown aspects of this disease. This report presents the case of a 31-year-old woman with PCOS and type B insulin resistance syndrome (TBIRS). The patient had repeated hyperglycemia and hypoglycemia, and prominent hyperinsulinemia. The insulin receptor antibody was positive, leading to a diagnosis of TBIRS. She also had amenorrhea during the previous 3 months, high blood testosterone levels, and enlarged polycystic ovaries, leading to a diagnosis of PCOS at the same time. The patient was treated with glucocorticoid for TBIRS. The insulin receptor antibody eliminated at 8 weeks after initiation of glucocorticoid treatment, and the blood glucose levels and hyperinsulinemia improved at 9 weeks. Then, the enlargement of both ovaries diminished at 32 weeks, and the menstruation had normalized since 36 weeks. The blood testosterone level normalized at 41 weeks. To the best of our knowledge, this is the first report to demonstrate that enlarged polycystic ovaries and a menstrual disorder in TBIRS improved after glucocorticoid treatment. It is possible that elimination of insulin receptor antibodies by glucocorticoid treatment attenuated insulin resistance and subsequently improved PCOS in TBIRS.

Clinical Features and Outcome Analysis of Type B Insulin Resistance Syndrome: A Single-Center Study in China.

CONTEXT: Type B insulin resistance syndrome (TBIRS) is a rare condition, for which effective treatment remains challenging. OBJECTIVE: This work aimed to summarize the clinical characteristics of TBIRS and explore effective therapeutic strategies. METHODS: The clinical manifestations, biochemical indices, and treatment of 8 patients (3 men and 5 women) with TBIRS from Peking Union Medical College Hospital were retrospectively analyzed and their clinical outcomes were evaluated. RESULTS: The average age of the patients was 49.5 ± 16.5 years, and the duration of the disease ranged from 2 months to 1 year. Seven patients with hyperglycemia had normal/lower triglycerides (TGs) and lower insulin-like growth factor 1 (IGF-1) levels. One patient complained of intractable hypoglycemia. Five patients had accompanied systemic lupus erythematosus, 2 had mixed connective tissue disease, and 1 had undifferentiated connective tissue disease. Five patients had acanthosis nigricans and 3 women of child-bearing age had hyperandrogenism. All 8 patients were treated with glucocorticoids combined with immunosuppressants, among whom, 5 received high-dose glucocorticoid pulse therapy followed by conventional-dose glucocorticoid therapy, all of whom achieved partial remission within 2 to 4 weeks. Among the 3 patients receiving conventional glucocorticoid therapy, 2 achieved partial remission within 2 to 4 weeks. Six patients were tracked for 10 weeks to 4 years; 4 and 2 achieved complete and partial remission, respectively. CONCLUSION: Decreased serum complement 3 and IGF-1 levels and normal/decreased TG levels act as striking biochemical features of TBIRS. High-dose glucocorticoid pulse therapy followed by conventional-dose long-term therapy combined with immunosuppressants achieves good clinical efficacy.

Connections between Diabetes Mellitus and Metabolic Syndrome and the Outcome of Cardiac Dysfunctions Diagnosed during the Recovery from COVID-19 in Patients without a Previous History of Cardiovascular Diseases.

(1) Background: Throughout the COVID-19 pandemic, it became obvious that individuals suffering with obesity, diabetes mellitus (T2DM), and metabolic syndrome (MS) frequently developed persisting cardiovascular complications, which were partially able to explain the onset of the long-COVID-19 syndrome. (2) Methods: Our aim was to document, by transthoracic echocardiography (TTE), the presence of cardiac alterations in 112 patients suffering from post-acute COVID-19 syndrome and T2DM, MS, and/or obesity, in comparison to 91 individuals without metabolic dysfunctions (MD); (3) Results: in patients with MD, TTE borderline/abnormal left (LVF) and/or right ventricular function (RVF), alongside diastolic dysfunction (DD), were more frequently evidenced, when compared to controls (p ˂ 0.001). Statistically significant associations between TTE parameters and the number of factors defining MS, the triglyceride-glucose (TyG) index, the severity of the SARS-CoV-2 infection, and the number of persisting symptoms (p ˂ 0.001) were noted. Significant predictive values for the initial C-reactive protein and TyG index levels, both for the initial and the 6-month follow-up levels of these TTE abnormalities (p ˂ 0.001), were highlighted by means of a multivariate regression analysis. (4) Conclusions: in diabetic patients with MS and/or obesity with comorbid post-acute COVID-19 syndrome, a comprehensive TTE delineates various cardiovascular alterations, when compared with controls. After 6 months, LVF and RVF appeared to normalize, however, the DD-although somewhat improved-did persist in approximately a quarter of patients with MD, possibly due to chronic myocardial changes.

Síndrome metabólico en el adulto mayor vinculado a los programas de actividad física comunitaria / Metabolic Syndrome in the Elderly Adult Involved in the Community Physical Activity Programs

Introducción: El síndrome metabólico es una situación clínica compleja que se asocia a un incremento de la morbilidad y mortalidad. Los elementos que lo componen aumentan el riesgo de diabetes mellitus tipo II y enfermedad cardiovascular. Objetivo: Determinar el comportamiento del síndrome metabólico en el adulto mayor vinculado a los programas de actividad física comunitaria del proyecto Lindo Amanecer del municipio Arroyo Naranjo. Métodos: Se realizó un estudio observacional descriptivo de corte transversal. El universo de estudio lo constituyeron 120 adultos mayores, de los que se entrevistaron a 106, en el período de abril a octubre de 2018. Se siguieron los criterios del Adult Treatment Panel III para el diagnóstico de síndrome metabólico. Las variables descriptivas se expresaron en porcientos y para la comparación de variables en estudio se utilizó el método estadístico de ji al cuadrado. Resultados: Los resultados obtenidos mostraron un 41,51 por ciento de personas con síndrome metabólico, predominaron las personas de 70 y más años de edad (54,54 por ciento y el sexo femenino (93,18 por ciento). El 100 por ciento tuvieron cifras de presión arterial ≥ 130/85 mmHg. El 100 por ciento de los pacientes desconocían su enfermedad. Conclusiones: Se encontró predominio en los pacientes con síndrome metabólico del sexo femenino y del grupo de edad de 70 y más años. El diagnóstico a nivel de la Atención Primaria de Salud es deficiente. Se asocia a la hipertensión arterial, obesidad abdominal y al riesgo de enfermedad cardiovascular(AU)

Introduction: Metabolic syndrome is a complex clinical situation associated with an increase in morbidity and mortality. The elements that mark it up increase the risk of type 2 diabetes mellitus and cardiovascular disease. Objective: To determine the behavior of metabolic syndrome in elderly adults involved in the community physical activity programs of the Lindo Amanecer project in the municipality of Arroyo Naranjo. Methods: A cross-sectional descriptive observational study was carried out. The study universe was made up of 120 elderly adults, 106 of which were interviewed in the period from April to October 2018. The Adult Treatment Panel III criteria for the diagnosis of metabolic syndrome were followed. The descriptive variables were expressed in percentages and, for the comparison of variables under study, the chi-square statistical method was used. Results: The obtained results showed 41.51percent of people with metabolic syndrome, with a predominance of people aged 70 years and older (54.54percent) and the female sex (93.18percent). One hundred percent had blood pressure values over or equal to 130/85 mmHg. One hundred percent of the patients did not have any knowledge of their disease. Conclusions: In patients with metabolic syndrome, the predominance corresponded to the female sex, as well as the age group of 70 years and older. Diagnosis at the primary healthcare level is deficient. It is associated with arterial hypertension, abdominal obesity and the risk of cardiovascular disease(AU)

The Metabolic Syndrome Puzzles; Possible Pathogenesis and Management.

BACKGROUND AND AIMS: Metabolic syndrome is a multifactorial pathophysiological process with complicated homeostatic disorders that arise from various systematic metabolic defects. Various theories underlie the development of metabolic syndrome but are fully not understood. METHODS: Revising PubMed and Scopus literature data on metabolic syndrome pathogenesis and management. RESULTS: The most accepted hypothesis is that a cluster of risk factors combined to obtain a truly metabolic syndrome. The pathophysiology of the metabolic syndrome depends on the underlying development path due to insulin resistance or chronic inflammation and is usually combined with neurohormonal disturbance. Meanwhile, these defects can be inherited via loss of function of certain genes that lead to severe obesity, early diabetes, or severe insulin resistance (with or without lipodystrophy). Chronic inflammation is also a driver of metabolic syndrome. Lifestyle is still the therapy of choice in managing metabolic syndrome, but unfortunately, during the lockdown, most people could not reserve a healthy regime; therefore, it can also be referred to as a pandemic with COVID-19. CONCLUSIONS: This powerful illustration shows how defects in specific encoded proteins located predominantly in the brain, pancreatic beta-cell, muscle, or fat give rise to these distinct components of the metabolic syndrome. Primarily, obesity and its sequela are the initiators of metabolic syndrome. The presence of metabolic syndrome increases the risk and severity of other pathologies' emergence, even in non-related metabolic syndrome diseases such as COVID-19. The article provides new insights into the pathogeneses and management of the metabolic syndrome.

Metabolic syndrome is associated with aggressive prostate cancer regardless of race.

PURPOSE: Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race. METHODS: Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85 mmHg), dyslipidemia (HDL < 40 mg/dL), hypertriglyceridemia (≥ 150 mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100 ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3-5 components) vs. no MS (0-2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested. RESULTS: Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21-2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88-1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62-1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25). CONCLUSION: Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.

Endogenous hyperinsulinemic hypoglycemia: case series and literature review.

PURPOSE: Endogenous hyperinsulinemic hypoglycemia (EHH) is an uncommon disease characterized by inappropriately high plasma insulin levels despite low plasma glucose levels. Some rare etiologies can lead to EHH. Correct diagnosis is a prerequisite for treatment. Hence, although challenging, it is crucial for patients with EHH to identify the different causes. METHODS: We describe a case series of three patients, all of whom had obvious hypoglycemic symptoms and extraordinary hyperinsulinemia. Their plasma glucose, insulin, and C-peptide levels were tested simultaneously when hypoglycemia occurred. Moreover, other biochemical indices and relevant antibody levels were measured and imaging examinations were conducted. RESULTS: According to their medical history, physical examination, laboratory results, and imaging findings, the three patients were diagnosed with insulinoma, type B insulin resistance syndrome, and insulin autoimmune syndrome. After precise treatments, hypoglycemia was ultimately eliminated. CONCLUSION: Although these diseases have similar symptoms and biochemical abnormalities, the treatment and prognosis are different. The case series presented here highlights the challenges in the differential diagnosis of EHH. An accurate diagnosis is necessary for hypoglycemia treatment.

A novel heterozygous missense mutation of Trp1220Gly in the insulin receptor gene associates with type A insulin resistance syndrome: A case report / 中华内分泌代谢杂志

We report a case of type A insulin resistance syndrome. A 16-year-old girl with BMI of 19.1 kg/m 2 presented with primary amenorrhea and hyperglycemia for two years. Baseline HbA 1C was 10.8%, along with severe hyperinsulinemia, increased total testosterone and free androgen index(FAI). Ultrasonography showed polycystic ovaries. Next generation sequencing identified a novel and de novo heterozygous missense mutation of Trp1220Gly in the insulin receptor gene. Short-term intensive insulin pump treatment was initiated, followed by insulin glargine, pioglitazone and acarbose combination regiment. Fasting blood glucose and insulin levels decreased significantly, but post-load hyperglycemia and hyperinsulinemia remained unsatisfactory. HbA 1C dropped to 7.6% at 1-year follow up. Patients with polycystic ovarian syndrome who are adolescent-onset and with lean body type should be taken into account of type A insulin resistance syndrome. Currently, there is no standardized treatment protocol, and therapy should be individualized based on the specific gene mutation of each patient.

The impact of Ramadan fasting on the metabolic syndrome severity in relation to ethnicity and sex: Results of a systematic review and meta-analysis.

AIMS: The primary goal of this meta-analysis was to examine the changes in various components of metabolic syndrome (MetS) in healthy adults who observed Ramadan fasting (RF) before Ramadan (T1) and at the end of RF (T2). A secondary goal was to assess the impact of RF on MetS severity in various ethnic and sex groups using the MetS z-score. DATA SYNTHESIS: Using PRISMA2020, seven databases were searched for relevant studies published between January 1950 and March 2022. Data extraction involved high-density lipoprotein cholesterol (HDL), triglycerides (TG), fasting blood glucose (FBG), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) for T1 and T2, respectively. The MetS z-score was computed according to international diabetes federation criteria. At T1, the pooled estimates of HDL, TG, FBG, WC, SBP, DBP, and MAP were 1.20 [1.13; 1.27] mmol/L, 1.32 [1.23; 1.42] mmol/L, 4.98 [4.82; 5.15] mmol/L, 87.21 [84.21; 90.21] Cm, 114.22 [101.45; 126.99] mmHg, 76.80 [70.12; 83.47] mmHg, and 89.27 [80.56; 97.98] mmHg, respectively. At T2, the pooled estimates of HDL, TG, FBG, WC, SBP, DBP, and MAP were 1.24 [1.18; 1.31] mmol/L, 1.24 [1.14; 1.34] mmol/L, 4.77 [4.55; 4.99] mmol/L, 85.73 [82.83; 88.64] Cm, 109.48 [97.20; 121.75] mmHg, 74.43 [68.01; 80.85] mmHg, and 86.11 [77.74; 94.48] mmHg, respectively. The MetS z-score showed improvement at T2 for all ethnic groups and both sexes by -0.22 [-0.24; -0.01]. CONCLUSIONS: The current meta-analysis suggests that the RF positively impact the MetS components and the overall MetS z-score. PROSPERO REGISTRATION NUMBER: ID CRD42022329297 OPEN SCIENCE FRAMEWORK IDENTIFIER: DOI 10.17605/OSF.IO/U9H7T.

Management challenges of Rabson Mendenhall syndrome in a resource limited country: a case report.

OBJECTIVES: Rabson Mendenhall syndrome  (RMS) is a rare form of insulin resistance syndrome caused by insulin receptor mutation. In term of severity, it lies at an intermediate point on spectrum of insulin resistance with Donohue syndrome flanking the severe and Type A insulin resistance at the mild end. We are reporting a 3.5-month-old boy with RMS along with its management challenges in a resource limited country. CASE PRESENTATION: An infant presented at 3.5-month of an age with failure to thrive and fluctuating blood glucose level (hyperglycaemia and hypoglycaemia) along with clinical features of insulin resistance. He was found to have raised HbA1C, high insulin and C peptide level and a homozygous mutation in INSR gene c.1049C>T, (p.Ser350 Leu) confirming the diagnosis of RMS. He was managed with long-acting insulin (Detemir) along with frequent feeding. CONCLUSIONS: RMS in resource limited countries could be managed with frequent feeding along with insulin. Early diagnosis and management can improve long term outcome.

Case Report: A Chinese Family of Type A Insulin Resistance Syndrome With Diabetes Mellitus, With a Novel Heterozygous Missense Mutation of the Insulin Receptor Gene.

Type A Insulin resistance syndrome (TAIRS) is an autosomal dominant or recessive genetic disorder caused by insulin dysfunction resulting from insulin receptor (INSR) gene mutation. The main features of TAIRS include hyperinsulinemia, abnormal glucose metabolism, and changes in acanthosis nigricans. We identified, in China, a TAIRS family with a novel heterozygous missense gene mutation type. One patient from the Chinese Han family exhibited signs and symptoms of TAIRS and was presented for evaluation. Whole-exome sequencing revealed a heterozygous mutation. Both the patient proband and his father were identified with insulin receptor exon 19c.3472C>T(p.Arg1158Trp), which resulted in a missense mutation that led to replace by a base in the amino acid codon. We found that the patient proband and his father exhibited high insulin and C-peptide release after glucose stimulation by insulin and C-peptide release tests. At the same time, we also ruled out the possibility of islet ßcell tumor through relevant examinations. These findings indicate that the INSR gene mutation may cause pancreatic ß cell functional impairment and contribute to the development of diabetes.