Nandu KS Thalange

Background: The countries of the Gulf Cooperation Council (GCC) face a significant diabetes burden. Preventing, or at least delaying onset of Type 2 diabetes mellitus (T2DM) requires accurate and timely identification of at-risk individuals with prediabetes. Traditional screening focuses on glucose and HbA1c alone and does not include other readily available data that can better identify risk and guide intervention. Methods: We developed a comprehensive web-based cardiometabolic risk calculator combining the classic homeostasis model assessment (HOMA1), triglyceride-glucose (TyG) index, metabolic syndrome evaluation (ATP III and IDF criteria), diabetes risk prediction adapted from validated models including QDiabetes-2018 and UK Biobank cohort studies, and cardiovascular risk trajectory with Lipoprotein(a) integration. The calculator uses ethnicity-specific thresholds for Middle Eastern, South Asian, and other populations, and provides AI-generated clinical summaries with multi-language patient education materials. Case: An 18-year-old Emirati male with obesity, prediabetes, severe insulin resistance, and compensatory beta-cell hypersecretion had a calculated 10-year diabetes risk exceeding 55%. This quantitative risk estimate motivated intensive lifestyle modification combined with tirzepatide and metformin. After six months, he achieved 17% weight loss, normalization of insulin resistance and beta-cell function, prediabetes resolution and diabetes risk reduction to under 10%. Conclusion: Comprehensive metabolic phenotyping with quantitative risk communication can identify high-risk individuals, characterize their metabolic dysfunction, and motivate behavioral change. This freely available tool addresses the need to identify individuals at high 10-year risk of progression to T2DM and elevated lifetime cardiovascular risk, thereby allowing more timely intervention.

Background: Leptin receptor (LEPR) deficiency is a rare autosomal recessive disorder causing severe early-onset obesity, hyperphagia, and multiple endocrine abnormalities. Hypopituitarism is a significant but underrecognized complication of this genetic condition. Case Presentation: We report a 14-year-old girl with homozygous LEPR mutation (c.3132delC; p.Asn1045Thrfs*2) presenting with severe obesity (BMI 62.7 kg/m²), new-onset type 2 diabetes (HbA1c 6.5%), and multiple pituitary hormone deficiencies including hypogonadotropic hypogonadism (undetectable LH/FSH), likely growth hormone deficiency, and central hypothyroidism. Despite advanced bone age indicating she was at near final height, the patient remained prepubertal with significant short stature (7th percentile for height) well below her mid-parental target height of 165 cm (75th percentile). Management included planned therapy with setmelanotide, an MC4R agonist specifically approved for LEPR deficiency, along with pituitary hormone replacement and management of diabetes and dyslipidemia. Conclusions: This case highlights the complex endocrine manifestations of LEPR deficiency beyond obesity, emphasizing the importance of systematic evaluation for hypopituitarism in affected patients. The availability of targeted therapies like setmelanotide represents a paradigm shift in management, offering hope for improved outcomes in this challenging condition. Early recognition and comprehensive endocrine assessment are crucial for optimal patient care and long-term prognosis.