Saudi Arabia is a country with high prevalence of diabetes, uncontrolled diabetes, and diabetes-related complications. Poor glycemic control is multifactorial and could be explained in part by physician and patient reluctance toward insulin or insulin inertia. This study aimed to address physician barriers toward insulin therapy in primary care settings. It included 288 physicians from 168 primary healthcare centers (PHC) in the Jazan region of Saudi Arabia. Participants responded to questionnaire investigating physicians’ attitude and barriers to insulin initiation and intensification in PHCs. In physician opinion, the most common barriers among their patients were fear of injection, lack of patient education, fear of hypoglycemia, and difficult administration. Physicians were reluctant to initiate insulin for T2D patients mostly due to patient non-adherence to blood sugar measurement, non-adherence to appointment or treatment, elderly patients, or due to patient refusal. Physicians’ fear of hypoglycemia, lack of staff for patient education, and lack of updated knowledge were the primary clinician-related barriers. Exaggerated fears of insulin side effects, patient non-adherence, limited staff for patient’s education, patient refusal, and inadequate consultation time were the main barriers to insulin acceptance and prescription.

Background and Objectives: The link between celiac disease (CD) and type 1 diabetes (T1D) has been well-documented in the medical literature and is thought to be due to a shared genetic predisposition in addition to environmental triggers. This study aimed to determine the seroprevalence and biopsy-proven CD (PBCD) prevalence in individuals with T1D from Saudi Arabia and identify their clinical characteristics and the impact on glycemic control. Materials and Methods: A total of 969 children and adolescents with confirmed T1D were investigated. Prospective and retrospective data were collected to include clinical, anthropometric, and biochemical data. Total IgA and anti-TTG-IgA antibodies were screened to detect seropositive cases. Upper intestinal endoscopy and biopsy were performed to find BPCD. Results: The seroprevalence of CD was 14.6% (141/969), while BPCD prevalence was 7.5%. Females had a higher prevalence than males: 17.8% vs. 9.8%, p < 0.001. The CD group had lower HbA1c and more frequent hypoglycemia than the seronegative group. Conclusions: This study highlighted the high prevalence of CD in T1D Saudi patients. CD has multiple effects on glycemic control, growth, and puberty in children and adolescents with T1D. We emphasize the importance of early screening for CD at the time of diabetes diagnosis and periodically after that or if any atypical features present, especially anemia, growth delay, underweight, or frequent hypoglycemia.

Familial partial lipodystrophies (FPLDs) are very rare inherited disorders characterized by partial loss of adipose tissue from the upper and lower extremities. At least seven subtypes of FPLD have been identified and are mostly dominantly inherited. FPLD type 3 is caused by mutations in the PPARγ gene, which encodes for the protein peroxisome proliferator-activated receptor gamma (PPARγ). We identified a Saudi female with PFLD3 presented with partial lipoatrophy, uncontrolled diabetes, severe hypertriglyceridemia, and recurrent pancreatitis. The clinical and biochemical findings in this proband were described before and after treatment with Pioglitazone in addition to the conventional treatment. DNA extraction and whole exome sequencing (WES) were performed to detect the variant. The mutant gene was subjected to Sanger analysis to confirm the results. We applied five specific computational prediction tools to assess the pathogenicity of variation, namely the MT, DANN, CADD, BayesDel, and fitCons tools. We assessed protein modeling and stability with the AlphaFold-generated structures for both wild-type and mutant proteins. Finally, we conducted molecular docking using the AutoDock Vina virtual docking. Upon whole exome sequencing, a c.1024C>T p.(Gln342Ter) missense mutation was detected in the PPARγ gene associated with FPLD3. This variant is a novel mutation that has not been described in all genome databases. Sanger analysis confirmed the heterogenicity and pathogenicity of this variant. All five computational prediction tools indicate that this variant is considered highly pathogenic. Our patient showed a dramatic response to Pioglitazone, a synthetic PPARγ agonist. From structural modeling, we found that the enhanced binding affinity of the mutant PPARγ protein to Pioglitazone likely improves the activation of PPARγ, enhancing its transcriptional activity and resulting in better clinical outcomes. These findings extend the spectrum of PPARγ mutations responsible for FPLD3 and highlight the potential for personalized treatment strategies based on genetic mutations.

Background and Objectives: Familial type 1 diabetes (FT1D) represents a distinct subgroup of T1D potentially influenced by shared genetic and environmental factors. Data from Middle Eastern populations—where both T1D incidence and consanguinity are high—remain limited. This study aimed to determine the prevalence of FT1D and to compare the clinical, metabolic, and immunological features of FT1D with non-familial T1D (NFT1D) among children and adolescents in Saudi Arabia. Materials and Methods: A retrospective analytic study was conducted among 987 individuals diagnosed with T1D before 18 years of age and followed at the Jazan Endocrinology and Diabetes Center between 2015 and 2023. Participants were categorized as FT1D if they had at least one affected first-degree relative. Demographic, clinical, and biochemical data—including autoantibody profiles, associated autoimmune diseases, glycemic indices, and acute complications—were compared. Multivariate regression analyses were performed to assess independent associations after adjustment for age at diagnosis, sex, and parental consanguinity. Results: FT1D accounted for 19.5% of all T1D cases, with siblings being the most affected relatives (11.3%). FT1D patients were diagnosed at a younger age (8.2 ± 3.4 y vs. 9.3 ± 3.7 y; p = 0.001), had lower HbA1c (10.7 ± 1.5 vs. 12.0 ± 1.5; p < 0.001), less DKA at presentation (33.9% vs. 49.7%; p < 0.001), and fewer ICU admissions (13.5% vs. 20.8%; p = 0.023). In adjusted models, FT1D remained independently associated with lower odds of DKA (OR = 0.54, 95% CI 0.39–0.76, p < 0.001) and ICU admission (OR = 0.58, 95% CI 0.37–0.92, p = 0.019), and with higher odds of extra-pancreatic autoantibody positivity (OR = 1.78, 95% CI 1.21–2.61, p = 0.003) and anti-tissue transglutaminase antibodies (OR = 1.64, 95% CI 1.05–2.56, p = 0.031). Conclusions: FT1D constitutes a considerable proportion of pediatric T1D in Saudi Arabia and is characterized by earlier onset, milder metabolic decompensation at diagnosis, higher consanguinity, and higher likelihood of associated extra-pancreatic autoimmune diseases. Despite these differences, short-term glycemic outcomes remain similar to non-familial cases. These findings emphasize the need for family-based screening, genetic counseling, and early detection programs in high-risk populations.