The risk of developing type 2 diabetes mellitus (T2DM) is exceptionally high among both native and migrant South Asians. T2DM occurs more often and at a younger age and lower BMI, and the risk of coronary artery and cerebrovascular disease, and renal complications is higher for South Asians compared with people of White Caucasian descent. The high prevalence of T2DM and its related complications in South Asians, which comprise one-fifth of the total world's population, poses a major health and socioeconomic burden. The underlying cause of this excess risk, however, is still not completely understood. Therefore, gaining insight into the pathogenesis of T2DM in South Asians is of great importance. The predominant mechanism, in this ethnicity seems to be insulin resistance (IR) rather than an impaired β-cell function. In this systematic review, we describe several possible mechanisms that may underlie or contribute to the increased IR observed in South Asians.
Abstract A 5-day High-Fat High-Calorie diet (HFHC-diet) reduces insulin-stimulated glucose disposal (Rd) in South Asian, but not Caucasian healthy lean males. We aimed to investigate if differences in myocellular lipid handling are underlying this differential response. A two-step hyperinsulinemic-euglycemic clamp and muscle biopsies were performed in 12 healthy lean Caucasian and South Asian males (BMI < 25 kg/m 2 , 19–25 years) before and after a 5-day HFHC-diet (regular diet + 375 mL cream/day; 1275 kcal/day; 94% fat). Triglyceride extractions and Western Blots for lipid droplet and mitochondrial proteins were performed. Intramyocellular lipid content and HFHC-diet response were similar between ethnicities (group effect: P = 0.094; diet effect: +~30%, P = 0.044). PLIN5 protein content increased upon the HFHC-diet (P = 0.031) and tended to be higher in South Asians (0.87 ± 0.42 AU vs. 1.35 ± 0.58 AU, P = 0.07). 4-HNE tended to increase in South Asians upon the HFHC-diet (interaction effect: P = 0.057). In Caucasians ΔPLIN5 content correlated with ΔR d (Caucasians: r = 0.756, P = 0.011; South Asians: r = −0.085, P = 0.816), while in South Asians Δ4-HNE associated with ΔPLIN5 content (Caucasians: r = 0.312, P = 0.380; South Asians: r = 0.771, P = 0.003). These data indicate that in Caucasians, PLIN5 may be protective against HFHC-diet induced insulin resistance, which for reasons not yet understood is not observed in South Asians, who possess increased lipid peroxidation levels.
Abstract Purpose To report our experience with 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with MRI (FET-PET/MRICR) in the care trajectory for complex acromegaly patients. Methods In 10 patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options, FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. Results FET-PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In 5 patients FET-PET/MRICR was fully concordant with conventional MRI, and in 1 patient partially concordant. FET-PET/MRICR identified new suspicious foci in 4 other patients. Surgical re-exploration was performed in 9 patients (aimed at total resection (6), debulking (2), diagnosis (1)), and 1 patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRICR findings were confirmed intraoperatively, and in 6 patients (67%) also histologically. IGF-1 decreased significantly in 8 patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in 3 patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in 5 and was unchanged in 1 patient. No permanent complications occurred. Outcome categorized by integrated outcome quadrants (IOQs) defined by preoperative intended effect versus permanent complications at 6 months was IOQ-1 (goal achieved without complications) in 6 (67%) and IOQ-3 (goal not achieved, no complications) in 3 patients. Conclusion In complex acromegaly cases FET-PET/MRICR can provide additional information to aid decision-making by the multidisciplinary pituitary team, especially when (further) surgery is being considered.
To evaluate patients with prolactinoma treated surgically in a time when elective prolactinoma surgery became routine in our center, using a comprehensive outcome set, focusing on preoperative assessments, surgical outcomes, and health-related quality of life (HR-QoL).
Abstract Purpose To describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery. Methods Retrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment. Results 40 patients were included (31 females (77.5%), median age 26.5 (14–63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0–27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1. Conclusion Care trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team’s assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients’ needs were prerequisites for adequate counseling in treatment of patients with prolactinoma.
