Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile.

Constitutional thinness (CT) is a nonpathological state of underweight. The current study aimed to explore skeletal muscle energy storage in individuals with CT and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsy specimens before and after overfeeding. In the skeletal muscle of CT participants compared with controls, we observed a lower content of intramuscular triglycerides for type I (-17%, p < 0.01) and type IIA (-14%, p < 0.05) muscle fibers, a lower glycogen content for type I (-6%, p < 0.01) and type IIA (-5%, p < 0.05) muscle fibers, a specific fiber-type distribution, a marked muscle hypotrophy (-20%, p < 0.001), a low capillary-to-fiber ratio (-19%, p < 0.001), and low citrate synthase activity (-18%, p < 0.05). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (+10%, p < 0.01) and type IIA (+9%, p < 0.01) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared with normal-weight individuals, suggesting a specific energy metabolism and muscle adaptations. ClinicalTrials.gov registration no. NCT02004821. Novelty Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals. Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin individuals. Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.

Rational and design of an overfeeding protocol in constitutional thinness: Understanding the physiology, metabolism and genetic background of resistance to weight gain.

BACKGROUND: Constitutional thinness (CT) is a natural state of underweight (13-17.5kg/m2) without the presence of any eating disorders and abnormal hormonal profile, and with preserved menses in women. We previously conducted a four-week fat overfeeding study showing weight gain resistance in CT women and one of our main results was the identification of an energy gap: a positive energy balance (higher energy intake than energy expenditure). OBJECTIVE: This new overfeeding study is designed to confirm the energy gap and propose mechanistic hypothesis. DESIGN: A 2-week overfeeding (daily consumption of one bottle of Renutryl® Booster (600kcal, 30g protein, 72g carbohydrate, 21g fat) on top of the dietary intake) is performed to compare 15 women and men in each CT group (Body Mass Index [BMI]<18.5kg/m2) to their controls (BMI 20-25kg/m2). Bodyweight, food intake, energy expenditure (canopy, calorimetric chamber and Actiheart), body composition (DXA), appetite regulatory hormone profiles after a test meal, proteomics, metabolomics, urinary metabolic profiles, stool microbiome and lipids, fat and muscle transcriptomics are monitored before and after overfeeding. RESULTS AND CONCLUSIONS: Data inter-linking will be able to be established with results of this study. The findings could possibly open to therapeutic approaches to help CT patients to gain weight as well as provide a better understanding of energy regulation with regard to treat obesity (resistance to weight loss), a mirror image of CT (resistance to weight gain).

No loss of chance of diabetic retinopathy screening by endocrinologists with a digital fundus camera.

OBJECTIVE: To compare the efficacy of the diabetic retinopathy (DR) screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of "loss of chance." RESEARCH DESIGN AND METHODS: In a cross-sectional study, 500 adult diabetic patients (1,000 eyes) underwent three-field retinal photography with a digital fundus camera following pupillary dilatation. Five endocrinologists and two ophthalmology residents underwent 40 h of training on screening and grading of DR and detection of associated retinal findings. A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists. Screening efficiency of endocrinologists was evaluated in terms of "loss of chance," i.e., missed diagnoses that required ophthalmologist referrals. RESULTS: The mean weighted κ of DR screening performed by endocronologists was similar to that of ophthalmology residents (0.65 vs. 0.73). Out of 456 DR eyes, both endocrinologists and ophthalmology residents misdiagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral. There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training. CONCLUSIONS: The endocrinologist with specific training for DR detection using a three-field digital fundus camera with pupillary dilatation can perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.