Emotional Distress Predicts Reduced Type 2 Diabetes Treatment Adherence in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: We examined longitudinal associations between emotional distress (specifically, depressive symptoms and diabetes distress) and medication adherence in Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), a large randomized controlled trial comparing four glucose-lowering medications added to metformin in adults with relatively recent-onset type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: The Emotional Distress Substudy assessed medication adherence, depressive symptoms, and diabetes distress in 1,739 GRADE participants via self-completed questionnaires administered biannually up to 3 years. We examined baseline depressive symptoms and diabetes distress as predictors of medication adherence over 36 months. Bidirectional visit-to-visit relationships were also examined. Treatment satisfaction, beliefs about medication, diabetes care self-efficacy, and perceived control over diabetes were evaluated as mediators of longitudinal associations. RESULTS: At baseline, mean ± SD age of participants (56% of whom were White, 17% Hispanic/Latino, 18% Black, and 66% male) was 58.0 ± 10.2 years, diabetes duration 4.2 ± 2.8 years, HbA1c 7.5% ± 0.5%, and medication adherence 89.9% ± 11.1%. Higher baseline depressive symptoms and diabetes distress were independently associated with lower adherence over 36 months (P < 0.001). Higher depressive symptoms and diabetes distress at one visit predicted lower adherence at the subsequent 6-month visit (P < 0.0001) but not vice versa. Treatment assignment did not moderate relationships. Patient-reported concerns about diabetes medications mediated the largest percentage (11.9%-15.5%) of the longitudinal link between emotional distress and adherence. CONCLUSIONS: Depressive symptoms and diabetes distress both predict lower adherence to glucose-lowering medications over time among adults with T2DM. Addressing emotional distress and concerns about anticipated negative effects of taking these treatments may be important to support diabetes treatment adherence.

Thyroid carcinoma in the McCune-Albright syndrome: contributory role of activating Gs alpha mutations.

McCune-Albright syndrome (MAS) is defined by the triad of café-au-lait skin pigmentation, polyostotic fibrous dysplasia, and hyperfunctioning endocrinopathies, such as precocious puberty, hyperthyroidism, GH excess, and Cushing's syndrome. This disorder is caused by sporadic, postzygotic activating mutations in the GNAS1 gene, which codes for the G(s)alpha protein in the cAMP signaling cascade. Nodular and diffuse goiters (with and without hyperthyroidism), as well as benign thyroid nodules, have been reported in association with MAS. Herein we report two cases of thyroid carcinoma in patients with MAS. The first is a case of papillary thyroid cancer detected incidentally during a hemithyroidectomy for hyperthyroidism in a 14-yr-old girl. The second is one of a 41-yr-old woman with long-standing MAS and an enlarging thyroid nodule, which was diagnosed as a clear cell thyroid carcinoma, a rare variant of thyroid cancer. Molecular analysis revealed that foci of malignancy and adjacent areas of hyperplasia and some areas of normal thyroid harbored activating mutations of Arg(201) in the GNAS1 gene. These findings suggest that the infrequent development of thyroid carcinoma in MAS patients involves additional mutational or epigenetic events.

Variants in the LEPR gene are nominally associated with higher BMI and lower 24-h energy expenditure in Pima Indians.

Genome-wide association studies (GWASs) have been used to search for susceptibility genes for type 2 diabetes and obesity in the Pima Indians, a population with a high prevalence of both diseases. In these studies, a variant (rs2025804) in the LEPR gene was nominally associated with BMI in 1,082 subjects (P = 0.03 adjusted for age, sex, birth year, and family membership). Therefore the LEPR and leptin overlapping transcript (LEPROT) genes were selected for further sequencing and genotyping in larger population-based samples for association analyses with obesity-related phenotypes. Selected variants (n = 80) spanning these genes were genotyped in a sample of full-heritage Pima Indians (n = 2,842) and several common variants including rs2025804 were nominally associated with BMI (P = 0.05-0.003 adjusted for age, sex, birth year, and family membership). Four common tag variants associated with BMI in the full-heritage Pima Indian sample were genotyped in a second sample of mixed-heritage Native Americans (n = 2,969) and three of the variants showed nominal replication (P = 0.03-0.006 adjusted as above and additionally for Indian heritage). Combining both samples provided the strongest evidence for association (adjusted P = 0.0003-0.0001). A subset of these individuals (n = 403) had been metabolically characterized for predictors of obesity and the BMI risk alleles for the variants tagged by rs2025804 were also associated with lower 24-h energy expenditure (24hEE) as assessed in a human respiratory chamber (P = 0.0007 adjusted for age, sex, fat mass, fat-free mass, activity, and family membership). We conclude that common noncoding variation in the LEPR gene is associated with higher BMI and lower energy expenditure in Native Americans.