; for the PCORnet Bariatric Study Collaborative IMPORTANCE Bariatric surgery can lead to substantial improvements in type 2 diabetes (T2DM), but outcomes vary across procedures and populations. It is unclear which bariatric procedure has the most benefits for patients with T2DM. OBJECTIVE To evaluate associations of bariatric surgery with T2DM outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted in 34 US health system sites in the National Patient-Centered Clinical Research Network Bariatric Study. Adult patients with T2DM who had bariatric surgery between January 1, 2005, and September 30, 2015, were included. Data analysis was conducted from April 2017 to August 2019. INTERVENTIONS Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). MAIN OUTCOME AND MEASURES Type 2 diabetes remission, T2DM relapse, percentage of total weight lost, and change in glycosylated hemoglobin (hemoglobin A 1c). RESULTS A total of 9710 patients were included (median [interquartile range] follow-up time, 2.7 [2.9] years; 7051 female patients [72.6%]; mean [SD] age, 49.8 [10.5] years; mean [SD] BMI, 49.0 [8.4]; 6040 white patients [72.2%]). Weight loss was significantly greater with RYGB than SG at 1 year (mean difference, 6.3 [95% CI, 5.8-6.7] percentage points) and 5 years (mean difference, 8.1 [95% CI, 6.6-9.6] percentage points). The T2DM remission rate was approximately 10% higher in patients who had RYGB (hazard ratio, 1.10 [95% CI, 1.04-1.16]) than those who had SG. Estimated adjusted cumulative T2DM remission rates for patients who had RYGB and SG were 59.2% (95% CI, 57.7%-60.7%) and 55.9% (95% CI, 53.9%-57.9%), respectively, at 1 year and 86.1% (95% CI, 84.7%-87.3%) and 83.5% (95% CI, 81.6%-85.1%) at 5 years postsurgery. Among 6141 patients who experienced T2DM remission, the subsequent T2DM relapse rate was lower for those who had RYGB than those who had SG (hazard ratio, 0.75 [95% CI, 0.67-0.84]). Estimated relapse rates for those who had RYGB and SG were 8.4% (95% CI, 7.4%-9.3%) and 11.0% (95% CI, 9.6%-12.4%) at 1 year and 33.1% (95% CI, 29.6%-36.5%) and 41.6% (95% CI, 36.8%-46.1%) at 5 years after surgery. At 5 years, compared with baseline, hemoglobin A 1c was reduced 0.45 (95% CI, 0.27-0.63) percentage points more for patients who had RYGB vs patients who had SG. CONCLUSIONS AND RELEVANCE In this large multicenter study, patients who had RYGB had greater weight loss, a slightly higher T2DM remission rate, less T2DM relapse, and better long-term glycemic control compared with those who had SG. These findings can help inform patient-centered surgical decision-making.

GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) is a 36-center unmasked, parallel treatment group, randomized controlled trial evaluating four diabetes medications added to metformin in people with type 2 diabetes (T2DM). We report baseline characteristics and compare GRADE participants to a National Health and Nutrition Examination Survey (NHANES) cohort. RESEARCH DESIGN AND METHODS Participants were age ‡30 years at the time of diagnosis, with duration of T2DM <10 years, HbA 1c 6.8-8.5% (51-69 mmol/mol), prescribed metformin monotherapy, and randomized to glimepiride, sitagliptin, liraglutide, or insulin glargine. RESULTS At baseline, GRADE's 5,047 randomized participants were 57.2 6 10.0 years of age, 63.6% male, with racial/ethnic breakdown of 65.7% white, 19.8% African American, 3.6% Asian, 2.7% Native American, 7.6% other or unknown, and 18.4% Hispanic/ Latino. Duration of diabetes was 4.2 6 2.8 years, with mean HbA 1c of 7.5 6 0.5% (58 6 5.3 mmol/mol), BMI of 34.3 6 6.8 kg/m 2 , and metformin dose of 1,944 6 204 mg/day. Among the cohort, 67% reported a history of hypertension, 72% a history of hyperlipidemia, and 6.5% a history of heart attack or stroke. Applying GRADE inclusion criteria to NHANES indicates enrollment of a representative cohort with T2DM on metformin monotherapy (NHANES cohort average age, 57.9 years; mean HbA 1c , 7.4% [57 mmol/mol]; BMI, 33.2 kg/m 2 ; duration, 4.2 6 2.5 years; and 7.2% with a history of cardiovascular disease). CONCLUSIONS The GRADE cohort represents patients with T2DM treated with metformin requiring a second diabetes medication. GRADE will inform decisions about the clinical effectiveness of the addition of four classes of diabetes medications to metformin. The optimal medication management of hyperglycemia in type 2 diabetes (T2DM) is not established. In addition to lifestyle intervention, metformin is the recommended initial medication in T2DM due to its glycemic effectiveness, lack of associated hypoglycemia or weight gain, low cost, and evidence of long-term benefit and safety

Background. The concurrent use of a postprandial insulin sensitizing agent, such as bromocriptine-QR, a quick release formulation of bromocriptine, a dopamine D2 receptor agonist, may offer a strategy to improve glycemic control and limit/reduce insulin requirement in type 2 diabetes (T2DM) patients on high-dose insulin. This open label pilot study evaluated this potential utility of bromocriptine-QR. Methods. Ten T2DM subjects on metformin (1-2 gm/day) and high-dose (TDID ≥ 65 U/day) basal-bolus insulin were enrolled to receive once daily (morning) bromocriptine-QR (1.6–4.8 mg/day) for 24 weeks. Subjects with at least one postbaseline HbA1c measurement (N = 8) were analyzed for change from baseline HbA1c, TDID, and postprandial glucose area under the curve of a four-hour mixed meal tolerance test (MMTT). Results. Compared to the baseline, average HbA1c decreased 1.76% (9.74 ± 0.56 to 7.98 ± 0.36, P = 0.01), average TDID decreased 27% (199 ± 33 to 147 ± 31, P = 0.009), and MMTT AUC60–240 decreased 32% (P = 0.04) over the treatment period. The decline in HbA1c and TDID was observed at 8 weeks and sustained over the remaining 16-week study duration. Conclusion. In this study, bromocriptine-QR therapy improved glycemic control and meal tolerance while reducing insulin requirement in T2DM subjects poorly controlled on high-dose insulin therapy.

Background Hyperinsulinemia has been associated with hepatic fat deposition and ensuing insulin resistance. It is unknown if treatment with exogenous insulin in patients with type 2 diabetes, who are most prone to hepatic fat accumulation, would promote the occurrence or worsening of nonalcoholic fatty liver disease (NAFLD). Methods Patients with treatment-naïve type 2 diabetes (N=16) were treated with insulin and metformin for a 3-month lead-in period, then assigned triple oral therapy (metformin, glyburide and pioglitazone) or continued treatment with insulin and metformin. Hepatic triglyceride content (HTC) – measured by magnetic resonance spectroscopy, serum lipids, glucose, liver function tests, and inflammatory and thrombotic biomarkers were followed for a median of 31 months. Results The 45% decline in HTC during the lead-in period persisted through the follow-up period with no difference between treatment groups at the end of the study (5.26±4.21% in the triple oral therapy versus 7.47±7.40% for insulin/metformin), while glycemic control was comparable. Conclusions Improvements in HTC with initial insulin/metformin therapy persisted through the median 31-month follow-up period regardless of the treatment. More importantly, insulin-based treatment does not appear to promote or worsen NAFLD.

Unintentional parathyroidectomy during thyroid surgery has an incidence ranging between 1% and 31% across institutions. Many studies have identified malignancy and central neck dissection as risk factors for losing parathyroid glands, but few studies have evaluated the impact of other factors such as lymphocytic thyroiditis, hyperthyroidism, or concomitant primary hyperparathyroidism. The purpose of this study was to investigate which factors contribute to parathyroid loss during thyroid surgery. Charts of 269 patients undergoing thyroid surgery at a tertiary care medical center from 2010 to 2013 were retrospectively reviewed. Sixty-six patients (24.5%) experienced unintentional parathyroidectomy. Bivariate analysis showed no significant differences in patient characteristics. Patients with unintentional parathyroid removal had a significantly smaller largest thyroid nodule size (P ¼ 0.002), higher rate of central neck dissection (30.3% vs 7.9%, P < 0.0001), and higher rate of malignancy (50% vs 36.0%, P ¼ 0.04). Multivariable analysis showed that the strongest risk factor for unintentional parathyroidectomy was central neck dissection (P ¼ 0.0008; odds ratio 4.72, confidence interval 1.91-11.71). In conclusion, central neck dissection for thyroid malignancy is the strongest risk factor for unintentional thyroidectomy. The presence of concomitant primary hyperparathyroidism, lymphocytic thyroiditis, or hyperthyroidism did not appear to increase the risk of unintentional parathyroidectomy.