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AIMS. Post-bariatric hypoglycemia (PBH) is an increasingly-recognized complication of bariatric surgery, but current therapies are limited. We hypothesized pramlintide would reduce hypoglycemia by slowing gastric emptying and reducing postprandial glucagon secretion, thus limiting postprandial glycemic excursions and insulin secretion. We thus determined the efficacy of pramlintide on frequency and severity of hypoglycemia in PBH. MATERIALS AND METHODS. Participants with PBH following gastric bypass were recruited from outpatient clinics at Joslin Diabetes Center, Boston, MA for an open-label study of pramlintide efficacy over 8 weeks. 23 participants were assessed for eligibility, 20 participants had at least 1 pramlintide dose, and 14 completed the study. Mixed meal tolerance test (MMTT) was performed at baseline and following 8 weeks of subcutaneous pramlintide with sequential dose increase to maximum of 120 micrograms (mean 69±32 mcg) 3 times daily. The primary endpoint was change in glucose excursions during MMTT. Secondary measures included MMTT insulin response, satiety and dumping score, percentage time with sensor glucose

Emerging literature suggests that obesity may be “protective” against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9 years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02–1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60–0.96). However, after excluding underweight individuals (body mass index [BMI]

Micro- and macrovascular diseases are major causes of morbidity and mortality in the diabetic population, but the cellular and molecular mechanisms that link hyperglycemia to these complications remain incompletely understood. We proposed that in human diabetes, inhibition by glycation of the complement regulatory protein CD59 increases deposition of the membrane attack complex (MAC) of complement, contributing to the higher vascular risk. We report here 1) the generation and characterization of an anti-glycated human CD59 (hCD59) specific antibody, 2) the detection with this antibody of glycated hCD59 colocalized with MAC in kidneys and nerves from diabetic but not from nondiabetic subjects, and 3) a significantly reduced activity of hCD59 in erythrocytes from diabetic subjects, a finding consistent with glycation inactivation of hCD59 in vivo. Because hCD59 acts as a specific inhibitor of MAC formation, these findings provide a molecular explanation for the increased MAC deposition reportedly found in the target organs of diabetic complications. We conclude that glycation inactivation of hCD59 that leads to increased MAC deposition may contribute to the extensive vascular pathology that complicates human diabetes.