Search

OBJECTIVE To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth. RESEARCH DESIGN AND METHODS Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide. RESULTS Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes. CONCLUSIONS These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.

BACKGROUND: Guidelines recommend sodium–glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo–based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

Background Cataracts secondary to Type 1 or Type 2 Diabetes is not uncommon in adults, however, it is a rare finding in pediatrics patients with Type 1 Diabetes. Clinical Case A 15-year-old girl presented with progressively worsened bilateral vision for 6 months, however, vision rapidly deteriorated over the previous month, prompting visit to optometrist. No history of weight loss, however, did report 1.5 years of polydipsia, polyuria, and polyphagia. Outside optometrist reported concerns for cataracts. She presented to our Ophthalmology department one week later, who found bilateral cataracts with haziness in all layers and swollen lenses. Labs were done due to findings, glucose was 668 mg/dL with HbA1C >20%. She presented next day to ER, reported no symptoms other than blurry vision but was found to be in mild DKA with a venous pH of 7.285, Ketones 5.41 mmol/L, Glucose 480 mg/dL, and C-peptide 0.32 pmol/mL. Patient was started on insulin infusion at 0.1u/kg/hour and transitioned quickly to subcutaneous insulin. Pancreatic antibodies were significant for positive GAD65 and ZnT8 antibodies. She had cataract surgery for her left eye 1 week after presentation, found to have intumescent white cataract with "hand motion" vision. Vision in left eye is now 20/20 with plans to operate on the right eye in the near future. Literature Review: The prevalence of early diabetic cataracts in the pediatric population can range from 0.7%- 3.4% (1); and more common in female patients (2). Pathophysiology includes defect in the polyol pathway, combined with oxidative stress, leading to increased fluid retention (3). Treatment involves cataract surgery and improved glycemic control. Current ISPAD guidelines recommend initial evaluation for cataracts, and subsequent surveillance concomitant with diabetic retinopathy monitoring biennially with those with good glycemic control (4). Conclusion Diabetic cataracts are extremely rare in the pediatric population. However, diabetes should be considered as an etiology for juvenile cataracts. Given the rapid formation and severity of onset of bilateral cataracts for this patient, early and frequent ophthalmologic surveillance should be recommended for Type 1 diabetes pediatric population. Reference: 1. Šimunović, M, et al (2018). Cataract as early ocular complication in children and adolescents with type 1 diabetes mellitus. International Journal of Endocrinology, 2018, 1–6. 2. Lu, W. -L, et al (2020). High risk of early cataracts in young type 1 diabetes group: A nationwide cohort study. International Journal of Endocrinology, 2020, 1–8. 3. Pollreisz, A, et al (2010). Diabetic cataract pathogenesis, epidemiology and treatment. Journal of Ophthalmology, 2010, 1–8. 4. Donaghue, KC, et al (2018). ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatric Diabetes, 19, 262–274. Presentation: No date and time listed