PRESERVED PROINSULIN SECRETION IN LONG-STANDING TYPE 1 DIABETES.

OBJECTIVE: Recent literature has reported preserved residual beta-cell function (C-peptide "microsecretion") in many individuals with long-standing type 1 diabetes (T1D). However, the concentrations of detectable insulin/C-peptide in the serum are usually very low, and beta-cell mass is typically negligible. Proinsulin is measurable in the early years after diagnosis, consistent with the presence of residual functioning beta cells. However, individuals are not expected to secrete significant amounts of proinsulin beyond the early years after diagnosis. Our primary objective was to measure the prohormone, proinsulin, in a heterogeneous cohort of individuals with long-standing T1D. We also sought to assess whether proinsulin secretion might occur in certain individuals despite the absence of measurable C-peptide. METHODS: Random postmeal proinsulin concentrations were measured in 97 subjects with T1D (disease duration >3 years) recruited from within the T1D Exchange Clinic Network participants who took part in the Residual C-peptide Study. RESULTS: Forty-nine of these subjects had undetectable baseline and stimulated C-peptide (C-peptide [-]), and 48 of them had detectable C-peptide concentrations (C-peptide [+]). All the C-peptide (+) subjects had detectable serum proinsulin. Eight (16%) of the C-peptide (-) subjects had detectable serum proinsulin. CONCLUSION: We report the observation that proinsulin secretion persists in a proportion of individuals with long-standing T1D, even in the absence of measurable C-peptide. It is not yet clear why certain patients with T1D retain the ability to secrete proinsulin many years after diagnosis. ABBREVIATIONS: CP = C-peptide CV = coefficient of variation ELISA = enzyme-linked immunosorbent assay IQR = inter-quartile range MMTT = mixed-meal tolerance test NIBSC = National Institute for Biological Standards and Control PI = proinsulin T1D = type 1 diabetes.

Pharmacotherapy of type 2 diabetes: An update and future directions.

Type 2 diabetes (T2D) is a widely prevalent disease with substantial economic and social impact for which multiple conventional and novel pharmacotherapies are currently available; however, the landscape of T2D treatment is constantly changing as new therapies emerge and the understanding of currently available agents deepens. This review aims to provide an updated summary of the pharmacotherapeutic approach to T2D. Each class of agents is presented by mechanism of action, details of administration, side effect profile, cost, and use in certain populations including heart failure, non-alcoholic fatty liver disease, obesity, chronic kidney disease, and older individuals. We also review targets of novel therapeutic T2D agent development. Finally, we outline an up-to-date treatment approach that starts with identification of an individualized goal for glycemic control then selection, initiation, and further intensification of a personalized therapeutic plan for T2D.

Learning in a virtual world: experience with using second life for medical education.

BACKGROUND: Virtual worlds are rapidly becoming part of the educational technology landscape. Second Life (SL) is one of the best known of these environments. Although the potential of SL has been noted for health professions education, a search of the world's literature and of the World Wide Web revealed a limited number of formal applications of SL for this purpose and minimal evaluation of educational outcomes. Similarly, the use of virtual worlds for continuing health professional development appears to be largely unreported. METHODS: We designed and delivered a pilot postgraduate medical education program in the virtual world, Second Life. Our objectives were to: (1) explore the potential of a virtual world for delivering continuing medical education (CME) designed for physicians; (2) determine possible instructional designs using SL for CME; (3) understand the limitations of SL for CME; (4) understand the barriers, solutions, and costs associated with using SL, including required training; and (5) measure participant learning outcomes and feedback. We trained and enrolled 14 primary care physicians in an hour-long, highly interactive event in SL on the topic of type 2 diabetes. Participants completed surveys to measure change in confidence and performance on test cases to assess learning. The post survey also assessed participants' attitudes toward the virtual learning environment. RESULTS: Of the 14 participant physicians, 12 rated the course experience, 10 completed the pre and post confidence surveys, and 10 completed both the pre and post case studies. On a seven-point Likert scale (1, strongly disagree to 7, strongly agree), participants' mean reported confidence increased from pre to post SL event with respect to: selecting insulin for patients with type 2 diabetes (pre = 4.9 to post = 6.5, P= .002); initiating insulin (pre = 5.0 to post = 6.2, P= .02); and adjusting insulin dosing (pre = 5.2 to post = 6.2, P= .02). On test cases, the percent of participants providing a correct insulin initiation plan increased from 60% (6 of 10) pre to 90% (9 of 10) post (P= .2), and the percent of participants providing correct initiation of mealtime insulin increased from 40% (4 of 10) pre to 80% (8 of 10) post (P= .09). All participants (12 of 12) agreed that this experience in SL was an effective method of medical education, that the virtual world approach to CME was superior to other methods of online CME, that they would enroll in another such event in SL, and that they would recommend that their colleagues participate in an SL CME course. Only 17% (2 of 12) disagreed with the statement that this potential Second Life method of CME is superior to face-to-face CME. CONCLUSIONS: The results of this pilot suggest that virtual worlds offer the potential of a new medical education pedagogy to enhance learning outcomes beyond that provided by more traditional online or face-to-face postgraduate professional development activities. Obvious potential exists for application of these methods at the medical school and residency levels as well.

Self-monitoring of blood glucose with finger tip versus alternative site sampling: effect on glycemic control in insulin-using patients with type 2 diabetes.

OBJECTIVE: This study compared glycemic control in finger tip versus forearm sampling methods of self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODS: One hundred seventy-four insulin-using patients with type 2 diabetes were randomized to SMBG using either finger-tip testing (FT) or forearm alternative site testing (AST) and followed up for 7 months. Hemoglobin A1C (HbA1C) was measured at baseline, month 4, and month 7. The study was designed to test the noninferiority of the AST method for the primary end point of change in HbA1C from baseline to month 7. Adherence with the testing schedule and frequency of hypoglycemic episodes were also measured. RESULTS: The FT (n = 85) and AST (n = 89) groups each had significant decreases in mean HbA1C from baseline to month 7 (FT, -0.4 +/- 1.4%, P = 0.008; AST, -0.3 +/- 1.2%, P = 0.045), and noninferiority between groups was demonstrated with a margin of equivalence of 0.5 (P = 0.043). There was no observable difference in HbA1C change between the groups (P = 0.442). Adherence was better in the FT (87%) than the AST (78%) group (P = 0.003), which may have been because of the difficulty some subjects had in obtaining blood samples for AST. The number of hypoglycemic episodes was too small to assess for a difference between groups. CONCLUSIONS: SMBG by the AST, rather than FT, method did not have a detrimental effect on long-term glycemic control in insulin-using patients with type 2 diabetes. Although adherence with testing was expected to be better in the AST group, it was actually better in the FT group.

Pharmacotherapy of type 2 diabetes: An update.

Type 2 diabetes (T2DM) is a leading cause of morbidity and mortality worldwide and a major economic burden. The prevalence of T2DM is rising, suggesting more effective prevention and treatment strategies are necessary. The aim of this narrative review is to summarize the pharmacologic treatment options available for patients with T2DM. Each therapeutic class is presented in detail, outlining medication effects, side effects, glycemic control, effect on weight, indications and contraindications, and use in selected populations (heart failure, renal insufficiency, obesity and the elderly). We also present representative cost for each antidiabetic category. Then, we provide an individualized guide for initiation and intensification of treatment and discuss the considerations and rationale for an individualized glycemic goal.

Preserved proinsulin production in homozygous protein tyrosine phosphatase nonreceptor type 22 C1858T variant type 1 diabetes: a possible explanation for absence of overt ketoacidosis despite omission of exogenous insulin.

OBJECTIVE: To report a postulated mechanism for resistance to overt ketoacidosis due to prolonged insulin omission in a severely hyperglycemic woman with a 14-year history of autoimmune type 1 diabetes (T1D). METHODS: History, physical examination, laboratory testing, and genotyping were performed. We also review the medical literature pertinent to this patient's phenotype and genotype. RESULTS: Proinsulin levels remained within the normal range (suppressed with hypoglycemia) despite simultaneous almost unmeasurable C-peptide levels during hyperglycemia. We confirmed a homozygous (TT) variant of protein tyrosine phosphatase nonreceptor type 22 (PTPN22) 1858T, a T1D susceptibility gene associated with higher proinsulin levels. CONCLUSION: The extraordinarily preserved proinsulin biological activity may explain the unusual resistance to overt ketoacidosis despite omission of exogenous insulin administration for extended periods of time. The role of the associated PTPN22 1858TT variant remains speculative.