H Thabit1, K Kumareswaran, A Haidar, L Leelarathna, K Caldwell, D Elleri, J M Allen, M Nodale, M E Wilinska, N C Jackson, A M Umpleby, M L Evans, R Hovorka. 1. Metabolic Research Laboratories (H.T., K.K., L.L., K.C., D.E., J.M.A., M.N., M.E.W., M.L.E., R.H.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, and Department of Paediatrics (D.E., J.M.A., M.E.W., R.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Centre for Intelligent Machines (A.H.), McGill University, Montreal, Quebec H3A 0E9, Canada; and Postgraduate Medical School (N.C.J., A.M.U.), University of Surrey, Guildford GU2 7TE, United Kingdom.
Abstract
CONTEXT: Discontinuation of anti-hyperglycemic oral agents and initiation of insulin is recommended in certain clinical situations for inpatients with type 2 diabetes (T2D). The effects on glucose turnover when these agents are acutely withdrawn are poorly understood and may be of importance when insulin therapy is initiated. OBJECTIVE: Our objective was to investigate alterations in glucose turnoverafter acute withdrawal of noninsulin therapy. DESIGN AND SETTING: This was a randomized crossover study at a clinical research facility. PARTICIPANTS: Participants included 12 insulin-naive subjects with T2D. METHODS: Subjects attended two 24-hour visits. Standard therapy was discontinued and replaced by closed-loop insulin delivery during the intervention visit. Usual anti-hyperglycemic therapy was continued during the control visit. Systemic glucose appearance (Ra) and glucose disposal (Rd) were measured using a tracer dilution technique with iv [6,6-(2)H2]glucose. RESULTS:Plasma glucose profiles during both visits were comparable (P = .48). Glucose Ra increased during the day (21.4 [19.5, 23.5] vs 18.6 [17.0, 21.6) μmol/kg/min, P = .019) and decreased overnight (9.7 [8.5, 11.4] vs 11.6 [10.3, 12.9] μmol/kg/min, P = .004) when the usual therapy was discontinued and replaced with insulin. Increased daytime glucose Rd (21.2 [19.4, 23.9] vs 18.8 [18.3, 21.7] μmol/kg/min, P = .002) and decreased overnight Rd (10.4 [9.1, 12.0] vs 11.8 [10.7, 13.7] μmol/kg/min, P = .005) were observed when the usual therapy was discontinued, whereas daytime peripheral insulin sensitivity was reduced (47.8 [24.8, 66.1] vs 62.5 [34.8, 75.8] nmol/kg/min per pmol/L, P = .034). CONCLUSION: In T2D, acute discontinuation of anti-hyperglycemic therapy and replacement with insulin increases postprandial Ra and reduces peripheral insulin sensitivity. Insulin dose initiation may need to compensate for these alterations.
RCT Entities:
CONTEXT: Discontinuation of anti-hyperglycemic oral agents and initiation of insulin is recommended in certain clinical situations for inpatients with type 2 diabetes (T2D). The effects on glucose turnover when these agents are acutely withdrawn are poorly understood and may be of importance when insulin therapy is initiated. OBJECTIVE: Our objective was to investigate alterations in glucose turnover after acute withdrawal of noninsulin therapy. DESIGN AND SETTING: This was a randomized crossover study at a clinical research facility. PARTICIPANTS: Participants included 12 insulin-naive subjects with T2D. METHODS: Subjects attended two 24-hour visits. Standard therapy was discontinued and replaced by closed-loop insulin delivery during the intervention visit. Usual anti-hyperglycemic therapy was continued during the control visit. Systemic glucose appearance (Ra) and glucose disposal (Rd) were measured using a tracer dilution technique with iv [6,6-(2)H2]glucose. RESULTS: Plasma glucose profiles during both visits were comparable (P = .48). GlucoseRa increased during the day (21.4 [19.5, 23.5] vs 18.6 [17.0, 21.6) μmol/kg/min, P = .019) and decreased overnight (9.7 [8.5, 11.4] vs 11.6 [10.3, 12.9] μmol/kg/min, P = .004) when the usual therapy was discontinued and replaced with insulin. Increased daytime glucose Rd (21.2 [19.4, 23.9] vs 18.8 [18.3, 21.7] μmol/kg/min, P = .002) and decreased overnight Rd (10.4 [9.1, 12.0] vs 11.8 [10.7, 13.7] μmol/kg/min, P = .005) were observed when the usual therapy was discontinued, whereas daytime peripheral insulin sensitivity was reduced (47.8 [24.8, 66.1] vs 62.5 [34.8, 75.8] nmol/kg/min per pmol/L, P = .034). CONCLUSION: In T2D, acute discontinuation of anti-hyperglycemic therapy and replacement with insulin increases postprandial Ra and reduces peripheral insulin sensitivity. Insulin dose initiation may need to compensate for these alterations.
Authors: Lifeng Wang; Nasa Sinnott-Armstrong; Alexandre Wagschal; Abigail R Wark; Joao-Paulo Camporez; Rachel J Perry; Fei Ji; Yoojin Sohn; Justin Oh; Su Wu; Jessica Chery; Bahareh Nemati Moud; Alham Saadat; Simon N Dankel; Gunnar Mellgren; Divya Sri Priyanka Tallapragada; Sophie Madlen Strobel; Mi-Jeong Lee; Ryan Tewhey; Pardis C Sabeti; Anne Schaefer; Andreas Petri; Sakari Kauppinen; Raymond T Chung; Alexander Soukas; Joseph Avruch; Susan K Fried; Hans Hauner; Ruslan I Sadreyev; Gerald I Shulman; Melina Claussnitzer; Anders M Näär Journal: Cell Date: 2020-10-14 Impact factor: 41.582
Authors: D Elleri; M Biagioni; J M Allen; K Kumareswaran; L Leelarathna; K Caldwell; M Nodale; M E Wilinska; A Haidar; P Calhoun; C Kollman; N C Jackson; A M Umpleby; C L Acerini; D B Dunger; R Hovorka Journal: Diabetes Obes Metab Date: 2015-10-09 Impact factor: 6.577