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J Clin Endocrinol Metab. 2014 Jun;99(6):2225-32. doi: 10.1210/jc.2013-4519. Epub 2014 Feb 25.

Glucose turnover after replacement of usual therapy by insulin in insulin-naive type 2 diabetes subjects.

Author information

  • 1Metabolic 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 The effects on glucose turnover when these agents are acutely withdrawn are poorly understood and may be of importance when insulin therapy is initiated.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 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). 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.

[PubMed - indexed for MEDLINE]
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