β-cell function preservation after 3.5 years of intensive diabetes therapy

Lindsay B Harrison, Beverley Adams-Huet, Philip Raskin, Ildiko Lingvay, Lindsay B Harrison, Beverley Adams-Huet, Philip Raskin, Ildiko Lingvay

Abstract

Objective: To assess β-cell function preservation after 3.5 years of intensive therapy with insulin plus metformin (INS group) versus triple oral therapy (TOT group) with metformin, glyburide, and pioglitazone.

Research design and methods: This was a randomized trial of 58 patients with treatment-naïve newly diagnosed type 2 diabetes. All patients were treated with insulin and metformin for a 3-month lead-in period followed by random assignment to the INS or TOT group. β-Cell function was assessed using a mixed-meal challenge test at randomization and 6, 12, 18, 30, and 42 months. Analyses were intention to treat and performed with repeated-measures models.

Results: Completion rates at 3.5 years were 83% in the insulin group and 72% in the TOT group, with good compliance in both groups (87 ± 20% in the INS group vs. 90 ± 15% in the TOT group). β-Cell function was preserved at 3.5 years after diagnosis, with no significant change from baseline or difference between the two groups as measured by area under the curve (AUC) of C-peptide (P = 0.14) or the ratio of C-peptide to glucose AUC (P = 0.7). Excellent glycemic control was maintained in both groups (end-of-study HbA(1c) 6.35 ± 0.84% in the INS group vs. 6.59 ± 1.94% in the TOT group). Weight increased in both groups over time (from 102.2 ± 24.9 kg to 106.2 ± 31.7 kg in the INS group and from 100.9 ± 23.0 kg to 110.5 ± 31.8 kg in the TOT group), with no significant difference between groups (P = 0.35). Hypoglycemic events decreased significantly over time (P = 0.01) but did not differ between groups (P = 0.83).

Conclusions: β-Cell function can be preserved for at least 3.5 years with early and intensive therapy for type 2 diabetes with either insulin plus metformin or triple oral therapy after an initial 3-month insulin-based treatment period.

Trial registration: ClinicalTrials.gov NCT00232583.

Figures

Figure 1
Figure 1
Patient flow chart.
Figure 2
Figure 2
MMCT results. A: AUCG. B: iAUCG. C: AUCC. D: iAUCC. E: Ratio of AUCC to AUCG. F: Ratio of iAUCC to iAUCG. Data are means and 95% CIs.
Figure 3
Figure 3
Safety measures. A. Weight. B: Mild hypoglycemic episodes, defined as any symptoms associated with a capillary glucose level of <70 mg/dL. Data are reported as means and 95% CIs.

References

    1. Cusi K. The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr Diab Rep 2010;10:306–315
    1. Nathan DM, Buse JB, Davidson MB, et al. American Diabetes Association; European Association for Study of Diabetes Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193–203
    1. Turner RC, Cull CA, Frighi V, Holman RR, UK Prospective Diabetes Study (UKPDS) Group Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA 1999;281:2005–2012
    1. Steffes MW, Sibley S, Jackson M, Thomas W. β-Cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 2003;26:832–836
    1. UK Prospective Diabetes Study (UKPDS) Group Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–853
    1. Brown JB, Nichols GA. Slow response to loss of glycemic control in type 2 diabetes mellitus. Am J Manag Care 2003;9:213–217
    1. Gleason CE, Gonzalez M, Harmon JS, Robertson RP. Determinants of glucose toxicity and its reversibility in the pancreatic islet beta-cell line, HIT-T15. Am J Physiol Endocrinol Metab 2000;279:E997–E1002
    1. Garvey WT, Olefsky JM, Griffin J, Hamman RF, Kolterman OG. The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes 1985;34:222–234
    1. Ilkova H, Glaser B, Tunçkale A, Bagriaçik N, Cerasi E. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment. Diabetes Care 1997;20:1353–1356
    1. Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care 2004;27:1028–1032
    1. Weng J, Li Y, Xu W, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 2008;371:1753–1760
    1. Chen HS, Wu TE, Jap TS, Hsiao LC, Lee SH, Lin HD. Beneficial effects of insulin on glycemic control and beta-cell function in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy. Diabetes Care 2008;31:1927–1932
    1. Kahn SE, Haffner SM, Heise MA, et al. ADOPT Study Group Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427–2443
    1. Lingvay I, Kaloyanova PF, Adams-Huet B, Salinas K, Raskin P. Insulin as initial therapy in type 2 diabetes: effective, safe, and well accepted. J Investig Med 2007;55:62–68
    1. Lingvay I, Legendre JL, Kaloyanova PF, Zhang S, Adams-Huet B, Raskin P. Insulin-based versus triple oral therapy for newly diagnosed type 2 diabetes: which is better? Diabetes Care 2009;32:1789–1795
    1. Tura A, Ludvik B, Nolan JJ, Pacini G, Thomaseth K. Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT. Am J Physiol Endocrinol Metab 2001;281:E966–E974
    1. Kilpatrick ED, Robertson RP. Differentiation between glucose-induced desensitization of insulin secretion and beta-cell exhaustion in the HIT-T15 cell line. Diabetes 1998;47:606–611
    1. Yki-Järvinen H. Thiazolidinediones. N Engl J Med 2004;351:1106–1118
    1. Finegood DT, McArthur MD, Kojwang D, et al. β-Cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death. Diabetes 2001;50:1021–1029
    1. Juhl CB, Hollingdal M, Pørksen N, Prange A, Lönnqvist F, Schmitz O. Influence of rosiglitazone treatment on beta-cell function in type 2 diabetes: evidence of an increased ability of glucose to entrain high-frequency insulin pulsatility. J Clin Endocrinol Metab 2003;88:3794–3800
    1. Ovalle F, Bell DS. Effect of rosiglitazone versus insulin on the pancreatic β-cell function of subjects with type 2 diabetes. Diabetes Care 2004;27:2585–2589
    1. Xiang AH, Peters RK, Kjos SL, et al. Effect of pioglitazone on pancreatic β-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes 2006;55:517–522

Source: PubMed

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