Beneficial Effects of Insulin Versus Sulphonylurea on Insulin Secretion and Metabolic Control in Recently Diagnosed Type 2 Diabetic Patients

Clinical Care/Education/Nutrition

Michael Alvarsson, MD, PHD1, Göran Sundkvist, MD, PHD2, Ibe Lager, MD, PHD3, Marianne Henricsson, MD, PHD4, Kerstin Berntorp, MD, PHD2, Eva Fernqvist-Forbes, MD, PHD5, Lars Steen, MD6, Gunilla Westermark, MD, PHD7, Per Westermark, MD, PHD7, Thomas Örn, MD8 and Valdemar Grill, MD, PHD1

1 Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden; 2 Department of Endocrinology, Malmö University Hospital, Malmö, Sweden; 3 Department of Medicine, Kristianstad Hospital, Kristianstad, Sweden; 4 Department of Ophthalmology, Helsingborg Hospital, Helsingborg, Sweden; 5 Department of Medicine, Visby Hospital, Visby, Sweden; 5 Department of Medicine, Mälarsjukhuset, Eskilstuna, Sweden; 6 Division of Cell Biology, Faculty of Health Sciences, Linköping, Sweden; 7 Department of Medicine, Blekingesjukhuset, Karlskrona, Sweden

Address correspondence and reprint requests to Michael Alvarsson, Department of Endocrinology and Diabetology, Karolinska Hospital, SE-171 76 Stockholm, Sweden. E-mail: michael.alvarsson@ks.se

OBJECTIVE—To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment.

RESEARCH DESIGN AND METHODS—ß-Cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0–2 years before inclusion in a Swedish multicenter randomized clinical trial.

Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5–10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2–3 days of temporary withdrawal of treatment.

RESULTS—After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 ± 0.08 nmol/l, whereas it was decreased by 0.12 ± 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups.

After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA1c levels decreased significantly during the first year in both groups; however, at the end of the second year, HbA1c had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA1c during the second year was significant between groups, P < 0.02. A questionnaire indicated no difference in well-being related to treatment.

CONCLUSIONS—Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.

Abbreviations: GADA, GAD antibody • IA2, insulinoma-associated protein 2 • IA-2A, IA2 antigen • ICA, islet cell anitbody • IAPP, islet amyloid polypeptide • LADA, latent autoimmune diabetes in adults • RIA, radioimmunoassay • UKPDS, U.K. Prospective Diabetes Study

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