title: Diet is critical for prolonged glycemic control after short-term insulin treatment in high-fat diet-induced type 2 diabetic male mice.
abstract: BACKGROUND
  Clinical studies suggest that short-term insulin treatment in new-onset type 2 diabetes (T2DM) can promote prolonged glycemic control. The purpose of this study was to establish an animal model to examine such a "legacy" effect of early insulin therapy (EIT) in long-term glycemic control in new-onset T2DM. The objective of the study was to investigate the role of diet following onset of diabetes in the favorable outcomes of EIT.
  
  
  METHODS
  As such, C57BL6/J male mice were fed a high-fat diet (HFD) for 21 weeks to induce diabetes and then received 4 weeks of daily insulin glargine or sham subcutaneous injections. Subsequently, mice were either kept on the HFD or switched to a low-fat diet (LFD) for 4 additional weeks.
  
  
  RESULTS
  Mice fed a HFD gained significant fat mass and displayed increased leptin levels, increasing insulin resistance (poor HOMA-IR) and worse glucose tolerance test (GTT) performance in comparison to mice fed a LFD, as expected. Insulin-treated diabetic mice but maintained on the HFD demonstrated even greater weight gain and insulin resistance compared to sham-treated mice. However, insulin-treated mice switched to the LFD exhibited a better HOMA-IR compared to those mice left on a HFD. Further, between the insulin-treated and sham control mice, in spite of similar HOMA-IR values, the insulin-treated mice switched to a LFD following insulin therapy did demonstrate significantly better HOMA-B% values than sham control and insulin-treated HFD mice.
  
  
  CONCLUSIONS
  Early insulin treatment in HFD-induced T2DM in C57BL6/J mice was only beneficial in animals that were switched to a LFD after insulin treatment which may explain why a similar legacy effect in humans is achieved clinically in only a portion of cases studied, emphasizing a vital role for diet adherence in diabetes control.
authors: Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.
authors: Aili
authors: A
authors: Guo
authors: Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.
authors: Nigel A
authors: NA
authors: Daniels
authors: Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.
authors: Jean
authors: J
authors: Thuma
authors: Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.
authors: Kelly D
authors: KD
authors: McCall
authors: Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.
authors: Ramiro
authors: R
authors: Malgor
authors: Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.
authors: Frank L
authors: FL
authors: Schwartz
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004032:Diet; D059305:Diet, High-Fat; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin
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