title: The therapeutic efficacy of intensive medical therapy in ameliorating high-density lipoprotein dysfunction in subjects with type two diabetes.
abstract: BACKGROUND
  To determine whether 12 months of intensive medical therapy (IMT) improves HDL functionality parameters in subjects with type II diabetes (T2D).
  
  
  METHODS
  Retrospective, randomized, and controlled 12-month IMT intervention trial that enrolled 13-subjects with T2D (age 51- years, fasting glucose 147 mg/dL, body mass index [BMI] 36.5 kg/m(2)) and nine healthy control (46-years, fasting glucose 90 mg/dL, BMI 26.5 kg/m2). Subjects with T2D underwent IMT and HDL functionality measures (pro-inflammatory index of high-density lipoprotein (pHDL)), paraoxonase one (PON1), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity were performed on samples at baseline and at 12-months following IMT.
  
  
  RESULTS
  At baseline, pHDL index was significantly higher in subjects with T2D (p < 0.001) and apolipoprotein A-1 levels were significantly lower (p = 0.013) vs.
  
  
  METHODS
  After 12-months, there was a trend for improved pHDL activity (p = 0.083), as indicated by intent-to-treat analysis, but when the non-adherent subject was omitted (per-protocol), significant attenuations in pHDL activity (p = 0.040) were noted; Δ pHDL activity at 12-months was associated with Δ weight (r = 0.62, p = 0.032) and Δ fasting glucose (r = 0.65, p = 0.022). Moreover, PON1 activity significantly improved (p < 0.001). The aforementioned occurred in association with improvements in inflammatory markers (i.e., C-reactive protein & tumor necrosis factor), hemoglobin A1C, fasting glucose, triglycerides, high-density lipoprotein levels and adipokines.
  
  
  CONCLUSIONS
  IMT ameliorates pHDL index and significantly improves anti-oxidative function, as measured by PON1. Improvements in weight and fasting glucose mediated the decrease in pHDL index. Pharmacological aids and lifestyle modification are required to improve cardiovascular risk factors, subsequent mortality risk, and promote T2D remission. Application of either form of therapy alone may only have relatively miniscule effects on the aforementioned factors, in relation to the aggregate.
authors: Departemnt of Endocrinology and Metabolism, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. Kashyas@ccf.org.
authors: Sangeeta
authors: S
authors: Kashyap
authors: Departemnt of Endocrinology and Metabolism, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors: Karim
authors: K
authors: Kheniser
authors: Department of Core Facilities, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors: Ling
authors: L
authors: Li
authors: Department of Quantitative Health Sciences, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors: James
authors: J
authors: Bena
authors: Department of Hepatology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. tkasumov@neomed.edu.|Present address: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, 4209 St. R. 44, PO Box 95, Rootstown, OH, 44272, USA. tkasumov@neomed.edu.
authors: Takhar
authors: T
authors: Kasumov
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D001645:Biguanides / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000628:therapy*; D003927:Diet, Diabetic; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D052456:Hypoalphalipoproteinemias / Q000150:complications / Q000178:diet therapy / Q000188:drug therapy / Q000628:therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D016632:Apolipoprotein A-I; D001645:Biguanides; D007004:Hypoglycemic Agents; D007328:Insulin; D008075:Lipoproteins, HDL
keywords: Intensive medical therapy; Myeloperoxidase; Paraoxonase one; Pro-inflammatory high-density lipoproteins