Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial.
Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34(+) and CD34(+)KDR(+) progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p < 0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21-1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41-19.5, p < 0.02). Baseline CD34(+)KDR(+) were higher in rs753482AA (166.2 ± 154.0 × 10(6) events) than in rs753482AC+CC (63.1 ± 26.9 × 10(6) events, p < 0.01). At the end of the study, the highest circulating CD34(+)KDR(+) were found in IIT rs753482AA (246.9 ± 194.0 × 10(6) events) while the lowest levels were found in SC rs753482AC+CC (70.9 ± 45.0 × 10(6) events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.
Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science Division, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. piatti.piermarco@hsr.it
Pier Marco
PM
Piatti
Enrico
E
Marone
Manuela
M
Mantero
Emanuela
E
Setola
Elena
E
Galluccio
Pietro
P
Lucotti
Ermal
E
Shehaj
Valentina
V
Villa
Francesca
F
Perticone
Massimo
M
Venturini
Alessio
A
Palini
Flavio
F
Airoldi
Ezio
E
Faglia
Alessandro
A
Del Maschio
Antonio
A
Colombo
Roberto
R
Chiesa
Emanuele
E
Bosi
Lucilla D
LD
Monti
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005121:Extremities / Q000098:blood supply; D005215:Fasting; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D015994:Incidence; D007328:Insulin / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D058729:Peripheral Arterial Disease / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000502:physiology; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III