RESUMEN
AIM: In patients with type 2 diabetes, insulin therapy is commonly initiated with either a single dose of basal insulin or twice-daily premixed (basal plus prandial) insulin despite no widely accepted recommendation. We compared the glycaemic control, as measured by a change in HbA1c, of intensive mixture therapy (IMT), a basal plus prandial regimen using insulin lispro mixture 50/50 (50% lispro and 50% NPL) before breakfast and lunch and insulin lispro mixture 25/75 (25% lispro and 75% NPL) before dinner, vs. once-daily insulin glargine therapy, while continuing patients on oral antidiabetes medications. METHODS: Following inadequate glycaemic control (HbA1c 1.2-2.0 times the upper limit of normal) and at least 2 months of two or more oral antidiabetes agent therapy, 60 insulin-naïve patients with type 2 diabetes were randomized to one of the insulin regimens for 4 months with crossover to the alternative regimen for an additional 4 months. Glycaemic goals were preprandial blood glucose <120 mg/dl (6.7 mmol/l) and 2-h postprandial blood glucose <180 mg/dl (10.0 mmol/l). The insulin dose was optimized by investigators without forced titration. RESULTS: Mean prestudy (baseline) HbA1c for all patients was 9.21 +/- 1.33% (+/-s.d.). IMT compared to glargine resulted in both a lower endpoint in HbA1c (7.08 +/- 0.11% vs. 7.34 +/- 0.11%; p = 0.003) and a greater change in HbA1c from pretherapy (-1.01 +/- 0.10% vs. -0.75 +/- 0.10%; p = 0.0068). Forty-four per cent of patients receiving IMT and 31% of patients receiving insulin glargine achieved HbA1c < or = 7%. Two-hour postprandial glucose values (for all three meals) and predinner glucose values were significantly less with IMT than with insulin glargine (p = 0.0034, 0.0001, 0.0066 and 0.0205). Overall hypoglycaemia throughout the complete treatment period was infrequent (IMT vs. Glargine: 3.98 +/- 4.74 vs. 2.57 +/- 3.22 episodes/patient/30 days, p = 0.0013), and no severe hypoglycaemia was observed during the study with either therapy. There was no difference in nocturnal hypoglycaemia between the two therapies. The mean insulin dose at the end of therapy was greater for IMT than for once-daily insulin glargine (0.353 +/- 0.256 vs. 0.276 +/- 0.207 IU/kg, p = 0.0107). CONCLUSIONS: In combination with oral antidiabetes agents, multiple daily injections of a basal plus prandial insulin IMT regimen (using premixed insulin lispro formulations) resulted in greater improvements and a lower endpoint in HbA1c compared with a basal-only insulin regimen. IMT also resulted in improved postprandial blood glucose control at each meal and enabled administration of a greater daily dose of insulin, which most likely contributed to these lower HbA1c measures. This greater reduction in HbA1c with IMT is accompanied by a small increased occurrence of mild hypoglycaemia but without any severe hypoglycaemia. Greater consideration should be given to initiating insulin as a basal plus prandial regimen rather than a basal-only regimen.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/análogos & derivados , Adulto , Anciano , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Esquema de Medicación , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/uso terapéutico , Insulina Glargina , Insulina de Acción Prolongada , Masculino , Persona de Mediana EdadRESUMEN
Oxidative stress, through the production of reactive oxygen species (ROS), has been proposed as the root cause underlying the development of insulin resistance, beta-cell dysfunction, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). It has also been implicated in the progression of long-term diabetes complications, including microvascular and macrovascular dysfunction. Excess nourishment and a sedentary lifestyle leads to glucose and fatty acid overload, resulting in production of ROS. Additionally, reaction of glucose with plasma proteins forms advanced glycation end products, triggering production of ROS. These ROS initiate a chain reaction leading to reduced nitric oxide availability, increased markers of inflammation and chemical modification of lipoproteins, all of which may increase the risk of atherogenesis. With the postulation that hyperglycaemia and fluctuations in blood glucose lead to generation of ROS, it follows that aggressive treatment of fasting and postprandial hyperglycaemia is important for prevention of micro and macrovascular complications in T2DM.