Effect of Meal Frequency and Timing on Insulin Dose and Clock Gene in Type 2 Diabetic Patients
Condition: Type 2 Diabetes
Study type: Interventional

Summary: 
      This study is undertaken to explore in patients with uncontrolled T2D treated with insulin,
      whether a diet with large breakfast and lunch with small dinner (Bdiet) will enhance CG
      expression and will be more effective for weight loss and for achieving glycemic control and
      reduction of total daily insulin dose (first end point), compared to an isocaloric diet with
      6 small meals distributed evenly along the day
    

Detailed description: 
      Obese patients with type 2 diabetes (T2D) and insulin resistance (IR), often require
      sequential increments of total daily insulin dose (TDID). This causes weight gain, worsens
      IR, leading to further increase of TDID and persistent hyperglycemia. In these patients,
      weight loss (WL) and reduction of IR are mandatory in order to achieve glucose control with
      less TDID. Impaired clock gene (CG) expression is linked to obesity and IR in T2D and it was
      shown in animals and T2D patients treated with oral anti-hyperglycemic drugs, that WL diet
      with restricted meal timing to specific hours, restored CG expression and was more effective
      for WL and for reduction of hyperglycemia compared to isocaloric WL diet, (commonly
      recommended for T2D), consisting of small meals randomly distributed along the day.

      The investigators hypothesized that in patients with uncontrolled T2D treated with insulin, a
      diet with large breakfast and lunch with small dinner (Bdiet) will enhance CG expression and
      will be more effective for WL and for achieving glycemic control and reduction of TDID,
      compared to an isocaloric diet with 6 small meals distributed evenly along the day (6Mdiet).

      This will be a randomized parallel, open label clinical study. Thirty overweight and obese
      insulin-treated T2D patients with HbA1c>7.5% will be assigned to 12 weeks of 2 isocaloric
      diets: either Bdiet or 6Mdiet. HbA1c and CG mRNA expression in white blood cells and overall
      daily glycemia measured during 14 days, will be assessed before diet, after 14 days and at
      the end of the diet intervention. The TDID (first end point ) will be adjusted by physician,
      according to the results of self-monitoring of blood glucose on 3 consecutive days at
      baseline and before each of the visits.
    

Intervention name(s): Breakfast Diet (Bdiet); 6Meal Diet (6Mdiet
Intervention type(s): Other; Other
Intervention description(s): The Breakfast Ddiet consist of high-energy breakfast, medium-sized lunch and reduced in energy dinner, with distribution of calories: breakfast 50%, lunch 33% and dinner 17%. In this diet, the investigators will evaluate at baseline and at the end of 12 weeks of diet intervention, the diet efficacy on reducing HbA1c, the total daily insulin dose requirements (TDID), the efficacy on reducing body weight, fasting plasma glucose (FPG) and overall glycemic excursion assessed with continuous monitoring system. The investigators will assess also the Clock Genes mRNA expression in white blood cells. at baseline and after 12 weeks of diet intervention; The 6meal diet (6Mdiet) will consist in the traditional antidiabetic diet, consuming 6 small meals: breakfast, lunch and dinner and 3 snacks, with caloric distribution: breakfast 20%, lunch 25%, dinner 25% and 10% each of the 3 snacks. In this diet, the investigators will evaluate at the beginning and at the end of the study (12 weeks), the diet effects on reducing HbA1c, total daily insulin dose requirements (TDID), and the diet efficacy on reducing body weight, fasting plasma glucose (FPG) and overall glycemic excursion, using continuous monitoring system, The investigators will assess also at baseline and at the end of the diet intervention the Clock Genes mRNA expression in white blood cells.
Other intervention name(s): Bdiet; 6Mdiet
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment