Influence of Dairy Protein Breakfast on Overall Daily Glycemia, Weight Loss HbA1c and Clock Genes mRNA Expression, in Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Clock genes mRNA expression
研究概览
简要总结
This study in T2D patients is undertaken to evaluate the effect of previously studied 3Meals Diet, high energy breakfast (Bdiet) with milk and dairy proteins (MBdiet) versus isocaloric diet with same meal distribution but with other sources of protein (OBdiet) overall postprandial glycemia (PPG), weight loss (WL), HbA1c, CG expression and on PPG, insulin, C-peptide, GLP-1, gut peptide YY (PYY), cholecystokinin (CCK), ghrelin, dipeptidyl peptidase-4 plasma activity (DPP-4) and appetite responses after high protein breakfast. challenge including milk and dairy products (MBdiet) and after breakfast challenge with same protein content but different source of protein (OBdiet)
详细描述
Increased circadian glucose excursions and overall postprandial glycemia (PPG) are linked to HbA1c and cardiovascular risk in T2D.
Most of the metabolic pathways involved in PPG i.e. secretion of insulin and glucagon-like peptide-1 (GLP-1), are controlled by circadian clock genes (CG). However, the CG regulation is bidirectional, indeed high protein breakfast (B), by increasing insulin and GLP-1 upregulate CG expression leading to reduced overall PPG, HbA1c and weight loss (WL) in T2D. Furthermore in recent study the investigators have shown that in type 2 diabetic patient treated with insulin a diet with 3 Meal Diet consisting in high energy and protein breakfast, medium sized lunch and low energy dinner, with selective time restriction from carbohydrate consumption after 15:00, designed as Bdiet; was more effective approach for reduction of overall PPG, HbA1c and for upregulation of Clock Genes (CG) mRNA expression compared to isocaloric 6 Meal Diet, with calories and macronutrient evenly distributed along the day in three main meals and 3 snack in between.
As the beneficial effects of high energy and protein breakfast in 3Meal diet on the reduction of body weight, overall glycemia and up regulation CG expression, have been demonstrated, in recent studies, we hypothesized that some sources of protein in the breakfast may exert be more beneficial than other source of protein on body weight, PPG, HbA1c and on CG expression Milk consumption is linked to lower risk for obesity and T2D. In acute studies, the addition of milk to carbohydrates in B, displayed greater lowering effect of glucose response after breakfast, lunch and dinner compared with other protein sources.
However the effect of a diet 3Mdiet with high energy and dairy protein breakfast (MBdiet), on overall PPG, weight loss HbA1c, the effect on effect on circadian clock genes and AMPK mRNA expression and on the postprandial glucose, insulin, C-peptide, GLP-1, PYY, CCK, ghrelin, DPP4 plasma activity and appetite has never been explored and never were compared to isocaloric 3Mdiet with other then dairy protein source of protein (OBdiet) in long term study in T2D individuals .
The investigators hypothesize that a diet with high energy and protein breakfast consisting on milk and dairy proteins (MBdiet), by enhancing clock gene expression will lead to more efficient weight loss reduction of overall PPG, and glucose control (HbA1c), compared to a diet with other (non dairy) proteins in the breakfast (OBdiet). The investigators also hypothesize that the dairy breakfast effects in MBdiet may be mediated, at least in part, by integration of events that promote greater postprandial glucose insulin, C-peptide, GLP-1, PYY, and CCK, and greater suppression of ghrelin appetite and DPP4 plasma activity,
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients diagnosed with T2D < 20 years;
- •HgA1c ≥ 7.0 %.
- •BMI - 28-40 kg/m2
- •Men and women 30 -75 years of age inclusive.
- •Normal liver, kidney and thyroid functions, negative urinary microalbumin test (urMA) and estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m
- •Type 2 diabetes controlled with diet and lifestyle alone or with antidiabetic treatment other than insulin (i.e. buguanides, sulfonylureas, glinides, SGLT2 inhibitors, DPP4 inhibitors, GLP-1 analogs), with stable doses for at least 3 months before entering the study.
- •Stable weight (less than 5% change in body weight in last 3 months before the study - determined by self-reporting or documentation in clinical records).
- •Concomitant medication i.e. antihypertensive, anti-lipidemic, anti-thrombotic drugs will be allowed also on stable dose for at least 3 months before the beginning of the trial.
- •Patients that usually wake up between 06:00 and 08:00 and go to sleep between 22:00 and 24:
- •Should not have shift work within 6 month of the study and should not have crossed time zones within 2 weeks of the study.
排除标准
- •Type 1 diabetes or secondary forms of diabetes.
- •Patients with latent autoimmune diabetes in adults (LADA).
- •Treatment with insulin.
- •Serum creatinine level >2mg/dl. Renal dysfunction: (estimated glomerular filtration rate eGFR < 45 mL/min/1.73 m2).
- •Hepatic dysfunction: liver disease or transaminase levels > 2.5-fold above normal. Major illness with life expectancy < 5 years.
- •Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer). Those taking psychotropic, anorectic medication, steroid treatment or with illicit drug abuse or alcoholism within one year prior to study onset. Pregnancy or lactation. Known hypersensitivity to milk components or lactose intolerance. Night or rotating shift workers or those who crossed more than 2 time zones during the 2- week period prior to study onset. No change in medication or nutrition supplements or physical activity will be made during the study. Not able to give informed consent
研究组 & 干预措施
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Ghrelin (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Continuous glucose monitoring CGM (Device)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Clock Genes m RNA expression (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Postprandial Glucose (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Postprandial Insulin (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Plasma GLP-1 (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: DPP4 plasma activity (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Plasma CCK (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Plasma PYY (Diagnostic Test)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Body Weight (Other)
MBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.
干预措施: Blood levels of HbA1c (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Continuous glucose monitoring CGM (Device)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Clock Genes m RNA expression (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Postprandial Glucose (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Postprandial Insulin (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Plasma GLP-1 (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: DPP4 plasma activity (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Plasma CCK (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Plasma PYY (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Body Weight (Other)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Blood levels of HbA1c (Diagnostic Test)
OBdiet
This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.
干预措施: Ghrelin (Diagnostic Test)
结局指标
主要结局
Clock genes mRNA expression
时间窗: two weeks
The effect of the two diets (MBdiet and OBdiet) will be compared on their efficacy on changing the clock genes expression
次要结局
- Continuous Glucose Monitoring (CGM)(two weeks)
- Body Weight(3 months)
- HbA1c(3 months)
研究者
Daniela Jakubowicz
Professor
Tel Aviv University