Effects of Standardized Meals on the Metabolic, Hormonal and Inflammatory Responses in Human
Condition: Diabetes Mellitus
Study type: Interventional

Summary: 
      Meal composition is important for blood sugar levels in patients with diabetes. The aim of
      this study is to investigate if a meal composition of fat, protein and carbohydrate is
      important for the hormonal and inflammatory responses Patients with type 1 and type 2
      diabetes and healthy controls will be included in the study. At four different occasions the
      participants will receive lunch with the same amount of calories but different composition of
      fat, protein, carbohydrate and fiber. Blood samples will be taken before and after the meals.
      The participants will estimate their satiety. In addition participant will fill in
      questionnaires about their food habits and wellbeing.

      This study is the first study to compare both hormonal and inflammatory responses, as well as
      psychological aspect of the meals, after meals with different composition. Results from this
      study will help to make recommendation about meal composition which is beneficial for
      patients with diabetes type 1 and type 2.
    

Detailed description: 
      Food is an important part of human beings life. During most part of human beings history the
      shortage of food has been a problem. Today the shortage of food is unknown phenomena in the
      industrial countries. Instead human being is facing a challenge in obesity epidemic. The
      number of obese persons has increased since 1980 in all industrial countries. Today only 20 -
      25 % of the population in the US has a normal body mass index (BMI). The populations in
      Europe and Asia are following the same trend. It is known that increased waist (in women > 80
      cm and in men > 94 cm) are correlated to insulin resistance, especially in liver because of
      increased hepatic fat storage. Increased prevalence of obese persons is followed by increased
      prevalence of patients with impaired glucose tolerance with increased risk for diabetes type
      2, cardiovascular disease and cancer.

      It is known that impaired glucose tolerance and diabetes type 2 can be prevented efficiently
      with weight loss, reduced total intake of fat and carbohydrate, increased intake of fiber and
      physical activity. Three popular diets, 1) low fat, 2) low carbohydrate (high-protein and
      high-fat) and 3) low glycemic load, have recently received much attention. Long term studies
      of these different diets have shown inconsistent results. There is a discussion today if a
      better metabolic control is achieved with low-carbohydrate diet compared to low-fat diet in
      patients with diabetes type 2 compared to the diet recommended by Swedish National Food
      Administration. In regards of dietary composition, hyperglycemia and dyslipidemia is
      determined by the amount and quality of ingested carbohydrates and dietary fats. It has been
      suggested that postprandial hyperglycemia and hypertriglyceridemia triggers oxidative stress
      and causes inflammation, metabolic alterations associated with endothelial dysfunction.

      An important aspect of satisfaction after a meal is the feeling of satiety. Subjective
      feelings of hunger are also obviously related to initiation of food behaviors such as intake
      of snacks. Neophobia, the fear of new or unfamiliar foods, can also be related to the success
      or failure of food related behavior change. These feelings of satiety are in turn related to
      factors such as blood glucose levels. Thus the effect of ingested macronutrients on the
      postprandial glycemic response is one potential mechanism by which foods may affect satiety.
      Compared to fats and proteins, dietary carbohydrates may have the greatest effect on
      postprandial glycemia and insulinemia, and may therefore elicit greater appetitive ratings
      several hours after consumption compared to lower-glycemic meals. Lately some neuroendocrine
      hormones (ghrelin, resistin etc) and adipokines (leptin and adiponectin) have received
      attention as regulators of satiety and plausible causes of obesity. The effect of high-fat,
      high-protein or low-carbohydrate meals on these hormones are not known.

      The adverse effects of factors such as chronic stress and depression on general health have
      been documented for many decades. Apart from having an influence on specific health
      behaviors, other interacting influences such as general life stress appear to be related
      directly to alterations in pro-inflammatory and hemostasis processes. The physiological
      pathways by which psychosocial factors might exert both positive and negative effects on
      health are numerous and incompletely understood. However, examples of particular interest are
      findings that suggest that even in relatively healthy persons, chronic negative appraisals of
      minor life events (hassles) are associated with increased circulating levels of inflammatory
      factors, whereas persistent positive appraisals of minor life events (uplifts) are associated
      with decreased levels of such factors. It is thus important to consider general Quality of
      Life, as well as food-related quality of life together with health and taste attitudes and
      nutritional knowledge.

      Finally the gender aspect is also of importance. Previously it has been presumed that the
      inflammatory and hormonal responses to different diets are the same in men and women. There
      are known biological and hormonal differences between men and women. One may question why
      women get heart infarction later in life compared to men and if the risk factors including
      inflammatory responses, cholesterol levels and other hormonal changes after different diets
      are the same in men and women.

      The aim of this study is to compare the high-fat, high-protein and low-carbohydrate meal
      regarding post prandial glucose and triglycerides concentrations in blood as well as the fast
      inflammatory response, oxidative stress and appetite regulating hormones in healthy subjects
      and patients with diabetes. Gender differences will be investigated. In general this study
      will provide information on which meal compositions that are beneficial for patients with
      diabetes and healthy subjects. Another aim of this study is to investigate if the
      psychosocial aspect of the meal such as health locus of control, neophobia, satiety and food
      related Quality of Life is important for the hormonal responses after the meals.

      Hypothesis :

        1. Meal with high concentration of fiber (15 g) is beneficial for metabolic control in
           patients with diabetes.

        2. Low-carbohydrate meal is beneficial for the metabolic control in patients with diabetes.

        3. High-fat meal results in hyperlipidemia which worsens hepatic insulin sensitivity and
           increases the oxidative stress.

        4. High-protein and high-fat meal give earlier satiety and lower blood sugar levels
           compared to high carbohydrate diet.

        5. The perception of the meal affects the metabolic control.

      Design:

      30 patients with type 1 (T1DM) and 30 patients with type 2 diabetes (T2DM)and 30 healthy
      Controls (HC) will be included in the study. At four different occasions the participants
      will eat lunch with different composition of fat, protein, carbohydrate and fiber. All groups
      are divided in subgroups of men and women. Healthy subjects will receive an oral glucose
      tolerance test before they are included in the study.

      The composition of the meals is: Low-fat / high-carbohydrate meal (18 Eenergi % (E%)
      proteins, 28 E% fat and 54% carbohydrates), high-fat meal (18 E% protein, 50 E% fat and 31 E%
      carbohydrate), high-protein meal (40 E% protein, 30 E% fat and 30 E% carbohydrates) and
      low-fat / high-carbohydrate and high fiber (18 E% proteins, 28 E% fat and 54% carbohydrates
      and 15 gram of fibers).

      Before the study and before the last meal we will measure the waist/hip ratio, BMI and body
      composition (Bioimpedance). Before the study the participant will document their daily meals
      during three days. Patients with diabetes should at the same time also document their blood
      sugar levels (7 times per day, fasting levels, levels before and 2 hours after lunch and
      dinner and before they go to sleep). Before the other occasions patients will measure their
      blood sugar levels during one day (7 times).

      The participants will eat a standardized breakfast at home in the morning before
      participating in the study. They will eat one of following meals as lunch at 11:30 am: a
      low-fat and high-carbohydrate diet recommended by Swedish National Food Administration, a
      high-protein meal, a high-fat meal or a low-fat and high-carbohydrate diet with 15 g of
      fibers. At each occasions blood samples will be taken 30 minutes and 5 minutes before the
      lunch and on 30-minute intervals for the following four hours after the lunch. The blood
      samples will be analysed for hormones regulating blood sugar levels, appetite regulating
      hormones, marker of oxidative stress and markers of inflammation and endothelia dysfunctions.
      We have previously shown that insulin sensitivity in liver can be estimated measuring Insulin
      like Growh factor- I (IGF-I) and Insulin like Growth Factor Binding Protein-1 (IGFBP-1).
      These hormones will be analyzed in blood samples.

      The participants will estimate their satiety and their desire to eat in parallel at the time
      blood samples are withdrawn. At each occasion participants will fill in forms about their
      general perception of the food and how they estimate their own health.

      In case a participant do not follow throughout the whole study the results will be analyzed
      and used in group wise comparisons.
    

Intervention name(s): Meals
Intervention type(s): Other
Intervention description(s): At 4 different occasions the participants will receive meals with the same amount of calories and different composition of fat, protein, carbohydrate and fiber.The composition of the meals is: Low-fat / high-carbohydrate meal (18 E% proteins, 28 E% fat and 54% carbohydrates), high-fat meal (18 E% protein, 50 E% fat and 31 E% carbohydrate), high-protein meal (40 E% protein, 30 E% fat and 30 E% carbohydrates) and low-fat / high-carbohydrate and high fiber (18 E% proteins, 28 E% fat and 54 E% carbohydrates and 15 gram of fibers).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: high fat; high protein; high carbohydrate; insulin; glucose