Diabetes type2, Insulin Secretion, Intermittent Fasting, PreDiabetes
Conditions
Brief summary
Type 2 diabetes (T2D) mellitus is a challenge for health care systems as the numbers increases constantly. In 2014, 422 million people had been living with diabetes worldwide. The absolute numbers of people with prediabetes have also grown substantially over 25 years worldwide. In Germany, about 10% of the population has T2D and another 21 % of the population has prediabetes.Overall, 16% of all deaths in Germany are attributable to type 2 diabetes. Macro- and microvascular complications of diabetes imply a significant threat for the patients and are already present in the prediabetic state. Short term and long term complications, the burden of treatment, and reduced quality of life are major burdens of the disease. Accumulating data indicate that currently recommended therapeutic diet regimens in patients with obesity and diabetes are not sustainable on the long term. Novel concepts are therefore urgently needed. T2D occurs when insulin secretion from pancreatic beta-cells cannot sufficiently be increased to compensate for insulin resistance. Causes of beta-cell dysfunction are heterogeneous. In addition, the most important determinants of diabetes remission are the extend of weight loss and restoration of beta-cell function. In the course of diabetes progression, the inability to recover insulin secretion might identify the state of no return to normal glucose tolerance. It is therefore crucial to improve insulin secretion in treatment and prevention of diabetes. Up to now lifestyle intervention trials in prediabetes or pharmacological intervention trials in diabetes did not show improvement of insulin secretion after intervention. However, one recent small human trial shows that intermittent fasting (early time restricted fasting) is able to improve insulin secretion.Currently, there are no trials that examine the effect of intermittent fasting in individuals with a broad range of impaired glucose metabolism (from prediabetes to diabetes). Recently novel subtypes of diabetes and prediabetes with high risk for the early manifestation of diabetes complications have been identified. Currently, prevention strategies for this high risk individuals have not been examined yet. We will study for the first time the effectiveness of 4 weeks intermittent fasting on changes in insulin secretion capacity in subphenotypes of diabetes and in prediabetes.
Interventions
BEHAVIORALIntermittent fasting
The intermittent fasting intervention consists of a decreased daily caloric intake of 400 kcal below individual requirements (Harris Benedict Formula) combined with early time restricted fasting according to the schema 16:8. fasting will be performed over 4 weeks.
BEHAVIORALControl diet
Control group will be advised to reduce daily caloric intake of 400 kcal below individual requirements (Harris Benedict formula)
Sponsors
University Hospital Tuebingen
German Institute of Human Nutrition
Charite University, Berlin, Germany
University Hospital Carl Gustav Carus
University of Leipzig
Ludwig-Maximilians - University of Munich
University Hospital Heidelberg
University of Luebeck
German Diabetes-Center, Leibniz-Institut in Düsseldorf
German Center for Diabetes Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants wil either receive a control diet or join the intermittent fasting group stratified by glycemia (prediabetes/diabetes) as well as by subphenotype.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index (BMI) between 25 - 40 kg/m² * Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. * Subjects with prediabetes (IFG and/or IGT, HbA1c 5,4 % - 6,4 %, subphenotype cluster 3 or 5) or * Subjects with type 2 diabetes mellitus (diagnosed \<5 years prior to screening), HbA1c 6.0% - 9.5%, not receiving insulin or thiazolidinediones, and with an appropriate washout period for all other antidiabetic medications)
Exclusion criteria
* Subjects with diabetes mellitus type 1 (GAD-, IA2-AB positive) * Women during pregnancy and lactation * Treamtent with any medication effecting on glucose metabolism like anti-diabetic drugs or steroids * Subjects with a haemoglobin (Hb) ≤ 11.5 g/dl (for males) and Hb ≤ 10.5 g/dl (for females) at screening * Any pancreatic disease * Medical history of cancer and/or treatment for cancer within the last 5 years. * Known current presence or history of severe neurological or psychiatric diseases, schizophrenia, bipolar disorder * Known history of bariatric surgery * Severe liver or kidney diseases (Alanine Aminotransferase (ALT \[SGPT\]), Aspartate Aminotransferase (AST \[SGOT\]) above 3 x upper limit of normal (ULN) or Glomerular Filtration Rate (eGFR) ≤ 60 ml/min (MDRD formula) * Systemic infection (CRP \> 1 mg/dl) * Severe diabetic complications like chronic kidney disease (CKD), proliferating retinopathy or symptomatic cardiovascular disease * Presence of any contraindication for the conduct of an MRI investigation, such as cardiac pacemakers, ferromagnetic haemostatic clips in the central nervous system, metallic splinters in the eye, ferromagnetic or electronically operated active devices like automatic cardioverter defibrillators, cochlear implants, insulin pumps and nerve stimulators, prosthetic heart valves etc. * Persons with limited temperature sensation and / or elevated sensitivity to warming of the body * Persons with a hearing disorder or a increased sensitivity for loud noises * Claustrophobia * Participation in other clinical trials or observation period of competing trials up to 30 days prior to this study * Refusal to get informed of unexpected detected pathological findings
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in first phase insulin secretion. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effect of intermittent fasting vs. a control diet on glucose stimulated first phase insulin secretion adjusted for insulin sensitivity during an hyperglycemic clamp. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in second phase insulin secretion. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effect of intermittent fasting vs. a control diet on glucose stimulated second phase insulin secretion adjusted for insulin sensitivity during an hyperglycemic clamp. |
| Change in insulin sensitivity. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effect of intermittent fasting vs. a control diet on insulin sensitivity using insulin sensitivity index during an hyperglycemic clamp. |
| Change in BMI. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effect of intermittent vs. a control diet fasting on BMI. |
| Change in liver fat content. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effects of intermittent fasting vs. a control diet on liver fat content (%) measured by magnetic resonance spectroscopy (3 T whole body imaging). |
| Change in pancreatic fat content. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effects of intermittent fasting on pancreatic fat content (%) measured by magnetic resonance spectroscopy (3 T whole body imaging). |
| Change in body fat content. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effects of intermittent fasting vs. a control diet on total adipose tissue (TAT) measured by magnetic resonance tomography (3 T whole body imaging). |
| Change in visceral adipose tissue. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effects of intermittent fasting vs. a control diet on visceral adipose tissue (VAT) measured by by magnetic resonance tomography (3 T whole body imaging) |
| Change in subcutaneous adipose tissue. | Before, after 4 weeks and after 24 weeks of lifestyle intervention. | Effects of intermittent fasting vs. a control diet on subcutaneous adipose tissue (SCAT) measured by by magnetic resonance tomography (3 T whole body imaging) |
Countries
Germany
Contacts
CONTACTAndreas Fritsche, MD
CONTACTMichael Roden, MD
Outcome results
None listed