Prolonged Fasting on Glucose Metabolism and Hormonal Regulation in Healthy, Obese and Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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In a previous study investigating the effects of intermittent fasting, our research group found evidence for higher glucose excursions and a reduced insulin response after a 36 hour fasting period as compared to an overnight fasting period in healthy subjects. The aim of this research project is to investigate the effect of short and midterm fasting (12 hours versus 36 hours) on glucose metabolism, glucose regulatory hormones, insulin secretion and resting energy expenditure in healthy and obese people as well as in patients with type 2 diabetes.

Detailed Description
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In this clinical study, we want to examine the effects of different fasting periods (12 hours versus 36 hours) on blood sugar levels and other metabolic parameters and hormones. For this the following investigations are carried out: Oral glucose tolerance test with detailed laboratory evaluation Bio-impedance measurement to determine body composition (muscle and fat mass) The examinations are carried out on 4 different cohorts (normal healthy persons, obese patients, patients with type 2 diabetes and patients with type 1 diabetes).

Official Title
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The Effects of Prolonged Fasting on Glucose Metabolism and Hormonal Regulation in Healthy, Obese and Subjects With Type 2 Diabetes

Conditions
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Healthy, Obesity, Type 2 Diabetes Mellitus, Type 1 Diabetes

Intervention / Treatment
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* Behavioral: 12h fasting
* Behavioral: 36h fasting


Participation Criteria
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Eligibility Criteria
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Gender: Both, male and female Minimum Age: 18 years Inclusion Criteria Cohort I (Healthy, non-obese subjects) Age >18 years; body mass index in the range of 20.0-27.0 kg/m2; fasting plasma glucose <110mg/dL Inclusion criteria cohort II (Obese subjects) Age >18 years; body mass index >30 kg/m2; fasting plasma glucose <110mg/dL Inclusion Criteria Cohort III (Cohort with subjects with Type 2 Diabetes Mellitus) Age >18 years; established Diabetes mellitus type 2 on either diet or a monotherapy or combination of metformin, Dipeptidylpeptidase (DPP)-4-inhibitors or sulfonylurea Inclusion Criteria Cohort IV (Cohort with subjects with Type 1 Diabetes Mellitus) Age >18 years; diagnosed with Type 1 Diabetes Mellitus >12 months; treated with multiple daily Insulin injectioins (MDII) or continuous subcutaneous Insulin Infusion (CSII); stable Insulin therapy as clinically assessed by the study physician; C-Peptide negative defined as 0.3 nmol/L; HbA1c <9.5%; no diabetic ketoacidosis within the last 12 months; no severe hypoglycaemia requiring external assistance within the last 12 months; running on the FreeStyle Libre 1 (Abbott, USA) intermittently-viewed continuous Glucose Monitoring System (iCGM) as Standard of care for Glucose monitoring Exclusion Criteria (for all participants) History of cardiovascular disease; acute or chronic inflammatory disorder; heavy drinking (more than 15 drinks/week); dietary restrictions (e.g. vegetarianism and vegan); insulin Treatment (excluded subjects with Type 1 Diabetes Mellitus); corticosteroid therapy; known malignancy; women who are pregnant, breast-feeding or trying to become pregnant; history of any chronic disease process that could interfere with interpretation of study results; therapy with antidepressants within past 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy<br>Age >18 years; BMI 20-27 kg/m2; Fasting plasma Glucose <110 mg/dL | Behavioral: 12h fasting<br>* 12h fasting (overnight)<br>Behavioral: 36h fasting<br>* 36h fasting ( one day and two nights fasting)<br>|
| Other: Obese people<br>Age >18 years; BMI >30 kg/m2; Fasting Plasma Glucose <110 mg/dL | Behavioral: 12h fasting<br>* 12h fasting (overnight)<br>Behavioral: 36h fasting<br>* 36h fasting ( one day and two nights fasting)<br>|
| Other: Type 2 Diabetes<br>Age >18 years; Diagnosed Type 2 Diabetes mellitus (diet or a monotherapy or combination of metformin, DPP-4-inhibitors or sulfonylurea) | Behavioral: 12h fasting<br>* 12h fasting (overnight)<br>Behavioral: 36h fasting<br>* 36h fasting ( one day and two nights fasting)<br>|
| Other: Type 1 Diabetes<br>Age >18 years; Diagnosed Type 1 Diabetes mellitus >12 months; Treated with multiple daily Insulin injections (MDII) or continuous subcutaneous Insulin Infusion (CSII); Stable Insulin therapy as clinically assessed by the study physician C-Peptide negative defined as 0.3 nmol/L; No diabetic ketoacidosis within the last 12 months; No severe hypoglycaemia requiring external assistance within the last 12 months; Running on the FreeStyle Libre 1 (Abbott, USA) intermittently-viewed continuous Glucose Monitoring System (iCGM) as Standard of care for Glucose monitoring | Behavioral: 12h fasting<br>* 12h fasting (overnight)<br>Behavioral: 36h fasting<br>* 36h fasting ( one day and two nights fasting)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of 2h glucose levels | Difference in the change of 2h glucose levels in an oral glucose tolerance test | after 12 and 36 hours of fasting | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in insulin sensitivity (QUICKI) | differences in QUICKI | after 12 and 36 hours of fasting | 
| changes in insulin sensitivity (Matsuda Index) | differences in Matsuda Index | after 12 and 36 hours of fasting | 
| changes in insulin sensitivity (ISI) | differences in ISI | after 12 and 36 hours of fasting | 
| changes in insulin sensitivity (HOMA-Index) | differences in HOMA-Index | after 12 and 36 hours of fasting | 
| Changes in glycaemic pattern | differences in area under the curve (AUC) of glycaemic pattern in Oral glucose tolerance test | after 12 and 36 hours of fasting | 
| Changes in body composition | differences in bioimpedance analysis | after 12 and 36 hours of fasting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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starvation, healthy people, obese, Type 2 diabetes mellitus, glucose metabolism, Type 1 diabetes mellitus