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Reduction in Glycated Hemoglobin and Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes Consuming a Three-Meal Diet: A Randomized Clinical Trial.

Authors
  • Jakubowicz, Daniela1
  • Landau, Zohar2
  • Tsameret, Shani3
  • Wainstein, Julio2
  • Raz, Itamar4
  • Ahren, Bo5
  • Chapnik, Nava3
  • Barnea, Maayan6
  • Ganz, Tali2
  • Menaged, Miriam2
  • Mor, Naomi2
  • Bar-Dayan, Yosefa2
  • Froy, Oren7
  • 1 Diabetes Unit, Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Holon, Israel [email protected] , (Israel)
  • 2 Diabetes Unit, Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Holon, Israel. , (Israel)
  • 3 Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel. , (Israel)
  • 4 Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, The Hebrew University of Jerusalem, Jerusalem, Israel. , (Israel)
  • 5 Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden. , (Sweden)
  • 6 Department of Molecular Genetics, Faculty of Biochemistry, Weizmann Institute of Science, Rehovot, Israel. , (Israel)
  • 7 Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel [email protected] , (Israel)
Type
Published Article
Journal
Diabetes care
Publication Date
Dec 01, 2019
Volume
42
Issue
12
Pages
2171–2180
Identifiers
DOI: 10.2337/dc19-1142
PMID: 31548244
Source
Medline
Language
English
License
Unknown

Abstract

In type 2 diabetes, insulin resistance and progressive β-cell failure require treatment with high insulin doses, leading to weight gain. Our aim was to study whether a three-meal diet (3Mdiet) with a carbohydrate-rich breakfast may upregulate clock gene expression and, as a result, allow dose reduction of insulin, leading to weight loss and better glycemic control compared with an isocaloric six-meal diet (6Mdiet). Twenty-eight volunteers with diabetes (BMI 32.4 ± 5.2 kg/m2 and HbA1c 8.1 ± 1.1% [64.5 ± 11.9 mmol/mol]) were randomly assigned to 3Mdiet or 6Mdiet. Body weight, glycemic control, continuous glucose monitoring (CGM), appetite, and clock gene expression were assessed at baseline, after 2 weeks, and after 12 weeks. 3Mdiet, but not 6Mdiet, led to a significant weight loss (-5.4 ± 0.9 kg) (P < 0.01) and decreased HbA1c (-12 mmol/mol [-1.2%]) (P < 0.0001) after 12 weeks. Fasting glucose and daily and nocturnal glucose levels were significantly lower on the 3Mdiet. CGM showed a significant decrease in the time spent in hyperglycemia only on the 3Mdiet. Total daily insulin dose was significantly reduced by 26 ± 7 units only on the 3Mdiet. There was a significant decrease in the hunger and cravings only in the 3Mdiet group. Clock genes exhibited oscillation, increased expression, and higher amplitude on the 3Mdiet compared with the 6Mdiet. A 3Mdiet, in contrast to an isocaloric 6Mdiet, leads to weight loss and significant reduction in HbA1c, appetite, and overall glycemia, with a decrease in daily insulin. Upregulation of clock genes seen in this diet intervention could contribute to the improved glucose metabolism. © 2019 by the American Diabetes Association.

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