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Reductioninglycatedhemoglobin and daily insulin dose alongside circadian clock upregulation in patients with type 2 diabetes consuming a three-meal diet : A randomized clinical trial

Jakubowicz, Daniela ; Landau, Zohar ; Tsameret, Shani ; Wainstein, Julio ; Raz, Itamar ; Ahren, Bo LU ; Chapnik, Nava ; Barnea, Maayan ; Ganz, Tali and Menaged, Miriam , et al. (2019) In Diabetes Care 42(12). p.2171-2180
Abstract

OBJECTIVE In type 2 diabetes, insulin resistance and progressive b-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). RESEARCH DESIGN AND METHODS Twenty-eight volunteers with diabetes (BMI 32.4 6 5.2 kg/m2 and HbA1c 8.1 6 1.1% [64.5 6 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... (More)

OBJECTIVE In type 2 diabetes, insulin resistance and progressive b-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). RESEARCH DESIGN AND METHODS Twenty-eight volunteers with diabetes (BMI 32.4 6 5.2 kg/m2 and HbA1c 8.1 6 1.1% [64.5 6 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. RESULTS 3Mdiet, but not 6Mdiet, led to a significant weight loss (25.4 6 0.9 kg) (P < 0.01) and decreased HbA1c (212 mmol/mol [21.2%]) (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 6 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. CONCLUSIONS 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.

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Contribution to journal
publication status
published
subject
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Diabetes Care
volume
42
issue
12
pages
10 pages
publisher
American Diabetes Association
external identifiers
  • pmid:31548244
  • scopus:85075814961
ISSN
0149-5992
DOI
10.2337/dc19-1142
language
English
LU publication?
yes
id
3ed07992-e401-4dbf-b96f-c93089e48911
date added to LUP
2019-12-16 11:10:59
date last changed
2020-07-08 05:09:25
@article{3ed07992-e401-4dbf-b96f-c93089e48911,
  abstract     = {<p>OBJECTIVE In type 2 diabetes, insulin resistance and progressive b-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). RESEARCH DESIGN AND METHODS Twenty-eight volunteers with diabetes (BMI 32.4 6 5.2 kg/m<sup>2</sup> and HbA<sub>1c</sub> 8.1 6 1.1% [64.5 6 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. RESULTS 3Mdiet, but not 6Mdiet, led to a significant weight loss (25.4 6 0.9 kg) (P &lt; 0.01) and decreased HbA<sub>1c</sub> (212 mmol/mol [21.2%]) (P &lt; 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 6 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. CONCLUSIONS A 3Mdiet, in contrast to an isocaloric 6Mdiet, leads to weight loss and significant reduction in HbA<sub>1c</sub>, 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.</p>},
  author       = {Jakubowicz, Daniela and Landau, Zohar and Tsameret, Shani and Wainstein, Julio and Raz, Itamar and Ahren, Bo and Chapnik, Nava and Barnea, Maayan and Ganz, Tali and Menaged, Miriam and Mor, Naomi and Bar-Dayan, Yosefa and Froy, Oren},
  issn         = {0149-5992},
  language     = {eng},
  number       = {12},
  pages        = {2171--2180},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Reductioninglycatedhemoglobin and daily insulin dose alongside circadian clock upregulation in patients with type 2 diabetes consuming a three-meal diet : A randomized clinical trial},
  url          = {http://dx.doi.org/10.2337/dc19-1142},
  doi          = {10.2337/dc19-1142},
  volume       = {42},
  year         = {2019},
}