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

Daniela Jakubowicz*, Zohar Landau, Shani Tsameret, Julio Wainstein, Itamar Raz, Bo Ahren, Nava Chapnik, Maayan Barnea, Tali Ganz, Miriam Menaged, Naomi Mor, Yosefa Bar-Dayan, Oren Froy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)2171-2180
Number of pages10
JournalDiabetes Care
Volume42
Issue number12
DOIs
StatePublished - 1 Dec 2019

Funding

FundersFunder number
Ministry of Health, State of Israel3-00000-12856

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