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Reversing the Metabolic Syndrome (MetS) & Preventing Type 2 Diabetes

Oct 26, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Marian Ayad, BPharm, PharmD candidate, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

This study discusses how restricting carbohydrates can reverse and prevent the metabolic syndrome (MetS).

Metabolic syndrome (MetS) can be defined as a set of interconnected, physiological, biochemical, clinical, and metabolic factors that increase risk of CV disease, type 2 diabetes, and all-cause mortality. A few characteristics of MetS include high BP, high blood glucose, and excess body fat around the waist. Carbohydrate intake stimulates insulin secretion, which in turn stimulates fat storage and inhibits adipose tissue lipolysis and fatty acid oxidation and increases hyperinsulinemia, which is highly correlated with MetS. This indicates that a high carbohydrate diet may play an important role in the pathogenesis of MetS. Treatment/prevention of MetS is of great importance for people at risk of diabetes as it was found that patients with MetS are at a 5-fold increase in the risk of type 2 diabetes mellitus. It was previously thought that reduced-fat and low-calorie diets treat MetS without the focus on low carbohydrate diets for treatment. This Ohio State University study was conducted with the objective to test whether dietary carbohydrate intolerance, irrespective of obesity, plays a major role in MetS. In other words, if a high carbohydrate diet can exacerbate MetS, can a low carbohydrate diet prevent or reverse MetS (and in turn prevent type 2 diabetes) independent of weight loss?


The study included men and women with obesity, 21 to 65 years of age, with MetS (defined as having 3 or more of these characteristics: waist circumference > 40in in men and 35in in women, triglycerides ³ 150mg/dL, HDL-C < 40 mg/dL in men and 50mg/dL in women, BP ³ 130/85 mmHg, fasting glucose ³ 100mg/dL. Briefly, participants were excluded if they had high total cholesterol, diabetes, liver, kidney or other metabolic or endocrine dysfunction. 

This study was a randomized cross-over study where a total of 16 participants were enrolled with MetS and each completed 3 controlled-feeding periods (low, moderate and high carbohydrate diet), each lasting 4 weeks with a 2-week washout period between diets. There was a 2-week run-in period where participants were fed a moderate carbohydrate (standard American diet) to determine the appropriate energy expenditure to maintain the same weight. The diets were formulated to contain the same number of calories to maintain weight stability where the protein was constant, carbohydrate varied (low, moderate, high carbohydrate) and fat was adjusted proportionally across all diets.

It was found that there was no change in body mass and there was a trend for a lower liver fat (P=0.072) after low carbohydrate diet (9.7%) > moderate (10.1%) >high carbohydrate diet (11.5%). The study findings also reported that a low carbohydrate diet enhances fat oxidation and rapidly reverses MetS in most people independent of weight loss, and glucose levels were lower on the low carbohydrate diet. Furthermore, it was stated that more than half of participants after 4 weeks on the low carbohydrate diet no longer had MetS, and only 3 out of 16 on moderate carbohydrate diet and 1 out of 16 after the high carbohydrate diet had MetS reversed.

In conclusion, the results of the study clearly show that a low carbohydrate diet (high fat intake as fat is adjusted proportionally) usually leads to the reversal and improvement of MetS independent of weight loss in people who have obesity, and hence can reverse features of insulin resistance and type 2 diabetes. The authors of the study believe that any further studies on long-term diets for participants with MetS should include low carbohydrate diets.

Practice Pearls:

  • Metabolic syndrome can lead to a 5-fold increase in the risk of type 2 diabetes.
  • Low carbohydrate intake led to lower glucose levels and enhanced fat oxidation which rapidly reversed MetS in most people, independent of weight loss.
  • More than half of the participants after 4 weeks on a low carbohydrate diet no longer had MetS, while only 3 out of 16 on moderate carbohydrate and 1 out of 16 on high carbohydrate had MetS reversed.

Hyde PN, Sapper TN, Crabtree CD, et al. Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss. JCI Insight. 2019 Jun 20;4(12). pii: 128308. doi: 10.1172/jci.insight.128308

Kaur J. A Comprehensive Review on Metabolic Syndrome. Cardiol Res Pract. 2014; 2014: 943162.

Marian Ayad, BSPharm, BCPS, PharmD candidate, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.