Normalized Glucose Levels in Type 2 Diabetes With Carbohydrate or Caloric Restriction: a Randomized Controlled Trial (CarborCal)

Background Overweight and obesity raise the risk of hyperglycemia which is among the strongest risk factors for morbidity and mortality globally, linked to type 2 diabetes (T2D) as well as, e.g., cardiovascular diseases (CVD), several cancers, dementia, complicated pregnancies and non-alcoholic fatty liver disease.1 The link between obesity, T2D and CVD is partially explained by the visceral adiposity and ectopic (e.g., hepatic) fat associated with insulin resistance, glucose intolerance, arterial stiffness, high blood pressure and dyslipidaemia constituting the metabolic syndrome.2,3 Recent studies have demonstrated that diet-induced weight loss, averaging just over 10 kg at 12-months, can effectively normalize blood glucose levels in T2D in a large proportion of patients. While energy-restrictive diets can enable rapid weight loss, any restrictive diet can be difficult to maintain over time. Strict weight loss diet is difficult to follow. Less restrictive approaches that can be adopted as part of a healthy lifestyle would be ideal.

Cardiovascular complications are the leading cause of morbidity and mortality among patients with diabetes. 29 The mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood. Hyperglycemia has been shown to cause increased oxidative stress arising from oxi-dative degradation of glucose metabolites. Similarly, advanced glycosylation endproducts (AGEs), which are the result of intracellular hyperglycemia, have been shown to be involved in mediating vascular damage. Furthermore hyperglycemia has been reported that to lead to a hypercoagulable state.29 Low carbohydrate diet has recently gained popularity. Rresearch questions remain on if LC diet with low GI can lead to normalization of blood glucose levels and decrease cardiovascular risk markers. The ideal energy percentage (E%) of carbohydrate in the diet for optimal glucose levels is unclear. Caloric restriction diet has shown best results for normalisation of blood glucose levels. There are no previous studies comparing LC diet with caloric restricted diet in regard to normalization of blood glucose levels. The main goal of this study is to evaluate if LC with low GI can lead to normalization or improvement of blood glucose levels in type 2 diabetes (T2D) and to explore the mechanism for normalization of blood glucose levels after LC diet and caloric restricted diet.

The main hypothesis in this study is that Low carbohydrate diet can results in normalization or improvement of blood glucose levels in patients with T2D with short duration of disease both in the shorter term (3 months) and longer term (15 months).

286 patients with type 2 diabetes will be included in this study. Patients will be randomized to a low Carb diet or a low caloric diet for 15 months.

Previous study on caloric restriction diet (DIRECT trial) showed normalization of blood glucose levels in 46% of participants after 12 months. Previous studies on LC diet have shown different results on blood glucose levels based on differences in study design. The greater the carbohydrate restriction, the greater glucose lowering effect. There is a lack of studies reporting normalisation of blood glucose levels. Therefore, it was assumed that LC dietary strategies can result in normalization of blood glucose levels in 30% of patients with T2D after 3 and 15 months. Using an online sample size calculator for a study power of 80% and alpha value of 0.05 the sample size was calculated to 143 participants in each group.