**1. Introduction**

Thus far, type 2 diabetes mellitus (DM) is recognized as an incurable metabolic disease by common therapies. Obesity and type 2 DM are intrinsically correlated, and low-grade chronic inflammation at a local and systemic site has been suggested as a key component in the progression toward the disease [1, 2]. In this regard, very low-calorie diet (VLCD) regimens, providing <800 kcal/d, have demonstrated to exert a beneficial and rapid effect on glucose metabolism in individuals with type 2 DM, which are not seen with pharmacological therapies [3]. Since 1970, VLCD has been used to induce rapid weight loss with a favorable safety profile [4]. Benefits of VLCD in T2DM patients with obesity include weight loss, fat mass reduction, reversion of hyperglycemia, elimination of pharmacologic treatment and normalization of both beta cell function and hepatic insulin sensitivity [3, 5]. The main mechanism by which VLCD regimens exert their beneficial effects on metabolism of type 2 DM subjects appears to be their capacity to induce weight loss and modulate inflammation via cytokines and adipokines [6–8]. However, there are considerable limitations of VLCD regimens in certain individuals. The most common issue to resolve in clinical trials evaluating VLCD regimens is noncompliance of patients due to previous dietary patterns, psychological aspects, vitamin deficiency manifestations and renounce to undergo lifestyle changes [9, 10]. In addition, initial weight loss by VLCD treatment is associated with greater weight regain; thus, long-term weight maintenance after VLCD has been an elusive goal when compared to surgical procedures like bariatric surgery [11, 12].

loss. In 1997, Capstick et al. performed a clinical trial in 14 patients with obesity and type 2 DM aiming to evaluate the effects of a VLCD (425 kcal/day) regimen for 12 weeks on weight and metabolic control. In this clinical trial, body weight (from 108.9 to 94.5 kg), waist circumference (from 116 to 103 cm) and systolic blood pressure (SBP) (−8 mmHg) were reduced. The authors also reported a total reduction in exogenous insulin utilization by 50% in the VLCD cohort individuals who were taking a high dose of insulin per day at baseline, accompanied by a decrease in the number of oral antidiabetic drugs (8–2, median tablets/day). In addition, this regimen was well tolerated with a favorable safety profile [17]. Since then, several studies have implemented a diet treatment for type 2 DM. In 2011, Lim et al. evaluated the clinical effects of a 600 kcal/day VLCD regimen for 8 weeks in 11 middle-aged patients with obesity and type 2 DM. Results showed an average weight loss of 15.3 kg, equivalent to 15% of their initial body weight, with a sustained reduction of 3 kg after a 12-week follow-up [18]. Nevertheless, the majority of these studies have been pursued for <6 months, with limited

Very Low-Calorie Diets in Type 2 Diabetes Mellitus: Effects on Inflammation, Clinical and…

http://dx.doi.org/10.5772/intechopen.72167

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In regard to the long-term study of VLCD regimens, Paisey et al. compared the clinical effects of a VLCD regimen with an intensive conventional diet plus exercise for 5 years in obese type 2 DM subjects. Fifteen patients in both cohorts finished the program. After 3 years of therapy, subjects in the VLCD regimen lost more body weight (mean ~15 kg weight loss) than their counterparts; however, by 5 years of follow-up, most of the weight was regained. On the other hand, the intensive group had a more sustained and progressive weight loss than the VLCD. The authors demonstrated that VLCD was safe to perform but difficult to follow for more than 6 months and showed a relative low patient compliance rate of ~60% in those individuals [19].

Similarly, Lim et al. showed a persistent beneficial effect on weight control after 6 months of an 8-week VLCD [20]. However, there could be some concerns about the tolerability and safety of VLCD in the long term based on the limited calorie content of these types of diets. Interestingly, Rolland et al. performed a study comparing weight loss and safety in obese subjects of three types of restricted calorie diets: VLCD, low-carbohydrate/high-protein diet and low fat, reduced-energy diet. At 3 months, a greater loss in body weight, total cholesterol, low-density lipoprotein cholesterol (LDL), fasting glucose and diastolic blood pressure in the VLCD cohort was observed. At 9 months, there were no significant differences, with the exception of fasting glucose, among the VLCD (average 550 kcal/day) and low-carbohydrate/ high-protein diet (800–1500 kcal/day) regimens. Dropout rates were similar in the VLCD and low-carbohydrate/high-protein diet groups and no adverse effects were reported at 3 and 9 months in both groups [21]. Thus, at least for 9 months, VLCD seems to possess a favorable

A recent systematic review and meta-analysis compared weight loss following VLCD (<800 kcal/ day) and low-energy liquid-formula regimens (>800 kcal/day) in people with and without type 2 DM [5]. The analysis of five studies varying from 4 to 52 weeks in length revealed no significant differences in weight loss among both regimens. Further, data showed that the efficacy on weight loss depended on several factors, including duration of diet and clinical characteristics of the subjects. In addition to effects on body weight, VLCD regimens were associated with a

safety profile compared to less intense restricted calorie diets (>800 kcal/day).

lack of adverse effects.

evidence on their long-term efficacy in the treatment of diabetes.

The purpose of the present chapter is to focus on the metabolic and clinical effects of VLCD regimens in type 2 DM subjects as well as on the role of inflammation and oxidative stress (OS).
