Type 2 diabetes mellitus and obesity
Obesity is a complex disease in which genetic predisposition interacts with environmental influences, resulting in a heterogeneous phenotype [Comuzzie AG, Williams JT]. Some of these obesity phenotypes are associated with a high risk of developing type 2 diabetes mellitus (T2DM) [Dvorak RV, DeNino WF]. There is also compelling evidence that this form of obesity is characterized by significant heterogeneity of metabolic risk, mainly related to the distribution of excess adipose tissue. Accumulation of visceral adipose tissue is an important prognostic factor for lipid, glucose, or atherogenic disturbances, whereas fat distribution in the lower body is not associated with an increase in metabolic alterations.
Studies have shown that body mass index (BMI) is a strong predictor of T2DM. Visceral fat is an important source of inflammatory cytokines such as tumor necrosis factor alpha (TNF- α), transforming growth factor β (TGF-β), interleukin-6 (IL-6), resistin, and plasminogen activator inhibitor type 1 (PAI-1), which can directly affect insulin-mediated glucose uptake (insulin resistance). On the other hand, the secretion of other factors, such as adiponectin, which reduce insulin resistance, is decreased. This imbalance leads to a pro-inflammatory state that is associated with an increased risk of cardiovascular complications.
Recent epidemiological data on T2DM indicate that we are in the midst of an epidemic. T2DM is one of the most common non-communicable diseases. It is the fourth leading cause of death in most high-income countries, and there is strong evidence that it represents an epidemic in many economically developing countries. T2DM is one of the most serious health problems of the twenty-first century. It is estimated that there are currently 415 million adults aged 20 to 79 years living with diabetes worldwide, including 193 million who remain undiagnosed. An additional 318 million adults are estimated to have impaired glucose tolerance, placing them at high risk of developing the disease. By 2040, this number is expected to rise to 642 million, with an additional half a billion people at high risk [International Diabetes Federation, 2016]. According to 2018 estimates, diabetes will account for five million deaths, and healthcare expenditures will range from 673 billion to 1.197 trillion US dollars [International Diabetes Federation, 2016]. The global prevalence of T2DM is rapidly increasing due to “obesity,” which promotes a sedentary lifestyle and easier access to convenient high-calorie foods acting on susceptible genotypes.
The onset of T2DM is characterized by an irreversible complex cycle that involves severe detrimental effects on glucose metabolism.
Recently, new medications have become available, such as glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors. However, the average level of glycemic control in patients with T2DM remains suboptimal [Stark Casagrande S, Fradkin JE, Grant RW, Buse JB]. The overall risk of death among individuals with T2DM is at least twice as high as that of their peers without T2DM [Carlsson LM, Peltonen M].
The use of medications and lifestyle modifications in patients with T2DM can delay cardiovascular and other serious complications, but requires patient adherence to treatment regimens, frequent medical monitoring, and lifelong medication use. Nevertheless, despite significant advances, glycemic control in T2DM remains elusive [Stark Casagrande S, Fradkin JE], with fewer than 20% of patients able to achieve the three endpoints of metabolic control (glycemia, blood pressure, and lipid levels). However, gastrointestinal (GI) surgery is effective in the treatment and prevention of T2DM, reducing long-term mortality compared with medical therapy in patients with morbid obesity, as demonstrated in large clinical studies [Carlsson LM, Peltonen M].
Metabolic surgery includes any intervention that alters the passage of food through the gastrointestinal tract, leading to improved control of T2DM. Such outcomes are not solely dependent on weight loss. In some cases, effects may be observed within a few days after bariatric surgery, before significant weight loss occurs, which excludes a direct antidiabetic effect. The term “bariatric” is gradually being replaced by “metabolic,” as procedures previously recommended for morbid obesity (defined as body mass index (BMI) > 40 kg/m² or > 35 kg/m² with comorbidities) have demonstrated excellent results in achieving remission of T2DM.
In 2011, the International Diabetes Federation (IDF) issued a statement that bariatric surgery is an acceptable option for patients with T2DM and a body mass index (BMI) greater than 35, and may be an alternative therapy for patients with a BMI less than 35 who do not respond to standard medical therapy. Metabolic surgery includes standard bariatric procedures (Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion (BPD) with or without duodenal switch, sleeve gastrectomy (SG), and mini-gastric bypass (MGB)) as well as newer procedures (ileal interposition, duodenojejunal bypass) designed to achieve metabolic effects independent of significant weight loss [Dixon JB, Zimmet P].
Remission of T2DM occurs due to mechanisms such as increased insulin sensitivity associated with improved β-cell function, as a result of increased production of endogenous glucagon-like peptide-1 (GLP-1). Remission of T2DM is observed in the early postoperative days after surgery [Pajecki D, Riccioppo D].
