Is Absence of Carbohydrate Metabolism Disorders in Patients with Prolonged History of Obesity due to Low Insulin Resistance or Preserved Insulin Secretion?

Background: At present a lot of attention is paid to the so-called “metabolically healthy obesity”. More than a half of patients with prolonged history of obesity lack any carbohydrate metabolism disorders. Unfortunately, physiological factors forming the foundation of a favorable metabolic profile in such patients are not sufficiently defined. Aims: Evaluation of insulin resistance (IR) degree, the level of insulin secretion by pancreatic β-cells, and the contribution of both these mechanisms to the maintenance of normal carbohydrate metabolism in patients with prolonged history of obesity. Methods: An observational cross-sectional non-blinded selective comparative case-control study was performed. Patients with prolonged history of obesity without carbohydrate metabolism disorders and with type 2 diabetes mellitus (DM2) were included into the study. The following parameters were analyzed: IR parameters (М-index, HOMA-IR); insulin secretion parameters (НОМА-%β and insulinogenic index, glucose disposition index, GDI); body composition indices (total body fat and visceral fat area). Results: 68 patients participated in the study: 34 patients with obesity and normal carbohydrate metabolism («Obesity and NCM» group), and 34 patients with obesity and DM2 («Obesity and DM2» group); both groups were matched by body mass index, known obesity duration, and sex ratio (males/females) in each group. «Obesity and NCM» groups significantly differed from «Obesity and DM2» group by the following parameters: lower IR level (М-index median 4.13 vs 1.52 mg/kg/min, p<0.001; HOMA-IR median 4.84 vs 9.94, p<0.001); better insulin secretion (insulinogenic index median 28.15 vs 15.24, p<0.002; HOMA-%β median 115.63 vs 25.94, p<0.001); higher GDI (median 115.63 vs 25.94, p<0.001); lower visceral fat area (median 170.00 vs 230.00 cm², p<0.001). Differences in total body fat (%) were not statistically significant. Conclusions: Patients with obesity and NCM compared to patients with DM2 have a less significant IR and a more preserved basal & stimulated insulin secretion, which allows to maintain normal carbohydrate metabolism. Low visceral fat grade also contributes to this. Most likely, the most important factor contributing to the “maintenance” of normal carbohydrate metabolism in patients with obesity is preserved insulin secretion, which is confirmed by the high glucose disposal index (almost 4.5-fold higher than that in patients with DM2) characterizing the ability of β-cells to secrete the amount of insulin required to overcome IR.