Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals

Abstract

Background: Large cohort longitudinal studies have almost unanimously concluded that metabolic health in obesity is a transient phenomenon, diminishing in older age. We aimed to assess the fate of insulin sensitivity per se over time in overweight and obese individuals. Methods: Individuals studied using the hyperinsulinaemic-euglycaemic clamp at the Garvan Institute of Medical Research from 2008 to 2010 (n = 99) were retrospectively grouped into Lean (body mass index (BMI) < 25 kg/m2) or overweight/obese (BMI ≥ 25 kg/m2), with the latter further divided into insulin-sensitive (ObSen) or insulin-resistant (ObRes), based on median clamp M-value (M/I, separate cut-offs for men and women). Fifty-seven individuals participated in a follow-up study after 5.4 ± 0.1 years. Hyperinsulinaemic-euglycaemic clamp, dual-energy X-ray absorptiometry and circulating cardiovascular markers were measured again at follow-up, using the same protocols used at baseline. Liver fat was measured using computed tomography at baseline and proton magnetic resonance spectroscopy at follow-up with established cut-offs applied for defining fatty liver. Results: In the whole cohort, M/I did not change over time (p = 0.40); it remained significantly higher at follow-up in ObSen compared with ObRes (p = 0.02), and was not different between ObSen and Lean (p = 0.41). While BMI did not change over time (p = 0.24), android and visceral fat increased significantly in this cohort (ptime ≤ 0.0013), driven by ObRes (p = 0.0087 and p = 0.0001, respectively). Similarly, systolic blood pressure increased significantly over time (ptime = 0.0003) driven by ObRes (p = 0.0039). The best correlate of follow-up M/I was baseline M/I (Spearman’s r = 0.76, p = 1.1 × 10−7). Conclusions: The similarity in insulin sensitivity between the ObSen and the Lean groups at baseline persisted over time. Insulin resistance in overweight and obese individuals predisposed to further metabolic deterioration over time.

Lipid Profile and Soluble E-Selectin Levels Differences Between Type 2 Diabetes Mellitus Overweight-Obese and Under-Normoweight Patients

“…Insulin resistance (IR), coagulation disorders, dyslipidemia, and cardiovascular complications are considered the most causes of morbidity and mortality in obese diabetic patients (Songa et al, 2015;Al-Shreef and El-Kader, 2017). A significant increase in insulin resistance occurred in T2DM patients with obesity compared to T2DM patients without obesity (Tang et al, 2019).…”

Rationale and design of a randomised controlled trial testing the effect of personalised diet in individuals with pre-diabetes or type 2 diabetes mellitus treated with metformin

“…Specifically, total body fat mass and fat-free mass (enCORE software), the android and gynoid region, and visceral fat (CoreScan software, GE Healthcare) are recorded. 24 Liver steatosis (controlled attenuation parameter, CAP) and liver fibrosis (liver stiffness measurements, LSMs) are assessed using FibroScan (Touch 502 by Echosens) by a trained technician. CAP and LSMs have been reported to correlate closely with steatosis and fibrosis assessed using the gold standard liver biopsy.…”

“…Fat, fat-free mass and android/gynoid fat distribution and visceral fat measurements by DXA are repeated at 6 months of treatment. 24 Similarly, resting energy expenditure and fat/carbohydrate oxidation is measured after 6 months of treatment.…”

Identifying pathways to early‐onset metabolic dysfunction, insulin resistance and inflammation in young adult inpatients with emerging affective and major mood disorders

“…Insulin resistance (IR) is a promising alternative measure (Scott et al, 2019) and assessed based on paired fasting plasma insulin and glucose levels (Wallace et al, 2004) using the Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR). When present at a young age, IR predisposes to adverse metabolic outcomes (Tang et al, 2019). Notably, increased HOMA2-IR scores are already prevalent early in the course of young people presenting to ambulatory care settings with major mood or psychotic disorders (Scott et al, 2019).…”