1184-P: Return to Normal Glucose Control by Weight Loss in Nonobese People with Type 2 Diabetes: The ReTUNE Study Free

Type 2 diabetes (T2D) in the non-obese has been regarded as etiologically distinct from that in obese people. However, clinical observation suggests that loss of fat mass above a personal fat threshold brings about remission in the same way. ReTUNE aimed to determine what proportion of T2D people with BMI <27kg/m² could achieve remission, and to assess the fat threshold for this. 25 participants have been studied to date (T2D: 4M/10F, 58.3±2.1years, BMI 24.5±0.6kg/m²; matched nondiabetic controls: n=11). Other types of diabetes were excluded by anti-islet cell antibodies and MODY gene tests (2/14). From baseline, weight loss of 5% was achieved in 2-4 weeks using low calorie diet (800 kcal/day), then 6 weeks of weight maintenance. The cycle of weight loss plus maintenance was repeated 2-3 times until the clinical end point of remission was reached (HbA1c < 6.5%). Only 2 cycles (~10% weight loss) were required in 8/12 participants. The planned decrease in weight (baseline to clinical endpoint: 69.0±3.5 to 60.8±2.9kg, p<0.001) decreased total body fat from 33.1±1.9 to 27.4±2.0% (p<0.001). Fasting plasma glucose decreased from 7.3±0.3 to 6.3±0.3 mmol/l, p<0.05). HbA1c decreased from 7.1±0.2 to 6.5±0.1%, p<0.05 with 8/12 in remission (<6.5%). Fasting plasma insulin decreased (52.2±9.5 to 23.7±3.6 pmol/L, p=0.007) as did plasma triglyceride (1.6±0.2 to 1.0±0.1mmol/L, p=0.002). Liver fat fell from 4.4±0.8 to 1.4±0.1% (p=0.004) becoming similar to 11 matched healthy controls (1.9%). Pancreas fat content in T2D fell (5.1± 0.6 to 4.5±0.6%, p=0.026) towards control levels (3.3±0.3%, p=0.029 vs. T2D at baseline). Post meal insulin sensitivity (Si) and insulin secretion (disposition index and β-cell responsivity Φ_tot) improved after weight loss.

In conclusion, 2/14 people with BMI <27kg/m² were found to have other diagnoses, and weight loss brought about remission in 8/12 people accompanied by pathophysiological changes similar to those seen during remission in obesity-associated T2D.