Background and aims: Mechanisms underlying weight loss induced remission of type 2 diabetes (T2DM) have been reported only in people with BMI >27kg/m2. The Personal Fat Threshold hypothesis postulated that the same mechanisms in people with BMI <27kg/m2. Pathophysiology during stepwise dietary weight loss was studied in this group.

Methods: People with T2DM (13/20 female, mean (±1SD) 59.3±7.1 years, BMI 24.8±1.7kg/m2) were studied before and after up to three 5% weight loss cycles, each comprising a 2-4 week low energy diet (800kcal/day formula meal replacements plus non starchy vegetables) , followed by 4-6 weeks of weight maintenance. All hypoglycemic agents were stopped before weight loss. Studies were repeated at 12 months. Outcomes were compared to normoglycemic matched controls (n=20) . Intrahepatic and intrapancreatic fat was quantified by magnetic resonance, and a standard meal test assessed insulin secretion by Disposition Index (DI) .

Results: 70% achieved remission (HbA1c <6.5%; 14/20) , accompanied by decrease in adipose tissue distress (Median (IQR) PAI-1 8.64 (6.97-11.01) to 5.99 (3.94--7.73) p<0.02 [control 4.87 (3.49-7.03] ng/ml; GDF-15 591 (439-872) to 444 (395-554) [446 (383-614] pg/ml p<0.05. Between baseline and 12 months, decrease was (mean±SE; control data in square brackets) : BMI 24.8±0.4 to 22.5±0.4 kg/m2 (p<0.0001) [21.5±0.5]; total body fat 32.1±1.5 to 27.6±1.8% (p<0.0001) [24.6±1.5]; Fasting plasma insulin 47±6 to 24±6pmol/l (p<0.001) [23±2]; liver fat 4.0±0.6 to 1.6±0.2% (p=0.02) [1.9±0.3]; plasma triglycerides 1.4±0.2 to 0.9±0.1mmol/l (p<0.02) [0.9±0.1]; Intrapancreatic fat (6.1±0.5 to 5.0±0.6% (p=0.03) [4.1±0.3]. DI increased from median (IQR) 289 (183-373) to 774 (486-1709) dl/kg/min per pmol/l (p<0.05) but remained subnormal [2751 (1524-3526].

Conclusion: Mechanistic changes underpinning remission after weight loss in non-obese people with T2DM are the same as in obese people. T2DM occurs if a person becomes too heavy for their own constitution, irrespective of BMI. Weight loss of ∼10% can bring about T2DM remission in people classified as having a ‘normal’ BMI.


R. Taylor: Speaker's Bureau; Janssen Global Services, LLC, Lilly Diabetes, Nestlé Health Science, Novartis AG. C. Cobelli: None. K. M. Irvine: None. A. C. Barnes: None. T. L. Kelly: None. L. G. Clark: None. K. G. Hollingsworth: None. A. Al-mrabeh: None. R. R. Holman: Advisory Panel; Anji Pharmaceuticals, Novartis AG, Novo Nordisk, Consultant; AstraZeneca, Research Support; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. D. Romeres: None.


Diabetes UK (17/0005645)

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