Aetiology of type 2 diabetes: twin-cycle hypothesis Positive calorie - PowerPoint PPT Presentation

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Aetiology of type 2 diabetes: twin-cycle hypothesis Positive calorie balance ++ Pre-existing insulin resistance liver fat Liver Resistance to insulin cycle suppression of HGP VLDL triglyceride basal insulin secretion plasma

Aetiology of type 2 diabetes: twin-cycle hypothesis Positive calorie balance ++ Pre-existing insulin resistance ↑ liver fat Liver Resistance to insulin cycle suppression of HGP ↑ VLDL triglyceride ↑ basal insulin secretion ↑ plasma glucose Pancreas ↑ islet triglyceride cycle ↓ acute insulin response to food Taylor. Diabetologia 2008; 51: 1781
BMI distribution of participants – Start of UK Prospective Diabetes Study Taylor & Holman, Clin Sci 128: 405-410 2015
BMI distribution of individuals with type 2 diabetes 20 35 40 25 30 Taylor & Holman, Clin Sci 128: 405-410 2015
Personal vs population A Individuals The top panel shows the BMI distribution of individuals at diagnosis of type 2 diabetes. B However, a generation ago, Individuals the alter egos of those people would have been ~15 mg lighter and would not have had diabetes (blue dots). C OR – Individuals If those people with T2DM lose 15kg, they lose their type 2 diabetes 20 25 30 35 40 BMI Taylor & Holman, Clin Sci 128: 405-410 2015
Personal vs population A Individuals Take 3 individuals for example. Each lost 15kg and reversed their diabetes. But by BMI B criteria they remain obese, overweight and normal Individuals respectively. Each individual must have crossed a threshold of fat mass, personal to them. C Individuals 20 25 30 35 40 BMI Taylor & Holman, Clin Sci 128: 405-410 2015
Personal vs population A Individuals B Individuals C Individuals explains the “Why me” factor – indivduals have personal capacity to store fat safely. If the PFT is exceeded, 20 25 30 35 40 T2DM slowly develops. BMI Taylor & Holman, Clin Sci 128: 405-410 2015
Amount of weight lost and effect on reversal of diabetes – 92 people after bariatric surgery 80 reversing diabetes Percentage 60 40 20 0 10-20 20-30 >30 <10 Weight loss (%) Steven, Carey, Small & Taylor; Diabetic Med 2014

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