Weight gain and insulin therapy

• over 80% of type 2 diabetics are overweight - insulin therapy often exacerbates this problem (1)
  • in the UKPDS (2) - weight gain was highest in insulin-treated patients - the amount of weight gain correlated directly with mean serum insulin levels
  • in type 1 diabetes patients are often underweight at diagnosis - it is often assumed that weight gain associated with insulin treatment represents normalisation of body weight but:
    • evidence from DCCT revealed that weight gain is greater with intensive treatment (3); weight gain may proceed to levels that are beyond ideal weight (1)
  • weight gain is known to adversely affect cardiovascular risk (1)

Why does insulin treatment promote weight gain? Various mechanisms have been described:

• calorie conservation - insulin therapy can, in some cases, restore blood glucose levels to below the renal threshold for glucose excretion - leading to an improved conservation of ingested calories (1)
• compensation for hypoglycaemia or ‘defensive snacking’ - this is a widely accepted theory although difficult to prove (1)
• deranged pharmacodynamic and metabolic profile
  • insulin treatment regimens do not perfectly recreate normal physiological’ insulin secretion profiles - there are often show considerable day-to-day variations
    • the unpredictability of insulin could result in hypoglycaemic episodes and may affect compliance and promote weight gain through ‘defensive snacking’ (1)
  • endogenous insulin is secreted into the portal circulation. This contrasts with subcutaneous insulin which circulates systemically before reaching the liver
    • therefore in insulin therapy via the sc route, the liver is ‘underinsulinised’ and the periphery ‘over insulinsed’ (and hence exposing the systemic circulation to increased metabolic effects associated with circulating insulin)

Decreasing insulin requirement:

• exercise and weight loss increase insulin sensitivity and therefore the required dose of insulin
  • also metformin is used in insulin-treated obese type 2 diabetic patients can lead to reductions in HbA1C and BMI whilst also reducing insulin requirements (4)
• balancing insulin availability to physiological requirements
  • various measures such as modern basal-bolus and CSII regimens attempt to recreate a more physiological insulin profile. Also the basal insulin analogue, insulin detemir, is associated with a reduced risk of weight gain

Reference:

1. Khan R. British Journal of Diabetes and Vascular Disease 2004; 4(4):264-7.
2. Lancet 1998;352:837-53.
3. Diabetes Care. 1988;11(7):567-73
4. Clin Ther 1998;20:691-8.