Type 1 Diabetes Treatment Challenge
At diagnosis, patients with type 1 diabetes are often underweight following a period of glucosuria, osmotic diuresis, and catabolism due to insulin deficiency. The initial weight gain upon commencing insulin treatment is viewed as normalization. However, as patients work to bring their glycated hemoglobin (HbA_1c) level as close to the target level of ²7% as possible, a subset will not just normalize to their pre-diabetes weight but begin to exceed it.^2,3 In the DCCT, weight gain with intensive diabetes therapy was greater than with conventional treatment (5.1 versus 3.7kg; p<0.0001 during the first 12 months of therapy). After 12 months, the intensively treated cohort continued to gain weight that was, on average, 10% above ideal,⁴ and one-quarter of the intensively treated subjects attained an average body mass index (BMI) that exceeded 30kg/m2,² the current cut-off for obesity. The subgroup that gained this excess weight had larger waist-to-hip measurements (central obesity), higher triglyceride levels, and lower high-density lipoprotein (HDL) cholesterol, and required more insulin (on a unit/kg/day basis) to achieve the same glycemic targets as a matched group that did not gain weight with intensive therapy2— all outcomes we now associate with the metabolic syndrome and increased risk for cardiovascular disease. Taken together, these observations suggest that weight gain with intensive therapy of type 1 diabetes should not be overlooked in the everyday clinical setting.

The analysis of this problem raises two questions: how do patients cope with the insulin-induced weight gain, and does this weight gain negate the improvements achieved by lowering blood glucose? Regarding the first question, early in the feasibility study DCCT researchers attempted to limit weight gain through intensive nutritional management.⁵ Despite these efforts, excess weight gain still emerged as a significant complication of intensive management in the full trial.⁶ Instead, it has become evident that to avoid unwanted weight gain some patients with type 1 diabetes deliberately ignore the prescribed insulin advice. A US study of 341 women (aged between 13 and 60 years) with type 1 diabetes reported that 31% intentionally omitted insulin,⁷ with half of them citing weight control as their primary reason. These women had more diabetes-related hospitalizations and microvascular complications and displayed greater psychological distress than patients that adhered to treatment. The authors concluded that: “Patients pre-occupied with weight concerns may also become emotionally overwhelmed by insulin treatment and the associated weight-related consequences, thus reinforcing the desire to omit insulin and maintain elevated blood glucose levels.”

The problem of insulin omission was confirmed in a small UK study of 65 young individuals with type 1 diabetes who were followed during the transition from adolescence to young adulthood.⁸ In that study, 30% of the women admitted to having underdosed insulin to manipulate their weight, while 45% of women who developed microvascular complications had intentionally misused insulin doses to prevent weight gain. Despite the omission, average weight and BMI increased during the 10-year study; women were overweight as both adolescents and adults, while men became overweight as young adults. Concern about bodyweight and form increased significantly with time for both sexes, resulting in increased dietary restraint. Given the benefits of improved glycemic control on both microvascular and macrovascular events in patients with type 1 diabetes,^9,10 such suboptimal glycemic control arising from insulin misuse has worrying prognostic implications.