Improved In Vivo Insulin Effect During Continuous Subcutaneous Insulin Infusion in Patients with IDDM

Abstract

It has recently been shown that conventionally treated IDDMs are insulin resistant. Using the insulin clamp technique, we studied the influence of metabolic status on the in vivo insulin effect in these patients. Eleven IDDMs, treated conventionally with diet and insulin for 10.7 +/- 5.6 yr, were studied before and after continuous subcutaneous insulin infusion (CSII) treatment (with a portable pump) for 6 mo. We found that conventionally treated diabetic subjects were extremely insulin resistant with regard to peripheral glucose uptake. Glucose uptake, at an insulin concentration of about 80 microU/ml, was 4.3 +/- 2.0 mg/kg X min before treatment compared with 11.5 +/- 4.0 mg/kg X min in normals (P less than 0.01). After pump treatment for 6 mo, metabolic control improved significantly (HbA1c decreased from 8.9 +/- 1.9% to 7.4 +/- 1.2%, P less than 0.01) and, parallel to that, glucose uptake increased about 80% to 7.5 +/- 3.5 mg/kg X min (P less than 0.01). The mean daily plasma FFA level decreased from 0.32 +/- 0.10 mmol/L to 0.21 +/- 0.07 mmol/L (P less than 0.01); this variable was negatively correlated to the glucose clearance rate (r = -0.62, P less than 0.01). There was no statistically significant change in mean daily plasma insulin and plasma growth hormone levels or in 24-h cortisol excretion in the urine (P greater than 0.1). The insulin binding capacity of serum IgG was also unchanged, and there was no significant relationship between this quantity and glucose clearance rates (r = 0.18, P greater than 0.1). We conclude that conventionally treated IDDMs are insulin resistant with regard to peripheral glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: A model for weight gain with intensive insulin therapy

“…After 11 mo of RH, the insulin-treated animals had a mean body mass of 951 vs. 543 g for their control counterparts, an increase of 75%. 23), which was not evident in the present model with RH and control animals showing similar levels of insulin sensitivity; this suggests that weekly, insulin-induced hypoglycemic episodes may provide a more appropriate model for weight gain seen with IIT, as human studies suggest that responses to insulin administration are maintained or improved with such therapy (2). One possibility is that the early period during which animals responded to hypoglycemia with bouts of hyperphagia (shown in Fig.…”

Hyperglycemia Decreases Glucose Uptake in Type I Diabetes

“…However, an improvement in insulin action has been observed in these patients during CSII therapy in the face of both diminished (18) and unchanged (19,20) insulin requirements, indicating that factors other than insulin deficiency were responsible for enhanced insulin action. Although during CSII therapy a decrease in the level of insulinantagonistic hormones has been found (21) In conclusion, short-term hyperglycemia decreases glucose uptake in type I diabetic patients.…”

“…First, the deleterious effect of hyperglycemia per se on glucose uptake may contribute to the development of insulin (or glucose) resistance in various hyperglycemic states and/or aggravate insulin resistance due to other causes. Second, an improvement in glycemic control should be considered a contributing factor to the enhanced glucose uptake observed during therapeutic interventions, e.g., diet (39), oral antidiabetic drugs (40)(41)(42), and CSII (18)(19)(20).…”

Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials

“…This finding is consistent with the known effect of pump therapy in improving insulin sensitivity and reducing insulin resistance in people with type 1 diabetes. 27 28…”