Repeat courses of intensive insulin do not ‘reset the clock’ in type 2 diabetes
medwireNews: A recurring brief intensive course of insulin every 3 months does not build on metabolic improvements gained from an induction course in people with type 2 diabetes of relatively short duration, say researchers.
All 108 participants in the randomized controlled trial had a 3-week induction course of intensive basal–bolus insulin. At the point of enrollment, these people had type 2 diabetes lasting a median of 1.3 years, and had a median glycated hemoglobin level of 6.6% (49 mmol/mol).
As expected, results from oral glucose tolerance tests done before and after the initial insulin therapy showed that this significantly improved beta-cell function (based on the Insulin Secretion-Sensitivity Index-2), whole-body insulin sensitivity, hepatic insulin resistance, and blood glucose levels.
Over the following 2 years, all participants took metformin, but whereas 53 took it throughout, 55 participants suspended it for 2 weeks every 3 months, during which they again received basal–bolus insulin therapy.
Although these intensive treatment periods successfully reduced glucose levels to the same degree as the initial course, they did not have any lasting metabolic effects, report Ravi Retnakaran (Mount Sinai Hospital, Toronto, Ontario, Canada) and study co-authors.
The primary outcome of baseline-adjusted Insulin Secretion-Sensitivity Index-2 at 2 years was not significantly different between the groups and was in fact slightly higher in the metformin-only group.
There were also no treatment-related differences in other measures of beta-cell function, nor in glycated hemoglobin or fasting glucose levels.
“These findings may reflect the limited window of time in the natural history of diabetes during which there exists a significant reversible component of beta-cell dysfunction that is responsive to [intensive insulin therapy],” write the researchers in Diabetes, Obesity and Metabolism.
They add that the data “suggest that, despite inducing initial metabolic benefit, short-term [intensive insulin therapy] does not reset the clock underlying the window of reversibility of beta-cell dysfunction in early [type 2 diabetes].”
In exploratory analyses, the team found no difference in beta-cell function between the treatment groups among people with diabetes of less than 2.5 years’ duration. By contrast, there was a marked difference among those with a longer diabetes duration, with better beta-cell function observed in those using metformin only.
The researchers speculate that, given the lack of benefit from repeated courses of insulin, the interruptions to metformin treatment could have been detrimental in people with longer-established diabetes.
“Thus, in practical terms, our findings do not support the use of intermittent [intensive insulin therapy] as a long-term strategy for preserving beta-cell function,” they conclude.
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