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Early Short-term Intensive Insulin Causes the Remission of Type 2 Diabetes

Starting patients diagnosed within the last 7 years on 2-4 weeks of intensive insulin therapy could help keep them off additional medications for at least 48 weeks.

In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2-4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to one year in some patients.

Data was evaluated from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM.

For the study design, data from the placebo arm of the double-blind randomized controlled trial in which 25 patients within 7 y of T2D diagnosis received 4 weeks of intensive basal/bolus insulin therapy followed by placebo for 48 wk.  An oral glucose tolerance test (OGTT) every 12 weeks used to assess insulin sensitivity and beta-cell function. Then diabetes remission was defined as HbA1c <6.5% with no T2D medications.

The results showed that at 48 weeks after stopping intensive insulin, 14 participants (56%) were in diabetes remission. At baseline, the remission group had shorter duration of diabetes (1.2 vs 2.6 y; p=.03), lower A1c (6.2% vs 7.1%, p=.006), and better β-cell function.

The 2 groups did not differ in clinical characteristics such as age, gender, ethnicity, pre-study diabetes treatment, body mass index, waist circumference, blood pressure, liver enzymes, or insulin sensitivity.

Then, in logistic regression analyses, shorter duration of diabetes supplanted baseline A1c (p=.24) and β-cell function (p=.19) as an independent predictor of remission at 48 weeks (OR, 0.22; 95% CI 0.05-0.92; p=.04)

At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function

The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis. And reversing or delaying type 2 diabetes may help prevent morbidity and reduce healthcare costs.

In another study for newly diagnosed type 2 patients within days of being diagnosed, (Short-Term Intensive Insulin Therapy in Newly Diagnosed Type 2 Diabetes), they were able to get their A1c down to 6.6% with a short term treatment with insulin.

Previous studies have shown that acute correction of hyperglycemia in subjects with long-standing type 2 diabetes gives only short-term improvement in glycemic control after discontinuation of insulin. This study attempts to identify any characteristics of patients with newly diagnosed type 2 diabetes (fasting glucose >180 mg/dL),(11.0 mmol/l) who would have a long-term benefit, in terms of glycemic control, from a brief course of insulin therapy.

In this study, a total of 16 subjects (52 ± 2 years old [range 36–64], BMI 30.8 ± 1.9 kg/m2) with newly diagnosed type 2 diabetes had a 2–3 week course of intensive insulin therapy that was then discontinued.

What was found was that fasting glucose fell from 230mg/dL to 126 mg/dL. and this improvement was maintained at the 1-year follow-up.. The insulin area under the curve for the post treatment oral glucose tolerance test also improved directly after insulin therapy, and at 1 year, seven of the subjects maintained good glycemic control on diet therapy alone, eight required oral hypoglycemic agent (OHA) therapy, and one required insulin therapy. The distinguishing features of those who did not require OHA or insulin therapy were that they required less insulin during the active insulin therapy phase (0.37 ± 0.05 vs. 0.73 ± 0.07 units · kg−1 · day−1) and were able to attain a lower fasting serum glucose at the end of the period of insulin therapy 106 mg/dL vs. 139 mg/dL + 7 mg/dL. (5.9 ± 0.3 vs. 7.7 ± 0.4 mmol/l).

Again these results demonstrate that in newly diagnosed type 2 diabetes with elevated fasting glucose levels, a 2- to 3-week course of intensive insulin therapy can successfully lay a foundation for prolonged good glycemic control. The ease with which normoglycemia is achieved on insulin may predict those patients who can later succeed in controlling glucose levels with attention to diet alone. As we get closer to an oral pill for insulin, most people probably would not opt for early insulin injection before trying other treatments.

Practice Pearls:

  • Early at diagnosis, short-term insulin treatment can provide better glucose control.
  • Starting on insulin soon after diagnosis can impact future treatments.
  • Insulin sooner than later that is reducing glucotoxicity has many benefits, including reducing the complications from diabetes.

References:

Kramer CK, Zinman B, Choi H, Retnakaran R. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes. BMJ Open Diabetes Res Care. 2016;4:e000270. doi: 10.1136/bmjdrc-2016-000270. PMID: 27547422  ClinicalTrials.Gov NCT01270789; Post-results.

Diabetes Care 2004 May; 27(5): 1028-1032. http://dx.doi.org/10.2337/diacare.27.5.1028