Early Insulin Hit Leads to Diabetes Remission



GUANGZHOU, China, May 22 -- Giving newly diagnosed type 2 diabetes patients intensive insulin therapy for a few days or weeks can drive the disease into extended remission and at least partly restore β-cell function, researchers here said.
Action Points
  • Explain to interested patients that insulin therapy is usually not initiated in patients with newly diagnosed type 2 diabetes until diet and lifestyle changes and oral hypoglycemics have been tried.

  • Note that this study suggests that early, intensive insulin treatment might restore normal blood glucose and allowed extended remission without the need for treatment other than diet or exercise.

In a randomized controlled trial, patients treated with intensive insulin achieved normal glucose levels faster than those treated with oral hypoglycemic agents, according to Jianping Weng, M.D., of Sun Yat-Sen University, and colleagues.

Once blood glucose levels were normal, all patients in the trial stopped medication and attempted to control their diabetes with diet and exercise alone, Dr. Weng and colleagues reported in the May 24 issue of The Lancet.

But a year later, the rate of remission among the patients given insulin was significantly higher (at P=0.0012) than among those who got oral agents, Dr. Weng and colleagues found.

The findings "support the initiation of early, transient, intensive insulin treatment" in newly diagnosed diabetes patients, the researchers concluded.

Their study randomized 381 patients newly diagnosed with type 2 diabetes to get either a continuous subcutaneous insulin infusion, multiple daily insulin injections, or oral hypoglycemic agents (gliclazide, metformin, or both.)

Overall, 92.1% of patients achieved normal glucose levels in 7.9 days on average. But more of those getting the insulin reached normal levels and they did so more quickly, Dr. Weng and colleagues said.

Among those getting continuous insulin, 97.1% reached normal levels, in 4.0 days on average, while 95.2% of those getting multiple injections reached the target, in 5.6 days on average.

In contrast, 83.5% of those on the oral agents reached the target, in 9.3 days on average. The differences were significant at P<0.0001>P=0.01 for the injections.

Dr. Weng and colleagues also found that immediately after the treatment period, acute insulin response was partly restored, β-cell function was significantly increased, and insulin resistance was significantly decreased in all patients (at P<0.0001).>

A year after stopping therapy, the remission rate was 42% among those who reached normal blood glucose levels during the treatment period, the researchers said.

But the rates were 51.1% among those who were treated with insulin infusion, 44.9% among those given insulin injections, and only 26.7% in the oral hypoglycemic agents group.

The risk of relapse was reduced by 44% with the insulin infusion and 31% with injections compared with the oral hypoglycemic agents, reductions that were significant at P=0.001 and P=0.032, respectively.

The data suggest that the use of intensive insulin therapy early in the course of the disease "warrants further clinical investigation," wrote Ravi Retnakaran, M.D., of the University of Toronto, and Daniel Drucker, M.D., of the Banting and Best Diabetes Centre in Toronto, in an accompanying comment.

They said the findings might support the idea that the insulin therapy allows damaged β-cells to rest and perhaps recover -- the so-called "β-cell rest" theory.

But other biological mechanisms might also play a role, they said, adding that an "increased mechanistic understanding" of the process might lead to an explanation of why and how the β-cells decline in the first place.

They also pointed out some limitations of the study, including limited description of β-cell function and glycemic control during the year, absence of clinical characterization of the remission and non-remission

groups at 1 year; and the single ethnic group under study.

The study was supported by the 973 Programme of the Chinese government, Natural Science Foundation of Guangdong Province Government, Novo Nordisk (China), and Roche Diagnostics (Shanghai). Sun Yat-Sen University has an unrestricted research grant from Novo Nordisk (China) and Roche Diagnostics (Shanghai).

The study authors said they have no conflicts of interest.

Dr. Retnakaran receives research support from Merck. Dr. Drucker has served as an adviser for or consultant to Amylin Pharmaceuticals, Arisaph Pharmaceuticals, Conjuchem, Eli Lilly, Emisphere Technologies, GlaxoSmithKline, Glenmark Pharmaceuticals, Isis Pharmaceuticals, Merck Research Laboratories, Novartis Pharmaceuticals, Novo Nordisk, Phenomix, Takeda, and Transition Pharmaceuticals. He also receives research support from Merck and Novo Nordisk.


By Michael Smith, North American Correspondent, MedPage Today
Published: May 22, 2008
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

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