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New paradigm for treatment of type 1 diabetes

New paradigm for treatment of type 1 diabetes

In a breakthrough study of type 1 diabetes published in the journal Diabetes Care, the scientists have found that the rapid decline in insulin production responsible for the condition continues to fall by almost 50 percent each year for seven years and then stabilizes.

The study was conducted by Beverley Shields, statistician at the University of Exeter Medical School, and colleagues to examine the association between log-transformed C-peptide levels and the duration of diabetes up to 40 years after diagnosis.

Type 1 diabetes affects around 69 million people in India. The disease commonly starts in childhood but can develop at any age, and causes the body’s own immune system to attack and destroy the insulin-producing cells in the pancreas, leaving the patient dependent on life-long insulin injections.

The study measured the levels of C-peptide, which is produced at the same time and in the same quantities as the insulin that regulates our blood sugar. By measuring C-peptide levels in urine or in blood, the scientists determined the amount of insulin produced by a person themselves, even if they are taking insulin injections for the treatment.

For the study, the scientists assessed the pattern of association between urinary C-peptide/creatinine ratio (UCPCR) and duration of diabetes in cross-sectional data from 1,549 individuals with type 1 diabetes using nonlinear regression approaches. The findings were then replicated in longitudinal follow-up data for both UCPCR (n = 161 individuals, 326 observations) and plasma C-peptide (n = 93 individuals, 473 observations).

Key Findings:

  • Two clear phases of C-peptide decline were identified: an initial exponential fall over 7 years (47% decrease/year [95% CI −51%, −43%]) followed by a stable period thereafter.
  • The two phases had similar durations and slopes in patients above and below the median age at diagnosis (10.8 years), although levels were lower in the younger patients irrespective of duration.
  •  Patterns were consistent in both longitudinal UCPCR (n = 162; ≤7 years duration: −48%/year [−55%, −38%]; >7 years duration −0.1% [−4.1%, +3.9%]) and plasma C-peptide (n = 93; >7 years duration only: −2.6% [−6.7%, +1.5%]).

The finding is a major step forward in understanding Type 1 diabetes and contradicts previous beliefs that the insulin produced by people with the condition drops relentlessly with time. It offers the hope that by understanding what changes after seven years, new strategies could be developed to preserve insulin secreting beta-cells in patients.

Dr. Shields, said: “This finding is really exciting. It suggests that a person with Type 1 diabetes will keep any working beta-cells they still have seven years after diagnosis. We are not sure why this is; it may well be that there is a small group of “resilient” beta-cells resistant to immune attack and these are left after all the “susceptible” beta-cells are destroyed. Understanding what is special about these “resilient” beta-cells may open new pathways to treatment for Type 1 diabetes.”

Professor Andrew Hattersley, a Consultant in Diabetes at the Royal Devon and Exeter Hospital and Research Professor at the University of Exeter Medical School, looked forward. “Now we know there is a “seven-year switch”, the next question is why? Has the immune attack stopped or are we left with “super beta-cells” that can resist the immune onslaught. Any insights into halting the relentless destruction of the precious insulin-producing cells are valuable. We could not have made this progress without the help of over 1,500 patients. We owe it to them to try to find answers that might help patient care quickly.”

Based on the study, the authors concluded that these data support two clear phases of C-peptide decline: an initial exponential fall over a 7-year period, followed by a prolonged stabilization where C-peptide levels no longer decline. Understanding the pathophysiological and immunological differences between these two phases will give crucial insights into understanding β-cell survival.

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Source: With inputs from Diabetes Care

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