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paresh dandona, md

A study led by Paresh Dandona, MD, PhD, is the first to show that insulin essentially suppresses a protein involved in pro-inflammatory processes.

Published June 6, 2013

Study Shows Strong Effect of Insulin, Glucose on Inflammation

A University at Buffalo study has discovered that insulin injections exert a strong anti-inflammatory effect at the cellular and molecular level in Type 1 diabetics.

“Without the protection of injectable insulin, Type 1 diabetics risk inflammation with even a small amount of carbohydrate over a short period.”
Paresh Dandona, MD, PhD
SUNY Distinguished Professor of medicine

The study also found that even small amounts of glucose result in “profound inflammation” in these patients.

Insulin Suppresses Pro-Inflammatory Protein

This study is the first to show that insulin essentially suppresses HMG-B1.

This protein facilitates the synthesis of pro-inflammatory cytokines―messenger proteins released by injured cells that, in turn, induce further inflammation.

Type 1 Diabetics Show Some Delayed Responses

The researchers found that insulin’s anti-inflammatory effect takes three times as long to occur in Type 1 diabetics (about six hours), compared to Type 2 diabetics and obese patients (two hours).

Similarly, glucose infusion led to inflammatory markers known as reactive oxygen species after about six hours in Type 1 diabetics, compared to approximately one-to-two hours in Type 2 diabetics and obese patients.

“The reason for this delayed response is not clear and requires further investigation,” says first author on the study, Paresh Dandona, MD, PhD, SUNY Distinguished Professor of medicine, and chief of endocrinology and metabolism.

“It is possible that Type 1 diabetes patients have a more intense level of inflammation, which requires a greater effort to induce a change.”

Even Small Amounts of Glucose Inflammatory

“Our findings also show that without the protection of injectable insulin, Type 1 diabetics risk inflammation with even a small amount of carbohydrate over a short period,” he says.

When given small amounts of glucose without insulin, Type 1 diabetics experienced a small but significant increase in glucose concentrations; Type 2 diabetics and obese patients were not affected.

In Type 1 diabetics, the infusion of 20 grams of glucose―the equivalent of just four teaspoons of sugar―over four hours “leads to a profound inflammatory effect, including the generation of the HMG-B1 protein,” says Dandona.

Blood Sugar Spiked without Insulin

In the study, after an overnight fast, 10 Type 1 diabetics received either two units of insulin with 100 milliliters of 5 percent dextrose per hour, or just the dextrose. Blood samples were collected immediately after the fast and two, four and six hours later.

In the insulin-plus-dextrose group, markers of inflammation were suppressed and blood sugar readings stayed normal, at around 100 mg/dl (milligrams per deciliter).

Those who received just dextrose, however, experienced a blood sugar spike from 115 mg/dl after fasting to 215 mg/dl at four and six hours, as well as an increase in the generation of key inflammatory markers.

These markers include reactive oxygen species and toll-like receptors. The latter are proteins that play a key role in the innate immune system and may be involved in inflammatory processes, including those leading to gram positive and gram negative infections, as well as metabolic inflammation associated with obesity, diabetes and atherosclerosis.

Type 1 Diabetics Risk Infection

“This has extremely important implications for Type 1 diabetics” in terms of the severity of inflammation in patients with infections and the importance of taking insulin with meals, Dandona notes.

Although Type 1 diabetics are already being treated with insulin injections, “they can be susceptible to infections and other inflammatory conditions, which lead to serious, even life-threatening, complications, such as septicemia,” he explains.

The researchers have already begun a follow-up study to “better understand what missing even a single insulin injection at mealtime means to a Type 1 diabetic patient,” he says.

Paper Published in American Journal of Physiology

The study, “Insulin Infusion Suppresses While Glucose Infusion Induces Toll-Like Receptors and High-Mobility Group-B1 Protein Expression in Mononuclear Cells of Type 1 Diabetes Patients,” has been published in the American Journal of Physiology: Endocrinology and Metabolism.

Co-authors include Ajay Chaudhari, MD, clinical associate professor of medicine, Husam Ghanim, MD, research assistant professor of medicine; Nitesh Kuhadiya, MD, and Manav Batra, MD, both UB medical residents; and Sandeep Dhindsa, MD, former associate professor of medicine.

The study builds on previous UB research documenting insulin’s anti-inflammatory effects in obese and Type 2 diabetes patients.