Beta-cell dysfunction typifies type 2 diabetes without obesity – Healio

February 24th, 2020 11:43 am

The response to a glucose-potentiated arginine test varied between those with and without obesity among a cohort of adults with type 2 diabetes, particularly in insulin sensitivity and proinsulin secretory ratio, which suggests that beta-cell function is compromised in patients without obesity, according to findings published in Diabetes/Metabolism Research and Reviews.

These data demonstrate that in nonobese type 2 diabetes, early in the disease course insulin secretion defects predominate with impaired beta-cell sensitivity to glucose and less efficient processing of proinsulin, together contributing to compromised beta-cell function, Michael R. Rickels, MD, MS, professor of medicine in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues wrote. We did not find a significant reduction in insulin sensitivity in the nonobese type 2 diabetes subjects, supporting a primary beta-cell defect as the etiology of their impaired glucose regulation.

Rickels and colleagues employed a glucose-potentiated arginine test on 28 adults with type 2 diabetes and obesity (mean age, 54.7 years; 14 women), 12 adults with type 2 diabetes and no obesity (mean age, 58.8 years; one woman) and 12 adults with neither condition (mean age, 32.2 years; two women). The test allowed the researchers to assess acute insulin response to arginine, glucose potentiation of arginine-induced insulin release, beta-cell secretory capacity, beta-cell sensitivity to glucose, insulin sensitivity, the insulin secretion disposition index and the proinsulin secretory ratio. The researchers assessed the disposition index and proinsulin secretory ratio three times during the test.

The response to a glucose-potentiated arginine test varied between those with and without obesity among a cohort of adults with type 2 diabetes, particularly in insulin sensitivity and proinsulin secretory ratio, which suggests that beta-cell function is compromised in patients without obesity

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The researchers found that participants with type 2 diabetes and no obesity had greater proinsulin secretory ratios at the first (5 vs. 2.8), second (4.9 vs. 2.1) and third (2.6 vs. 1.7) assessment as well as greater insulin sensitivity (0.44 vs. 0.21 [mg/kg1/min1]/[U/mL]) compared with participants with type 2 diabetes and obesity (P < .05 for all). In addition, participants with type 2 diabetes and no obesity had greater levels of beta-cell sensitivity to glucose (208 vs. 160 mg/dL) compared with those without diabetes or obesity (P < .05). Participants with type 2 diabetes and no obesity also had a reduced mark on the disposition index on the second (28.6 vs. 54.5 mg/kg1/min1) and third (45.6 vs. 79.2 mg/kg1/min1) assessment compared with those without diabetes or obesity (P < .05 for both).

The present evidence supports the characteristic association of obese type 2 diabetes with insulin resistance, and that decreased beta-cell sensitivity to glucose and impaired proinsulin processing represent the predominant early pathophysiologic defects in nonobese type 2 diabetes, the researchers wrote. These findings help to differentiate a phenotype for the early presentation of type 2 diabetes wherein future therapeutic interventions may target beta-cell dysfunction as the primary defect in nonobese individuals and insulin resistance as the dominate problem in obese individuals. by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.

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Beta-cell dysfunction typifies type 2 diabetes without obesity - Healio

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