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Insulin sensitivity signals favorable metabolic profiles in adults with obesity
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Adults with obesity and insulin sensitivity in muscle or liver or both appear to be metabolically healthy with lower blood pressure and less visceral and liver fat, according to recent findings.
In the study, Jerry R. Greenfield, PhD, FRACP, of the Garvan Institute of Medical Research in Australia, and colleagues evaluated 64 adults without diabetes but with obesity (29 men) recruited between 2011 and 2013 to determine phenotypic and metabolic factors associated with insulin sensitivity in muscle and liver.
Participants underwent 6-hour, two-step hyperinsulinemic-euglycemic clamps with deuterated glucose traces. The researchers computed tertiles of insulin sensitivity based on the glucose infusion assessed during high-dose insulin clamp. Participants in the top tertile for glucose infusion were classified as muscle insulin-sensitive and those in the lower two tertiles were designated muscle insulin-resistant.
Tertiles of endogenous glucose production (EGP) suppression during the low-dose insulin clamp were assigned. Those in the top tertile for EGP were categorized as liver insulin-sensitive and the rest were classified as liver insulin-resistant.
The researchers compared metabolic phenotypes of those who were muscle insulin-sensitive vs. those who were muscle insulin-resistant and repeated these analyses through comparisons based on hepatic insulin sensitive vs. resistant participants.
The researchers found that while BMI and total fat were comparable between muscle insulin-sensitive and muscle insulin-resistant participants, those who were muscle insulin-sensitive had lower HbA1c (P < .001), systolic BP (P = .01) and diastolic BP (P = .03).
Participants had comparable subcutaneous fat. Muscle insulin-sensitive participants had lower visceral and liver fat (P < .001 for both).
Compared with participants who were liver insulin-resistant, participants who were liver insulin-sensitive had lower visceral and liver fat (P < .01 for both) and lower C-reactive protein (P = .02).
Insulin sensitivity at the muscle or liver appeared to be protective against adverse metabolic features seen in participants with insulin resistance at both locations. A total of 54% of the variation in muscle insulin-sensitivity was attributable to HDL-cholesterol, 1-hour glucose, systolic BP and triglycerides.
“While the debate regarding the long-term protective value of insulin sensitivity in obesity persists, insulin resistance in both muscle and liver is associated with the poorest cardiometabolic profile and is characterized by visceral and liver fat accumulation,” the researchers wrote. “Identification of obese individuals at high risk of metabolic disease is vital for early and effective interventions to minimize disease and health costs. Factors readily measured in clinical practice may serve as early detection tools, guiding targeted intervention.” – by Jennifer Byrne
Disclosure: Greenfield reports being a recipient of the Don Chisholm Fellowship.
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