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Fasting insulin, insulin resistance may predict weight gain over 10 years

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February 17, 2018

Nicholas Pennings
Nicholas Pennings

In a population-based cohort, each 1 µU/mL increase in fasting insulin level was associated with an average half-pound increase in body weight over 10 years, whereas each unit increase in insulin resistance was associated with an average 1.32-pound increase in body weight over the same period, according to findings published in Diabetes Metabolism Research and Reviews.

“Past reports have shown mixed results on the role of endogenous insulin levels in weight gain,” Nicholas Pennings, DO, assistant professor and chair of family medicine at Campbell University School of Osteopathic Medicine in Buies Creek, North Carolina, told Endocrine Today. “This study examined the relationship between fasting insulin levels and weight gain and identified that weight occurred as insulin levels began to rise, triggering weight gain before glucose rose to abnormal levels. The impact of rising insulin levels is seen at fairly low fasting insulin levels and diminishes at higher levels where insulin resistance is more significant.”

Pennings and colleagues analyzed self-reported 10-year weight change from 3,840 participants of the 2011-2014 cycles of the U.S. National Health and Nutrition Examination Survey (mean age, 46 years; 49.3% men; 41% white; 31.5% with overweight; 29.6% with obesity; 20.5% current smokers). Researchers stratified the cohort into six groups based on fasting glucose, defined as normal, prediabetic or diabetic, and by fasting insulin levels, which were categorized as normal ( 25th percentile) or elevated ( 25th percentile), and calculated insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR). Researchers used linear regression analysis to predict the linear relationship between insulin and HOMA-IR and weight change over 10 years. Participants who intentionally lost weight through diet or exercise or prescribed weight-loss medications were excluded from the study.

Within the cohort, 25% hada normal insulin concentration with mean insulin resistance 0.9; 75% had an elevated insulin concentration with mean insulin resistance 3.68.

Researchers found that participants with elevated insulin level and diabetes saw the greatest weight gain over 10 years, a mean of 11.82 pounds, followed by participants with an elevated insulin level and prediabetes, who experienced a mean gain of 11.68 pounds over 10 years. Those with elevated insulin level but normal glucose level saw an average gain of 10.67 pounds.

In contrast, participants with a normal insulin level but considered prediabetic by blood glucose had the lowest weight gain over 10 years, an average of 0.84 pounds, followed by participants with a normal insulin level and normal glucose level, who experienced a mean gain of 2.39 pounds over 10 years. Those with a normal insulin level but with diabetes experienced a mean weight loss of 14 pounds, according to researchers.

The researchers found that each 1 µU/mL increase in insulin caused an average 0.52-pound increase in body weight over 10 years (P < .0001), whereas each unit increase in HOMA-IR caused an average 1.32-pound increase in weight over 10 years (P < .0001).

“This study provides further insight on the dynamic relationship between endogenous insulin production and insulin resistance,” Pennings said in an interview. “Dietary actions that stimulate endogenous insulin production, such as excess consumption of sugar and refined carbohydrates, result in weight gain, but as insulin resistance and glycemic state progress, weight gain is attenuated. However, the reduction in weight gain may be at metabolic expense, as excess calories are no longer effectively stored in the face of insulin resistance, but instead circulate as elevated glucose and free fatty acids. This, in turn, contributes toward the progression of type 2 diabetes.”

Pennings said the to prevent weight gain, it is important clinicians work with patients to avoid actions that increase insulin release, such as consumption of sugar and refined carbohydrates, as well as encourage activities that improve insulin sensitivity, such as exercise. – by Regina Schaffer

For more information:

Nicholas Pennings, DO, can be reached at Campbell University School of Osteopathic Medicine, 129 TT Lanier St., Buies Creek, North Carolina 27506; email: pennings@campbell.edu.

Disclosures: The authors report no relevant financial disclosures.

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Osama Hamdy
Perspective

This study is unique in explaining the triangle relationship between hyperinsulinemia, weight gain and hyperglycemia over time. It supports our long-time clinical observation that dysglycemia and onset of diabetes is frequently preceded by an accelerated period of weight gain. It seems now that the sequence of events in the roadmap to diabetes is much clearer. It all starts with slight weight gain in a genetically determined individual that is followed by hyperinsulinemia, and then a period of accelerated weight gain, mostly caused by the anabolic effect of insulin, which results in further, more-severe insulin resistance. Insulin resistance is then associated by a slower weight gain due to increased lipolysis from visceral adipose tissue, which in turn increases free fatty acids and lipotoxicity, which leads to beta-cell dysfunction and hyperglycemia. A perfect storm is brewing. The question is: When is the better time to intervene when you see these signals in order to prevent diabetes?

Osama Hamdy, MD, PhD, FACE

Medical Director, Obesity Clinical Program
Director of Inpatient Diabetes Program
Joslin Diabetes Center
Harvard Medical School

Disclosure: Hamdy reports no relevant financial disclosures.