In my literature review, I have come across many articles that blame hyperinsulinemia for inflammation in the diabetic patients with “insulin resistance.” [1, 2, 3] I have also reviewed articles that proclaim the wonder of insulin in reducing the magnitude of hyperglycemia, at the same time, the level of inflammation. Insulin has been used for saving lives in emergency and critical care. Based on all the articles that I have sampled, it really does not make sense to blame hyperinsulinemia for inflammation [4, 5, 6]. However, persuading the medical establishment for a review for anytime soon seems very difficult. So, my odd arguments are just like that of the innocent child in the story of “The Emperor’s New Clothes.” [7]
Insulin is produced by the beta cells of the pancreas, in response to a rising blood glucose level, to help the cells of the body take glucose in for producing energy for life, storing as glycogen in the liver and muscle, and as fat in the fatty tissue. Thus, insulin reduces the blood glucose level, which is kept within a normal range if the beta cells produce an adequate amount of insulin. However, studies have found that a rising blood glucose level triggers a swarm of inflammatory factors including interleukin-6 (IL-6), tumor necrosing factor-alpha (TNF-alpha), interleukin-18 (IL-18), as well as C-reactive protein (CRP.) Interestingly, the increase of these inflammatory factors was observed even in absence of an increase of insulin production. Thus, inflammation is present solely in a state of hyperglycemia.
One study, published in 2002 by Esposito K. et al., reported that when blood glucose level was maintained at 270 mg%, by suppressing the insulin produced by the subjects’ pancreas, an increase of inflammatory factors including IL-6 and IL-18 was sustained during the period of hyperglycemia. TNF-alpha was also increased but not as dramatic as both IL-6 and IL-18. When blood glucose level was increased to 270 mg% periodically of every two hours, all the inflammatory factors were increased again, however, their levels were fluctuating following the periodical increase of the blood glucose level. In both experiments, the diabetic subjects had higher levels of inflammatory factors in response to the same magnitude of increase in blood glucose than the “non-diabetic” subjects for control did. [8]
In another study, published in 2007 by Cifarelli V, et al., reported the titer of an inflammatory activator, CD11b antigen on monocyte phenotype, was higher in type 1 diabetic patients who were diagnosed within one week prior to the test than other type 1 patients who were diagnosed within two months. In other words, the newly diagnosed type1 diabetic with no insulin therapy had higher level of inflammation than those patients who had started insulin treatment. In the same study, the titer of CD11b was found positively correlated to the Hemoglobin A1c, or HbA1c. The highest CD11b was found in those with more than 8% of HbA1c. The study underscores hyperglycemia is responsible for inflammation. [9]
The question on the role of hyperinsulinemia in inflammation arose in the cases of insulin resistance and metabolic syndrome, which are characterized with inflammation and complications. The current consensus is apparently based on the increase of the titer of insulin, which “fails” to facilitate the cells in taking up blood glucose, and to result in hyperglycemia and inflammation in the cases of insulin resistance and metabolic syndrome. This is really a matter of interpretation between chicken and egg. It is a case of misidentification, one of many wrong ideas that the medical establishment believes! Keep in mind, hyperglycemia is most likely present ahead of hyperinsulinemia, and is simply a result of carbohydrate-abuse. Studies have shown adopting the carbohydrate-restricted diet reversed insulin resistance and improved metabolic syndrome, because reducing the supply of blood glucose immediately stop burdening the body with blood glucose, without having to involve the utilization of glucose facilitated by insulin. Evidently, by reducing the overflow of blood glucose, inflammation is subsided without the concern of hyperinsulinemia, which is eased spontaneously. [10, 11, 12]
The findings are evident that we should blame hyperglycemia, but not hyperinsulinemia for inflammation.
Robert Su, Pharm B., M.D.
References:
1. Setola E. et al. “Fasting hyperinsulinemia associates with increased sub-clinical inflammation in first-degree relatives normal glucose tolerant women independently of the metabolic syndrome” Diabetes Metabolism Research & Review. 2009 Oct;25(7):639-46.
2. Fishel MA, et al.“Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults.” Archive of Neurology. 2005 Oct;62(10):1539-44.
3. Krogh-Madsen R, et al. “Insulin stimulates interleukin-6 and tumor necrosis factor-a gene expression in human subcutaneous adipose tissue.” Am J Physiol Endocrinol Metab 286: E234–E238, 2004.
4. Dandona P, et al. “Insulin infusion in acute illness.” J Clin Invest. 2005;115(8):2069–2072
5. Jeschke MG, et al. “Effect of insulin on the inflammatory and acute phase response after burn injury.” Critcal Care Medicine. September 2007 – Volume 35 – Issue 9 – pp S519-S523
6. Chaudhuri, A, et al. “Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction.” Circulation 2004;109;849-854
7. Hans Christian Anderson. “The Emperor’s New Clothes.”
8. Esposito K. et al. “Plasma glucose concentrations attained during hyperglycemic clamps and after consecutive glucose pulses.” Circulation 2002;106:2067-2072
9. Cifarelli V, et al. “Increased Expression of Monocyte CD11b (Mac-1) in Overweight Recent-Onset Type 1 Diabetic Children.” The Review of Diabetic Studies. Vol. 4 ⋅ No. 2 ⋅ 2007.
10. Boden G, et al. “Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes.” Annals of Internal Medicine, Volume 142, Number 6, Pages 403-11. March 15, 2005.
11. Gannon MC and Nuttal FQ. “Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes.” Diabetes, Volume 53, Number 9, Pages 2375-2382. 2004.
12. Nuttall FQ and Gannon MC. “The metabolic response to a high-protein, low-carbohydrate diet in men with type 2 iabetes mellitus.” Metabolism. Volume 55, Issue 2, Pages 243-251. February 2006.
