Carbohydrates Can Kill: Hyperglycemia is problematic but preventable by restricting carbohydrates. (1 of 3)

Based on today’s prevalence of diabetes mellitus in the population, your body may be developing the disease before you and your doctor realize. The course of losing the mass of pancreatic beta cells is ongoing in the environment of hyperglycemia. By the time when diagnosis of diabetes mellitus is made, the mass of beta cells has already lost about 50% of its normal size.

Why should diabetes mellitus concern you? Based on the information from the American Heart Association, diabetes mellitus killed 75,119 people in the US between 2005 and 2006. Among them, 48.68% of the total deaths (or 36,538) were men and 51.32% (or 38,581) were women. During that time, 17 millions of American adults were diagnosed with diabetes mellitus; 1.6 millions of new cases would develop a year; and at least 65% of the diabetics died of some forms of heart disease or stroke. [1]

Diagnosis of diabetes mellitus in most of the cases is made when abnormal results of glucose were found in the routine blood tests, urine tests or incidental discovery in the workup for cardiovascular diseases. Thus, there are many people who still do not know that they have been diabetic or pre-diabetic. By the time when about 25% of the original mass of one’s beta cells is damaged, he is pre-diabetic and, as said, when about 50% of the mass is damaged, he is diabetic.

Hyperglycemia is problematic! It is the main pathology shared by diabetes mellitus and many diseases, if not all. Hyperglycemia has at least five roles in disease development, namely (1) inflammatory and pro-inflammatory; (2) pro-thrombotic; (3) vasoconstrictive and pro-hypertensive; (4) arteriosclerotic and atherosclerotic; and (5) Glycosylative and pro-glycation. Many studies have affirmed the above roles.

(1) Inflammatory and pro-inflammatory:

Katherine Esposito, et al. published an article, in Circulation, a journal of the American Heart Association, in 2002, titled, “Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress.” They evaluated changes of IL6 (interleukin-6) TNF (tumor necrosis factor), and IL-18 (interleukin-18) in the participants’ circulation, in response to acute hyperglycemia, and the effects of glutathione (an antioxidant) on the changes.

We have known that diabetic patients have an increase in both IL-6 and TNF. IL-6, TNF, and IL-18 belong to the family of cytokines and are inflammatory factors. This study used 20 non-diabetics for the control and 15 participants with impaired glucose tolerance (IGT.) The study used Octreotide to suppress the endogenous secretion of insulin from the pancreas. Three test projects were conducted. The first experiment (sustaining) used continuous intravenous injection (IV) of glucose to sustain the individual’s blood glucose level at 15 mmol/L or 270 mg% for five hours, and collected their blood samples for measuring the titers of IL-6, TNF, and IL-18. The second (pulse) used boluses of IV glucose (33 g/kg) to raise the individual’s blood glucose level at 15 mmol/L or 270 mg% every two hours for five hours, and collected their blood samples every hour for the titers of IL-6, TNF, and IL-18. Lastly, the individual was given glutathione ahead of IV glucose to raise their blood glucose levels at 15 mmol/L, and collected their blood samples for the titers of these cytokines. The study found the IGTs had higher levels of cytokines before tests than those of control. All participants in the sustaining test had increases of all cytokines, especially the IGTs who had greater increase for a longer period than those of the non-diabetics, except IL-18. In the pulse test, all participants had greater increases at the 3, 4, and 5 hour-point, especially the IGTs had much greater increases than the non-diabetics. When the participants were treated with glutathione before the tests, all participants had only insignificant increases of the cytokines. [2]

Also, studies have shown that, in the presence of hyperglycemia, especially those with diabetes mellitus, infection is complicated with a greater degree of inflammation.

Speaking of hyperglycemia and infection, Carel J. van Oss in 1971 reported that the phagocytosis of Staphylococcus epidermidis, S. aureus, and Escherichia coli by the neutrophils was best at various glucose concentrations between 50 and 100 mg%. The phagocytosis was adversely linked to a higher glucose concentration than 100 mg%. [3]

Similarly, Albert Sanchez et al., in 1973, studied the phagocytosis of Staphylococcus epidermidis by the neutrophils after the study participants ingested 100 grams of glucose, fructose, sucrose, honey, orange juice, and starch respectively. The participants’ venous blood samples were collected at half an hour, one, two, three, four, and five hours after ingesting these carbohydrates respectively. The study found that following ingesting each carbohydrate above, especially the simple sugars, significantly and rapidly decreased the phargocytotic index of the neutrophil. The phagocytotic index is the number of bacteria engulfed by each neutrophil. The decrease in phargocytotic index happened rapidly within the first two hours and lasted for five hours even after their blood sugar returned to the fasting level within the first two hours. Following ingesting starch, the decrease in phargocytotic index did not occur rapidly but lasted longer. The ability of phargocytosis did not seem related to the number of neutorphils. The findings of this study explain why the diabetic patients have little resistance to infection. A noteworthy finding of this study is fasting for a period of 36 to 60 hours significantly augmented the phargocytotic index. [4]

During the recent decade, the roles of hyperglycemia and inflammation have received more attention. Professors Koichi Node and Teruo Inoue of Japan reported in 2009, that “[P]ostprandial hyperglycemia is characterized by hyperglycemic spikes that induce endothelial dysfunction, inflammatory reactions and oxidative stress, which may lead to progression of atherosclerosis and occurrence of cardiovascular events. Emerging data indicate that postprandial hyperglycemia or even impaired glucose tolerance may predispose to progression of atherosclerosis and cardiovascular events. There is evidence that postprandial hyperglycemia, but not fasting hyperglycemia, independently predicts the occurrence of cardiovascular events. We proposed a concept of ‘vascular failure’ as a comprehensive syndrome of vascular dysfunction extending from risk factors to advanced atherosclerotic disease. Postprandial hyperglycemia is therefore one of the very important pathophysiological states contributing to vascular failure. Accordingly, controlling postprandial hyperglycemia should be the focus of future clinical investigation as a potential target for preventing vascular failure.” This statement was well said. The key question is what we can do to control postprandial hyperglycemia. [5]

In 2002, Kathrin Maedler and her colleagues reported that an increase of IL-1beta -producing beta-islet cells in the pancreas of the type 2 diabetic participants, but not in the pancreas of the non-diabetic participants in comparison. The consequence is High blood sugar beta-cell of the pancreas Producing IL-1 beta Starting Fas-triggering cell death by activating NF-kB Death and destruction of cells with increase of DNA fragments. They concluded that exposing the beta-islet cells of the non-diabetic person to chronic hyperglycemia could cause diabetes (DM). in other studies, trace of inflammation was found in the pancreas of type 1 diabetics too. [6]

Now, we know how hyperglycemia can damage beta cells and develop diabetes mellitus. Interestingly, in 1992, a group of Swedish researchers reported that three lots of the pancreatic beta cells were harvested from 14 cadavers who were non-diabetic during their life, incubated in three media with 5.6 mmol/L (109.76 mg%). 16.7 mml/L (215.00 mg%), and 28 mmol/L (548.80 mg%) of glucose respectively for seven days. Then, they were exposed to various glucose solutions for testing their abilities of producing insulin. Those incubated in 109.76 mg% fared very well like the non-diabetic. Those incubated in 215 mg% and 548.80 mg% fared worse and worst accordingly like the pre-diabetic and diabetic. This study illustrates diabetes mellitus is not a genetic disorder, rather is an acquired and preventable disease. [7]

Robert P. Robertson and his co-workers had previously cultured HITT-15 cell lines, which were developed from the SV-40 transformed Syrian hamster pancreatic islets of Langhorn, and found that chronically exposing these cell lines to supraphysiological glucose solution (11.0 mmol/L or 198 mg%) resulted in reducing the insulin production and secretion, as well as the level of insulin mRNA. In 1996, Professor Robertson and his colleagues used betaTC-6 cell lines derived from the pancreatic beta cells of the transgenic mice. They reported that similar results were observed like those with the HITT-15 cell lines. They also affirmed that the changes in the insulin mRNA level had nothing to do with the osmolarity of the glucose solution. [8]

Robert Su, Pharm.B., M.D.

Wish to invite Dr. Su to speak at your meeting, contact us at jevpublishing@verizon.net

References:

1. The American Heart Association. “Trends in Diabetes Prevalence in Adults Age 20 and Older by Sex: NHANES: 1988–94 and 2005–06.” Statistical Fact Sheet — Risk Factors 2009 Update.

2. Esposito K, et al. “ Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans Role of Oxidative Stress.” Circulation, Published online Volume 106, Number 16, Pages 2067-2072. September 30, 2002

3. van Oss CJ. “Influence of Glucose Levels on the In Vitro Phagocytosis of Bacteria by Human Neutrophils.” Infection and Immunity, Volume 4, Number 1, Pages 54–59. July 1971.

4. Sanchez A, et al. “Role of sugars in human neutrophilic phagocytosis.” American Journal of Clinical Nutrition, Vol 26, 1180-1184

5. Koichi Node and Teruo Inoue, “Postprandial hyperglycemia as an etiological factor in vascular failure.” Cardiovascular Diabetology 2009, 8:23doi:10.1186/1475-2840-8-23,

6. Maedler K, et al. “Glucose-induced ß cell production of IL-1b contributes to glucotoxicity in human pancreatic islets.” Journal of Clinical Investigation, 2002 September 15; 110(6): 851–860.

7. Eizirik DL, Korbutt GS, and Hellerström C. “Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the beta-cell function.” Journal of Clinical Investigation, Volume 90, Number 4, Pages 1263–1268. October 1992.

8. Poitout, V, et al. “Chronic Exposure of beta-TC-6 Cells to Supraphysiologic Concentrations of Glucose Decreases Binding of the RIPE3b1 Insulin Gene Transcription Activator.” Journal of Clinical Investigation. Volume 97, Number 4, February 1996, 1041–1046