That serving of french toast may be doing more to contribute to cardiovascular disease than promoting insulin resistance and dyslipidemia. A paper just published in the journal Diabetes details how excess blood sugar causes LDL cholesterol to stick more readily to arterial plaque. Inflamed vulnerable plaque on arterial walls is the main precipitating factor for heart attacks and strokes. The authors set out to…

“…study whether modification of LDL by methylglyoxal (MG), a potent arginine-directed glycating agent that is increased in diabetes, is associated with increased atherogenicity.”

Glycation is the damaging process by which sugar binds to substances in the body that it shouldn’t do normally. As the practitioners reading this know, hemoglobin A1c (HbgA1c, produced by glycation of hemoglobin) is an important laboratory metric for determining how high a person’s blood sugar has been on average over the previous few months. People with pre-diabetes (metabolic syndrome) and type 2 diabetes have higher levels. By modifying human LDL by methylglyoxal to reproduce what happens in vivo, the authors were able to measure the effect on LDL particle characteristics and its tendency to deposit in the arterial wall. What did they find?

“MGmin-LDL [glycated LDL] had decreased particle size, increased binding to proteoglycans, and increased aggregation in vitro. Cell culture studies showed that MGmin-LDL was bound by the LDL receptor but not by the scavenger receptor and had increased binding affinity for cell surface heparan sulfate–containing proteoglycan. Radiotracer studies in rats showed that MGmin-LDL had a similar fractional clearance rate in plasma to unmodified LDL but increased partitioning onto the aortal wall…A computed structural model predicted that MG modification of apoB100 induces distortion, increasing exposure of the N-terminal proteoglycan–binding domain on the surface of LDL. This likely mediates particle remodeling and increases proteoglycan binding.”

In other words, glycated LDL is a nasty compound that is less likely to be scavenged from the bloodstream; and it is smaller, denser and stickier than normal LDL so that it has a higher tendency to adhere to the blood vessel well. Glycated LDL has been called the “ultra-bad cholesterol“. It also shows part of the reason why blood sugar lowering therapies reduce cardiovascular disease. The authors conclude:

“MG modification of LDL forms small, dense LDL with increased atherogenicity that provides a new route to atherogenic LDL and may explain the escalation of cardiovascular risk in diabetes and the cardioprotective effect of metformin.”

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It’s disturbing and worrisome to see how few doctors seem to be alert to the blood sugar dysregulation that precedes type 2 diabetes and many other chronic diseases in their patients as evidenced by a study just published in the journal Diabetes Care. The authors conducted their investigation to…

“…estimate the rates of prevalence, diagnosis, and treatment of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).”

They examined a representative sample of the U.S. population that included 1,547 nondiabetic adults without a history of heart attack to determine the proportion who met the criteria for IFG/IGT, and the proportion of them who: 1) received a diagnosis from their physicians; 2) were prescribed lifestyle modification or medication for blood sugar; or 3) were currently on therapy. Their data painted a dismal picture:

“Of the 1,547 subjects, 34.6% had pre-diabetes; 19.4% had IFG only; 5.4% had IGT only, and 9.8% had both IFG and IGT. Only 4.8% of those with pre-diabetes reported having received a formal diagnosis from their physicians. No subjects with pre-diabetes received oral antihyperglycemics, and the rates of recommendation for exercise or diet were 31.7% and 33.5%, respectively.”

Yikes. It’s really up to the patient to be informed (one of the purposes of this blog) and seek proper care. Blood sugar dysregulation wrecks almost everything that clinicians practicing according to the functional model try to do to correct brain, hormone and immune dysregulation. It’s importance as a clinical focus is hard to over-emphasize. The authors’ disappointment is almost palpable in their conclusion:

“Three years after a major clinical trial demonstrated that interventions could greatly reduce progression from IFG/IGT to type 2 diabetes, the majority of the U.S. population with IFG/IGT was undiagnosed and untreated with interventions. Whether this is due to physicians being unaware of the evidence, unconvinced by the evidence, or clinical inertia is unclear.”

Perhaps this says something about why the scientists who authored another paper in the same issue of Diabetes Care saw fit to ask whether sugar-sweetened beverages would contribute to the risk of metabolic syndrome and type 2 diabetes (!):

“Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed.”

Their meta-analysis included 310,819 participants from 11 acceptable studies. It’s troubling to allow that there may be physicians who might not anticipate the conclusion that their data defined:

“In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases.”

It seems that even fewer physicians and their patients are aware of the role of glucose in ‘feeding’ cancer and the research being done to block the metabolism of sugar by tumor cells as described in a paper just published in the journal Oncogene. The authors state:

“Tumors show an increased rate of glucose uptake and utilization. For this reason, glucose analogs are used to visualize tumors by the positron emission tomography technique, and inhibitors of glycolytic metabolism are being tested in clinical trials.”

While research investigates possible interventions to aggressively interrupt the glycolytic metabolism of tumor cells, doctors should assist their patients in controlling blood sugar and insulin (another tumor promoter) with the appropriate tools:

“Upregulation of glycolysis confers several advantages to tumor cells: it promotes tumor growth and has also been shown to interfere with cell death at multiple levels…Moreover, inhibition of glucose metabolism sensitizes cells to death ligands. Glucose deprivation and antiglycolytic drugs induce tumor cell death…”

Blood sugar dysregulation contributes to most chronic diseases including cardiovascular, autoimmune, neurodegenerative and malignant conditions. Supporting healthy blood sugar and insulin regulation is one of the most important things that practitioners and their patients can do together.

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Readers and patients here know how higher levels of insulin from a high glycemic diet can result in an increase in the harmful kinds of fat in the blood. It will come as no surprise that a paper just published in the Journal of the American Medical Association adds more evidence to the association. The the objective of the authors was to…

“…assess the association between consumption of added sugars and blood lipid levels in US adults.”

They analyzed the data for 6,113 adults collected over seven years for sugars in the diet and levels of HDL and LDL cholesterol and triglycerides. A clear correlation between higher levels of sugars and lower HDL (“good” cholesterol), higher LDL (“bad” cholesterol) and higher triglycerides emerged. There was strong evidence for maintaining a low glycemic diet to regulate cholesterol:

“Among higher consumers (≥10% added sugars) the odds of low HDL-C levels were 50% to more than 300% greater compared with the reference group (<5% added sugars).”

Their conclusion was mildly stated:

“In this study, there was a statistically significant correlation between dietary added sugars and blood lipid levels among US adults.”

Have you been trying but not succeeding in getting cholesterol and/or triglycerides down with a low fat diet? There has been so much science done on the correlation between insulin sensitivity and cholesterol levels; it’s surprising this wasn’t noted by the authors. Just one example is a fresh paper in the Journal of Lipid Research that begins with the well-known fact:

“Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 diabetes.”

Interestingly, the authors wanted to see if any level of insulin resistance would have an effect on cholesterol synthesis:

“We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes…”

What conclusions did they draw from their data?

“In conclusion, cholesterol metabolism was altered already in subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.”

How to eat healthy fat and oil is another topic, but if cholesterol and triglycerides are the issue—pay attention to sugars and insulin.

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You are probably aware of earlier studies that demonstrated increase in life span of experimental animals by the effect of caloric restriction on insulin regulating pathways. This interesting study recently published in the journal Cell Metabolism elucidates the flip side: “We found that adding a small amount of glucose to the medium (2%) shortened the life span of C. elegans by inhibiting the activities of life span-extending transcription factors that are also inhibited by insulin signaling…” The authors conclude: “Together, these findings raise the possibility that a low-sugar diet might have beneficial effects on life span in higher organisms.”

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According to this report on a paper published in the British Journal of Psychiatry, “boys who ate sweets daily at age 10 are significantly more likely to commit violent crimes in adulthood”. This robust association was evident even though confounding factors were controlled: “Try as I did, I couldn’t get rid of the sweets-violence connection,” says the lead researcher.

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