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Life Extension Magazine

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As We See It

Tragedy of Delayed Prevention

May 2019

By William Faloon

William Faloon
William Faloon

We at Life Extension® interact with new supporters who come to us with serious disorders, such as failing kidneys.

A record number of Americans now require dialysis treatments to remove waste products from their blood. Dialysis is not nearly as efficient as healthy kidneys that work around the clock.1,2

To put this into perspective, the five-year survival rate for patients who start dialysis was only 36% compared to 86% for those who received a kidney transplant.3 Neither scenario comes close to having healthy kidneys.

Type II diabetes is a risk factor for kidney disease. Around 10%-40% of type II diabetics will experience kidney failure.4 Research shows that before diabetes is diagnosed, higher-than-normal blood sugar levels damage kidneys.5

What you need to know

The public is failing to realize the serious complications that arise from elevated blood sugar and insulin. Approximately 86 million people in the United States fit the clinical definition of prediabetic. Because they are not yet diabetic, they do not receive glucose lowering drugs that provide many ancillary benefits. This has led to prediabetics having higher rates of several diseases, in comparison to diabetics.

A significant part of the American population (about 27%) has blood sugar levels that are higher-than-normal—but not high enough to meet the threshold for type II diabetes.6

This “prediabetic” phase places people at risk for kidney disease,5,7 potentially crippling neuropathy,8,9 heart disorders,10,11 cancer,12,13 and stroke.14

Our longstanding position is that the term “prediabetes” should be abolished. Anyone with less-than-optimal glucose, insulin and hemoglobin A1c (HbA1c) blood levels should aggressively intervene to reverse these glycemic markers.

Instead of this logical approach, what usually happens is that elevated glucose and insulin smolder for years.

In many of these cases, type II diabetes is not diagnosed until permanent damage is inflicted.

Drugs to treat type II diabetes are frequently advertised. Too bad TV commercials don’t promote comprehensive blood tests to identify diabetic risk factors before they cripple or kill.

The tragedy for most victims of degenerative illness is that their disease was preventable with early-diagnosis.

This editorial will review recent findings indicating that many Americans needlessly suffer diabetic complications. I will also describe an easy way to detect diabetes risk at an earlier stage, before significant damage is done.

Most readers of this magazine take steps to reduce their risk of diabetes, such as supplementing with vitamin D.

In people with higher vitamin D blood levels (>50 ng/mL), transition from prediabetes to type II diabetes may be reduced as much as 80%.15

But as I wrote on the previous page, we at Life Extension® advocate for the term “ prediabetes” to be abolished. Our rationale is that the risk of diabetic complications is substantially increased even in those with high-normal blood glucose levels.

Nerve Damage Starts Early

Man having feet checked

Small, capillary-like blood vessels that are embedded in nerve bundles feed the nerves throughout our bodies, including small and large nerves in our feet.

An elevation of glycemic markers means that excessive blood sugar and glycation are inflicting damage to small nerve fibers by cutting off blood circulation. This is the reason why crippling neuropathic pain is often the first sign of type II diabetes. This nerve damage may have begun decades before.

A 2018 study looked at hemoglobin A1c levels in groups of people with and without diabetes.16

Hemoglobin A1c is a marker of long-term sugar control, whereas fasting glucose only tells us what blood sugar levels are, at a single point in time

This study found subclinical, small nerve-fiber impairments in non-diabetics whose hemoglobin A1c levels were only 5.5% to 6%, whereas those with HbA1c of less than 5.5% did not have these changes.16

This study corroborates what we’ve argued for decades — that sugar-related pathologies begin long before full-blown type II diabetes is diagnosed. The authors of this study concluded:

“These findings underscore the importance of early treatment at the prediabetes and early diabetes stages to prevent nerve fiber decline that is likely irreversible.”16

Most of you have your hemoglobin A1c tested each year. This 2018 study and others validate the importance of targeting HbA1c below 5.5%.


Keep Your Heart From “Shrinking”

To evaluate the effect of abnormal blood sugar levels on the heart muscle, MRI scans were performed on the hearts of diabetics and prediabetics and compared to a control group of normal-glycemic subjects. None of the study subjects had a history of cardiovascular disease.17

There was a stepwise decrease in right ventricular (heart) volume in men with prediabetes (-20.4) and diabetes (-25.6) in comparison with non-diabetic controls.17

This study shows that atrophy (shrinkage) of the heart muscle occurs in both prediabetes and frank diabetes,17 which is why we want the term “prediabetes” to be abolished.

The authors of this 2018 study that looked at the heart via MRI imaging concluded:


“This study points towards early subclinical changes in right ventricular volumes in men with diabetes and prediabetes.”17

Higher Blood Sugar Increases Atrial Fibrillation Risk

Doctor showing blood sugar test

In atrial fibrillation, the heart’s upper chambers beat irregularly (quiver) instead of beating normally.18

Quivering of the heart’s upper chambers increases the risk of a clot forming. When these clots break off and enter the bloodstream, they readily lodge in arteries in the brain causing an ischemic stroke.18

Atrial fibrillation causes about 15% to 25% of strokes. The danger of these clots is so high that atrial fibrillation patients are usually placed on anticoagulant drugs (warfarin or Pradaxa®).19

These drugs carry the side effect of risk of internal bleeding.19 Yet the incidence of abnormal blood clot formation is so high in atrial fibrillation that the risk-to-reward ratio often favors use of these anti-coagulant drugs.

Atrial fibrillation is the most prevalent cardiac rhythm disorder in the elderly.20 A meta-analysis of 32 studies found that prediabetics have a 20% increased risk of atrial fibrillation while diabetics have a 28% increased risk.21

Stroke was long ago shown to be a diabetic complication. One pathological factor is damage inflicted on the brain’s arteries by elevated blood sugar.22

This new data reveals another reason why diabetics suffer more strokes. They have higher incidences of atrial fibrillation. This analysis also reveals that atrial fibrillation risk in prediabetics is not that much lower than in full-blown diabetics.22

Diabetes Increases Cancer Risk
Doctor reviewing test with patient

Data collected from 47 prior studies further confirm that diabetes heightens the risk for cancer.

The overall findings showed that women with diabetes are 27% more likely to develop cancer while diabetic men are at 19% increased risk.27

Higher blood sugar levels have been associated with elevated cancer risks, including pancreatic and breast malignancies.28,29

Long before type II diabetes is diagnosed, huge amounts of insulin are produced to suppress surging blood glucose levels. The combination of elevated insulin and glucose in diabetics fuels unwanted cell proliferation and damages cell regulatory mechanisms.

The result is an increased risk of deadly cancers. Authors of this 2018 analysis concluded:

“We have also demonstrated for the first time that women with diabetes are more likely to develop any form of cancer (than men), and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”30

We have previously reported on studies showing that higher-than-normal blood sugar sharply increases breast cancer risk in non-diabetic women.31,32

Keeping your glycemic markers in low normal ranges should be part of a cancer prevention strategy.

Impaired Cardiac Fitness

Not all overweight people are diabetic.

A group of researchers examined relationships between glycemic control (as measured by hemoglobin A1c) and cardiovascular fitness in overweight/obese subjects with and without type II diabetes.23

A statistically significant relationship was observed between lower hemoglobin A1c and better cardiovascular fitness.23

The authors of this published study commented that even a mild worsening of glycemic control can adversely influence cardiovascular health measures.23

Recognizing “Prediabetic” Risks

About 86 million people in the United States fit the clinical definition for prediabetes.6 This represents about 27% of the entire population of the United States.

Prevalence of prediabetes increased each year between 2011 and 2014, which contributed to the nearly 2 million new diagnoses of type II diabetes made each year.6

A detailed analysis published in 2018 found that type II diabetics had higher adjusted odds of suffering cardiovascular and kidney diseases compared to prediabetics.6

Prediabetics, on the other hand had more of the following disorders compared to diagnosed type II diabetics:6

  • Cancer
  • Arthritis
  • Depressive disorder
  • Chronic obstructive pulmonary disease

One reason prediabetics have higher rates of the above diseases is that most type II diabetics are treated with a drug (metformin) that increases cellular AMPK activity.

Activating AMPK has been shown to help protect against a host of degenerative diseases.24-26

Prediabetes and Hypertension

High blood pressure and high blood sugar severely impact the heart and kidneys.

A study published in 2018 looked at hypertensive patients with and without prediabetes. The following “cardiovascular events” were evaluated:10

  • Cardiovascular death
  • Stroke
  • Heart failure
  • Myocardial infarction

The incidences of these cardiovascular events were 61% higher in the prediabetic group compared to those with normal blood glucose levels.10

This study also found a correlation between kidney impairment and increased cardiovascular events. This finding corroborates similar conclusions from previous studies.10

How Diabetes Hides from Physicians

Young people who eat properly and are physically active typically maintain optimal glycemic control.

When a meal is consumed, their pancreas secretes insulin to move glucose into cells for energy metabolism. After meals, insulin production drops to a low level, just enough to keep blood glucose in proper balance.

With aging, our cells lose insulin sensitivity. This requires more insulin to be secreted to drive glucose into cells, including fat cells.34,36

Increased fat storage occurs when the body is overloaded with more glucose than is needed for healthy energy production. Excess insulin helps cells convert glucose into fat. Unwanted weight gain is a frequent consequence.

As people become more sedentary and consume excess calories, even more insulin is secreted to maintain balanced glucose levels.

Excess Insulin Can Cover Up Glycemic Control Problems

Long before type II diabetes is diagnosed, many people secrete large amounts of insulin from their pancreas to keep glucose from spiking too high.

The problem is that continuous secretion of insulin from the pancreas can keep fasting glucose and hemoglobin A1c at deceptively low levels.

To put this in perspective, late-stage type II diabetics often require insulin injections. This exogenous-administered insulin reduces glucose and hemoglobin A1c blood levels. But these people are still diabetic from the standpoint of their risk for complications.

Common blood measures of diabetes (glucose and hemoglobin A1c) may also be suppressed in many people whose pancreas are secreting large amounts of insulin around the clock.

In other words, a person can suffer from the damaging pathologies that we usually associate with diabetes even when glucose and HbA1c blood levels appear normal. That’s because chronically elevated insulin can push down glucose (and hemoglobin A1c) for years (or decades) before cellular insulin sensitivity becomes so impaired that full-blown type II diabetes is diagnosed.

Chronically elevated fasting insulin has been associated in many studies with greater risk of diabetic complications, even before diabetes shows up on conventional blood tests.37-40

For these reasons, we are adding a fasting insulin test to this year’s popular Male and Female Panels…at no extra charge!

This will better enable our supporters to assess their glycemic control status by reviewing their glucose, hemoglobin A1c and insulin blood levels simultaneously.

How to Lower Elevated Insulin

If fasting insulin is higher than 5 uIU/mL, this is an indicator of insulin resistance and can be useful as an early warning sign to be more vigilant in preventing diabetes.

This includes healthier food choices, more physical activity, and initiation of a preventive program with AMPK activators like the drug metformin41,42 and/or nutrients that have similar effects (like gynostemma leaf extract43-45 and hesperidin46-48).

The article beginning on page 56 of this month’s issue describes health concerns, including inability to lose surplus body fat that are associated with excess fasting insulin. We also convey observational data that associate higher fasting insulin levels with increased prevalence of degenerative disorders.

(References can be found on page 14.)

IMAGE DESCRIPTION HERE

Hemoglobin A1c Blood Level and Stroke Risk

A systematic review of 29 prior studies assessed the association between rising hemoglobin A1c and first stroke risk.22

In this review, the risk of ischemic strokes—the most common type—increased with each 1% increase in HbA1c. In diabetics the risk of ischemic stroke increased 24% with each 1% increase in HbA1c. But in those without diabetes, stroke risk increased a whopping 49% for each 1% increase in HbA1c.22

You may wonder why stroke risk is higher in non-diabetics. My opinion is that it’s because diabetics usually receive preventive treatment for stroke risk factors (such as elevated blood pressure and lipids), adhere to healthier diets, and are prescribed AMPK activator drugs like metformin.

Non-diabetics may not take their elevated glycemic markers seriously.

This study showed that a small increase in HbA1c blood levels is associated with increased first-ever ischemic or hemorrhagic stroke risk, whether or not one is diagnosed with diabetes. This led the authors of this 2018 analysis to conclude:

“These findings suggest that more intensive HbA1c glycemic control targets may be required for optimal ischemic stroke prevention.”22

Optimal HbA1c is under 5.5%. When HbA1c levels rise to 6.5%, there is a substantially greater risk of stroke. This observational analysis suggests non-diabetics (in addition to diabetics) benefit from better glycemic control.22

Tragedy of Delayed Prevention

Each day, 5,000 Americans perish from a degenerative illness.33 Far more suffer from a chronic disease that impairs their quality of life.

The majority of these disabilities and deaths are preventable with annual comprehensive blood tests.

The absurdity is that many Americans wait for a diabetic complication to manifest (such as neuropathy, stroke, or kidney failure) before paying attention to their glycemic risk markers.

Several times a week, I review new data confirming that even slightly elevated blood glucose or hemoglobin A1c predisposes us to increased risks faced by diabetics.

The good news is that these risk factors can be lowered using a variety of proven interventions.

Annual Blood Test Super Sale

Blood test vial

With normal aging, our cellular insulin sensitivity decreases.34,35 The result is higher blood sugar that can be measured with readily available blood tests.

Comprehensive blood tests uncover early markers of disease that are reversible if detected in time.

Yet the inconvenience of doctors’ appointments (and increasing cost) causes many people to delay having their blood tested.

Life Extension® broke down these barriers decades ago by offering comprehensive blood testing direct to our supporters.

Once a year we discount prices to enable our readers to have comprehensive testing done for only $199. These same tests at commercial labs cost far more.

With thousands of blood-drawing stations available across most of the United States, either on a walk-in basis or by appointment, there is no need to delay.

These tests provide evaluations for cardiovascular and cancer risk factors. This enables individuals to change their unhealthy behavior patterns before serious illness manifests.

Turn this page to see the descriptions of the many tests that are included in our Male and Female Blood Test Panels. These panels include hemoglobin A1c, glucose, and measures of kidney function.

This year we’ve added fasting insulin to these popular panels to better enable our readers to achieve optimal glycemic control. See the box on the next page to learn why it is so important to know your fasting insulin level when seeking to protect against hidden pathologies caused by excessive blood sugar.

To order the Male or Female Panel at the year’s lowest prices, call 1-800-208-3444 or log on to LifeExtension.com/blood

For longer life,

For Longer Life

William Faloon

References

  1. Available at: https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease. Accessed February 25, 2019.
  2. Available at: https://www.kidney.org/news/newsroom/factsheets/End-Stage-Renal-Disease-in-the-US. Accessed February 25, 2019.
  3. Available at: https://www.niddk.nih.gov/-/media/Files/Kidney-Disease/KU_Diseases_Stats_508.pdf. Accessed February 25, 2019.
  4. Available at: https://www.medicalnewstoday.com/articles/304528.php. Accessed February 25, 2019.
  5. Melsom T, Schei J, Stefansson VT, et al. Prediabetes and Risk of Glomerular Hyperfiltration and Albuminuria in the General Nondiabetic Population: A Prospective Cohort Study. Am J Kidney Dis. 2016 Jun;67(6):841-50.
  6. Iranfar N, Smith TC. When Should “Pre” Carry as Much Weight in the Diabetes Comorbidity Debate? Insights From a Population-Based Survey. Prev Chronic Dis. 2018 Mar 22;15:E36.
  7. Plantinga LC, Crews DC, Coresh J, et al. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol. 2010 Apr;5(4):673-82.
  8. Tabak AG, Herder C, Rathmann W, et al. Prediabetes: a high-risk state for diabetes development. Lancet. 2012 Jun 16;379(9833):2279-90.
  9. Papanas N, Vinik AI, Ziegler D. Neuropathy in prediabetes: does the clock start ticking early? Nat Rev Endocrinol. 2011 Jul 12;7(11):682-90.
  10. Garcia-Carretero R, Vigil-Medina L, Mora-Jimenez I, et al. Cardiovascular risk assessment in prediabetic patients in a hypertensive population: The role of cystatin C. Diabetes Metab Syndr. 2018 Sep;12(5):625-9.
  11. Despres JP, Lamarche B, Mauriege P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996 Apr 11;334(15):952-7.
  12. Xu WG, Qian YF, Wu J. The effect of prediabetes on hepatocellular carcinoma risk: a systematic review and meta-analysis. Minerva Med. 2017 Apr;108(2):185-90.
  13. Crispo A, Augustin LS, Grimaldi M, et al. Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes. J Cell Physiol. 2017 May;232(5):1144-50.
  14. Mijajlovic MD, Aleksic VM, Sternic NM, et al. Role of prediabetes in stroke. Neuropsychiatr Dis Treat. 2017;13:259-67.
  15. Park SK, Garland CF, Gorham ED, et al. Plasma 25-hydroxyvitamin D concentration and risk of type 2 diabetes and pre-diabetes: 12-year cohort study. PLoS One. 2018;13(4):e0193070.
  16. Abraham A, Barnett C, Katzberg HD, et al. Nerve function varies with hemoglobin A1c in controls and type 2 diabetes. J Diabetes Complications. 2018 Apr;32(4):424-8.
  17. Patscheider H, Lorbeer R, Auweter S, et al. Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes. Eur Radiol. 2018 Jul;28(7):3105-13.
  18. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76.
  19. Available at: https://emedicine.medscape.com/article/151066-treatment#showall. Accessed February 26, 2019.
  20. Curtis AB, Karki R, Hattoum A, et al. Arrhythmias in Patients >/=80 Years of Age: Pathophysiology, Management, and Outcomes. J Am Coll Cardiol. 2018 May 8;71(18):2041-57.
  21. Aune D, Feng T, Schlesinger S, et al. Diabetes mellitus, blood glucose and the risk of atrial fibrillation: A systematic review and meta-analysis of cohort studies. J Diabetes Complications. 2018 May;32(5):501-11.
  22. Mitsios JP, Ekinci EI, Mitsios GP, et al. Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2018 May 17;7(11).
  23. Moxley EW, Smith D, Quinn L, et al. Relationships Between Glycemic Control and Cardiovascular Fitness. Biol Res Nurs. 2018 Jul;20(4):422-8.
  24. Available at: https://www.lifeextension.com/magazine/2014/ss/ampk/page-01. Accessed February 26, 2019.
  25. Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev. 2012 Apr;11(2):230-41.
  26. Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41.
  27. Ohkuma T, Peters SAE, Woodward M. Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events. Diabetologia. 2018 Oct;61(10):2140-54.
  28. Ryu TY, Park J, Scherer PE. Hyperglycemia as a risk factor for cancer progression. Diabetes Metab J. 2014 Oct;38(5):330-6.
  29. Chang SC, Yang WV. Hyperglycemia, tumorigenesis, and chronic inflammation. Crit Rev Oncol Hematol. 2016 Dec;108:146-53.
  30. Available at: https://www.sciencedaily.com/releases/2018/07/180719195650.htm. Accessed February 26, 2019.
  31. Available at: https://www.lifeextension.com/Magazine/2013/2/elevated-glucose-increases-incidence-of-breast-cancer-and-brain-shrinkage/Page-01. Accessed February 26, 2019.
  32. Available at: https://www.lifeextension.com/magazine/2014/2/when-will-doctors-recognize-this-leading-cause-of-death/page-01?p=1. Accessed February 26, 2019.
  33. Available at: https://www.cdc.gov/nchs/fastats/deaths.htm. Accessed February 26, 2019.
  34. Evans JL, Goldfine ID. Aging and insulin resistance: just say iNOS. Diabetes. 2013 Feb;62(2):346-8.
  35. de la Monte SM. Insulin Resistance and Neurodegeneration: Progress Towards the Development of New Therapeutics for Alzheimer’s Disease. Drugs. 2017 Jan;77(1):47-65.
  36. Ryan AS. Insulin resistance with aging: effects of diet and exercise. Sports Med. 2000 Nov;30(5):327-46.
  37. Pennings N, Jaber J, Ahiawodzi P. Ten-year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation. Diabetes Metab Res Rev. 2018 May;34(4):e2986.
  38. Wang F, Han L, Hu D. Fasting insulin, insulin resistance and risk of hypertension in the general population: A meta-analysis. Clin Chim Acta. 2017 Jan;464:57-63.
  39. Zhang X, Li J, Zheng S, et al. Fasting insulin, insulin resistance, and risk of cardiovascular or all-cause mortality in non-diabetic adults: a meta-analysis. Biosci Rep. 2017 Oct 31;37(5).
  40. Jung JY, Park SK, Choi JM, et al. Evaluation of risk for metabolic syndrome according to the fasting insulin concentration in Korean men. Clin Chim Acta. 2017 Jan;464:123-7.
  41. Hawley SA, Gadalla AE, Olsen GS, et al. The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes. 2002 Aug;51(8):2420-5.
  42. Crawley D, Chandra A, Loda M, et al. Metformin and longevity (METAL): a window of opportunity study investigating the biological effects of metformin in localised prostate cancer. BMC Cancer. 2017 Jul 21;17(1):494.
  43. Gauhar R, Hwang SL, Jeong SS, et al. Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol Lett. 2012 Sep;34(9):1607-16.
  44. Huyen VT, Phan DV, Thang P, et al. Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients. Horm Metab Res. 2010 May;42(5):353-7.
  45. Park SH, Huh TL, Kim SY, et al. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial. Obesity (Silver Spring). 2014 Jan;22(1):63-71.
  46. Pu P. [Protection mechanisms of hesperidin on mouse with insulin resistance]. Zhongguo Zhong Yao Za Zhi. 2016 Sep;41(17):3290-5.
  47. Rizza S, Muniyappa R, Iantorno M, et al. Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome. J Clin Endocrinol Metab. 2011 May;96(5):E782-92.
  48. Salden BN, Troost FJ, de Groot E, et al. Randomized clinical trial on the efficacy of hesperidin 2S on validated cardiovascular biomarkers in healthy overweight individuals. Am J Clin Nutr. 2016 Dec;104(6):1523-33.
  49. Chu NF, Spiegelman D, Hotamisligil GS, et al. Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men. Atherosclerosis. 2001 Aug;157(2):495-503.
  50. Burnol AF, Morzyglod L, Popineau L. [Cross-talk between insulin signaling and cell proliferation pathways]. Ann Endocrinol (Paris). 2013 May;74(2):74-8.
  51. Nilsen TI, Vatten LJ. Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis. Br J Cancer. 2001 Feb 2;84(3):417-22.
  52. Balkau B, Kahn HS, Courbon D, et al. Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: the Paris Prospective Study. Diabetes Care. 2001 May;24(5):843-9.
  53. Godsland IF, Crook D, Walton C, et al. Influence of insulin resistance, secretion, and clearance on serum cholesterol, triglycerides, lipoprotein cholesterol, and blood pressure in healthy men. Arterioscler Thromb. 1992 Sep;12(9):1030-5.
  54. Salonen JT, Lakka TA, Lakka HM, et al. Hyperinsulinemia is associated with the incidence of hypertension and dyslipidemia in middle-aged men. Diabetes. 1998 Feb;47(2):270-5.
  55. Stannard SR, Johnson NA. Insulin resistance and elevated triglyceride in muscle: more important for survival than “thrifty” genes? J Physiol. 2004 Feb 1;554(Pt 3):595-607.
  56. Mykkanen L, Kuusisto J, Haffner SM, et al. Hyperinsulinemia predicts multiple atherogenic changes in lipoproteins in elderly subjects. Arterioscler Thromb. 1994 Apr;14(4):518-26.
  57. Karhapaa P, Malkki M, Laakso M. Isolated low HDL cholesterol. An insulin-resistant state. Diabetes. 1994 Mar;43(3):411-7.
  58. Ko GT, Cockram CS, Woo J, et al. Obesity, insulin resistance and isolated low high-density-lipoprotein cholesterol in Chinese subjects. Diabet Med. 2001 Aug;18(8):663-6.
  59. Goldstein BJ. Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol. 2002 Sep 5;90(5A):3G-10G.
  60. Haffner SM, Stern MP, Mitchell BD, et al. Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution. Diabetes. 1990 Mar;39(3):283-8.
  61. Modan M, Halkin H, Almog S, et al. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest. 1985 Mar;75(3):809-17.
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