Stout RW. Insulin and atheroma. 20-yr perspective. Diabetes Care. 1990 Jun;13(6):631-54. Review. PMID: 2192848 Department of Geriatric Medicine, Queen's University of Belfast, Northern Ireland.
Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.
The researchers Lemarche et al have done a great deal of research examining 'non-traditional risk factors '(see Table 2) and also showed the same link between insulin and associated ischemic heart disease.
Lamarche B, Tchernof A, Mauriège P, Cantin B, Dagenais GR, Lupien PJ, Després JP. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA. 1998 Jun 24;279(24):1955-61. (Full PDF here) PMID: 9643858
In fact, their results uncovered the fact that the largest odds ratio between traditional (LDL, TG, HDL) and nontraditional (small dense LDL, apo B and fasting insulin) fell to the Hyperinsulinemia risk factor. So high fasting insulin correlated stronger with the presence of evidence of coronary artery disease than than LDL-cholesterol. Triglyericides (TGs) even associated to a higher degree than LDL-cholesterol. HHmmmm?
Why do we always call LDL the 'bad' cholesterol? It appears that TGs is a bad character, indeed it appears TGs are the worse cholesterol out of all the traditional risk factors! Dr. Davis has pursued a lower TG goal lower than 'traditional' guidelines for many years. Current 'conventional' cardiovascular advice aims for TGs less than 150 however the Track Your Plaque program advocates an aggressive TG goal of 'normal' less than 60.
Is the 'LDL-cholesterol hypothesis' completely bunk?
Shouldn't Triglyerides be known as the 'lousy/bad' cholesterol?
Is this why statin-monotherapy fail to prevent signficant mortality and morbidity caused by plaque in heart disease and strokes?
The TYP goals for regression of ischemic heart disease are 60-60-60-60 (TG-HDL-LDL-25(OH)D). Many achieve this and beyond -- HDLs 80-90s and TGs 25-50s in the program!
And Elevated Fasting Insulin goal is not just less than 12 mU/L as discussed in the 2nd study above but at TYP the goal for regression is normal fasting insulin levels less than 5-10 mU/mL (30-60 pmol/L).
Is this why the Track Your Plaque program controls plaque comprehensively and trumps all 'conventional' cardiology programs by controlling triglycerides and insulin by a multifaceted strategy?
Conclusions by the above authors Lamarche, et al:
'Beyond the mechanisms underlying the atherogenicity of hyperinsulinemia, hyperapobetalipoproteinemia, and small, dense LDL, and irrespective of whether these mechanisms share common paths, results of the present study suggest that the risk of IHD is increased substantially when these metabolic abnormalities cluster. The synergistic contribution of the nontraditional cluster of risk factors to IHD risk and the fact that almost 1 of every 2 IHD cases had these abnormalities simultaneously reflect the multifactorial etiology of IHD. It also emphasizes the importance of defining the risk of IHD based on more than 1 risk factor.
There are a number of critical issues that have to be considered before any decision can be made toward the measurement of these nontraditional risk factors on a routine basis. Among others, results of this prospective case-control study will have to be confirmed through larger population-based studies, as the relatively low number of IHD cases allowed only a gross assessment of risk. The relatively large CIs associated with the estimated risk in some of the subgroups reflect this phenomenon. Population reference values such as those used for LDL-C, triglycerides, and HDL-C also will be needed before critical levels of fasting insulin, apolipoprotein B levels, and LDL particle size or density at which a person becomes at greater risk for IHD are identified. Means to achieve effective treatment of the nontraditional risk factors is also a critical issue that deserves a great deal of scrutiny before decisions can be made toward use of these variables in the risk management of IHD. There are data to suggest that LDL particle size can be modulated by changes in plasma triglyceride levels.41 Studies have shown that triglyceride-lowering therapy with fibric acid derivatives can lead to a significant increase in LDL particle size.42-43 There is also a large body of evidence demonstrating that LDL particle size, apolipoprotein B level, and insulin resistance and/or hyperinsulinemia can be effectively altered by diet and exercise-induced weight loss.44-45 Thus, the ability to favorably modify the nontraditional risk factors by diet, exercise, and appropriate pharmacotherapy provides further support for the use of these risk factors in the management of IHD risk...'
Lawlor DA, Fraser A, Ebrahim S, Smith GD. Independent associations of fasting insulin, glucose, and glycated haemoglobin with stroke and coronary heart disease in older women. PLoS Med. 2007 Aug;4(8):e263. PMID: 17760500
CRACK DOWN on insulin... CRACK DOWN on plaque (and cancer)...
Hunger will disappear away as well. Part of insulin's purpose is to drive energy into cells for storage. Insulin drives hunger as well. (...and mainly the consumption of carbs drive insulin secretion)
Importance of controlling triglycerides and insulin:
INSULIN ==> TG/HDL ratio ==> SMALL DENSE LDL
Zavaroni I, Dall'Aglio E, Alpi O, Bruschi F, Bonora E, Pezzarossa A, Butturini U.
Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride.
Atherosclerosis. 1985 Jun;55(3):259-66.
PMID: 3893447 [PubMed - indexed for MEDLINE]
Ghiselli G, Bon GB, Soldan S, Avogaro P.
Regulatory function of glucose and insulin on high-density lipoprotein cholesterol in normolipidemic subjects.
Metabolism. 1994 Nov;43(11):1332-7.
PMID: 7968586 [PubMed - indexed for MEDLINE]
Cominacini L, Garbin U, Davoli A, Campagnola M, De Santis A, Pasini C, Pastorino AM, Bosello O.
High-density lipoprotein cholesterol concentrations and postheparin hepatic and lipoprotein lipases in obesity: relationships with plasma insulin levels.
Ann Nutr Metab. 1993;37(4):175-84.
PMID: 8215234 [PubMed - indexed for MEDLINE]
Laws A, King AC, Haskell WL, Reaven GM.
Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men.
Arterioscler Thromb. 1991 Nov-Dec;11(6):1636-42.
PMID: 1931867 [PubMed - indexed for MEDLINE]
Stalder M, Pometta D, Suenram A.
Relationship between plasma insulin levels and high density lipoprotein cholesterol levels in healthy men.
Diabetologia. 1981 Dec;21(6):544-8.
PMID: 7040144 [PubMed - indexed for MEDLINE]
Tchernof A, Lamarche B, Prud'Homme D, Nadeau A, Moorjani S, Labrie F, Lupien PJ, Després JP.
The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men.
Diabetes Care. 1996 Jun;19(6):629-37.
PMID: 8725863 [PubMed - indexed for MEDLINE]
Laws A, Reaven GM.
Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations.
J Intern Med. 1992 Jan;231(1):25-30.
Katzel LI, Coon PJ, Rogus E, Krauss RM, Goldberg AP.
Persistence of low HDL-C levels after weight reduction in older men with small LDL particles.
Arterioscler Thromb Vasc Biol. 1995 Mar;15(3):299-305.
McNamara JR, Jenner JL, Li Z, Wilson PW, Schaefer EJ. ***
Change in LDL particle size is associated with change in plasma triglyceride concentration.
Arterioscler Thromb. 1992 Nov;12(11):1284-90.
Folsom AR, Szklo M, Stevens J, Liao F, Smith R, Eckfeldt JH. **
A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study.
Diabetes Care. 1997 Jun;20(6):935-42.