Richard A. Savage
A. The ratio of triglyceride to high-density lipoprotein cholesterol
(Tg/ HDL-C ratio) is often related to a patient’s level of insulin resistance.
Insulin-resistant patients commonly display elevated triglyceride levels
and depressed HDL-C levels, increasing the Tg/ HDL-C ratio. The classic
lipid findings in insulin-resistance syndrome—for example, the
metabolic syndrome or dysmetabolic syndrome X (ICD-9:277.7)—include
hypertriglyceridemia, low HDL-C, and an increased concentration of dense
low-density lipoprotein particles that are depleted of cholesterol. Researchers
have established that states of insulin resistance are associated with
an increased risk for developing type 2 diabetes and cardiovascular disease.1–4
The tissues most responsive to insulin are skeletal muscle, adipose tissue, and the liver. In nondiabetic, yet insulin-resistant, patients, insulin levels can be elevated as pancreatic beta cells attempt to compensate for decreased insulin action. Therefore, there is a positive correlation between the Tg/ HDL-C ratio and the fasting insulin concentration in nondiabetic individuals. However, because this correlation is modest at best and varies considerably throughout the general population, the calculation of Tg/ HDL-C ratio cannot be substituted for a measurement of the fasting insulin concentration should the physician want an assessment of insulin resistance.
The gold standard assessments of insulin resistance are dynamic tests carried
out in research settings using the glucose or insulin clamp techniques or the
frequently sampled intravenous glucose tolerance test.5 Whereas
the fasting insulin concentration in nondiabetic individuals is positively
correlated with the subject’s degree of insulin resistance, fasting insulin
by itself is not the best static measurement of insulin resistance. Even dividing
the insulin concentration into 40 improves the correlation of fasting insulin
with insulin sensitivity.6
The more sophisticated, although controversial,7 static
assessments of insulin resistance available to physicians include the homeostasis
model assessment (Fig. 1),8 quantitative
insulin sensitivity check index (Fig. 2),9 fasting
glucose-to-insulin ratio (Fig. 3),10 and
insulin sensitivity index, or ISI, corrected for fat-free mass divided by average
insulin Mffm/I = exp[2.63 – 0.28 ln insulin – 0.31 ln (Tg)]; M = glucose disposal
rate, ffm = fat-free mass; I= insulin.11 Oral
glucose tolerance tests have also been used to estimate insulin sensitivity.12 For
example, when insulin is expressed in microunits per milliliter and glucose
is measured as milligrams per deciliter, a [glucosefasting] / [insulinfasting]
ratio of less than 4.5 is considered abnormal.
Measurements of insulin resistance are not presently used to monitor the success
of diabetes treatment. Glycemic monitoring is the providence of hemoglobin
A1c measurements and self-monitoring of blood glucose.13 Lipid profile
assessments are also a routine part of diabetes monitoring. However, the American
Diabetes Association has no recommendations to calculate the Tg/HDL-C ratio
or use such a ratio in assessing diabetic control. The lipid assessment of
diabetic control is based on the absolute concentrations of LDL-C, triglycerides,
and HDL-C. Similarly, in assessing any patient’s risk for cardiovascular disease,
the National Cholesterol Education Program Adult Treatment Panel III, or NCEP
ATP III, has no recommendations to calculate the Tg/HDL-C ratio or the total
cholesterol-to-HDL-C ratio. This is because risk assessment and therapy are
based on the absolute levels of LDL-C and because HDL-C, triglycerides, and
the patient’s 10-year risk for cardiovascular disease are not based on ratios.14-15
In short, the Tg/HDL-C ratio cannot be recommended as a routine tool for assessing diabetic control or risk for cardiovascular disease based on current recommendations from the ADA or NCEP ATP III.
- Reaven GM. Banting lecture 1988. Role of insulin resistance in
human disease. Diabetes. 1988;37(12):1595–1607.
- Despres JP, Lamarche
B, Mauriege P, et al. Hyperinsulinemia as an independent risk factor
for ischemic heart disease. N Engl J Med. 1996;334(15):952–957.
- Stolk RP, Pols HA, Lamberts SW, et al. Diabetes mellitus, impaired
glucose tolerance, and hyperinsulinemia in an elderly population. The
Rotterdam Study. Am J Epidemiol. 1997;145(1): 24–32.
- Chien KL, Lee YT, Sung FC, et al. Hyperinsulinemia and related atherosclerotic
risk factors in the population at cardiovascular risk: a community-based
Chem. 1999;45(6 Pt 1): 838–846.
- Scheen AJ, Paquot N, Castillo MJ, et al. How to measure insulin
action in vivo. Diabetes Metab Rev. 1994;10(2):151–188.
- Raynaud E, Perez-Martin A, Brun JF, et al. Revised concept for
the estimation of insulin sensitivity from a single sample. Diabetes
Care. 1999;22(6): 1003–1004.
- Yeni-Komshian H, Carantoni M, Abbasi F, et al. Relationship between
several surrogate estimates of insulin resistance and quantification
of insulin-mediated glucose disposal in 490 healthy nondiabetic volunteers.
Diabetes Care. 2000;23(2):171–175.
- Radziuk J. Insulin sensitivity and its measurement: structural
commonalities among the methods. J Clin Endocrinol
- Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity
check index: a simple, accurate method for assessing insulin sensitivity
in humans. J Clin Endocrinol Metab. 2000;85(7): 2402–2410.
- Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin
ratio is a useful measure of insulin sensitivity in women with polycystic
ovary syndrome. J Clin Endocrinol Metab. 1998;83(8):2694–2698.
- McAuley KA, Williams SM, Mann JI, et al. Diagnosing insulin resistance
in the general population. Diabetes Care. 2001;24(3):460–464.
- Stumvoll M, Mitrakou A, Pimenta W, et al. Use of the oral glucose
tolerance test to assess insulin release and insulin sensitivity. Diabetes
Care. 2000;23(3): 295–301.
- American Diabetes Association. Standards of Medical Care in Diabetes—2006.
Diabetes Care. 2006;29:S4–42.
- Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults. Executive Summary of the Third Report
of the National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
(Adult Treatment Panel III). JAMA. 2001;285:2486–2497.
- Grundy SM, Cleeman JI, Merz CN, et al. National Heart, Lung,
and Blood Institute; American College of Cardiology Foundation; American
Heart Association. Implications of recent clinical trials for the National
Cholesterol Education Program Adult Treatment Panel III guidelines.
William E. Winter, MD
Department of Pathology
University of Florida
Member, CAP Special Chemistry Committee