Type 2 Diabetes 101
What you need to know about insulin resistance and its impact on your diabetic risk and your overall cardiometabolic risk.
Type 2 diabetes is a chronic condition that hampers your ability to metabolizes sugar (glucose) — the body’s primary source of fuel. Type 2 diabetes develops over many years due to the combination of two problems. First, cells in the liver, muscles, and fat cells become resistant to the effects of insulin, a hormone produced by your pancreas to move glucose into cells. Second, insulin levels eventually decline causing a rapid increase in blood glucose levels.
The Toll of Diabetes
In addition to the 34.1 million Americans that have been diagnosed with diabetes, an estimated 7.3 million Americans have undiagnosed diabetes, and 88 million Americans have pre-diabetic glucose values and are at risk of developing diabetes.[1] Along with these soaring numbers, diabetes is the 7th leading cause of death in the United States.
Diabetes is also one of the most expensive disease facing our country. The total cost of diagnosed diabetes treatments in 2017 were $327 billion and that number continues to grow every year. At the individual level, people with diagnosed diabetes can attribute about $9,601 to diabetes care of their average annual medical expenditures of $16,752.[2]
“I thought I could avoid (type 2 diabetes) by removing the buns from my cheeseburgers. Well, it takes a little bit more than that.”
What You Need to Know About Insulin Resistance and Cardiometabolic Risk
Insulin is a hormone produced by the pancreas that works in liver cells, muscle cells and fat cells (adipose tissue) to regulate glucose and energy metabolism. Insulin sensitive (IS) individuals have cells that react normally to insulin. In contrast, insulin resistance (IR) is a condition in which liver cells, muscle cells and fat cells are progressively more resistant to insulin over time.
As insulin resistance increases, many cardiometabolic risk factors worsen together including abdominal obesity, blood pressure, blood glucose, blood lipid (cholesterol and triglyceride) and atherogenic particle number (LDL particle number and apolipoprotein B) levels.[3,4,5]
Insulin resistance significantly increases the risk of cardiovascular events, risk of developing diabetes, and can limit the effectiveness of therapies used to treat other risk factors.[6,7]
Unfortunately, it is common for insulin resistance to be present for many years before blood glucose values, blood pressure or other clinical features appear abnormal.[8]
What You Need to Know About Insulin Resistance and Risk of Diabetes
Risk for development of diabetes is most commonly determined by measurement of blood glucose levels. In the fasting state, glucose values less than 100 mg/dL are considered “normal”, while values 100-125 mg/dL are considered “pre-diabetic”. Diabetes is diagnosed at fasting glucose of greater than or equal to 126 mg/dl on two separate occasions.[9]
While the risk of diabetes increases as glucose levels rise, there is a wide range of individual diabetic risk at any given glucose value.[10,11] This can be seen in men and women followed in the Multi-Ethnic Study of Atherosclerosis (MESA).
As a result, blood glucose is an insensitive predictor of individual risk for developing diabetes.
Insulin resistance is the principal metabolic disorder that leads to increased blood glucose levels and development of type 2 diabetes mellitus.[12,13] As cells become resistant to insulin, blood glucose levels rise.[14]
Insulin resistance is a condition that progresses over time. As insulin resistance worsens, the pancreas releases increasing amounts of insulin in an attempt to “force” liver cells, muscle cells and fat cells to respond and maintain normal blood glucose levels.[14,15]
Over time, fasting blood glucose values reach “prediabetic” levels (100 - 125 mg/dL) and usually stay in this range for many years. So long as the pancreas produces higher levels of insulin needed to overcome cellular insulin resistance, glucose levels remain fairly stable.[14]
Eventually, the pancreas is unable to maintain high levels of insulin production. The combination of cellular insulin resistance and declining insulin levels lead to progressively higher blood glucose levels and risk for development of type 2 diabetes.[14]
Your risk of developing diabetes depends on your degree of insulin resistance and fasting glucose levels.[16,17] As one moves from being insulin sensitive (IS) to insulin resistant (IR), the risk of diabetes increases at any given fasting glucose value. Likewise, as fasting glucose increases, risk of diabetes increases at a given level of insulin resistance.[17]
What to Remember
Dr. William Cromwell, MD, is the Chief Medical Officer for Precision Health Reports. He is a leading expert in the management of metabolic disorders and lipoprotein disorders including diabetes management. Through our products, he extends his three decades of research and in-clinic experience to enable practicing healthcare providers across the U.S. to better deliver personalized care to their patients. Our analyses change the conversation from trying to explain data to instead having a meaningful conversation about a person’s individual risks of developing serious and costly cardiometabolic diseases.
References
1. CDC. National Diabetes Statistics Report. Atlanta, GA2020.
2. Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care 2018;41:917-28.
3. Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training. Compr Physiol 2013;3:1-58.
4. Garvey WT, Kwon S, Zheng D, et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 2003;52:453-62.
5. Haas ME, Attie AD, Biddinger SB. The regulation of ApoB metabolism by insulin. Trends Endocrinol Metab 2013;24:391-7.
6. Reaven G. Insulin Resistance and Coronary Heart Disease in Nondiabetic Individuals. Arteriosclerosis, Thrombosis, and Vascular Biology 2012;32:1754-9.
7. Haffner SM. Epidemiology of Type 2 Diabetes: Risk Factors. Diabetes Care 1998;21:C3-C6.
8. Tabak AG, Jokela M, Akbaraly TN, Brunner EJ, Kivimaki M, Witte DR. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 2009;373:2215-21.
9. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41:S13-S27.
10. Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: a high-risk state for diabetes development. Lancet 2012;379:2279-90.
11. Connelly M, Winegar D, Shalaurova I, Otvos J. Nuclear Magnetic Resonance Measured Serum Biomarkers and Type 2 Diabetes Risk Stratification. Journal of Diabetes, Metabolic Disorders and Control 2015;2:2015.
12. Taylor R. Insulin Resistance and Type 2 Diabetes. Diabetes 2012;61:778-9.
13. DeFronzo RA. From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes 2009;58:773-95.
14. Kasuga M. Insulin resistance and pancreatic beta cell failure. J Clin Invest 2006;116:1756-60.
15. Frazier-Wood AC, Garvey WT, Dall T, Honigberg R, Pourfarzib R. Opportunities for using lipoprotein subclass profile by nuclear magnetic resonance spectroscopy in assessing insulin resistance and diabetes prediction. Metabolic syndrome and related disorders 2012;10:244-51.
16. Flores-Guerrero JL, Connelly MA, Shalaurova I, et al. Lipoprotein insulin resistance index, a high-throughput measure of insulin resistance, is associated with incident type II diabetes mellitus in the Prevention of Renal and Vascular End-Stage Disease study. J Clin Lipidol 2019;13:129-37 e1.
17. Harada PHN, Demler OV, Dugani SB, et al. Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study. J Clin Lipidol 2017;11:1257-67 e2.
18. Ellsworth DL, Costantino NS, Blackburn HL, Engler RJM, Kashani M, Vernalis MN. Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles. Obes Sci Pract 2016;2:282-92.
19. Fernández-Castillejo S, Valls R-M, Castañer O, et al. Polyphenol rich olive oils improve lipoprotein particle atherogenic ratios and subclasses profile: A randomized, crossover, controlled trial. Mol Nutr Food Res 2016;60:1544-54.
20. Bhanpuri NH, Hallberg SJ, Williams PT, et al. Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study. Cardiovasc Diabetol 2018;17:56-.
21. Niswender KD, Fazio S, Gower BA, Silver HJ. Balanced high fat diet reduces cardiovascular risk in obese women although changes in adipose tissue, lipoproteins, and insulin resistance differ by race. Metabolism - Clinical and Experimental 2018;82:125-34.
22. Goldberg R, Temprosa M, Otvos J, et al. Lifestyle and metformin treatment favorably influence lipoprotein subfraction distribution in the Diabetes Prevention Program. J Clin Endocrinol Metab 2013;98:3989-98.
23. Kitabchi AE, Temprosa M, Knowler WC, et al. Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. Diabetes 2005;54:2404-14.