Understanding your Lab Results – Allison Hull, DO

 

In Well-Being we recommend our members obtain certain laboratory studies both pre and post program to best evaluate the impact of their lifestyle changes during our 12 week program. This data is meant to educate you, the member, in learning how changes in nutrition, sleep, stress resiliency, and fitness affect your metabolic health.

It is important you communicate directly with your healthcare provider to obtain and then review these laboratory studies. Well-Being, LLC does not provide medical care. We are simply here to provide education.  It is vital you communicate directly with your health care provider to appreciate and customize your care. 

You can provide a list of these recommended labs to your provider.  There are cases in which providers elect not to order certain labs.  This will be left to the discretion of your provider.  Also, please be aware that your health insurance may not cover the expense of these labs.  It is your responsibility to learn which tests are covered.

Labs are considered fasting when we have gone at least 8 hours without food or beverage other than water.  Please be aware that a prolonged fast, greater than 18-24 hours, may alter some of your values.  For example, we often see LDL particle number increase with prolonged fasting. For this reason, I recommend you aim for 8-12 hours of fasting when completing labs.

 

  • Comprehensive Metabolic Panel (CMP)
    • CMP includes fasting blood glucose, electrolytes, liver function, and renal (kidney) function. I will focus here on the details pertaining to Well-Being, LLC and Metabolic health.
      • Please refer to your individual lab results to identify normal and abnormal results. There are subtle variations from one lab to another.
      • Once again, reach out to your healthcare provider to discuss your results in detail.
    • Fasting Blood Glucose
      • Normal is defined as less than 99 mg/dl
      • Impaired fasting glucose is defined as 100-125 mg/dl
      • Diabetes Mellitus is defined as greater than 126 mg/dl
      • There are no current societal guidelines identifying optimal fasting glucose levels.
      • Levels Health has provided proposed recommendations based on the review of current research and their own research. Levels currently recommends a fasting glucose of 72-85 mg/dl.  Visit levelhealth.com to learn more.
      • Fasting glucose levels can vary for numerous reasons outside of insulin resistance, prediabetes, and diabetes. For example, an early morning cortisol surge can increase your fasting glucose levels.  Also, insulin’s counterregulatory hormone, glucagon, can induce hepatic gluconeogenesis, glycogenolysis, and overall increase glucose in the overnight fasting state. 
      • The presence of glucagon secretion is essential in countering the suppressive effects of basal insulin (1). This is the human body’s protective mechanism to prevent hypoglycemia (low blood glucose levels) while we sleep.  However, this response can often overshoot its goal resulting in an elevated fasting glucose level.
      • We discuss this in greater detail during our 12 week program.
    • Liver Function
      • AST and ALT are liver enzymes, which can be elevated for many reasons but are commonly elevated in the face of non-alcoholic fatty liver disease (NAFLD). Normal values vary slightly from one lab to another.  We most commonly see an elevation in ALT with non-alcoholic fatty liver disease, however, non-alcoholic fatty liver disease can be present without an elevation in the enzymes.  US or CT imaging can also be done to better determine the presence of non-alcoholic fatty liver disease.  
      • We see significant improvement and often resolution of NALFD in members completing our 12 week Well-Being program.
      • Monitor your AST and ALT trend pre and post program. Chances are, you will see your “normal” levels lower compared to baseline at the completion of the 12 weeks.
      • Please speak to your healthcare provider if you would like to be evaluated for the presence of NAFLD.
    • Renal Function
      • We focus on creatinine and GFR (Glomerular Filtration Rate) when evaluating the CMP. Chronic Kidney Disease is defined as a GFR  level less than 60 mg/dl. 
      • An elevation in the BUN (Blood Urea Nitrogen) may be a sign of mild dehydration.
      • We recommend any Well-Being member with chronic kidney disease obtain permission from their primary care provider before beginning Well-Being. It is important you be monitored closely given the nutritional goals. 
      • If your provider does recommend you participate in Well-Being with a diagnosis of chronic kidney disease, we recommend your protein macronutrient goal not exceed 1 gm per kilogram of ideal body weight. This calculation will be explained in detail during week 4 of the 12 week program.
    • Electrolytes
      • Evaluates Sodium (Na), Potassium (K), Calcium (Ca), Chloride (Cl).
      • There are several variables that can impact our electrolyte levels. Those details will need to be discussed with your healthcare provider as it is outside the scope of this educational guide.
      • In Well-Being we discuss the effects of low carbohydrate/ketogenic nutrition on electrolyte levels and how to ensure adequate daily intake.
      • Both dehydration and overhydration can alter Sodium (Na) levels. It is, therefore, important we monitor and meet hydration goals while following a low carbohydrate/ketogenic nutritional plan. 
      • All electrolyte and hydration goals are discussed in detail during our 12 week program.
    • Fasting Insulin Level
      • A normal fasting insulin level is typically from 2-20 mIU/ml, however, this may vary slightly from one lab center to another.
      • Fasting insulin levels are typically elevated in the face of insulin resistance, prediabetes, diabetes, and metabolic syndrome.
      • Type 1 diabetics typically have a very low insulin level as their pancreatic beta cells reduce and event discontinue insulin production as result of an autoimmune cause.
      • The average insulin level in the US, according to the NHANES III survey, is 8.8 uIU/mL for men and 8.4 for women (2).
      • What is an optimal fasting insulin level? There are no current guideline recommendations defining optimal fasting insulin.
        • One study reveals a fasting insulin less than 8.0 mIU/ml most closely correlates with a non-prediabetic level (3).
        • Many experts extrapolate from studies correlating the risk of diabetes and prediabetes, to predict ideal fasting insulin levels. You will find some recommendations to be less than 5 mIU/ml, however, there are no standard guidelines to support this. 
      • Can we lower insulin too low for too long? The short answer is, yes.  As mentioned in the fasting glucose section.  Insulin has a counter regulatory hormone called glucagon.  Glucagon will increase when insulin levels decrease for prolonged periods.  Just exactly when this happens in each person is individualized. 
      • This physiologic response is one of the many reasons we recommend carbohydrate cycling after the completion of the 12 weeks.
      • You will learn far more detail on this subject week 12 of our program.
    • Hemoglobin A1c (glycated hemoglobin test)
      • Represents your average glucose level over 2 to 3 months. The A1c test measures how much glucose is bound to hemoglobin, which is the oxygen carrying compartment of the red blood cell. 
      • This number provides more information than a simple fasting glucose level. However, it also has its limitations. 
      • The life span of your red blood cells affects determination of HbA1C levels. This means your HbA1c result can be falsely misrepresented as lower or higher than its actual value. The following circumstances often misrepresent your HgA1c levels to present lower:
        • Rapid red blood cell turnover due to hemolysis
        • Increased production of red blood cells due to anemia treatment with iron, B12, folic acid, or erythropoietin
        • Recent blood transfusion
        • Splenomegaly (enlarged spleen)
      • HgA1C is a screening tool for prediabetes and diabetes
        • Normal HgA1C is defined as less than 5.6 percent
        • Prediabetes is defined as 5.7-6.4 percent
        • Diabetes is defined as greater than 6.5 percent
        • What is an optimal HgA1C level?
          • Once again, there are no current societal guidelines defining optimal hgA1C levels.
          • Levels above 5.4 percent in nondiabetics are associated with increased relative risk for developing coronary atherosclerotic heart disease (CAD), ischemic stroke (CVA) and mortality from any cause, as compared to those with levels in the 5.0-5.4 percent range (4).
          • Based on these and other studies, we could extrapolate an ideal hgA1C goal is possibly 5.0-5.4 percent.
        • Lipid panel with Direct LDL
          • To interpret these test results, we must first understand lipoprotein biology, because the commonly measured serum cholesterol and triglycerides are carried in these lipoproteins.
          • Cholesterol and triglycerides are hydrophobic fats that must be packaged in hydrophilic lipoproteins for transport in plasma (5).
          • A traditional lipid panel typically evaluates a calculated LDL as opposed to a direct LDL. There are limitations with a calculated LDL.  If triglycerides are elevated, the LDL result will not be accurate.  For this reason, we always recommend a lipid panel with a direct LDL. 
          • Lipoprotein particles are identified by their surface apo-lipoproteins.
          • All lipoprotein particles that carry an apo-lipoprotein B surface protein (VLDL, IDL, LDL, and Lp (a) are atherogenic, meaning they contribute to plaque development and cardiovascular disease (5).
          • Labs measure, and healthcare providers historically treat the serum level of cholesterol and triglycerides. The reason this has historically been accepted is because under ideal physiologic conditions, the lipoprotein LDL Particles carry 90% of the LDL-cholesterol and the lipoprotein VLDL Particles carry 90% of the triglycerides. However, this reasoning is flawed greatly when we see triglyceride levels exceed 100 mg/dl.
            • When triglyceride levels exceed 100 mg/dl, cholesterol ester transfer protein (CTEP) transfers triglycerides from VLDL Particles to LDL Particles in exchange for LDL- cholesterol. Therefore, many individuals with prediabetes, diabetes and metabolic syndrome appear to have a low LDL-cholesterol level when, we are seeing a misrepresentation of the true picture (5).
            • When Well-Being tribe members follow a lower carbohydrate/ketogenic nutritional plan, we see significant reductions in triglycerides. This is because the body adapts to using triglycerides for fuel in place of glucose or glycogen.
            • As triglyceride levels decrease, there is a shift in the “representation” of LDL-cholesterol. VLDL particles transfer LDL-cholesterol back to LDL particles and LDL Particles in return delivers triglycerides back to VLDL.  Total cholesterol is therefore, not necessarily going up, it is just being presented differently. 
            • Please be aware of this when you review your lab results with your provider. It is possible your provider may not be aware of this process.
          • Once again, the lipid panel with a direct LDL focuses on direct LDL number compared to a calculated LDL, which can be affected by elevated triglycerides.
          • Let’s dig a little deeper into the traditional lipid panel:
            • Total Cholesterol level
              • This number is not very meaningful as it can be misrepresented by a high or low HDL level.
              • Labs will denote a total cholesterol as elevated if it exceeds 200 mg/dl, however, a high HDL, which is protective against cardiovascular disease will skew this number.
              • We do not recommend you hyper-focus on this value, it is often times meaningless.
            • LDL (Low Density Lipoprotein) cholesterol
              • Elevated LDL- cholesterol levels are associated with increased risk for cardiovascular disease, however, there are many other contributing factors affecting both our total LDL-cholesterol number and overall risk for atherogenic cardiovascular disease.
              • Current guideline recommendations are set by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and Framingham Risk Score. Goals for LDL-cholesterol are largely dependent upon a person’s overall risk for atherogenic cardiovascular disease.
              • The current NCEP ATP III guideline recommendations are as follows:
                • Very High Risk – Less than 70 mg/dl
                • High Risk – Less than 100 mg/dl
                • Moderate risk- Less than 130 mg/dl
                • Low risk – less than 160 mg/dl
              • Unfortunately, these guidelines do not consider the total Non-HDL cholesterol or the LDL particle size, which largely dictates its resonance time within systemic circulation and therefore its ability to become oxidized and further contribute to atherosclerosis.
              • More details on this subject in the Advance Lipid Panel section noted below.

 

  • HDL (High Density Lipoprotein) cholesterol
    • Higher HDL levels are associated with a decreased risk for cardiovascular disease.
    • HDL Particles are referred to as the “non-atherogenic lipoprotein”. We can think of them as the Pac-Men of the lipoprotein family. 
    • HDL Lipoproteins are defined by their surface protein, Apolipoprotein A-1 or Apolipoprotein A-2.
    • HDL-Particles carries HDL-cholesterol from the vascular intima macrophages back to the liver to be catabolized.
    • Low carbohdydrate/ketogenic nutrition and exercise increases HDL Particle numbers represented as HDL-cholesterol on your standard lipid panel.
    • Much research is still needed to better evaluate the function of HDL-Particles and its role both in the prevention and contribution to atherosclerotic cardiovascular disease.
    • HDL-cholesterol goals vary depending upon sex:
      • Greater than 50 mg/dl in women
      • Greater than 40 mg/dl in men
      • Optimal levels for both sex is greater than 60 mg/dl, which negates a risk factor for CAD
    • Triglycerides
      • Normal levels are defined as less than 150 mg/dl, however, optimal levels are less than 100 mg/dl.
      • As discussed above, triglyceride levels greater than 100 mg/dl leads to a shift in triglycerides from VLDL Particles to LDL Particles through CTEP. When LDL Particles carry a greater burden of triglycerides, they reduce in size, thereby prohibiting the liver receptors to identify LDL Particles, which leaves them out in systemic circulation longer leading to greater oxidation and risk for atherosclerosis. 
      • Once again, we typically see significant reductions in triglyceride levels in our members. This is due to the shift in using fat/triglycerides for fuel.
      • Lowering Triglyceride levels is the primary treatment to resolve fatty liver disease.
    • Total Cholesterol/HDL ratio
      • This ratio takes into consideration the benefit of a high HDL- cholesterol.
      • Simply take your total cholesterol number and divide by your HDL-cholesterol.
      • What is the target? In general:
        • The higher the ratio, the higher the risk
        • Less than 5.0 is considered normal
        • A ratio below 3.5 is considered very good.
      • Non-HDL Cholesterol (Total Cholesterol – HDL Cholesterol = Non-HDL Cholesterol)
        • Represents all Non-HDL cholesterol, including cholesterol found within VLDL, LDL, and IDL lipoprotein particles.
        • Provides a much more complete clinical picture than LDL cholesterol alone as an individual can have a greater or lesser amount of cholesterol housed within the VLDL and IDL lipoprotein particles that would be missed if only LDL cholesterol is evaluated.
        • The value of a Non-HDL cholesterol level increases when triglyceride levels exceed 100 mg/dl.
        • Like LDL cholesterol, non-HDL cholesterol goals are dependent upon a person’s overall risk for CAD.
        • The current NCEP ATP III guideline recommendations are as follows:
          • Very high risk – Less than 100 mg/dl
          • High risk – Less than 130 mg/dl
          • Low to Moderate risk- Less than 160 mg/dl

 

 

  • Apolipoprotein B level (ApoB level)
    • ApoB level represents the surface protein on VLDL, LDL, IDL lipoprotein particles, which contributes to the atherogenicity of the lipoprotein particle.
    • ApoB permits the lipoprotein particle to enter the intima of the arterial endothelium (lining) and then delivers cholesterol to contribute to the development of atherosclerosis.
    • Measuring ApoB levels eliminates that “misrepresentation” picture we see when evaluating LDL-cholesterol alone.
    • Many experts compare the value of ApoB levels to that of non-HDL cholesterol levels. Both account for discordance in triglyceride levels.  There is some conflicting data on this subject. 
    • Some studies reveal circumstances in which ApoB levels provide superior risk stratification compared to non-HDL cholesterol alone.
    • The American Diabetes Association/American College of Cardiology (ADA/ACC) recommendations for ApoB levels are as follows:
      • Very high risk, defined as a known history of atherosclerotic cardiovascular disease or diabetes mellitus + additional risk factor – goal is less than 80 mg/dl
      • High risk, defined as those without atherosclerotic cardiovascular disease or diabetes mellitus, but with 2 cardiometabolic risk factors – goal is less than 90 mg/dl (6).
    • We do feel there is value in evaluating an ApoB level to fully appreciate an individual’s risk profile for atherosclerotic cardiovascular disease.
    • While we often see optimization post program of a lipid profile with a reduction in triglycerides, increase in LDL-Particle size, and an increase in HDL-Particle number and HDL-cholesterol, if ApoB level increases out of proportion to these improvements, it is reasonable to adjust nutritional goals for the individual. Long and short, this may help you customize your nutritional plan.  Once again, you must discuss these results with your healthcare provider.
  • Advanced Lipid Profile including Lipoprotein fractionation with LDL particle size and pattern
    • This laboratory study is meant to better identify Lipoprotein Particle type, size, and number.
    • Depending upon the specific panel ordered, it will often include both LDL and HDL Particle number and size, Apolipoprotein B (discussed separately), and Lipoprotein (a).
    • You can also evaluate a Lipoprotein fractionation with LDL particle size and pattern alone. This will reveal the LDL and HDL particle size and number as well as identify a pattern A compared to a pattern B.  Pattern A signifies less of the smaller, denser, atherogenic LDL Particles and more of the large, less atherogenic LDL Particles. The goal is to see a shift to pattern A post program. More details below.
    • Lipoprotein (a) is especially important to evaluate when there is a strong family history of heart disease or when an individual’s LDL cholesterol exceeds 190 mg/dl. It is estimated to be elevated in 20% of the world’s population (7). This significantly increases an individual’s risk for atherosclerosis in the face of high LDL-cholesterol levels. If an individual has a higher Lipoprotein(a) level, their healthcare provider will want to best stratify their treatment plan accordingly.
    • As mentioned above, there are some limitations on measuring our standard lipid panel.
    • Advanced Lipid Profiles fractionate the LDL particle size and pattern. As previously discussed, smaller LDL Particles are at greater risk for oxidation due to their increased resonance time of 5 days compared to 2 days within system circulation.  This occurs due to a mismatch between the liver receptors and the LDL Particle size.  The liver is responsible for catabolizing LDL particles and therefore, reducing the time in which LDL Particles can contribute to the development of atherosclerosis. 
    • Smaller, dense LDL Particles also contribute to atherosclerosis as they are at greater risk for entering the intima of the arterial endothelium, which then contributes to the cascade of events leading to the development of a fatty streak and ultimately an atherosclerotic plaque.
    • Lastly, plaque comprised of smaller, denser LDL particles is more inflammatory, less stable, and more likely to rupture igniting an advance cardiac event, such as a heart attack.
    • How are Advanced Lipoproteins typically measured? There are multiple types of technology, however, the most common used today are as follows:
      • Nuclear Magnetic Resonance (NMR)
        • This is the technology used by Labcorp.
        • NMR uses magnetic resonance to estimate the lipoprotein distribution using proton spectroscopy methods.
      • Ion Mobility
        • This is the technology used by Quest.
        • Ion Mobility measures the drift of charged particles as they are dragged through the air by the force of an electric field and then determine particle size from drift velocity.
      • Unfortunately, there is significant variability among these different technologies, which highlights the importance of using the same method of measurement to compare pre and post program.
      • There is no international standard for lipoprotein subclass composition assessment. For this reason, I recommend this test be used as another tool to assess our changes, however, it alone is not enough to determine change or risk stratify for atherosclerotic disease.
      • Research reveals both fasting and lower carbohydrate diets increase LDL Particle size, therefore, reducing its contribution to atherogenic cardiovascular disease (8).

 

  • 25 Hydroxyvitamin D level to represent your Vitamin D levels
    • This lab is a good indication of how much vitamin D your body has stored. Vitamin D is necessary for optimal growth, development, and disease prevention.
    • Heath effects of Vitamin D deficiency reach far beyond Osteoporosis. These effects are mostly supported by circumstantial evidence of epidemiologic studies and laboratory research.  These include prevention of cancer, autoimmune disease, diabetes, and cardiovascular disease.  We see improvement in immune health and respiratory function with higher Vitamin D levels (9).
    • While lab values define a normal value at 30 ng/ml or greater, there are no current standard guidelines to support an optimal
    • There are some studies recommending an optimal serum 25 hydroxyvitamin D levels are between 36-48 ng/ml (9). However, some anecdotal data suggests a higher level. It is evident more research is needed to best determine an individual’s optimal Vitamin D level.
    • Being that Vitamin D is a fat-soluble vitamin, we can develop toxicity if Vitamin D levels exceed the upper limit of normal of 100 ng/ml.
    • There are no standard guideline recommendations for supplementation, however, evidence supports 2,000 IU of Vitamin D 3 daily may successfully and safely achieve this goal (10).
    • When 25 Hydroxyvitamin D levels fall below 20 ng/ml, healthcare providers will often supplement with a prescription dose at 50,000 IU once weekly x 12 weeks.
    • Knowing your personal Vitamin D level, measured as 25 Hydroxyvitamin D level, will allow you and your healthcare provider to best determine your ideal supplementation needs.

 

 

References:

  1. Ramnanan, C.J, Edgerton, D.S, Physiologic action of glucagon on liver glucose metabolism, Diabetes, obesity and metabolism, 2011 Oct;13(Suppl 1): 118-125.
  2. Johnson JL, Duick DS, Chui MA, Aldasouqi SA. Identifying prediabetes using fasting insulin levels. Endocr Practice. 2010 Jan-Feb; 16(1)47-52.
  3. Harris MI, Cowie CC, Gu K, Franics ME, Flegal K, Eberhardt MS. Higher fasting insulin but lower fasting C-peptide levels in African Americans in the US population. Diabetes Metab Res Rev. 2002 Mar-Apri;18(2):149-55
  4. Selvin E, et al. Glycated Hemoglobin, Diabetes and Cardiovascular Risk in Nondiabetic Adults, NEJM 2010, 362(9):800-11.
  5. Gleeson, Robert, Davidson, Michael, Lipidology a Primer: the what, why, and how of better lipid management, Prevent CVD, LLC, 2010.
  6. Harper, Charles, Jacobson, Terry. Using Apolipoprotein B to Manage Dyslipidemic Patients: Time for a Change? Mayo Clin Proc. 2010 May; 85(5): 440-445.
  7. Wilson DP, Jacobson TA, Jones PH, et al. Use of Lipoprotein(a) in Clinical Practice: a biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol 2019:13:374-92.
  8. Guay V, Lamarche B, Charest A, Tremblay AJ, Couture P. Effect of short-term low-and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects. Metabolism: clincal and experimental. 2012:61:76-83.
  9. Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):575-9
  10. Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Bio. 2008;624:55-71.