Insulin Resistance 101 & 2 Things You can do to Avoid It

Listened to another great podcast by Dr Peter Attia. Peter interviewed Dr Gerald Shulman an expert on insulin resistance. “If you have an interest in being healthy you can’t be insulin resistant. If you are insulin resistant, you’re not going to be healthy. . .But if you’re in the business of wanting to live the healthiest life you can live, which means longer and better, you’ve got to be insulin sensitive, full stop.” —Peter Attia Definition of Insulin

• Insulin is a hormone secreted by the pancreas
• Insulin as a very anabolic (building/growing) hormone – it makes fat cells more fat, it makes muscle cells more glycogen rich, and it makes the liver more glycogen rich. It is a pro-building hormone

Definition of Insulin resistance (IR):

• Insulin resistance is probably best defined as an impaired ability for insulin to perform it’s required tasks.
  • e.g., if insulin’s job is to take glucose into a muscle so that a muscle can make glycogen, when that gets impaired, that is insulin resistance in the muscle
  • However, fat cells and liver cells have a slightly different explanation/manifestation of insulin resistance.
• Typically there is a 4 step path to severe insulin resistance:
  1. Glucose stays relatively low after the ingestion and so does insulin (normal)
  2. Insulin goes up while glucose stays down (this is the earliest indication that something is wrong)
  3. Glucose goes up while insulin stays up
  4. Fasting glucose going up and then fasting insulin going up (once fasting glucose gets high enough you’re very close to diabetes)

Measuring IR – The Oral Glucose Tolerance Test:

• Patients show up after a fast (typically over night) and you draw blood to measure fasting glucose and insulin levels.
• Patients then ingest 75 grams of glucose
• Every 30 minutes for 2 hours you draw blood, checking glucose and insulin levels
• From this you generate 2 curves:
  • Patient’s glycaemic response (how does their glucose change over the next two hours)
  • Patient’s insulin response over those 2 hours
• You’re trying to measure how much glucose gets taken up into the muscles (glucose level over time), and then how much insulin was required to do it (insulin levels).
• As discussed in the 4 step method above - The earliest indication of insulin resistance is an elevation of insulin levels. Peter notes that he sees patients all the time that have normal glucose levels but their insulin levels are sky high!

Metabolic Syndrome – Another Way to Diagnose Risk of IR:

• 5 Criteria used to measure Metabolic Syndrome (there are different ways to measure each criteria):
  1. Obesity: Waist circumference: Male >= 94/102 cm (~37 / ~41 inches) or Female >= 80/88cm (~31 / ~34 inches)
  2. Serum Triglycerides: >150 mg / dl (associated with an increased risk of atherosclerosis, coronary artery disease and stroke)
  3. Serum HDL Cholesterol (the good cholesterol): Male: < 40mg/dl, Female: < 50mg/dl
  4. Blood Pressure: > 130/85
  5. Fasting Plasma Glucose: > 100mg/dl or > 5.5 mmol/l
• If you have 3 or more of the 5 criteria present you are technically defined as having metabolic syndrome. Your risk for all metabolic diseases: cancer, cardiovascular disease, Alzheimer’s disease, and type 2 diabetes rises considerably!
• Peter’s comments:
  1. Amount of visceral fat is more important than subcutaneous fat
  2. Peter believes triglycerides should always be below 100 and always less than twice your HDL cholesterol.
  3. Peter is very aggressive with blood pressure — Anything over 120 over 80 is reason to start to pay attention!
  4. Peter is not particularly alarmed with fasting glucose above 100, depending on how it responds
     • For example, a fasting glucose of 105 is not terribly alarming if the average blood glucose is below 100 (which is not uncommon in people where they have a bit of a “dawn effect” - a natural rise in blood sugar that occurs in the early morning hours)

Insulin Resistance Fix 1 – Exercise!

• Study published in 1996 in the NEJM: Increased Glucose Transport–Phosphorylation and Muscle Glycogen Synthesis after Exercise Training in Insulin-Resistant Subjects
• Found that one 45-minute bout of aerobic exercise—three 15-minute sets at ~65% of your maximal aerobic capacity boosted insulin sensitivity and glucose disposal.
• Peter has had patients with type 1 diabetes who used long duration, submaximal exercise to reduce their dependence on insulin
• Over time (i.e., chronically) more exercise reduces intramuscular lipid, increases oxidative phosphorylation, and therefore reduces TAG and DAG

Insulin Resistance Fix 2 – Dietary Intervention

• Specifically, fructose reduction and glucose reduction (less carbs overall and especially refined carbs) until a homeostasis is achieved.
• Low Carb / Keto diets seem to perform a re-set in people who are previously insulin resistant.

In summary: Exercise and nutrition are a first line of defence against metabolic syndrome!