ENDOCRINE EXPLAINED

What is insulin? Insulin is what allows sugar into cells. All cells use sugar as their basic fuel. Sugar is absorbed from food we eat directly, or is broken down from more complex carbohydrates. Sugar is also created in our liver between meals and overnight in a process called gluconeogenesis. This glucose circulates in our blood to be delivered to our body's cells. In every cell, glucose is used as the basic fuel for proteins to be made, for upkeep and repair, and for cell division and growth. Insulin receptors in cells respond to insulin as a keyhole to a key that unlocks a door to the glucose transporters, allowing sugar to enter. As a result, sugar enters most cells only when insulin levels are sufficient to "open the door" to the cell. 

 

And what is insulin resistance?  When someone has insulin resistance, a typical, low level of insulin doesn't open the door. The amount of insulin needed for the body to process sugar and use it for energy is significantly elevated.  As a result, sugar can't enter cells easily; there is a lag from the time sugar is available until enough insulin is released to allow its passage into the cells. We can picture the usual cell's "keyhole" for insulin to be sticky, or the door itself being stuck, so that a high insulin level is needed to smooth or expand that keyhole, or force open the door. During this lag, blood sugar continues to rise, cells are still awaiting energy, and chemical stress hormones are released. As a result of insulin resistance and the delay in cells receiving energy, the liver creates and releases extra sugar, and more food - especially carbohydrates - are craved and consumed. 

 

Is insulin resistance the same thing as having diabetes? Thankfully, no. IR is far more common than diabetes, and a diagnosis of IR is not a diagnosis of diabetes. With insulin resistance, the liver creates and releases extra sugar, and more food - especially carbohydrates - are craved and consumed. When the insulin resistance is high enough that insulin levels can't rise to meet the demand, then blood sugars rise to above normal ranges. This is called diabetes. 

Diabetes is a condition of chronically elevated blood sugar, diagnosed by measuring elevated blood glucose levels on multiple occasions. If a fasting blood sugar level rises to 125 mg/dl or above, or if blood sugar reaches 200 mg/dl or above at any time, then a person is diagnosed with diabetes. There are intermediate stages of "impaired glucose tolerance", and "impaired fasting glucose" where there is significant insulin resistance that has begun to affect blood sugar control.

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That said, the vast majority of people with insulin resistance have normal blood sugar levels. This is because as long as someone can make enough insulin, they can have severe insulin resistance without developing diabetes. Other people have more limited ability to make insulin, so even a little resistance results in high blood sugar. The ability to make insulin is strongly influenced by family/genetic factors, and the general health of the pancreas. As long as a person's ability to make insulin matches their insulin resistance, then diabetes does not develop. 

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But, why does having insulin resistance matter? 

As we reviewed last newsletter, in its most severe consequence, insulin resistance can lead to diabetes, chronically high blood sugars. The majority of people with insulin resistance have normal blood sugar levels. This is because as long as someone can make enough insulin to match their insulin resistance, they can move sugar into cells, feeding them.  Other people have much more limited ability to make insulin, so even a little resistance results in high blood sugar, with energy unavailable to the cells. As long as a person's ability to make insulin matches their insulin resistance, then diabetes does not develop. But high levels of insulin can also lead to health challenges. 

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Insulin resistance can lead to subsequent low blood sugars. This happens when, following a rise in blood sugar, the insulin level reaches the threshold for passage of the glucose from the bloodstream into the body's cells. Sometimes insulin resistance is mild, and insulin levels are only double the typical level, but sometimes they are 30x the level. The higher the insulin levels climb, the more rapidly blood glucose levels subsequently fall, as the body's hungry cells quickly use up their delivered fuel.  

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How does insulin resistance lead to weight gain? The role of insulin in providing cells energy is described above. As high levels of insulin more rapidly drive sugar from the bloodstream into cells, the cells accumulate extra energy, and do it faster. This extra energy then needs to be put somewhere. Excess energy in the body is stored as fat - so insulin resistance leads to weight gain. And since weight gain leads to greater insulin resistance, it can lead to a seemingly insurmountable snowball effect. 

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Why else does having insulin resistance matter? Unfortunately, elevated insulin levels have other impacts in the body, leading to health concerns. Insulin resistance is associated with diabetes and weight gain, but also impaired fertility - particularly due to a hormone imbalance/PCOS (learn more here), heart disease and cancers. Rapid weight gain also tends to mature a child's skeleton, leading to shorter adult stature than had been anticipated (learn more about children's growth here). As a result, trying to halt and reverse insulin resistance - at any age - is a worthwhile goal.

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How do I know if I have - or my child has - insulin resistance?

In general, endocrinologists don't need to measure insulin levels in someone with rapid gain and abdominal weight - clear signs of insulin resistance. That said, some lab tests make it clear that insulin resistance is present, which can spur people to start making changes. For many, triglyceride levels rise with insulin resistance.  For some, it can be significant enough that there is "impaired fasting glucose," where fasting blood sugar level is at least 100, or cause impaired glucose tolerance, where blood sugar rises to at least 140 two hours after a meal. With a lag in insulin response, the average blood sugar may rise, leading to an elevated  "Hemoglobin-A-1-C" (aka HgbA1C > 5.6%). On physical examination, several aspects speak to insulin resistance: persistent or rapid weight gain, elevated BMI associated with higher waist circumference, and the presence of acanthosis nigricans - dark, velvety patches around the neck, in underarms, groin and skin folds.

 

Why does insulin resistance start? IR is strongly inherited, along with a family history of PCOS, gestational diabetes and Type 2 Diabetes. This initial risk for high insulin levels markedly increases with weight gain, low physical activity, and diet high in saturated fat (animal fats and processed vegetable oils) and/or simple carbohydrates (foods that break down quickly into sugar). Other contributing factors to IR are health conditions associated with chronic inflammation, steroid use, chronic stress and depression, and lack of nighttime sleep - working and eating overnight or having sleep apnea.

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At what age can insulin resistance start? There can be hints of it at a very young age. There is a strong correlation between early and rapid weight gain and insulin resistance. And rapid gain can be the result of family history, diet, steroid use, sleep apnea, and chronic stress. These can occur even in early childhood.

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How is insulin resistance treated? Over the years, insulin resistance has been treated with insulin sensitizing medications, appetite suppressants, as well as with lifestyle changes - exercise, dietary changes, and weight loss.  

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Insulin sensitizing medications have been a mainstay of treatment for decades. Metformin is approved for children, and reduces insulin resistance. Other medication used to reduce insulin resistance and treat diabetes (PPAR-gamma medications) are commonly used to treat adults, but due to their higher risk of side effects, are not recommended for children. A set of supplements - myo-inositol and D-chiro-inositol - also appear to aid insulin's effects within cells. 

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Lifestyle changes include multiple modalities for reversing insulin resistance. Exercise - both aerobic and strength training - has been associated with decreasing insulin resistance in all ages. For those with familial insulin resistance, there is often extra fat cells within and between muscle fibers, called "intramyocellular lipid deposition" that improves with greater use of those muscles, as in weight training, high intensity interval training and Pilates.

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Dietary changes that are successful typically reduce processed foods and simple sugars, and expand produce and lean proteins within meals. Some have found success with very low carbohydrate diets, intermittent fasting and ketogenic diets, but a plan that is focused on whole grains, legumes, lean proteins, and expanding produce - also termed a "Mediterranean diet" - is more likely sustainable and socially acceptable for teens and young adults.

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Weight stored in the midsection, highly correlated with insulin resistance, is termed "visceral fat" and is treated with weight loss, rather than any specific activity, in those who have completed their growth. Indeed, a 5-10 pound weight loss in teens and adults who carry weight in their abdomen can cause marked changes in insulin resistance. With this decade's emergence of more effective weight-loss medications (phentermine and topiramate, and GLP-1 agonists and receptor blocking medications), many adults have found weight loss to be more rapid and consistent with medication, thereby sharply reducing insulin resistance quickly. Some of these medications are approved for teens, but with use needed indefinitely for ongoing weight management, it is considered by many pediatric endocrinologist an important but not uncomplicated modality for treatment.

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For growing children - even those with significant extra weight - weight loss often results in reduced growth with height permanently reduced. For this reason, I strongly urge families to build habits and meal plans that aim for weight maintenance. This allows their child to grow into the weight, with reductions in BMI and adiposity and insulin resistance over time - with continued growth and health and confidence.

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For most children with insulin resistance, it is likely multiple factors - heredity, as well as nutritional, medical, and functional challenges - that are additive and contributing to a child's insulin resistance. Each of these must be addressed in a comprehensive evaluation and to decide on an optimal treatment plan. Addressing the unique set of underlying causes for a particular child can avoid treatment that may superficially promote a desired effect in the short term that fails to optimize health for a child's lifetime. 

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To schedule a two-hour appointment with Dr. Lerner to learn more, 

to discuss a child/teen's evaluation and diagnosis with insulin resistance,

and ask your questions about health and endocrinology,

PRESS HERE.

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Resources for learning around the web:

1. WebMD: https://www.webmd.com/diabetes/insulin-resistance-syndrome

2. CDC: https://www.cdc.gov/diabetes/basics/insulin-resistance.html

3. NIDDK: https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance

4. KidsHealth: https://kidshealth.org/en/parents/insulin-resistant.