On Insulin Resistance

facilis descensus averno: the path to hell is easy.

You live as if you were destined to live forever, no thought of your frailty ever enters your head, of how much time has already gone by you take no heed. You squander time as if you drew from a full and abundant supply, though all the while that day which you bestow on some person or thing is perhaps your last. - Seneca

Insulin

Insulin is a peptide hormone secreted by the pancreas in response to increases in blood sugar, usually following a meal. However, one doesn’t have to eat a meal to secrete insulin. In fact, the pancreas always secretes a low level of insulin.

After a meal, the amount of insulin secreted into the blood increases as blood sugar rises. Similarly, as blood sugar falls, insulin secretion by the pancreas decreases. Insulin thus acts as an “anabolic” or storage hormone. In fact, many have called insulin “the most anabolic hormone”. Once insulin is in the blood, it shuttles glucose (carbohydrates), amino acids, and blood fats into the cells of the body. If these nutrients are shuttled primarily into muscle cells, then the muscles grow and body fat is managed. If these nutrients are shuttled primarily into fat cells, then muscle mass is unchanged and body fat is increased.

What To Know

Due to the anabolic power of insulin, many overly fat individuals want to avoid insulin release. This is because they want to avoid storing body fat. One needs insulin, but the trick is to learn how to balance the anabolic effects in muscle tissue against the fat storage effects. This can be done by increasing insulin sensitivity in the muscle while decreasing insulin sensitivity in the fat cells. Controlling insulin release during the day is important for long-term sensitivity.

What keeps insulin sensitivity high?

• Exercising 5 hours per week, especially resistance training

• Muscle mass

• Supplements like omega-3 fatty acids, alpha-lipoic acid, and chromium

• Adequate vitamin D status

• 7-9 hours of sleep per night

What lowers insulin sensitivity?

• High processed carbohydrate diets

• Sedentary lifestyle

• Cigarette smoking

• Vitamin D deficiency

• Sporadic sleep patterns

• Excessive alcohol consumption

Insulin Resistance

Insulin resistance increases one’s risk of developing diabetes. One could be insulin resistant for years without knowing it. This condition typically does not trigger any noticeable symptoms, so it’s important to have a doctor regularly check one’s blood glucose levels. Insulin is a peptide hormone secreted by the pancreas in response to increases in blood sugar, usually following a meal. However, one doesn’t have to eat a meal to secrete insulin. In fact, the pancreas always secretes a low level of insulin.

Insulin resistance is a hallmark of obesity and is thought to be the cause of or an associated factor in the metabolic syndrome associated with cardiac disease.

Symptoms of insulin resistance

If you have prediabetes, it’s important to work with your doctor. They will routinely monitor your blood sugar or hemoglobin A1C (HbA1c) so they can recognize whether you’ve developed diabetes.

Classic diabetes symptoms include:

• extreme thirst or hunger

• feeling hungry even after a meal

• increased or frequent urination

• tingling sensations in hands or feet

• feeling more tired than usual

• frequent infections

• evidence of high blood sugar levels in blood work

Some people with insulin resistance may also develop a skin condition known as acanthosis nigricans. It appears as dark, velvety patches often on the backs of the neck, groin, and armpits. There’s no cure for this condition.

Insulin resistance increases the risk of:

• being overweight

• having high triglycerides

• having high blood pressure

• developing major depression

Risk factors for insulin resistance

Testing for diabetes should begin at about age 40, along with the usual tests for cholesterol and other markers of health. Ideally, one’s doctor will request testing at one’s annual physical exam or preventive screening.

One’s doctor may recommend testing at a younger age if one has these risk factors:

• have a sedentary, or inactive, lifestyle

• have a low HDL (good cholesterol) level or high triglyceride level

• have a parent or sibling with diabetes

• have high blood pressure (140/90 mm Hg or above)

• have symptoms of prediabetes

• were diagnosed with gestational diabetes (a temporary condition that causes diabetes only while pregnant)

• had a baby who weighed more than 9 pounds

• have had a stroke

Children and teens ages 10 to 18 may also benefit from diabetes screening if they are overweight and have two or more of the above risk factors for diabetes.

If one doesn’t have obvious symptoms, one’s doctor can usually detect pre-diabetes or diabetes with lab tests. Though doctors don’t usually test for insulin resistance, the most accurate test is a euglycemic insulin clamp that’s used for research purposes.

Testing and diagnosis of insulin resistance

Euglycemic clamp

Eugylcemic Clamp techniques are the gold standard for measurement of insulin resistance. Fasting insulin concentrations offer little insight into insulin resistance in an individual, and equations such as the homeostatic model assessment(HOMA) that are based on fasting insulin levels offer little more; however, fasting insulin values are used in epidemiological studies and offer more useful information.

The fasting insulin concentration increases twofold to threefold with PHV, insulin secretion after a glucose load increases over prepubertal levels, and insulin-mediated glucose disposal in peripheral tissues decreases in the hyperinsulinemic euglycemic clamp or the minimal model frequently sampled intravenous glucose tolerance test (IVGTT), showing increased insulin resistance during normal puberty. Insulin sensitivity is inversely related to pubertal stage and BMI.

A1C test

Another way to diagnose pre-diabetes or diabetes is with an A1C test. This test measures one’s average blood sugar over the previous 2 to 3 months.

• An A1C under 5.7 percent is considered normal.

• An A1C between 5.7 and 6.4 percent is diagnostic for prediabetes.

• An A1C equal to or above 6.5 percent is diagnostic for diabetes.

One’s doctor may want to reconfirm the test results later. However, depending on the lab where one has one’s blood drawn, these numbers could vary by 0.1 to 0.2 percent.

Fasting blood glucose test

A fasting blood glucose test will show fasting blood sugar level. One has this test done after not eating or drinking for at least 8 hours.

A high level may require a second test a few days later to confirm the reading. If both tests show high levels of blood glucose, one’s doctor may diagnose one with pre-diabetes or diabetes.

• Fasting blood sugar levels under 100 milligrams/deciliter (mg/dL) are considered normal.

• Levels between 100 and 125 mg/dL indicate prediabetes.

• Levels equal to or greater than 126 mg/dL are diagnostic for diabetes.

Depending on the lab, these numbers could vary up to 3 mg/dL points in the cutoff numbers.

Glucose tolerance testing

A 2-hour glucose tolerance test may be another way to diagnose pre-diabetes or diabetes. One’s blood glucose level will be determined before this test begins. One then receives a pre-measured sugary drink, and one’s blood glucose level is checked again in 2 hours.

• A blood sugar level of less than 140 mg/dL after 2 hours is considered normal.

• A result between 140 mg/dL and 199 mg/dL is considered prediabetes.

• A blood sugar level of 200mg/dL or higher is considered diabetes.

Random blood draws

Random blood sugar tests are useful if one is experiencing significant diabetes symptoms. However, the American Diabetes Association (ADA) doesn’t recommend random blood glucose tests for routine diabetes screening or for identifying prediabetes.

Preventing insulin resistance problems

If one has pre-diabetes, one may be able to prevent the condition from developing into diabetes with these health-promoting behaviors:

• Work toward including exercise as a part of daily routine, preferably getting in 30 minutes at least 5 days a week.

• Making lifting weights a priority

• Try to eat a nutrient-rich, balanced diet as often as possible comprised of lean proteins and healthy fats.

• If overweight, consider losing weight — even reducing one’s body weight by just 7 percent can help lower one’s risk of developing diabetes.

With the increased prevalence of type 2 diabetes (non–insulin-dependent diabetes mellitus [NIDDM]), proposed screening criteria are being evaluated. Currently, children with a BMI higher than the 85th percentile should be screened if they (1) have a family history of type 2 diabetes, (2) have signs of insulin resistance (e.g., acanthosis nigricans, functional ovarian hyperandrogenism, hypertension, dyslipidemia), or (3) belong to one of several specific ethnic groups (e.g., African American, Native American, Hispanic American, Asian American).

If a fasting plasma glucose level is higher than 126 mg/dL or a 2-hour postprandial value is higher than 200 mg/dL, or if there are symptoms such as weight loss, polyuria, or polydipsia and a casual plasma glucose level higher than 200 mg/dL, the diagnosis of diabetes is likely, and determination of the type of diabetes (type 1 or 2) is appropriate.

Patients with type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) usually require an increase in the dose of insulin for euglycemic control at puberty. The cause of insulin resistance has been attributed in part to increased fat oxidation at puberty, which correlates with rising serum IGF1 levels and may be linked to increased GH secretion. However, there is no evidence that GH treatment alone increases the likelihood of development of type 2 diabetes or impaired glucose tolerance.

Weight gain increases in children with type 1 diabetes during puberty, leading to a higher incidence of obesity in children with IDDM than would be expected from family patterns. Some adolescents with IDDM, predominantly girls, reduce their insulin use to lose weight, with dire consequences. Retinopathy due to IDDM characteristically appears in the teenage years or later, but duration and control of diabetes in the prepubertal years are contributing factors. The American Diabetes Association recommends screening for microalbuminuria, an indicator of the development of diabetic nephropathy during puberty.

Obesity, type 2 diabetes mellitus and the metabolic syndrome are major risk factors for cardiovascular disease. Studies have demonstrated an association between low levels of testosterone and the above insulin-resistant states, with a prevalence of hypogonadism of up to 50% in men with type 2 diabetes mellitus. Low levels of testosterone are also associated with an increased risk of all-cause and cardiovascular mortality. Hypogonadism and obesity share a bidirectional relationship as a result of the complex interplay between adipocytokines, proinflammatory cytokines and hypothalamic hormones that control the pituitary–testicular axis. Interventional studies have shown beneficial effects of testosterone on components of the metabolic syndrome, type 2 diabetes mellitus and other cardiovascular risk factors, including insulin resistance and high levels of cholesterol. Biochemical evidence indicates that testosterone is involved in promoting glucose utilization by stimulating glucose uptake, glycolysis and mitochondrial oxidative phosphorylation. Testosterone is also involved in lipid homeostasis in major insulin-responsive target tissues, such as liver, adipose tissue and skeletal muscle.

Points For Men

• Testosterone deficiency is highly prevalent in men with the metabolic syndrome and type 2 diabetes mellitus

• Low levels of testosterone are an independent risk factor that predicts subsequent development of the metabolic syndrome and type 2 diabetes mellitus

• Population studies in community-dwelling men have shown that testosterone deficiency is associated with increased all-cause mortality and cardiovascular mortality

• The hypogonadal–obesity–adipocytokine hypothesis summarises the complex interaction of the above components and their contribution to the vicious cycle of obesity causing hypogonadism and vice versa

• Interventional studies of testosterone replacement therapy have shown improvements in insulin resistance, body composition, glycaemic control, lipid metabolism and other cardiovascular risk factors

• The benefit of testosterone on insulin sensitivity might be attributable to a complex regulatory influence on insulin signalling and glucose homeostasis in the major insulin-responsive target tissues

Making health-promoting lifestyle choices is the best way to help get blood glucose levels in the desired range. Focus on lifting weights, eating a protein rich diet, and avoiding added sugar at all costs. Lifestyle choices and daily habits need to be top of mind when one is combatting insulin resistance. It is something that can be overcome/avoided with discipline.