Fasting Insulin

Insulin secretion by pancreatic beta cells (pancreas) undergoes significant physiologic fluctuations throughout the day. Pathologically altered pancreatic beta cell function may be associated with the following conditions. Hypoinsulinemia – decreased insulin levels – associated with:

Hyperinsulinemia – elevated insulin levels – associated with:

In the following, insulin resistance will be discussed in more detail, as it plays a special role in the development of type 2 diabetes mellitus. Insulin resistance is also at the heart of the so-called metabolic syndrome – which is closely linked to the development of arteriosclerotic sequelae.

Insulin Resistance

In recent years, research into type 2 diabetes mellitus has shown that insulin deficiency is not the main problem in this disease, but rather insulin resistance in particular. Previously, insulin resistance was used to describe the fact that an “insulin-injecting diabetic” required a large amount of insulin to normalize blood glucose. Since 1985, however, the term insulin resistance has been defined as a reduced effectiveness of the body’s own insulin on the target organs skeletal muscle, adipose tissue and liver.Both glucose, lipid and protein metabolism and on the vessels are affected. The pancreas initially produces excessive amounts of insulin to compensate, but this is unable to exert its effect; the patient exhibits insulin resistance. Initially, the increased insulin production succeeds in keeping the blood glucose level within the normal range. This condition can precede the development of manifest diabetes mellitus type 2 by years! At some point, however – usually after several years of increased insulin production – the secretion by the pancreas can no longer be increased. Patients then exhibit impaired glucose tolerance – which can be well detected by the oral glucose tolerance test (oGTT). If the process progresses further, manifest diabetes mellitus may eventually develop. In addition to disturbances in glucose and lipid metabolism, insulin resistance also affects the vasculature and thus plays an important role in the development of macrovascular and microvascular complications. Among other things, nitric oxide (NO) production is decreased, leading to increased vasoconstriction (vasoconstriction). High fasting glucose (fasting blood sugar) – as subsequently occurs in diabetes mellitus – was associated with an increased risk of cancer, according to the results of a large prospective cohort study in Korea – men had a 27% and women a 31% increased risk of dying from cancer. Among these, the main associated cancers were pancreatic cancer (cancer of the pancreas), hepatic cancer (cancer of the liver), esophageal cancer (cancer of the esophagus), colon cancer (colorectal cancer; cancer of the rectum and colon), and also cervical cancer (cancer of the cervix).

Risk factors for the development of insulin resistance

The following risk factors or diseases are associated with an increased risk for insulin resistance:

  • Biographic causes
    • Family history of diabetes mellitus or gestational diabetes (pregnancy diabetes)
    • Advanced age
  • Behavioral causes
    • Smoking
    • Low physical activity; even one week of strict bed rest promotes insulin resistance
    • Overweight (BMI ≥ 25; obesity).
  • Disease-related causes
    • Acanthosis nigricans – dirty-brown to -gray skin lesions, usually bilaterally symmetrical in armpits, flexures, and neck and genital areas
    • Atherosclerosis – Coronary artery disease (CAD; coronary artery disease).
    • Dyslipidemia (lipid metabolism disorder) – especially hypertriglyceridemia and lowered HDL cholesterol.
    • Fatty liver (steatosis hepatis)
    • Hypertension (high blood pressure) – it is estimated that up to 50% of all patients with hypertension have insulin resistance!
    • Polycystic ovary syndrome (PCO syndrome) – symptom complex characterized by hormonal dysfunction of the ovaries (ovaries).

Diagnostics

The single determination of insulin is not very informative, so the determination after stimulation is more often performed (eg, oral glucose tolerance test). Frequently, the determination of the so-called C-peptide – a cleavage product of proinsulin – can also increase the informative value of the insulin determination or even replace it in individual cases, since it is formed in exactly the same quantity as insulin. This also has the advantage that exogenous (external) insulin administration cannot falsify the determination, since it does not contain C-peptide and endogenous insulin antibodies also have no influence. Nevertheless, determination of fasting insulin is required for the following health risks or diseases:

  • Early detection of insulin resistance
  • If insulinoma is suspected – insulin-producing islet cell adenoma.
  • Differential diagnosis of hypoglycemic syndromes associated with lowered blood glucose levels.

Material needed

  • Serum, frozen: to avoid hemolysis, centrifuge whole blood within 30 min. after collection, pipette off serum and freeze → request refrigerated container for transport from laboratory.
  • Due to the short biological half-life (insulin plasma half-life: 10 min.), a significant decrease in the measured insulin value occurs with delayed preanalytics.

Preparation of the patient

  • Blood collection fasting (12 hrs food abstinence) or in the context of a functon diagnostics (specify collection time).

Normal value

Insulin 5-30 mU/l or µU/ml

Interpretation

Different testing methods have been developed to determine insulin resistance. The so-called euglycemic-hyperinsulinemic clamp test is considered the most scientific method. However, this will not be discussed here, as it is very complicated and is not used in practice, but in clinical research. The so-called HOMA index (Homeostasis Model Assessment) is a simpler method. It is a mathematical model that allows calculation of insulin resistance and beta cell function. After 12 hours of food abstinence, fasting insulin and fasting glucose (fasting blood sugar) are determined in the morning. The calculation is done as follows:

  • HOMA index = insulin (fasting, µU/ml) x blood glucose (fasting, mg/dl) / 405 or
  • HOMA index = insulin (fasting, µU/ml) x blood glucose (fasting, mmol/l) / 22.5

Interpretation of the HOMA index

Stage HOMA index Description
1 < 2 Insulin resistance rather unlikely
2 2,0 – 2,5 Indication of possible insulin resistance
3 2,5 – 5,0 Insulin resistance very likely
4 > 5,0 Average value in type 2 diabetics

In clinical practice, the patient’s triglyceride concentrations and HDL cholesterol may be used preferentially to assess insulin resistance. These correlate significantly with insulin resistance.Also, a fasting insulin of more than 15 mU/l may indicate insulin resistance. If other risk factors are also present, this can be used to estimate the presence of insulin resistance. Likewise, an increasing need for insulin or oral antidiabetic drugs may indicate insulin resistance. The insulin resistance score according to Standl/Biermann, which was developed by the Institute for Diabetes Research in Munich, is described below.This also allows an assessment of insulin resistance.Insulin resistance score according to Standl/Biermann.

1 point 2 points
Body mass index (kg/m2) > 26 > 30
Blood pressure (mmHg) > 140/90 (high blood pressure)
Fasting glucose(fasting blood glucose) > 100 mg/dl (> 5.6 mmol/l) > 110 mg/dl (> 6.1 mmol/l) (diabetes mellitus)
Triglycerides > 230 mg/dl (2.62 mmol/l)
Total cholesterol > 230 mg/dl (5.98 mmol/l)

Evaluation

  • Total 0 to 3 points: Insulin sensitive to mildly insulin resistant.
  • Sum 4 to 8 points: Significantly insulin resistant