Laboratory Testing:
Insulin Resistance

The following article on Diatest (Insulin Resistance)
is from the Rocky Mountain Labs web site.
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Diatest

Insulin resistance is often referred to as pre-diabetes, because it precedes the
development of type ii diabetes.

What is insulin resistance?

Insulin is a polypeptide hormone secreted by the beta cells of the pancreas. One of the major functions of insulin is to stimulate glucose uptake into tissues for utilization. transport of glucose into tissue keeps blood glucose levels within a specific range of ”normal‘ values. with insulin resistance, tissues become resistant to the effects of insulin, which means the pancreas must produce more insulin to maintain normal blood glucose levels. over time, the pancreas no longer produces sufficient amounts of insulin, which results in high blood glucose levels and a probable diagnosis of type ii diabetes. in fact, several prospective studies have concluded that insulin resistance is the best predictor of whether a person will go on to develop diabetes.

How does the Diatest breath test for insulin resistance work?

Insulin stimulates the uptake of glucose into tissues. approximately 50% of ingested glucose is metabolized to carbon dioxide (CO2) and water. the Diatest breath test measures expired CO2 before and after ingestion of stable c universally labeled glucose (non-radioactive). patients with normal insulin function exhale a greater percentage of CO2 because moreC13 labeled glucose is transported to tissue by insulin. the glucose in tissue is eventually metabolized to CO2 and water and exhaled. insulin resistant patients exhale less CO2 because resistance to the effects of insulin reduces the transport of c labeled glucose into tissues, and therefore Less CO2 is produced.

In other words, the Diatest breath test is a functional test for insulin resistance: it measures how well insulin functions at delivering glucose to tissues. if insulin is functioning well, more glucose is delivered to tissues and the result is more CO2. if insulin is functioning poorly, less glucose is delivered to tissue and the result is less CO2.

Diseases and conditions associated with insulin resistance

Diabetes: Insulin resistance is strongly correlated with the development of diabetes. over an eight year period, patients in the highest quartile for fasting insulin levels (another measure of insulin resistance) were over five times more likely to develop diabetes than those in the lowest quartile.

Hypertension: Approximately 50% of hypertensive patients have insulin resistance, and there is at least one study indicating that insulin resistance precedes hypertension.3 there is also evidence that reducing insulin levels has a direct effect on lowering blood pressure. over an eight year period, patients in the highest quartile for fasting insulin levels were approximately twice as likely to develop hypertension as those without.

Cardiovascular disease: High insulin levels, independent of blood glucose levels and other risk factors like triglyc erides, have been shown to increase the risk of cardiovascular disease.

Polycystic ovarian syndrome (PCOS): Women with PCOS have approximately 7 times greater likelihood of having impaired glucose. Tolerance (a measure of insulin resistance) than women without PCOS.

Insulin Resistance Test Results
Results Clinical Interventations: Testing
Abnormal
0 to 6.9 % increase
in
exhaled CO2
An increase of less than 7% (from baseline) in exhaled CO2, after ingestion of 25 mg of 13C labeled glucose, indicates seriously impaired glucose uptake. Glucose uptake is impaired in insulin resistance, pre-diabetes and diabetes. Lifestyle and nutritional measures should be undertaken to improve insulin sensitivity. Prescription medications may also be required.

Additional tests to confirm diagnosis of diabetes or
pre-diabetes include:


Fasting Blood Glucose
(FBG)
Tests blood glucose levels after a minimum 8 hour fast. Canadian Diabetes Association clinical guidelines state that levels greater than 6.1 mmol/L but less than 6.9 mmol/L indicate impaired fasting glucose or pre-diabetes. A blood glucose level over 7.0 mmol/L is indicative of diabetes.

Oral Glucose Tolerance Test
(OGTT)

A fasting glucose is collected; patient is then given a standard amount (75 g) of a glucose solution as a "challenge". This is followed by one or more blood draws at specific intervals to track glucose levels over time. The Canadian Diabetes Association clinical guidelines state that levels greater than 7.8 mmol/L and less than 11.1 mmol/L indicate impaired glucose tolerance. A blood glucose level over 11.1 mmol/L indicates diabetes.

Fasting insulin
Fasting insulin levels may be ordered when there has been an abnormal fasting blood glucose. If insulin levels are elevated and blood glucose is normal, insulin resistance is likely. Ranges for fasting insulin vary significantly from lab to lab.

Other tests that may be beneficial include:

Cholesterol panel
LDL, HDL, ratio of HDL to LDL. High blood sugar and/or diabetes are independent risk factors for heart disease, so tests for other cardiovascular risk factors may be indicated.

Blood pressure
Insulin resistance is often associated with hypertension.

Omega 3 Fatty acid test
20:1 ratio of AA to EPA is associated with increased incidence of diabetes while a 6:1 ratio was associated with decreased incidence of diabetes. Repeat the 13C Glucose Breath Test after 3 months to determine efficacy of therapeutic interventions.
Borderline 7.0
to
11.9 %
increase
in
exhaled CO2
An increase between 7 and 11% (from baseline) in exhaled 13CO2 , after ingestion of 25 mg of 13C labeled glucose, indicates impaired glucose uptake. Glucose uptake is impaired in insulin resistance, pre-diabetes and diabetes. Lifestyle and nutritional measures may be undertaken to improve insulin sensitivity. Repeat the 13C Glucose Breath Test after 3 months to determine efficacy of therapeutic interventions.
Normal
> 12.0 % increase
in
exhaled CO2
An increase of 12% or greater (from baseline) in exhaled 13CO2 , after ingestion of 25 mg of 13C labeled glucose, indicates normal glucose uptake by tissues.

Repeat 13C Glucose Breath Test annuallyto ensure adequate insulin sensitivity is maintained.

Lifestyle and
Nutrtional Interventions

Lifestyle: There is good evidence that lifestyle changes in insulin resistant patients can decrease their likelihood of developing diabetes. A Finnish study of over 500 men and women with impaired glucose tolerance found that lifestyle interventions like exercise, weight loss and dietary changes reduced the incidence of diabetes by 58% in the intervention group compared to the control group.

Exercise: Increasing physical activity in insulin resistant patients has been shown to reduce incidence of diabetes.

Diet: Reduced intake of refined carbohydrates and saturated fats helps increase insulin sensitivity and promote weight loss. Increased consumption of complex carbohydrates and fibre is recommended. One study showed that reducing the percentage of carbohydrates in the diet resulted in decreased fasting insulin levels.

Stress: Acute and chronic stress are associated with insulin resistance.

Vitamins and Minerals

  • Calcium: There is at least one study indicating calcium supplementation improves insulin sensitivity in non-diabetic hypertensive patients.
  • Chromium: It has been hypothesized that a reduced ability to retain chromium may contribute to insulin resistance in diabetes. Supplementing with chromium in normal and/or diabetes patients decreases fasting insulin levels, which indicates improved insulin sensitivity.
  • Magnesium: A magnesium deficient diet can lead to insulin resistance, which can be corrected by restoring magnesium levels to normal. When magnesium is supplemented in the presence of deficiency, insulin sensitivity improves.
  • Potassium: A potassium deficient diet can lead to insulin resistance, which can be corrected by restoring potassium levels to normal. When potassium is supplemented in the presence of deficiency, insulin sensitivity improves.
  • Vanadium: Helps regulate fasting blood sugar and improve receptor sensitivity to insulin in patients with diabetes and/or insulin resistance.
  • Vitamin D: Patients with vitamin D deficiencies may experience significant improvement in insulin sensitivity when vitamin D is supplemented. Vitamin D deficiency is common, particularly in Northern climates.
  • Zinc: Deficiencies of zinc are frequently found in conditions associated with insulin resistance. Low zinc levels may correlate with insulin resistance, and supplementation in the presence of deficiency may improve insulin sensitivity.

Nutritional Supplements

  • Alpha lipoic acid: Has been shown to improve insulin mediated glucose transport, thus improving insulin sensitivity. Is also a water and fat-soluble anti-oxidant.
  • Amino acids: L-arginine, L-carnitine, L-taurine have shown some potential for improving insulin sensitivity, although oral forms have not been studied.
  • Antioxidants: Excessive amounts of reactive oxygen species (ROS) cause oxidative stress and have been linked to insulin resistance. In theory, anti-oxidants may improve insulin sensitivity.
  • CoEnzyme Q10: May help lower fasting glucose and insulin levels in hypertensive patients.
  • Fish oil (omega 3 fatty acid): Controlled trials of fish oil for insulin resistance and diabetes have not shown a clear benefit, however epidemiologic evidence indicates that a higher ratio of omega 6 to omega 3 fatty acids is associated with increased incidence diabetes.

Botanicals: A number of botanicals help lower blood glucose levels and/or improve insulin sensitivity. These include: cinnamon, fenugreek, gymnema, banaba, pricky pear cactus, American ginseng, panax ginseng, and bitter melon.

It is important to monitor patients closely to ensure that blood glucose levels remain relatively stable.

Identifying Who Is at Risk

Insulin resistance leads to impaired fasting glucose which in turn leads to impaired glucose tolerance. A diagnosis of insulin resistance, impaired fasting glucose or impaired glucose tolerance indicates an increased risk of diabetes.

Impaired Fasting Glucose (IFG)

IFG is diagnosed when levels are above the normal fasting glucose range but lower than is what is considered diagnostic for diabetes. According to the Canadian Diabetes Association, a diagnosis of "prediabetes" is based on a blood glucose reading in the IFG range.

Impaired Glucose Tolerance (IGT)

IGT is diagnosed when, after a glucose challenge (75grams), blood glucose levels are above the normal range but lower than what is considered diagnostic for diabetes.

Individuals with IFG or IGT are at increased for cardiovascular disease and type 2 diabetes. Impaired glucose tolerance is more strongly associated with cardiovascular disease outcomes than IFG. Individuals with both IFG and IGT are at increased risk for diabetes and cardiovascular disease than those with isolated IFG or isolated IGT.

The following factors and conditions are associated with increased risk of insulin resistance:

  • Age greater than 40 years
  • First-degree relative with diabetes
  • High risk ethnic group: Aboriginal, Hispanic, Asian, African
  • History of Impaired Glucose Tolerance (IGT) or Impaired Fasting Glucose (IFG)
  • History of Gestational Diabetes
  • Presence of complications associated with diabetes
  • Hypertension
  • Overweight
  • Abdominal obesity
  • Polycystic ovarian syndrome
  • Dyslipidemia
  • Vascular disease
  • Acanthosis nigricans
  • Schizophrenia

References

  1. Lewanczuk RZ et al. Correlation of 13C glucose breath test with the hyperinsulinemic, euglycemic clamp in the diagnosis of insulin resistance. University of Alberta
  2. Haffner S. Epidemiology of Insulin Resistance and Its Relation to Coronary Artery Disease. . Am J Cardiol. 1999;84:11J-14J
  3. Falkner B et al. Insulin resistance and blood pressure in young black men. Hypertension. 1990; Dec;16(6):706-11.
  4. Osei K. Insulin Resistance and Systemic Hypertension. Am J Cardiol 1999;84:33J-36J
  5. Bhatia V. Insulin Resistance in Polycystic Ovarian Disease. South Med; 98(9):2005: 903-910
  6. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Definition, classification and diagnosis of diabetes and other dysglycemic categories. Can J Diabetes 2003;27 (Suppl 2):S7-S9
  7. Simopolous AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56:365-79
  8. Lindstrom J. Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish diabetes prevention study: results from a andomized clinical trial. J Am Soc Nephrol. 2003 Jul;14(7 Suppl 2):S108-13.
  9. Laaksonen DE et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes. 2005 Jan;54(1):158-65.
  10. Golay R. et al Int J Obes Relat Metab Disord. 1996 Dec;20(12):1067-72.
  11. Kelly G. Insulin Resistance: Lifestyle and Nutritional Interventions. Alt Med Review. 2000;5(2):109-132
  12. Lamson D, Plaza S. The Safety and Efficacy of High Dose Chromium. Alternative Medicine Review. 2002;7(3):218-35.
  13. Cusi K et al. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab
  14. Chiu KC. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004 May;79(5):820-5
  15. Borissova AM et al. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract. 2003 May;57(4):258-61
  16. Evans JL et al. The molecular basis for oxidative stress-induced insulin resistance. Antiox Redox Signal. 2005: Jul-Aug;7(7-8): 1040-52.
  17. Singh RB et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. Hum Hypertens. 1999 Mar;13(3):203-8.