September 18, 2016

Insulin Resistance

Medical researchers and physicians are paying more attention to the metabolic disorder called insulin resistance. The very early detection of insulin resistance could halt or even reverse the onset of diabetes for millions of individuals. It has been predicted that by the year 2020 there will be approximately 250 million people worldwide affected by type 2 diabetes mellitus. It is now accepted by clinicians and public health specialist that insulin resistance is playing a major role in this epidemic.

The Critical Role of Insulin

Diabetes is a metabolic disorder which if not diagnosed early and managed properly can be life-threatening. The organ which produces insulin is the pancreas and it is insulin which allows the body to metabolize and utilize sugar efficiently. Insulin acts on the cell membrane to facilitate sugar crossing the barrier to provide energy. In the diabetic child or adult, there is either little production of insulin or poor utilization of insulin by cells and tissue. The three (3) types of Diabetes are Type 1, Type 2 and gestational Diabetes. Diabetes if not controlled causes damage to blood vessels and tissues of major target organs (kidney failure, heart failure, impaired vision and neuropathy of the lower limbs).

Most individuals are insulin sensitive and so insulin keeps the blood sugar level from hyperglycemia (high blood sugar) or hypoglycemia (too low). The cells in our bodies must have sugar for energy. However, sugar cannot pass through the cell membrane directly into the cell. When we eat the blood sugar rises and the beta cells in the pancreas release insulin into the bloodstream. Insulin attaches to the cells to facilitate the absorption of the sugar molecules from the bloodstream. Some have referred to insulin as the “key,” which unlocks the cell membrane to allow sugar to enter the cell to provide the energy needed for cell functions.

Insulin helps store excess sugar in the liver and releases it when your blood sugar level is low or if you need more sugar, such as in between meals or during physical activity. Therefore, insulin helps balance out blood sugar levels and keeps them in a normal range. As blood sugar levels rise, the pancreas secretes more insulin.

When the body does not produce adequate amounts of insulin or your cells are resistant to the effects of insulin, we may develop high blood sugar. Sustained high blood sugar over time can cause long-term complications.

Persons with type 1 diabetes cannot make insulin because the beta cells in their pancreas are damaged or destroyed. These individuals are insulin dependent and will need daily insulin injections to allow their body to metabolize and utilize sugar.

Persons with type 2 diabetes do not respond well or are resistant to insulin. They may need insulin shots to help them better process sugar and. Many are initially treated with oral medications, in addition to a well-balanced diet and exercise. Since type 2 diabetes is a chronic progressive condition, eventually diabetics will require insulin to maintain blood sugar levels to prevent long-term complications from this disease.

What is Insulin Resistance?

High levels of insulin over a period of time result in the body’s sensitivity to be reduced to the hormone. The high levels of insulin circulating in the blood coupled with weight gain further compounds the insulin resistance. This is a precursor to prediabetes and ultimately type 2 diabetes. Raeven et al were able to demonstrate resistance to insulin-stimulated glucose uptake was present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of non-obese individuals with normal oral glucose tolerance.

 

Individuals at risk of developing insulin resistance include:

  • Persons who are overweight with a body mass index (BMI) more than 25 kg/m2. To calculate your BMI use your weight (in kilograms) and divide twice by your height (in meters). The association of obesity with type 2 diabetes has been recognized for decades, and the major basis for this link is the ability of obesity to engender insulin resistance.
  • Men with a waist circumference greater than 40 inches and women with a waist circumference greater than 35 inches are at higher risk of insulin resistance
  • Women with a history of gestational diabetes
  • Persons diagnosed with the metabolic syndrome i.e. high blood pressure, high blood triglycerides, low HDL cholesterol, arteriosclerosis
  • Young women diagnosed with polycystic ovarian syndrome (PCOS)
  • Persons with skin tags or acanthosis nigricans
  • Adults over age 40 years
  • Ethnic groups of Latinos, African Americans, Native Americans, an persons of Asian- American decent
  • Individuals with a family history of type 2 diabetes or cardiovascular disease

Types of Insulin Resistance

  1. Type 2 Diabetes Insulin Resistance
  2. Polycystic Ovarian Syndrome
  3. Adipose tissue insulin resistance
  4. Skeletal Muscle Insulin Resistance
  5. Inflammation Insulin Resistance
  6. Metabolic Insulin Resistance
  7. Hepatic insulin Resistance

Causes of Insulin Resistance

One theory is the inflammatory response associated with central obesity (around the waist). It has been postulated that the preponderance of fat cells causes the fat cells to compress each other and be starved of oxygen. As a result of this some fat cells die and trigger the inflammatory response.

Another theory is that diets high in refined carbohydrates, processed foods, saturated fats and trans-fats predisposes individuals to obesity, chronic inflammatory disorders and ultimately insulin resistance.

Symptoms of Insulin Resistance

  • Weight gain
  • Hunger
  • Lethargy
  • Elevated blood sugar
  • Inability to focus and concentrate
  • High blood sugar levels
  • Symptoms of Diabetes
    • Increased frequency of urination
    • Unexplained weight loss
    • Nausea, Vomiting
    • Skin issues which include fungal Infections
    • Slow healing wounds

Diagnosis

A health-care professional can identify individuals likely to have insulin resistance by taking a detailed history, performing a physical examination, and simple laboratory testing based on individual risk factors.

In general practice, the fasting blood glucose and insulin levels are usually adequate to determine whether insulin resistance and/or diabetes is present. The exact insulin level for diagnosis varies by assay (by laboratory). However, a fasting insulin level above the upper quartile in a non-diabetic patient is considered abnormal.

Treatment for Insulin Resistance

Management of insulin resistance is through lifestyle changes (such as diet, exercise, and disease prevention) and medications. Insulin resistance can be managed in two ways. First, the need for insulin can be reduced. Second, the sensitivity of cells to the action of insulin can be increased

Insulin resistance may be treated by primary care professionals, including internists, family professionals, or pediatricians. Endocrinologists, specialists in hormonal disorders, also treat patients with insulin resistance.

  • Metformin is a medication used for treating type 2 diabetes. The generic name is Glucophage. It has two mechanisms of action: 1) it regulates the release of glucose from the liver into the blood, and 2) it increases the sensitivity of fat cells and muscle to insulin. This sensitivity facilitates the movement of glucose from the blood. Metformin decreases the body weight in obese individuals.  Some persons may experience gastrointestinal discomfort but the FDA has approved the drug as safe for the treatment of insulin resistance.
  • Acarbose is a drug which slows the gut’s absorption of sugars. This in turn reduces the demand for insulin after a meal. Acarbose is included as part of the regime for insulin resistance and weight loss.
  • Thiazolidinediones increase sensitivity to insulin. Actos (pioglitazone) and Avandia ( rosiglitazone) have been restricted by the FDA for use in persons whose blood sugar has not been controlled by other medications. This is due to the association of liver toxicity and also an increased risk of heart attack and stroke.

For the patient who has circulatory issues or high cholesterol it is very helpful to have other medical conditions treated. Weight management (diet and exercise) must be a part of the treatment for obese patients with insulin resistance.

Tips for the Prevention and Management of Insulin Resistance

  • Insulin resistance cannot always be prevented, but there are ways to modify risk factors with lifestyle changes such as keeping a healthy weight and getting regular exercise.
  • Insulin resistance is associated with the development of type 2 diabetes unless measures are taken to reverse the insulin resistance. Weight loss for overweight individuals, eating a healthy diet (high fiber, low saturated fats, lean meat, 3-5 servings of fruits and vegetables), not smoking, and adequate physical exercise can all help to reverse insulin resistance.
  • Metformin is the only drug recommended by guidelines, for those patients at highest risk.
  • Diabetes education about the disease and prevention tips must be directed to all groups at risk for type 2 diabetes.
  • Childhood obesity is epidemic and on the rise in the developed countries. Changes must be made in homes and school cafeterias to ensure healthier nutrition

              

References

  1. Role of insulin resistance in human disease, GM Reaven – Diabetes, 1988 – Am Diabetes AssociationFewer
  2. [HTML]Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance, H Xu, GT Barnes, Q Yang, G Tan, The Journal of …, 2003 – Am Soc Clin Investig
  3. Cellular mechanisms of insulin resistance, GI Shulman – The Journal of clinical investigation, 2000 – Am Soc Clin Investig
  4. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction a potential role for cytokines originating from adipose, JS Yudkin, CDA Stehouwer, JJ Emeis, and vascular biology, 1999 – Am Heart AssocFewer
  5. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians, PM McKeigue, B Shah, MG Marmot – The Lancet, 1991 – Elsevier
  6. Inflammation and insulin resistance, SE Shoelson, J Lee… – The Journal of clinical …, 2006 – Am Soc Clin Investig
  7. Obesity and insulin resistance BB Kahn, JS Flier – The Journal of clinical investigation, 2000 – Am Soc Clin Investig
  8. Protection from obesity-induced insulin resistance in mice lacking TNF-α function KT Uysal, SM Wiesbrock, MW Marino, GS Hotamisligil – Nature, 1997 – nature.com
  9. Mechanisms linking obesity to insulin resistance and type 2 diabetes SE Kahn, RL Hull, KM Utzschneider – Nature, 2006 – nature.com
  10. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 N Maeda, I Shimomura, K Kishida, H Nishizawa… – Nature medicine, 2002 – nature.com
  11. Mitochondrial dysfunction in the elderly: possible role in insulin resistance KF Petersen, D Befroy, S Dufour, J Dziura, 2003 – science.sciencemag.org
  12. Recent advances in the relationship between obesity, inflammation, and insulin resistance JP Bastard, M Maachi, C Lagathu, MJ Kim… – European cytokine, 2006 – jle.comFewer
  13. Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ M Yuan, N Konstantopoulos, J Lee, L Hansen, 2001 – science.sciencemag.org
  14. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study BC Martin, JH Warram, AS Krolewski, JS Soeldner – The Lancet, 1992 – ElsevierFewer
  15. Disruption of adiponectin causes insulin resistance and neointimal formation N Kubota, Y Terauchi, T Yamauchi, T Kubota – Journal of Biological, 2002 – ASBMB

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