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Insulin Resistance

Insulin resistance is a diminished ability of cells to respond to insulin. Insulin resistance is a condition, characterized by failure of the cell to respond to the hormone insulin. Such a condition gives rise to hyperglycemia and hyperinsulinemia.


Presentation

Insulin resistance presents with the following signs and symptoms.

  • High blood sugar and triglyceride levels
  • Feeling of sleepiness after having meals
  • Intestinal bloating
  • High blood pressure
  • Increase in hunger pangs 
  • Depression
  • Reduced ability to focus

In many instances, insulin resistance does not produce signs and symptoms, and individuals are often unaware, that they are living with such a condition. The disease goes undiagnosed, until the blood glucose levels are monitored on a regular basis. Individuals affected by insulin resistance, suffer from a condition known as acanthosis nigricans, which is characterized by development of black patches in areas of groin, arm pits and neck [6].

Atrial Septal Defect
  • Echocardiography revealed ostium secundum type atrial septal defect (ASD). Blood glucose normalized with pioglitazone (30 mg/day).[ncbi.nlm.nih.gov]
Pneumonia
  • Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents.[ncbi.nlm.nih.gov]
  • Later, the patient's course was complicated by hemorrhagic shock due to duodenal ulcer and she died of subsequent pneumocystis carinii pneumonia.[ncbi.nlm.nih.gov]
  • The patient was diagnosed with pneumonia due to Pseudomonas aeruginosa. When the patient's plasma glucose level was 22.5 mmol/l, her plasma C-peptide level was 0.9 nmol/l and her serum insulin level was 294 pmol/l.[ncbi.nlm.nih.gov]
  • Liu , Chlamydophila pneumoniae Inhibits Differentiation of Progenitor Adipose Cells and Impairs Insulin Signaling , The Journal of Infectious Diseases , 10.1086/525045 , 197 , 3 , (439-448) , (2008) . Harold A. Franch, William C.[doi.org]
Skeletal Dysplasia
  • KEYWORDS: POC1A; centriole; centrosome; diabetes; dyslipidaemia; insulin resistance; primary cilium; short stature; skeletal dysplasia[ncbi.nlm.nih.gov]
Hirsutism
  • Case 1 presented with premature adrenarche aged 7 years, then by age 12 years had hirsutism, acne, acanthosis nigricans, and asymptomatic diabetes.[ncbi.nlm.nih.gov]
  • Our first case is a 42-year-old female with a history of RA, SLE and Hashimoto-thyroiditis that presented with cachexia, acanthosis-nigricans, hirsutism, negative anti-insulin-ab and glucose level between 400 to 700 mg/dl, despite a total insulin dose[ncbi.nlm.nih.gov]
  • […] ways: (1) disordered glucose metabolism including both diabetes and/or paradoxical hypoglycaemia; (2) acanthosis nigricans, a velvety hyperpigmentation of axilliary and flexural skin often associated with skin tags; or (3) hyperandrogenism in girls (hirsutism[ncbi.nlm.nih.gov]
  • CASE REPORT: A Niuean women, first evaluated at age 6 years for severe acanthosis nigricans, hirsutism, poor growth and cognitive impairment, had extremely elevated fasting insulin levels of 10740 IU/l (fasting reference range 4-24 IU/l) and a normal[ncbi.nlm.nih.gov]
  • Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4).[ncbi.nlm.nih.gov]
Subcutaneous Nodule
  • Two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans.[ncbi.nlm.nih.gov]

Workup

Routine laboratory tests are done to diagnose insulin resistance. Blood test is carried out for the following parameters:

  • Fasting insulin levels are conducted; wherein the serum insulin levels of 60 pmol/L is considered as insulin resistance.
  • GTT – Glucose tolerance test: In this method, a glucose load of 75grams is given to the patient, and the serum levels of glucose tested over the period of 2 hours.

Hyperinsulinemic euglycemic lamp is considered to be gold standard, in diagnosing the condition of insulin resistance. The test takes about 2 hours to complete, but is not performed in all clinical settings. This test works on the principle of the amount of glucose that is necessary, to compensate for rise in the levels of insulin without causing hyperglycemia [7].

Hyperreninemia
  • Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively.[ncbi.nlm.nih.gov]
White Matter Lesions
  • Abstract The present study was to examine the relationship between white matter lesions (WMLs) and insulin resistance (IR) in patients with acute stroke and evaluate clinical prognosis.Around 200 patients with initial onset of acute stroke including 146[ncbi.nlm.nih.gov]

Treatment

Insulin resistance can be effectively controlled by the weight loss program, clubbed with exercise. Changes in dietary habits, and switching over to low carbohydrate diet, has been shown to improve insulin resistance. Moreover, certain medication, such as metformin, which is used for type 2 diabetes, has promising effects on individuals with insulin resistance [8].

According to the Diabetes Prevention Program, exercise and weight loss, are twice as effective as metformin, for arresting the progression of the condition to type 2 diabetes.

Therefore, modification in lifestyle factors, and dietary changes, along with medications, can reverse insulin resistance, thereby controlling the progression of the condition to other diseases [9].

Prognosis

The prognosis of the condition depends on the type of insulin resistance. The condition paves way for development of diabetes, coronary artery disease and glucose intolerance. It is estimated that diabetes is the 6th leading cause of death by disease and it is also the 7th leading cause of death in US. It has also been reported that, about 80% of 200 million individuals with diabetes will die due to cardiovascular diseases. Reports also point towards alarming statistics, which state that, coronary artery disease, is also the leading cause of death in US and in rest of the world [5].

Etiology

Insulin resistance occurs, due to heredity and acquired factors. Heredity factors include, mutations occurring in glucose transporter, signaling proteins and insulin receptors. Acquired factors, such as physical inactivity, poor dietary habits, certain medications and the process of aging, all predispose an individual, to develop insulin resistance. Increase in the production of insulin antagonists, that causes poor insulin uptake by the cells, is also one of the major causative factors. These include stress, trauma, surgery, infection, liver cirrhosis and uremia [2].

Epidemiology

It has been estimated that in US, insulin resistance occurs in 3% of the population. The incidence increases by several folds in individuals with glucose intolerance. The middle aged population is known to be more affected by this condition. In addition, it was also reported, that younger individuals are more prone to develop Type A insulin resistance; while older women fall prey to the Type B [3].

Sex distribution
Age distribution

Pathophysiology

When food containing glucose is consumed, it causes the blood levels of glucose to rise. This then signals the beta cells of the pancreas to release insulin, which in turn causes the glucose to be absorbed by the body cells. During the condition of insulin resistance, the levels of insulin rises, and the blood levels of glucose do not fall as they are unabsorbed by the cells. In cases where the beta cells of pancreas, are unable to secrete enough insulin, then the condition of hyperglycemia sets in, which further causes development of several other metabolic syndromes.

Insulin resistance is associated with obesity and type 2 diabetes. The condition of obesity causes decrease in the number of receptors, which in turn fail to activate tyrosine kinase. All these sequence of events, causes development of insulin resistance [4].

Prevention

Insulin resistance can be prevented, and those who have developed the condition can also reverse it by following certain steps:

  • Keeping weight under check, and exercising regularly, helps keep insulin resistance at bay.
  • Being physically active, and eating less calorie dense foods, can go a long way in preventing insulin resistance, and its associated complications.
  • Insulin resistance is a sign, that the body will soon develop pre diabetes or diabetes, if the condition is not controlled. Therefore, it is necessary that adhering to a healthy diet, and leading an active lifestyle, be followed [10].

Summary

In this type of condition, glucose does not get absorbed by the cells, and its level rises, leading to diabetes or prediabetes. Insulin resistance goes undetected for several years, and individuals continue to live with the condition, without being aware of it, and gradually develop diabetes later in their lives. On the other hand, if the condition is detected on time, then the onset of diabetes can be prevented. Insulin resistance also has a strong association, with the development of other chronic degenerative diseases, such as obesity and cardiovascular disorders [1].

Patient Information

Definition: Insulin resistance is a condition, wherein the body cells do not respond to the action of insulin, as a result of which the glucose concentration in the blood increases. It is a physiological condition, characterized by increased production of insulin by the pancreas, which eventually causes hyperinsulinemia.

Cause: Faulty dietary habits, sedentary lifestyle, obesity, heredity, infections and underlying disease conditions, are known to play foul in causation of insulin resistance. In addition, compounds of drugs, such as protease inhibitors found in HIV drugs, are also known to cause insulin resistance.

Symptoms: Symptoms of insulin resistance include, high blood sugar levels, increased hunger, weight gain, rise in blood pressure, raise in triglyceride levels, sleepiness, and inability to focus, along with poor concentration.

Diagnosis: Insulin resistance is diagnosed, using the glucose intolerance tests, and measuring the fasting insulin levels. In addition, hyperinsulinemia euglycemic clamp tests, and modified insulin suppression test, are also used for diagnosing the condition.

Treatment: Treatment includes modification in dietary habits, and leading an active life style. Individuals are also advised to undergo weight loss program, and exercise regularly to keep blood glucose levels under check.

References

Article

  1. Reaven G, Abbasi F, McLaughlin T. Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res. 2004;59:207-23.
  2. Steiner DF, Tager HS, Chan SJ. Lessons learned from molecular biology of insulin-gene mutations. Diabetes Care 1990; 13:600.
  3. Sarti C, Gallagher J. The metabolic syndrome: prevalence, CHD risk, and treatment. J Diabetes Complications. Mar-Apr 2006;20(2):121-32.
  4. Brennan AM, Mantzoros CS. Leptin and adiponectin: their role in diabetes. Curr Diab Rep 2007; 7:1.
  5. Barb, D, Mantzoros, C. Diagnosing obesity, diabetes mellitus and the insulin resistance syndrome. In: Obesity and Diabetes, Mantzoros, C. (Eds), Humana Press, Inc., Totowa, NJ 2006. p.129.
  6. Rogers DL. Acanthosis nigricans. Semin Dermatol 1991; 10:160.
  7. Katz A, Nambi SS, Mather K. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. Jul 2000;85(7):2402-10.
  8. Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med. Feb 2008;121(2):149-157.e2
  9. Fargnoli JL, Fung TT, Olenczuk DM. Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study. Am J Clin Nutr 2008; 88:1213.
  10. Dushay J, Abrahamson MJ. Insulin resistance and type 2 diabetes: a comprehensive review. Medscape Today [serial online]. Apr 8 2005

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Last updated: 2018-06-22 06:16