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Fortnightly Review: Insulin resistance

Andrew J Krentz, consultant physician a

a Diabetes Resource Centre, Royal South Hants Hospital, Southampton SO14 0YG


Syndromes of Severe Insulin Resistance 

Nicholas A. Tritos and Christos S. Mantzoros1

Division of Endocrinology, Beth Israel Deaconess Medical Center and Joslin Diabetes Center, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., D.Sc., Division of Endocrinology, RN 325, 99 Brookline Avenue, Boston, Massachusetts 02215. E-mail: cmantzor@bidmc.harvard.edu.

Conference News:
2006 Conference on Nutritional and Metabolic Aspects of Carbohydrate Restriction
January 20-22, 2006
Brooklyn, New York
written by
Valerie Berkowicz, M.S., R. D.

Professional Articles


Insulin Resistance Medicine

By Paul B. Berez, M.D.


Insulin Resistance is a dangerous disease process which has many effects on an individual’s health. The following disease processes have been found to be strongly associated with insulin resistance:

  • Hypertension
  • Hyperlipidemia
  • Hypercoagulable State
  • Proinflammatory State
  • Promitotic State

The hypercoagulable and proinflammatory states are strongly associated with increased cardiovascular event risk. The promitotic state promotes cellular proliferation, i.e. cancer or increased benign tumors, such as colonic polyps.

It is my intent, through a series of articles for health professionals, to outline the important points and concepts in the practice of what I will call “Insulin Resistance Medicine”.  This is the future of both internal and diabetes medicine. 

I am committed to research, including randomized trials in this field and am actively seeking collaborators in these research efforts. The Professional Section of SXA will be the nexus for both Investigators for this research, and grant application efforts.   

We invite you to join the Professional Section of the Syndrome X Association, and to plan to attend our first scientific session in February, 2004, in Ohio--more information will be forthcoming.

Literature references for this article are available by Emailing me at DrPaulBerez@syndromexassoc.org Please refer to “Insulin Resistance Medicine” and the specific point you need referenced when you write.

Dr. Paul Berez is an Assistant Clinical Professor of Medicine, GWU Volunteer Faculty; Attending Physician in Internal Medicine, Anne Arundel Medical Center, Annapolis MD; Medical Director, Dr. Berez’ Insulin Resistance, Diabetes, and Lipid Clinic, MD


Signs and Symptoms of Insulin Resistance


In  this series, we will be addressing many of the signs and symptoms on Insulin Resistance. If you have a specific question or comment on this topic, please email me at: DrPaulBerez@syndromexassoc.org
Paul B. Berez, M.D., is the director of the Insulin Resistance and Diabetes and Lipids Clinic, Crofton, Maryland and heads the Professional Section of the Syndrome X Association.

Insulin Resistance and Lipids


Insulin resistance causes hyperlipidemia by 3 mechanisms. The initial mechanism is caused by elevated insulin levels with elevated glucose levels (such as in impaired glucose tolerance). These elevated levels turn on the SREBP family of lipid synthesis regulators, which increase productions of cholesterol, triglycerides, HDL and LDL 1. This pattern is seen in early insulin resistance disease.


The second mechanism is that insulin resistance increases activity of cholesterol ester transfer protein (CETP) which transfers triglycerides from VLSL particles to LDL and HDL particles, and hepatic lipase and lipoprotein lipase (HL, LL) which cause HDL and LDL to “shrink down” 2, which causes HDL to decrease since small particles are eliminated by the kidneys.


Finally, as insulin resistance becomes more severe, insulin’s action of fat cells, especially visceral fat cells, is impaired--insulin holds fat in fat cells 3. When this impairment occurs, it leads to high levels of free fatty acids especially in the visceral portal giving the “full blown” phenotype of very high cholesterol, low HDL, variable LDL (calculated) and very high Apo B, which represents LDL particles.



1           Stinson, J 35 al DIABETIC MED 10:412-419, 1993

2           Riemans, S SCAN J CLINIC LAB INVEST 61:1-10, 2001

3           Kwiterovich, P. AM J CARDIOL 90 (SUPPL) 301-471, 2002


 This article was originally printed in the XChanges newsletter, Vol.2 No.5 Sept/Oct, copyright 2004

Other articles by Dr. Berez:



By Michael Menolasino, III, D.O., F.A.C.O.I.



There’s more to a heart healthy lifestyle than just cholesterol.  Your cardiac disease risk factors include non-modifiable risks such as age, sex and family history, as well as modifiable risk factors.  These include tobacco use, activity level, weight, high blood pressure, diabetes/metabolic syndrome and lipid profile. 

There is more to the lipid profile than just cholesterol.  A fasting Cardiac Risk Profile should be performed on healthy adults every five years beginning at age 15 and then annually after the age of 45.  For individuals with Diabetes or Metabolic Syndrome, I recommend annual testing.  The Standard Cardiac Risk Profile includes testing for total cholesterol, LDL cholesterol (bad cholesterol), HDL cholesterol (good cholesterol) and triglycerides (fats in the blood). 

Other cardiac risk tests are also available and include specialized blood tests, which may be recommended by your physician to evaluate for genetic lipid disorders.  The guidelines for acceptable levels in each of these categories have varied over the past ten years.  Our most recent guidelines from the Adult Treatment Panel (ATP) III, published by the National Cholesterol Education Program (NCEP), has provided physicians and patients with new guidelines and treatment goals based on individual risk factors you may have. 

The most important new insights from medical research indeed supports what many doctors have suspected for years…that diabetes is a cardiac disease equivalent.  This means that a person with diabetes should be evaluated and treated just as if they already have coronary artery disease.  This requires aggressive measures and low total and LDL cholesterol targets. 

What we do not yet know is how aggressive Metabolic Syndrome patients should be treated, what are the goals and what are the end points of treatment.  The NCEP notes the following issues unique to the Metabolic Syndrome Lipid Profile:

  • Atherogenic dyslipidemia
  • Elevated triglycerides
  • Small LDL particles
  • Low HDL cholesterol
  • Raised blood pressure
  • Insulin resistance (± glucose intolerance)
  • Prothrombotic state
  • Proinflammatory state

This combination of lipid disorder (Atherogenic dyslipidemia), elevated blood pressure and Prothrombotic Proinflammatory states (meaning high risk of blood clotting in the arteries) leads to a very high five-year risk of heart attack (myocardial infarction) or cardiac related death. 

In diabetic patients this risk exceeds 20% over five years, independent of other heart disease risk factors.  Therefore, my recommendations to my patients with Metabolic Syndrome is the same as if they had full blown Diabetes, and include dietary moderation, exercise (walking 30 minutes daily), and Total Cholesterol score less than 150, LDL Cholesterol score less than 80, HDL Cholesterol score greater than 45 and Triglyceride score then than 130. 

These goals are more stringent than the goals put forth by the NCEP, and emphasize my belief that individual patients require individualized care plans.  You should discuss your individual goals with your physician.  Most importantly, you should always be able answer the question, “What’s your Profile?”



Dr. Menolasino is a Medical Advisor to the Syndrome X Association


The Psychological Effects of Being Overweight in our Society

By Al Grzegorek, PhD


Being overweight can cause frustration, embarrassment, shame, anxiety, depression, a sense of hopelessness and, for some, desperation.  Self-esteem and self-confidence are damaged. Relationships with others are negatively effected.  Even the relationship with one’s spouse can be negatively impacted. They  may be unhappy with his or her partner’s weight or the overweight person may feel less loveable or desirable to their spouse because of the excess weight.

One of the major reasons that being overweight causes such significant psychological impact is our standard of attractiveness.  The examples of “beautiful people” in our magazines and catalogs are all thin. It’s hard to pick up a magazine or catalog in which products are presented by even moderately overweight people. It just doesn’t happen. This is amazing in a country where over 60 % of all of the people, 120 million, are overweight to morbidly obese.  The result is that self-esteem and self-confidence are shaken.  It becomes proof that the overweight person is deficient and not attractive.

There is a negative psychological impact because of the frustration that a person encounters trying to lose the weight.  Diet after diet is tried and failed.  Either no weight is lost or a little weight is lost and then comes back again, and more.  Each attempt makes the dieter feel more and more like a failure. The chance of ever being thin becomes hopeless. She still believes that obesity is her fault. What is even worse is that she thinks losing weight is simply a matter of will power. Her doctor may even agree. She feels guilty. She is deficient again. As a result, the overweight person suffers from prejudice, social stigma, and employment, academic and social discrimination.

We know that obesity is the result of genetic, metabolic, medical, environmental, psychological and social/cultural issues. Psychologically we are beginning to realize just how much stress, depression, boredom and anger also effect eating tendencies and patterns. Beyond a physical, social and health issue, being overweight has psychological effects that can cause frustration,  embarrassment, shame, guilt, and emotional pain.


Dr. Alfred E. Grzegorek  has a Ph.D. in Counseling Psychology from Michigan State University, a Masters Degree in Rehabilitation Counseling, and Bachelor’s degree in Psychology from the State University of New York at Buffalo.  He has been a practicing psychologist for the past thirty-three years both in private practice and with University Psychological Services at Kent State University.  He is currently in full time private practice.  He is also a medical advisor for the Syndrome X Association.

Dr. Grzegorek provides counseling help to patients with a wide range of concerns including problems with depression, anxiety, marital issues, adult attention deficit disorder as well as problems with anger, self-confidence and self-esteem.  His office is at 4466 Darrow Road, Stow, Ohio. He can be reached at 330-688-6921.


The information provided on this website is intended for your general knowledge only. It is not a substitute for professional medical advice or treatment for specific medical conditions. You should not use this information to diagnose or treat a health problem or disease without consulting with a qualified health professional. Please contact your health care provider with any questions or concerns you may have regarding your condition.