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Redefinition of the metabolic syndrome—useful or creating illness?

The existence and definition of pre-diabetes and the metabolic syndrome have been sources of controversy over recent years and were further debated by Kahn and Grundy in the July 2006 edition of Diabetes Care.1,2

Pre-diabetes is a term used to describe individuals with either impaired fasting glycaemia (IFG) or impaired glucose tolerance. The metabolic syndrome has been used to describe the clustering of several risk factors (visceral obesity, dyslipidaemia, hyperglycaemia, and hypertension) for cardiovascular disease.

The key reason for defining pre-diabetes or the metabolic syndrome is that it helps to identify individuals at high risk of developing diabetes or cardiovascular disease. Recently the American Diabetes Association (ADA) recommended that the definition of impaired fasting glycaemia be reduced from a fasting plasma glucose (FPG) of ≥6.1 mmol/L to ≥5.6 mmol/Ll.3 The metabolic syndrome has also been dogged by redefinition. Most recently, the International Diabetes Federation (IDF) has redefined the diagnosis of the metabolic syndrome: lowering abdominal circumference and fasting glycaemia cut-offs.4

In a recent audit based in Wellington Hospital we sought to determine the frequency of impaired glucose metabolism (type 2 diabetes, impaired glucose tolerance, and impaired fasting glucose) and the metabolic syndrome in 297 patients presenting for elective cardiac catheterisation.5

We analysed the data using both definitions of IFG (≥6.1 and ≥5.6 mmol/L). We also assessed the frequency of the metabolic syndrome utilising the recently developed IDF consensus worldwide definition of the metabolic syndrome4 and the National Cholesterol Education Programs Adult Treatment Panel III (ATP III) criteria.6  The ATP III criteria previously being the most widely used in clinical practice and epidemiological studies.

In our study, established or newly diagnosed diabetes was present in 82 (30.5%) patients. Using a FPG cut-off of ≥6.1 mmol/L, IFG was diagnosed in a further 25 patients (9.3%). Use of the newer ADA definition more than doubled the number of patients diagnosed as having IFG 68 patients (22.9%, p<0.001).

Growing evidence suggests that the higher FPG cut-off level of ≥6.1 mmol/L is predictive of increased cardiovascular mortality.7–9 However, when the FPG cut-off is lowered to ≥5.6, the predictive power for cardiovascular mortality is removed completely.7 It is beyond the scope of this report to explore all the reasons for lowering the FPG cut-offs for IFG, however the change was not based on long-term outcome studies.

The rates of the metabolic syndrome also varied depending upon the definition used with 39.1% meeting the ATP III criteria. Using the lower cut-offs for abdominal obesity and impaired fasting glucose as outlined in the IDF definition diagnosis of the metabolic syndrome increased to 49.2% (p=0.01).

In our study, patients with the metabolic syndrome as defined by the ATP III criteria were more likely to have 3-vessel coronary artery disease compared to those without (42.9% vs. 29.3%, odds ratio 1.8; 95% CI 1.1 to 2.9). However, use of the new IDF criteria to define the metabolic syndrome reduced the strength of this association between the metabolic syndrome and the presence of 3-vessel disease (39.0% versus 31.8%, odds ratio 1.4; 95% CI 0.9 to 2.2).

Consistent with our findings, Athyros and colleagues10 recently reported that the prevalence of the metabolic syndrome was more frequent using the IDF criteria compared to the ATP III criteria (43.4% versus 24.5%, p<0.0001) and that the age-adjusted prevalence of cardiovascular disease was significantly less common in patients with the metabolic syndrome defined by the IDF compared to the ATP III criteria (18.3% versus 23.3%, p<0.0001). More importantly, those who meet the IDF criteria for the metabolic syndrome, but not the ATP III criteria, had a similar CVD prevalence to the population as a whole.

Our study along with others suggests that the new definitions have resulted in increased rates of diagnosis of both IFG and the metabolic syndrome. However, we need to ask (in moving the goalposts defining normal metabolism) have we better identified patients at increased risk of morbidity and mortality? Or, are we merely labelling patients unnecessarily? What really matters is the ability of these definitions to predict risk. Prospective studies to evaluate this are urgently required before the goalposts are moved for another season.

Russell Anscombe
Cardiology
Registrar Department of Cardiology, Wellington Hospital

Jeremy Krebs
Endocrinologist Department of Endocrinology, Wellington Hospital

Mark Weatherall
Geriatrician Department of Medicine, Wellington School of Medicine and Health Sciences

Scott A Harding
Cardiologist Department of Cardiology, Wellington Hospital Wellington

References:

  1. Kahn R. The metabolic syndrome (emperor) wears no clothes. Diabetes Care. 2006;29:1693–6.
  2. Grundy SM. Does the metabolic syndrome exist? Diabetes Care. 2006;29:1689–92.
  3. American Diabetes Association. Position statement. Standards of medical care in diabetes. Diabetes Care. 2004;27:S15–35.
  4. Alberti KGMM, Zimmet PZ, Shaw JE. The Metabolic Syndrome—a new world-wide definition from the International Diabetes Federation consensus. Lancet. 2005;366:1059–62.
  5. Harding SA, Anscombe R, Weatherall M, et al. Abnormal glucose metabolism and features of the metabolic syndrome are common in patients presenting for elective cardiac catheterisation. Intern Med J. 2006;36:759–64.
  6. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002; 106:3143–21.
  7. Chi Pang Wen, Shi Li Wang. Increased mortality risks of pre-diabetes (impaired fasting glucose) in Taiwan. Diabetes Care. 2005;28:2756–61.
  8. Bjornholt J, Erikssen G. Fasting Blood glucose: An underestimated risk factor for cardiovascular death. Results from a 22 year follow-up of healthy non-diabetic men. Diabetes Care. 1999; 22:45–9.
  9. The expert committee on the diagnosis and classification of diabetes mellitus: Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003;26:3160–7.
  10. Athyros VG, Ganotakis ES, Elisaf MS, et al. Prevalence of vascular disease in metabolic syndrome using three proposed definitions. International Journal of Cardiology. Epublished 2006 Jul 17.

Joseph Putnoki said,

August 11, 2009 @ 10:13 am

The complexity of metabolism necessitates that investigation of glucose issues will be widely enough based. Hormonal interactions to be considered. Cholesterol at present still erroneously blamed as it was the villain it is not. Elevated cholesterol apart from some Apo E alleles is more usefully considered a bio indicator rather then a culprit. Being the base material for hormones when hormone depletion occurs of course the liver try producing more! Vested interests, ignorance and propaganda drives this scare mongering effort and aggressive statin-promotion. For an eye-opening and educative site look up: thecholesterollie.com.
It is almost a fashion to produce guidelines of lowering cutoff points. Different labs use varied reference ranges depending on the equipment they use and this is confusing to the patient who monitors his/her glucose home. In my experience fasting glucose 5.9 cutoff correlates very closely with the lab reading of HbA1c. Home monitoring of blood sugar through the day as well as blood pressure helps to give a more coherent picture then the one at the doctors rooms.
(Some doctors don’t even take the blood pressure correctly!) It varies during the day so at the appointment time it is taken as diagnostic, most time only one reading. The rush and time restrictions also an impediment to best practice.-

Eric Bakker ND said,

August 12, 2009 @ 2:03 pm

Hi Joseph,

Thanks for your comments. You are correct, people have been fed a lot of “pseudo-science” when it comes to the statin drug/cholesterol debate. There are currently over 600,000 Kiwis on cholesterol lowering drugs and many experience debilitating side-effects.
It is important to consider cortisol levels in the cholesterol equation as well, the 1984 Schwertner, Troxler, Uhl and Jackson study was most interesting.
A statistically significant association (p less than 0.05) was found between cortisol and cholesterol for individuals who had either minimal CAD (20% to 49% narrowing) or significant CAD (greater than or equal to 50% narrowing), but not for subjects without CAD. An association between cortisol and cholesterol was also found to be significant for the group of individuals with Type A behavior patterns. These findings suggest that hormonal mechanisms involving cortisol and cholesterol metabolism may be operative in individuals with CAD as well as in individuals with Type A behavior.

Regards,

Eric Bakker ND

Anonymous said,

September 22, 2009 @ 11:41 pm

For a Person suffering from Metabolic Syndrome, they may well have ailments like excessive fat around waistline, soaring levels of blood pressure, blood glucose and lipids and sapped HDL cholesterol levels. It can lead to hypertension, type 2 diabetes, excess weight. One should maintain healthy lifestyles, eating right and exercising. Thank you for your article, much appreciated and insightful information.

Elke van Beek said,

October 5, 2009 @ 4:28 pm

Im doing a research proposal on the prevalence of metabolic syndrome in Wellington middle age men who purchase read to eat meals during the week. Im still in the research process, but I was wondering, other then going to the doctor for a check up and then being diagnosed with MS, is there any other way people are being diagnosed?

Eric Bakker ND said,

October 5, 2009 @ 4:55 pm

Hi Elke,

As far as I know, there is no other way people are being diagnosed with Metaolic Syndrome, purely because it is not a “classically diagnosed condition”, but rather what it says it is: a syndrome, which is a collection of signs and symptoms. Medicine is not good at diagnosing or treating syndromes because they are an umbrella for many different conditions in their own right and if they diagnose and treat this condition (Metabolic Syndrome) the patient would no doubt end up on up to a half dozen pharma drugs such as statins (cholesterol), blood pressure drugs, blood sugar modifiers (Type 2 DM) and more. I’m rather surprised the drug companies haven’t cashed in here as yet, they would have a field day! Take a look at Chronic Fatigue Syndrome, another condition too many medical doctors place in the “too hard basket” with many actually refusing to believe that this syndrome even exists. Metabolic Syndrome is a condition brought about by modern Western lifestyles, and with correct and healthy modes of living it is not around. You may want to research further into the cultural and social aspects and will find for example that this condition did not exist in Japan UNTIL they adopted the white man’s ways. Now look at Japan, the same pathway that America is heading – too many overweight and obese individuals.

Eric Bakker ND

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