To the Editor: I congratulate Samaras et al for opening the debate on insulin levels, insulin resistance and the metabolic syndrome.1 It is true that, when measuring insulin levels, by the hyperinsulinaemic eu-glycaemic clamp, we define the lowest quartile of the population as insulin resistant. As insulin resistance is frequently a component of the metabolic syndrome, this method is already an underestimate. In 1999–2000, the prevalence of the metabolic syndrome among adults in the United States was 26.7%.2 The prevalence of the metabolic syndrome among participants of the Framingham Offspring Study and San Antonio Heart Study ranged from 21.3% to 32.8% during the early to mid 1990s.3
Various indices have been developed as surrogate markers of insulin resistance. HOMA-IR (homeostatic model approach — insulin resistance) is highly correlated with insulin resistance as measured by the euglycaemic clamp. HOMA-IR was useful in predicting type 2 diabetes and impaired glucose tolerance in the Mexico City Diabetes Study.4 Another study using HOMA-IR found that insulin resistance was positively associated with carotid plaque formation in subjects with normal fasting glucose and normal glucose tolerance. The associations remained significant even after adjusting for known atherogenic risk factors.5
Reducing insulin resistance reduces cardio-vascular risk factors. The United Kingdom Prospective Diabetes Study reported that metformin is associated with a significant reduction in combined diabetes-related end points, diabetes-related deaths, all-cause deaths and myocardial infarction.6
By the time patients present to endocrinologists, they commonly already have many, if not all, of the elements of the metabolic syndrome. In primary care, we commonly see patients who only have one or two of those elements. Identifying insulin resistance early in at-risk patients is vital to prevent development of glucose intolerance as well as the various elements of the metabolic syndrome.
Patients and their family doctors are interested in disease prevention and would like to know whether they are at risk of diabetes or the metabolic syndrome. As there is evidence which suggests that insulin sensitisers in conjunction with lifestyle modifications may be helpful in preventing progression to diabetes and reducing cardiovascular risk factors, their “demand’ is not unjustified. Further, in obese, non-diabetic patients with insulin resistance, hyperinsu-linaemia may act as a barrier to successful weight loss.7 Identifying insulin resistance in these patients is important, as metformin may have a role in assisting weight loss.
- 1. Samaras K, McElduff A, Twigg SM, et al. Insulin levels in insulin resistance: phantom of the metabolic opera? Med J Aust 2006; 185: 159-161. <MJA full text>
- 2. Ford ES, Giles EH, Mokdad AH. Increasing prevalence of the metabolic syndrome among US adults. Diabetes Care 2004; 27: 2444-2449.
- 3. Meigs JB, Wilson PW, Nathan DM, et al. Prevalence and characteristics of the metabolic syndrome in the San Antonio Heart and Framingham Offspring Studies. Diabetes 2003; 52: 2160-2167.
- 4. Haffner SM, Gonzalez C, Miettinen H, et al. A prospective analysis of the HOMA model: the Mexico City Diabetes Study. Diabetes Care 1996; 19: 1138-1141.
- 5. Ishizaka N, Ishizaka Y, Takahashi E, et al. Association between insulin resistance and carotid arterioscler-osis in subjects with normal fasting glucose and normal glucose tolerance. Arterioscler Thromb Vasc Biol 2003; 23: 295-301.
- 6. American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care 1998; 21: 2180-2184.
- 7. Freemark M, Bursey D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinaemia and a family history of type 2 diabetes. Pediatrics 2001; 107: E55.