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Prevalence of risk factors may vary widely among similarly obese individuals
Insulin sensitivity is a mediating risk factor regardless of BMI.
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There is substantial variation in the prevalence and magnitude of cardiovascular and diabetes risk factors among moderately obese individuals, according to data from a new study.
People who are more insulin resistant appear to be at substantially greater risk than others of similar BMI.
“There is this general widespread belief that everybody who is obese is going to develop diabetes or heart disease because they are all insulin-resistant. This is simply not the case,” said Gerald Reaven, MD, professor emeritus of medicine at Stanford University in Palo Alto, Calif. “It is a straightforward point, but one that seems to be overlooked in the passion and mania for obesity as the cause of all evil.”
Reaven, who described in 1988 the clustering of abnormalities associated with insulin resistance now used as diagnostic criteria for metabolic syndrome, and colleagues conducted a study measuring the variability in insulin sensitivity and connections with various risk factors among moderately obese individuals. The results were published in the Archives of Internal Medicine.
The study included 211 volunteers for various weight loss studies with a BMI of 30 to 34.9. All of these individuals completed a medical history and physical examination, an oral glucose tolerance test and a test for insulin-mediated glucose uptake. Measurements of steady-state plasma glucose concentrations were used to determine participants’ level of insulin resistance.
Variation in insulin resistance
The researchers divided the cohort into tertiles based on insulin resistance. Demographic characteristics of the three groups were similar with the exception of BMI, which increased from the least to the most insulin-resistant tertile (P=.04). Notably, there was substantial overall variation in insulin resistance as measured by steady-state plasma glucose concentration, with mean concentrations of 81 mg/dL, 166 mg/dL and 247 mg/dL in the three groups.
Every measured metabolic variable, with the exception of LDL cholesterol, varied as a function of the degree of insulin resistance. These variables included systolic and diastolic blood pressure, triglycerides, HDL cholesterol, fasting plasma glucose, 2-h plasma glucose level and several others (P<.001 for all). Reaven said that the most striking difference was found in the rate of impaired glucose tolerance: in the lowest insulin resistance tertile, the prevalence of IGT was 2% compared with 47% in the highest tertile.
Risk and insulin resistance
The investigators also calculated odds ratios — both unadjusted and adjusted for age, sex and BMI — for belonging to a diagnostic category of increased risk for developing cardiovascular disease or type 2 diabetes. Individuals in the second tertile of insulin resistance had a significantly increased risk for being hypertriglyceridemic (adjusted OR=4.3; 95% CI, 2.0-9.6) and for having IGT (adjusted OR=27.2; 95% CI, 3.4-220) compared with the first tertile. Those in the third tertile were at increased risk for all five of the measured risk factors (adjusted ORs ranged from 3 to 54.8) compared with the first tertile.
A univariate analysis uncovered that every marker, with the exception of LDL cholesterol, was significantly correlated with insulin resistance (correlation coefficiencies ranged from 0.17 to 0.46; P<.05 for all). BMI, however, correlated only with the fasting plasma glucose level.
‘Astounding’ variability
“In an apparently healthy population, insulin resistance can vary 600% to 800% from person to person,” Reaven told Endocrine Today. “How heavy you are probably contributes 25% to that variability. Fitness may be as important as how heavy you are, but most studies never measure fitness; they just stick to fatness.”
Reaven noted that the participants in this study who fit into the least insulin-resistant tertile were generally metabolically healthy. These individuals’ BP, cholesterol and glucose concentrations were within a normal, healthy range, and Reaven called the difference, from 2% with IGT up to 47% in the most insulin-resistant tertile, astounding.
Because of this clear variability in the degree of risk among similarly obese individuals, these results indicate a need to focus weight loss and risk management efforts on a certain subset of the population.
“It will require a shift in physician behavior. When a physician sees a person who is overweight or obese, it is important to get some measurements and see if the individual fits into the subgroup that really needs something done,” Reaven said. “Then you act in a more intensive fashion in those people. In other words, there should be a different level of management depending on the metabolic characteristics of the obese individual. All obese people are not the same.” – by Dave Levitan
For more information:
- McLaughlin T, Abbasi F, Lamendola C, Reaven G. Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals: effect of differences in insulin sensitivity. Arch Intern Med. 2007;167:642-648.