We compared estimates of in vivo insulin action derived from insulin tolerance tests (ITT) and euglycemic and hyperglycemic glucose clamp studies in 17 normal subjects and 19 patients with various diseases characterized by insulin resistance. Fifteen subjects underwent an ITT and a euglycemic clamp study, 17 subjects underwent an ITT and a hyperglycemic clamp study, and 4 subjects underwent all 3 tests. The ITT consisted of a bolus iv injection of regular insulin (0.1 U/kg BW). The plasma glucose disappearance rate during the 3- to 15-min period following the insulin injection was taken as a measure of insulin action. In both euglycemic and hyperglycemic clamp studies, which were carried out with standard techniques, the ratio between the amount of glucose infused to maintain glycemia at the desired level and the mean plasma insulin concentration from 60-120 min (M) (euglycemic clamp studies) or 20-120 min (I) (hyperglycemic clamp studies) was used as a measure of insulin action. A close correlation was found between plasma glucose disappearance rate and the M/I ratio during either the euglycemic (r = 0.811; P less than 0.001) or the hyperglycemic (r = 0.826; P less than 0.001) clamp studies. These results suggest that the 15-min ITT is suitable as a simple and rapid estimation of in vivo insulin action when glucose clamp studies are not feasible, as in large series of subjects or serial studies.
OBJECTIVE -To evaluate whether homeostasis model assessment-estimated insulin resistance (HOMA-IR) is an independent predictor of cardiovascular disease (CVD) in type 2 diabetes.RESEARCH DESIGN AND METHODS -Conventional CVD risk factors (sex, age, smoking, plasma lipids, blood pressure, and metabolic control) and insulin resistance (estimated by HOMA) were evaluated at baseline in 1,326 patients with type 2 diabetes examined within the Verona Diabetes Complications Study. At baseline and after a mean follow-up of 4.5 years, CVD was assessed by medical history, physical examination, electrocardiography, and echo-Doppler of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were carefully scrutinized to identify cardiovascular deaths. In statistical analyses, CVD was an aggregate end point including both fatal and nonfatal coronary, cerebrovascular, and peripheral vascular disease as well as ischemic electrocardiographic abnormalities and vascular lesions identified by echo-Doppler.RESULTS -At baseline, 441 subjects were coded positive for CVD (prevalent cases). Incident cases numbered 126. Multiple logistic regression analyses showed that, along with sex, age, smoking, HDL/total cholesterol ratio, and hypertension, HOMA-IR was an independent predictor of both prevalent and incident CVD. A 1-unit increase in (log)HOMA-IR value was associated with an odds ratio for prevalent CVD at baseline of 1.31 (95% CI 1.10 -1.56, P ϭ 0.002) and for incident CVD during follow-up of 1.56 (95% CI 1.14 -2.12, P Ͻ 0.001).CONCLUSIONS -HOMA-IR is an independent predictor of CVD in type 2 diabetes. The improvement of insulin resistance might have beneficial effects not only on glucose control but also on CVD in patients with type 2 diabetes.
This population-based survey aimed to determine the prevalence of known diabetes mellitus on 31 December 1986, and to assess all-cause mortality in the subsequent 5 years (1987-1991) in Verona, Italy. In the study of prevalence, 5996 patients were identified by three independent sources: family physicians, diabetes clinics, and drug prescriptions for diabetes. Mortality was assessed by matching all death certificates of Verona in 1987-1991 with the diabetic cohort. Overall diabetes prevalence was 2.61% (95% confidence interval 2.56-2.67). Prevalence of insulin-dependent and non-insulin-dependent diabetes mellitus was 0.069% (0.059-0.078) and 2.49% (2.43-2.54), respectively. Diabetes prevalence sharply increased after age 35 years up to age 75-79, and finally declined. Prevalence was higher in men up to age 69 years, in women after age 75 years. Of the diabetic cohort 1260 patients (592 men, 668 women) died by 31 December 1991, yielding an overall standardized mortality ratio of 1.46 (CI 1.38-1.54). Even though the differences narrowed with age, mortality rates in the diabetic cohort were higher than in the non-diabetic population at all ages. Women aged 65-74 years showed observed/expected ratio higher than men (2.27, CI 1.92-2.66, vs 1.50, CI 1.30-1.72), while in other age groups the sex-related differences were not significant. Pharmacological treatment of diabetes was associated with an excess mortality, while treatment with diet alone showed an apparent protective effect on mortality (observed/expected ratio 0.73, CI 0.58-0.92).(ABSTRACT TRUNCATED AT 250 WORDS)
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