The Clamp-Like Index

Abstract

OBJECTIVE -Insulin resistance, the underlying pathophysiological mechanism of the metabolic syndrome, can not only predict type 2 diabetes development but also cardiovascular disease. Thus, precise insulin resistance measurement in individuals at risk for metabolic diseases would support clinical risk stratification. However, the gold standard for measuring insulin resistance, the hyperinsulinemic clamp test, is too labor intensive to be performed in large clinical studies/settings.RESEARCH DESIGN AND METHODS -Using plasma glucose and C-peptide concentrations from oral glucose tolerance tests (OGTTs), we developed the novel "clamp-like index" (CLIX) for insulin sensitivity calculation and compared CLIX to clamp glucose infusion rates (GIR) (100 -120 min). We evaluated CLIX in 89 nondiabetic subjects (58 female and 31 male, aged 45 Ϯ 1 years, BMI 27.5 Ϯ 0.8 kg/m 2 ) who underwent frequently sampled 3-h 75-g OGTTs and 2-h hyperinsulinemic-isoglycemic clamp (40 mU/min per m 2 ) tests.RESULTS -CLIX, calculated as serum creatinine (ϫ0.85 if male)/(mean AUC glucose ϫ mean AUC C-peptide ) ϫ 6,600, was highly correlated (r ϭ 0.670, P Ͻ 10 Ϫ12 ) with and comparable to clamp GIRs 100 -120 min . In subgroup analyses, GIRs 100 -120 min were lower (P Ͻ 0.005) in type 2 diabetic offspring (6.2 Ϯ 0.7 mg ⅐ min Ϫ1 ⅐ kg Ϫ1 ) than in sex-, age-, and BMI-matched subjects without a family history of type 2 diabetes (8.6 Ϯ 0.5 mg ⅐ min Ϫ1 ⅐ kg Ϫ1 ), which was also reflected by CLIX (insulin-resistant offspring 6.4 Ϯ 0.6 vs. those without a family history of type 2 diabetes 9.0 Ϯ 0.5; P Ͻ 0.002). When compared with normal-weight subjects (GIR 8.8 Ϯ 0.4 mg ⅐ min Ϫ1 ⅐ kg Ϫ1 ; CLIX 9.0 Ϯ 0.5), both GIRs 100 -120 min and CLIX of obese (5.2 Ϯ 0.9 mg ⅐ min Ϫ1 ⅐ kg Ϫ1 ; 5.7 Ϯ 0.9) and morbidly obese (2.4 Ϯ 0.4 mg ⅐ min Ϫ1 ⅐ kg Ϫ1 ; 3.3 Ϯ 0.5) humans were lower (each P Ͻ 0.02).CONCLUSIONS -CLIX, a novel index obtained from plasma OGTT glucose and Cpeptide levels and serum creatinine, without inclusion of anthropometrical measures to calculate insulin sensitivity in nondiabetic humans, highly correlates with clamp GIRs and reveals even slight insulin sensitivity alterations over a broad BMI range and is as sensitive as the hyperinsulinemic clamp test. Diabetes Care 30:2374-2380, 2007I nsulin resistance, the underlying pathophysiological mechanism of the metabolic syndrome, is closely associated with common metabolic and inflammatory diseases, such as type 2 diabetes, obesity, nonalcoholic fatty liver disease, and cardiovascular disease (1-3). The degree of insulin resistance in the insulinresistant offspring of parents with type 2 diabetes, but not in humans without a family history of type 2 diabetes, serves as a predictor for later onset of the disease (4 -6). Overweight or obesity also results in a tremendous fall in insulin sensitivity, combined with a markedly increased risk for type 2 diabetes and other disturbances (such as hyperlipidemia or arterial hypertension) (1,7).Insulin sensitivity can best be measured with the labor-intensive h...

Beta cell (dys)function in non-diabetic offspring of diabetic patients

“…In this study, healthy offspring of type 2 diabetes patients were less insulin sensitive, as they had a lower M/I measured by the gold-standard isoglycaemic-hyperinsulinaemic clamp test, in comparison with age-, BMI-and sex-matched controls, which is in line with numerous studies by others Table 4 Pearson's product moment correlations of anthropometric characteristics, routine laboratory measurements including circulating lipids, renal function, fasting and 2 h clamp plasma glucose and serum insulin, with the AUC(60 min) of insulin, the IGI(60 min), IGI (120 min) and with M/I from the hyperinsulinaemic clamp test in all participants and ourselves [2,8,14]. This was also reflected in higher plasma glucose concentrations after oral glucose challenge and in hyperinsulinaemia in the second phase of OGTT.…”

“…Total AUCs during the 2 h OGTT of glucose (glucose AUC), insulin (insulin AUC) and C-peptide (C-peptide AUC) were calculated with the trapezoidal rule. Dynamic AUC (ΔAUC) was calculated as total AUC−basal concentration ×120 min [14,15]. Beta cell function was evaluated as the C-peptide response to the glycaemic stimulus.…”

“…As, in addition to the M/I value, all major anthropometric and routine laboratory characteristics of offspring in the third M/I quartile were comparable with those of the controls (Table 1), the third M/I quartile of the offspring group was chosen to investigate beta cell function without insulin insensitivity [14].…”

The Relationship between Insulin Resistance and the Cardiovascular Biomarker Growth Differentiation Factor-15 in Obese Patients

“…The oral glucose insulin sensitivity (OGIS) was calculated as explained in http://webmet.pd.cnr.it/ogis (14 ). The clamp-like insulin resistance index (CLIX) was calculated as previously reported (15 ). We calculated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease formula (16 ).…”

Insulin resistance is not associated with myocardial steatosis in women

“…Study volunteers were recruited from the local cohort participating in the Relationship between Insulin Sensitivity and Cardiovascular Disease Risk (RISC) Study [24,25] and the outpatient ward of our department. From the RISC cohort, we selected women with normal glucose tolerance (glucose at 120 min post challenge ≤7.77 mmol/l) and with insulin sensitivity from the highest (insulin-sensitive) and lowest (insulin-resistant) quartile of its distribution, as well as women with IGT (normal fasting plasma glucose and insulin concentration, but with 120 min post challenge glucose of 7.77-11.11 mmol/l, n=3).…”