This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Katsuki, A. Articles by Adachi, Y. Search for Related Content PubMed PubMed Citation Articles by Katsuki, A. Articles by Adachi, Y.

QUICKI Is Useful for Following Improvements in Insulin Sensitivity after Therapy in Patients with Type 2 Diabetes Mellitus

Third Department of Internal Medicine (A.K., Y.S., E.C.G., H.U., K.M., N.K., T.T., R.A.-S., Y.H., Y.Y., Y.A.), Department of Radiology (S.M.) and Department of Laboratory Medicine (K.N.), Mie University School of Medicine, Mie 514-8507, Japan

Address all correspondence and requests for reprints to: Akira Katsuki, M.D., Third Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. E-mail: . katuki-a{at}clin.medic.mie-u.ac.jp

Abstract

To investigate whether quantitative insulin sensitivity check index (QUICKI) would be useful as an index of insulin resistance during the clinical course of type 2 diabetes mellitus, correlation between QUICKI and the index of the euglycemic hyperinsulinemic clamp study [clamp insulin resistance (clamp IR)] was evaluated in 60 patients with type 2 diabetes mellitus before and after treatment. The therapy program consisted of diet (1440–1720 kcal/d) and exercise (walking 10,000 steps daily) for 6 wk.

QUICKI and clamp IR were significantly correlated before (r = 0.598, P < 0.0001) and after (r = 0.583, P < 0.0001) treatment. Neither the slope nor the intercept of the linear correlation between QUICKI and clamp IR measured before treatment was significantly different from those measured after treatment (slopes; F = 0.002, P = 0.96, intercepts; F = 2.65, P = 0.11). During treatment, the values of both QUICKI (8% change; P < 0.0001) and clamp IR (38% change; P < 0.0001) significantly increased and their changes were significantly correlated (r = 0.415, P < 0.01).

In conclusion, QUICKI may become a useful method for the follow-up of insulin resistance during the treatment of patients with type 2 diabetes mellitus.

INSULIN RESISTANCE PLAYS an important role in the pathophysiology of type 2 diabetes mellitus (1). To date, various methods have been used to evaluate insulin sensitivity in vivo (2, 3, 4, 5). Of these, the quantitative insulin sensitivity check index (QUICKI) has been recently reported to be a useful marker of insulin resistance in patients with type 2 diabetes mellitus (5, 6, 7, 8, 9). Previous studies have demonstrated the usefulness of QUICKI in different conditions, and it is particularly suitable for epidemiological survey (10, 11, 12, 13, 14). QUICKI has been studied in sedentary nondiabetic adults, obese adolescents, and patients with polycystic ovary syndrome during treatment and in women with normal glucose tolerance and gestational diabetes mellitus during pregnancy (7, 15, 16, 17). However, its use in clinical practice for the follow-up of insulin resistance in type 2 diabetic patients during treatment has not been as yet evaluated.

In the present study, we investigated whether QUICKI is correlated with the index of the euglycemic hyperinsulinemic clamp study [clamp insulin resistance (clamp IR)] in patients with type 2 diabetes mellitus before and after treatment.

Subjects and Methods

Subjects

This study comprised 60 Japanese patients with type 2 diabetes mellitus (age from 22–69 yr old; Table 1). Type 2 diabetes mellitus was   diagnosed in our patients at a local clinic 8.4 ± 6.9 yr before the beginning of this study. All patients received dietary (1440–1720 kcal/d) and exercise (walking 10,000 steps/d) therapy without any drugs. Their blood sugar was in good control [hemoglobin A1c (HbA1c) 6.5%] during the initial years; however, thereafter their blood sugar gradually increased (HbA1c 8%) because of overeating and inactivity. Five of 60 patients received sulfonylureas (glibenclamide 2.5–5.0 mg/d) for about 3 yr before the beginning of the study; the blood sugar of these patients also worsened several months before admission due to overeating and inactivity. They were admitted in our clinical department for glycemia control. We categorized them as having type 2 diabetes mellitus based on the diagnostic criteria of the American Diabetes Association (18). There were 16 patients with peripheral neuropathy, 16 with simple diabetic retinopathy and 10 with microalbuminuria. None of them had macrovascular complications. Informed consent was obtained from all subjects before the beginning of the study.

After admission, the patients participated in a program of diet and exercise for 6 wk. The dietary treatment was as follows: 1440–1720 kcal/d with a diet consisting of 20 energy percent (en%) protein, 25 en% fat, and 55 en% carbohydrates. During the exercise therapy, the patients walked 10,000 steps daily.

The blood levels of glucose, HbA1c and insulin, and the values of QUICKI, clamp IR, the body fat area, and blood pressure were measured in all subjects within 1 wk after admission and 1 wk before discharge. Sulfonylureas were withdrawn 1 d before the clamp study.

The plasma glucose level was measured by an automated enzymatic method. The HbA1c (normal value: 4.3–5.8%) was measured by HPLC. Serum insulin was measured using an immunoradiometric assay kit (Insulin Riabead II kit, Dainabot, Tokyo, Japan). The intra and interassay coefficients of variation of the assay were 2.0% and 2.1%, respectively. No significant cross-reactivity or interference were observed between insulin and proinsulin, C peptide, glucagon, secretin, and gastrin-I.

QUICKI was calculated using the following formula: 1/ [log fasting serum insulin (µU/ml) + log fasting plasma glucose (mg/dl)] (5).

Clamp IR was evaluated by the euglycemic hyperinsulinemic clamp technique using an artificial pancreas (STG-22, Nikkiso, Tokyo, Japan) (2, 4). At 0800 h, a priming dose of insulin (Humulin R, Eli Lilly \|[amp ]\| Co. Japan, Kobe, Japan) was administered during the initial 10 min in a logarithmically decreasing manner to rapidly raise serum insulin to the desired level (1200 pmol/liter); this level was then maintained by continuous infusion of insulin at a rate of 13.44 pmol/kg·min for 120 min. The mean insulin level from 90–120 min after starting the clamp study was stable (before treatment: 1227.6 ± 201.0 pmol/liter, after treatment: 1185.6 ± 232.2 pmol/liter). Blood glucose was monitored continuously and maintained at the target clamp level (5.24 mmol/liter) by infusing 10% glucose. The mean amount of glucose given during the last 30 min was defined as a clamp IR.

Body fat area was evaluated by a previously described method (19). At 0800 h, after an overnight fast of 12 h, all patients underwent single abdominal computed tomography scanning at the umbilical level in respiratory phase. Any ip regions having the same density as the sc fat layer were defined as a visceral fat area; this area was measured by tracing object contours on films using a computerized planimetric method. In addition, we measured blood pressure in supine position after a rest of 5 min.

Statistical methods

Data were expressed as the means ± SD. A t test was performed to compare the means of variables measured before and after treatment. The relationship of QUICKI with clamp IR was evaluated by univariate regression analysis. The regression lines before and after treatment were compared by analysis of covariance. The t test and correlations were carried out using the StatView 4.0 software program (Abacus Concepts, Berkeley, CA). Analysis of covariance was performed using the PRISM 2.0 software program (GraphPad Software, Inc., San Diego, CA). P value less than 0.05 was considered as statistically significant.

Results

Significant correlations were observed between QUICKI and clamp IR before (r = 0.598, P < 0.0001, Fig. 1, closed circles and solid line) and after (r = 0.583, P < 0.0001, Fig. 1, open circles and dotted line) treatment. Analysis of covariance showed that neither the slopes (50.93 ± 9.05 vs. 50.37 ± 8.66, F = 0.002, P = 0.96) nor the intercepts (y-intercept = -11.20 vs. -8.29, x-intercept = 50.68 vs. 45.39, F = 2.65, P = 0.11) of the regression lines between QUICKI and clamp IR before and after treatment were statistically different in magnitude. During treatment, in addition to improvement in the blood concentrations of glucose (26% change; P < 0.0001) and HbA1c (15% change; P < 0.0001), there was a significant increase in QUICKI (8% change; P < 0.0001) and clamp IR (38%change; P < 0.0001) (Table 1). Percent change of QUICKI was significantly correlated with that of clamp IR (r = 0.415, P < 0.01, Fig. 2).

View larger version (18K): [in this window] [in a new window]   Figure 1. Correlation between QUICKI and clamp IR in patients with type 2 diabetes mellitus before and after treatment. QUICKI was significantly correlated with clamp IR before (r = 0.598, P < 0.0001, •, solid line) and after (r = 0.583, P < 0.0001, , dotted line) treatment. Neither the slopes (F = 0.002, P = 0.96) nor the intercepts (F = 2.65, P = 0.11) of the regression lines were significantly different before and after treatment.

View larger version (15K): [in this window] [in a new window]   Figure 2. Correlation between the percent change of QUICKI and clamp IR in patients with type 2 diabetes mellitus after therapy. There was a significant correlation between the percent changes of QUICKI and clamp IR (r = 0.415, P < 0.01).

Discussion

The present study clearly demonstrated that QUICKI correlates significantly with clamp IR before and after treatment in patients with type 2 diabetes mellitus.

Homeostasis model assessment has been reported to be of value for evaluating insulin resistance in type 2 diabetic patients treated with sulfonylureas (20). It was not possible to prove in our present study the accuracy of QUICKI in patients with type 2 diabetes mellitus under medication. In future studies, it would be necessary to assess the usefulness of QUICKI in type 2 diabetic patients receiving different types of medication.

It is known that the degree of adipocity affects the relationship between QUICKI and clamp IR (5, 21). Although patients enrolled in our present study were nonobese as judged by their body mass index values, they were metabolically obese subjects because they had abnormal increase of visceral fat (22). However, further studies including typically obese patients should be performed.

Duncan et al. (16) previously reported that QUICKI may not be useful as a clinical index of insulin resistance during exercise therapy in sedentary adults. However, the comparison of QUICKI with an index derived from the minimal model analysis of the unmodified frequently sampled iv glucose tolerance test (FSIVGTT) (23), and not with the index calculated during the gold standard euglycemic hyperinsulinemic clamp technique may explain the negative result (24).

In conclusion, QUICKI may be a useful method not only for diagnosing insulin resistance but also for its follow-up during the treatment of patients with type 2 diabetes mellitus.

Acknowledgments

Footnotes

Abbreviations: clamp IR, Insulin resistance assessed by the euglycemic hyperinsulinemic clamp study; en%, energy percent; HbA1c, hemoglobin A1c; QUICKI, quantitative insulin sensitivity check index.

Received December 27, 2001.

Accepted March 8, 2002.

References

1. DeFronzo RA, Bonadonna RC, Ferrannini E 1992 Pathogenesis of NIDDM. A balanced overview. Diabetes Care 15:318–368[Abstract]
2. DeFronzo RA, Tobin JD, Andres R 1979 Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223
3. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC 1985 Homeostasis model assessment: insulin resistance and ß-cell function from fasting glucose and insulin concentrations in man. Diabetologia 28:412–419[CrossRef][Medline]
4. Katsuki A, Sumida Y, Gabazza EC, Murashima S, Furuta M, Araki-Sasaki R, Hori Y, Yano Y, Adachi Y 2001 Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes Care 24:362–365[Abstract/Free Full Text]
5. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ 2000 Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410[Abstract/Free Full Text]
6. Quon MJ 2001 Editorial: limitations of the fasting glucose to insulin ratio as an index of insulin sensitivity. J Clin Endocrinol Metab 86:4615–4617[Free Full Text]
7. Mather KJ, Hunt AE, Steinberg HO, Paradisi G, Hook G, Katz A, Quon MJ, Baron AD 2001 Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab 86:5457–5464[Abstract/Free Full Text]
8. Bastard JP, Robert JJ, Jardel C, Bruckert E, Grimaldi A, Hainque B 2001 Is quantitative insulin sensitivity check index, a fair insulin sensitivity index in humans? Diabetes Metab 27:69–70[Medline]
9. Rabasa-Lhoret R, Laville M 2001 How to measure insulin sensitivity in clinical practice? Diabetes Metab 27:201–208[Medline]
10. Gonzalez-Albarran O, Garcia-Robles R 2001 Correlation between insulin suppression test and quantitative insulin sensitivity check index in hypertensive and normotensive obese patients. Diabetes Care 24:1998–2000[Free Full Text]
11. Dixon JB, Bhathal PS, O’Brien PE 2001 Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 121:91–100[CrossRef][Medline]
12. Escobar-Morreale HF, Calvo Sancho J, San Millan JL 2001 TNF- and hyperandrogenism: a clinical, biochemical, and molecular genetic study. J Clin Endocrinol Metab 86:3761–3767[Abstract/Free Full Text]
13. Silfen ME, Manibo AM, MacMahon DJ, Levine LS, Murphy AR, Oberfield SE 2001 Comparison of simple measures of insulin sensitivity in young girls with premature adrenarche: the fasting glucose to insulin ratio may be a simple and useful measure. J Clin Endocrinol Metab 86:2863–2868[Abstract/Free Full Text]
14. Hrebicek J, Janout V, Malincikova J, Horakova D, Cizek L 2002 Detection of insulin resistance by simple quantitative insulin sensitivity check index QUICKI for epidemiological assessment and prevention. J Clin Endocrinol Metab 87:144–147[Abstract/Free Full Text]
15. Freemark M, Bursey D 2001 The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Pediatrics 107:E55
16. Duncan GE, Hutson AD, Stacpoole PW 2001 QUICKI does not accurately reflect changes in insulin sensitivity with exercise training. J Clin Endocrinol Metab 86:4115–4119[Abstract/Free Full Text]
17. Kirwan JP, Huston-Presley L, Kalhan SC, Catalano PM 2001 Clinically useful estimates of insulin sensitivity during pregnancy. Diabetes Care 24:1602–1607[Abstract/Free Full Text]
18. 1997 The expert committee on the diagnosis and classification of diabetes mellitus: report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 10:1183–1197
19. Tokunaga K, Matsuzawa Y, Ishikawa K, Tarui S 1983 A novel technique for the determination of body fat by computed tomography. Int J Obes 7:437–445[Medline]
20. Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, Kawagishi T, Shoji T, Okuno Y, Morii H 1999 Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care 22:818–822[Abstract/Free Full Text]
21. Perseghin G, Caumo A, Caloni M, Testolin G, Luzi L 2001 Incorporation of the fasting plasma FFA concentration into QUICKI improves its association with insulin sensitivity in nonobese individuals. J Clin Endocrinol Metab 86:4776–4781[Abstract/Free Full Text]
22. Matsuzawa Y 1997 Pathophysiology and molecular mechanism of visceral fat syndrome: the Japanese experience. Diabetes Metab Rev 13:1–13[Medline]
23. Bergman RN 1989 Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes 38:1512–1527[Abstract]
24. Quon MJ 2002 QUICKI is a useful and accurate index of insulin sensitivity. J Clin Endocrinol Metab 87:949–950[Free Full Text]

This article has been cited by other articles:

				B. Antuna-Puente, E. Disse, M. Faraj, M.-E. Lavoie, M. Laville, R. Rabasa-Lhoret, and J.-P. Bastard Evaluation of insulin sensitivity with a new lipid-based index in non-diabetic postmenopausal overweight and obese women before and after a weight loss intervention Eur. J. Endocrinol., July 1, 2009; 161(1): 51 - 56. [Abstract] [Full Text] [PDF]

				R. Muniyappa, S. Lee, H. Chen, and M. J. Quon Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E15 - E26. [Abstract] [Full Text] [PDF]

				R. J. Karne, H. Chen, G. Sullivan, and M. J. Quon Letter re: Limited Accuracy of Surrogates of Insulin Resistance during Puberty in Obese and Lean Children at Risk for Altered Glucoregulation J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4418 - 4419. [Full Text] [PDF]

				H. Chen, G. Sullivan, and M. J. Quon Assessing the Predictive Accuracy of QUICKI as a Surrogate Index for Insulin Sensitivity Using a Calibration Model Diabetes, July 1, 2005; 54(7): 1914 - 1925. [Abstract] [Full Text] [PDF]

				K. K. Koh, S. H. Han, M. J. Quon, J. Yeal Ahn, and E. K. Shin Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia Diabetes Care, June 1, 2005; 28(6): 1419 - 1424. [Abstract] [Full Text] [PDF]

				K. K. Koh, M. J. Quon, S. H. Han, J. Y. Ahn, D. K. Jin, H. S. Kim, D. S. Kim, and E. K. Shin Vascular and Metabolic Effects of Combined Therapy With Ramipril and Simvastatin in Patients With Type 2 Diabetes Hypertension, June 1, 2005; 45(6): 1088 - 1093. [Abstract] [Full Text] [PDF]

				M. Rosenbaum, C. Nonas, M. Horlick, I. Fennoy, I. Vargas, H. Schachner, P. Kringas, K. Stanton, R. Weil, and and the El Camino Diabetes Prevention Group {beta}-Cell Function and Insulin Sensitivity in Early Adolescence: Association with Body Fatness and Family History of Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5469 - 5476. [Abstract] [Full Text] [PDF]

				R. J. Karne, H. Chen, and M. J. Quon Diagnosing Insulin Resistance by Simple Quantitative Methods in Subjects With Normal Glucose Metabolism: Response to Ascaso et al. Diabetes Care, May 1, 2004; 27(5): 1247 - 1248. [Full Text] [PDF]

				H. Yokoyama, M. Emoto, S. Fujiwara, K. Motoyama, T. Morioka, M. Komatsu, H. Tahara, H. Koyama, T. Shoji, M. Inaba, et al. Quantitative Insulin Sensitivity Check Index and the Reciprocal Index of Homeostasis Model Assessment Are Useful Indexes of Insulin Resistance in Type 2 Diabetic Patients with Wide Range of Fasting Plasma Glucose J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1481 - 1484. [Abstract] [Full Text] [PDF]

				R. Z. Lewanczuk, B. W. Paty, and E. L. Toth Comparison of the [13C]Glucose Breath Test to the Hyperinsulinemic-Euglycemic Clamp When Determining Insulin Resistance Diabetes Care, February 1, 2004; 27(2): 441 - 447. [Abstract] [Full Text] [PDF]

				R. Rabasa-Lhoret, J.-P. Bastard, V. Jan, P.-H. Ducluzeau, F. Andreelli, F. Guebre, J. Bruzeau, C. Louche-Pellissier, C. MaItrepierre, J. Peyrat, et al. Modified Quantitative Insulin Sensitivity Check Index Is Better Correlated to Hyperinsulinemic Glucose Clamp than Other Fasting-Based Index of Insulin Sensitivity in Different Insulin-Resistant States J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4917 - 4923. [Abstract] [Full Text] [PDF]

				A. Katsuki, Y. Sumida, H. Urakawa, E. C. Gabazza, S. Murashima, N. Maruyama, K. Morioka, K. Nakatani, Y. Yano, and Y. Adachi Increased Visceral Fat and Serum Levels of Triglyceride Are Associated With Insulin Resistance in Japanese Metabolically Obese, Normal Weight Subjects With Normal Glucose Tolerance Diabetes Care, August 1, 2003; 26(8): 2341 - 2344. [Abstract] [Full Text] [PDF]

				H. Yokoyama, M. Emoto, S. Fujiwara, K. Motoyama, T. Morioka, M. Komatsu, H. Tahara, T. Shoji, Y. Okuno, and Y. Nishizawa Quantitative Insulin Sensitivity Check Index and the Reciprocal Index of Homeostasis Model Assessment in Normal Range Weight and Moderately Obese Type 2 Diabetic Patients Diabetes Care, August 1, 2003; 26(8): 2426 - 2432. [Abstract] [Full Text] [PDF]

				H. Chen, G. Sullivan, L. Q. Yue, A. Katz, and M. J. Quon QUICKI is a useful index of insulin sensitivity in subjects with hypertension Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E804 - E812. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Katsuki, A. Articles by Adachi, Y. Search for Related Content PubMed PubMed Citation Articles by Katsuki, A. Articles by Adachi, Y.