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Insulin Sensitivity Index, Acute Insulin Response, and Glucose Effectiveness in a Population-Based Sample of 380 Young Healthy Caucasians

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Insulin Sensitivity Index, Acute Insulin Response, and Glucose Effectiveness in a Population-Based Sample of 380 Young Healthy Caucasians Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J O Clausen, … , K Winther, O Pedersen J Clin Invest. 1996;98(5):1195-1209. https://doi.org/10.1172/JCI118903. Research Article BACKGROUND: Insulin sensitivity and insulin secretion are traits that are both genetically and environmentally determined. AIM: The aim of this study was to describe the distribution of the insulin sensitivity index (Si), the acute insulin response, and glucose effectiveness (Sg) in young healthy Caucasians and to estimate the relative impact of anthropometric and environmental determinants on these variables. METHODS: The material included 380 unrelated Caucasian subjects (18-32 yr) with measurement of Si, Sg and insulin secretion during a combined intravenous glucose (0.3 grams/kg body weight) and tolbutamide (3 mg/kg body weight) tolerance test. RESULTS: The distributions of Si and acute insulin response were skewed to the right, whereas the distribution of Sg was Gaussian distributed. Sg was 15% higher in women compared with men (P < 0.001). Waist circumference, body mass index, maximal aerobic capacity, and women's use of oral contraceptives were the most important determinants of Si. Approximately one-third of the variation of Si could be explained by these factors. Compared with individuals in the upper four-fifths of the distribution of Si, subjects with Si in the lowest fifth had higher waist circumference, higher blood pressure, lower VO2max, and lower glucose tolerance and fasting dyslipidemia and dysfibrinolysis. Only 10% of the variation in acute insulin response could be explained by measured determinants. CONCLUSION: Estimates of body fat, maximal aerobic […] Find the latest version: https://jci.me/118903/pdf Insulin Sensitivity Index, Acute Insulin Response, and Glucose Effectiveness in a Population-based Sample of 380 Young Healthy Caucasians Analysis of the Impact of Gender, Body Fat, Physical Fitness, and Life-Style Factors Jesper O. Clausen,*** Knut Borch-Johnsen,* Hans Ibsen,* Richard N. Bergman,‡ Philip Hougaard,§ Kaj Winther,ʈ¶ and Oluf Pedersen** *The Glostrup Population Studies, Medical Department C, Glostrup Hospital, University of Copenhagen, 2600 Glostrup, Denmark; ‡Department of Physiology and Biophysics, University of Southern California Medical School, Los Angeles, California 90007; §Statistics HRT, CNS, GH, Novo Nordisk A/S, 2880 Bagsvaerd, Denmark; ʈDepartment of Clinical Chemistry, Glostrup Hospital, University of Copenhagen, 2600 Glostrup, Copenhagen, Denmark; ¶Department of Clinical Chemistry, Kolding Hospital, 6000 Kolding; and **Steno Diabetes Center 2820, Gentofte, Copenhagen, Denmark Abstract Introduction Background. Insulin sensitivity and insulin secretion are Diabetes and hypertension are common clinical disorders traits that are both genetically and environmentally deter- which particularly affect middle-aged and elderly individuals. mined. Both disorders confer an increased risk of premature coronary Aim. The aim of this study was to describe the distribu- atherosclerosis (1, 2). The pathogenic mechanisms leading to tion of the insulin sensitivity index (Si), the acute insulin re- disease are assumed to begin decades before overt disease is sponse, and glucose effectiveness (Sg) in young healthy present and several pieces of evidence suggest that impaired Caucasians and to estimate the relative impact of anthropo- insulin sensitivity may be one such factor (1, 3). For example, metric and environmental determinants on these variables. in prospective studies low insulin sensitivity has been found to Methods. The material included 380 unrelated Caucasian be a risk factor for the subsequent development of non–insu- subjects (18–32 yr) with measurement of Si, Sg and insulin lin-dependent diabetes mellitus (NIDDM)1 (4, 5). The cluster- secretion during a combined intravenous glucose (0.3 ing in some individuals of NIDDM or impaired glucose tolerance grams/kg body weight) and tolbutamide (3 mg/kg body with obesity, hypertension, dyslipidemia, and dysfibrinolysis, all weight) tolerance test. states which separately or in combination are characterized by Results. The distributions of Si and acute insulin response reduced whole body insulin sensitivity, has been designated were skewed to the right, whereas the distribution of Sg was the insulin resistance syndrome (1). Gaussian distributed. Sg was 15% higher in women com- Low insulin sensitivity is thought to have a multifactorial pared with men (P Ͻ 0.001). Waist circumference, body basis (6). First degree relatives of subjects with NIDDM or hy- mass index, maximal aerobic capacity, and women’s use of pertension are in some ethnic groups reported to be insulin re- oral contraceptives were the most important determinants sistant (7, 8) pointing to a genetic influence. Life-style factors of Si. Approximately one-third of the variation of Si could causing impaired insulin sensitivity like excessive intake of sat- be explained by these factors. Compared with individuals in urated fatty acids, cigarette smoking, or lack of physical activ- the upper four-fifths of the distribution of Si, subjects with ity may alter the degree of and timing of expression of associ- Si in the lowest fifth had higher waist circumference, higher ated disorders like subsets of NIDDM, hypertension, and pre- blood pressure, lower VO2max, and lower glucose tolerance mature ischemic cardiovascular disorders (9, 10). Each disor- and fasting dyslipidemia and dysfibrinolysis. Only 10% of der in the insulin resistance syndrome also increases in prevalence the variation in acute insulin response could be explained by as the population ages. In subjects having NIDDM, premature measured determinants. ischemic cardiovascular disorders, or morbid obesity, the level of Conclusion. Estimates of body fat, maximal aerobic ca- risk factors, for example maximal aerobic capacity (VO2max), pacity, and women’s use of oral contraceptives explain is also influenced by the disease state. Therefore, studies ex- about one-third of the variation in Si in a population-based amining the impact of various factors modulating insulin sensi- sample of young healthy Caucasians. (J. Clin. Invest. 1996. tivity might ideally be undertaken in young healthy subjects. 98:1195–1209.) Key words: insulin sensitivity • insulin se- The interindividual level of insulin sensitivity in the general cretion • glucose effectiveness • body fat • life-style factors population varies widely (11, 12). However, insulin sensitivity and environmental factors influencing insulin sensitivity have not been systematically evaluated in any population survey of young adult subjects. Therefore, the objectives of the present investigation were: (a) to describe the distribution of the insu- lin sensitivity index, acute insulin response, and glucose effec- Address correspondence to Jesper O. Clausen, M.D., Steno Diabetes tiveness in a population-based sample of young healthy Cauca- Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark. Phone: sians; (b) to identify the potential modulators with high impact 45-3962-9830; FAX: 45-4443-8232. Received for publication 28 September 1995 and accepted in re- vised form 13 June 1996. 1. Abbreviations used in this paper: AUC, area under the curve; BMI, J. Clin. Invest. body mass index; IVGTT, intravenous glucose tolerance test; © The American Society for Clinical Investigation, Inc. NIDDM, non–insulin-dependent diabetes mellitus; PAI-1 activity, 0021-9738/96/09/1195/15 $2.00 plasminogen activator inhibitor 1 activity; t-PA antigen, tissue plas- Volume 98, Number 5, September 1996, 1195–1209 minogen activator antigen; VO2max, maximal aerobic capacity. Insulin Sensitivity Index in Young Healthy Danish Caucasians 1195 on the insulin sensitivity index as well as acute insulin response ing the maximum circumference over the buttocks. These parameters and glucose effectiveness; and (c) to offer an operational defi- were measured with the individuals in an upright position and taken nition of insulin resistance, which may be used in prospective to the nearest 0.5 cm. Height was measured to the nearest 0.5 cm with studies of the role of a low insulin sensitivity index in the the subjects standing without shoes, the heels together, and the head pathogenesis of artherosclerotic disorders and diabetes. in the horizontal plane. Body weight was measured to the nearest 0.1 kg with subjects wearing only light clothes. BMI was calculated as weight divided by squared height (kg/m2). Fat mass was measured Methods with an impedance technique (15). VO2max was measured by means of a submaximal bicycle exercise test as described by Åstrand (16). Subjects. The study participants were randomly recruited from a Blood pressure was determined by means of a London School of population of young individuals aged 18–32 yr, who in 1979/80 and Hygiene sphygmomanometer (17), making the readings unbiased, as again in 1984/85 as children participated in blood pressure surveys in the scale is not visible during deflation of the cuff. Recording of blood a representative and specified part of Copenhagen city (13, 14). The pressure took place between noon and 2:00 p.m., when the subjects present examination took place in 1992 and 1993. All subjects from had participated in the study for a minimum of 4 h and were in a re- the initial sample except one could be traced in the Danish
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