test in relatively small numbers of subjects have suggested that smoking may cause ... every BMI-tertile, smokers and ex-smokers had higher plasma insulin than ...
N A L
A R T I C L E
Smoking Is Independently Associated With High Plasma Insulin Levels in Nondiabetic Men TAPANI RONNEMAA, MD EI.INA M. RONNEMAA PAULI PUUKKA, MPOL
KALEVI PYORALA, MD MARKKU LAAKSO, MD
OBJECTIVE — Studies using the euglycemic clamp technique or the insulin suppression test in relatively small numbers of subjects have suggested that smoking may cause insulin resistance. Our aim was to study the association between smoking status and fasting plasma insulin in a large nondiabetic male population. RESEARCH DESIGN A N D M E T H O D S — A total of 616 nondiabetic men aged 45-64 years were taken from a population register. Fasting plasma insulin and blood pressure were measured, and smoking history and medication were evaluated by interview. RESULTS — Age- and BMl-adjusted insulin levels were significantly higher in smokers and ex-smokers than in nonsmokers (92.4, 86.4, and 78.6 pmol/1, respectively; P = 0.009). In every BMI-tertile, smokers and ex-smokers had higher plasma insulin than nonsmokers. After adjustment for factors potentially affecting insulin sensitivity (hypertension, systolic or diastolic blood pressure, use of P-blockers and/or diuretics, use of vasodilating antihypertensive drugs, physical exercise, alcohol use, parental history of NIDDM, coronary heart disease, and previous myocardial infarction), insulin concentrations were still highest in smokers (91.2 pmol/1), intermediate in ex-smokers (86.8 pmol/1), and lowest in nonsmokers (78.9 pmol/1, P = 0.008 between groups). CONCLUSIONS — Our results show that chronic smoking is associated with high ageand BMI-adjusted plasma insulin levels, independent of other factors known to influence insulin sensitivity. The effect of smoking may be partially reversible after quitting.
P
rospective population-based studies suggest that insulin resistance is a probable risk factor for coronary heart disease, as exemplified by the classic finding that high plasma insulin concentrations predict future cardiovascular mortality (1). In subjects with normal glucose tolerance, fasting plasma insulin levels are a rough but reliable estimate for insulin resistance (2). Cigarette smoking has consistently been shown to be a major risk factor for cardiovascular diseases (3). It has so far
been unclear how smoking elicits its harmful effects. Recent clinical studies using either an insulin suppression test or a euglycemic clamp technique have suggested that smokers exhibit reduced insulin sensitivity compared with nonsmokers (4,5). The purpose of this study was to investigate the independent effect of smoking on fasting plasma insulin levels in a large population-based cohort of nondiabetic men, taking into account BMI, hypertension, and other factors known to influence insulin sensitivity.
From the Department of Medicine (T.R., E.M.R.), University of Turku, Turku; the Research and Development Centre (T.R., EE), Social Insurance Institution, Turku; and the Department of Medicine (K.E, M.L.), University of Kuopio, Kuopio, Finland. Address correspondence and reprint requests to T. Ronnemaa, MD, Department of Medicine, University ol lurku, FIN-20520 Turku, Finland. Received for publication 14 November 1995 and accepted in revised form 27 June 1996. CUD, coronary heart disease; ECG, electrocardiogram; GLM, general linear models; MI, myocardial inlarction.
CARE, VOLUME 19, NUMBER 11, NOVEMBER
1996
RESEARCH DESIGN A N D M E T H O D S — The study population consisted of 640 nondiabetic men, aged 45-64 years, who were participating in a population-based study investigating the prevalence of atherosclerotic diseases and their risk factors in NIDDM patients and nondiabetic controls in 1982-1984 (6). The nondiabetic subjects were taken randomly from the population registers of the Turku and Kuopio University hospital areas in Finland. A detailed description of the formation of the study population has been given previously (6). Subjects with a fasting plasma glucose >7.8 mmol/l (corresponding to a blood glucose >6.7 mmol/l) were excluded. Thus, there were no diabetic subjects in the study population, but subjects with impaired glucose tolerance were included. One nonsmoking man with a traumatic unilateral leg amputation was excluded. All subjects gave their informed consent to the study. Approval for this study was given by the ethics committees of the University of Kuopio and the University of Turku. Smoking habits were assessed by a structured interview. Subjects were divided into three categories: nonsmokers (people who have never smoked) (n = 185), ex-smokers (n = 233), and smokers (n = 197). Ex-smokers were defined as subjects who had smoked for at least 1 year but who had not smoked during the previous year, and smokers were defined as subjects who had smoked for at least 1 year before the examination. Subjects whose smoking status had changed during the previous year (n = 22) or whose insulin value was not available (n = 2) were excluded from the study. BMI was calculated as weight (in kilograms) divided by height (in meters) squared. Blood pressure was measured to the nearest 2 mmHg in the sitting position after 10 min rest (6). Hypertension was denned as the use of antihypertensive drugs and/or actual systolic blood pressure >160 mmHg or diastolic blood pressure >95 mmHg. All medications were recorded, and history of NIDDM in parents was noted in an interview. Physical 1229
Smoking and plasma insulin
Table 1—Characteristics of nondiabetic men by smoking status
n Age (years) Weight (kg) Height (cm) BMI (kg/m2) Smoking time (years) Cigarettes/day Hypertension (%) Systolic BP (mmHg) Diastolic BP (mmHg) (3-blocker/diuretic (%) Vasodilator (%) Alcohol use (%) Exercisers (%) Parental NIDDM (%) CHD by symptoms and ECG changes (%) Previous MI (%)
Nonsmoker
Smoking status Ex-smoker
185 53.1 ±5.4 78.4 ±12.1 172.8 ±7.6 26.2 ±3.4 — — 30.3 137 ±18 86 ±11 17.8 3.2 61.1 38.4 14.1 6.0
233 55.4 ± 5.5* 79.6 ±11.0 172.3 ±6.5 26.8 ±3.2 18.6 ±10.0 18.7 ±10.0 31.8 142 ± 19t 86 ±11 18.0 3.4 70.8* 39.9 16.7 7.3
197 54.0 ±5.4 74.5 ± 11.5^ 171.8 ±7.1 25.2±3.2t 31.3 ±6.5 17.1 ±9.9 25.9 136 ±21 83 ±12* 16.2 2.0 82.71: 22.31 18.3 12.2*
