Several studies have reported that serum levels of leptin, an adipocyte-secreted hormone, increase exponentially with increasing body fat mass (1). However, there is considerable variability in leptin levels at a given level of adiposity, suggesting that other factors may influence circulating leptin levels. In this context, there is little and somewhat conflicting information regarding the effects of diabetic state per se on leptin levels, particularly in type 1 diabetes. Serum leptin concentrations have been found to be normal (2,3) or higher (4) in type 1 diabetic patients compared with control subjects. Moreover, although significantly lower serum leptin levels have been demonstrated in nondiabetic smokers versus nonsmokers (1,5–7), to our knowledge, there is a lack of available data regarding the impact of smoking on leptin levels in young adults with type 1 diabetes. On the other hand, the clarification of smoking’s impact may have important implications for risk management and our understanding of the pathophysiological mechanisms of weight gain after smoking cessation. Thus, the main purposes of the present study were to compare serum leptin levels in nondiabetic subjects and type 1 diabetic patients and to assess the effects of chronic smoking on leptin levels in type 1 diabetic patients.

We measured serum leptin concentrations (RIA-kit; Linco Research, St Louis, MO) in 54 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 20 healthy control subjects who were matched for age (31.6 ± 1.3 vs. 31.8 ± 1.3 years), sex (M/F = 30/24 vs. 12/8), BMI (23.8 ± 0.6 vs. 23.3 ± 0.7 kg/m2), systolic blood pressure (125 ± 2 vs. 122 ± 2 mmHg), diastolic blood pressure (81 ± 1 vs. 80 ± 1 mmHg), and smoking status (smokers n = 20 vs. 10). The average glycometabolic control of diabetic patients was fairly good (HbA1c 6.7 ± 0.1%); the diabetes duration was 14.8 ± 0.2 years. More details on clinical and biochemical characteristics of the subjects have been reported previously (8). Type 1 diabetic patients had leptin concentrations substantially similar to the healthy control subjects (mean ± SEM 4.13 ± 0.5 vs. 4.36 ± 0.7 ng/ml). After stratification by smoking status, diabetic smokers (n = 34) had values for age, sex, BMI, lipids, blood pressure, glycometabolic control, creatinine, diabetes duration, and its microvascular complications (i.e., presence of retinopathy and/or microalbuminuria) that were superimposable upon their nonsmoking counterparts (n = 20). Nevertheless, serum leptin levels were markedly reduced in diabetic smokers versus nonsmokers (2.62 ± 0.4 vs. 4.91 ± 0.7 ng/ml; P < 0.01). Similarly, healthy subjects who smoked had significantly lower leptin levels than healthy nonsmokers (3.7 ± 1.1 vs. 5.7 ± 0.8 ng/ml; P < 0.05). Leptin levels decreased markedly with the increase in the number of cigarettes smoked daily in both diabetic patients (nonsmokers vs. <11 cigarettes/day vs. >11cigarettes/day: 4.91 ± 0.7 vs. 3.1 ± 0.7 vs. 2.3 ± 0.6 ng/ml, respectively; P < 0.02 for comparison by one-way analysis of variance) and control subjects, although this trend did not achieve a statistical significance (P = 0.058). The dose-response relationship found in diabetic patients between leptin levels and the number of cigarettes smoked per day remained statistically significant even after adjustment for potential confounders, such as age, sex, BMI, glycometabolic control, lipids, diabetes duration, and complication status.

Overall, therefore, the evidence from this study and other studies (2,3) suggests that type 1 diabetic patients have serum leptin levels similar to those of healthy control subjects with comparable BMI, and that chronic cigarette smoking itself may be one of the major life-style determinants of leptin levels in both normal subjects (5–7) and type 1 diabetic individuals. Although no straightforward explanation is available, cigarette smoking may directly or indirectly modify the sensitivity of hypothalamic leptin receptors and, consequently, modulate leptin synthesis (5).

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Mantzoros CS: The role of leptin in human obesity and disease: a review of current evidence.
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Verrotti A, Basciani F, Morgese G, Chiarelli F: Leptin levels in non-obese and obese children and young adults with type 1 diabetes.
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Ruige JB, Dekker JM, Blum WF, Stehouwer CDA, Nijpels G, Mooy J, Kostense PJ, Bouter LM, Heine RJ: Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study: The Hoorn Study.
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22
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1999

Address correspondence to Giovanni Targher, MD, Servizio di Diabetologia, Ospedale Sacro Cuore, via Sempreboni 5, 37024 Negrar (VR), Italy. E-mail: [email protected].

2001