Effect of cigarette smoking and of a transdermal nicotine delivery system on glucoregulation in type 2 diabetes mellitus
The effect of nicotine absorbed transdermally from a patch (TNS) and. from cigarette smoking on insulin secretion and action in Type 2 diabetes has been compared. Twelve Type 2 diabetic smoking patients, aged 51 y, with diabetes for 9 y, treated either with diet and/or oral hypoglycaemic agents, were studied on three occasions according to a double-blind, placebo-controlled cross-over design. The subjects were investigated 12 h after their last cigarette or application of one patch of TNS 30 cm2 or TNS placebo, or whilst smoking their usual cigarette. Insulin secretion was assessed by a glucagon (1 mg IV) stimulation test. On a second occasion, insulin action was assessed by a hyperglycaemic-hyperinsulinaemic clamp, the spontaneous hyperglycaemia of the fasting state (8.61 mmol·l−1) being maintained during a 4 h insulin infusion (at 0.1 mU · kg−1 · min−1 for the initial 2 h, and 1 mU · kg−1 . min−1 during the last 2 h). TNS and the cigarette did not affect endogenous insulin secretion as compared to placebo. During the initial 2 h of the clamp study, plasma insulin increased from 88 to 155 pmol · l−1, hepatic glucose production (3-3H-glucose) was less suppressed after TNS (4.31 μmol · kg−1 · min−1) than after placebo (2.5 μmol · kg−1 min−1), but was more suppressed than after cigarette smoking (5.61 μmol · kg−1 · min−1). In the last 2 h of the clamp (plasma insulin 646 pmol · l−1), glucose utilization was less stimulated after TNS (36.1 μmol · kg−1 · min−1) vs placebo (39.8 μmol · kg−1 · min−1), but more than after cigarette smoking (33.6 μmol · kg−1 · min−1), primarily because of a decrease in glucose storage. Free fatty acid and lipid oxidation were significantly less suppressed by hyperinsulinaemia after TNS and cigarette smoking vs placebo. Nicotine impairs insulin action on the liver, adipose tissue and muscle and may contribute to hyperglycaemia in Type 2 diabetes. TNS diminishes the action of insulin to a lesser extent than cigarette smoking. Thus, TNS may represent a “metabolically” safe measure to help patients with Type 2 diabetes to quit smoking.