Strong Link Between Smoking and Diabetes

Nathalie Raffier

April 18, 2023

Smoking is the main risk factor for all-cause mortality among patients with type 1 and 2 diabetes. It ranks higher than glucose, lipids, and blood pressure.

Worsening micro- and macroangiopathy complications, increased cardiovascular and renal risk, and poorer blood glucose control are also key issues.

These factors should be convincing enough to prompt any patient with diabetes to stub out their last cigarette and avoid the toxic mix of smoking and diabetes. Or at the very least, this was the hope held by experts at the annual conference of the French-speaking Diabetic Society (SFD) this year.

High Smoking Prevalence

Type 2 diabetes and smoking are chronic diseases that are major public health problems. Each significantly reduces life expectancy: 10 years on average for smoking and 6 years for type 2 diabetes.

The latest figures for the number of smokers with diabetes in France were published by the country's public health authority in November 2022 in its weekly epidemiology surveillance report. It stated that a quarter of adults with type 1 diabetes (25.3%) and 13.4% of adults with type 2 diabetes reported being casual or daily smokers.

"The numbers are quite high," observed Philippe Thuillier, MD — a doctoral student and research student at the University of Western Brittany and Brest University Hospital — in a session dedicated to tobacco consumption at the SFD's 2023 conference. He added that "although there is a downward trend in the general population, smoking levels remain high in diabetic patients, with a favorable yet very modest decrease of 1.1% since 2007."

A Vicious Circle

This observation is not new. Without exception, epidemiologic studies point toward a link between active and, to a lesser extent, passive smoking and the risk of developing type 2 diabetes. This finding is supported by several meta-analyses. The relative risk (RR) has been reported to be about 1.40 on average. "Smoking increases a person's risk of type 2 diabetes by 40%," noted Thuillier, "and this relationship is dose dependent, in terms of both cigarettes per day and pack-years."

A 2015 meta-analysis included 88 prospective studies with nearly six million participants (RR, 1.37; 95% CI, 1.33 – 1.42). The famous Nurses' Health Study, spearheaded by researchers from the Channing Laboratory at the Brigham and Women's Hospital, Harvard Medical School, and the Harvard T. H. Chan School of Public Health, also identified the increased diabetes risk in smokers. There was a dose-dependent relationship among patients who smoked 1 to 14 cigarettes per day (RR, 1.39, 95% CI, 1.17 – 4.64).

This risk rose to 1.98 (95% CI, 1.57 – 2.36) among patients who smoked more than 25 cigarettes per day. The authors concluded that this link also exists for passive smoking (RR, 1.16; CI 95%, 1.00 – 1.35).

Although smokers tend to have lower body mass index (BMI) and lower weight than nonsmokers, smoking favors abdominal body fat accumulation. Therefore, the more one smokes, the more BMI increases. and fat is characteristically stored around the midriff. This excess adipose tissue around the abdomen, along with a greater waist-to-hip ratio, is associated with decreased glucose tolerance and insulin sensitivity.

In a cross-sectional cohort study that included 6123 patients aged 35 to 75 years, investigators analyzed data on smoking and body fat. They found that the risk of developing abdominal obesity was nearly two times higher among patients who smoked more than 20 cigarettes per day (2.15 in women, 1.94 in men), compared with patients who smoked more moderately (1 to 10 cigarettes per day).

Insulin Resistance

"There is very likely to be a link between smoking and the accumulation of visceral fat, which promotes metabolic syndrome," said Vincent Durlach, MD, a diabetes and smoking expert at Reims University Hospital for the SFD–French society for research into smoking. "This condition can include a combination of type 2 diabetes, hypertension, hypertriglyceridemia, and low HDL cholesterol, all occurring as part of insulin resistance." The direct and indirect pathophysiologic mechanisms are still to be determined.

In cigarettes, the main established offender is nicotine, which stimulates the production of blood glucose counterregulatory hormones, such as catecholamines, growth hormone, and adrenocorticotropic hormone, causing an increase in cortisol.

Nicotine also has an antiestrogenic effect, promoting android fat distribution.

What's more, nicotine is associated with endothelial dysfunction and oxidative stress, the result of hypoxia caused by carbon monoxide. Add to this the proinflammatory effect of cigarette smoke and it results in low-grade inflammation. The effects of nicotine are also associated with increased hepatic secretion of very-low-density lipoprotein cholesterol and reduced insulin-stimulated glucose uptake.

"These studies on the effects of cigarette toxins, mainly nicotine, have for the most part been conducted in animals in small cohorts, and then cigarettes contain more than 4700 substances, including heavy metals, which complicates studies into the pathophysiological mechanisms leading to insulin resistance," warned Thuillier.

Insulin resistance is promoted by active smoking (+40%) and passive smoking (+28%). Genetic factors that predispose a person to this condition, which mainly affect nicotinic acetylcholine receptors, could also be a contributing factor. One bit of good news is that insulin resistance is reversible if smoking is stopped.

Regarding beta-cell function, smoking seems to reduce insulin secretion. A study of two prospective cohorts of Asian male persons provided new information. In the first study, HOMA-B (a method for assessing beta-cell function) was decreased in a dose-responsive manner with cigarette smoking. In the second study, insulin secretion abnormalities were found in nearly half of the Japanese participants (adjusted HR, 1.95; CI 95%, 1.44 – 2.63) in smokers vs nonsmokers.

"Overall, smoking is associated with decreased beta-cell function, but the potential mechanisms, mediated by nicotine, which is said to increase beta-cell apoptosis, remain insufficiently documented," Thuillier added.

Blood Glucose Management

To keep diabetes under control, it's best to abstain from smoking. A meta-analysis that included nearly 88,000 patients with type 1 and 2 diabetes, of whom 15.21% were smokers, indicated that smoking was associated with a 0.61% increase in glycated hemoglobin.

A1c levels increased progressively with increases in the number of cigarettes per day and the number of pack-years of cigarette smoking, compared with never-smokers, as shown by a study that included data for just under 2500 men with type 2 diabetes from the Japanese Fukuoka Diabetes Registry.

The association between smoking and hypoglycemia in patients with type 1 diabetes was first described in the 1950s. This link was confirmed by a 2007 cross-sectional study that found that current smokers have 2.4 times greater odds of developing severe hypoglycemia.

The same finding was made in a Danish study. From a multivariate analysis, the authors estimated that smoking was independently associated with a risk of severe hypoglycemia (RR, 1.47; 95% CI, 1.13 – 1.91).

However, Thuillier advises that these data be taken with a pinch of salt. He says, "All this data must be regarded with caution, as the profiles of patients who smoke differ significantly from those who don't, the former often having a lower level of education and socioeconomic status and lower levels of compliance with lifestyle and dietary measures, et cetera, which explains the need for additional studies."

The question of blood glucose variability is not clear cut, either. A retrospective study of the Onset 5 trial, which involved 367 patients with type 1 diabetes who were treated with an insulin pump or a basal-bolus regimen and who wore a continuous glucose monitoring device, found a positive association between smoking and blood glucose variability, with more time experiencing hyperglycemia and severe hypoglycemia (<45 mg/dL). An examination of the coefficient of variation found no conclusive or significant association, however.

All-Cause Mortality

When it comes to smoking and all-cause mortality among patients with diabetes, the data are clear. Unsurprisingly, smoking increases all-cause mortality among patients with type 1 and 2 diabetes by 58% on average and by 64% and 39%, respectively. These figures are clearly driven by deaths caused by cancer and cardiovascular disease.

Being a smoker is the number one risk factor for all-cause mortality among patients with type 2 diabetes, more so than physical inactivity, A1c and lipid profile abnormalities, and more, according to a Swedish study. The study included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register. Participants were matched with 1,355,870 control persons according to age, sex, and county.

Among participants with type 1 and 2 diabetes, the increased risk for cardiovascular diseases linked to smoking has been confirmed (pooled RR, 2.26 and 1.42, respectively), cerebrovascular accident (1.39 and 1.55, respectively), coronary artery disease (1.33 and 1.53, respectively), peripheral artery disease, heart failure (1.29 for type 1), and cardiovascular deaths (1.91 and 1.44, respectively).

A study conducted with patients with type 1 diabetes showed the link with coronary artery disease and cerebrovascular accident to be dose dependent for type 1 diabetes.

Data from the Nurses' Health Study from patients with type 2 diabetes support this link for coronary artery disease. For consumption of between 1 to 14 cigarettes per day, the relative risk was 1.66; it was 2.68 beyond this amount.

Micro- and Macroangiopathic Complications

In addition to its own complications ― notably, cancer and vascular diseases ― smoking worsens the complications of diabetes and diabetic nephropathy. But on the basis of the current level of understanding, it's not that simple. Published data show with certainty that smoking increases the risk of macro- and microangiopathic complications, specifically, nephropathy among patients with type 2 diabetes and retinopathy and neuropathy among patients with type 1 diabetes.

The scientific literature is in agreement about the harmful aspects of smoking for patients with type 1 diabetes, with an increase in diabetic retinopathy (odds ratio [OR] = 1.23and 1.17 all stages combined and proliferative, respectively), diabetic nephropathy, all stages (cumulative risk over 12 years of 10.3%, vs 5.6% among nonsmokers for end-stage renal failure) and neuropathy (OR, 1.74; 95% CI, 1.48 – 2.04).

However, the association is less clear regarding those with type 2 diabetes. The risk of microangiopathy with, conversely, the "protective" effect of smoking on diabetic retinopathy must be verified.

Furthermore, meta-analyses of diabetic nephropathy appear to contradict each other. In a recent meta-analysis of 13 cross-sectional or prospective studies, the risk of microalbuminuria among patients with type 2 diabetes was increased among smokers (OR, 2.13; CI 95%, 1.32 – 3.45; P = .002), and there was a linear relationship between smoking and the duration of type 2 diabetes with albuminuria. The question regarding the risk for diabetic neuropathy also remains unanswered.

Thuillier and Durlach have disclosed no relevant financial relationships.

This article was translated from the Medscape French edition.

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