Managing vascular risk factors among obese quitters with diabetes: how intensive lifestyle intervention and novel pharmacotherapy can work in concert?

Debasish Kar, Samuel Seidu, Melanie Davies, Kamlesh Khunti


 Obese smokers with diabetes are a special risk category for all-cause mortality and major adverse cardiovascular events (MACE). Weight loss and smoking cessation are key interventions advocated for the management of diabetes in almost all the guidelines across the globe. However, there is a substantial risk of weight gain following smoking cessation which may, in some cases, cause a transient worsening of glycaemic control in people with diabetes. The risk of weight gain and the potential for worsening of HbA1c may put off some obese smokers to quit. The cardiometabolic sequelae of smoking cessation in people with and without diabetes are different. The benefit of smoking cessation, in terms of reduced cardiovascular and all-cause mortality, in people without diabetes is evident within three years of quitting. However, it may take up to 10 years for people with diabetes to get this benefit. Post-cessation weight gain is much more detrimental to obese quitters with diabetes than those without. The aim of this review is to explore how best these high-risk individuals can be supported to remain abstinent long-term, and manage their vascular risk profile proactively, by concerted lifestyle intervention with judicious use of new and novel pharmacotherapy.


Diabetes Mellitus, vascular risk factors, multifactorial intervention, pharmacotherapy.

Full Text:



Chaturvedi N, Stephenson JM, Fuller JH. The relationship between smoking and microvascular complications in the EURODIAB IDDM Complications Study. Diabetes Care 1995;18(6):785-92.

Blomster JI, Woodward M, Zoungas S, et al. The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial. BMJ Open 2016;6(1):e009668-2015-009668.

Samuel VT, Shulman GI. Integrating mechanisms for insulin resistance: common threads and missing links. Cell 2012;148(5):852-71.

Magis D, Geronooz I, Scheen AJ. [Smoking, insulin resistance and type 2 diabetes]. Rev Med Liege 2002;57(9):575-81.

Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and β-cell dysfunction. Endocr Rev 2008;29(3):351-66.

Bergman BC, Perreault L, Hunerdosse D, et al. Novel and reversible mechanisms of smoking-induced insulin resistance in humans. Diabetes 2012;61(12):3156-66.

Jurgens CA, Toukatly MN, Fligner CL, et al. β-cell loss and β-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition. Am J Pathol 2011;178(6):2632-40.

DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991;14(3):173-94.

De Boer IH, Sibley SD, Kestenbaum B, et al. Central obesity, incident microalbuminuria, and change in creatinine clearance in the Epidemiology of Diabetes Interventions and Complications study. JASN 2007;18:235-43.

Pan A, Wang Y, Talaei M, Hu FB. Relation of smoking with total mortality and cardiovascular events among patients with diabetes mellitus: a meta-analysis and systematic review. Circulation 2015;132(19):1795-804.

DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991;14(3):173-94.

Delaimy WKA. Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus. JAMA 2002;287(19):2478.

Lanza GA, Spera FR, Villano A, et al. Effect of smoking on endothelium-independent vasodilatation. Atherosclerosis 2015;240(2):330-2.

Rodríguez A. Risk factors associated with metabolic syndrome in type 2 diabetes mellitus patients according to World Health Organization, Third Report National Cholesterol Education Program, and International Diabetes Federation definitions. Diabetes Metab Syndr Obes: Targets and Therapy 2011:1-4.

Afghahi H, Cederholm J, Eliasson B, et al. Risk factors for the development of albuminuria and renal impairment in type 2 diabetes – the Swedish National Diabetes Register (NDR). Nephrol Dial Transplant 2011;26:1236-43.

Agewall S, Fagerberg B. Risk factors that predict development of microalbuminuria in treated hypertensive men. The Risk Factor Intervention Study Group. Angiology 1996;47:963-72.

Papanas N, Katsiki N, Putz Z, Mikhailidis DP. Diabetes, obesity and vascular disease – an update. Curr Pharm Des 2013;19:4900-03.

Kiowski W, Linder L, Stoschitzky K, et al. Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers. Circulation 1994;90(1):27-34.

Sayk F, Iwen KA, Lehnert H. Diabetes and hypertension. Deutsche medizinische Wochenschrift 2009;134:2296-301.

Martinez Ocana JC, Romero R. Tobaccoism and albuminuria in hypertension and diabetes: is tobacco also harmful for the kidney? Med Clin (Barc) 1999;112:176-8.

Kong C, Nimmo L, Elatrozy T, et al. Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in type 2 diabetes. Atherosclerosis 2001;156(2):37-8.

Parving HH, Gall MA, Nielsen FS. Dyslipidaemia and cardiovascular disease in non-insulin-dependent diabetic patient with and without diabetic nephropathy. J Intern Med 1994;Suppl 736:89-94.

Anon. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995;75(14):894-903.

Turner RC, Millns H, Neil HA, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ 1998;316(7134):823-8.

Gæde P, Oellgaard J, Carstensen B, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016;59(11):2298-307.

Kar D, Gillies C, Zaccardi F, et al. Relationship of cardiometabolic parameters in non-smokers, current smokers, and quitters in diabetes: a systematic review and meta-analysis. Cardiovasc Diabetol 2016;15(1):158.

Lycett D, Nichols L, Ryan R, et al. The association between smoking cessation and glycaemic control in patients with type 2 diabetes: a THIN database cohort study. Lancet Diabetes Endocrinol 2015;3(6):423-30.

Chaturvedi N, Stevens L, Fuller JH. Which features of smoking determine mortality risk in former cigarette smokers with diabetes? The World Health Organization Multinational Study Group. Diabetes Care 1997;20(8):1266-72.

Chaturvedi N, Fuller JH. Mortality risk by body weight and weight change in people with NIDDM. The WHO Multinational Study of Vascular Disease in Diabetes. Diabetes Care 1995;18(6):766-74.

Al-Delaimy WK, Willett WC, Manson JE, Speizer FE, Hu FB. Smoking and mortality among women with type 2 diabetes: The Nurses' Health Study cohort. Diabetes Care 2001;24(12):2043-8.

Dobson AJ, Alexander HM, Heller RF, Lloyd DM. How soon after quitting smoking does risk of heart attack decline? J Clin Epidemiol 1991;44(11):1247-53.

Look AHEAD Research Group, Pi-Sunyer X, Blackburn G, Brancati FL, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007;30(6):1374-83.

Wing RR, Lang W, Wadden TA, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 2011;34(7):1481-6.

Malarcher AM, Ford ES, Nelson DE, et al. Trends in cigarette smoking and physicians' advice to quit smoking among people with diabetes in the U.S. Diabetes Care 1995;18(5):694.

Tian J, Venn A, Otahal P, Gall S. The association between quitting smoking and weight gain: a systemic review and meta-analysis of prospective cohort studies. Obes Rev 2015;16(10):883-901.

Aubin HJ, Farley A, Lycett D, Lahmek P, Aveyard P. Weight gain in smokers after quitting cigarettes: meta-analysis. BMJ 2012;345:e4439.

Aveyard P, Lycett D, Farley A. Managing smoking cessation related weight gain. Pol Arch Med Wewn 2012;122(10):494-8.

Levine MD, Marcus MD, Perkins KA. Women, weight, and smoking: a cognitive behavioral approach to women's concerns about weight gain following smoking cessation. Cognit Behav Pract 2003;10(2):105-11.

Clair C, Rigotti NA, Porneala B, et al. Association of smoking cessation and weight change with cardiovascular disease among adults with and without diabetes. JAMA 2013;309(10):1014-21.

Stamford BA, Matter S, Fell RD, Papanek P. Effects of smoking cessation on weight gain, metabolic rate, caloric consumption, and blood lipids. Am J Clin Nutr 1986;43(4):486-94.

Kawachi I, Troisi RJ, Rotnitzky AG, Coakley EH, Colditz GA. Can physical activity minimize weight gain in women after smoking cessation? Am J Public Health 1996;86(7):999-1004.

Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 2004;99(1):29-38.

Le Foll B, Melihan-Cheinin P, Rostoker G, Lagrue G. Smoking cessation guidelines: evidence-based recommendations of the French Health Products Safety Agency. Eur Psychiatry 2005;20(5):431-41.

Dinneen, Davies MJ, Heller S, et al. Effectiveness of the Diabetes Education and Self Management for Ongoing and Newly Diagnosed (DESMOND) Programme for people with newly diagnosed type 2 diabetes: cluster randomised controlled trial. BMJ 2008;336(7642):491-5.

Skinner TC, Carey ME, Cradock S, et al. Depressive symptoms in the first year from diagnosis of type 2 diabetes: results from the DESMOND trial. Diabet Med 2010;27(8):965-7.

Viberti G, Lachin J, Holman R, et al. A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of type 2 diabetic patients in North America and Europe. Diabetic Medicine 2006;23:1289-94.

Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38(1):140-09.

Heaf J. Metformin in chronic kidney disease: time for a rethink. Peritoneal Dialysis Int 2014;34(4):353-7.

Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999;281(21):2005-12.

Paul SK, Klein K, Majeed A, Khunti K. Association of smoking and concomitant metformin use with cardiovascular events and mortality in people newly diagnosed with type 2 diabetes. J Diabetes 2016;8(3):354-62.

Fontbonne A, Charles MA, Juhan-Vague I, et al. The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group. Diabetes Care 1996;19(9):920-6.

Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA 2010;303(14):1410-8.

Chao ECDO. SGLT-2 inhibitors: a new mechanism for glycemic control. Clin Diabetes 2014;32(1):4-11.

Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens 2014;8(4):262-75.e9.

Davidson JA. Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. Cleve Clin J Med 2009;76(Suppl 5):S28-38.

Kawalec P, Mikrut A, Łopuch S. The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab Res Rev 2014;30(4):269-83.

Aroda VR, Henry RR, Han J, et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther 2012; 34(6):1247–58.e22.



  • There are currently no refbacks.

The Journal of the Association of British Clinical Diabetologists