Brief Article
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World J Diabetes. Oct 15, 2013; 4(5): 210-218
Published online Oct 15, 2013. doi: 10.4239/wjd.v4.i5.210
Impaired fasting glucose: Pro-diabetic, “atheroprotective” and modified by metabolic syndrome
Altan Onat, Mesut Aydın, Günay Can, H Altuğ Çakmak, Bayram Köroğlu, Ayşem Kaya, Evin Ademoğlu
Altan Onat, Turkish Society of Cardiology, and Emeritus, Department of Cardiology, Cerrahpaşa Medical Faculty, Istanbul University, 34335 Etiler, Turkey
Mesut Aydın, Department of Cardiology, Dicle University Medical Faculty, 21200 Diyarbakır, Turkey
Günay Can, Department of Public Health, Cerrahpaşa Medical Faculty, Istanbul University, 34099 Istanbul, Turkey
H Altuğ Çakmak, Department of Cardiology, Cerrahpaşa Medical Faculty, Istanbul University, 34099 Istanbul, Turkey
Bayram Köroğlu, Siyami Ersek Center for Cardiovascular Surgery, Research and Training Hospital, 34668 Istanbul, Turkey
Ayşem Kaya, Section of Biochemistry, Cardiology Institute, Istanbul University, 34096 İstanbul, Turkey
Evin Ademoğlu, Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, 34093 İstanbul, Turkey
Author contributions: Onat A designed the study and wrote manuscript; Aydın M, Çakmak HA and Köroğlu B collected data, revised critically for intellectual content and approved the final version; Can G provided data analyses and approved the final version; Kaya A and Ademoğlu E performed biochemical analyses and approved the final version.
Supported by The Turkish Society of Cardiology
Correspondence to: Dr. Altan Onat, Professor, Turkish Society of Cardiology, and Emeritus, Department of Cardiology, Cerrahpaşa Medical Faculty, Istanbul University, Nisbetiye cad. 59/24, 34335 Etiler, Istanbul, Turkey. alt_onat@yahoo.com.tr
Telephone: +90-212-3516217 Fax: +90-212-2211754
Received: January 16, 2013
Revised: March 24, 2013
Accepted: August 12, 2013
Published online: October 15, 2013
Processing time: 272 Days and 16.8 Hours
Abstract

AIM: To investigate whether impaired fasting glucose (IFG) confers cardiovascular risk.

METHODS: A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’ follow-up for incident diabetes and coronary heart disease (CHD). Metabolic syndrome (MetS) was defined by ATP-III criteria modified for male abdominal obesity, and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association. Stratification by presence of MetS was used. Outcomes were predicted providing estimates for hazard ratio (HR) obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.

RESULTS: In 3181 adults (aged 52 ± 11.5 years at baseline), analysis stratified by MetS, gender and IFG status distinguished normoglycemic subjects by a “hypertriglyceridemic waist” phenotype consisting of significantly higher waist circumference, fasting triglyceride and lower high-density lipoprotein-cholesterol, regardless of gender and MetS. Additionally, lipoprotein (Lp) (a) tended to be lower in (especially female) participants with MetS. Multivariable linear regression in a subset of the sample demonstrated decreased Lp (a) levels to be associated with increased fasting glucose and insulin concentrations, again particularly in women. In Cox regression analysis, compared with normoglycemia, baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS. Cox models for developing CHD in 339 individuals, adjusted for conventional risk factors, revealed that IFG status protected against CHD risk [HR = 0.37 (95%CI: 0.14-0.998)] in subjects free of MetS, a protection that attenuated partly in male and fully in female participants with MetS.

CONCLUSION: IFG status in non-diabetic people without MetS displays reduced future CHD risk, yet is modulated by MetS, likely due to autoimmune activation linked to serum Lp (a).

Keywords: Autoimmune activation; Coronary disease risk; Diabetes, type 2; Impaired fasting glucose; Lipoprotein (a); Metabolic syndrome

Core tip: The study investigated whether and to what extent impaired fasting glucose (IFG) conferred risk of type 2 diabetes or coronary heart disease in 3181 middle-aged adults, by separately stratifying to gender and metabolic syndrome. Follow-up over 8.5 years revealed both factors to modulate future risk. In women without metabolic syndrome, IFG was not associated with either cardiometabolic disorder, while in men, IFG imparted risk of diabetes alone. Coronary heart disease risk appeared to depend on the core components of the metabolic syndrome, especially in the female. The results implicate autoimmune activation involving lipoprotein(a) to be of high relevance in the pathogenesis of new-onset diabetes.