Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

Atrial fibrillation and prediabetes:A liaison that merits attention!

Atrial fibrillation(AF)and prediabetes share common pathophysiological mechanisms with endothelial dysfunction and inflammation playing a key role.The resultant vicious cycle which sets in culminates in a higher atherogenicity and thermogenicity of the vascular system resulting in increased major adverse cardiac or cerebrovascular event(MACCE)events.However,the same has not convincingly been verified in real-world settings.In the recent retrospective study by Desai et al amongst AF patients being admitted to hospitals following MACCE,prediabetes emerged as an independent risk factor for MACCE after adjusting for all confounding variables.However,certain questions like the role of metformin,quantifying the risk for MACCE amongst prediabetes compared to diabetes,the positive impact of reversion to normoglycemia remain unanswered.We provide our insights and give future directions for dedicated research in this area to clarify the exact relationship between the two.

Age-specific differences in the association between prediabetes and cardiovascular diseases in China:A national cross-sectional study

BACKGROUND Cardiovascular disease(CVD)is a leading cause of morbidity and mortality worldwide,the global burden of which is rising.It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults.To develop a focused screening plan and treatment for Chinese adults with prediabetes,it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.AIM To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.METHODS The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008.A thorough evaluation was conducted.Individuals with prediabetes were categorized into two groups based on age.Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years.Random forest was established in both age groups.SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.RESULTS In total,6948 people were diagnosed with prediabetes in this study.In prediabetes,prevalences of CVD were 5(0.29%)in the younger group and 148(2.85%)in the older group.Overall,11.11%of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years.In the younger age group,the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle,whereas in the older age group,resident status was more closely linked.CONCLUSION The susceptibility to CVD is age-specific in newly diagnosed prediabetes.It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.

Metabolic disorders in prediabetes:From mechanisms to therapeutic management

Diabetes,one of the world's top ten diseases,is known for its high mortality and complication rates and low cure rate.Prediabetes precedes the onset of diabetes,during which effective treatment can reduce diabetes risk.Prediabetes risk factors include high-calorie and high-fat diets,sedentary lifestyles,and stress.Consequences may include considerable damage to vital organs,including the retina,liver,and kidneys.Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments.However,while these options are effective in the short term,they may fail due to the difficulty of long-term implementation.Medications may also be used to treat prediabetes.This review examines prediabetic treatments,particularly metformin,glucagon-like peptide-1 receptor agonists,sodium glucose cotransporter 2 inhibitors,vitamin D,and herbal medicines.Given the remarkable impact of prediabetes on the progression of diabetes mellitus,it is crucial to intervene promptly and effectively to regulate prediabetes.However,the current body of research on prediabetes is limited,and there is considerable confusion surrounding clinically relevant medications.This paper aims to provide a comprehensive summary of the pathogenesis of prediabetes mellitus and its associated therapeutic drugs.The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.

Prevalence and impact of diabetes and prediabetes on presentation and complications of primary hyperaldosteronism at diagnosis

BACKGROUND Primary hyperaldosteronism(PH)is considered to contribute to increased risk of developing type 2 diabetes mellitus(T2DM)and prediabetes.Both PH and DM are associated with increased risk for hypertension,cardiovascular diseases,and chronic kidney diseases.However,data on prevalence of T2DM and prediabetes in PH,and impact of T2DM and prediabetes on presentation and cardio renal complications in PH at presentation is sparse.AIM To determine the prevalence of T2DM and prediabetes in PH at diagnosis and impact on presentation and complications of PH.METHODS A retrospective cohort study was conducted in tertiary care settings in individuals with confirmed diagnosis of PH at presentation.Demographic variables,clinical presentations,duration and degree of hypertension,complications,laboratory parameters including sodium,potassium levels,plasma aldosterone concentration(PAC),plasma renin activity(PRA),and aldosterone to renin ratio(ARR)and cardio-renal parameters were collected.Comparison was done between three groups:PH with no DM(Group A)or with pre-diabetes(Group B)or with T2DM(Group C).P<0.05 was statistically significant.RESULTS Among 78 individuals with confirmed PH,62%had pre-diabetes or diabetes;with 37%having DM.Mean duration of T2DM was 5.97±4.7 years.The mean levels of glycaemic parameters among the group A vs B vs C individuals were fasting plasma glucose(mg/dL):87.9±6.5,105.4±9.02,130.6±21.1;post prandial plasma glucose(mg/dL):122.7±9.8,154.9±14,196.7±38.0;glycated haemoglobin(%)(5.3±0.2,5.9±0.2,7.5±0.6,P<0.05),respectively.There was no significant difference in the biochemical parameters(PAC,PRA,ARR,sodium,potassium levels),presentation and complications between the groups.Cardio renal parameters or degree and duration of hypertension were comparable between the groups.CONCLUSION Significant prevalence of T2DM and prediabetes in PH at diagnosis does not impact its presentation or complications.Early screening for undetected PH in T2DM and prediabetes subjects with hypertension may prevent complications.

Atrial fibrillation and prediabetes:Interplay between left atrium and systemic diseases

Atrial fibrillation(AF)is associated with multiple other comorbidities,i.e.multimorbidity.Prediabetes is one of the multiple comorbidities observed in patients with AF,whereby these two disease entities share the same pathophysiological mechanisms,namely oxidative stress and inflammation.Although prediabetes is reported to have a negative impact on major adverse cardiac or cerebrovascular events in hospitalized AF patients,information about the interactions between prediabetes and AF remains inconsistent.A more in-depth exploration of pathophysiology and more comprehensive prospective clinical studies of AF and diabetes would provide a thorough understanding of the timing of events and further treatment strategies.Deeper investigations are needed to clarify the interactions and causal relationships between AF and prediabetes.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

Prediabetes in children and adolescents:A ticking bomb!

Prediabetes in children and adolescents is on the rise which has drawn significant attention over the past decade.It is an early warning sign of the underlying pathophysiological changes which in due course of time might compound into type II diabetes mellitus.The incidence of prediabetes in adolescents ranges from 4%-23%which is alarmingly high and requires active intervention from the system.We have discussed early identification of high-risk patients,prompt screening and active intervention to manage this growing problem.

A Machine Learning Classification Model for Detecting Prediabetes

The incidence of prediabetes is in a dangerous condition in the USA. The likelihood of increasing chronic and complex health issues is very high if this stage of prediabetes is ignored. So, early detection of prediabetes conditions is critical to decrease or avoid type 2 diabetes and other health issues that come as a result of untreated and undiagnosed prediabetes condition. This study is done in order to detect the prediabetes condition with an artificial intelligence method. Data used for this study is collected from the Centers for Disease Control and Prevention’s (CDC) survey conducted by the Division of Health and Nutrition Examination Surveys (DHANES). In this study, several machine learning algorithms are exploited and compared to determine the best algorithm based on Average Squared Error (ASE), Kolmogorov-Smirnov (Youden) scores, areas under the ROC and some other measures of the machine learning algorithm. Based on these scores, the champion model is selected, and Random Forest is the champion model with approximately 89% accuracy.

Evaluation and Intervention Methods for Patients with Prediabetes of Different Phenotypes

Prediabetes is a heterogeneous condition,encompassing various pathological phenotypes such as hyperinsulinemia,tissue-specific insulin resistance(IR),systemic IR,andβ-cell dysfunction.A significant proportion of individuals with prediabetes remain undiagnosed.Furthermore,although lifestyle interventions have demonstrated efficacy in improving prediabetic conditions,some individuals with prediabetes progress to type 2 diabetes mellitus.This study aims to summarize effective evaluation methods for identifying distinct pathological phenotypes of prediabetes and targeted lifestyle intervention strategies to mitigate the progression from prediabetes to diabetes.

Prediabetes diagnosis and treatment: A review

Prediabetes is an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold. While, the diagnostic criteria of prediabetes are not uniform across various international professional organizations, it remains a state of high risk for developing diabetes with yearly conversion rate of 5%-10%. Observational evidence suggests as association between prediabetes and complications of diabetes such early nephropathy, small fiber neuropathy, early retinopathy and risk of macrovascular disease. Several studies have shown efficacy of lifestyle interventions with regards to diabetes prevention with a relative risk reduction of 40%-70% in adults with prediabetes. While there is increasing evidence to prove the efficacy of pharmacotherapy in prevention of diabetes in adults with prediabetes, pharmaceutical treatment options other than metformin are associated with adverse effects that limit their use for prediabetes. There are no reports of systematic evaluation of health outcomes related to prediabetes in children. The effects of pharmacotherapy of prediabetes on growth and pubertal development in children remains unknown. Secondary intervention with pharmacotherapy with metformin is advocated for high-risk individuals but criteria for such consideration benefit of early intervention, long term cost effectiveness of such interventions and the end point of therapy remain unclear. Pharmacotherapy must be used with caution in children with prediabetes. Prediabetes is a condition defined as having blood glucose levels above normal but below the defined threshold of diabetes. It is considered to be an at risk state, with high chances of developing diabetes. While, prediabetes is commonly an asymptomatic condition, there is always presence of prediabetes before the onset of diabetes. The elevation of blood sugar is a continuum and hence prediabetes can not be considered an entirely benign condition. This aim of this review is to describe the challenges associated with diagnosis of prediabetes, the possible adverse medical outcomes associated with prediabetes and the treatment options and rationale for their use in context of prediabetes.

Treatment of prediabetes

Progression of normal glucose tolerance(NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance(IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus(type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options(lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed.

Incretin-based therapies in prediabetes: Current evidence and future perspectives

The prevalence of type 2 diabetes(T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance(NGT) and the clinical entity of T2 D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2 D. The huge burden resulting from the complications of T2 D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists, on β-cell function in patients with T2 D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2 D.

Are body mass index and waist circumference significant predictors of diabetes and prediabetes risk: Results from a population based cohort study

AIM To determine the predictive role of body mass index(BMI) and waist circumference(WC) for diabetes and prediabetes risk in future in total sample as well as in men and women separately. METHODS In a population based cohort study, 1765 with mean ± SD age: 42.32 ± 6.18 healthy participants were followed up from 2003 till 2013(n = 960). Anthropometric and biochemical measures of participants were evaluated regularly during the follow up period. BMI and WC measures at baseline and diabetes and prediabetes status of participants at 2013 were determined. Multivariable logistic regression analysis was used for determining the risk of diabetes and prediabetes considering important potential confounding variables. Receiver operatingcharacteristic curve analysis was conducted to determine the best cut of values of BMI and WC for diabetes and prediabetes. RESULTS At 2013, among participants who had complete data, 45 and 307 people were diabetic and prediabetic, respectively. In final fully adjusted model, BMI value was a significant predictor of diabetes(RR = 1.39, 95%CI: 1.06-1.82 and AUC = 0.68, 95%CI: 0.59-0.75; P < 0.001) however not a significant risk factor for prediabetes. Also, WC was a significant predictor for diabetes(RR = 1.2, 95%CI: 1.05-1.38 and AUC = 0.67, 95%CI: 0.6-0.75) but not significant risk factor for prediabetes. Similar results were observed in both genders.CONCLUSION General and abdominal obesity are significant risk factors for diabetes in future.

Metal Exposure and Risk of Diabetes and Prediabetes among Chinese Occupational Workers

Objective To study the association between metal exposure and risk of diabetes and prediabetes among Chinese workers exposed to metals.Methods We used data obtained from the baseline survey of the Jinchang Cohort Study of workers in Jinchang Industry,the largest nickel production company in China.A total of 42,122 workers ≥20 years of age were included in the study.A standardized,structured questionnaire was used to collect epidemiological information.Physical examinations and laboratory tests were conducted to evaluate the health status of the participants and to measure various biomarkers including blood sugar,lipids,and urinary metal concentrations.Logistic regression was used to study the association between occupational groups categorized according to the measured metal levels(office workers,low-level;mining/production workers,mid-level;and smelting/refining workers,high-level)and risk of diabetes and prediabetes.Results The overall prevalence of diabetes and prediabetes was 7.5% and 16.8%,respectively.The adjusted odds ratios for diabetes among mining/production workers and smelting/refining workers compared to office workers were 1.5(95% CI:1.3,1.7)and 3.8(95% CI:3.4,4.3),respectively.No association was observed between these occupational groups and prediabetes in this study.Conclusion Occupations associated with higher levels of metal exposure were associated with an increased risk of diabetes in this cohort.More studies are needed to confirm this observed association.

Different metabolic/obesity phenotypes are differentially associated with development of prediabetes in adults: Results from a 14-year cohort study

BACKGROUND The risk of developing prediabetes based on the metabolic/obesity phenotypes has been poorly investigated. AIM To examine the association of baseline metabolic/obesity phenotypes and their changes over time with the risk of prediabetes development. METHODS In a population-based cohort study, 1741 adults (aged > 19 years) with normal blood glucose were followed for 14 years. Anthropometric and biochemical measures were evaluated regularly during the follow-up period. According to body mass index and metabolic health status, participants were categorized into four groups: Metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy obese (MUO). Multivariable Cox regression analysis was used to measure the risk of prediabetes according to the baseline metabolic/obesity phenotype and their changes during the follow-up. RESULTS In the whole population with a mean (95CCI for mean) follow up duration of 12.7 years (12.6-12.9), all three MUNW, MHO, MUO groups were at higher risk for developing prediabetes compared to the MHNW group (P = 0.022). The MUNW group had the highest risk for developing prediabetes (hazard ratio (HR): 3.84, 95%CI: 1.20, 12.27). In stratified analysis by sex, no significant association was found in men, while women in the MUNW group were at the greatest risk for prediabetes (HR: 6.74, 95%CI: 1.53, 29.66). Transforming from each phenotype to MHNW or MHO was not related to the risk of prediabetes development, whereas transforming from each phenotype to MUO was associated with an increased risk of prediabetes (HR > 1;P < 0.05). CONCLUSION Our findings indicate that MHO is not a high risk, unless it transforms into MUO over time. However, people in the MUNW group have the greatest risk for developing prediabetes, and therefore, they should be screened and treated.

Bone health in diabetes and prediabetes

Bone fragility has been recognized as a complication of diabetes,both type 1 diabetes (T1D) and type 2 diabetes (T2D),whereas the relationship between prediabetes and fracture risk is less clear.Fractures can deeply impact a diabetic patient’s quality of life.However,the mechanisms underlying bone fragility in diabetes are complex and have not been fully elucidated.Patients with T1D generally exhibit low bone mineral density (BMD),although the relatively small reduction in BMD does not entirely explain the increase in fracture risk.On the contrary,patients with T2D or prediabetes have normal or even higher BMD as compared with healthy subjects.These observations suggest that factors other than bone mass may influence fracture risk.Some of these factors have been identified,including disease duration,poor glycemic control,presence of diabetes complications,and certain antidiabetic drugs.Nevertheless,currently available tools for the prediction of risk inadequately capture diabetic patients at increased risk of fracture.Aim of this review is to provide a comprehensive overview of bone health and the mechanisms responsible for increased susceptibility to fracture across the spectrum of glycemic status,spanning from insulin resistance to overt forms of diabetes.The management of bone fragility in diabetic patient is also discussed.

Severity of the metabolic syndrome as a predictor of prediabetes and type 2 diabetes in first degree relatives of type 2 diabetic patients:A 15-year prospective cohort study

BACKGROUND Type 2 diabetes mellitus(T2DM)has high morbidity and mortality worldwide,therefore there is of paramount importance to identify the risk factors in the populations at risk early in the course of illness.A strong correlation between severity of metabolic syndrome(MetS)and HbA1c,fasting insulin and insulin resistance has been reported.Accordingly,the MetS severity score(or MestS Zscore)can potentially be used to predict the risk of T2DM progression over time.AIM To evaluate the association the of MestS Z-score in first degree relatives(FDRs)of T2DM with the risk of prediabetes and type 2 diabetes in future.METHODS A prospective open cohort study was conducted between 2003-2018.At baseline,the sample comprised of 1766 FDRs of patients with T2DM who had a normal glucose tolerance test.Relative risk(RR)and 95%confidence interval were calculated based on logistic regression.The receiver-operator characteristic analysis and area under the curve based on MetS Z-score were used to evaluate the risk of prediabetes and diabetes among the FDR population.RESULTS Baseline MetS Z-scores were associated with the its latest values(P<0.0001).Compared with individuals who were T2DM free at the end of follow up,those who developed T2DM had higher MetS Z-score at baseline(P<0.001).In multivariable logistic regression analyses for every unit elevation in MetS Z-score at the baseline,the RR for developing future T2DM and prediabetes was(RR=1.94,RR=3.84),(RR=1.5,RR=2.17)in total population and female group,respectively(P<0.05).The associations remained significant after adjusting the potential confounding variables.A cut off value of 0.97 and 0.94 was defined in the receiver-operator characteristic curve based on the MetS Z-score for differentiating female patients with diabetes and prediabetes from the normal population,respectively.CONCLUSION The MetS Z-score was associated with an increased risk of future T2DM.Appropriate interventions at earlier stages for preventing and attenuating MetS effects may be considered as an effective strategy for FDR as at-risk population.

Clinical Effect of Zishenwan on Elderly Patients with Prediabetes Based on the Method of Sweet-Bitter Therapeutic

[Objectives]To study the clinical effect of Zishenwan on elderly patients with prediabetes based on the method of Sweet-Bitter Therapeutic.[Methods]Total 64 elderly patients with prediabetes in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine from April,2020 to July,2021 were randomly divided into control group(32 cases)and Zishenwan group(32 cases).The control group received basic treatment(diet control and regular luck exercise),while the Zishenwan group was treated with Zishenwan on the basic treatment.[Results]The results of intragroup comparisons after treatment show that both of the groups improved plasma glucose,insulin,plasma lipid metabolism and other related indexes.The results of inter-group comparisons were as follows.(i)The FPG and 2hPG of the Zishenwan group were significantly lower than the control group(P<0.05).(ii)The FINS and HOMA-IR of the Zishenwan group were significantly lower than the control group(P<0.05).(iii)The LDL-C of the Zishenwan group were significantly lower than the control group(P<0.05).(iv)The ADP,hs-CRP,and GLP-1 of the Zishenwan group were significantly improved compared to those of the control group(P<0.05).Although there was no significant difference in other indicators,the improvement trend is better than that of the control group.[Conclusions]Zishenwan can further improve plasma glucose level of the elderly patients with prediabetes on the basis of basic treatment,and to a certain extent,reduce the plasma glucose to normal,which is beneficial to the benign outcome of the elderly patients with prediabetes.In addition,it can improve insulin secretion and reduce insulin resistance,which provides a basis for the disease control of elderly patients with prediabetes.It can also improve the lipid metabolism of elderly patients with prediabetes,and the effect on LDL-C is significant.It is speculated that its mechanism may be closely related to the changes of ADP,hs-CRP and GLP-1 in the body of elderly patients with prediabetes.

Comparative efficacy between glimepiride and metformin in preventing progression of prediabetes to type 2 diabetes

Background: Several recent studies have shown that treatment with therapeutic lifestyle changes, and/or several drugs retard progression of prediabetes to type 2 diabetes. However, none of these studies used a Sulfonylurea (SU), although in UKPDS, SUs delayed the progression of hyperglycemia and several subjects would have been categorized as having prediabetes by present diagnostic criteria. Thus, SUs may have delayed the progression in this group as well. Objective: Therefore, we examined comparative efficacy of glimepiride and metformin in progression to diabetes in subjects with prediabetes. Methods: Twenty men and 18 women ages 28 - 81 years with prediabetes were followed for 5 - 9 years. Prediabetes was diagnosed by impaired fasting glucose and HbA1Cbetween 5.7% - 6.4% with two consecutive determinations as recommended by American Diabetes Association. Twenty obese subjects were administered metformin 500 mg/day and 18 non obese subjects received glimepiride 0.5 mg/day, in addition to dietary and exercise counseling. Results: Mean duration of follow up was 5.8 ± 0.2 years. Fasting Plasma Glucose (FPG) and HbA1Cdeclined to <100 mg/dl and <5.7% in all subjects by 6 months. During the follow up period, 9 of 20 (45%) subjects receiving metformin and 5 of 18 (27%) in glimepiride group progressed to diabetes (p < 0.01) as determined by FPG ≥ 126 mg/dl and HbA1C≥ 6.5% (RR, 1.61 with Confidence Interval, 1.43 - 1.74 for metformin vs glimepiride;p < 0.01). The mean duration to progression was 32 ± 4 months in metformin group and 47 ± 5 months in subjects receiving glimepiride. FPG and HbA1clevels promptly returned to <100 mg/dl and <5.7% on increasing daily dose of both metformin (1000 - 1500 mg) and glimepiride (2 - 4 mg). The glycemic control was maintained till the end of observation period. None of the subjects in either group manifested a cardiovascular event nor any of the subjects died during the period of observation. Conclusion: Glimepiride may be more effective in delaying the progression of prediabetes to diabetes in non-obese subjects in comparison to metformin in obese subjects with no significant difference in cardiovascular morbidity or overall mortality.