Articles on Inflammation & Type 2 Diabetes 

Donath MY. Schumann DM. Faulenbach M. Ellingsgaard H. Perren A. Ehses JA. Islet inflammation in type 2 diabetes: from metabolic stress to therapy. [Review] [55 refs] Diabetes Care. 31 Suppl 2:S161-4, 2008. Decreases in both mass and secretory function of insulin-producing beta-cells contribute to the pathophysiology of type 2 diabetes. The histology of islets from patients with type 2 diabetes displays an inflammatory process characterized by the presence of cytokines, apoptotic cells, immune cell infiltration, amyloid deposits, and eventually fibrosis. This inflammatory process is probably the combined consequence of dyslipidemia, hyperglycemia, and increased circulating adipokines. Therefore, modulation of intra-islet inflammatory mediators, in particular interleukin-1 beta, appears as a promising therapeutic approach. 

Greenfield JR. Campbell LV. Relationship between inflammation, insulin resistance and type 2 diabetes: 'cause or effect'?. [Review] [192 refs] Current Diabetes Reviews. 2(2):195-211, 2006. Inflammation has been implicated as an important aetiological factor in the development of both insulin resistance and type 2 diabetes mellitus. This conclusion is predominantly drawn from studies demonstrating associations between elevated (but 'normal range') levels of circulating acute phase inflammatory markers, typified by C-reactive protein (CRP), and indices of insulin resistance and the development of type 2 diabetes. There is debate as to whether these associations are independent of body fatness or, rather, an epiphenomenon of obesity, particularly central obesity, a strong predictor of insulin resistance and type 2 diabetes and an important source of inflammatory cytokines, such as interleukin-6. Some of this controversy and the inability to draw definitive conclusions from these studies relate to the fact that most studies measure body fat and its distribution indirectly using anthropometric estimates, such as Body Mass Index and waist circumference, rather than directly by dual-energy X-ray absorptiometry, computed tomography or magnetic resonance imaging. Furthermore, use of the term inflammation may be inappropriate when describing mild elevations of CRP in the 'normal range' in the absence of the other changes that characterise classical inflammatory diseases, such as a reduction in levels (or evidence of consumption) of complement proteins. Debate as to whether obesity mediates the association between circulating levels of inflammatory markers and insulin resistance can be resolved by well-designed studies using body fat measured by gold-standard methods. In this review, we present evidence to support the suggestion that body fat is the primary determinant of circulating inflammatory marker levels in the basal state and that marginally elevated levels of circulating interleukin-6 and CRP in obesity are a consequence rather than a cause of insulin resistance. The importance of genetic influences in determining both body fatness and circulating CRP levels will also be discussed. The review will conclude with a discussion of possible mechanisms linking body fat and insulin resistance to elevated circulating levels of inflammatory markers, including the possible role of the toll-like family of immune receptors. 

You T. Nicklas BJ. Chronic inflammation: role of adipose tissue and modulation by weight loss. [Review] [83 refs] Current Diabetes Reviews. 2(1):29-37, 2006. Chronic inflammation has been linked with an increased risk of type 2 diabetes and cardiovascular disease. As an endocrine and inflammatory organ, adipose tissue is an important source of circulating pro-inflammatory cytokines. Current evidence strongly supports that chronic inflammation is associated with enlarged body fat mass. Moreover, inflammation is independently linked with abdominal, especially visceral fat mass, possibly due to the regional variation in adipose tissue cytokine production. In addition to pharmacological approaches, lifestyle modifications have been advocated for the treatment of chronic inflammation. A number of studies have indicated that either weight loss via energy restriction, or energy restriction plus other strategies (aerobic exercise, behavioral counseling, and liposuction), could reduce chronic inflammation. While the amount of weight loss tends to be important, exercise and other strategies may have additional effects. A few studies have reported weight loss effects on adipose tissue cytokine production. Weight loss reduces subcutaneous adipose tissue production of pro-inflammatory cytokines (i.e. interleukin 6, tumor necrosis factor alpha) and increases adipose expression of anti-inflammatory cytokines (i.e. interleukin 10, interleukin 1 receptor antagonist). More studies are needed to investigate the role of regional adipose tissue cytokine production in regulation of inflammation and the modulating effects of weight loss. 

Pradhan A. Obesity, metabolic syndrome, and type 2 diabetes: inflammatory basis of glucose metabolic disorders. [Review] [33 refs] Nutrition Reviews. 65(12 Pt 2):S152-6, 2007. The latter half of the 20th century has witnessed rapid advances in medicine. Concurrently, secular trends in lifestyle practices in our increasingly sedentary society have led to burgeoning rates of obesity, metabolic syndrome, and type 2 diabetes. The number of Americans with type 2 diabetes more than doubled between 1980 and 2004 and the prevalence increases with age. Potential causes of this growing epidemic include changes in dietary patterns, physical inactivity, and obesity but may also include as yet unidentified genetic and environmental determinants. In this regard, experimental data provide evidence for a direct link between obesity and subclinical inflammation and support the concept that the metabolic syndrome and type 2 diabetes are, at least in part, inflammatory conditions. Furthermore, elevated levels of inflammatory biomarkers are not only associated with the development of future diabetes but cardiovascular disease as well. These findings suggest that subclinical inflammation may be a contributing factor not only to the etiology of these metabolic disorders but also their cardiovascular complications. 

Johnson RB. Periodontitis as a component of hyperinflammation: treating periodontitis in obese diabetic patients. Compendium of Continuing Education in Dentistry. 28(9):500-4; quiz 506, 528, 2007. Increasing evidence points to periodontal disease as a significant risk factor in the etiology of other diseases with inflammatory components, such as cardiovascular disease and type 2 diabetes mellitus. Thus, it may be possible to reduce the risk for other diseases with an inflammatory component by maintaining a healthy periodontium. In addition to plaque and calculus, other factors such as diet, body weight, lifestyle, and environmental stress complicate the maintenance of a healthy periodontium. It is becoming more important for the general dentist to address these additional risk factors in addition to providing conventional treatment for periodontal disease. This review addresses a multifactorial approach to the treatment of periodontal disease and suggests that the "focal theory" of infection may still be relevant for oral inflammation. 

Kornum JB. Thomsen RW. Riis A. Lervang HH. Schonheyder HC. Sorensen HT. Type 2 diabetes and pneumonia outcomes: a population-based cohort study. Diabetes Care. 30(9):2251-7, 2007. OBJECTIVE: We sought to examine whether type 2 diabetes increases risk of death and complications following pneumonia and to assess the prognostic value of admission hyperglycemia. RESEARCH DESIGN AND METHODS: This was a population-based cohort study of adults with a first-time hospitalization for pneumonia between 1997 and 2004 (n = 29,900) in northern Denmark. Information on diabetes, comorbidity, laboratory findings, pulmonary complications, and bacteremia was obtained from medical databases. We used regression to compute adjusted relative risks of pulmonary complications, bacteremia, and mortality rate ratios (MRRs) within 90 days following hospitalization among patients with and without type 2 diabetes. The prognostic impact of admission hyperglycemia was studied in a subcohort (n = 13,574). RESULTS: In total, 2,931 (9.8%) pneumonia patients had type 2 diabetes. Mortality among diabetic patients was greater than that among other patients: 19.9 vs. 15.1% after 30 days and 27.0 vs. 21.6% after 90 days, respectively, corresponding to adjusted 30- and 90-day MRRs of 1.16 (95% CI 1.07-1.27) and 1.10 (1.02-1.18). Presence of type 2 diabetes did not predict pulmonary complications or bacteremia. Adjustment for hyperglycemia attenuated the association between type 2 diabetes and mortality. High glucose level on admission was a predictor of death among patients with diabetes and more so among those without diagnosed diabetes: adjusted 30-day MRRs for glucose level >or=14 mmol/l were 1.46 (1.01-2.12) and 1.91 (1.40-2.61), respectively. CONCLUSIONS: Type 2 diabetes and admission hyperglycemia predict increased pneumonia-related mortality. 

Liu S. Tinker L. Song Y. Rifai N. Bonds DE. Cook NR. Heiss G. Howard BV. Hotamisligil GS. Hu FB. Kuller LH. Manson JE. A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. Archives of Internal Medicine. 167(15):1676-85, 2007. BACKGROUND: Inflammatory cytokines, including tumor necrosis factor alpha, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations. METHODS: Among 82,069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor alpha receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease. RESULTS: After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor alpha receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups. CONCLUSION: These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women. 

Giulietti A. van Etten E. Overbergh L. Stoffels K. Bouillon R. Mathieu C. Monocytes from type 2 diabetic patients have a pro-inflammatory profile. 1,25-Dihydroxyvitamin D(3) works as anti-inflammatory. Diabetes Research & Clinical Practice. 77(1):47-57, 2007. The exact factors contributing to the pathogenesis of type 2 diabetes remain elusive. Lately, it was suggested that inflammation and activation of the innate immune system could be linked to type 2 diabetes pathogenesis and also to the development of common diabetic complications, mainly atherosclerosis. The aim of this study was to investigate the role of monocytes in this sub-clinical inflammatory state and test 1,25-dihydroxyvitamin D(3), the active form of Vitamin D, as an anti-inflammatory agent. For this purpose, monocytes from type 2 diabetic patients were compared to monocytes from healthy controls and type 1 diabetic patients. The expression profile of inflammatory markers in freshly isolated and immune-stimulated monocytes was measured by quantitative real-time RT-PCR. Type 2 diabetic patients showed significantly higher expression levels of TNF-alpha, IL-6, IL-1, IL-8, COX-2, ICAM-1 and B7-1 compared to controls and type 1 diabetic patients. 1,25-Dihydroxyvitamin D(3) was able to down-regulate the expression of TNF-alpha, IL-6, IL-1, and IL-8, confirming its immunomodulatory properties. From these data we concluded that monocytes from type 2 diabetic patients have a pro-inflammatory profile. In addition, 1,25-dihydroxyvitamin D(3) was able to modulate inflammation in these monocytes. 

Rana JS. Nieuwdorp M. Jukema JW. Kastelein JJ. Cardiovascular metabolic syndrome - an interplay of, obesity, inflammation, diabetes and coronary heart disease. [Review] [114 refs] Diabetes, Obesity & Metabolism. 9(3):218-32, 2007. Cardiovascular disease is currently one of the biggest causes of morbidity and mortality facing humanity. Such a paradigm shift of disease pattern over the last century has only worsened due to the alarming global prevalence of obesity and type 2 diabetes. In recent years there is increasing focus on inflammation as one of the key players in the patho-physiology of these disorders. In addition to these overt risk factors new research is unraveling the significance of a constellation of early metabolic abnormalities that include weight gain, insulin resistance, prehypertension and a specific pattern of dyslipidaemia. There exists a complex interrelationship of these various metabolic disorders and their effect on cardiovascular system. Simplified explanation can be that inflammation increases insulin resistance, which in turn leads to obesity while perpetuating diabetes, high blood pressure, prothrombotic state and dyslipidaemia. While inflammation and insulin resistance have direct adverse effects on cardiac muscle, these metabolic abnormalities as a whole cause causes cardiovascular complications; warranting a multi pronged therapeutic and preventive approach for the 'Cardiovascular Metabolic Syndrome' as an entity. 

Hotamisligil GS. Inflammation and metabolic disorders. [Review] [100 refs] Nature. 444(7121):860-7, 2006. Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare. 

Alexandraki K. Piperi C. Kalofoutis C. Singh J. Alaveras A. Kalofoutis A. Inflammatory process in type 2 diabetes: The role of cytokines. [Review] [285 refs] Annals of the New York Academy of Sciences. 1084:89-117, 2006. Population-based studies have shown strong relationship between inflammatory markers and metabolic disturbances, obesity, and atherosclerosis, whereas inflammation has been considered as a "common soil" between these clinical entities and type 2 diabetes (T2D). The accumulation of macrophages in adipose tissue (AT), the common origin of macrophages and adipocytes, the prevalent presence of peripheral mononuclear cells, and apoptotic beta cells by themselves seem to be the sources of inflammation present in T2D, since they generate the mediators of the inflammatory processes, namely cytokines. The main cytokines involved in the pathogenesis of T2D are interleukin-1beta (IL-1beta), with an action similar to the one present in type 1 diabetes, tumor necrosis factor-alpha (TNF-alpha), and IL-6, considered as the main regulators of inflammation, leptin, more recently introduced, and several others, such as monocyte chemoattractant protein-1, resistin, adiponectin, with either deleterious or beneficial effects in diabetic pathogenesis. The characterization of these molecules targeted diabetes treatment beyond the classical interventions with lifestyle changes and pharmaceutical agents, and toward the determination of specific molecular pathways that lead to low grade chronic inflammatory state mainly due to an immune system's unbalance. 

Kempf K. Rose B. Herder C. Kleophas U. Martin S. Kolb H. Inflammation in metabolic syndrome and type 2 diabetes: Impact of dietary glucose. [Review] [99 refs] Annals of the New York Academy of Sciences. 1084:30-48, 2006. Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose-induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease. 

Kontogianni MD. Zampelas A. Tsigos C. Nutrition and inflammatory load. [Review] [180 refs] Annals of the New York Academy of Sciences. 1083:214-38, 2006. Chronic inflammation has been suggested to play an important role in metabolic diseases, such as atherothrombosis and type 2 diabetes. A lot of research has focused on the immunomodulatory effects of several nutrients, such as fatty acids, antioxidants, carbohydrates, specific amino acids, micronutrients, and alcohol, which play a crucial role in the maintenance of an "optimal" immune response. In addition, specific dietary patterns, such as the Mediterranean diet, are evolving as protective against cardiovascular disease, because of their anti-inflammatory properties. In this article, the existing data concerning the nutrients' pro- and anti-inflammatory properties are presented, as well as dietary patterns that could protect from chronic inflammation and its metabolic and atherothrombotic complications. 

Mora C. Navarro JF. Inflammation and diabetic nephropathy. [Review] [78 refs] Current Diabetes Reports. 6(6):463-8, 2006. Diabetic nephropathy has become the main cause of renal failure, but unfortunately the intimate mechanisms leading to the development and progression of renal injury are not yet fully known. Activated innate immunity and inflammation are relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including chemokines, adhesion molecules, and proinflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective leads to important therapeutic considerations, with new pathogenic pathways becoming important therapeutic targets that can be translated into clinical treatments for diabetic nephropathy. 

Bo S. Durazzo M. Guidi S. Carello M. Sacerdote C. Silli B. Rosato R. Cassader M. Gentile L. Pagano G. Dietary magnesium and fiber intakes and inflammatory and metabolic indicators in middle-aged subjects from a population-based cohort. American Journal of Clinical Nutrition. 84(5):1062-9, 2006. BACKGROUND: Type 2 diabetes (DM), metabolic syndrome (MetS), and inflammation are linked to reduced magnesium and fiber intakes; these associations are attenuated by adjustment for each of these nutrients. OBJECTIVE: We investigated the association among magnesium and fiber intakes, metabolic variables, and high-sensitivity C-reactive protein (hs-CRP) values. DESIGN: Cross-sectional analyses were performed in a representative cohort of 1653 adults and in a subgroup with normal body mass index without dysmetabolisms (n = 205). A validated semiquantitative food-frequency questionnaire was used; magnesium intake was computed by multiplying its content in each food by the frequency of food consumption. RESULTS: The prevalence of DM, MetS, and hs-CRP >/= 3 mg/L significantly decreased from the lowest to the highest tertile of magnesium and fiber intakes. Subjects within the lowest tertiles of magnesium and fiber intakes were 3-4 times as likely to have DM, MetS, and hs-CRP >/= 3 mg/L, after multiple adjustments. After the analysis was additionally controlled for fiber intake, associations with hs-CRP >/= 3 mg/L proved to be significant (odds ratio: 2.05; 95% CI: 1.30, 3.25), whereas reduced magnesium intake and DM and MetS were no longer significant. The lowest tertile of fiber intake remained associated with DM, hs-CRP >/= 3 mg/L, and MetS after adjustments for multiple confounders and magnesium intake. In the lean, healthy subject subgroup, hs-CRP values were inversely associated with magnesium and fiber intakes in a multivariate model (P < 0.001). CONCLUSIONS: Reduced fiber intake was significantly associated with metabolic abnormalities; the magnesium effect might be confounded by fiber being in foods that also provided magnesium. Lower magnesium and fiber intakes were linked to hs-CRP >/= 3 mg/L in both the entire cohort and healthy persons. 

Boden G. Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver. [Review] [40 refs] Current Diabetes Reports. 6(3):177-81, 2006. Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. FFA also produces low-grade inflammation in skeletal muscle and liver through activation of nuclear factor-kappaB, resulting in release of several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which contributes to the development of atherosclerotic vascular diseases and NAFLD. 

de Jager J. Dekker JM. Kooy A. Kostense PJ. Nijpels G. Heine RJ. Bouter LM. Stehouwer CD. Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study. Arteriosclerosis, Thrombosis & Vascular Biology. 26(5):1086-93, 2006. OBJECTIVE: The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention. METHODS AND RESULTS: In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75]; P interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained approximately 43% of the increase in cardiovascular mortality risk conferred by T2D. CONCLUSIONS: These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients. 

Deans KA. Sattar N. "Anti-inflammatory" drugs and their effects on type 2 diabetes. [Review] [60 refs] Diabetes Technology & Therapeutics. 8(1):18-27, 2006. There is a growing body of evidence for the role of inflammation in type 2 diabetes. In addition to the evidence presented elsewhere, evidence is emerging that many drugs that have apparent "anti-inflammatory" properties may reduce the incidence and/or delay the onset of type 2 diabetes. Statins have been found to lower inflammatory markers, and a post hoc analysis of the West of Scotland Coronary Prevention Study (WOSCOPS) suggested that pravastatin may reduce the risk of developing diabetes, although the Lipid Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) found no statistically significant effect of atorvastatin on risk of developing diabetes. Fibrates have been found to lower some markers of inflammation, and a prospective trial found that bezafibrate reduces risk of developing diabetes. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers appear to reduce some markers of inflammation, and a meta-analysis concluded that ACE inhibitors and angiotensin receptor blockers reduce risk of developing type 2 diabetes. Metformin is known to reduce the risk of developing diabetes, and more recent evidence suggests it also lowers C-reactive protein, in part because of its modest weight-reducing effect. Thiazolidinediones reduce risk of developing diabetes, and consistently lower inflammatory markers independent of adiposity effects. High-dose aspirin inhibits cyclooxygenase and IkappaB kinase-beta and reduces fasting plasma glucose concentration, although there has not, as yet, been a large-scale trial to examine the effect of aspirin on the risk of developing diabetes. We conclude that although many drugs with potential anti-inflammatory properties reduce the risk of developing diabetes, it is difficult to prove that such anti-inflammatory properties contribute to their diabetes prevention since nearly all drugs have other, often more pronounced, actions. Studies with more specific inhibitors of inflammatory pathways (e.g., interleukin- 6 blockers) and mendelian randomization (genetic studies) will help determine whether targeting the inflammation axis is a fertile mechanism to treat or prevent type 2 diabetes. 

Koshiyama H. Honjo S. Hamamoto Y. Ikeda H. Wada Y. Drugs share antidiabetic and antiatherosclerotic actions through "the common soil". Medical Hypotheses. 66(3):473-5, 2006. There have been increasing evidences that atherosclerosis is not the result of diabetes mellitus, but that both type 2 diabetes mellitus and atherosclerosis may share common pathogenesis, as Stern proposed as 'common soil' hypothesis in 1995. There are several candidates for 'common soil', such as insulin resistance, vascular inflammation and endothelial dysfunction. Recently many of clinical studies have indicated that some drugs can prevent or delay the development of cardiovascular diseases (CVD). Furthermore, many studies have suggested that some classes of drugs may prevent the development of type 2 diabetes. It is to be noted that most of the drugs may have both actions, i.e., to prevent development of new diabetes and to prevent CVD. Furthermore, they are reported to inhibit inflammation or endothelial dysfunction. Taken together, it is hypothesized that the drug which may have antiatherogenetic action may also have antidiabetic action, and vice versa. This hypothesis may provide the new insights into perspectives of drug development both to prevent type 2 diabetes and to prevent CVD.