Obesity and the risk of cardiovascular disease and diabetes mellitus

The increasing prevalence of obesity worldwide has many experts concerned about the worsening health of a large proportion of the population. It is well recognized that obesity is associated with a higher mortality, an increased risk of hypertension and hyperlipidemia, cardiovascular disease, diabetes mellitus, osteoarthritis, gall bladder disease and possibly some cancers. Currently it is estimated that over two thirds of adults in the United States are overweight and nearly one third are clinically obese. Of special concern is the rapid increase     

The metabolic syndrome in type 1 diabetes: does it exist and does it matter?

The significance of the metabolic syndrome in type 1 diabetes is not well understood. This study aimed to estimate its prevalence and attendant complications. Four hundred twenty-seven type 1 diabetic subjects were grouped according to the presence or absence of metabolic syndrome (WHO criteria). Macro- and microvascular complications were compared between the groups as individual and as composite endpoints. Data were analyzed for the total cohort and in subgroups according to duration of diabetes quartiles (<6.9, 7-12.9, 13-19.9, and >20 years) and year of presentation. Fifteen percent of individuals fulfilled the WHO criteria for metabolic syndrome, and of these, 26.9% were insulin resistant, as compared with 3.4% of those without metabolic syndrome [odds ratio (OR)=8.9, P=.001]. Both BMI and metabolic syndrome showed an increasing trend from 1992 to 2003. Those with metabolic syndrome required significantly higher insulin dosage [0.9 (0.7-1.2) vs. 0.6 (0.5-0.9) units/kg, P=.03], were older [35.0 (26.2-47.3) vs. 29.7 (23.4-36.4) years, P=.002], and had longer duration of diabetes [19.7 (10.7-25.6) vs. 12.1 (6.3-17.9) years, P=.0001]. They also had a significantly higher macrovascular composite endpoint (OR=3.3, P=.02) as well as higher macrovascular and microvascular composite endpoint (OR=3.1, P=.0001). The prevalence of stroke (OR=22.8, P=.008), peripheral vascular disease (OR=7.3, P=.05), and severe retinopathy (OR=3.7, P=.01) is higher in subjects with metabolic syndrome in the >or=20-year quartile group; in addition, these subjects have higher macrovascular composite endpoint (OR=3.9, P=.03) and macrovascular and microvascular composite endpoint (OR=2.9, P=.03). This remained so even when subjects with albuminuria were excluded. Some individuals with type 1 diabetes can also have metabolic syndrome. They are more prone to complications and require even more intensive glycemic control and reduction of macrovascular risk factors.     

Continuity of care in diabetes: to whom does it matter?

The Australian health care system allows patients to move around to seek medical treatment. This may impact negatively on continuity of care. To determine factors associated with continuity of care for persons with diabetes, the profiles of 479 patients attending the Diabetes Centre, Royal Prince Alfred Hospital, Sydney, Australia, were examined. The majority of patients (87.7%) attended only one general practitioner and had been under the care of the referring doctor for a median of 6.2 years. These patients were older (P=0.02), but were comparable with those attending multiple doctors in terms of their type, duration and treatment of diabetes as well as their clinical and complication profile. There was also a relationship between age and the length of time under the care of the referring doctor (P=0.0002). The HbA(1c), lipid, blood pressure and treatment profiles of patients attending the referring doctor short, medium or long-term were comparable. However, there was an upward trend in the proportion of patients with a history of cerebrovascular disease, ischaemic heart disease or any complication of diabetes with each incremental increase in length of time under the referring doctor. Appropriately, patients seek continuity of care as they age and their health needs become more complex.     

The metabolic syndrome in type 2 diabetes: When does it matter?

AIMS: Young adults with type 2 diabetes (T2Dm) present the clinician with the problem of when to start therapies for the primary prevention of vascular disease and how to identify those at most vascular risk. We examine whether the metabolic syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this context. METHODS: Data were collected from 5928 subjects with T2Dm, and subjects were categorized as having MetS by World Health Organization criteria (body mass index criteria modified for Asians using >23 kg/m2). The prevalence of macrovascular disease was examined by MetS status and age. RESULTS: The overall MetS prevalence was 72.3%. MetS was associated with an increased prevalence of ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001), coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across all age groups. MetS subjects had an IHD prevalence equivalent to that seen in subjects who were one decade older without MetS. The most significant impact of MetS was for the age group of 40-49 years with much lesser impact seen with progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with no MetS at age 40-50 years, p < 0.05; falling progressively to OR = 1.5 at age >70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft (CABG) and PVD. There was a strong relationship between the number of MetS risk factors and IHD prevalence (r = 0.99, p = 0.0001). CONCLUSIONS: These data suggest that MetS is particularly useful in stratifying vascular risk in younger T2Dm patients and in those with a high number of MetS components. For patients with MetS, especially those with a full house of MetS risk factors, commencing risk-lowering interventions 10 years earlier than their MetS-free counterparts could be considered.     

Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study

Objective

Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD), but longitudinal observations are limited and the precise magnitude is unknown. We prospectively assessed the incidence of CVD in patients with RA compared with patients with type 2 diabetes mellitus (DM) and the general population.

Methods

The 3‐year incidence rate of CVD was determined in a prospective cohort (the Cardiovascular Research and Rheumatoid Arthritis Study) of 353 outpatients with RA, and was compared with that in 1,852 population‐based cohort study participants (155 had type 2 DM). We investigated fatal and nonfatal CVD (according to International Classification of Diseases, Ninth Revision criteria) and used Cox proportional hazards models to assess the incidence of CVD in RA, type 2 DM, and the general population.

Results

The 3‐year incidence of CVD was 9.0% in patients with RA and 4.3% in the general population, corresponding with an incidence rate of 3.30 per 100 patient‐years (95% confidence interval [95% CI] 2.08–4.25) and 1.51 per 100 person‐years (95% CI 1.18–1.84), respectively. Compared with the general population, the age‐ and sex‐adjusted hazard ratio (HR) for RA was 1.94 (95% CI 1.24–3.05, P = 0.004). Neither exclusion of patients with prior CVD at baseline nor adjustment for cardiovascular risk factors significantly influenced this. Compared with the nondiabetic population, nondiabetic patients with RA and those with type 2 DM had comparable HRs, 2.16 (95% CI 1.28–3.63, P = 0.004) and 2.04 (95% CI 1.12–3.67, P = 0.019), respectively.

Conclusion

The risk of CVD in RA was significantly elevated compared with the general population, and comparable with the magnitude of risk in type 2 DM.     

The role of IGF-I in the development of cardiovascular disease in type 2 diabetes mellitus: is prevention possible?

The incidence of peripheral, cerebro- and cardiovascular disease (CVD) in patients with type 2 diabetes mellitus is approximately twice as high as in the non-diabetic population. Conventional cardiovascular risk factors such as plasma lipids, lipoproteins and hypertension only partially explain this excessive risk of developing atherosclerosis and CVD. Meta-analysis of studies performed in non-diabetic populations indicates that the risk of CVD increases continuously with glucose levels above 4.2 mmol/l. The glucose hypothesis suggests that treatment which normalizes glucose levels prevents or delays the long-term complications of diabetes mellitus. However, the outcome of the UK Prospective Diabetes Study demonstrates that glucose control does not completely prevent CVD.In healthy subjects, serum IGF-I levels peak in early adulthood, after which they gradually decrease with increasing age. Several observations suggest that there is a premature and progressive age-related decline in serum IGF-I bioactivity in type 2 diabetics, which eventually results in a (relative) IGF-I deficiency. In type 2 diabetics, close relationships have been demonstrated between glycaemic control and serum IGF-I levels, with worse control being associated with lower IGF-I levels. Several studies (in non-diabetics) suggest that lowered circulating IGF-I levels account for a poor outcome of CVD. We previously observed in a population-based study that a genetically determined lowered IGF-I expression increases the risk of myocardial infarction with type 2 diabetes.This genetic approach overcomes the problem that cross-sectional studies cannot distinguish whether changes in IGF-I levels are a cause or a consequence of a disease. IGF-I is an important metabolic regulatory hormone. In addition, IGF-I suppresses myocardial apoptosis and improves myocardial function in various models of experimental cardiomyopathy. Compared with other growth factors, the 'survival' effect of IGF-I on myocardium seems rather unique.Therefore, we hypothesize that the premature and progressive decline in serum IGF-I bioactivity in ageing patients with type 2 diabetics is an important pathophysiological abnormality. It contributes not only to elevated glucose and lipid levels, but also to the progression and the poor outcome of CVD. If this hypothesis is proven to be right, treatment with IGF-I as an adjunct to insulin offers great potential and might not only improve metabolic control but also reduce the incidence and prevalence of CVD in type 2 diabetes patients. However, there is as yet no experimental evidence that long-term (replacement) treatment with IGF-I prevents, delays or reduces CVD in type 2 diabetes patients. Clinical trials are necessary to prove that long-term IGF-I treatment, preferably in the form of a better-tolerated IGF-I/IGF-binding protein-3 complex, improves the overall cardiovascular risk in type 2 diabetes.     

Telomeres and cardiovascular disease: does size matter?

Telomeres-the specialized DNA-protein structures at the ends of eukaryotic chromosomes-are essential for maintaining genome stability and integrity and for extended proliferative life span in both cultured cells and in the whole organism. Telomerase and additional telomere-associated proteins are necessary for preserving telomeric DNA length. Age-dependent telomere shortening in most somatic cells, including vascular endothelial cells, smooth muscle cells, and cardiomyocytes, is thought to impair cellular function and viability of the aged organism. Telomere dysfunction is emerging as an important factor in the pathogenesis of hypertension, atherosclerosis, and heart failure. In this Review, we discuss present studies on telomeres and telomere-associated proteins in cardiovascular pathobiology and their implications for therapeutics.     

Severity of coronary artery disease in type 2 diabetes mellitus: Does the timing matter?

AimThe aim of our study was to compare the angiographic changes in 53 nondiabetic patients, 54 type 2 diabetic patients of less than 5 years of duration, 41 patients with 5–10 years of diabetes, and 27 with more than 10 years of diabetic duration.MethodsIn this cross-sectional study, 175 patients, who underwent coronary angiogram for the evaluation of the coronary artery disease (CAD), were recruited. Based on the angiographic findings, syntax score, vessel score, and coronary collaterals grading were analyzed. The biochemical analysis was done by using the auto analyzer.ResultsA significant increase in the mean syntax score (p = 0.019), vessel score (p = 0.007), and coronary collateral grade (p = 0.008) was observed in the patients with 5–10 years of diabetes when compared to those with less than 5 years of diabetic duration. There was no significant difference in the mean syntax score (p = 0.979), vessel score (p = 0.299), and collateral grade (p = 0.842) between the patients with 5–10 years and more than 10 years of diabetes. The difference in the mean syntax score (p = 0.791), vessel score (p = 0.098), and collateral grade (p = 0.661) between the nondiabetic and the patients with less than 5 years of diabetes was not significant.ConclusionA significant structural change in the coronary arteries was found among the patients with 5–10 years of diabetes.     

The impact of diabetes mellitus on survival after myocardial infarction: can it be modified by drug treatment?

Aims/hypothesis. Mortality of diabetic patients after myocardial infarction remains high despite recent improvement in their management. This study population-based evaluates the impact of cardiovascular drug therapy on mortality within 28 days and during 5-year follow-up in diabetic compared with non-diabetic patients.¶Methods. Using the MONICA Augsburg register from 1985 to 1992, 2210 inpatients with incident Q-wave myocardial infarction aged 25–74 years were included, of whom 468 had diabetes. Primary end point was mortality within 28 days and over 5 years. General linear model procedures were used for age-adjustment, controlling for sex, and testing significance; hazard risk ratios were calculated using multivariable Cox proportional hazards model procedures.¶Results. During the 5-year follow-up, 598 subjects died (396 diabetic, 202 non-diabetic). The mortality rate within 28 days was 12.6 % in diabetic patients (women 18.0 %, men 9.9 %) and 7.3 % in non-diabetic patients (p = 0.001). Mortality in diabetic patients over 5 years was increased by 64 % (95 % confidence interval 1.39–1.95) compared with non-diabetic patients. This was considerably reduced (p < 0.001) in patients treated with thrombolytic drugs (risk ratio: diabetes 0.57, no diabetes 0.65) and with beta blockers (0.62 and 0.64) and antiplatelets (0.76 and 0.74) at hospital discharge. Mortality of diabetic patients treated with these drugs was reduced to that of non-diabetic patients without such treatment (risk ratio 1.01 to 1.27; p > 0.1).¶Conclusion/interpretation. Diabetic patients after myocardial infarction are at particularly high risk of dying, but benefit clearly from treatment with thrombolytics, beta blockers and antiplatelets. This study does not, however, allow any inferences to be drawn for treatment with angiotensin converting enzyme inhibitors or the impact of left ventricular function. [Diabetologia (2000) 43: 218–226]     

Type 2 diabetes, socioeconomic status and risk of cancer in Scotland 2001–2007

Aims/hypothesis

The objective of this study was to use Scottish national data to assess the influence of type 2 diabetes on the risk of cancer at 16 different sites, while specifically investigating the role of confounding by socioeconomic status in the diabetes–cancer relationship.

Methods

All people in Scotland aged 55–79 years diagnosed with any of the cancers of interest during the period 2001–2007 were identified and classified by the presence/absence of co-morbid type 2 diabetes. The influence of diabetes on cancer risk for each site was assessed via Poisson regression, initially with adjustment for age only, then adjusted for both age and socioeconomic status.

Results

There were 4,285 incident cancers in people with type 2 diabetes. RR for any cancers (adjusted for age only) was 1.11 (95% CI 1.05, 1.17) for men and 1.33 (1.28, 1.40) for women. Corresponding values after additional adjustment for socioeconomic status were 1.10 (1.04, 1.15) and 1.31 (1.25, 1.38), respectively. RRs for individual cancer sites varied markedly.

Conclusions/interpretation

Socioeconomic status was found to have little influence on the association between type 2 diabetes and cancer.